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Bruce Rigsby Bruce Rigsby (born 1937) is an American-Australian anthropologist specializing in the languages and ethnography of native peoples on both continents. He is now professor emeritus at Queensland University, and a member of both the Australian Anthropological Society and the American Anthropological Association. Career Bruce Rigsby was born in 1937. He obtained his bachelor's degree at the University of Louisville in international studies, specializing in the area of the Soviet bloc. He then went on to obtain a PhD in anthropology at the University of Oregon, doing fieldwork to gather materials on the Umatilla and Yakima. in 1963. He absorbed the Boasian-Sapir tradition of American ethnolinguistics, combining linguistics and anthropology. His doctoral dissertation was on the southern tribes and languages of the Columbia Plateau. He developed a particular research focus on and specialization in Sahaptin ethnography, Sahaptin language and Nass-Gitksan people, their language and history. In 1975 he became head of the new department of Anthropology at University of Queensland, and directed his interests towards the languages and tribes of the Eastern Cape York Peninsula, and Princess Charlotte Bay. Rigsby has also been active in defending indigenous claims for native title and represented the Cape York Land Council regarding the Lakefield and Cliff Island National Parks land claims. Notably in his court appearance, when interviewing George Musgrave for his testimony, Rigsby adopted the elder's idiom of Australian English in deference to the Musgrave's age and status. He was adopted into the Lamalama tribe. Generations of students have been the beneficiaries of what Alice Gaby has called Rigsby's 'phenomenal generosity'. Comments by Peter Sutton and other colleagues on his career are available at a video recording the launching of a festschrift in his honour, available on YouTube. Publications 1975 'Nass-Gitksan: An Analytic Ergative Syntax,' International Journal of American Linguistics vol.41 Issue 4 December 1975 pp. 344–354 1999 with Finlayson, J. D., and Bek, H.). Introduction. In J. D. Finlayson, B. Rigsby and H. Bek (Ed.), Connections in Native Title: Genealogies, Kinship and Groups, Australian National University, Canberra: Centre for Aboriginal Economic Policy Research pp. 1–13. 1999 'Genealogies, kinship and local group composition: Old Yintjingga (Port Stewart) in the late 1920s,' In J. D. Finlayson, B. Rigsby and H. Bek (Ed.), Connections in Native Title: Genealogies, Kinship and Groups, Canberra: Cen. for Aboriginal Economic Policy Res., ANU pp. 107–123 2005 'The Languages of Eastern Cape York Peninsula and Linguistic Anthropology,' In B. Rigsby and N. Peterson (eds.), Donald Thomson. The Man and Scholar, Canberra, ACT, Australia: The Academy of the Social Sciences in Australia pp. 129–142. 2005 with and Peterson, N. 'Introduction,' in B. Rigsby and N. Peterson (eds.), Donald Thomson. The Man and Scholar, Canberra: The Academy of the Social Sciences in Australia, pp. 1–16 2008 'The Stevens Treaties, Indian Claims Commission docket 264, and the Ancient One known as Kennewick Man,' in Alexander Harmon (ed.), The power of promises: Rethinking Indian treaties in the Pacific Northwest, Seattle, WA, U.S.A.: University of Washington Press pp. 244–276 2010 'The origin and history of the name 'Sahaptin',' in Virginia Beaert and Sharon Hargus (Ed.), Ichishkíin Sínwit: Yakama/Yakima Sahaptin Dictionary, pp.xviii-xxi, Toppenish, WA, U.S.A.: Heritage University; University of Washington Press. 2010 'The origin and history of the name Yakama/Yakima,' in Virginia Beavert and Sharon Hargus (eds.), Ichishkíin Sínwit: Yakama/Yakima Sahaptin Dictionary, Toppenish, WA, U.S.A.: Heritage University; University of Washington Press pp.xxii-xxxiv (c) 'Social theory, expert evidence and the Yorta Yorta rights appeal decision,' in Louis Knafla and Haijo Westra (Eds.), Aboriginal title and indigenous peoples: Canada, Australia, and New Zealand, Vancouver, BC, Canada: UBC Press pp. 53–84. 2011 With Diane Hafner,'Place and property at Yintjingga/ Port Stewart under Aboriginal law and Oueensland law,' In Brett Baker, Ilana Mushin, Mark Harvey and Rod Gardner (Eds.), Indigenous language and social identity: Papers in honour of Michael Walsh, Canberra, ACT, Australia: Pacific Linguistics pp. 33–44. 2015 with Christophe Verstraete,A Grammar and Lexicon of Yintyingka, Walter de Gruyter Notes and references Notes References Category:1937 births Category:Australian anthropologists Category:Living people Category:University of Louisville alumni Category:University of Oregon alumni
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Nikola Krajačević Nikola Krajačević Sartorius or Mikula Krajačević (1582–1653) was a Jesuit Catholic priest, missionary and prominent person of Counter-reformation movement in Habsburg Slavonia. Krajačević was born in a family whose members were military officers at Habsburg Military Frontier against the Ottomans. In his early life he was military officer. Krajačević completed his education in Graz, Brno, Rome and Eberndorf and had successful career in Catholic church in the Roman Catholic Archdiocese of Zagreb reaching positions of teacher, canon and archdeacon. He published at least two books in which he translated religious texts to "Slovenski" language of Kajkavian dialect. To promote religious poems and make them more acceptable to population he replaced or adopted texts of folk poems with texts of religious poems. Education and religious positions Krajačević's father Vuk was Habsburg military officer at Military Frontier. Krajačević was also military officer at the beginning of his adult life and even participated in battles against the Ottomans. According to some views, after Krajačević left military service he studied philosophy in Graz and theology probably in Rome. In 1612 Krajačević returned to Zagreb and began his career as Catholic priest. By 1614 Krajačević reached positions of the canon in Zagreb and archdeacon in Čazma. In 1615 he joined Jesuits and studied in Brno for a year and for two years in Eberndorf. Krajačević is also referred to as Sartorius, which was his Latinized name. Krajačević was a teacher at the Jesuit college in Zagreb. Among his students was Juraj Križanić. Bibliography Krajačević referred to the Kajkavian as Slovenski language to differentiate it from Čakavian and Štokavian to which he referred as Horvatski. Miroslav Vanino was one of main researchers of Krajačević's life and works. He believes that Krajačević published at least one of his works before 1629. Since 1640 Krajačević authored two books: the Prayer Book and Saint Evangelions. Krajačević published Prayer Book ("Molitvene knjižice Kristušovem vernei slovenskoga jezika, pristojne i hasnovite") in 1640 in Požun on Kajkavian. Although this work was anonymous publication at the beginning of the 20th century it was proven to be authored by Krajačević. In his works Krajačević wanted to make spiritual texts more acceptable to the common public and published them together with adapted folk poetry, which he considered filthy and inappropriate. Sometimes he would adopt or replace text of folk poems with religious texts expecting that religious texts will gradually be accepted and sung by population. Krajačić's Saint Evangelions were published by Petar Petretić who wrote its prologue in Graz in 1651. In this book Krajačić introduced orthographic rephorm which was later both praised and criticized. It was praised by Pavao Ritter Vitezović, who mistakenly attributed it to Petretić who only published the book. On the other hand, Ljudevit Gaj heavily criticized it, also mistakenly attributing it to Petretić. According to some authors, Saint Evangelions were authored by multiple different authors whose texts Krajačević compiled and edited. Krajačević's works were also widespread in the Slovene regions, primarily in Prekmurje, and had an influence on Prekmurje Slovene. Krajačević's life work largely inspired the works of Miklós Küzmics. References Sources Category:1582 births Category:1653 deaths Category:17th-century Jesuits Category:Jesuit missionaries Category:Croatian Jesuits Category:Croatian Roman Catholic missionaries Category:Roman Catholic missionaries in Croatia
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Q: How to get a list off all server sessions in laravel? I'm using Laravel 3. I want to know how many users are online , so i thought i might count all server sessions. dose any one know how i could do this? Note : I'm using 'driver' => 'file', in the session configuration. A: You can configure sessions class to use a database to store session data, then you can query the sessions table to perform your queries, this is a feature in Laravel itself. The exact method of configuring sessions will vary by the type of DB you are using, here's a guide to setting up sessions using databases: http://laravel.com/docs/session/config#database
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All posts tagged ‘female leads’ High speed motion picture of jet engine, 1946. Photo from user “NASA on The Commons” at Flickr CC. I remember the time when my mom decided to educate us teenagers about classic movies. The only one I remember specifically was Grease, which you’d think would be a great one for teenagers due to all the underage drinking and the singing and dancing, but the whole thing was a horrible disaster. We teased her mercilessly about her film choices, complaining about everything from the granularity of the film to the ridiculous hairstyles. Now that I’m older and wiser, I finally understand the lesson that my mom was trying to teach us: Never have teenagers. But seriously, the lesson I did learn is that perhaps I should get my daughter started earlier on classic movies. Will that help cure the next generation’s jaded appetite for the new and the technologically advanced? Will it help her see the value of a good story over that of flashy graphics and gratuitous special effects? Unfortunately, I don’t have all the answers. But I do know is that I’m having fun in the process of learning the answers to those questions. One of the great things about classic movies, from a purely parental perspective, is that American movies made from 1930 to 1968 had to abide by the Motion Picture Production Code. The Production Code, also known at Hays Code, was a morality code instated in 1930 to allegedly save Hollywood’s reputation after an especially wild decade. It was made legally possible due to a 1915 Supreme Court ruling that motion pictures were not included in the free speech amendment. During its effective period, the Code required American motion picture companies to have their films approved by the Production Code Administration before release. The Code featured a long list of “Don’ts” and “Be Carefuls.” Don’ts were obviously going to get your film rejected, Be Carefuls were to be tread warily. For example, the Code included some now-considered-mild offenses like profanity (especially religious profanity), scenes encouraging empathy towards crimes against the law, detailed methods for petty crimes like theft, any presentation of illegal drug trafficking, and finally and obviously sex in just about any form (including overly passionate kissing, undressing, and suggestive dances or poses). Even just the use of a bedroom as the location for a scene had to be done very carefully. The Code was finally brought down in 1968. Its downfall came for many reasons. One was the threat of television to the motion picture industry. The motion picture industry needed to offer more incentive (read “scantily clad women”) to convince their audience to leave the comfort of their television set, which — thankfully for cinema — was guided under even stricter morality guides. The rising of foreign cinema also offered competition to the American industry. Moreover, the Supreme Court overturned their 1915 ruling in 1952, which returned free speech to the motion picture industry. It is also clear that the huge mentality change of the 1960s brought on more pressure for the industry to change. In the end, the Code was modified to become the Motion Picture Association of America’s rating system that we all know today. All of this serves as a background to say that, while I don’t agree with censorship, the Code brought along an entire era of generally “decent” films (in terms of appropriateness), a score for parents looking for family-friendly movies outside of the usual choices. Which is not to say that I’d pick any Code era film at random and show it to children without double-checking first. There are, after all, a lot of things that were considered good and wholesome morality then that we now consider sexist, racist, or discriminatory in some way. Nevertheless, there are definitively a lot of Code era movies worth perusing should you get sick of watching the latest explosion-laden, gadget-toting, oops-my-shirt-was-torn-in-the-exact-perfect-place-to-show-my-tight-abs-rocking blockbusters. Here’s a list of the GeekMoms’ favorite Code era movies. Boys? Yes, I’d like to recommend some books with female leads that your son would enjoy reading. If your next question is “Why?,” then ask your daughter why she liked Harry Potter. She might say it was a good story, great characters, and a fantastic world. Who cares if the main character was a boy? In fact, girls will pick up a book with a hero or heroine equally. According to my excellent librarian resources, boys will actively avoid books with a girl as the main character. What’s the problem? I have no idea. Why should you encourage your son to read books with heroines? That’s easy. You want your son to grow up knowing that a strong female for a friend, wife or boss is normal and good. Instead of getting into the psychology of it all, let’s change it. And the best way is to get ‘em while they’re young. Here are a few adventure graphic novels that feature girl go-getters. I picked comics because when my son was young those were the only kind of books he selected on his own. Giants Beware! By Rafael Rosado and Jorge Aguirre Claudette wants to battle giants. She’s a great heroine, and breaks the mold. But what makes this book stand out is her two companions. Her little brother Gaston would rather be a pastry chef than a killer, but saves the day when he needs to, and Claudette’s best friend Marie is a girly-girl who loves etiquette, but is brave and clever. In many books with a strong female lead there is rarely another main girl, and the boys are usually competitive. The threesome are silly adventurers, complete with a sweet ending. One of our GeekMoms is reading it to her kids now. The Courageous Princess By Rod Espinosa This is almost ten years old and a classic of graphic novels: Talking animals, a fearsome dragon, a long journey, an anthropomorphic rope, and a princess who has integrity while saving herself. Zita the Spacegirl By Ben Hatke My son said over breakfast this morning, “Here you egg.” A quote by Strong-Strong, beloved character from Zita. This book is fast-paced with weird aliens, comedy, betrayal, rescues, and cuteness. Zita is brave but alone in this strange world, trying to find her friend. She and her new alien companions save the day. Akiko on the Planet Smoo By Mark Crilley Another space adventure that was part of a book club with both boys and girls. This comes as a graphic novel and book series. There are some slight differences between them (not sure why). ALL the kids in the club loved the story. Akiko is a human girl who is taken up to space to help some aliens in trouble. She’s a cool character. And Spuckler- we loved this guy. If you read Akiko out loud, do him in a John Wayne voice. It works. Angelic Layer By Clamp. A manga (Japanese comic) about a world where the premier entertainment is fighting dolls (called Angels) using mental control in huge arenas. The main character is a little girl who gets into the game wanting her battle Angel to be “a short girl, but brave and happy.” I can’t say I ever got into this series, but both my kids were addicted at a young age. My son would tell me about the fighting moves ad nauseam. The Stonekeeper (Amulet, Book 1) By Kazu Kibuishi The art is entrancing, and the main characters are a brother and sister. When a tentacled monster grabs their mom, Em and Navin are the only ones to save her, entering a dark universe with a magic necklace to help. Scary at times (which makes it cool.) Nightschool By Svetlana Chmakova. Definitely for the older son in your life; this is my family’s favorite graphic series. A secret world within our world where different factions sometimes battle, sometimes work together to keep the really bad things away from humans. Epic fights along with cute comedy, and a reluctant heroine Alex, who is powerful beyond what anyone expects. You can read my full review here. This list gets progressively for older kids, so please flip through them before handing it to your impressionable boy (especially the manga which has provocative poses.) And of course, your girls will love them too! I love video games. Strike that. I love GOOD video games. The distinction is especially important right now because starting Friday, I’ll be at PAX East for three solid days of VG-playtime. For those who haven’t heard of it, PAX East is a big-deal video game convention where game developers large and small descend on Boston to ply fans and the press with exclusive demonstrations and freebies. They hope we’ll provide the buzz necessary to launch their latest releases like viral videos. As a gamer and a discerning person, I’m happy to draw attention to good games. Of course, the question is: How do I identify a good game? No two gamers are likely to answer that the same way because the criteria by which we judge games are strongly influenced by the context of our opinions. Who we are and what we want and expect from games, in other words. Over the course of the coming week, I’ll be reviewing the games I play at PAX East. Ahead of the event, I expect some disappointments. Most video games are clones of each other – pale imitators trying to be the next Mario Bros, Pole Position, World of Warcraft, or Doom. Most video games are made without women in mind. Where there are playable female characters at all, I expect to find highly sexualized vixens, and any non-player characters will probably be poorly nuanced damsels in distress. Like television shows, most of the video games designed for kids (and women) are vapid time sinks and I expect to see many examples of that sad trend at the convention. All that said, I anticipate some pleasant surprises. PAX East is where game developers go to make their best impressions on the masses, after all. Some of the art will be dazzling, some of the puzzles will bedevil me, and some of the jokes will not be offensive. And for all the weak-minded joystick jockeys out there who may argue that my reviews won’t matter because I’m just a girl? Watch out. This Geek Mom Pwns Noobs*. *To Pwn Noobs is to completely obliterate your opponent in any event where there is competition. This list immediately began forming when I was sitting next to two college girls on the subway. One girl was incredulous that the other had never seen 9 to 5. Overhearing this, I shared her incredulity. How can a young woman make it in this world if she lacks the historical and pop-culture awareness that only a screening of 9 to 5 can bring? Here are 20 characters that every geek girl should be introduced to before they leave for college, in order from characters you can introduce to young children to ones where you pretty much want to wait until they’re college-bound. These characters all persevere against hardships of one form or another, and they all play a starring role (with apologies to fabulous supporting players like Hermione, Elastigirl, and Lisa Simpson). 1. Olivia – Whether on the page or the TV screen, this diva for the preschool set always dreams big, imagining herself in a wide array of fantasy situations to get through the nuisances of everyday life. 2. WordGirl – Designed as an educational superhero, WordGirl is hilarious, unafraid, and her big words are mightier than the villains’ swords (or cuts of meat). Kiki's Delivery Service 3. Kiki from Kiki’s Delivery Service – At 13, Kiki is ready to strike out on her own, figuring out how to become a real witch (and quite an entrepreneur). See also: any other Miyazaki girl character. 5. Pippi Longstocking – Who wouldn’t want Pippi next door, with her horse, her monkey, and her world without limits? 6. Wonder Woman – Her Superfriends self is great for the younger kids, but save the awesomeness of the Lynda Carter twirl and the comic world for the older ones. 7. Nancy Drew – She’s gone through many changes over her long history, but you can always count on Nancy’s intelligence as she cracks the case. See also: Harriet the Spy. 8. Meg Murray from A Wrinkle in Time – An awkward heroine makes her way through a sci-fi world to save her family. What more do you need? 9. Daria – Daria is the perfect role model for coming up with intelligent zingers in the face of stupidity. 10. Buffy from Buffy The Vampire Slayer – I really don’t have to explain the awesomeness of vampire slaying to GeekMom readers, right? Add Willow, Faith, and Anya and you’ve got a show every girl should see. The Legend of Billie Jean 11. Billie Jean from The Legend of Billie Jean – Three words: fair is fair! (Note: this should be disqualified for the makeover-to-be-powerful, but it’s too awesome not to include.) 12. Katniss Everdeen from The Hunger Games – Katniss is flawed, complex, rebellious, and powerful, and my need to root for her is what keeps me reading and rereading The Hunger Games trilogy. 13. Violet, Judy, and Doralee from 9 to 5 – Yes, they inspired this list, but they also overthrew a corrupt and sexist corporate structure to become the head honchos. See also: Murphy Brown, Mary Tyler Moore, and J.C. from Baby Boom. 14. Natalie, Dylan, and Alex from Charlie’s Angels – I’m going to go with the McG movie version of the angels over the classic TV show, simply because of the angels’ amazing action sequences. Bad taste in men, though. 15. Dana Scully from The X-Files – Always grounded in science and logic, Scully held her own against Mulder’s ongoing conspiracy theories. See also: Temperance Brennan from Bones. 16. Charly from The Long Kiss Goodnight – Geena Davis blossoming from Samantha the schoolmarm to Charly the killer spy is nothing but fun to watch. (Note: this movie also gets the Billie Jean makeover exemption.) 17. Sydney Bristow from Alias – Sure, every episode is a makeover for Sidney, but the combination of her amazing ability to take on different personas with her fighting and technical abilities with her love of family and friends make her a complex character to be reckoned with. 18. Starbuck from Battlestar Galactica – The best thing they did when they revamped Battlestar Galactica is make Starbuck into a woman and put her at the very center of the path to Earth. Kill Bill: Vol. 1 19. Beatrix Kiddo aka The Bride from Kill Bill: Vol. 1 and Kill Bill: Vol. 2 – Does anything say perseverance more than the relentless training Black Mamba endured that enabled her to punch her way out of a coffin buried six feet under? Plus, there’s the unforgettable sword fight against O-Ren Ishii. See also: Jackie Brown and Shosanna from Inglorious Basterds. 20. Marge Gunderson from Fargo – My favorite movie character of all time, pregnant Marge is able to take down the über-violent bad guy single-handedly. Bonus points for her pregnancy having nothing to do with the movie’s plot. This is the list I can’t wait to work my way through with my daughter (and my son, for that matter). Who am I missing? Who’s on your list?
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HOME Tuesday, January 31, 2012 Saturation {teaching photographer in suwanee georgia} I spoke with new photographer today about saturation today and she had some questions. I thought I would share with you all what we discussed. In my experience, if one person has a question about a topic at least 10 other people have those same questions! So here goes... Saturation - Color saturation is used to describe the intensity of color in the image. De-Saturate: To take out the intensity of color in the image. Sometimes photographers will intentioally overly saturate to pop the color in an image. Sometimes photographer will intentionally de-saturate an image to create mood. A lot of images taken in the 70's were de-saturated! :) One thing I would personally stay away from is de-saturting skin tones. It makes people look dull and lifeless. If you want the desaturated look on your image you can use a hue/saturated adjustment layer in photoshop and then mask back in your skin tones to taste. Below I have shown an image saturated 4 different ways. I did this by adding a hue/saturation adjustment layer to each image and pulling the saturation out with the slider to the left. As you can see, when you completely de-saturate an image, you end up with no color. These images are referred to as a greyscale or a black & white images. I do not recommend achieving black and white images by pulling out all of the saturation. Remember light has a color. Photography is the art of painting with light so, If you rid an image of all color....you are making the light in your image colorless and flat as well. As you can see a completely de-saturated image results in a flat B&W's because the image has been rid of all color. I prefer to use the channel mixer or a gradient map for B&W's. They keep the "color" of light in tact and therefore give your black and whites more dimension.
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Amos Sutton Amos Sutton (1802 in Sevenoaks in Kent – 17 August 1854 in Cuttack, Odisha) was an English General Baptist missionary to Odisha, India, and hymn writer. He published the first English grammar of the Odia language (1831), a History (1839), and Geography (1840), then the first dictionary of Odia (1841–43), as well as a translation of the Bible (1842–45). He also composed a hymn to the tune of "Auld Lang Syne": "Hail, sweetest, dearest tie, that binds" and wrote a History of the mission to Orissa: the site of the temple of Juggernaut (1835). Biography At the age of 21, he was recruited by General Baptist Foreign Missionary Society for missionary service. He was trained for the ministry under J.G. Pike, founder of the Connexion's Missionary Society in Derby. After a brief period in home ministry, he was sent as a missionary to India in 1824 by Baptist Missionary Society, two years after William Bampton and James Peggs, the first two Baptist missionaries, had entered Odisha. Sutton along with his wife, Charlotte Sutton née Collins, sailed to Calcutta (now Kolkata) and joined the missionary work at station Cuttack in modern-day Odisha on 11 March 1825. Soon after their arrival to his mission station, his first wife Charlotte died in Puri due to sickness. He later married Elizabeth Coleman, an American Baptist missionary widow. Missionary work The missionary began the evangelism and recorded the first Odia conversion in 1828. By 1841, Sutton had trained three Odia evangelists at Cuttack. By 1846, when the students increased to eight, he formalised the class as the Cuttack Mission Academy. By 1805, the Baptist missionary society and later Amos Sutton under the auspices of Serampore Trio — William Carey, Joshua Marshman, and William Ward—attempted to preach to Telugu-speaking people in the northernmost parts of present Andhra Pradesh — adjoining areas of Odisha such as Chicacole (present Srikakulam) and Vizagapatnam (present Vizag or Visakhapatnam). Baptist missionary attempts and Amos Sutton's objective to evangelize Telugus failed and the missionaries didn't venture to the Telugu regions again, confining themselves to Odia-speaking districts. As the Baptist Missionary Society was not able to support the Odisha missionary work, through his second wife he was able to get contact details of the American Free Will Baptists. Sutton contacted the Free Will Baptists Mission mentioning the great needs of Odisha and adjoining Telugu-speaking areas; accordingly, he received an invitation from the convention to visit America. Sutton and his wife visited England and the United States and spent two years between 1833 and 1835 sharing their mission fields. During their visit to United States, he spoke at the seventh General conference of the Free Will Baptists in October 1833 before an audience of 3,000 people inspiring them to devote their life to the missionary service. At this conference, Jeremiah Phillips and Eli Noyes came forward to offer their service to Odia-speaking people. While visiting his relatives in the United States in 1835, he urged the Baptist convention in Virginia to take over the abandoned work among the Telugus; accordingly, Samuel S. Day, a Canadian-born American Baptist missionary, and E. L. Abbot, including their wives were sent by American Baptist Foreign Mission Board to the Telugu-speaking provinces along with Sutton. On 22 September 1835, Amos Sutton, Jeremiah Phillips, Eli Noyes, Samuel S. Day, including their wives and several other missionaries sailed to India. After 136 days of sailing, they arrived Calcutta. From Calcutta, they travelled by land and joined their respective mission stations – E. L. Abbot departed to Burma, while the Day family proceeded to the Telugu-speaking provinces and arrived at Vizagapatnam – Amos Sutton, Eli Noyes, and Jeremiah Phillips proceeded to the Odia-speaking provinces and arrived at Cuttack where the British Baptist Missionaries were already working – Jeremiah Phillips and Eli Noyes dedicated their missionary service to Santals. Amos Sutton soon became the corresponding secretary of the new Free Will Baptist Missionary. Bibliography Sutton devoted himself to learning the local Odia language, as soon as he arrived the mission station. Sutton being a gifted translator, soon compiled an Odia grammar, and dictionary in three volumes, as well as translating a number of English books such as Pilgrim's Progress by John Bunyan – in Odia named Swaga Jatrira Britanta – and also a complete translation of the Bible. Amos Sutton's Introductory Grammar of Oriya language published in 1831, happens to be the oldest publication available in the Oriya Language Collection to date. He published the first volume of his Odia dictionary in 1841, and the next two volumes by 1843. It was printed in the Odisha mission press at Cuttack. The Odia dictionary gives Odia meaning of Odia words with English synonyms. Sutton also prepared a dictionary named Sadhu Bhasharthabhidhan, a vocabulary of current Sanskrit terms with Odia definitions which was also printed in Odisha mission press in 1844. He published Dharmapustakara Adibhaya between 1842 and 1843. He also published the History of the Mission To Orissa: The Site of the Temple of Juggernaut in 1835. In addition to Odia tracts, he published A Narrative of the Mission to Orissa in 1844, Orissa and its Evangelization in 1850, an autobiography, the Happy Transformation in 1844, and compiled Padarthavidyasara to be taught as textbook in the schools of Odisha. As a hymn writer, he prepared the first Odia hymn book—179 of the hymns being of his own composition. He composed hymns, especially for divine worship, public, private, and social occasions. Amos Sutton's hymns appear to have been the first Protestant hymnal printed in India. On his visit to England in 1833, he composed a farewell hymn to the tune of Auld Lang Syne – "Hail sweetest, dearest tie, that binds". This soon became very popular and is still in common use. Awards A degree of D.D. was conferred on him by the College of Waterville, USA. See also The British missionary societies Pyarimohan Acharya References 15. Unnavimsa Satabdiku Missionary Dr. Amos Suttonnka Dana by Dr. Smaran Kumar Nayak (The Contribution of Missionary Dr. Amos Sutton to Nineteenth Century Orissa, Published by Jagannath Ratha, Cuttack. 16. History of the Oriya Missionary Literature by Dr. Smaran Kumar Nayak. 17. The History of Orissa Mission Press by Dr. Smaran Kumar Nayak. External links Annual report, Issues 1–18 – American and Foreign Bible Society, Bible Convention Missionary Position: The Irony of Translational Activism in Colonial Orissa ORISSA in the CROSSFIRE Category:1854 deaths Category:Baptist missionaries in India Category:1802 births Category:19th-century English people Category:English Baptist missionaries Category:English hymnwriters Category:19th-century Baptist ministers Category:English Baptist ministers Category:19th-century English musicians Category:Odia-language writers
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Summary The activities of some non-governmental organizations (NGOs) challenge governments on politically sensitive issues such as social, humanitarian, and environmental policies. As a result, these organizations are often exposed to increased government-directed threats aimed at monitoring their activities, discrediting their work, or stealing their intellectual property. BRONZE PRESIDENT is a likely People's Republic of China (PRC)-based targeted cyberespionage group that uses both proprietary and publicly available tools to target NGO networks. Secureworks® Counter Threat Unit™ (CTU) researchers have observed BRONZE PRESIDENT activity since mid-2018 but identified artifacts suggesting that the threat actors may have been conducting network intrusions as far back as 2014. CTU™ researchers divided the threat intelligence about this threat group into two sections: strategic and tactical. Executives can use the strategic assessment of the ongoing threat to determine how to reduce risk to their organization's mission and critical assets. Computer network defenders can use the tactical information gathered from incident response investigations and research to reduce the time and effort associated with responding to the threat group's activities. Key points The BRONZE PRESIDENT cyberespionage group targets NGOs, as well as political and law enforcement organizations in countries in South and East Asia. The threat group appears to have developed its own remote access tools that it uses alongside publicly available remote access and post-compromise toolsets. After compromising a network, the threat actors elevate their privileges and install malware on a large proportion of systems. The group runs custom batch scripts to collect specific file types and takes proactive steps to minimize detection of its activities. Strategic threat intelligence Analysis of a threat group's targeting, origin, and competencies can determine which organizations could be at risk. This information can help organizations make strategic defensive decisions in relation to the BRONZE PRESIDENT threat group. Intent CTU researchers have observed BRONZE PRESIDENT targeting multiple NGOs. The threat actors steal data from compromised systems over a long period of time, which likely indicates a long-term objective of monitoring the target's network. BRONZE PRESIDENT uses custom batch scripts to collect either specific file types (including files with .pptx, .xlsx, .pdf extensions) or all files within a specific location. CTU researchers also observed evidence that the threat actors collect credentials from high-privilege network accounts and reputationally sensitive accounts, such as social media and webmail accounts. Additionally, CTU researchers have observed evidence of BRONZE PRESIDENT targeting political and law enforcement organizations in countries adjacent to the PRC, including Mongolia and India. Some of the group's phishing lures suggest an interest in national security, humanitarian, and law enforcement organizations in the East, South, and Southeast Asia (see Figure 1). These examples reveal BRONZE PRESIDENT's likely intent to conduct political espionage in other countries in addition to targeting NGOs. Figure 1. August 2019 phishing lure referencing Mongolian national security topics. (Source: Secureworks) Attribution It is highly likely that BRONZE PRESIDENT is based in the PRC due to the following observations: The NGOs targeted by BRONZE PRESIDENT conduct research on issues relevant to the PRC. Strong evidence links BRONZE PRESIDENT's infrastructure to entities within the PRC. There are connections between a subset of the group's operational infrastructure and PRC-based Internet service providers. Tools such as PlugX have historically been leveraged by threat groups operating in the PRC. It is likely that BRONZE PRESIDENT is sponsored or at least tolerated by the PRC government. The threat group's systemic long-term targeting of NGO and political networks does not align with patriotic or criminal threat groups. Capability BRONZE PRESIDENT has deployed a variety of remote access tools. The use of tools not previously observed by CTU researchers suggests that the group could have access to malware development capabilities. BRONZE PRESIDENT also uses widely available or modified open-source tools, which could be a strategic effort to reduce the risk of attribution or to minimize the need for tool development resources. Following a network compromise, the threat actors typically delete their tools and processes. However, the group is content leaving some malware on the network, likely to provide a contingency if other access channels are removed. When the group's activities were detected in one incident, it had elevated privileges and had maintained access to the targeted environment for several months. This finding indicates the group's effectiveness at maintaining long-term access to a targeted network. Tactical threat intelligence Incident response engagements have given CTU researchers insight into the threat group's tools and tactics. Tools CTU researchers and Secureworks incident responders have observed BRONZE PRESIDENT using the following tools, along with several custom batch scripts for locating and archiving specific file types: Cobalt Strike — This popular and commercially available penetration tool gains shell access to an infected system. It allows threat actors to execute additional tools and perform post-intrusion actions on compromised systems. Cobalt Strike appears to be one of BRONZE PRESIDENT's preferred remote access tools. During one intrusion, the threat actors installed it on over 70% of accessible hosts. The group's Cobalt Strike installation typically uses a payload named svchost.exe in an attempt to disguise Cobalt Strike activity as the legitimate Windows svchost.exe executable. PlugX — This remote access trojan (RAT) is popular among PRC-based targeted threat groups. Its functionality includes uploading and downloading files, and it has configurable network protocols. BRONZE PRESIDENT installs PlugX using DLL side-loading. In June and August 2019, BRONZE PRESIDENT delivered PlugX via government and law enforcement-themed phishing lures. ORat — CTU researchers have only observed this basic loader tool in the context of BRONZE PRESIDENT intrusions. ORat is the name assigned by the malware author, as denoted by the program debug database string in the analyzed sample: D:\vswork\Plugin\ORat\build\Release\ORatServer\Loader.pdb. The tool uses the Windows Management Instrumentation (WMI) event consumer for persistence by installing a script to the system's WMI registry. Messages sent from ORat to its command and control (C2) server start with the string "VIEWS0018x". If the data received from the C2 server starts with the same string, then the remainder of the payload is decompressed using ORat's "deflate" algorithm and called as a function. ORat acts as a flexible loader tool rather than a fully featured remote access tool. RCSession — This basic RAT is installed via DLL side-loading, and CTU researchers observed BRONZE PRESIDENT installing it on multiple hosts during intrusions. RCSession was extracted from a file called English.rtf and launched via a hollowed svchost.exe process. RCSession connects to its C2 server via a custom protocol, can remotely execute commands, and can launch additional tools. CTU researchers have no evidence of other threat actors using RCSession or of wide proliferation of the tool, suggesting it may be exclusively used by BRONZE PRESIDENT. Nbtscan — This publicly available command-line tool scans systems for NetBIOS name information (see Figure 2). In an example observed by CTU researchers, the Nbtscan executable was named Adobe.exe and was installed in several working directories on compromised hosts, including: C:\Recovery\. Figure 2. Nbtscan being used via RCSession to scan an internal IP range. (Source: Secureworks) Figure 2. Nbtscan being used via RCSession to scan an internal IP range. (Source: Secureworks) Nmap — BRONZE PRESIDENT used this freely available network scanning tool from the C:\PerfLogs\ folder. Wmiexec — This publicly available tool uses WMI to create SYSTEM-level shells on remote hosts. Links to other malware While analyzing hosts compromised by BRONZE PRESIDENT, CTU researchers identified other malware artifacts. Although there was no evidence of the group using the malware, the threat actors may have leveraged its access or capabilities during earlier phases of the intrusions. The BRONZE PRESIDENT intrusions observed by CTU researchers appear to have taken place over several months or years. China Chopper web shell files named error404.aspx included the "eval(Request.Item["|"],"unsafe");" string. To successfully interact with the web shell, a threat actor sent HTTP requests that included the "|" parameter. The web shell files appeared to be installed during the timeframe that BRONZE PRESIDENT was active on the system (see Figure 3). Figure 3. Timeline of malicious tool use on a compromised host. (Source: Secureworks) CTU researchers identified a variety of post-compromise tools stored under %AppData% (e.g., \AppData\Roaming\Temp) on several compromised systems. The widespread proliferation and use of the following tools suggest that the group likely has the knowledge and capability to use them as part of its operations: Powerview.ps1 — This PowerShell-based module for network reconnaissance is part of the PowerSploit penetration testing framework. PVE Find AD User — This command-line tool identifies login locations of Active Directory (AD) users. AdFind — This command-line tool conducts AD queries. NetSess — This publicly available tool enumerates NetBIOS sessions. Netview — This tool enumerates networks. TeamViewer — This remote control and desktop-sharing tool has applications for legitimate and malicious system users. Its installation in a temporary directory alongside network reconnaissance and enumeration tools likely indicates malicious intent. Initial access and working directories At the time of detection, observed BRONZE PRESIDENT incidents had likely been ongoing for several months or even years. As a result, CTU researchers were unable to ascertain the initial access vector. In October 2019, third-party researchers described a phishing campaign that used C2 infrastructure that CTU researchers attribute to BRONZE PRESIDENT. This connection suggests that the group uses phishing emails with ZIP attachments that contain LNK files as an initial access vector. During one intrusion, the threat actors gained administrator access to all systems within a targeted business unit and installed their remote access tools on 80% of the hosts. The group installed multiple tools within the environment, including three different tools on a strategically important server, likely to provide contingency access options (see Table 1). HOST Cobalt Strike RCSession ORat Host 1 (Server) X X X Host 2 (User PC) X Host 3 (User PC) X X Host 4 (User PC) X Host 5 (User PC) X Host 6 (User PC) X X Host 7 (User PC) X Table 1. Remote access tools identified on infected hosts during a BRONZE PRESIDENT intrusion. BRONZE PRESIDENT used multiple directories to install tools on compromised hosts (see Table 2). Directory Associated tool C:\RECYCLER\ ORat C:\Windows\Help\Help\ Cobalt Strike C:\Windows\debug\WIA\ Cobalt Strike C:\Windows\Logs\DPX\ Cobalt Strike C:\PerfLogs\ RCSession C:\Recovery\ Nbtscan Table 2. Directories used by BRONZE PRESIDENT to execute or store tools. Network enumeration, lateral movement, and credential access During multiple intrusions, the threat actors employed various tools and techniques to understand the network environments. For example, they used Nmap to scan various internal IP address ranges and SMB ports (see Figure 4). They also relied on Nbtscan, net user, and ping commands to obtain insights and identify opportunities for lateral movement. Figure 4. Nmap network scanning tool use via RCSession. (Source: Secureworks) BRONZE PRESIDENT regularly leverages Wmiexec to move laterally. During one intrusion, the threat actors extensively used this tool to execute WMI commands on remote hosts in the environment (see Figure 5). Figure 5. Wmiexec used to execute commands on a targeted host. (Source: Secureworks) They also frequently leverage net commands to connect to other hosts (see Figure 6) using compromised credentials collected during early phases of the intrusion. Figure 6. BRONZE PRESIDENT Nbtscan use and net commands. (Source: Secureworks) During one intrusion observed by CTU researchers, the group used the native vssadmin tool on a domain controller to create a volume shadow copy: vssadmin create shadow /for=c: The threat actors retrieved the NTDS.dit file from the volume shadow copy. NTDS.dit contains Active Directory data, including password hashes for all users on a domain. Extracting hashes from the NTDS.dit file requires access to the SYSTEM file in the system registry: reg save hklm\system c:\windows\temp\system.hive The threat actors saved both the SYSTEM file (system.hive) and NTDS.dit in the compromised host's c:\windows\temp directory. These files were likely exfiltrated and exploited offline to retrieve user password hashes, which could then be cracked or used to perform pass-the-hash attacks. C2 communications and infrastructure BRONZE PRESIDENT's C2 techniques are dictated by its remote access tools. The group's primary and likely proprietary RCSession RAT communicates with a hard-coded C2 server using a custom protocol over TCP port 443. After connecting to its C2 server, RCSession checks in with an encrypted beacon and then awaits instruction. The ORat tool, which appears to be used less frequently by the group, communicates over TCP port 80 using a raw socket protocol (not HTTP). The Cobalt Strike tool has malleable C2 profiles. During one intrusion, it connected to multiple C2 domains on TCP port 80, including mail . svrchost . com, using the following request. Subsequent Cobalt Strike C2 servers included subdomains of svchosts . com, svrchost . com, and strust . club. GET /Dv9i HTTP/1.1 User-Agent: Mozilla/4.0 (compatible; MSIE 8.0; Windows NT 5.1; Trident/4.0) Host: mail . svrchost . com Connection: Keep-Alive Cache-Control: no-cache Some BRONZE PRESIDENT C2 domains analyzed by CTU researchers were hosted on infrastructure owned by Dutch VPS provider Host Sailor, Hong Kong-based New World Telecoms, and Malaysia-based Shinjiru Technology (see Figure 7). The threat actors have used discrete infrastructure clusters that share matching hosting and registration characteristics. The pattern of infrastructure hosting suggests that the group parks its domains when not in use, an operational security technique that limits exposure of the group's overall hosting infrastructure. Figure 7. Hosting for a subset of BRONZE PRESIDENT C2 domains. (Source: Secureworks) Persistence, defensive evasion, and exfiltration Some of BRONZE PRESIDENT's malware has persistence capabilities. For example, ORat uses a WMI event consumer to maintain its presence on a compromised host. The group also creates and maintains scheduled tasks to achieve this purpose. Figure 8 shows a Sysdriver scheduled task that periodically executes a Cobalt Strike payload. Figure 8. BRONZE PRESIDENT scheduled task created for Cobalt Strike persistence. (Source: Secureworks) The threat actors tend to install malware on a large proportion of hosts during their intrusions. However, the group exercises restraint and defensive evasion tactics to minimize opportunities for network defenders to detect or investigate its activities. For example, the threat actors deleted volume shadow copies after using them for NTDS.dit retrieval: vssadmin delete shadows /for=c: /quiet Likewise, the group demonstrated diligence by killing local and remote processes after they had been used: taskkill /im svchosts.exe /F taskkill /S <REMOTE SYSTEM NAME> /U <USERNAME> /P <PASSWORD> /im svchost.exe BRONZE PRESIDENT targets specific data types. The threat actors use custom batch scripts to create a list of files with predefined criteria and collate the identified files into a .rar archive (see Figure 9). CTU researchers have observed BRONZE PRESIDENT batch scripts named doc.bat, xls.bat, xlsx.bat, ppt.bat, pptx.bat, pdf.bat, and txt.bat. Figure 9. Batch script (pptx.bat) used to collate and archive all .pptx files in a defined location. (Source: Secureworks) The group also uses the all.bat batch script to collect all files stored on a specific user's desktop. CTU researchers observed RCSession and Cobalt Strike on systems that BRONZE PRESIDENT targeted for data theft. Either of these tools could have been used to exfiltrate the archived data. Conclusion BRONZE PRESIDENT has demonstrated intent to steal data from organizations using tools such as Cobalt Strike, PlugX, ORat, and RCSession. The concurrent use of so many tools during a single intrusion suggests that the group could include threat actors with distinct tactics, roles, and tool preferences. It is likely that BRONZE PRESIDENT has additional unobserved operational tools and capabilities. CTU researchers recommend that organizations apply controls to mitigate common intrusion techniques and behaviors along with controls that address the tools and techniques discussed in this analysis. Threat indicators The threat indicators in Table 3 are associated with BRONZE PRESIDENT threat campaigns. Note that IP addresses can be reallocated. The IP address and domains may contain malicious content, so consider the risks before opening them in a browser. Indicator Type Context ipsoftwarelabs.com Domain name PlugX C2 server toshibadrive.com Domain name RCSession C2 server strust.club Domain name ORat and Cobalt Strike C2 server svchosts.com Domain name Cobalt Strike C2 server svrhosts.com Domain name Cobalt Strike C2 server 116.93.154.250 IP address Cobalt Strike download location forexdualsystem.com Domain name Used by BRONZE PRESIDENT to check a compromised system's connectivity apple-net.com Domain name Linked to BRONZE PRESIDENT domain (forexdualsystem . com) lionforcesystems.com Domain name Linked to BRONZE PRESIDENT domain (forexdualsystem . com) wbemsystem.com Domain name Linked to BRONZE PRESIDENT domain (forexdualsystem . com) a0758535cf8eb689782b95d3791d23d5 MD5 hash ORat malware sample 774a9c3ff01a3e734b7bec0c312120126295fad9 SHA1 hash ORat malware sample 2e8762c984468ee309dad30a6c5f6d3308676ac721357da 442a8a5b9d9d65d82 SHA256 hash ORat malware sample 7101fff478290d4db8a1c11a8d3b40cb MD5 hash Cobalt Strike payload 4c81777551a772218519fb6dd1a6672aade4a936 SHA1 hash Cobalt Strike payload bdf1452b55b9974f3e9a4aea4439769a02fd931660ed 655df92519a2a4df1261 SHA256 hash Cobalt Strike payload 5f626148bb2505f91f82da718487ca45 MD5 hash Cobalt Strike payload c72cc22ad328946201b069cddae0eee021d687b1 SHA1 hash Cobalt Strike payload cfa73718e16b499c34951cc5c857cd35bf263f94efa7e1 518cddf27766fb0d2f SHA256 hash Cobalt Strike payload dllhosts.exe Filename Cobalt Strike payload 0617cad9e5d559356c43d4037c86227f MD5 hash Modified DLL file (goopdate.dll) used by BRONZE PRESIDENT to install RCSession f14eaf5d648aebb2ed7b00b2cf4349263b30fb1c SHA1 hash Modified DLL file (goopdate.dll) used by BRONZE PRESIDENT to install RCSession 2ea9ccf653f63bcc3549a313ec9d0bada341556 cc32dd2ca4b73e0c034492740 SHA256 hash Modified DLL file (goopdate.dll) used by BRONZE PRESIDENT to install RCSession 2433a0a2b1bfcbdccdca665cd758a6ad MD5 hash RCSession payload (English.rtf) 603babf64a62989bf00e124955471519f0d8e8ed SHA1 hash RCSession payload (English.rtf) 357943c55c7d6580dd7b91b832b6424403e9d 22b38c615ebac0990eb4cce104c SHA256 hash RCSession payload (English.rtf) 3935da25054700d7b996f5f67de39492 MD5 hash Modified DLL file (goopdate.dll) used by BRONZE PRESIDENT to install RCSession fcb799d02e6c1b4ac76ec8c5e704c7c511762d2d SHA1 hash Modified DLL file (goopdate.dll) used by BRONZE PRESIDENT to install RCSession d0df97adc2a98c02c0adc407fd13040af972106c 2bb24726e963c63f7ab4634d SHA256 hash Modified DLL file (goopdate.dll) used by BRONZE PRESIDENT to install RCSession 6f88260cbc97e60c03e9d91b7e4761a5 MD5 hash RCSession payload (English.rtf ed8ad981c73ed444f1b89c4bda71ed99ca966c5a SHA1 hash RCSession payload (English.rtf) 41ca0ea774b3fdee2ac5b23c95aba0d e6e24e261e71c26bf1d880932ba954e15 SHA256 hash RCSession payload (English.rtf) NATIONAL SECURITY CONCEPT OF MONGOLIA.exe Filename ORat malware sample 0d3fbc842a430f5367d480dd1b74449b MD5 hash Associated with BRONZE PRESIDENT phishing lure delivering PlugX bd2533005a2eaed203054fd649fdbdcd3e3a860a SHA1 hash Associated with BRONZE PRESIDENT phishing lure delivering PlugX 59aaa2b8116ba01c1b37937db37213ff1f4a855 2a7211ab21f73ffac2c0c13ce SHA256 hash Associated with BRONZE PRESIDENT phishing lure delivering PlugX DSR & CSR of Special Branch Sind.exe Filename Associated with BRONZE PRESIDENT phishing lure delivering PlugX e5a23e8a2c0f98850b1a43b595c08e63 MD5 hash Associated with BRONZE PRESIDENT phishing lure delivering PlugX 9136eed34bea473d0f8554fb1d914502b832f219 SHA1 hash Associated with BRONZE PRESIDENT phishing lure delivering PlugX 918de40e8ba7e9c1ba555aa22c8acbfdf77f9 c050d5ddcd7bd0e3221195c876f SHA256 hash Associated with BRONZE PRESIDENT phishing lure delivering PlugX Daily News (19-8-2019)(Soft Copy).lnk Filename Associated with BRONZE PRESIDENT phishing lure delivering PlugX 5f094cb3b92524fced2731c57d305e78 MD5 hash Associated with BRONZE PRESIDENT phishing lure delivering PlugX 1a2f1c97a5883e8bb4edcdacfe176da98b266b42 SHA1 hash Associated with BRONZE PRESIDENT phishing lure delivering PlugX fb3e3d9671bb733fcecd6900def15b9a6b4f36b 0a35bdc769b0a69bc5fb7e40d SHA256 hash Associated with BRONZE PRESIDENT phishing lure delivering PlugX Table 3. BRONZE PRESIDENT indicators.
Mid
[ 0.5550660792951541, 31.5, 25.25 ]
/** * Licensed to the Apache Software Foundation (ASF) under one * or more contributor license agreements. See the NOTICE file * distributed with this work for additional information * regarding copyright ownership. The ASF licenses this file * to you under the Apache License, Version 2.0 (the * "License"); you may not use this file except in compliance * with the License. You may obtain a copy of the License at * * http://www.apache.org/licenses/LICENSE-2.0 * * Unless required by applicable law or agreed to in writing, software * distributed under the License is distributed on an "AS IS" BASIS, * WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied. * See the License for the specific language governing permissions and * limitations under the License. */ package org.apache.hadoop.yarn.server.nodemanager.containermanager.scheduler; import org.apache.hadoop.yarn.api.records.ResourceUtilization; import org.apache.hadoop.yarn.server.nodemanager.containermanager.container.Container; import org.apache.hadoop.yarn.server.nodemanager.containermanager.monitor.ContainersMonitor; import org.slf4j.Logger; import org.slf4j.LoggerFactory; /** * An implementation of the {@link ResourceUtilizationTracker} that equates * resource utilization with the total resource allocated to the container. */ public class AllocationBasedResourceUtilizationTracker implements ResourceUtilizationTracker { private static final Logger LOG = LoggerFactory.getLogger(AllocationBasedResourceUtilizationTracker.class); private ResourceUtilization containersAllocation; private ContainerScheduler scheduler; AllocationBasedResourceUtilizationTracker(ContainerScheduler scheduler) { this.containersAllocation = ResourceUtilization.newInstance(0, 0, 0.0f); this.scheduler = scheduler; } /** * Get the accumulation of totally allocated resources to a container. * @return ResourceUtilization Resource Utilization. */ @Override public ResourceUtilization getCurrentUtilization() { return this.containersAllocation; } /** * Add Container's resources to the accumulated Utilization. * @param container Container. */ @Override public void addContainerResources(Container container) { ContainersMonitor.increaseResourceUtilization( getContainersMonitor(), this.containersAllocation, container.getResource()); } /** * Subtract Container's resources to the accumulated Utilization. * @param container Container. */ @Override public void subtractContainerResource(Container container) { ContainersMonitor.decreaseResourceUtilization( getContainersMonitor(), this.containersAllocation, container.getResource()); } /** * Check if NM has resources available currently to run the container. * @param container Container. * @return True, if NM has resources available currently to run the container. */ @Override public boolean hasResourcesAvailable(Container container) { long pMemBytes = container.getResource().getMemorySize() * 1024 * 1024L; return hasResourcesAvailable(pMemBytes, (long) (getContainersMonitor().getVmemRatio()* pMemBytes), container.getResource().getVirtualCores()); } private boolean hasResourcesAvailable(long pMemBytes, long vMemBytes, int cpuVcores) { // Check physical memory. if (LOG.isDebugEnabled()) { LOG.debug("pMemCheck [current={} + asked={} > allowed={}]", this.containersAllocation.getPhysicalMemory(), (pMemBytes >> 20), (getContainersMonitor().getPmemAllocatedForContainers() >> 20)); } if (this.containersAllocation.getPhysicalMemory() + (int) (pMemBytes >> 20) > (int) (getContainersMonitor() .getPmemAllocatedForContainers() >> 20)) { return false; } if (LOG.isDebugEnabled()) { LOG.debug("before vMemCheck" + "[isEnabled={}, current={} + asked={} > allowed={}]", getContainersMonitor().isVmemCheckEnabled(), this.containersAllocation.getVirtualMemory(), (vMemBytes >> 20), (getContainersMonitor().getVmemAllocatedForContainers() >> 20)); } // Check virtual memory. if (getContainersMonitor().isVmemCheckEnabled() && this.containersAllocation.getVirtualMemory() + (int) (vMemBytes >> 20) > (int) (getContainersMonitor() .getVmemAllocatedForContainers() >> 20)) { return false; } LOG.debug("before cpuCheck [asked={} > allowed={}]", this.containersAllocation.getCPU(), getContainersMonitor().getVCoresAllocatedForContainers()); // Check CPU. if (this.containersAllocation.getCPU() + cpuVcores > getContainersMonitor().getVCoresAllocatedForContainers()) { return false; } return true; } public ContainersMonitor getContainersMonitor() { return this.scheduler.getContainersMonitor(); } }
Mid
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848 F.2d 701 56 USLW 2714 MacArthur DRAKE, et al., Plaintiffs-Appellants,v.Keith L. GORDON, et al., Defendants-Appellees. No. 86-2031. United States Court of Appeals,Sixth Circuit. Argued Oct. 23, 1987.Decided June 3, 1988. Gilbert King (argued), Gary, Ind., for plaintiffs-appellants. Macarthur Drake, Gary, Ind., pro se. R. Stephen Olsen (argued), Ann Arbor, Mich., for defendants-appellees. Before LIVELY and WELLFORD, Circuit Judges; and McRAE, District Judge.* WELLFORD, Circuit Judge. 1 Plaintiffs, Indiana residents, were passengers in an automobile struck from the rear in Jackson County, Michigan, by an automobile owned by defendant Cynthia Gordon and driven by defendant Keith Gordon. Plaintiffs filed suit against defendants alleging that at the time of the collision they had been in Michigan less than 30 days during the year 1984 and that their vehicle was not covered by an insurer filing a certification in compliance with Sec. 3163 of the Michigan No Fault Statute ("MNFS").1 Defendants respond that these claims are not substantiated in the record, but, in any event, defendants claim that MNFS bars the damage claims of the plaintiffs. 2 At the time of the accident, August 12, 1984, the parties agree that defendant Cynthia Gordon was registered in Michigan and was covered by an automobile insurance policy procured in compliance with MNFS. Defendant, Keith Gordon, was not a named insured on a policy certified under Sec. 3163, but defendants assert that he was an insured under Cynthia Gordon's policy as a permissive driver or user. Defendants claim that this action is controlled by the MNFS, and for the purposes of summary judgment they admitted that the injuries and damages claimed by plaintiffs were proximately caused by negligence attributable to defendants. The question in this case is whether MNFS is controlling under these circumstances. 3 The district court held that the mere fortuity of involvement in an auto accident with non-residents should not require the Michigan resident defendants to be subject to tort liability which is expressly barred by the MNFS. The court held that: 4 ... a non-resident, like a Michigan resident, may not recover non-economic damages for injuries sustained in a motor vehicle accident in Michigan unless his injuries satisfied the standard prescribed by M.C.L.A. Sec. 500.3135 and Cassidy v. McGovern [, 415 Mich. 483, 330 N.W.2d 22 (1982) ]. Such a result is not violative of the First and the Fourteenth Amendment rights of the non-residents. A non-resident should not be placed on a superior footing than a resident motorist with respect to his right to recover damages from a negligent operator of an automobile. 5 Drake v. Gordon, 644 F.Supp. 376, 379 (E.D.Mich.1986) (footnote omitted). 6 The first and basic issue is whether MNFS Sec. 3135 applies to a cause of action in tort by a non-resident victim of an automobile accident in Michigan caused by the negligence of a Michigan resident insured under the MNFS where the non-resident claimant had been travelling or operating a vehicle in Michigan less than 30 days and where the claimant's insurance was not certified under the MNFS. We conclude that MNFS is controlling under these circumstances. 7 M.S.A. Sec. 24.13102 [M.C.L. Sec. 500.3102] (1987) (MNFS Sec. 3102) provides in part that "(1) A nonresident owner or registrant of a motor vehicle not registered in this state shall not operate or permit the vehicle to be operated in this state for an aggregate of more than 30 days in any calendar year unless he or she continuously maintains security for the payment of benefits." Criminal penalties are set out for violators of the section. M.S.A. Sec. 24.13113 [M.C.L. Sec. 500.3113] (MNFS Sec. 3113) establishes that a "person is not entitled to be paid personal protection insurance benefits for accidental bodily injury if at the time of the accident any of the following circumstances existed: ... The person was not a resident of this state, was an occupant of a motor vehicle ... not registered in this state, and was not insured by an insurer which has filed a certification in compliance with section 3163 [MCL Sec. 500.3163]." Finally, M.S.A. Sec. 24.13135(2) [M.C.L. Sec. 500.3135(2) ] abolishes all "tort liability arising from the ownership, maintenance, or use within this state of a motor vehicle with respect to which the security required by section 3103(3) and (4) was in effect" with four exceptions. Section (1) of the statute provides that a "person remains subject to tort liability for noneconomic loss caused by his or her ownership, maintenance, or use of a motor vehicle only if the injured person has suffered death, serious impairment of bodily function, or permanent serious disfigurement." There is no such claim of impairment or disfigurement here involved. I. JURISDICTION 8 We first address in this appeal a jurisdictional question raised by this court at oral argument. Defendants initially denied the allegations of the complaint, specifically denying that plaintiffs were entitled to any recovery for property damage under the MNFS. Later, defendants filed a motion for partial summary judgment, asserting that no plaintiff had asserted a threshold claim of serious impairment, or otherwise, under the MNFS. In this motion, defendants did not specifically deal with liability for any part of the property damage claim. Plaintiffs responded to defendants' motion, and also filed a cross-motion for summary judgment, acknowledging that they did not fall within a specified exception to the MNFS. "Damages up to $400 to motor vehicles, to the extent that the damages are not covered by insurance" constitute an exception under MSA Sec. 24.13135(2)(d) [M.C.L. Sec. 500.3135(2)(d) ], MNFS Sec. 3135. Plaintiffs made no claim to an award under this exception, but did assert in a memorandum in support of their cross-motion that "Plaintiffs' vehicle was not covered by an insurer filing a certification in compliance with Section 3163 of the MNFS." 9 In ruling on these motions for summary judgment, the district court made no reference to the style of defendants' motion--that it was for partial summary judgment--and in making his ruling thereon, the district judge did not discuss the issue of property damage. At oral argument, defendants' counsel indicated that they owed plaintiffs $400 pursuant to the Sec. 24.13135(2)(d) exception of the MNFS.2 Plaintiffs, as pointed out, have made no specific claim of entitlement to this amount, although the complaint did assert that "plaintiff, Linda Drake, has incurred property loss." The parties apparently considered Judge LaPlata's oreder to have dealt with all the issues raised. His summary conclusion was simply that "a non-resident should not be placed on a superior footing than a resident motorist with respect to his right to recover damages from a negligent operator of an automobile." 644 F.Supp. at 379 (emphasis added). He did not indicate that "damages" referred only to those for injuries to the person exclusive from property damages. 10 Apparently in response to our question about the finality of the district court's order of October 6, 1986, the district judge entered a nunc pro tunc order of October 26, 1987 stating that the prior order had "disposed of the case in its entirety." Defendants have filed no supplemental or responsive brief dealing with this question. Plaintiffs maintain that there was a clear intent to adjudicate all claims on October 6, 1986; and that "nothing remains to be done before the district court in the instant case." (Appellant's supplemental brief filed November 5, 1987, at p. 2). They further maintain, without contravention, that the "parties understood the district court's 10/6/86 order to be a final, appealable order." (Id.). 11 We recognize that parties, even by express agreement, cannot confer jurisdiction on this court to entertain an appeal from something less than a final, appealable order which deals with all issues between all the parties to a controversy. 28 U.S.C. Sec. 1291; William B. Tanner Co. v. United States, 575 F.2d 101 (6th Cir.1978). Once a notice of appeal has been filed, the district court ordinarily loses jurisdiction to make any further determinative ruling in the case which is the subject of the notice of appeal. Island Creek Coal Sales Co. v. City of Gainesville, Fla., 764 F.2d 437 (6th Cir.), cert. denied, 474 U.S. 948, 106 S.Ct. 346, 88 L.Ed.2d 293 (1985). 12 Plaintiffs have made it clear at all times in the district court that they take the position that this action is not governed by the MNFS. They make no claim under that statute, nor do they make a claim under any of its expressed exceptions. They simply assert instead that its limitations upon tort recovery were "not intended ... to pertain to non-residents of Michigan under the circumstances." (Plaintiff's Memorandum in support of plaintiffs' cross-motion for summary judgment, J/A A-62, A-63). In their brief in opposition to defendants' motion as one for "Summary Judgment" not partial summary judgment. (J/A A-75). Defendants' own responsive brief to plaintiffs' motion in the district court refers to their "motion for summary judgment," not for partial summary judgment. (J/A A-76). The latter also referred to purported deposition testimony of MacArthur Drake that "he thought his wife did have liability insurance on the motor vehicle but there was no collision coverage," and that Linda Drake stated "that she thought her vehicle was uninsured at the time." (J/A A-78). 13 While the question is not free from doubt, we conclude that plaintiffs expressly waived a property damage claim in the district court if the MNFS statute were held applicable to their causes of action set forth in their complaint. The district court order of October 6, 1986, therefore, did deal with all the issues before it and was an appealable order. Defendants' counsel's reference at oral argument to an amount which he felt may be owed to plaintiffs for property damage to their car was not a matter remaining before the district court for disposition. We therefore determine that there is jurisdiction for us to decide the merits of this appeal. 14 II. APPLICABILITY OF MICHIGAN NO FAULT STATUTE 15 Plaintiffs do not seek personal injury protection benefits under the MNFS, but instead seek recovery under the common law tort of negligence. Plaintiffs claim that they were not required to maintain security for the payment of benefits under MNFS Sec. 3102(1) because they were not operating a motor vehicle in the state for more than 30 days in the calendar year of 1984. MNFS Sec. 3113(c) excludes such plaintiffs, who are not insured by an insurer who has filed a certification, from entitlement to the no-fault benefits. Thus, plaintiffs assert that MNFS totally excludes persons who are non-residents, travelling in the state for less than 30 days, and who do not carry insurance certified under the Act. They therefore seek a common law remedy for negligence. Plaintiffs interpret MNFS as permitting their common law remedy to remain available to them, relying upon Shavers v. Kelley, 402 Mich. 554, 267 N.W.2d 72 (1978), cert. denied sub nom. Allstate Ins. Co. v. Kelley, 442 U.S. 934, 99 S.Ct. 2869, 61 L.Ed.2d 303 (1979) and the "rule of literalness" so that MNFS would apply only to tortfeasors and victims subject to the security requirement provisions of the statute. Plaintiffs argue that a common law tort remedy is still recognized in Michigan under MNFS, because there remains a continuing right to recover for loss of consortium. See Cotton v. Minter, 469 F.Supp. 199 (E.D.Mich.1979). 16 Defendants argue, on the other hand, that Sec. 3135(1) establishes a "threshold" requirement for recovery for non-economic loss for tort liability in Michigan as to any plaintiff injured on Michigan highways. This threshold requires that plaintiff must first establish death, serious impairment of body funciton or permanent serious disfigurement as a result of the accident before there can be any recovery. Defendants claim that this threshold test applies to all plaintiffs whether insured or not. See Shavers, supra; Bradley v. Mid-Century Ins. Co., 409 Mich. 1, 294 N.W.2d 141 (1980). Since plaintiffs concede that no such threshold injury is here involved, defendants contend they are barred from recovering for non-economic injury, although defendants would admit liability for $400.00 in damages to the plaintiffs' motor vehicle under Sec. 3135(2)(d) of MNFS as a specified exception to the total abolishment of all tort liability under Sec. 3135(2) if properly asserted and proved by plaintiff. 17 Defendants emphasize that plaintiffs could have purchased insurance that complies with the Michigan no-fault requirements under Sec. 31633 and then would have been permitted to recover for both personal injuries and property damage. Thus, defendants maintain that those who pay into the system may receive the benefits provided for by the Michigan Act, which is applicable to all who travel on Michigan's roads whether residents or non-residents. Defendants claim therefore that residency has no bearing on the applicability of Sec. 3135. 18 Plaintiffs respond by urging that the purpose of the MNFS is to replace tort recovery with MNFS benefits for those complying with the statute. Plaintiffs claim that MNFS was not intended to exclude or deny recovery from those not bound by the MNFS, citing Rusinek v. Schultz, Snyder & Steele Lumber Co., 411 Mich. 502, 309 N.W.2d 163 (1981) (because the Michigan legislature did not expressly extinguish plaintiffs' common-law right to recover in tort, it should not be deemed to have done so implicitly.) In Rusinek, the Michigan Supreme Court held that since the language of Sec. 3135 did not expressly abolish the common law action for loss of consortium, it should decline to do so by implication. Rusinek held that permitting such a loss of consortium claim would not "contribute significantly to the problems the act was intended to alleviate", that is "to provide victims of motor vehicle accidents assured, adequate, and prompt reparation for certain economic losses through a system of compulsory insurance which would provide victims with benefits for their injuries as a substitute for their common-law remedy in tort." 309 N.W.2d at 164-66. Yet, in Rusinek, the statute was simply interpreted to permit a spouse of one who is seriously injured under Sec. 3135(1) to recover for loss of consortium. As explained in Cotton v. Minter, 469 F.Supp. 199, 201 (E.D.Mich.1979) "[n]o-fault's purpose was to litigate only cases where there are serious elements of noneconomic loss and bar those where such losses are small. Abolishing consortium would exclude no cases, and allowing it would not open the door to additional cases." Plaintiffs in this case do not claim severe injury and therefore do not fall within the provisions of Sec. 3135(1). We do not, therefore, believe that the Rusinek exception is applicable. 19 Gersten v. Blackwell, 111 Mich.App. 418, 314 N.W.2d 645 (1981) considered whether non-resident motorists in an accident in Michigan with a defendant insured under a Michigan no-fault automobile insurance policy could recover under Sec. 3135 of the Michigan No-Fault Act even though they suffered no serious impairment of a bodily function or a permanent serious disfigurement. Gersten found no problem with adhering to the MNFS statutory arrangement, holding that the non-resident motorists could not recover under the circumstances: "under Michigan's no-fault scheme, plaintiffs are denied personal injury protection benefits while simultaneously being prevented from pursuing tort remedies." 314 N.W.2d at 647. 20 Similarly, in Berrien County Road Commission v. Jones, 119 Mich.App. 315, 326 N.W.2d 495 (1982) the Michigan court held that a defendant truck driver had tort immunity under Sec. 3135(2) where he had voluntarily obtained no-fault Michigan insurance coverage, although not required to do so, and was involved later in an accident with a claimant who had not chosen to participate voluntarily in the Michigan plan. 21 No evidence of a legislative intent to exclude nonresident owners of motor vehicles appears. On the contrary, Sec. 3102 requires defendants' compliance with the security requirements of no-fault after a 30-day period. The 30-day period is to protect tourists and other transient nonresidents from the criminal sanctions imposed by the act. 22 326 N.W.2d at 496-97 (citation omitted) (emphasis in original). 23 It appears clear to us that under Gersten and the MNFS, plaintiff is denied the option of suing for common-law tort injury since the injuries claimed by plaintiffs to be attributable to defendants' negligence do not meet the threshold required under Sec. 3135(1), and because the plaintiffs did not choose to participate and to pay into the Michigan system. We must next consider whether under the facts of this case MNFS, as deemed applicable to plaintiffs' claims, violates due process or equal protection rights or the right to travel and thus is unconstitutional in its application. III. IS THE MNFS, AS APPLIED, CONSTITUTIONAL 24 Plaintiffs argue that the MNFS is facially overbroad because it imposes the same civil penalties upon transient non-resident plaintiffs as it does upon persons bound by Michigan law to comply with Secs. 3101-02 [M.C.L. Secs. 500.3101, 500.3102] but who fail to meet these requirements--the forfeiture of any civil recovery. They claim that this overbreadth and limitation upon a right to recover damages infringes upon their constitutional right to travel and is unconstitutional on its face. See Gooding v. Wilson, 405 U.S. 518, 92 S.Ct. 1103, 31 L.Ed.2d 408 (1972); Coates v. Cincinnati, 402 U.S. 611, 91 S.Ct. 1686, 29 L.Ed.2d 214 (1971). 25 Although the MNFS does impact upon travel within Michigan, it only does so through regulation of recovery for the negligence of another resulting in an automobile accident. Most states require motorists to carry insurance or furnish security in lieu of insurance as a necessary responsibility for the protection of all motorists while operating on the roads within that state. Such laws have been upheld as constitutional. See, e.g., Williams v. Newton, 236 So.2d 98 (Fla.S.Ct.1970); Bookbinder v. Hults, 19 Misc.2d 1062, 192 N.Y.S.2d 331 (1959). Plaintiffs complain about the loss of rights to recover civil damages, but they could have registered with the state, or they could have protected themselves by paying into the state's plan. In not taking these precautions, plaintiffs must look to their own insurance protection or their own resources for recovery of non-serious claims. Permitting plaintiffs under these circumstances to sue under common tort principles would circumvent the purpose of the MNFS. Michigan motorists or their insurance carriers would have to face litigation for non-serious injuries caused in an automobile accident contrary to the entire statutory scheme. Defendants argue that allowing plaintiffs to receive the benefits denied to those complying with MNFS would be unfair to all those who are required to pay into the plan. 26 We conclude that the MNFS does not penalize or punish plaintiffs for exercising their right to travel in the constitutional sense, but instead simply gives them options as to how they may want to protect themselves in the event, during a short visit, an accident occurs bringing about personal injuries within the State of Michigan. In view of the express purposes of MNFS and the growing and inhibiting expense of acquiring liability or other insurance absent such a law, we conclude that Michigan had a legitimate basis for its enactment, and that it is not unconstitutionally overbroad. 27 In a variation upon their charge of the statute's overbreadth, plaintiffs also contend that their equal protection rights have been violated because they have been treated differently from similarly situated persons under MNFS. The overbreadth argument is that the statute includes and abolishes tort remedies for a cognizant group, transient non-resident motorists. In asserting their equal protection claim, plaintiffs additionally contend that MNFS impermissibly distinguishes between resident and non-resident owners or registrants of motor vehicles operated within Michigan for more than thirty days within a year, and transient non-resident motorists (those only within Michigan for 30 days or less within a year). Those in the first group are required to maintain their entitlement to MNFS benefits and therefore have a remedy if in compliance with MNFS. Those in the second group, however, within which plaintiffs fall, are equally in compliance with the statute's prescriptions should they opt for travelling in Michigan for thirty days or less without obtaining coverage under MNFS, but are left with no other remedy. Plaintiffs also challenge the difference in treatment between automobile tort victims and the victims of other torts to whom traditional tort remedies remain available. 28 Defendants respond that plaintiffs have misapprehended the classifications imposed by MNFS. They argue that MNFS Sec. 3135 does not distinguish between automobile victims on the basis of Michigan residency but rather classifies victims according to the nature of their injury regardless of their residency, a classification which survived constitutional challenge in Shavers v. Kelley, 402 Mich. 554, 267 N.W.2d 72, cert. denied, 442 U.S. 934, 99 S.Ct. 2869, 61 L.Ed.2d 303 (1979). Defendants are correct insofar as all automobile victims, regardless of residency, have no remedy if they are injured by a tortfeasor who has availed himself or herself of the benefits provided by MNFS when the victim has not complied with the statute. However, plaintiffs argue that they have complied with MNFS and essentially contend that the statute cannot constitutionally allow them as transient nonresident motorists to choose not to avail themselves of the statutory remedy while depriving them of common law tort remedies. This treatment infringes upon their fundamental right to travel plaintiffs urge, and the state must demonstrate a countervailing and compelling interest in maintaining such a differential in treatment, which impairs plaintiffs' protected right to migrate freely from state to state. 29 We will concede the issue is a close one for the reasons previously discussed. We, nevertheless, conclude that the impact of MNFS upon plaintiffs' right to travel is not sufficient to rise to the level of a constitutional violation. Accordingly, in the absence of a suspect classification, we must examine MNFS's system to determine whether it is rationally related to a legitimate legislative purpose. McDonald v. Board of Election Comm'rs of Chicago, 394 U.S. 802, 806-09, 89 S.Ct. 1404, 1407-09, 22 L.Ed.2d 739 (1969). 30 As previously stated, the abolishment of tort liability with some exceptions and its replacement with a system of compulsory insurance is rationally related to the legitimate legislative purpose of lowering insurance costs and providing "victims of motor vehicle accidents assured, adequate, and prompt reparation for certain economic losses ... as a substitute for their common-law remedy in tort." Rusinek, 309 N.W.2d at 164-66. Of course, in order for the system to remain fiscally sound and to spread its costs equitably, only those who bear the scheme's burdens should be the recipients of its benefits. Plaintiffs may not successfully contend that they are entitled to the benefits of MNFS without having borne its burdens, which might be one method of equating plaintiffs with the group with which they contend they are similarly situated. Rather, plaintiffs seek to avoid both the financial burden of MNFS and its abolition of tort liability as applied to them. 31 We conclude that the exception to the insurance or security requirements of MNFS carved out by the Michigan legislature for transient non-resident motorists, while continuing to make them subject to the general statutory scheme, has a rational basis and that the distinctions drawn are constitutional. As stated by the Michigan Court of Appeals in Gersten: 32 This scheme, while encouraging compliance with the act on the part of a transient nonresident, does not go so far as to subject the nonresident to criminal sanctions. In this manner the legislation strikes a balance between the Legislature's interest in uniform application of the act to injuries arising out of motor vehicle accidents in our state and the transient non-resident's interest in the operation of his vehicle in our state. 33 314 N.W.2d at 648. 34 Finally, plaintiffs claim that they have been arbitrarily denied access to Michigan courts to pursue their remedies in tort with no provision for a substitute remedy without due process of law. However, plaintiffs could have obtained MNFS benefits and chose not to do so. The statute simply allows, but does not require, transient nonresident motorists who wish to traverse Michigan's borders to come within the aegis of MNFS and to obtain the benefits for which it provides, while granting them a thirty-day period before subjecting them to criminal penalties for noncompliance with MNFS. We conclude that MNFS is constitutional on its face and as applied to plaintiffs under the circumstances. 35 The district court's grant of summary judgment in favor of defendants is accordingly affirmed. * The Honorable Robert M. McRae, Jr., Senior U.S. District Judge, Western District of Tennessee, sitting by designation 1 M.S.A. Sec. 24.13163 [M.C.L. Sec. 500.3163] (1987) (MNFS Sec. 3163) provides in pertinent part: Certification of insurer. Sec. 3163. (1) An insurer authorized to transact automobile liability insurance and personal and property protection insurance in this state shall file and maintain a written certification that any accidental bodily injury or property damage occurring in this state arising from the ownership, operation, maintenance or use of a motor vehicle as a motor vehicle by an out-of-state resident who is insured under its automobile liability insurance policies, shall be subject to the personal and property protection insurance system set forth in this act. 2 This admission is unusual and inexplicable in view of the record before us; there is no clear evidence or even an inference as to whether or not plaintiffs carried property damage or collision insurance coverage on their vehicle 3 M.S.A. Sec. 24.13163 [M.C.L. Sec. 500.3163] (MNFS Sec. 3163) provides in subsection (2) that "A nonadmitted insurer may voluntarily file the certification described in subsection (1)."
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One thing that made the fairs fairs, rather than festivals, was the dominance of theatre and Incubus were the first among many fine troupes who brought street theatre to the fields of East Anglia. And Paddy was the constant, the writer and the director and the finest and funniest foul mouthed beggar, goblin and alien punk to be found in those fair fields. Bruce and Jill first came to the fairs for the Last Barsham in 1976, and they became a regular fixture from then on, moving to Wymondham two or three years later. In 1981 and 1982, they organised the fair at Lyng, under the name the Faerie Faire. As many of you will know, Old Hall in East Bergholt has been a community since 1974 and hosted 4 fairs: Fire (1979), Moon (1980), Rainbow (1981) and Earth (1982). We were invited to take the exhibition there as part of a Ceilidh organised by resident Dan Wheals, yet again it was like going home for the Archive! The Fairs Archive’s yurt was set up in the chapel, (now deconsecrated) and fitted perfectly in the area that once contained the altar below an ancient wall painting still resplendent with gold foil. We all jigged the night away to the SOAS Ceilidh band “fiddling in support of refugees”. Everyone had a wonderful time and Old Hall proved to be welcoming and generous hosts.
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[ 0.6079664570230601, 36.25, 23.375 ]
Pam's SOS offers a variety of lessons at convenient times through out the day. We also teach all levels and ages. We will start as young as 6 months and help you learn your entire life. As you get older, swimming is a great way to stay in shape without the stress on your joints. Our Little Seahorse classes are for parent and toddler. Each class teaches different safety elements for the children. Most of these elements can be practiced in your bath tub. At this very young age, safety is the most important thing. We have heard many stories from our clients of how their child fell into a friends pool. By the time the parent or other adult jumped in the pool, the child had already swam to the top of the water and rolled on their back. This is why Ms. Pam teaches safety skills to our Little Seahorses. Our group classes are no more than 3 to a class. This provides for more attention from our instructor during the class. This also brings a higher level of safety for the children and the instructor. We are able to work with anyone wanting to perfect their strokes. Whether it is free style, breast, back, or butterfly, our instructors are able to help you improve. This will make swimming much more fun when you are not struggling to get up and down the pool.Type your paragraph here. Classes are once a week for 30 minutes. We usually have no more than 3 in a group class. For our Little Seahorse classes, we will have up to 5 parent/ child set. We keep our classes small to provide better safety and more instruction for each child each week. We match like skill level children together. This provides a comfortable learning environment for the children. The children encourage each other which allows for greater learning.Sessions We have classes starting every week. Classes meet once a week for 30 minutes. You may come more than once a week if you prefer. You can pay by mailing your check with your registration form or by PayPal upon request.We are usually able to work around your summer vacation with our different session options.Our session options and consent form:Type your paragraph here.
High
[ 0.678217821782178, 34.25, 16.25 ]
/*- * #%L * Elastic APM Java agent * %% * Copyright (C) 2018 - 2020 Elastic and contributors * %% * Licensed to Elasticsearch B.V. under one or more contributor * license agreements. See the NOTICE file distributed with * this work for additional information regarding copyright * ownership. Elasticsearch B.V. licenses this file to you under * the Apache License, Version 2.0 (the "License"); you may * not use this file except in compliance with the License. * You may obtain a copy of the License at * * http://www.apache.org/licenses/LICENSE-2.0 * * Unless required by applicable law or agreed to in writing, * software distributed under the License is distributed on an * "AS IS" BASIS, WITHOUT WARRANTIES OR CONDITIONS OF ANY * KIND, either express or implied. See the License for the * specific language governing permissions and limitations * under the License. * #L% */ @NonnullApi package co.elastic.apm.agent.impl.payload; import co.elastic.apm.agent.sdk.NonnullApi;
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[ 0.48202959830866804, 28.5, 30.625 ]
Elihu B. Hayes Elihu Burritt Hayes (April 26, 1848 – April 1, 1903) was an American shoe manufacturer, newspaperman, and politician, who served as a member of the Massachusetts House of Representatives, representing the 18th Essex District, and as the 25th Mayor of Lynn, Massachusetts. Early life Hayes was born in West Lebanon, Maine on April 26, 1848, and moved to Lynn, Massachusetts in 1865. Family life In 1873 Hayes married Amy A. Farnum of Lynn, They had one child, Eugene. Business career Hayes worked in the shoe industry, indeed he may have been employed by the Hayes Cooperage Co. which was founded by John and Patrick Hayes in mid 1800s, until 1872. After he left the shoe industry, Hayes went into the newspaper business. Hayes took over ownership of The Lynn Bee. In 1885 Hayes took over The Boston Advertiser. Introduction of the secret ballot in Massachusetts In 1888, while in the Massachusetts Legislature, Hayes introduced the first bill in the United States to adopt the Australian style ballot system, initiating the successful movement for the adoption of the Secret ballot in the United States. References Bibliography Arrington, Benjamin F.: Municipal History of Essex County in Massachusetts: A Classified Work, Devoted to the County's Remarkable Growth in All Lines of Human Endeavor; More Especially to Within a Period of Fifty Years (1922) p. 402. Boston Daily Globe (November 6, 1889), Slick Work in Lynn. Elihu B. Hayes, Local Father of the System, Pleased., Boston, MA: Boston Daily Globe, (1889) p. 8. Boston Daily Globe (April 2, 1903), Hon. Elihu B. Hayes Dead Prominent Resident of Lynn Well Known to New England. He Had Never Completely Recovered from the Effects of Fall Down Stairs in His Home Last October. Born a Poor Boy. In Newspaper Work. In Municipal Affairs. Candidate for Congress. Spanish War Relief Work. Fond of His Home., Boston, Mass: Boston Daily Globe, (1903) p. 14. The New York Times (April 2, 1903) Death List of A Day.; Elihu Burritt Hayes, (1903), p. 9. Newhall, James Robinson.: History of Lynn Essex County, Massachusetts ; Including Lynnfield, Saugus, Swampscot, and Nahant: Massachusetts Including Lynnfield, Saugus, Swampscot, and Nahant Vol. II 1864 -1893. (1897) p. 362. Wigmore, John Henry.; (October, 1889), The Australian Ballot System as Embodied in the Legislation of Various Countries: With an Historical Introduction, and an Appendix of Decisions Since 1856 in Great Britain, Ireland, Canada, and Australia, Boston, MA: The Boston Book Company, (1889) p. 27. External links Mayors of the City of Lynn since its incorporation in 1850. From the official website of the City of Lynn. Category:1848 births Category:Massachusetts city council members Category:Mayors of Lynn, Massachusetts Category:People from Lebanon, Maine Category:American male journalists Category:19th-century American newspaper publishers (people) Category:Boston Daily Advertiser people Category:Members of the Massachusetts House of Representatives Category:1903 deaths Category:Massachusetts Republicans
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Direct synthesis of quinazolines through copper-catalyzed reaction of aniline-derived benzamidines. A novel synthesis of 2-phenyl-4-[(triisopropylsilyl)methyl]quinazolines from monosubstituted arenes has been developed. Treatment of N-phenylbenzamidines with 5-nitro-1-[(triisopropylsilyl)ethynyl]-1,2-benziodoxol-3(1H)-one and K(2)CO(3) in the presence of a catalytic amount of CuBr in benzene gives 2-phenyl-4-[(triisopropylsilyl)methyl]quinazolines in moderate to good yields.
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[ 0.643564356435643, 32.5, 18 ]
Life is a story Main menu Post navigation My Poor Chickens! Today is not a good day in ‘Lover’s Leap’.In fact it has not proved to be a good week at all.Last Friday my Elly returned from a working week in Israel.She phoned me from Dublin Airport as she waited for her baggage to come through.She always checks in like this a) to see if it is time to claim her inheritance or b) to let me know she has landed safely.We talked until I heard the baggage carousel start up and I let her go to concentrate on that.A little while later I had a text from her to say the case had not come home. Saturday she was involved at Barcamp Dublin, another long and busy day.The suitcase was delivered on Sunday mid morning so all seemed well. Monday and Tuesday were spent playing catch up at work while sorting her paperwork for the Visa, and vaccinations required for the next trip in May, which is to Vietnam with a stop off for two weeks on the way in Arizona.Taking the westward route she should come right round the world, passing the date line for the first time and cover 20,800 miles of flying. Her visit to the Post Office was slow and tedious but the Passport and paperwork were eventually sent on their merry way to London for the Visa Stamp.She returned to her car to discover a parking ticket on the wind-shield. Wednesday dawned and the effects of the Vaccinations hit home and she was suffering from a sore arm and rear end! At lunch time a young man decided to be friendly with my Sin-in-Law, far too friendly!He ‘rear ended him’; I think that is the term.The car is a mess I believe.‘S-i-L’ thought he was un-damaged so did not take my advice and go to his doctor. This morning ‘S-i-L’ had a very sore neck and Elly’s rear end was swollen, sore and not allowing her to sit down.They both headed to see the doctor and were given medication and told to take it easy today and not to try working. While I spoke to Elly on the phone this morning she was pacing up and down, ‘S-i-L’ put out his hand to touch her as she passed – to give her a sign of comfort.His hand was about 2” from her bottom when she gave him a ‘Moses’ look, like the look Moses used to part the Red Sea.When Elly does that you BACK OFF! Tonight they are a little better and the wedding is going ahead! Get well soon, I love you both! Advertisements Share this: Like this: Related 8 thoughts on “My Poor Chickens!” Grannymar,I’m happy that things are getting sorted out for Elly and SIL. They certainly lead an exciting life! Good for them. Elly must be very important to her company to be the one selected to represent them all over the World. Elly,I know the shots are an inconvenience but the alternative can be tragic. So, rub your sore backside and count your blessings that you won’t be coming home with some awful disease.Happy Wedding Planning. Nancy, the modern workplace means that the Laptop is your office, have laptop and cell phone and you can work anywhere. Elly thrives on the challenge of her work and loves the travel. She draws people around her like pins to a magnet, a gift she inherited from her Dad! It is nice to know my voice was missed.I have been concentrating on Wedding stuff for Elly and getting my outfit sorted. It has taken over for a short while.I realised the other day that I missed the podcasting as well. Give me another week and I might have some more time to resolve things.Don’t give up on me yet!
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Howard Simon's Blog Brandon says lease deal not imminent by Howard Simon,posted Oct 31 2012 9:12AM According to a published report, a new lease deal for the Buffalo Bills is imminent but Bills CEO Russ Brandon told WGR that isn't the case. According to a story in the Niagara Falls Reporter, New York State, Erie County and the Bills have reached agreement on a deal that will be in the 8-10 year range and it could be announced in 7 to 10 days. During his weekly segment on WGR, Brandon said "there is nothing imminent at all" but they are having very productive talks. Brandon added they are making progress but declined to give any timetable for an agreement. Brandon also said the Bills considered the idea of a new stadium and explored the concept of a complete retrofit, like Kansas City and Green Bay, before determining renovations to Ralph Wilson Stadium was the best way to proceed. If the Bills opted for a new facility or a complete retrofit, Brandon said most of the cost would be passed along to the consumer and that ticket prices would double or triple. You can listen to the entire interview with Brandon including his comments on the long term viability of Ralph Wilson Stadium as well the evaluation of Buddy Nix and Chan Gailey.
Mid
[ 0.6070686070686071, 36.5, 23.625 ]
// SPDX-License-Identifier: GPL-2.0-only /* * Intel SST Haswell/Broadwell IPC Support * * Copyright (C) 2013, Intel Corporation. All rights reserved. */ #include <linux/types.h> #include <linux/kernel.h> #include <linux/list.h> #include <linux/device.h> #include <linux/wait.h> #include <linux/spinlock.h> #include <linux/workqueue.h> #include <linux/export.h> #include <linux/slab.h> #include <linux/delay.h> #include <linux/sched.h> #include <linux/platform_device.h> #include <linux/firmware.h> #include <linux/dma-mapping.h> #include <linux/debugfs.h> #include <linux/pm_runtime.h> #include <sound/asound.h> #include "sst-haswell-ipc.h" #include "../common/sst-dsp.h" #include "../common/sst-dsp-priv.h" #include "../common/sst-ipc.h" /* Global Message - Generic */ #define IPC_GLB_TYPE_SHIFT 24 #define IPC_GLB_TYPE_MASK (0x1f << IPC_GLB_TYPE_SHIFT) #define IPC_GLB_TYPE(x) (x << IPC_GLB_TYPE_SHIFT) /* Global Message - Reply */ #define IPC_GLB_REPLY_SHIFT 0 #define IPC_GLB_REPLY_MASK (0x1f << IPC_GLB_REPLY_SHIFT) #define IPC_GLB_REPLY_TYPE(x) (x << IPC_GLB_REPLY_TYPE_SHIFT) /* Stream Message - Generic */ #define IPC_STR_TYPE_SHIFT 20 #define IPC_STR_TYPE_MASK (0xf << IPC_STR_TYPE_SHIFT) #define IPC_STR_TYPE(x) (x << IPC_STR_TYPE_SHIFT) #define IPC_STR_ID_SHIFT 16 #define IPC_STR_ID_MASK (0xf << IPC_STR_ID_SHIFT) #define IPC_STR_ID(x) (x << IPC_STR_ID_SHIFT) /* Stream Message - Reply */ #define IPC_STR_REPLY_SHIFT 0 #define IPC_STR_REPLY_MASK (0x1f << IPC_STR_REPLY_SHIFT) /* Stream Stage Message - Generic */ #define IPC_STG_TYPE_SHIFT 12 #define IPC_STG_TYPE_MASK (0xf << IPC_STG_TYPE_SHIFT) #define IPC_STG_TYPE(x) (x << IPC_STG_TYPE_SHIFT) #define IPC_STG_ID_SHIFT 10 #define IPC_STG_ID_MASK (0x3 << IPC_STG_ID_SHIFT) #define IPC_STG_ID(x) (x << IPC_STG_ID_SHIFT) /* Stream Stage Message - Reply */ #define IPC_STG_REPLY_SHIFT 0 #define IPC_STG_REPLY_MASK (0x1f << IPC_STG_REPLY_SHIFT) /* Debug Log Message - Generic */ #define IPC_LOG_OP_SHIFT 20 #define IPC_LOG_OP_MASK (0xf << IPC_LOG_OP_SHIFT) #define IPC_LOG_OP_TYPE(x) (x << IPC_LOG_OP_SHIFT) #define IPC_LOG_ID_SHIFT 16 #define IPC_LOG_ID_MASK (0xf << IPC_LOG_ID_SHIFT) #define IPC_LOG_ID(x) (x << IPC_LOG_ID_SHIFT) /* Module Message */ #define IPC_MODULE_OPERATION_SHIFT 20 #define IPC_MODULE_OPERATION_MASK (0xf << IPC_MODULE_OPERATION_SHIFT) #define IPC_MODULE_OPERATION(x) (x << IPC_MODULE_OPERATION_SHIFT) #define IPC_MODULE_ID_SHIFT 16 #define IPC_MODULE_ID_MASK (0xf << IPC_MODULE_ID_SHIFT) #define IPC_MODULE_ID(x) (x << IPC_MODULE_ID_SHIFT) /* IPC message timeout (msecs) */ #define IPC_TIMEOUT_MSECS 300 #define IPC_BOOT_MSECS 200 #define IPC_MSG_WAIT 0 #define IPC_MSG_NOWAIT 1 /* Firmware Ready Message */ #define IPC_FW_READY (0x1 << 29) #define IPC_STATUS_MASK (0x3 << 30) #define IPC_EMPTY_LIST_SIZE 8 #define IPC_MAX_STREAMS 4 /* Mailbox */ #define IPC_MAX_MAILBOX_BYTES 256 #define INVALID_STREAM_HW_ID 0xffffffff /* Global Message - Types and Replies */ enum ipc_glb_type { IPC_GLB_GET_FW_VERSION = 0, /* Retrieves firmware version */ IPC_GLB_PERFORMANCE_MONITOR = 1, /* Performance monitoring actions */ IPC_GLB_ALLOCATE_STREAM = 3, /* Request to allocate new stream */ IPC_GLB_FREE_STREAM = 4, /* Request to free stream */ IPC_GLB_GET_FW_CAPABILITIES = 5, /* Retrieves firmware capabilities */ IPC_GLB_STREAM_MESSAGE = 6, /* Message directed to stream or its stages */ /* Request to store firmware context during D0->D3 transition */ IPC_GLB_REQUEST_DUMP = 7, /* Request to restore firmware context during D3->D0 transition */ IPC_GLB_RESTORE_CONTEXT = 8, IPC_GLB_GET_DEVICE_FORMATS = 9, /* Set device format */ IPC_GLB_SET_DEVICE_FORMATS = 10, /* Get device format */ IPC_GLB_SHORT_REPLY = 11, IPC_GLB_ENTER_DX_STATE = 12, IPC_GLB_GET_MIXER_STREAM_INFO = 13, /* Request mixer stream params */ IPC_GLB_DEBUG_LOG_MESSAGE = 14, /* Message to or from the debug logger. */ IPC_GLB_MODULE_OPERATION = 15, /* Message to loadable fw module */ IPC_GLB_REQUEST_TRANSFER = 16, /* < Request Transfer for host */ IPC_GLB_MAX_IPC_MESSAGE_TYPE = 17, /* Maximum message number */ }; enum ipc_glb_reply { IPC_GLB_REPLY_SUCCESS = 0, /* The operation was successful. */ IPC_GLB_REPLY_ERROR_INVALID_PARAM = 1, /* Invalid parameter was passed. */ IPC_GLB_REPLY_UNKNOWN_MESSAGE_TYPE = 2, /* Uknown message type was resceived. */ IPC_GLB_REPLY_OUT_OF_RESOURCES = 3, /* No resources to satisfy the request. */ IPC_GLB_REPLY_BUSY = 4, /* The system or resource is busy. */ IPC_GLB_REPLY_PENDING = 5, /* The action was scheduled for processing. */ IPC_GLB_REPLY_FAILURE = 6, /* Critical error happened. */ IPC_GLB_REPLY_INVALID_REQUEST = 7, /* Request can not be completed. */ IPC_GLB_REPLY_STAGE_UNINITIALIZED = 8, /* Processing stage was uninitialized. */ IPC_GLB_REPLY_NOT_FOUND = 9, /* Required resource can not be found. */ IPC_GLB_REPLY_SOURCE_NOT_STARTED = 10, /* Source was not started. */ }; enum ipc_module_operation { IPC_MODULE_NOTIFICATION = 0, IPC_MODULE_ENABLE = 1, IPC_MODULE_DISABLE = 2, IPC_MODULE_GET_PARAMETER = 3, IPC_MODULE_SET_PARAMETER = 4, IPC_MODULE_GET_INFO = 5, IPC_MODULE_MAX_MESSAGE }; /* Stream Message - Types */ enum ipc_str_operation { IPC_STR_RESET = 0, IPC_STR_PAUSE = 1, IPC_STR_RESUME = 2, IPC_STR_STAGE_MESSAGE = 3, IPC_STR_NOTIFICATION = 4, IPC_STR_MAX_MESSAGE }; /* Stream Stage Message Types */ enum ipc_stg_operation { IPC_STG_GET_VOLUME = 0, IPC_STG_SET_VOLUME, IPC_STG_SET_WRITE_POSITION, IPC_STG_SET_FX_ENABLE, IPC_STG_SET_FX_DISABLE, IPC_STG_SET_FX_GET_PARAM, IPC_STG_SET_FX_SET_PARAM, IPC_STG_SET_FX_GET_INFO, IPC_STG_MUTE_LOOPBACK, IPC_STG_MAX_MESSAGE }; /* Stream Stage Message Types For Notification*/ enum ipc_stg_operation_notify { IPC_POSITION_CHANGED = 0, IPC_STG_GLITCH, IPC_STG_MAX_NOTIFY }; enum ipc_glitch_type { IPC_GLITCH_UNDERRUN = 1, IPC_GLITCH_DECODER_ERROR, IPC_GLITCH_DOUBLED_WRITE_POS, IPC_GLITCH_MAX }; /* Debug Control */ enum ipc_debug_operation { IPC_DEBUG_ENABLE_LOG = 0, IPC_DEBUG_DISABLE_LOG = 1, IPC_DEBUG_REQUEST_LOG_DUMP = 2, IPC_DEBUG_NOTIFY_LOG_DUMP = 3, IPC_DEBUG_MAX_DEBUG_LOG }; /* Firmware Ready */ struct sst_hsw_ipc_fw_ready { u32 inbox_offset; u32 outbox_offset; u32 inbox_size; u32 outbox_size; u32 fw_info_size; u8 fw_info[IPC_MAX_MAILBOX_BYTES - 5 * sizeof(u32)]; } __attribute__((packed)); struct sst_hsw_stream; struct sst_hsw; /* Stream infomation */ struct sst_hsw_stream { /* configuration */ struct sst_hsw_ipc_stream_alloc_req request; struct sst_hsw_ipc_stream_alloc_reply reply; struct sst_hsw_ipc_stream_free_req free_req; /* Mixer info */ u32 mute_volume[SST_HSW_NO_CHANNELS]; u32 mute[SST_HSW_NO_CHANNELS]; /* runtime info */ struct sst_hsw *hsw; int host_id; bool commited; bool running; /* Notification work */ struct work_struct notify_work; u32 header; /* Position info from DSP */ struct sst_hsw_ipc_stream_set_position wpos; struct sst_hsw_ipc_stream_get_position rpos; struct sst_hsw_ipc_stream_glitch_position glitch; /* Volume info */ struct sst_hsw_ipc_volume_req vol_req; /* driver callback */ u32 (*notify_position)(struct sst_hsw_stream *stream, void *data); void *pdata; /* record the fw read position when playback */ snd_pcm_uframes_t old_position; bool play_silence; struct list_head node; }; /* FW log ring information */ struct sst_hsw_log_stream { dma_addr_t dma_addr; unsigned char *dma_area; unsigned char *ring_descr; int pages; int size; /* Notification work */ struct work_struct notify_work; wait_queue_head_t readers_wait_q; struct mutex rw_mutex; u32 last_pos; u32 curr_pos; u32 reader_pos; /* fw log config */ u32 config[SST_HSW_FW_LOG_CONFIG_DWORDS]; struct sst_hsw *hsw; }; /* SST Haswell IPC data */ struct sst_hsw { struct device *dev; struct sst_dsp *dsp; struct platform_device *pdev_pcm; /* FW config */ struct sst_hsw_ipc_fw_ready fw_ready; struct sst_hsw_ipc_fw_version version; bool fw_done; struct sst_fw *sst_fw; /* stream */ struct list_head stream_list; /* global mixer */ struct sst_hsw_ipc_stream_info_reply mixer_info; enum sst_hsw_volume_curve curve_type; u32 curve_duration; u32 mute[SST_HSW_NO_CHANNELS]; u32 mute_volume[SST_HSW_NO_CHANNELS]; /* DX */ struct sst_hsw_ipc_dx_reply dx; void *dx_context; dma_addr_t dx_context_paddr; enum sst_hsw_device_id dx_dev; enum sst_hsw_device_mclk dx_mclk; enum sst_hsw_device_mode dx_mode; u32 dx_clock_divider; /* boot */ wait_queue_head_t boot_wait; bool boot_complete; bool shutdown; /* IPC messaging */ struct sst_generic_ipc ipc; /* FW log stream */ struct sst_hsw_log_stream log_stream; /* flags bit field to track module state when resume from RTD3, * each bit represent state (enabled/disabled) of single module */ u32 enabled_modules_rtd3; /* buffer to store parameter lines */ u32 param_idx_w; /* write index */ u32 param_idx_r; /* read index */ u8 param_buf[WAVES_PARAM_LINES][WAVES_PARAM_COUNT]; }; #define CREATE_TRACE_POINTS #include <trace/events/hswadsp.h> static inline u32 msg_get_global_type(u32 msg) { return (msg & IPC_GLB_TYPE_MASK) >> IPC_GLB_TYPE_SHIFT; } static inline u32 msg_get_global_reply(u32 msg) { return (msg & IPC_GLB_REPLY_MASK) >> IPC_GLB_REPLY_SHIFT; } static inline u32 msg_get_stream_type(u32 msg) { return (msg & IPC_STR_TYPE_MASK) >> IPC_STR_TYPE_SHIFT; } static inline u32 msg_get_stream_id(u32 msg) { return (msg & IPC_STR_ID_MASK) >> IPC_STR_ID_SHIFT; } static inline u32 msg_get_notify_reason(u32 msg) { return (msg & IPC_STG_TYPE_MASK) >> IPC_STG_TYPE_SHIFT; } static inline u32 msg_get_module_operation(u32 msg) { return (msg & IPC_MODULE_OPERATION_MASK) >> IPC_MODULE_OPERATION_SHIFT; } static inline u32 msg_get_module_id(u32 msg) { return (msg & IPC_MODULE_ID_MASK) >> IPC_MODULE_ID_SHIFT; } u32 create_channel_map(enum sst_hsw_channel_config config) { switch (config) { case SST_HSW_CHANNEL_CONFIG_MONO: return (0xFFFFFFF0 | SST_HSW_CHANNEL_CENTER); case SST_HSW_CHANNEL_CONFIG_STEREO: return (0xFFFFFF00 | SST_HSW_CHANNEL_LEFT | (SST_HSW_CHANNEL_RIGHT << 4)); case SST_HSW_CHANNEL_CONFIG_2_POINT_1: return (0xFFFFF000 | SST_HSW_CHANNEL_LEFT | (SST_HSW_CHANNEL_RIGHT << 4) | (SST_HSW_CHANNEL_LFE << 8 )); case SST_HSW_CHANNEL_CONFIG_3_POINT_0: return (0xFFFFF000 | SST_HSW_CHANNEL_LEFT | (SST_HSW_CHANNEL_CENTER << 4) | (SST_HSW_CHANNEL_RIGHT << 8)); case SST_HSW_CHANNEL_CONFIG_3_POINT_1: return (0xFFFF0000 | SST_HSW_CHANNEL_LEFT | (SST_HSW_CHANNEL_CENTER << 4) | (SST_HSW_CHANNEL_RIGHT << 8) | (SST_HSW_CHANNEL_LFE << 12)); case SST_HSW_CHANNEL_CONFIG_QUATRO: return (0xFFFF0000 | SST_HSW_CHANNEL_LEFT | (SST_HSW_CHANNEL_RIGHT << 4) | (SST_HSW_CHANNEL_LEFT_SURROUND << 8) | (SST_HSW_CHANNEL_RIGHT_SURROUND << 12)); case SST_HSW_CHANNEL_CONFIG_4_POINT_0: return (0xFFFF0000 | SST_HSW_CHANNEL_LEFT | (SST_HSW_CHANNEL_CENTER << 4) | (SST_HSW_CHANNEL_RIGHT << 8) | (SST_HSW_CHANNEL_CENTER_SURROUND << 12)); case SST_HSW_CHANNEL_CONFIG_5_POINT_0: return (0xFFF00000 | SST_HSW_CHANNEL_LEFT | (SST_HSW_CHANNEL_CENTER << 4) | (SST_HSW_CHANNEL_RIGHT << 8) | (SST_HSW_CHANNEL_LEFT_SURROUND << 12) | (SST_HSW_CHANNEL_RIGHT_SURROUND << 16)); case SST_HSW_CHANNEL_CONFIG_5_POINT_1: return (0xFF000000 | SST_HSW_CHANNEL_CENTER | (SST_HSW_CHANNEL_LEFT << 4) | (SST_HSW_CHANNEL_RIGHT << 8) | (SST_HSW_CHANNEL_LEFT_SURROUND << 12) | (SST_HSW_CHANNEL_RIGHT_SURROUND << 16) | (SST_HSW_CHANNEL_LFE << 20)); case SST_HSW_CHANNEL_CONFIG_DUAL_MONO: return (0xFFFFFF00 | SST_HSW_CHANNEL_LEFT | (SST_HSW_CHANNEL_LEFT << 4)); default: return 0xFFFFFFFF; } } static struct sst_hsw_stream *get_stream_by_id(struct sst_hsw *hsw, int stream_id) { struct sst_hsw_stream *stream; list_for_each_entry(stream, &hsw->stream_list, node) { if (stream->reply.stream_hw_id == stream_id) return stream; } return NULL; } static void hsw_fw_ready(struct sst_hsw *hsw, u32 header) { struct sst_hsw_ipc_fw_ready fw_ready; u32 offset; u8 fw_info[IPC_MAX_MAILBOX_BYTES - 5 * sizeof(u32)]; char *tmp[5], *pinfo; int i = 0; offset = (header & 0x1FFFFFFF) << 3; dev_dbg(hsw->dev, "ipc: DSP is ready 0x%8.8x offset %d\n", header, offset); /* copy data from the DSP FW ready offset */ sst_dsp_read(hsw->dsp, &fw_ready, offset, sizeof(fw_ready)); sst_dsp_mailbox_init(hsw->dsp, fw_ready.inbox_offset, fw_ready.inbox_size, fw_ready.outbox_offset, fw_ready.outbox_size); hsw->boot_complete = true; wake_up(&hsw->boot_wait); dev_dbg(hsw->dev, " mailbox upstream 0x%x - size 0x%x\n", fw_ready.inbox_offset, fw_ready.inbox_size); dev_dbg(hsw->dev, " mailbox downstream 0x%x - size 0x%x\n", fw_ready.outbox_offset, fw_ready.outbox_size); if (fw_ready.fw_info_size < sizeof(fw_ready.fw_info)) { fw_ready.fw_info[fw_ready.fw_info_size] = 0; dev_dbg(hsw->dev, " Firmware info: %s \n", fw_ready.fw_info); /* log the FW version info got from the mailbox here. */ memcpy(fw_info, fw_ready.fw_info, fw_ready.fw_info_size); pinfo = &fw_info[0]; for (i = 0; i < ARRAY_SIZE(tmp); i++) tmp[i] = strsep(&pinfo, " "); dev_info(hsw->dev, "FW loaded, mailbox readback FW info: type %s, - " "version: %s.%s, build %s, source commit id: %s\n", tmp[0], tmp[1], tmp[2], tmp[3], tmp[4]); } } static void hsw_notification_work(struct work_struct *work) { struct sst_hsw_stream *stream = container_of(work, struct sst_hsw_stream, notify_work); struct sst_hsw_ipc_stream_glitch_position *glitch = &stream->glitch; struct sst_hsw_ipc_stream_get_position *pos = &stream->rpos; struct sst_hsw *hsw = stream->hsw; u32 reason; reason = msg_get_notify_reason(stream->header); switch (reason) { case IPC_STG_GLITCH: trace_ipc_notification("DSP stream under/overrun", stream->reply.stream_hw_id); sst_dsp_inbox_read(hsw->dsp, glitch, sizeof(*glitch)); dev_err(hsw->dev, "glitch %d pos 0x%x write pos 0x%x\n", glitch->glitch_type, glitch->present_pos, glitch->write_pos); break; case IPC_POSITION_CHANGED: trace_ipc_notification("DSP stream position changed for", stream->reply.stream_hw_id); sst_dsp_inbox_read(hsw->dsp, pos, sizeof(*pos)); if (stream->notify_position) stream->notify_position(stream, stream->pdata); break; default: dev_err(hsw->dev, "error: unknown notification 0x%x\n", stream->header); break; } /* tell DSP that notification has been handled */ sst_dsp_shim_update_bits(hsw->dsp, SST_IPCD, SST_IPCD_BUSY | SST_IPCD_DONE, SST_IPCD_DONE); /* unmask busy interrupt */ sst_dsp_shim_update_bits(hsw->dsp, SST_IMRX, SST_IMRX_BUSY, 0); } static void hsw_stream_update(struct sst_hsw *hsw, struct ipc_message *msg) { struct sst_hsw_stream *stream; u32 header = msg->tx.header & ~(IPC_STATUS_MASK | IPC_GLB_REPLY_MASK); u32 stream_id = msg_get_stream_id(header); u32 stream_msg = msg_get_stream_type(header); stream = get_stream_by_id(hsw, stream_id); if (stream == NULL) return; switch (stream_msg) { case IPC_STR_STAGE_MESSAGE: case IPC_STR_NOTIFICATION: break; case IPC_STR_RESET: trace_ipc_notification("stream reset", stream->reply.stream_hw_id); break; case IPC_STR_PAUSE: stream->running = false; trace_ipc_notification("stream paused", stream->reply.stream_hw_id); break; case IPC_STR_RESUME: stream->running = true; trace_ipc_notification("stream running", stream->reply.stream_hw_id); break; } } static int hsw_process_reply(struct sst_hsw *hsw, u32 header) { struct ipc_message *msg; u32 reply = msg_get_global_reply(header); trace_ipc_reply("processing -->", header); msg = sst_ipc_reply_find_msg(&hsw->ipc, header); if (msg == NULL) { trace_ipc_error("error: can't find message header", header); return -EIO; } msg->rx.header = header; /* first process the header */ switch (reply) { case IPC_GLB_REPLY_PENDING: trace_ipc_pending_reply("received", header); msg->pending = true; hsw->ipc.pending = true; return 1; case IPC_GLB_REPLY_SUCCESS: if (msg->pending) { trace_ipc_pending_reply("completed", header); sst_dsp_inbox_read(hsw->dsp, msg->rx.data, msg->rx.size); hsw->ipc.pending = false; } else { /* copy data from the DSP */ sst_dsp_outbox_read(hsw->dsp, msg->rx.data, msg->rx.size); } break; /* these will be rare - but useful for debug */ case IPC_GLB_REPLY_UNKNOWN_MESSAGE_TYPE: trace_ipc_error("error: unknown message type", header); msg->errno = -EBADMSG; break; case IPC_GLB_REPLY_OUT_OF_RESOURCES: trace_ipc_error("error: out of resources", header); msg->errno = -ENOMEM; break; case IPC_GLB_REPLY_BUSY: trace_ipc_error("error: reply busy", header); msg->errno = -EBUSY; break; case IPC_GLB_REPLY_FAILURE: trace_ipc_error("error: reply failure", header); msg->errno = -EINVAL; break; case IPC_GLB_REPLY_STAGE_UNINITIALIZED: trace_ipc_error("error: stage uninitialized", header); msg->errno = -EINVAL; break; case IPC_GLB_REPLY_NOT_FOUND: trace_ipc_error("error: reply not found", header); msg->errno = -EINVAL; break; case IPC_GLB_REPLY_SOURCE_NOT_STARTED: trace_ipc_error("error: source not started", header); msg->errno = -EINVAL; break; case IPC_GLB_REPLY_INVALID_REQUEST: trace_ipc_error("error: invalid request", header); msg->errno = -EINVAL; break; case IPC_GLB_REPLY_ERROR_INVALID_PARAM: trace_ipc_error("error: invalid parameter", header); msg->errno = -EINVAL; break; default: trace_ipc_error("error: unknown reply", header); msg->errno = -EINVAL; break; } /* update any stream states */ if (msg_get_global_type(header) == IPC_GLB_STREAM_MESSAGE) hsw_stream_update(hsw, msg); /* wake up and return the error if we have waiters on this message ? */ list_del(&msg->list); sst_ipc_tx_msg_reply_complete(&hsw->ipc, msg); return 1; } static int hsw_module_message(struct sst_hsw *hsw, u32 header) { u32 operation, module_id; int handled = 0; operation = msg_get_module_operation(header); module_id = msg_get_module_id(header); dev_dbg(hsw->dev, "received module message header: 0x%8.8x\n", header); dev_dbg(hsw->dev, "operation: 0x%8.8x module_id: 0x%8.8x\n", operation, module_id); switch (operation) { case IPC_MODULE_NOTIFICATION: dev_dbg(hsw->dev, "module notification received"); handled = 1; break; default: handled = hsw_process_reply(hsw, header); break; } return handled; } static int hsw_stream_message(struct sst_hsw *hsw, u32 header) { u32 stream_msg, stream_id; struct sst_hsw_stream *stream; int handled = 0; stream_msg = msg_get_stream_type(header); stream_id = msg_get_stream_id(header); stream = get_stream_by_id(hsw, stream_id); if (stream == NULL) return handled; stream->header = header; switch (stream_msg) { case IPC_STR_STAGE_MESSAGE: dev_err(hsw->dev, "error: stage msg not implemented 0x%8.8x\n", header); break; case IPC_STR_NOTIFICATION: schedule_work(&stream->notify_work); break; default: /* handle pending message complete request */ handled = hsw_process_reply(hsw, header); break; } return handled; } static int hsw_log_message(struct sst_hsw *hsw, u32 header) { u32 operation = (header & IPC_LOG_OP_MASK) >> IPC_LOG_OP_SHIFT; struct sst_hsw_log_stream *stream = &hsw->log_stream; int ret = 1; if (operation != IPC_DEBUG_REQUEST_LOG_DUMP) { dev_err(hsw->dev, "error: log msg not implemented 0x%8.8x\n", header); return 0; } mutex_lock(&stream->rw_mutex); stream->last_pos = stream->curr_pos; sst_dsp_inbox_read( hsw->dsp, &stream->curr_pos, sizeof(stream->curr_pos)); mutex_unlock(&stream->rw_mutex); schedule_work(&stream->notify_work); return ret; } static int hsw_process_notification(struct sst_hsw *hsw) { struct sst_dsp *sst = hsw->dsp; u32 type, header; int handled = 1; header = sst_dsp_shim_read_unlocked(sst, SST_IPCD); type = msg_get_global_type(header); trace_ipc_request("processing -->", header); /* FW Ready is a special case */ if (!hsw->boot_complete && header & IPC_FW_READY) { hsw_fw_ready(hsw, header); return handled; } switch (type) { case IPC_GLB_GET_FW_VERSION: case IPC_GLB_ALLOCATE_STREAM: case IPC_GLB_FREE_STREAM: case IPC_GLB_GET_FW_CAPABILITIES: case IPC_GLB_REQUEST_DUMP: case IPC_GLB_GET_DEVICE_FORMATS: case IPC_GLB_SET_DEVICE_FORMATS: case IPC_GLB_ENTER_DX_STATE: case IPC_GLB_GET_MIXER_STREAM_INFO: case IPC_GLB_MAX_IPC_MESSAGE_TYPE: case IPC_GLB_RESTORE_CONTEXT: case IPC_GLB_SHORT_REPLY: dev_err(hsw->dev, "error: message type %d header 0x%x\n", type, header); break; case IPC_GLB_STREAM_MESSAGE: handled = hsw_stream_message(hsw, header); break; case IPC_GLB_DEBUG_LOG_MESSAGE: handled = hsw_log_message(hsw, header); break; case IPC_GLB_MODULE_OPERATION: handled = hsw_module_message(hsw, header); break; default: dev_err(hsw->dev, "error: unexpected type %d hdr 0x%8.8x\n", type, header); break; } return handled; } static irqreturn_t hsw_irq_thread(int irq, void *context) { struct sst_dsp *sst = (struct sst_dsp *) context; struct sst_hsw *hsw = sst_dsp_get_thread_context(sst); struct sst_generic_ipc *ipc = &hsw->ipc; u32 ipcx, ipcd; unsigned long flags; spin_lock_irqsave(&sst->spinlock, flags); ipcx = sst_dsp_ipc_msg_rx(hsw->dsp); ipcd = sst_dsp_shim_read_unlocked(sst, SST_IPCD); /* reply message from DSP */ if (ipcx & SST_IPCX_DONE) { /* Handle Immediate reply from DSP Core */ hsw_process_reply(hsw, ipcx); /* clear DONE bit - tell DSP we have completed */ sst_dsp_shim_update_bits_unlocked(sst, SST_IPCX, SST_IPCX_DONE, 0); /* unmask Done interrupt */ sst_dsp_shim_update_bits_unlocked(sst, SST_IMRX, SST_IMRX_DONE, 0); } /* new message from DSP */ if (ipcd & SST_IPCD_BUSY) { /* Handle Notification and Delayed reply from DSP Core */ hsw_process_notification(hsw); /* clear BUSY bit and set DONE bit - accept new messages */ sst_dsp_shim_update_bits_unlocked(sst, SST_IPCD, SST_IPCD_BUSY | SST_IPCD_DONE, SST_IPCD_DONE); /* unmask busy interrupt */ sst_dsp_shim_update_bits_unlocked(sst, SST_IMRX, SST_IMRX_BUSY, 0); } spin_unlock_irqrestore(&sst->spinlock, flags); /* continue to send any remaining messages... */ schedule_work(&ipc->kwork); return IRQ_HANDLED; } int sst_hsw_fw_get_version(struct sst_hsw *hsw, struct sst_hsw_ipc_fw_version *version) { struct sst_ipc_message request = {0}, reply = {0}; int ret; request.header = IPC_GLB_TYPE(IPC_GLB_GET_FW_VERSION); reply.data = version; reply.size = sizeof(*version); ret = sst_ipc_tx_message_wait(&hsw->ipc, request, &reply); if (ret < 0) dev_err(hsw->dev, "error: get version failed\n"); return ret; } /* Mixer Controls */ int sst_hsw_stream_get_volume(struct sst_hsw *hsw, struct sst_hsw_stream *stream, u32 stage_id, u32 channel, u32 *volume) { if (channel > 1) return -EINVAL; sst_dsp_read(hsw->dsp, volume, stream->reply.volume_register_address[channel], sizeof(*volume)); return 0; } /* stream volume */ int sst_hsw_stream_set_volume(struct sst_hsw *hsw, struct sst_hsw_stream *stream, u32 stage_id, u32 channel, u32 volume) { struct sst_hsw_ipc_volume_req *req; struct sst_ipc_message request; int ret; trace_ipc_request("set stream volume", stream->reply.stream_hw_id); if (channel >= 2 && channel != SST_HSW_CHANNELS_ALL) return -EINVAL; request.header = IPC_GLB_TYPE(IPC_GLB_STREAM_MESSAGE) | IPC_STR_TYPE(IPC_STR_STAGE_MESSAGE); request.header |= (stream->reply.stream_hw_id << IPC_STR_ID_SHIFT); request.header |= (IPC_STG_SET_VOLUME << IPC_STG_TYPE_SHIFT); request.header |= (stage_id << IPC_STG_ID_SHIFT); req = &stream->vol_req; req->target_volume = volume; /* set both at same time ? */ if (channel == SST_HSW_CHANNELS_ALL) { if (hsw->mute[0] && hsw->mute[1]) { hsw->mute_volume[0] = hsw->mute_volume[1] = volume; return 0; } else if (hsw->mute[0]) req->channel = 1; else if (hsw->mute[1]) req->channel = 0; else req->channel = SST_HSW_CHANNELS_ALL; } else { /* set only 1 channel */ if (hsw->mute[channel]) { hsw->mute_volume[channel] = volume; return 0; } req->channel = channel; } request.data = req; request.size = sizeof(*req); ret = sst_ipc_tx_message_wait(&hsw->ipc, request, NULL); if (ret < 0) { dev_err(hsw->dev, "error: set stream volume failed\n"); return ret; } return 0; } int sst_hsw_mixer_get_volume(struct sst_hsw *hsw, u32 stage_id, u32 channel, u32 *volume) { if (channel > 1) return -EINVAL; sst_dsp_read(hsw->dsp, volume, hsw->mixer_info.volume_register_address[channel], sizeof(*volume)); return 0; } /* global mixer volume */ int sst_hsw_mixer_set_volume(struct sst_hsw *hsw, u32 stage_id, u32 channel, u32 volume) { struct sst_hsw_ipc_volume_req req; struct sst_ipc_message request; int ret; trace_ipc_request("set mixer volume", volume); if (channel >= 2 && channel != SST_HSW_CHANNELS_ALL) return -EINVAL; /* set both at same time ? */ if (channel == SST_HSW_CHANNELS_ALL) { if (hsw->mute[0] && hsw->mute[1]) { hsw->mute_volume[0] = hsw->mute_volume[1] = volume; return 0; } else if (hsw->mute[0]) req.channel = 1; else if (hsw->mute[1]) req.channel = 0; else req.channel = SST_HSW_CHANNELS_ALL; } else { /* set only 1 channel */ if (hsw->mute[channel]) { hsw->mute_volume[channel] = volume; return 0; } req.channel = channel; } request.header = IPC_GLB_TYPE(IPC_GLB_STREAM_MESSAGE) | IPC_STR_TYPE(IPC_STR_STAGE_MESSAGE); request.header |= (hsw->mixer_info.mixer_hw_id << IPC_STR_ID_SHIFT); request.header |= (IPC_STG_SET_VOLUME << IPC_STG_TYPE_SHIFT); request.header |= (stage_id << IPC_STG_ID_SHIFT); req.curve_duration = hsw->curve_duration; req.curve_type = hsw->curve_type; req.target_volume = volume; request.data = &req; request.size = sizeof(req); ret = sst_ipc_tx_message_wait(&hsw->ipc, request, NULL); if (ret < 0) { dev_err(hsw->dev, "error: set mixer volume failed\n"); return ret; } return 0; } /* Stream API */ struct sst_hsw_stream *sst_hsw_stream_new(struct sst_hsw *hsw, int id, u32 (*notify_position)(struct sst_hsw_stream *stream, void *data), void *data) { struct sst_hsw_stream *stream; struct sst_dsp *sst = hsw->dsp; unsigned long flags; stream = kzalloc(sizeof(*stream), GFP_KERNEL); if (stream == NULL) return NULL; spin_lock_irqsave(&sst->spinlock, flags); stream->reply.stream_hw_id = INVALID_STREAM_HW_ID; list_add(&stream->node, &hsw->stream_list); stream->notify_position = notify_position; stream->pdata = data; stream->hsw = hsw; stream->host_id = id; /* work to process notification messages */ INIT_WORK(&stream->notify_work, hsw_notification_work); spin_unlock_irqrestore(&sst->spinlock, flags); return stream; } int sst_hsw_stream_free(struct sst_hsw *hsw, struct sst_hsw_stream *stream) { struct sst_ipc_message request; int ret = 0; struct sst_dsp *sst = hsw->dsp; unsigned long flags; if (!stream) { dev_warn(hsw->dev, "warning: stream is NULL, no stream to free, ignore it.\n"); return 0; } /* dont free DSP streams that are not commited */ if (!stream->commited) goto out; trace_ipc_request("stream free", stream->host_id); stream->free_req.stream_id = stream->reply.stream_hw_id; request.header = IPC_GLB_TYPE(IPC_GLB_FREE_STREAM); request.data = &stream->free_req; request.size = sizeof(stream->free_req); ret = sst_ipc_tx_message_wait(&hsw->ipc, request, NULL); if (ret < 0) { dev_err(hsw->dev, "error: free stream %d failed\n", stream->free_req.stream_id); return -EAGAIN; } trace_hsw_stream_free_req(stream, &stream->free_req); out: cancel_work_sync(&stream->notify_work); spin_lock_irqsave(&sst->spinlock, flags); list_del(&stream->node); kfree(stream); spin_unlock_irqrestore(&sst->spinlock, flags); return ret; } int sst_hsw_stream_set_bits(struct sst_hsw *hsw, struct sst_hsw_stream *stream, enum sst_hsw_bitdepth bits) { if (stream->commited) { dev_err(hsw->dev, "error: stream committed for set bits\n"); return -EINVAL; } stream->request.format.bitdepth = bits; return 0; } int sst_hsw_stream_set_channels(struct sst_hsw *hsw, struct sst_hsw_stream *stream, int channels) { if (stream->commited) { dev_err(hsw->dev, "error: stream committed for set channels\n"); return -EINVAL; } stream->request.format.ch_num = channels; return 0; } int sst_hsw_stream_set_rate(struct sst_hsw *hsw, struct sst_hsw_stream *stream, int rate) { if (stream->commited) { dev_err(hsw->dev, "error: stream committed for set rate\n"); return -EINVAL; } stream->request.format.frequency = rate; return 0; } int sst_hsw_stream_set_map_config(struct sst_hsw *hsw, struct sst_hsw_stream *stream, u32 map, enum sst_hsw_channel_config config) { if (stream->commited) { dev_err(hsw->dev, "error: stream committed for set map\n"); return -EINVAL; } stream->request.format.map = map; stream->request.format.config = config; return 0; } int sst_hsw_stream_set_style(struct sst_hsw *hsw, struct sst_hsw_stream *stream, enum sst_hsw_interleaving style) { if (stream->commited) { dev_err(hsw->dev, "error: stream committed for set style\n"); return -EINVAL; } stream->request.format.style = style; return 0; } int sst_hsw_stream_set_valid(struct sst_hsw *hsw, struct sst_hsw_stream *stream, u32 bits) { if (stream->commited) { dev_err(hsw->dev, "error: stream committed for set valid bits\n"); return -EINVAL; } stream->request.format.valid_bit = bits; return 0; } /* Stream Configuration */ int sst_hsw_stream_format(struct sst_hsw *hsw, struct sst_hsw_stream *stream, enum sst_hsw_stream_path_id path_id, enum sst_hsw_stream_type stream_type, enum sst_hsw_stream_format format_id) { if (stream->commited) { dev_err(hsw->dev, "error: stream committed for set format\n"); return -EINVAL; } stream->request.path_id = path_id; stream->request.stream_type = stream_type; stream->request.format_id = format_id; trace_hsw_stream_alloc_request(stream, &stream->request); return 0; } int sst_hsw_stream_buffer(struct sst_hsw *hsw, struct sst_hsw_stream *stream, u32 ring_pt_address, u32 num_pages, u32 ring_size, u32 ring_offset, u32 ring_first_pfn) { if (stream->commited) { dev_err(hsw->dev, "error: stream committed for buffer\n"); return -EINVAL; } stream->request.ringinfo.ring_pt_address = ring_pt_address; stream->request.ringinfo.num_pages = num_pages; stream->request.ringinfo.ring_size = ring_size; stream->request.ringinfo.ring_offset = ring_offset; stream->request.ringinfo.ring_first_pfn = ring_first_pfn; trace_hsw_stream_buffer(stream); return 0; } int sst_hsw_stream_set_module_info(struct sst_hsw *hsw, struct sst_hsw_stream *stream, struct sst_module_runtime *runtime) { struct sst_hsw_module_map *map = &stream->request.map; struct sst_dsp *dsp = sst_hsw_get_dsp(hsw); struct sst_module *module = runtime->module; if (stream->commited) { dev_err(hsw->dev, "error: stream committed for set module\n"); return -EINVAL; } /* only support initial module atm */ map->module_entries_count = 1; map->module_entries[0].module_id = module->id; map->module_entries[0].entry_point = module->entry; stream->request.persistent_mem.offset = sst_dsp_get_offset(dsp, runtime->persistent_offset, SST_MEM_DRAM); stream->request.persistent_mem.size = module->persistent_size; stream->request.scratch_mem.offset = sst_dsp_get_offset(dsp, dsp->scratch_offset, SST_MEM_DRAM); stream->request.scratch_mem.size = dsp->scratch_size; dev_dbg(hsw->dev, "module %d runtime %d using:\n", module->id, runtime->id); dev_dbg(hsw->dev, " persistent offset 0x%x bytes 0x%x\n", stream->request.persistent_mem.offset, stream->request.persistent_mem.size); dev_dbg(hsw->dev, " scratch offset 0x%x bytes 0x%x\n", stream->request.scratch_mem.offset, stream->request.scratch_mem.size); return 0; } int sst_hsw_stream_commit(struct sst_hsw *hsw, struct sst_hsw_stream *stream) { struct sst_ipc_message request, reply = {0}; int ret; if (!stream) { dev_warn(hsw->dev, "warning: stream is NULL, no stream to commit, ignore it.\n"); return 0; } if (stream->commited) { dev_warn(hsw->dev, "warning: stream is already committed, ignore it.\n"); return 0; } trace_ipc_request("stream alloc", stream->host_id); request.header = IPC_GLB_TYPE(IPC_GLB_ALLOCATE_STREAM); request.data = &stream->request; request.size = sizeof(stream->request); reply.data = &stream->reply; reply.size = sizeof(stream->reply); ret = sst_ipc_tx_message_wait(&hsw->ipc, request, &reply); if (ret < 0) { dev_err(hsw->dev, "error: stream commit failed\n"); return ret; } stream->commited = true; trace_hsw_stream_alloc_reply(stream); return 0; } snd_pcm_uframes_t sst_hsw_stream_get_old_position(struct sst_hsw *hsw, struct sst_hsw_stream *stream) { return stream->old_position; } void sst_hsw_stream_set_old_position(struct sst_hsw *hsw, struct sst_hsw_stream *stream, snd_pcm_uframes_t val) { stream->old_position = val; } bool sst_hsw_stream_get_silence_start(struct sst_hsw *hsw, struct sst_hsw_stream *stream) { return stream->play_silence; } void sst_hsw_stream_set_silence_start(struct sst_hsw *hsw, struct sst_hsw_stream *stream, bool val) { stream->play_silence = val; } /* Stream Information - these calls could be inline but we want the IPC ABI to be opaque to client PCM drivers to cope with any future ABI changes */ int sst_hsw_mixer_get_info(struct sst_hsw *hsw) { struct sst_ipc_message request = {0}, reply = {0}; int ret; request.header = IPC_GLB_TYPE(IPC_GLB_GET_MIXER_STREAM_INFO); reply.data = &hsw->mixer_info; reply.size = sizeof(hsw->mixer_info); trace_ipc_request("get global mixer info", 0); ret = sst_ipc_tx_message_wait(&hsw->ipc, request, &reply); if (ret < 0) { dev_err(hsw->dev, "error: get stream info failed\n"); return ret; } trace_hsw_mixer_info_reply(&hsw->mixer_info); return 0; } /* Send stream command */ static int sst_hsw_stream_operations(struct sst_hsw *hsw, int type, int stream_id, int wait) { struct sst_ipc_message request = {0}; request.header = IPC_GLB_TYPE(IPC_GLB_STREAM_MESSAGE); request.header |= IPC_STR_TYPE(type) | (stream_id << IPC_STR_ID_SHIFT); if (wait) return sst_ipc_tx_message_wait(&hsw->ipc, request, NULL); else return sst_ipc_tx_message_nowait(&hsw->ipc, request); } /* Stream ALSA trigger operations */ int sst_hsw_stream_pause(struct sst_hsw *hsw, struct sst_hsw_stream *stream, int wait) { int ret; if (!stream) { dev_warn(hsw->dev, "warning: stream is NULL, no stream to pause, ignore it.\n"); return 0; } trace_ipc_request("stream pause", stream->reply.stream_hw_id); ret = sst_hsw_stream_operations(hsw, IPC_STR_PAUSE, stream->reply.stream_hw_id, wait); if (ret < 0) dev_err(hsw->dev, "error: failed to pause stream %d\n", stream->reply.stream_hw_id); return ret; } int sst_hsw_stream_resume(struct sst_hsw *hsw, struct sst_hsw_stream *stream, int wait) { int ret; if (!stream) { dev_warn(hsw->dev, "warning: stream is NULL, no stream to resume, ignore it.\n"); return 0; } trace_ipc_request("stream resume", stream->reply.stream_hw_id); ret = sst_hsw_stream_operations(hsw, IPC_STR_RESUME, stream->reply.stream_hw_id, wait); if (ret < 0) dev_err(hsw->dev, "error: failed to resume stream %d\n", stream->reply.stream_hw_id); return ret; } int sst_hsw_stream_reset(struct sst_hsw *hsw, struct sst_hsw_stream *stream) { int ret, tries = 10; if (!stream) { dev_warn(hsw->dev, "warning: stream is NULL, no stream to reset, ignore it.\n"); return 0; } /* dont reset streams that are not commited */ if (!stream->commited) return 0; /* wait for pause to complete before we reset the stream */ while (stream->running && --tries) msleep(1); if (!tries) { dev_err(hsw->dev, "error: reset stream %d still running\n", stream->reply.stream_hw_id); return -EINVAL; } trace_ipc_request("stream reset", stream->reply.stream_hw_id); ret = sst_hsw_stream_operations(hsw, IPC_STR_RESET, stream->reply.stream_hw_id, 1); if (ret < 0) dev_err(hsw->dev, "error: failed to reset stream %d\n", stream->reply.stream_hw_id); return ret; } /* Stream pointer positions */ u32 sst_hsw_get_dsp_position(struct sst_hsw *hsw, struct sst_hsw_stream *stream) { u32 rpos; sst_dsp_read(hsw->dsp, &rpos, stream->reply.read_position_register_address, sizeof(rpos)); return rpos; } /* Stream presentation (monotonic) positions */ u64 sst_hsw_get_dsp_presentation_position(struct sst_hsw *hsw, struct sst_hsw_stream *stream) { u64 ppos; sst_dsp_read(hsw->dsp, &ppos, stream->reply.presentation_position_register_address, sizeof(ppos)); return ppos; } /* physical BE config */ int sst_hsw_device_set_config(struct sst_hsw *hsw, enum sst_hsw_device_id dev, enum sst_hsw_device_mclk mclk, enum sst_hsw_device_mode mode, u32 clock_divider) { struct sst_ipc_message request; struct sst_hsw_ipc_device_config_req config; int ret; trace_ipc_request("set device config", dev); hsw->dx_dev = config.ssp_interface = dev; hsw->dx_mclk = config.clock_frequency = mclk; hsw->dx_mode = config.mode = mode; hsw->dx_clock_divider = config.clock_divider = clock_divider; if (mode == SST_HSW_DEVICE_TDM_CLOCK_MASTER) config.channels = 4; else config.channels = 2; trace_hsw_device_config_req(&config); request.header = IPC_GLB_TYPE(IPC_GLB_SET_DEVICE_FORMATS); request.data = &config; request.size = sizeof(config); ret = sst_ipc_tx_message_wait(&hsw->ipc, request, NULL); if (ret < 0) dev_err(hsw->dev, "error: set device formats failed\n"); return ret; } EXPORT_SYMBOL_GPL(sst_hsw_device_set_config); /* DX Config */ int sst_hsw_dx_set_state(struct sst_hsw *hsw, enum sst_hsw_dx_state state, struct sst_hsw_ipc_dx_reply *dx) { struct sst_ipc_message request, reply = {0}; u32 state_; int ret, item; state_ = state; request.header = IPC_GLB_TYPE(IPC_GLB_ENTER_DX_STATE); request.data = &state_; request.size = sizeof(state_); reply.data = dx; reply.size = sizeof(*dx); trace_ipc_request("PM enter Dx state", state); ret = sst_ipc_tx_message_wait(&hsw->ipc, request, &reply); if (ret < 0) { dev_err(hsw->dev, "ipc: error set dx state %d failed\n", state); return ret; } for (item = 0; item < dx->entries_no; item++) { dev_dbg(hsw->dev, "Item[%d] offset[%x] - size[%x] - source[%x]\n", item, dx->mem_info[item].offset, dx->mem_info[item].size, dx->mem_info[item].source); } dev_dbg(hsw->dev, "ipc: got %d entry numbers for state %d\n", dx->entries_no, state); return ret; } struct sst_module_runtime *sst_hsw_runtime_module_create(struct sst_hsw *hsw, int mod_id, int offset) { struct sst_dsp *dsp = hsw->dsp; struct sst_module *module; struct sst_module_runtime *runtime; int err; module = sst_module_get_from_id(dsp, mod_id); if (module == NULL) { dev_err(dsp->dev, "error: failed to get module %d for pcm\n", mod_id); return NULL; } runtime = sst_module_runtime_new(module, mod_id, NULL); if (runtime == NULL) { dev_err(dsp->dev, "error: failed to create module %d runtime\n", mod_id); return NULL; } err = sst_module_runtime_alloc_blocks(runtime, offset); if (err < 0) { dev_err(dsp->dev, "error: failed to alloc blocks for module %d runtime\n", mod_id); sst_module_runtime_free(runtime); return NULL; } dev_dbg(dsp->dev, "runtime id %d created for module %d\n", runtime->id, mod_id); return runtime; } void sst_hsw_runtime_module_free(struct sst_module_runtime *runtime) { sst_module_runtime_free_blocks(runtime); sst_module_runtime_free(runtime); } #ifdef CONFIG_PM static int sst_hsw_dx_state_dump(struct sst_hsw *hsw) { struct sst_dsp *sst = hsw->dsp; u32 item, offset, size; int ret = 0; trace_ipc_request("PM state dump. Items #", SST_HSW_MAX_DX_REGIONS); if (hsw->dx.entries_no > SST_HSW_MAX_DX_REGIONS) { dev_err(hsw->dev, "error: number of FW context regions greater than %d\n", SST_HSW_MAX_DX_REGIONS); memset(&hsw->dx, 0, sizeof(hsw->dx)); return -EINVAL; } ret = sst_dsp_dma_get_channel(sst, 0); if (ret < 0) { dev_err(hsw->dev, "error: cant allocate dma channel %d\n", ret); return ret; } /* set on-demond mode on engine 0 channel 3 */ sst_dsp_shim_update_bits(sst, SST_HMDC, SST_HMDC_HDDA_E0_ALLCH | SST_HMDC_HDDA_E1_ALLCH, SST_HMDC_HDDA_E0_ALLCH | SST_HMDC_HDDA_E1_ALLCH); for (item = 0; item < hsw->dx.entries_no; item++) { if (hsw->dx.mem_info[item].source == SST_HSW_DX_TYPE_MEMORY_DUMP && hsw->dx.mem_info[item].offset > DSP_DRAM_ADDR_OFFSET && hsw->dx.mem_info[item].offset < DSP_DRAM_ADDR_OFFSET + SST_HSW_DX_CONTEXT_SIZE) { offset = hsw->dx.mem_info[item].offset - DSP_DRAM_ADDR_OFFSET; size = (hsw->dx.mem_info[item].size + 3) & (~3); ret = sst_dsp_dma_copyfrom(sst, hsw->dx_context_paddr + offset, sst->addr.lpe_base + offset, size); if (ret < 0) { dev_err(hsw->dev, "error: FW context dump failed\n"); memset(&hsw->dx, 0, sizeof(hsw->dx)); goto out; } } } out: sst_dsp_dma_put_channel(sst); return ret; } static int sst_hsw_dx_state_restore(struct sst_hsw *hsw) { struct sst_dsp *sst = hsw->dsp; u32 item, offset, size; int ret; for (item = 0; item < hsw->dx.entries_no; item++) { if (hsw->dx.mem_info[item].source == SST_HSW_DX_TYPE_MEMORY_DUMP && hsw->dx.mem_info[item].offset > DSP_DRAM_ADDR_OFFSET && hsw->dx.mem_info[item].offset < DSP_DRAM_ADDR_OFFSET + SST_HSW_DX_CONTEXT_SIZE) { offset = hsw->dx.mem_info[item].offset - DSP_DRAM_ADDR_OFFSET; size = (hsw->dx.mem_info[item].size + 3) & (~3); ret = sst_dsp_dma_copyto(sst, sst->addr.lpe_base + offset, hsw->dx_context_paddr + offset, size); if (ret < 0) { dev_err(hsw->dev, "error: FW context restore failed\n"); return ret; } } } return 0; } int sst_hsw_dsp_load(struct sst_hsw *hsw) { struct sst_dsp *dsp = hsw->dsp; struct sst_fw *sst_fw, *t; int ret; dev_dbg(hsw->dev, "loading audio DSP...."); ret = sst_dsp_wake(dsp); if (ret < 0) { dev_err(hsw->dev, "error: failed to wake audio DSP\n"); return -ENODEV; } ret = sst_dsp_dma_get_channel(dsp, 0); if (ret < 0) { dev_err(hsw->dev, "error: cant allocate dma channel %d\n", ret); return ret; } list_for_each_entry_safe_reverse(sst_fw, t, &dsp->fw_list, list) { ret = sst_fw_reload(sst_fw); if (ret < 0) { dev_err(hsw->dev, "error: SST FW reload failed\n"); sst_dsp_dma_put_channel(dsp); return -ENOMEM; } } ret = sst_block_alloc_scratch(hsw->dsp); if (ret < 0) return -EINVAL; sst_dsp_dma_put_channel(dsp); return 0; } static int sst_hsw_dsp_restore(struct sst_hsw *hsw) { struct sst_dsp *dsp = hsw->dsp; int ret; dev_dbg(hsw->dev, "restoring audio DSP...."); ret = sst_dsp_dma_get_channel(dsp, 0); if (ret < 0) { dev_err(hsw->dev, "error: cant allocate dma channel %d\n", ret); return ret; } ret = sst_hsw_dx_state_restore(hsw); if (ret < 0) { dev_err(hsw->dev, "error: SST FW context restore failed\n"); sst_dsp_dma_put_channel(dsp); return -ENOMEM; } sst_dsp_dma_put_channel(dsp); /* wait for DSP boot completion */ sst_dsp_boot(dsp); return ret; } int sst_hsw_dsp_runtime_suspend(struct sst_hsw *hsw) { int ret; dev_dbg(hsw->dev, "audio dsp runtime suspend\n"); ret = sst_hsw_dx_set_state(hsw, SST_HSW_DX_STATE_D3, &hsw->dx); if (ret < 0) return ret; sst_dsp_stall(hsw->dsp); ret = sst_hsw_dx_state_dump(hsw); if (ret < 0) return ret; sst_ipc_drop_all(&hsw->ipc); return 0; } int sst_hsw_dsp_runtime_sleep(struct sst_hsw *hsw) { struct sst_fw *sst_fw, *t; struct sst_dsp *dsp = hsw->dsp; list_for_each_entry_safe(sst_fw, t, &dsp->fw_list, list) { sst_fw_unload(sst_fw); } sst_block_free_scratch(dsp); hsw->boot_complete = false; sst_dsp_sleep(dsp); return 0; } int sst_hsw_dsp_runtime_resume(struct sst_hsw *hsw) { struct device *dev = hsw->dev; int ret; dev_dbg(dev, "audio dsp runtime resume\n"); if (hsw->boot_complete) return 1; /* tell caller no action is required */ ret = sst_hsw_dsp_restore(hsw); if (ret < 0) dev_err(dev, "error: audio DSP boot failure\n"); sst_hsw_init_module_state(hsw); ret = wait_event_timeout(hsw->boot_wait, hsw->boot_complete, msecs_to_jiffies(IPC_BOOT_MSECS)); if (ret == 0) { dev_err(hsw->dev, "error: audio DSP boot timeout IPCD 0x%x IPCX 0x%x\n", sst_dsp_shim_read_unlocked(hsw->dsp, SST_IPCD), sst_dsp_shim_read_unlocked(hsw->dsp, SST_IPCX)); return -EIO; } /* Set ADSP SSP port settings - sadly the FW does not store SSP port settings as part of the PM context. */ ret = sst_hsw_device_set_config(hsw, hsw->dx_dev, hsw->dx_mclk, hsw->dx_mode, hsw->dx_clock_divider); if (ret < 0) dev_err(dev, "error: SSP re-initialization failed\n"); return ret; } #endif struct sst_dsp *sst_hsw_get_dsp(struct sst_hsw *hsw) { return hsw->dsp; } void sst_hsw_init_module_state(struct sst_hsw *hsw) { struct sst_module *module; enum sst_hsw_module_id id; /* the base fw contains several modules */ for (id = SST_HSW_MODULE_BASE_FW; id < SST_HSW_MAX_MODULE_ID; id++) { module = sst_module_get_from_id(hsw->dsp, id); if (module) { /* module waves is active only after being enabled */ if (id == SST_HSW_MODULE_WAVES) module->state = SST_MODULE_STATE_INITIALIZED; else module->state = SST_MODULE_STATE_ACTIVE; } } } bool sst_hsw_is_module_loaded(struct sst_hsw *hsw, u32 module_id) { struct sst_module *module; module = sst_module_get_from_id(hsw->dsp, module_id); if (module == NULL || module->state == SST_MODULE_STATE_UNLOADED) return false; else return true; } bool sst_hsw_is_module_active(struct sst_hsw *hsw, u32 module_id) { struct sst_module *module; module = sst_module_get_from_id(hsw->dsp, module_id); if (module != NULL && module->state == SST_MODULE_STATE_ACTIVE) return true; else return false; } void sst_hsw_set_module_enabled_rtd3(struct sst_hsw *hsw, u32 module_id) { hsw->enabled_modules_rtd3 |= (1 << module_id); } void sst_hsw_set_module_disabled_rtd3(struct sst_hsw *hsw, u32 module_id) { hsw->enabled_modules_rtd3 &= ~(1 << module_id); } bool sst_hsw_is_module_enabled_rtd3(struct sst_hsw *hsw, u32 module_id) { return hsw->enabled_modules_rtd3 & (1 << module_id); } void sst_hsw_reset_param_buf(struct sst_hsw *hsw) { hsw->param_idx_w = 0; hsw->param_idx_r = 0; memset((void *)hsw->param_buf, 0, sizeof(hsw->param_buf)); } int sst_hsw_store_param_line(struct sst_hsw *hsw, u8 *buf) { /* save line to the first available position of param buffer */ if (hsw->param_idx_w > WAVES_PARAM_LINES - 1) { dev_warn(hsw->dev, "warning: param buffer overflow!\n"); return -EPERM; } memcpy(hsw->param_buf[hsw->param_idx_w], buf, WAVES_PARAM_COUNT); hsw->param_idx_w++; return 0; } int sst_hsw_load_param_line(struct sst_hsw *hsw, u8 *buf) { u8 id = 0; /* read the first matching line from param buffer */ while (hsw->param_idx_r < WAVES_PARAM_LINES) { id = hsw->param_buf[hsw->param_idx_r][0]; hsw->param_idx_r++; if (buf[0] == id) { memcpy(buf, hsw->param_buf[hsw->param_idx_r], WAVES_PARAM_COUNT); break; } } if (hsw->param_idx_r > WAVES_PARAM_LINES - 1) { dev_dbg(hsw->dev, "end of buffer, roll to the beginning\n"); hsw->param_idx_r = 0; return 0; } return 0; } int sst_hsw_launch_param_buf(struct sst_hsw *hsw) { int ret, idx; if (!sst_hsw_is_module_active(hsw, SST_HSW_MODULE_WAVES)) { dev_dbg(hsw->dev, "module waves is not active\n"); return 0; } /* put all param lines to DSP through ipc */ for (idx = 0; idx < hsw->param_idx_w; idx++) { ret = sst_hsw_module_set_param(hsw, SST_HSW_MODULE_WAVES, 0, hsw->param_buf[idx][0], WAVES_PARAM_COUNT, hsw->param_buf[idx]); if (ret < 0) return ret; } return 0; } int sst_hsw_module_load(struct sst_hsw *hsw, u32 module_id, u32 instance_id, char *name) { int ret = 0; const struct firmware *fw = NULL; struct sst_fw *hsw_sst_fw; struct sst_module *module; struct device *dev = hsw->dev; struct sst_dsp *dsp = hsw->dsp; dev_dbg(dev, "sst_hsw_module_load id=%d, name='%s'", module_id, name); module = sst_module_get_from_id(dsp, module_id); if (module == NULL) { /* loading for the first time */ if (module_id == SST_HSW_MODULE_BASE_FW) { /* for base module: use fw requested in acpi probe */ fw = dsp->pdata->fw; if (!fw) { dev_err(dev, "request Base fw failed\n"); return -ENODEV; } } else { /* try and load any other optional modules if they are * available. Use dev_info instead of dev_err in case * request firmware failed */ ret = request_firmware(&fw, name, dev); if (ret) { dev_info(dev, "fw image %s not available(%d)\n", name, ret); return ret; } } hsw_sst_fw = sst_fw_new(dsp, fw, hsw); if (hsw_sst_fw == NULL) { dev_err(dev, "error: failed to load firmware\n"); ret = -ENOMEM; goto out; } module = sst_module_get_from_id(dsp, module_id); if (module == NULL) { dev_err(dev, "error: no module %d in firmware %s\n", module_id, name); } } else dev_info(dev, "module %d (%s) already loaded\n", module_id, name); out: /* release fw, but base fw should be released by acpi driver */ if (fw && module_id != SST_HSW_MODULE_BASE_FW) release_firmware(fw); return ret; } int sst_hsw_module_enable(struct sst_hsw *hsw, u32 module_id, u32 instance_id) { int ret; struct sst_ipc_message request; struct sst_hsw_ipc_module_config config; struct sst_module *module; struct sst_module_runtime *runtime; struct device *dev = hsw->dev; struct sst_dsp *dsp = hsw->dsp; if (!sst_hsw_is_module_loaded(hsw, module_id)) { dev_dbg(dev, "module %d not loaded\n", module_id); return 0; } if (sst_hsw_is_module_active(hsw, module_id)) { dev_info(dev, "module %d already enabled\n", module_id); return 0; } module = sst_module_get_from_id(dsp, module_id); if (module == NULL) { dev_err(dev, "module %d not valid\n", module_id); return -ENXIO; } runtime = sst_module_runtime_get_from_id(module, module_id); if (runtime == NULL) { dev_err(dev, "runtime %d not valid", module_id); return -ENXIO; } request.header = IPC_GLB_TYPE(IPC_GLB_MODULE_OPERATION) | IPC_MODULE_OPERATION(IPC_MODULE_ENABLE) | IPC_MODULE_ID(module_id); dev_dbg(dev, "module enable header: %x\n", (u32)request.header); config.map.module_entries_count = 1; config.map.module_entries[0].module_id = module->id; config.map.module_entries[0].entry_point = module->entry; config.persistent_mem.offset = sst_dsp_get_offset(dsp, runtime->persistent_offset, SST_MEM_DRAM); config.persistent_mem.size = module->persistent_size; config.scratch_mem.offset = sst_dsp_get_offset(dsp, dsp->scratch_offset, SST_MEM_DRAM); config.scratch_mem.size = module->scratch_size; dev_dbg(dev, "mod %d enable p:%d @ %x, s:%d @ %x, ep: %x", config.map.module_entries[0].module_id, config.persistent_mem.size, config.persistent_mem.offset, config.scratch_mem.size, config.scratch_mem.offset, config.map.module_entries[0].entry_point); request.data = &config; request.size = sizeof(config); ret = sst_ipc_tx_message_wait(&hsw->ipc, request, NULL); if (ret < 0) dev_err(dev, "ipc: module enable failed - %d\n", ret); else module->state = SST_MODULE_STATE_ACTIVE; return ret; } int sst_hsw_module_disable(struct sst_hsw *hsw, u32 module_id, u32 instance_id) { int ret; struct sst_ipc_message request = {0}; struct sst_module *module; struct device *dev = hsw->dev; struct sst_dsp *dsp = hsw->dsp; if (!sst_hsw_is_module_loaded(hsw, module_id)) { dev_dbg(dev, "module %d not loaded\n", module_id); return 0; } if (!sst_hsw_is_module_active(hsw, module_id)) { dev_info(dev, "module %d already disabled\n", module_id); return 0; } module = sst_module_get_from_id(dsp, module_id); if (module == NULL) { dev_err(dev, "module %d not valid\n", module_id); return -ENXIO; } request.header = IPC_GLB_TYPE(IPC_GLB_MODULE_OPERATION) | IPC_MODULE_OPERATION(IPC_MODULE_DISABLE) | IPC_MODULE_ID(module_id); ret = sst_ipc_tx_message_wait(&hsw->ipc, request, NULL); if (ret < 0) dev_err(dev, "module disable failed - %d\n", ret); else module->state = SST_MODULE_STATE_INITIALIZED; return ret; } int sst_hsw_module_set_param(struct sst_hsw *hsw, u32 module_id, u32 instance_id, u32 parameter_id, u32 param_size, char *param) { int ret; struct sst_ipc_message request = {0}; u32 payload_size = 0; struct sst_hsw_transfer_parameter *parameter; struct device *dev = hsw->dev; request.header = IPC_GLB_TYPE(IPC_GLB_MODULE_OPERATION) | IPC_MODULE_OPERATION(IPC_MODULE_SET_PARAMETER) | IPC_MODULE_ID(module_id); dev_dbg(dev, "sst_hsw_module_set_param header=%x\n", (u32)request.header); payload_size = param_size + sizeof(struct sst_hsw_transfer_parameter) - sizeof(struct sst_hsw_transfer_list); dev_dbg(dev, "parameter size : %d\n", param_size); dev_dbg(dev, "payload size : %d\n", payload_size); if (payload_size <= SST_HSW_IPC_MAX_SHORT_PARAMETER_SIZE) { /* short parameter, mailbox can contain data */ dev_dbg(dev, "transfer parameter size : %zu\n", request.size); request.size = ALIGN(payload_size, 4); dev_dbg(dev, "transfer parameter aligned size : %zu\n", request.size); parameter = kzalloc(request.size, GFP_KERNEL); if (parameter == NULL) return -ENOMEM; memcpy(parameter->data, param, param_size); } else { dev_warn(dev, "transfer parameter size too large!"); return 0; } parameter->parameter_id = parameter_id; parameter->data_size = param_size; request.data = parameter; ret = sst_ipc_tx_message_wait(&hsw->ipc, request, NULL); if (ret < 0) dev_err(dev, "ipc: module set parameter failed - %d\n", ret); kfree(parameter); return ret; } static struct sst_dsp_device hsw_dev = { .thread = hsw_irq_thread, .ops = &haswell_ops, }; static void hsw_tx_msg(struct sst_generic_ipc *ipc, struct ipc_message *msg) { /* send the message */ sst_dsp_outbox_write(ipc->dsp, msg->tx.data, msg->tx.size); sst_dsp_ipc_msg_tx(ipc->dsp, msg->tx.header); } static void hsw_shim_dbg(struct sst_generic_ipc *ipc, const char *text) { struct sst_dsp *sst = ipc->dsp; u32 isr, ipcd, imrx, ipcx; ipcx = sst_dsp_shim_read_unlocked(sst, SST_IPCX); isr = sst_dsp_shim_read_unlocked(sst, SST_ISRX); ipcd = sst_dsp_shim_read_unlocked(sst, SST_IPCD); imrx = sst_dsp_shim_read_unlocked(sst, SST_IMRX); dev_err(ipc->dev, "ipc: --%s-- ipcx 0x%8.8x isr 0x%8.8x ipcd 0x%8.8x imrx 0x%8.8x\n", text, ipcx, isr, ipcd, imrx); } static void hsw_tx_data_copy(struct ipc_message *msg, char *tx_data, size_t tx_size) { memcpy(msg->tx.data, tx_data, tx_size); } static u64 hsw_reply_msg_match(u64 header, u64 *mask) { /* clear reply bits & status bits */ header &= ~(IPC_STATUS_MASK | IPC_GLB_REPLY_MASK); *mask = (u64)-1; return header; } static bool hsw_is_dsp_busy(struct sst_dsp *dsp) { u64 ipcx; ipcx = sst_dsp_shim_read_unlocked(dsp, SST_IPCX); return (ipcx & (SST_IPCX_BUSY | SST_IPCX_DONE)); } int sst_hsw_dsp_init(struct device *dev, struct sst_pdata *pdata) { struct sst_hsw_ipc_fw_version version; struct sst_hsw *hsw; struct sst_generic_ipc *ipc; int ret; dev_dbg(dev, "initialising Audio DSP IPC\n"); hsw = devm_kzalloc(dev, sizeof(*hsw), GFP_KERNEL); if (hsw == NULL) return -ENOMEM; hsw->dev = dev; ipc = &hsw->ipc; ipc->dev = dev; ipc->ops.tx_msg = hsw_tx_msg; ipc->ops.shim_dbg = hsw_shim_dbg; ipc->ops.tx_data_copy = hsw_tx_data_copy; ipc->ops.reply_msg_match = hsw_reply_msg_match; ipc->ops.is_dsp_busy = hsw_is_dsp_busy; ipc->tx_data_max_size = IPC_MAX_MAILBOX_BYTES; ipc->rx_data_max_size = IPC_MAX_MAILBOX_BYTES; ret = sst_ipc_init(ipc); if (ret != 0) goto ipc_init_err; INIT_LIST_HEAD(&hsw->stream_list); init_waitqueue_head(&hsw->boot_wait); hsw_dev.thread_context = hsw; /* init SST shim */ hsw->dsp = sst_dsp_new(dev, &hsw_dev, pdata); if (hsw->dsp == NULL) { ret = -ENODEV; goto dsp_new_err; } ipc->dsp = hsw->dsp; /* allocate DMA buffer for context storage */ hsw->dx_context = dma_alloc_coherent(hsw->dsp->dma_dev, SST_HSW_DX_CONTEXT_SIZE, &hsw->dx_context_paddr, GFP_KERNEL); if (hsw->dx_context == NULL) { ret = -ENOMEM; goto dma_err; } /* keep the DSP in reset state for base FW loading */ sst_dsp_reset(hsw->dsp); /* load base module and other modules in base firmware image */ ret = sst_hsw_module_load(hsw, SST_HSW_MODULE_BASE_FW, 0, "Base"); if (ret < 0) goto fw_err; /* try to load module waves */ sst_hsw_module_load(hsw, SST_HSW_MODULE_WAVES, 0, "intel/IntcPP01.bin"); /* allocate scratch mem regions */ ret = sst_block_alloc_scratch(hsw->dsp); if (ret < 0) goto boot_err; /* init param buffer */ sst_hsw_reset_param_buf(hsw); /* wait for DSP boot completion */ sst_dsp_boot(hsw->dsp); ret = wait_event_timeout(hsw->boot_wait, hsw->boot_complete, msecs_to_jiffies(IPC_BOOT_MSECS)); if (ret == 0) { ret = -EIO; dev_err(hsw->dev, "error: audio DSP boot timeout IPCD 0x%x IPCX 0x%x\n", sst_dsp_shim_read_unlocked(hsw->dsp, SST_IPCD), sst_dsp_shim_read_unlocked(hsw->dsp, SST_IPCX)); goto boot_err; } /* init module state after boot */ sst_hsw_init_module_state(hsw); /* get the FW version */ sst_hsw_fw_get_version(hsw, &version); /* get the globalmixer */ ret = sst_hsw_mixer_get_info(hsw); if (ret < 0) { dev_err(hsw->dev, "error: failed to get stream info\n"); goto boot_err; } pdata->dsp = hsw; return 0; boot_err: sst_dsp_reset(hsw->dsp); sst_fw_free_all(hsw->dsp); fw_err: dma_free_coherent(hsw->dsp->dma_dev, SST_HSW_DX_CONTEXT_SIZE, hsw->dx_context, hsw->dx_context_paddr); dma_err: sst_dsp_free(hsw->dsp); dsp_new_err: sst_ipc_fini(ipc); ipc_init_err: return ret; } EXPORT_SYMBOL_GPL(sst_hsw_dsp_init); void sst_hsw_dsp_free(struct device *dev, struct sst_pdata *pdata) { struct sst_hsw *hsw = pdata->dsp; sst_dsp_reset(hsw->dsp); sst_fw_free_all(hsw->dsp); dma_free_coherent(hsw->dsp->dma_dev, SST_HSW_DX_CONTEXT_SIZE, hsw->dx_context, hsw->dx_context_paddr); sst_dsp_free(hsw->dsp); sst_ipc_fini(&hsw->ipc); } EXPORT_SYMBOL_GPL(sst_hsw_dsp_free);
Low
[ 0.5248226950354611, 27.75, 25.125 ]
All Places Imagine Curaçao with a zoo like no zoo you can imagine, Where everybody can learn and Play, Help transform The Curaçao Zoo into a Magical, Educational and Ecologically correct Zoo, That opens our Hearts and Minds, Ignites our curiosity and Fires up our Wildest Imaginations. Grote Knip (also called Playa Abou) is a beach located at the western side of the island, between the villages of Westpunt and Lagun. The beach gives way to a small lagune between high rocks. It is freely accessible to the public. The beach is used as a starting point Read more [...] The view from above Playa Forti is right out of a postcard, with the fishing boats and a panorama of the island's western tip. Here you'll find pleasantly different coarse brown sand and tiny smooth pebbles but almost no shade. There are several snack bars and a restaurant at the Read more [...] Playa Piskado or Playa Grandi This tiny fishermen's beach is also popular for snorkeling and diving and has some good photo ops of the boats and nets. Manchineel trees provide some shade. A small snack bar is open on the weekend. Entrance to the water is somewhat rocky. This small cove is popular for snorkeling and diving, and has a roped-off area with a floating platform. It is located down steep stone steps from the parking area. Halfway between the parking area and the beach is a shaded terrace with a snack bar and dive shop. From Playa Read more [...] Consistent fuel quality and safety first, that is what we deliver! Take a tour on the island and find the gas station in your area. Curoil owns four gas stations and manages one on Curacao.All our gas stations carry atleast the three fuel types, Mogas 92, 95 and Diesel. All Read more [...] Consistent fuel quality and safety first, that is what we deliver! Take a tour on the island and find the gas station in your area. Curoil owns four gas stations and manages one on Curacao.All our gas stations carry atleast the three fuel types, Mogas 92, 95 and Diesel. All Read more [...] Consistent fuel quality and safety first, that is what we deliver! Take a tour on the island and find the gas station in your area. Curoil owns four gas stations and manages one on Curacao.All our gas stations carry atleast the three fuel types, Mogas 92, 95 and Diesel. All Read more [...] Consistent fuel quality and safety first, that is what we deliver! Take a tour on the island and find the gas station in your area. Curoil owns four gas stations and manages one on Curacao.All our gas stations carry atleast the three fuel types, Mogas 92, 95 and Diesel. All Read more [...] Consistent fuel quality and safety first, that is what we deliver! Take a tour on the island and find the gas station in your area. Curoil owns four gas stations and manages one on Curacao.All our gas stations carry atleast the three fuel types, Mogas 92, 95 and Diesel. All Read more [...]
Mid
[ 0.5762004175365341, 34.5, 25.375 ]
Q: Error in C: array type has incomplete element type I am working on a project that modifies part of the Android OS, and when I tried to implement a new system call to return the status of all the processes, I encountered the following error: kernel/sys.c: error: array tpye has incomplete element type. What I did in sys.c is the following: /***previous code in sys.c***/ SYSCALL_DEFINE2(new_syscall, struct info __user*, buf, int __user*, nr){ if(!buf || !nr) return -EINVAL; int nr_copy; int success; success = copy_from_user(&nr_copy, nr, sizeof(int)); if(success == 0) return -EINVAL; if(nr_copy < 1) return -EINVAL; struct info buf_copy[nr_copy]; /************* return 0; } Complier complained about the line marked with stars. My info.h file looks like this: #ifndef __LINUX_INFO_H #define __LINUX_INFO_H struct info { long state; pid_t pid; pid_t parent_pid; }; #endif I tried including the info.h in sys.c, but it didn't help at all. Can anyone provide me some directions on what I should look into? Thanks A: What compiler are you using? Dynamically sized arrays are a newish C feature that might not be supported. OTOH, they are allocated on the stack, and that is a very scarce commodity in-kernel. You should allocate memory for the array via kmalloc or one of its ilk.
Mid
[ 0.6221198156682021, 33.75, 20.5 ]
Q: Using .htaccess to redirect www URLs to non-www for https Please provide me with .htaccess syntax to do the following: Redirect from http to https Redirect from https://www.domain.com.uk to https://domain.com.uk I tried the following but it didn't work: RewriteCond %{HTTP_HOST} ^www.(.*) RewriteRule ^.*$ https://%1/$1 [R=301,L] A: Try adding the following to your htaccess file in the root folder of your domain. RewriteEngine on RewriteBase / #if not domain.com.uk then redirect to domaim.com.uk RewriteCond %{HTTP_HOST} !^domain\.com\.uk$ [NC] RewriteRule .* http://domain.com.uk%{REQUEST_URI} [L,R=301] #if not https RewriteCond %{HTTPS} off #redirect to https RewriteRule .* https://%{HTTP_HOST}%{REQUEST_URI} [L,R=301]
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Q: How to run multiple mongodb databases with same name on single mongodb instance? We are trying to minimize CI pipeline resource usage by running multiple apps (dev branch deployments of the same app) on a single physical mongodb instance. How can this be done best? Currently each branch has its own physical mongodb instance. The system has multiple logical databases for each single branch deployment. Example of current state: Branch A -> programatically (node.js) spawns own mongodb with logical databases UserDb, EventDb, CarDb Branch B -> also spawns its mongodb with logical databases UserDb, EventDb, CarDb Goal: single, shared mongodb instance Branch A -> logical databases UserDb, EventDb, CarDb running on the single mongodb instance Branch B -> same databases of Branch A and B are independent A: The best way of doing this will be to call the databases different names (like branch_b_UserDb, branch_b_EventDb, etc). by willis in How to run multiple mongodb databases with same name on single mongodb instance?
Mid
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Digital video capabilities can be incorporated into a wide range of devices, including digital televisions, digital direct broadcast systems, wireless communication devices, personal digital assistants (PDAs), laptop computers, desktop computers, video game consoles, digital cameras, digital recording devices, cellular or satellite radio telephones, and the like. Digital video devices can provide significant improvements over conventional analog video systems in processing and transmitting video sequences. Different video encoding standards have been established for encoding digital video sequences. The Moving Picture Experts Group (MPEG), for example, has developed a number of standards including MPEG-1, MPEG-2 and MPEG-4. Other examples include the International Telecommunication Union (ITU)-T H.263 standard, and the ITU-T H.264 standard and its counterpart, ISO/IEC MPEG-4, Part 10, i.e., Advanced Video Coding (AVC). These video encoding standards support improved transmission efficiency of video sequences by encoding data in a compressed manner. Various video encoding standards support video encoding techniques that utilize similarities between successive video frames, referred to as temporal or Inter-frame correlation, to provide Inter-frame compression. The Inter-frame compression techniques exploit data redundancy across frames by converting pixel-based representations of video frames to motion representations. Frames encoded using Inter-frame techniques are referred to as P (“predictive”) frames or B (“bi-directional”) frames. Some frames, referred to as I (“intra”) frames, are encoded using spatial compression, which is non-predictive.
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Researchers at the Yale School of Public Health have discovered a mathematical relationship that sheds new light on the rate at which cancer cells mutate and why some survive and rapidly multiply, yet others do not. The discovery by members of the laboratory of Jeffrey Townsend, Ph.D., the Elihu Professor of Biostatistics and of Ecology and Evolutionary Biology, will allow essential calculations to be performed that determine the likely scope of cancerous cells as they develop. The finding has implications for decision-making for precision-medicine tumor boards, the selection and design of clinical trials, the development of pharmaceuticals and basic research prioritization. The study is published in the Journal of the National Cancer Institute. “For the past 10 years we’ve been able to calculate from tumor sequencing which mutated genes are winners and losers—which mutated genes help the cancer survive and reproduce, and which do nothing,” Townsend said. “But we haven’t been able to compute their cancer effect size—how important one mutation is compared to another. Now we can.” A major goal of cancer biology is to not just identify the important and unimportant genes to the development of cancer, but to determine the relative importance of each cellular mutation to the survival and spread of cancer cells and, ultimately, what it means for the patient, Townsend explained. In the study, the researchers estimated the effect sizes of all recurrent single nucleotide variants in 22 major types of cancer, and quantified the relative importance of each. Tumor sequencing studies have typically reported how frequent mutations are seen and a statistical measure (a P value) indicating whether the gene is overburdened with mutations beyond expectation, both important measures. However, neither measure is an effect size for cancer. Neither measure communicates how important the gene is to tumorigenesis and cancer disease. To quantify cancer effect size, Townsend and colleagues broke down the frequency that a mutation is observed in tumors into two contributing factors: the baseline mutation rate, and the degree of selection for the mutation in the cancer lineage. Both mutation and selection contribute to the frequency of variants among cells. Townsend and colleagues were able to use diverse genome-scale data to calculate the mutation rate. By essentially dividing out the contribution of mutation from the frequency that mutations were observed in tumors, they showed how to calculate the cancer effect size Townsend credits the breakthrough to insights that come from having a background in evolutionary biology. “Whereas in the cancer world the focus has always been on mutation rates, the focus in evolutionary biology has been on the process of natural selection on those mutations. The quantification of cancer effect sizes is a great example of how interdisciplinary research is not only helpful, but essential to scientific progress,” he said. Why is the cancer effect size important? Townsend uses an example of a tumor, from which a DNA sequence shows that two genes known to be related to cancer have mutated. There are two highly effective drugs targeting these exact mutations but no clinical trial has been conducted to compare them. “By looking at cancer through the lens of evolution we can harness the wealth of molecular data made available through tumor DNA sequencing to both better understand what is driving cancer and to also expand and refine evolutionary theory,” said Vincent Cannataro, Ph.D., a postdoctoral associate and the study’s first author. The study was co-authored by Stephen Gaffney, Ph.D., an associate research scientist at the Yale School of Public Health. The research was funded by a grant from Gilead Sciences, Inc. Publication: Vincent L Cannataro, et al., “Effect Sizes of Somatic Mutations in Cancer,” Journal of the National Cancer Institute, 2018; doi:10.1093/jnci/djy168
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The cancellations also come as students nationwide, including in Massachusetts, planned walkouts to protest gun violence after 17 people were killed in a Florida high school shooting. In Revere, where schools are closed Wednesday, the superintendent said the walkout would take place at 10 a.m. at City Hall. The student walk out in support of the Marjory Stoneman Douglas High School families and gun control as well as the student demonstration to support gun rights will begin tomorrow at 10 AM on the steps of City Hall.
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1. Field of the Invention This invention relates to control centers and more particularly to insulated and isolated bus bars therein. 2. Description of the Prior Art In modern electrical apparatus there is increased attention devoted to operator safety as well as minimizing damage to equipment due to short-circuits. In particular, where electrical bus bars are so disposed that accidental personal contact could occur, then either steel barriers or insulating barriers are provided. Existing designs vary considerably both in execution and in the degree of safety provided by the barriers. However, the existing state of the art has a particular aspect in common, they all create a pocket of air around the bus bars. The size of the air pocket can be quite large so that the bars are regarded to be in a chimney. On the other hand, where the size of the air pocket is quite small, the air is trapped. Patents disclosing insulated bus bars in various aspects are U.S. Pat. Nos. 3,096,131, 3,113,820, 3,170,092, and 3,840,785. Some constructions of insulated bus bars are thermally inefficient because it is difficult to remove heat from hot bars across an insulating and/or trapped pocket of air. Air chimneys generally do not work well because of restrictions that impede significant air flow. Associated with the foregoing has been a problem of isolating adjacent bus bars from each other to prevent the initiation or propagation of fault currents. Moreover, there is a need for elimination of damage due to arcing and tracking between the bus bars.
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#include <stdio.h> struct S0 { unsigned f : 10; }; struct S1 { unsigned f : 32; }; int main(void) { struct S0 l = {1}; struct S1 m = {1}; printf("g = %d\n", (-1 >= l.f)); printf("h = %d\n", (-1 >= m.f)); return 0; }
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Euro Hockey League The Euro Hockey League is an annual men's field hockey cup competition organized by the EHF for the very top hockey clubs in Europe. The competition was launched at the start of the 2007-08 hockey season when it merged and replaced the men's EuroHockey Club Champions Cup (the champions competition) and the EuroHockey Cup Winners Cup (the Cup Winners' competition). Featuring many of the world's best players, the EHL is now seen as the pinnacle of club hockey in Europe (hockey's equivalent of the UEFA Champions League) with top clubs from across the continent playing what many consider to be the most exciting and dynamic club hockey in the world. The competition has been won by eight clubs, two of which have won it more than once. Bloemendaal and UHC Hamburg are the most successful clubs in the tournament's history; having won it three times. The Waterloo Ducks are the reigning champions and became the first Belgian club to win the tournament. Dutch clubs have the highest number of victories (6 wins), followed by Germany (5 wins). Format From the 2019–20 season onwards the tournament features 20 clubs from the 11 highest-ranked EHF member countries. Although the competition is called the Euro Hockey League, after round 1 the competition was a knock-out, rather than league format (similar to the UEFA Champions League in football). From the 2019–20 season onwards round one is also a knock-out format. Qualification From the 2019–20 season onwards each year the 20 available league places are allocated between 11 EHF member countries' National Associations, depending on those National Associations' EHF Club Ranking. National Associations ranked 1-3 in the EHL Ranking Table may enter three teams each in the Euro Hockey League, while National Associations ranked 4-6 may enter two teams each, and National Associations ranked 7-11 one team. National Associations rankings are derived from each country's results in the Euro Hockey League and EuroHockey Club Trophy over the previous 3 years, with the points in the earlier years discounted by 50% (year 2) and 75% (year 1). This ranking of National Associations is based on the performance of all their clubs in the Euro Hockey League and EuroHockey Club Trophy. The total number of points won by clubs from each country is divided by the number of clubs to which the National Association was entitled in that year's competitions. Each qualifying National Association is required to enter their national champion club but is otherwise free to decide the system of qualification for their own clubs for any remaining places to which they are entitled that year. To be eligible to play in the Euro Hockey League a country must enter 2 clubs in the EHF club competitions. Tournament For the 2019–20 season the EHL moves to a new format with the removal of the round-robin tournament in round one. Instead, a knock-out format will be used from the start of the tournament. Round one will be replaced by the knockout 16 with four sides advancing to the quarter-finals, or Final 8 as it's called, on Easter. The Final8 will consist of the champions from the top four nations on the EHL rankings table alongside the four sides that qualified from the knockout 16. This means that instead of a total of 24 teams from 12 associations there will be 20 teams from 11 associations. Sponsorship The much-improved presentation and packaging of the Euro Hockey League have attracted a number of high-profile sponsors, most notably Dutch bank ABN-AMRO, who are the presenting sponsor of the tournament. Volvo and Intersport are also named sponsors of the Euro Hockey League, while partnerships have been formed with McGregor, ErmaSport, ATP - The Advanced Travel Partner and Dutch advertising agency Ideas for Brands. Summaries Records and statistics Lower tournaments The Euro Hockey League is the top men's club competition in Europe. Below the Euro Hockey League is the EuroHockey Club Trophy, then below that the EuroHockey Club Challenge 1, the EuroHockey Club Challenge 2, and so on. This structure is designed to give every EHF member nation the opportunity to enter their best clubs into European competition at an appropriate level, and through that exposure to improve the level of their domestic hockey. See also EuroHockey Club Champions Cup EuroHockey Club Trophy Men's EuroHockey Indoor Club Cup Women's Euro Hockey League References External links Official website Category:International club field hockey competitions in Europe Category:Sports leagues established in 2007 Category:2007 establishments in Europe
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Site Mobile Navigation At Goldman, Partners Are Made, and Unmade On Wall Street, becoming a partner at Goldman Sachs is considered the equivalent of winning the lottery. This fall, in a secretive process, some 100 executives will be chosen to receive this golden ticket, bestowing rich pay packages and an inside track to the top jobs at the company. What few outside Goldman know is that this ticket can also be taken away. As many as 60 Goldman executives could be stripped of their partnerships this year to make way for new blood, people with firsthand knowledge of the process say. Inside the firm, the process is known as “de-partnering.” Goldman does not disclose who is no longer a partner, and many move on to jobs elsewhere; some stay, telling few of their fate. “I have friends who have been de-partnered who are still there, and most people inside think they are still partners,” said one former Goldman executive, who spoke only on the condition of anonymity. “It is something you just don’t talk about.” Goldman has roughly 35,000 employees, but only 375 or so partners. The former Treasury Secretaries Henry M. Paulson Jr. and Robert E. Rubin, and former Gov. Jon S. Corzine of New Jersey, now chief executive of financial firm MF Global, were all partners. It can take years to make partner, and being pushed from the inner circle can be wrenching. “Being partner at Goldman is the pinnacle of Wall Street; if you make it, you are considered set for life,” said Michael Driscoll, a visiting professor at Adelphi University and a senior managing director at Bear Stearns before that firm collapsed in 2008. “To have it taken away would just be devastating to an individual. There is just no other word for it.” The financial blow can be substantial as well. Executives stripped of partnership would retain their base salary, roughly $200,000, but their bonuses could be diminished, potentially costing them millions of dollars in a good year. While gaining the coveted status of partner, and then losing it, is certainly not unheard-of at private financial and law firms on Wall Street, Goldman’s partnership process stands out for its size and intricacy. Goldman weeds out partners because it is worried that if the partnership becomes too big, it will lose its cachet and become less of a motivational tool for talented up-and-comers, people involved in the process say. If too many people stay, it creates a logjam. The average tenure of a partner is about eight years, in part because of natural attrition and retirements. Goldman insiders also note they have what they call an “up-and-out” culture, leading to the active management of the pool. Photo The new Lower Manhattan headquarters for Goldman Sachs, where window views will be at a premium.Credit Rob Bennett for The New York Times The process of vetting new candidates for partner and deciding which existing partners must go began in earnest in recent weeks, according to people with knowledge of the process, which takes place every two years. They spoke on the condition of anonymity. The 2010 partners will most likely be announced in November. Candidates are judged on many qualities, primarily their financial contribution to the firm. But lawyers and risk managers — who are not big revenue producers — can also make it to the inner circle. The executives responsible for running the partner process this year are the vice chairmen, J. Michael Evans, Michael S. Sherwood and John S. Weinberg; the head of human resources, Edith W. Cooper; and the bank’s president, Gary D. Cohn. Goldman typically removes 30 or so partners every two years, said those people who described the process. The number is expected to be significantly higher this year because fewer senior executives have left the firm as a sluggish economy and uncertain markets limit their opportunities elsewhere. Removing partners like this is unique to Goldman among publicly traded firms. When companies go public, they shed the private partnership system, and ownership of the company is transferred to shareholders. Goldman’s ownership was also transferred to shareholders, but it created a hybrid partner model as an incentive for employees. Those whom Goldman does not want to keep are likely to be quietly told in the coming weeks. Each situation is handled differently, the people with knowledge of the process say. Some partners are given time to find other jobs outside the firm. Others are told they will not be made partner and are asked to consider what they want to do next within the company. While Goldman is on track to remove many more executives than usual, the process is in its early stages and no final decisions have been made, these people caution. A Goldman spokesman declined to comment on how it selects and removes partners. The process is at the heart of Goldman’s culture, a way for the firm to reward and retain top talent. Goldman was one of the last of the big Wall Street partnerships to go public, selling shares in 1999. When it was private, the partners were the owners, sharing in the profits, and in some cases having to put in money to shore up losses. To retain that team spirit as a public company, Goldman continued to name partners. In 1999, there were 221. Yet there are differences from past practices. When Goldman was a private partnership, it was rare that a partner would be asked to leave. Photo Former partners at the firm include, from top, the former Treasury Secretaries Henry M. Paulson Jr. and Robert E. Rubin, and New Jersey’s former governor, Jon S. Corzine.Credit From top: Andrew Harrer/Bloomberg News (2); David Goldman for The New York Times “Once you made partner, you typically retired as a partner,” said another former Goldman executive who used to be involved in the process. “If we asked someone to leave, it was because we had really screwed up and the person wasn’t pulling their weight.” It has been a rough year for Goldman. In July, it paid $550 million to settle civil fraud accusations that it had duped clients by selling mortgage securities while failing to make critical disclosures. The firm did not admit or deny guilt. Still, even in the worst of years, the chance to ascend into the private partnership at Goldman is a huge honor. Candidates can be up for partnership two or even three times before finally being chosen. Partners get investment opportunities not offered to other employees, and are typically the highest paid at the firm. Goldman will even book tables for them at fashionable New York restaurants. A big payday is not guaranteed, however. When the firm does not do well, partners tend to bear the brunt of it. Top Goldman executives did not receive bonuses in 2008, the peak of the financial crisis. But in 2007, a banner year for Goldman, the firm set aside $20.19 billion for compensation and benefits, and its chief executive, Lloyd C. Blankfein, took home $68.5 million in stock and cash. Candidates for partner are vetted by current partners. The review process is known inside Goldman as “cross-ruffing,” a reference to a maneuver in bridge. A few hundred people are typically nominated within the whole company, and the number is eventually whittled down to about 100. Each department compiles a list of potential candidates, with photos and performance reviews. Partners in another department review it. Candidates are not interviewed, and in many cases are unaware they are even up for partner. When final decisions are made, it is usually Mr. Blankfein who breaks the good news to the new partners. Few candidates ever find out why they missed the cut. And Goldman announces only inductees, not those who have been removed. Still, there may be a few telltale signs this year. Goldman recently moved to a new building, just steps away from the Hudson River in Lower Manhattan. Outer offices are hard to come by, and typically given only to partners. Goldman insiders are already speculating that de-partnered executives who decide to stay will have to give up their window view. A version of this article appears in print on September 13, 2010, on page A1 of the New York edition with the headline: At Goldman, Partners Are Made, and Unmade. Order Reprints|Today's Paper|Subscribe
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97 Cal.App.2d 717 (1950) F. W. MOON et al., Respondents, v. ALFRED PAYNE et al., Appellants. Civ. No. 4046. California Court of Appeals. Fourth Dist. May 24, 1950. Walch & Griswold for Appellants. Sidney J. W. Sharp, Herbert M. Braden and Lawrence W. Clawson for Respondents. MUSSELL, J. Plaintiff, Jean Ann Moon, aged 5 years, sustained injuries from a fire set by the defendant in the city of Coalinga. At the time defendant was burning dead bean vines which he had raked off his garden patch into a small pile in the alley near his home. After the defendant had ignited the bean vines and the fire had burned to coals, he noticed three children, including the plaintiff, Jean Ann Moon, in the vicinity. When the defendant first noticed the children, they were approximately 5 feet from the fire and he looked toward them, told them not to get around the fire and to go home. After the children had been thus warned, they all started down the alley and defendant watched them until they were about 20 feet away from the fire. He then turned back to his work of cleaning *718 the garden and remained within approximately 25 feet of the live coals. Within two or three minutes he heard a whimper, looked around and saw that the plaintiff's slacks had caught on fire. He picked her up, tore off the burning slacks and carried the child to her parents, who were next door. Plaintiff sustained disabling and painful burns and the present action was brought to recover damages for the injuries sustained. Trial was had by the court without a jury and judgment was rendered in favor of plaintiff. It was shown at the trial that the defendant violated ordinance Number 255 of the city of Coalinga, the pertinent part of which is as follows: "Section 4. It shall be unlawful for any person to burn or bury any garbage in the yard or open space within the city or to burn any rubbish, paper or other materials in any yard or open place within the city without first obtaining a written permit so to do from the fire chief." The trial court found that the defendant had violated the above provision of the ordinance; "that said violation is without justification or excuse and constitutes an act of negligence per se which the court finds to be the proximate cause of the injuries and loss and damages sustained by Jean Ann Moon, and the loss and damages sustained by F. W. Moon and Vernice Moon." The court further found "that the defendant was only guilty of the negligence above referred to"; "that by reason of said act of negligence of the defendant, Alfred Payne, which act of negligence the court finds to be the proximate cause of the injuries and loss and damages sustained by Jean Ann Moon and the loss and damages sustained by F. W. Moon and Vernice Moon." The question here involved is whether the foregoing findings are sufficient to support the judgment; it being conceded that the defendant failed to obtain the written permit required by the ordinance. [1] An act or failure to act below the statutory standard is negligence per se, or negligence as a matter of law and an act which is performed in violation of an ordinance or a statute is presumptively an act of negligence, but the presumption is not conclusive and may be rebutted by showing that the act was justifiable or excusable under the circumstances. Until so rebutted, it is conclusive. (Satterlee v. Orange Glenn School Dist., 29 Cal.2d 581, 588, 589 [177 P.2d 279].) It is also necessary to show that the violation was a proximate contributing cause of the injury. (Satterlee v. Orange Glenn *719 School Dist., supra, 590; Dennis v. Gonzales, 91 Cal.App.2d 203, 207 [205 P.2d 55]; Eigner v. Race, 54 Cal.App.2d 506, 512 [129 P.2d 444]; Le Blanc v. Browne, 78 Cal.App.2d 63, 72 [177 P.2d 347].) [2] In the instant case it is apparent from a reading of the ordinance in question that the act of burning rubbish, paper or other materials within the city is not prohibited. The prohibition is that a permit from the fire chief must first be obtained. There is no evidence in the record to create a causal connection between the failure of the defendant to procure a license and the injury sustained. In Arrelano v. Jorgensen, 52 Cal.App. 622 [199 P. 855], the parents of a minor were held not liable for damages sustained in a collision of an automobile owned by such minor and negligently operated by him, from the mere fact that they knowingly permitted him to operate the machine without the license required by law, in the absence of any evidence causally connecting the absence of the license with the injuries. The court said, at page 624: "By no stretch of the imagination could it be said that the plaintiff would have been saved these injuries had the operator of the automobile renewed his operator's license for the year 1920. Therefore, even if it be conceded that the parents had the full control of the son and consented to his operation of the machine without an operator's license, this violation of law on their part had nothing whatever to do with the injuries for which the plaintiff seeks to recover. As was said in Shimoda v. Bundy, 24 Cal.App. 675 [142 P. 109]: 'One who violates an ordinance wherein a penalty is fixed for noncompliance with its provisions may be subjected to the penalties therein prescribed, but he cannot, in addition thereto, be deprived of his civil right to recover damages, perhaps in many thousands of dollars, sustained by reason of the negligence or wrong of another, when such violation bore no relation to the injury and did not contribute in the remotest degree thereto'." In Strandt v. Cannon, 29 Cal.App.2d 509, 518 [85 P.2d 160], this court held, in an automobile collision case, that the operator's negligence is to be determined by the facts existing at the time of the accident, and whether the operator had a license to operate an automobile under the laws of this state is immaterial unless there is some causal relationship between the injuries and the failure to have a license or the violation of the statute in failing to have one. *720 In Shimoda v. Bundy, 24 Cal.App. 675 [142 P. 109], it was held that the failure of a driver of a motorcycle to register it as required by ordinance as a condition to lawfully operating it on the streets of a city, did not bar his right to recover for negligently being struck by the driver of an automobile. Roos v. Loeser, 41 Cal.App. 782 [183 P. 204], was an action for damages sustained by plaintiff by reason of the killing of a dog. It was there held that plaintiff could not be charged with contributory negligence because of the fact that her dog was upon the public streets without being licensed, where her omission to comply with the ordinance requiring dogs to be licensed did not contribute to the incident which caused the death of the dog. The principles set forth in the foregoing cases are applicable in the case before us and while the question of probable cause is ordinarily one for the trier of fact (Dennis v. Gonzales, supra, 207), it becomes one of law in the instant case when there is no evidence that the failure of defendant to obtain the permit was a proximate cause of the injuries sustained (Satterlee v. Orange Glenn School Dist., supra, 590). For aught that appears in the record, plaintiff might have sustained the injuries complained of even though the defendant had in fact procured the required permit. The trial court found that the defendant was only guilty of negligence in failing to comply with the ordinance and that such failure was the proximate cause of the injuries sustained. These findings are not sufficient to support the judgment. Judgment reversed. Griffin, Acting P. J., and Shepard, J. pro tem., concurred.
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Police in the eastern Indian state of Orissa have threatened to stop work if the government releases Maoist leaders in exchange for any hostages. The rebels are holding Italian tourist Paolo Bosusco since 14 March and state legislator Jhina Hikaka since 23 March. They have demanded the release of 30 cadres and supporters and set a Tuesday deadline for meeting their demands. But police unions say releasing any rebels will be "an affront to those officers who died fighting the rebels". Separately, a court in Orissa freed the wife of a top Maoist commander, Sabyasachi Panda, on Tuesday. Subhashree Panda is among the seven people whose release has been demanded by rebels in exchange for Mr Bosusco. The Orissa Police Association, which represents middle and lower-level policemen, has threatened to boycott counter-insurgency operations if the government gives in to the Maoists' demands. "It is sheer blackmail and we will protest if the government buckles under it," association president Sanwarmal Sharma told the BBC. "It will be an affront to those police officers who died fighting the Maoists in hostile terrain," he said. Negotiations between officials and the rebels over the release of Mr Bosusco have been deadlocked. The government had offered to release five of the six people named by the rebels in exchange for the Italian, but the rebels say it is not clear who the five men are and whether their other demands have been accepted. Mr Bosusco, 54, was seized along with Claudio Colangelo, 61, while trekking in a tribal area of Orissa, one of several regions of India where Maoist rebels are active. It was the first kidnap of foreigners by Maoists in Orissa state. Mr Colangelo was released on 25 March but Mr Bosusco remains held. The Maoists have a strong presence in many eastern states, and have been described by Prime Minister Manmohan Singh as India's biggest security threat. The rebels say they are fighting for a communist state and for the rights of tribal people and the rural poor.
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Q: JScrollPane not working on my JTextArea? I'm not very familiar with java GUIs and layouts but I gotta admit, I didn't think it would be this tricky! I'm not quite sure what I'm doing here. I merely want to add 2 textareas ontop of each other and add a jscrollpane to each of them. But I can't get the JScrollPanes to work. Here's how I currently got it. public class Class extends JFrame { public Class() { super("Title"); getContentPane().setLayout( new BoxLayout(getContentPane(), BoxLayout.Y_AXIS)); setResizable(false); JTextArea window1 = new JTextArea("text"); window1.setEditable(false); window1.setBorder(BorderFactory.createLineBorder(Color.BLACK)); window1.setPreferredSize(new Dimension(200, 250)); window1.setLineWrap(true); add(window1); JScrollPane scroll = new JScrollPane(window1); scroll.setHorizontalScrollBarPolicy(ScrollPaneConstants.HORIZONTAL_SCROLLBAR_NEVER); scroll.setVerticalScrollBarPolicy(ScrollPaneConstants.VERTICAL_SCROLLBAR_ALWAYS); add(scroll); JTextArea window2 = new JTextArea(); window2.setEditable(true); window2.setBorder(BorderFactory.createLineBorder(Color.BLACK)); window2.setPreferredSize(new Dimension(100, 50)); window2.setLineWrap(true); add(window2); setDefaultCloseOperation(EXIT_ON_CLOSE); pack(); setVisible(true); } } It looks good, there's a box with "text" and right of it there's the scrollpane. Below them both there's the second JTextArea (no scrollpane yet). The problem is that when I write text in window 1 and the text goes below, outside of the jtextarea, I expected the JScrollPane to actually be scrollable so I could scroll down to see the text at the bottom but nothing happens when I press it (and it doesn't change in size or anything either). Anything noticable I've missed? A: You add your JTextArea to JScrollPane you needn't to add it to your JFrame. Also setPreferedSize() use for JScrollPane, instead of directly to JTextArea, because your JTextArea will be not scrollable. I have changed your code, try it: public class Class extends JFrame { public Class () { super("Title"); getContentPane().setLayout( new BoxLayout(getContentPane(), BoxLayout.Y_AXIS)); setResizable(false); JTextArea window1 = new JTextArea("text"); window1.setEditable(false); window1.setBorder(BorderFactory.createLineBorder(Color.BLACK)); window1.setLineWrap(true); JScrollPane scroll1 = new JScrollPane(window1); scroll1.setPreferredSize(new Dimension(200, 250)); scroll1.setHorizontalScrollBarPolicy(ScrollPaneConstants.HORIZONTAL_SCROLLBAR_NEVER); scroll1.setVerticalScrollBarPolicy(ScrollPaneConstants.VERTICAL_SCROLLBAR_ALWAYS); add(scroll1); JTextArea window2 = new JTextArea(); window2.setEditable(true); window2.setBorder(BorderFactory.createLineBorder(Color.BLACK)); window2.setLineWrap(true); add(window2); JScrollPane scroll2 = new JScrollPane(window2); scroll2.setHorizontalScrollBarPolicy(ScrollPaneConstants.HORIZONTAL_SCROLLBAR_NEVER); scroll2.setVerticalScrollBarPolicy(ScrollPaneConstants.VERTICAL_SCROLLBAR_ALWAYS); scroll2.setPreferredSize(new Dimension(100, 50)); add(scroll2); setDefaultCloseOperation(EXIT_ON_CLOSE); pack(); setVisible(true); } public static void main(String... s){ new Class(); } }
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Hello World! Can Can Dancer has moved. Please visit www.cancandancer.com to see new DIY posts (and all past posts too!). Happy Crafting! DIY Moss Typography Hello World, Let's be honest. I have a typography problem. I love both sans serif and scripted typefaces. I sometimes pay more for a product just because it has great packaging. I know, #designerproblems. My hands-down favorite is Futura, and I use it for all my blog/Etsy branding. (Fun fact- Futura is so cool it actually is on the moon!) Now that I have put that on the table, you can see why I am really excited to share today's tutorial. This is a quick project that only cost me a dollar. I decided to go with handwritten lettering, and a simple "hello."
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Q: OpenGL - Question about the usage of glDepthMask I have rendered an objectA in a scene as follows. The scene has many other objects too. void Draw() { if( glIsList( displayListID ) ) { glPushAttrib( GL_COLOR_BUFFER_BIT|GL_DEPTH_BUFFER_BIT|GL_ENABLE_BIT ); glEnable( GL_BLEND ); glEnable( GL_DEPTH_TEST ); //glDepthMask( GL_FALSE ); glBlendFunc( GL_SRC_ALPHA, GL_ONE_MINUS_SRC_ALPHA ); glEnable( GL_LINE_SMOOTH ); glEnable( GL_POINT_SMOOTH ); glEnable( GL_POLYGON_SMOOTH ); glMatrixMode( GL_MODELVIEW ); color.setAlpha(alpha); // set alpha transparent of this objectA glCallList( displayListID ); //glDepthMask( GL_TRUE ); glDisable( GL_BLEND ); glPopAttrib(); } } Now here is the problem, As shown, I comment out two lines //glDepthMask( GL_FALSE ); //glDepthMask( GL_TRUE ); the scene renders the objectA and other objects correctly in depth. However, the modification of the objectA alpha doesn't work anymore (i.e. color.setAlpha(alpha) ). If I uncomment the above two lines, then alpha modification is back to work. However, the depth rendering is NOT correct. In other words, sometimes, the objectA should be behind other objects but it looks like the objectA is in front of all objects. How do I fix this problem? Thank you A: Turn on the depth mask glDepthMask( GL_TRUE ) Draw all opaque objects, in any order Turn off the depth mask glDepthMask( GL_FALSE ) Turn on a BLEND_MODE Draw translucent objects sorted from furthest away to nearest Why do you do this? There are 2 buffers you need to worry about: the depth buffer and the color buffer. These buffers are really just big 2d arrays, each the width x height of your screen. The color buffer naturally is going to hold the final coloration of each pixel. There is one entry in the color buffer per screen pixel. The depth buffer, is like the color buffer in that there is one entry per screen pixel, but it is used for something different. Entries in the depth buffer are a measure of "how close" each colored pixel really is. If you render 1 triangle, that is far away from the camera, it generates a set of colors and depth values for each pixel it "wants" to cover on the screen. Say you then render another poly that is closer, it also will generate a set of values for the depth and color buffers. Now, there is a sort of "contest" at pixel coloration time where the "further away" fragments (large depth buffer values) are discarded, and only the closest fragments are kept. The closer fragments end up coloring the pixel you had. (When two polygons are nearly overlapping, Z-fighting can occur) Start by rendering the objects in your scene with the depth mask on. This means every shape you render, when its pixels get colored, the depth buffer gets updated with the "winner" of the contest. Then, you 3) glDepthMask( GL_FALSE ) turns off the depth buffer for writing, 4) turn on blending, 5) render translucent shapes from furthest to nearest. Seems weird, huh? When you turn off the depth mask, and render the translucent shapes, OpenGL will still read the depth buffer to determine which fragments to throw away (i.e. if your translucent shape is behind an already rendered solid shape, then you throw that translucent shape's fragments away). But it will not write to the depth buffer, so if a translucent shape is really really close to the eye (say like a translucent windshield), those windshield fragments do not prevent other fragments that are actually further away from being drawn. This is important, because if your windshield is right in front of you and you render it translucent, and you let the windshield fragments update the depth buffer then you will see nothing else in your scene except the windshield, even though there are shapes behind it, because OpenGL will think "Hey, that windshield is the only thing the user should see, due to these depth buffer readings, so I won't bother rendering anything further away than this windshield, then." Turning off the depth mask is a way of "tricking" OpenGL into "not knowing" there are very close, but translucent, fragments. A: One possible solution: set glDepthMask to GL_TRUE at all times and draw all your non-transparent objects first (in any order, just as you seem to do it now), then draw all your (semi-)transparent objects sorted from back to front. In some cases, if you don't care about the order in which your (semi-)transparent objects are drawn and you only want the other, opaque objects to "shine through", you can skip sorting your (semi-)transparent objects.
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Nintendo has announced that Super Smash Bros. is coming to the Nintendo Switch this year, bringing the popular fighting game franchise to Nintendo’s newest console. The teaser came at the end of the company’s Nintendo Direct presentation today. There is virtually no information on the upcoming release other than the 2018 release window, but it seems that popular characters like Mario and Link will once again be returning to the franchise, along with newcomers from Splatoon (making their first appearance as playable characters in a Smash Bros. game). While Nintendo hasn’t provided too many details, the Switch version of the game will be the fifth title in the series, which has seen a version released on every Nintendo home console since the original Super Smash Bros. was released on the Nintendo 64 in 1999.
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It isn’t only Americans suffering racist stop-and-frisks. Minorities in Britain experience racially biased drug searches at rates comparable to their American counterparts, according to our new report, The Numbers in Black and White: Ethnic Disparities in the Policing and Prosecution of Drug Offences in England and Wales. Someone is frisked for drugs every 58 seconds in England and Wales, with black people six times more likely to be stopped and searched for drugs than white people. Asians, meanwhile, were 2.5 times more likely to be subject to such searches, according to the report, launched by Release and the London School of Economics and Political Science. Moreover, Release—an Open Society grantee that produced the report with support from the Getty Foundation—found that black people in Britain are arrested for drugs at a rate of six times that of white people, compared to the three-to-one ratio in the United States. This is despite the fact that drug use is lower among black and Asian people than whites. To hear the personal stories of those who have experienced such searches, please see the Open Society project titled Viewed with Suspicion. Discrimination, however, is not limited to searches. The Numbers in Black and White also found that the Metropolitan Police in London were treating black people caught in possession of drugs more harshly. Across London, black people are charged for possession of marijuana at five times the rate of white people. Whites were more likely to get “cautioned,” which is a formal warning that can be issued by police for an offense. While it still forms part of a criminal record, it does not require a person to go to court, as is the case when a person is charged. Beyond the damning figures, there is also a deafening silence from lawmakers who have not raised their voices against these disgraceful shakedowns. Though a lively debate about stop-and-frisk is taking place in the United States, particularly in New York, British leaders are mostly watching from the sidelines. But the numbers show silence is not an option. This report exposes the urgency of reviewing drug laws that are being enforced in a damaging and discriminatory manner. To call on the British government to review the national drug laws, please sign the petition initiated by Member of Parliament Caroline Lucas, which is open to citizens of the UK.
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Field Embodiments of the present invention generally relate to detection of malicious resources. In particular, embodiments of the present invention relate to active unified threat management (UTM) profiling and monitoring of client reputation scores by analyzing communication between a plurality of resources coupled to the network. Description of the Related Art In a network, such as a computing network or a telecommunication network, coupled to resources, such as, computers, laptops, mobiles, Personal Digital Assistants (PDAs), virtual server, virtual machines, widgets, and the like, the resources are susceptible to hostile attacks arising as a result of malicious objects such as malware, web robots or BOTS, phishing, modified virus codes, and other viruses. The malicious objects may contaminate resources and initiate risky activities in the network, such as, bad connection attempts, file sharing applications, session initiation for incoming connections, and so forth. Therefore, a resource contaminated with one or more malicious objects may be considered as a malicious resource for the network. Such malicious resources may further contaminate other resources in the network. Hence, detection of the malicious resources is essential for security and efficient performance of the resources coupled to the network. A known technique to detect potential malicious resources involves identification of a signature or a representative code pattern within a file or process on the resource being scanned. In this technique, a signature of a file or process at issue is compared with a list of signatures corresponding to malicious objects. If the signature being checked is present in the list of signatures, the resource is or has the potential of becoming a malicious resource. In this technique, the list of signatures must be frequently updated otherwise a lag period between new threats and anticipated signatures may develop. Moreover, this technique is less effective for modified virus codes and targeted attacks like spear phishing. Another existing technique involves scanning for potential intrusions based on behavior of the resources (e.g., requests involving file sharing or any acts of communication to or from the resources). Such scanning involves dynamic monitoring of internal and external functioning of the resources receiving/sending the requests, and accordingly observing the behavior of the resources. This technique involves heavy processing and like pattern matching can produce false positives and can miss newly developed threats. In view of the foregoing, there exists a need for new and more effective techniques for detection of malicious resources in the network.
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BTuFC Toscana Berlin BTuFC Toscana Berlin was an early German association football club from the city of Berlin. The club is notable as one of the founding clubs of the German Football Association (Deutscher Fussball Bund, en:German Football Association) at Leipzig in 1900. History Through most of the 1890s there were several competing football circuits in the city of Berlin. Little is known of Toscana beyond its occasional appearances in the Deutscher Fussball- und Cricket Bund, which was active from late 1891 through to 1901. The team earned a third-place result in second division play there in 1896, and then played a partial season in the league's first division in 1898, followed by another campaign there in 1900. The club's full name was Berliner Thorball -und Fußball Club Toscana and, like many other clubs of the era built around enthusiasm for the new English sports of football, rugby, and cricket, Toscana also fielded a cricket side. The term thorball was used at the time as the German language equivalent for cricket, while Toscana or Toskana is German for the Italian region of Tuscany. References Category:Football clubs in Germany Category:Defunct football clubs in Germany Toscana
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Chicago, Zimbabwe Chicago, Kwekwe, Zimbabwe, is a low density suburb located in the outskirts of Kwekwe CBD. Background Chicago is one of the oldest place names in Kwekwe. The suburb is situated in South of the CBD along the A5 Highway and in a hilly environment. The area was originally the east-end of a farm by the same name, covering the better part of Kwekwe Central, Feachlea, Hellandale and beyond. Gaika Mine also known as Chicago Gaika Mine is wholly in former Chicago Farm. The first plots in Kwekwe were pegged in Chicago. It was not considered the area for the rich elite the tag it carries today. Chicago is one of the most prominent low density suburban settlements in Kwekwe. Chicago Farm still exists, partly though, Southwest of Kwekwe. Chicago's fame started way back in when "Gaika Concession Store" owners Barney and Dora Kahn imported the first Cadillac into the country. Politics Chicago is within Kwekwe Central Constituency. Local Government Chicago falls under Kwekwe Municipality as one of the settlements within its jurisdiction. See also Kwekwe Globe and Phoenix Mine Gaika Mine References Category:Suburbs in Kwekwe
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ROCHESTER CITY CENTER: WHAT’S NEXT 2019 Overview Designing for Social Justice Citizens around the globe face a wide range of social injustices. Inequities within a community can be the result of systematic racism, sexism, classism, ableism and other biases. Historically we’ve seen design choices that unfortunately marginalize citizens. This What’s Next panel will discuss how interior design can be used as a tool for social justice. Venue Related Events Citizens around the globe face a wide range of social injustices. Inequities within a community can be the result of systematic racism, sexism, classism, ableism and other biases. Historically we’ve seen design choices that unfortunately marginalize citizens. This What's Next panel will discuss how interior design can be used as a tool for social justice.
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Q: Access to heroku toolbelt commands in a scheduled heroku dyno? I want to call heroku postgres backup/restore commands within a scheduled heroku task, but the heroku toolbelt isn't available from bash prompt, so I can't call heroku commands: $ heroku run bash --app myapp Running `bash` attached to terminal... up, run.4805 ~ $ heroku --version bash: heroku: command not found How can I get heroku commands available in my scheduled bash script? I don't know anything about Ruby or Ruby Gems. A: None of the other solutions worked for me since Heroku locks the filesystem after the buildpacks finish running. There's a third-party buildpack that installs the CLI for you. First you set your auth key as an ENV variable on your app: heroku config:set HEROKU_API_KEY=`heroku auth:token` -a myapp Then add the buildpack: heroku buildpacks:add https://github.com/heroku/heroku-buildpack-cli -a myapp Redeploy your app and it should be able to access your apps via the CLI. If you have https://devcenter.heroku.com/articles/dyno-metadata enabled, you can even access your current app's name with $HEROKU_APP_NAME. A: Put this at the top of your scheduled bash script: # install heroku toolbelt # inspired by https://toolbelt.heroku.com/install.sh curl -s https://s3.amazonaws.com/assets.heroku.com/heroku-client/heroku-client.tgz | tar xz mv heroku-client/* . rmdir heroku-client PATH="bin:$PATH" then, for example, you can call: heroku pg:reset HEROKU_POSTGRESQL_YELLOW_URL --app myapp-staging --confirm myapp-staging heroku pgbackups:restore HEROKU_POSTGRESQL_YELLOW_URL `heroku pgbackups:url --app myapp-production` --app myapp-staging --confirm myapp-staging and poof! Staging database is updated from production database. A: As Heather Piwowar said, you can indeed download and untar the heroku tollbelt yourself, but no need to move files around after this. Here is a shorter version: curl -s https://s3.amazonaws.com/assets.heroku.com/heroku-client/heroku-client.tgz | tar xz PATH="/app/heroku-client/bin:$PATH" You can now use the heroku command as you wish. For authentification, you may want to set the HEROKU_API_KEY env var (using heroku config:set HEROKU_API_KEY=1234567890 -a your-app-name). Also, note that the first use of the heroku command will run longer than expected because it will try to install the latest version, dependencies and core plugins.
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Introduction {#s1} ============ The claustrum is present in nearly all mammalian lineages (Kowianski et al., [@B24]), but its behavioral functions have not been elucidated because of its unusual geometry. Relatively narrow with a long rostrocaudal extent, the claustrum is difficult to study with standard lesion or recording techniques in a behavioral paradigm. Neuronal tracing techniques, however, have revealed many aspects of claustral circuitry, and most views about claustral functions are based on its cortical connectivity (Edelstein and Denaro, [@B14]; Crick and Koch, [@B13]; Smythies et al., [@B44]), which include several unique interhemispheric projections (Minciacchi et al., [@B31]; Li et al., [@B26]; Sloniewski et al., [@B39]; Sadowski et al., [@B37]). Using physiology-based tracing techniques in rats, we recently reported that the M1-Wh region projects strongly to the contralateral claustrum, but only weakly to the ipsilateral claustrum (Alloway et al., [@B4]; Colechio and Alloway, [@B12]; Smith and Alloway, [@B41]; Smith et al., [@B43]). While the M1-Wh region does not receive reciprocal feedback projections from the contralateral claustrum, it is strongly innervated by the ipsilateral claustrum. By contrast, claustral connections with the M1 forelimb regions are comparatively sparse and are exclusively ipsilateral. In addition, the whisker region in S1 barrel cortex is innervated by the ipsilateral claustrum even though S1 cortex does not project to the claustrum in either hemisphere. These findings are significant because exploratory whisking is an active sensory process that requires attention and is bilaterally-coordinated for the purpose of acquiring tactile information about the spatial features of the local environment (Towal and Hartmann, [@B48]; Mitchinson et al., [@B32]). By comparison, rodent forelimb movements are rarely if ever used used to perceive the spatial features of three-dimensional space, but are mainly concerned with supporting and moving the body through space. The discovery of an interhemispheric claustrum-based pathway that connects the cortical regions that process whisker-related information prompted us to hypothesize that the claustrum should have similar circuit connections with the visual system. Like whisking behavior, exploratory eye movements require attention and are concerned with actively acquiring visual information to perceive a broad spatial region (Chelazzi et al., [@B11]; Andrews and Coppola, [@B6]; Wallace et al., [@B51]). In rats the claustrum receives a few projections from visual area 18b, but virtually none from area 17 (Miller and Vogt, [@B29]; Carey and Neal, [@B10]). The ventral part of the rat claustrum projects to visual cortex (Li et al., [@B26]; Sadowski et al., [@B37]), but whether the claustrum has afferent or efferent connections with the FEF remains unknown. Indeed, no data indicate whether the rat claustrum is part of a disynaptic interhemispheric circuit that could coordinate the FEF and V1 areas. Therefore, to test this hypothesis, we injected anterograde and retrograde tracers into physiologically-defined sites in FEF and V1. We compared the results, along with unreported data from our previous rat study (Smith and Alloway, [@B41]), to tracing data accessible from the Allen Mouse Brain Connectivity Atlas. Our findings indicate that the claustrum is part of an interhemispheric circuit that enables the FEF in one hemisphere to transmit the same information to the V1 and FEF cortical areas in the other hemisphere. Materials and methods {#s2} ===================== Anatomical tracing experiments were performed on three adult male Sprague-Dawley rats (Charles River) weighing 300--350 g. All procedures conformed to National Institute of Health standards and were approved by Penn State University\'s Institutional Animal Care and Use Committee. Animal surgery -------------- Rats were initially anesthetized via intramuscular (IM) injection of a mixed solution of ketamine HCl (40 mg/kg) and xylazine (12 mg/kg). Additional IM injections of atropine methyl nitrate (0.5 mg/kg) to limit bronchial secretions, dexamethasone sodium phosphate (5 mg/kg) to reduce brain swelling, and enrofloxacin (2.5 mg/kg) to prevent infection were given before intubating the trachea through the oral cavity and ventilating the rat with oxygen. After placing the animal in a stereotaxic instrument, its heart rate, respiratory rate, end-tidal carbon dioxide, and blood oxygen were monitored (Surgivet) throughout the experimental procedure. Body temperature was regulated by a rectal probe attached to a homeothermic blanket placed on the dorsal side of the animal; a hot water blanket was placed underneath the rat as well. Ophthalmic ointment was applied to prevent corneal drying. After injecting bupivicaine into the scalp, a midline incision was performed to visualize the cranium, and a ground screw was inserted into a craniotomy over the cerebellum. Craniotomies were also made over motor cortex (1--3 mm rostral, 0.5--3 mm lateral to bregma) and visual cortex (5--7 mm caudal, 3--5 mm lateral to bregma) in both hemispheres according to coordinates in Paxinos and Watson ([@B34]). Intracranial microstimulation ----------------------------- Intracranial microstimulation (ICMS) was done in rats to map motor cortex. Microstimulation was performed under ketamine-xylazine anesthesia to produce forepaw, whisker, or eye movements. Following microstimulation mapping, the anesthetic state was maintained with \~1% isoflurane. Cortical stimulation was administered by \~1 MΩ saline-filled glass pipettes. Both short (80-ms, 250 Hz) and long (1-s, 100 Hz) pulse trains were administered. A biphasic constant current source (Bak Electronics, BSI-2) was used to test current levels of 10--250 μA to identify the lowest threshold at each site capable of eliciting a movement. Stimulation was conducted at multiple sites in each animal so that tracer injections could be centralized within the target region to avoid tracer leakage into surrounding representations. The stereotaxic coordinates that evoked movements were similar to previous reports (Hall and Lindholm, [@B18]; Neafsey et al., [@B33]; Hoffer et al., [@B19]; Brecht et al., [@B9]; Haiss and Schwarz, [@B17]). Electrodes were positioned orthogonal to the pial surface and inserted to depths (\~1 mm) that correspond to layer V, which contains corticobulbar and corticospinal neurons. The electrode was initially placed 2--3 mm lateral to the midline to identify the forepaw representation (M1-Fp). More medial sites (1--2 mm lateral) evoked brief whisker retractions (M1-Re) during 80-ms stimulation trains. At the most medial coordinates (\~1 mm lateral), the electrode was advanced deeper to determine the motor representations in the medial bank of frontal cortex. At sites located 1.5--3.0 mm rostral, stimulation at depths 1.5--2.5 mm below the pial surface evoked eye movements visible to the naked eye. Further caudally, 1-s long train stimulation evoked repetitive rhythmic whisker movements at M1 (M1-RW) sites located 0.5--1.7 mm rostral to bregma. Whisker movements at M1-RW sites were frequently bilateral (Haiss and Schwarz, [@B17]). Both FEF and M1-RW are located deep in the medial bank of frontal cortex, but they have distinct domains along the rostral and caudal axis. Extracellular neuronal recordings --------------------------------- To identify sites in primary visual cortex (V1), the same electrodes used for ICMS mapping were used to map visual cortex. After disconnecting the electrode from the constant current source, it was connected to the headstage of a Dagan amplifier (Model 2200) so that extracellular discharges could be amplified, bandpass filtered (300--3000 Hz), and monitored with an oscilloscope and acoustic speaker. Electrodes were placed at stereotaxic coordinates (5.0--7.0 mm caudal to bregma, 2.0--4.0 mm lateral) that correspond to V1 (Paxinos and Watson, [@B34]), and were advanced \~400 μm into the brain to reach layer IV. Neuronal responses to visual stimulation were tested by manipulating a handheld blue LED in different directions over the ipsilateral and contralateral eyes to identify responsive areas corresponding to the monocular or binocular regions of V1. Because this procedure may not distinguish V1 from adjacent visual areas, injection sites in V1 were verified by cytoarchitectonic criteria (see Results). Tracer injections ----------------- Tracers were injected either iontophoretically or by pressure. For anterograde tracing, 15% solutions of FluoroRuby (FR; D-1817, Invitrogen) or biotinylated dextran amine (BDA; D-7135, Invitrogen) in 0.01 M phosphate buffered saline (PBS) were used. For retrograde tracing, 2% solutions of True Blue chloride (TB; T-1323, Invitrogen) or Fluorogold (FG; H-22845, Fluoro-Chrome) were used. The FEF received iontophoretic injections of BDA or FG from glass pipettes (\~30 μm tip). A retention current (-7.0 μA) was used to limit tracer leakage while advancing the pipette to its injection depth, where the retention current was turned off and positive current pulses of 2--5 μA (7 s on/off duty cycle) were applied for 10--20 min to eject the tracer at two depths separated by 300 μm. In one rat, a mixture of FG and BDA was iontophoretically ejected in FEF. Visual cortex received pressure injections of FR or TB from Hamilton syringes in which glass pipettes (\~50 μm diameter tips) were cemented on the end of the needle. A summary of the tracer injections is in Table [1](#T1){ref-type="table"}. ###### **Summary of tracer injections from current study and previously published data (Smith and Alloway, [@B41])**. **Case** **Left hemisphere** **Right hemisphere** ---------- --------------------- ---------------------- -------------- --------- TI-14 -- V1 (FR) FEF (FG/BDA) V1 (TB) TI-15 FEF (BDA) V1 (FR) FEF (FG) V1 (TB) TI-16 FEF (BDA) V1 (FR) FEF (FG) V1 (TB) CL-01 M1-Re (FR) -- M1-Re (FG) -- CL-02 M1-Re (FR) -- M1-Re (FG) -- CL-03 M1-Fp (FR) -- M1-Fp (FG) -- CL-04 M1-Fp (FR) -- M1-Fp (FG) -- CL-05 M1-Re (FR) -- M1-Re (FG) -- CL-06 M1-Fp (FR) -- M1-Fp (FG) -- CL-21 M1-RW (FR) -- M1-RW (FG) -- CL-22 M1-RW (FR) -- M1-RW (FG) -- CL-23 M1-RW (FR) -- M1-RW (FG) -- *Anterograde tracers: BDA, biotinylated dextran amine; FR, FluoroRuby*. *Retrograde tracers: FG, FluoroGold; TB, True Blue Chloride*. Following tracer injections, the skin was sutured and treated with antibiotic ointment. Each animal received additional doses of atropine, dexamethasone, and enrofloxacin. Animals were returned to single housed cages for a 7--10 day survival period to allow for tracer transport. Histology --------- Rats were deeply anesthetized with IM injections of ketamine (80 mg/kg) and xylazine (18 mg/kg) and perfused transcardially with heparinized saline, 4% paraformaldehyde, and 4% paraformaldehyde with 10% sucrose. Brains were removed and stored in 4% paraformaldehyde and 30% sucrose at 4°C until saturated. All brains were sectioned bilaterally into 60-μm slices using a freezing microtome with a slit in the left hemisphere (ventral to the rhinal fissure) to allow proper orientation when mounting. Serially-ordered sections were divided into three series. The first series was mounted on gelatin-coated slides, and then dried and stained with thionin acetate to reveal cytoarchitecture. The second series was processed to visualize BDA using a heavy metal enhanced horse radish peroxidase immunohistochemical reaction as previously described (Kincaid and Wilson, [@B23]; Smith et al., [@B42]). Briefly, sections were first washed in 0.3% H~2~O~2~ to degrade endogenous enzyme activity, rinsed in two 0.3% Triton-X-100 (TX-100) washes, and then incubated for 2 h in avidin-biotin horse radish peroxidase solution mixed in 0.3% TX-100. Sections were then washed twice in 0.1 M PBS and incubated in 0.05% DAB, 0.0005% H~2~O~2~, 0.05% NiCl~2~, and 0.02% CoCl~2~ in 0.1 M tris buffer (pH = 7.2) for 10 min. Two subsequent washes in 0.1 M PBS stopped the reaction. Following immunohistochemistry to visualize BDA, sections were mounted on gelatin-coated slides, dried overnight, dehydrated in ethanol, cleared in xylene and coverslipped with Cytoseal. The third series was directly mounted, dried, dehydrated, defatted, and coverslipped to visualize fluorescent tracers alone. Anatomical analysis ------------------- All tissue was inspected with an Olympus BH-2 microscope equipped for both brightfield and fluorescent microscopy. Terminals labeled with BDA were visualized with brightfield, whereas TB and FG labeling were visualized with a near UV filter (11000v2; Chroma Technologies), and a TRITC filter (41002, Chroma Technologies) was used for FR labeling. Labeled soma and terminal synapses were plotted and digitally reconstructed using optical transducers attached to the microscope stage (MDPlot, Accustage). For anterograde tracers, beaded varicosities on the axonal terminals were plotted because they represent en passant synapses (Voight et al., [@B50]; Kincaid and Wilson, [@B23]). For retrograde tracers, only labeled cells with dendrites were plotted. Digital photomicrographs of brightfield and fluorescent labeling were acquired with a Retiga EX CCD digital camera mounted on the BH-2 microscope. Additional images were obtained with an Olympus FV1000 laser scanning confocal microscope using a 60× oil immersion objective. For TB (405 nm excitation, 410--460 nm emission) and FG (405 nm, excitation, 520--600 nm), sections were scanned sequentially to demonstrate both single and double labeled neurons and were then merged to produce a composite image. Quantitative analysis of tracer reconstructions was performed using MDPlot software (version 5.1; Accustage). Analysis of the claustrum was confined to sections that contained the striatum because more rostral levels do not contain the claustrum-associated Gng2 protein (Mathur et al., [@B28]). After the sections were plotted, a grid of 50 μm^2^ bins was superimposed on the reconstructions. Bins containing at least four labeled terminals and one labeled neuron were classified as containing overlapping tracer labeling. Analyses of BDA-FG and BDA-TB overlap were performed separately. The number of overlapping bins was expressed as a percentage of the total number of bins that contained tracer labeling. Statistical analysis was performed using Origin software (version 8.0; Origin Lab). Because BDA processing diminishes the intensity of fluorescence, the third series, which was processed for fluorescence but not BDA, was used to count FG- and TB-labeled and double-labeled neurons. In addition to our own neuroanatomical tracing experiments, corticoclaustral connectivity in mice was analyzed by accessing data in the Allen Mouse Brain Connectivity Atlas. The analyzed cases were chosen based on the Allen Brain Institute\'s designation of cortical injection site area. We chose homologous cytoarchitectonic regions and confirmed the functional representation of these regions based on labeling patterns in subcortical structures (see Results). Results {#s3} ======= To compare the claustral connections with FEF and V1, three rats received different anterograde and retrograde tracers in FEF and V1 of the left and right hemispheres, respectively, (Table [1](#T1){ref-type="table"}). Combining different tracer injections in the same animal allowed us to quantify tracer overlap in the claustrum bilaterally and determine the relative strength of corticoclaustral and claustrocortical connections with FEF and visual cortex. In the first rat, a combined solution of FG and BDA was iontophoretically injected into FEF of the right hemisphere, whereas FR and TB were separately injected into V1 of the left and right hemispheres, respectively. In the other two rats, BDA and FR were separately injected into respective sites in FEF and V1 of the left hemisphere, whereas FG and TB were separately injected into respective sites in FEF and V1 of the right hemisphere. Projections from FEF -------------------- In agreement with previous reports (Neafsey et al., [@B33]; Brecht et al., [@B9]; Haiss and Schwarz, [@B17]), cortical sites that evoked eye movements were consistently found at coordinates in the cingulate (Cg) cortex. As shown by Figures [1](#F1){ref-type="fig"}, [2](#F2){ref-type="fig"}, tracer injections at these sites were largely confined to CG cortex but some tracer occupied the most medial part of the medial agranular (med-AGm) cortex. While FEF is rostral to M1 sites that evoke rhythmic whisking movements, both FEF and M1-RW reside in Cg and, possibly, the most medial part of AGm (med-AGm) as defined by cytoarchitectonic criteria. ![**Case TI-16 demonstrates that the FEF projects to claustrum and other forebrain regions. (A)** Nissl-stained section through the lateral agranular (AGl), medial agranular (AGm), and cingulate (Cg) cortices. **(B)** Deposit of biotinylated dextran amine (BDA) at an M1 site in Cg cortex that evoked eye movements and produced labeled terminals in the contralateral Cg cortex. **(C--F)** The BDA deposit produced labeled terminals in the dorsomedial neostriatum (NS) and ventral claustrum (vCLA) in the left **(C,D)** and right **(E,F)** hemispheres. **(G)** Nissl-stained section of thalamus used to identify BDA-labeled projections **(G′)** in the anterior medial (AM), interanteromedial (IAM), mediodorsal (MD), reuniens (Re), ventromedial (VM), and ventroanterior (VA) nuclei. Box corresponds to **(I)**. **(H--J)** Terminal labeling was densest in the AM and MD nuclei. Boxes in **(I)** indicate **(H,J)**. ec, external capsule; lv, lateral ventricle; sm, stria medularis; AV, anteroventral; AD, anterodorsal; CM, centromedial; Rt, reticular nucleus; VL, ventrolateral. Numbers in **(B--G)** indicate distance from bregma in millimeters. Scale bars: 500 μm in **(A,G)**; 250 μm in **(C,I)**; 100 μm in **(H)**.](fnsys-08-00093-g0001){#F1} ![**Corticoclaustral projections from FEF and V1 in case TI-15. (A--B′)** Left hemisphere injections of BDA in FEF **(A,A′)** and FluoroRuby (FR) in V1 **(B,B′)** of the same rat. BDA labeling appeared bilaterally in vCLA **(D,F)**, but was noticeably denser on the contralateral side **(F)**. Sparse FR labeling was apparent only in the ipsilateral vCLA **(D′)**. Boxes in **(C)** and **(E)** correspond to **(D,D′)** and **(F,F′)**, respectively. Red arrowheads demarcate the dorsal claustrum (dCLA) from the vCLA. Black and white arrowheads denote common blood vessels. Scale bars: 500 μm in **(A)**; 250 μm in **(C)**; 100 μm in **(D)**.](fnsys-08-00093-g0002){#F2} Many BDA-labeled projections from FEF terminated in visual cortex and brainstem regions such as the dorsomedial superior colliculus, periaqueductal gray, oculomotor complex, and the pontine reticular formation. These results corroborate studies that placed rodent FEF in the Cg/med-AGm region on the basis of its connections with oculomotor-related nuclei in the brainstem (Leichnetz et al., [@B25]; Stuesse and Newman, [@B47]; Bosco et al., [@B8]; Guandalini, [@B16]). Labeled projections from FEF terminated in the contralateral Cg and other forebrain structures in both hemispheres, including the dorsomedial neostriatum, ventral claustrum (vCLA), and thalamus (see Figure [1](#F1){ref-type="fig"}). These patterns are similar, but not identical, to projections from the M1 whisker regions, (Alloway et al., [@B2], [@B4]). While projections from FEF terminate more medially in neostriatum than those from M1-Wh, both motor regions project to numerous thalamic regions including the anteromedial (AM), interanteromedial (IAM), paracentral (PC), centrolateral (CL), parafasicular (Pf), reuniens (Re), ventral anterior (VA), and ventromedial (VM) nuclei. The FEF also projects to the ipsilateral mediodorsal (MD) nucleus and, to a lesser extent, to the contralateral MD (Figures [1G′--J](#F1){ref-type="fig"}), and these projections to MD appear homologous to the FEF projections in primates (Stanton et al., [@B46]; Sommer and Wurtz, [@B45]). Inspection of the claustrum in both hemispheres revealed dense projections from the contralateral FEF. As seen in both Figures [1](#F1){ref-type="fig"}, [2](#F2){ref-type="fig"}, BDA injections in FEF produced dense terminal labeling in a large part of the contralateral vCLA, but produced noticeably weaker labeling in a smaller area in the ipsilateral vCLA. These corticoclaustral projections from FEF are remarkably similar to the pattern of corticoclaustral projections that originate from the M1 whisker regions (Smith and Alloway, [@B41]). Projections from V1 ------------------- We used physiology, cytoarchitecture, and demarcations in the Paxinos and Watson ([@B34]) atlas to confirm the injections in V1. Cytoarchitecturally, V1 is characterized by a prominent granular layer IV, which is not present in surrounding medial and lateral secondary visual cortices, areas 18a and b (Miller and Vogt, [@B30]). Substantial amounts of transported tracer in the lateral geniculate nucleus (LGN) of the thalamus further confirmed our injections into V1 (data not shown). Examination of the claustrum in both hemispheres revealed very sparse projections from V1 cortex. In fact, as shown in Figure [2](#F2){ref-type="fig"}, the few labeled projections from V1 to the claustrum that were most noticeable were generally located in the ipsilateral hemisphere. By contrast, projections from V1 were observed in several subcortical structures, and many of these overlapped with the projections from FEF. Labeled projections from FEF and V1 overlapped ipsilaterally in the dorsomedial neostriatum, superior colliculus, PC, CL, and lateroposterior (LP) thalamic nuclei. Non-overlapping projections from V1 and FEF appeared in the laterodorsal (LD) thalamus, the dorsal zona incerta (ZI), and in the basal pontine nuclei, in which labeled projections from FEF were observed on both sides of this structure. Claustral projections to FEF and V1 ----------------------------------- Injections of FG in FEF and TB in V1 of the same hemisphere produced a dense population of labeled soma in the vCLA of the ipsilateral hemisphere. As shown in Figure [3](#F3){ref-type="fig"}, FG- and TB-labeled neurons were intermingled in the ipsilateral vCLA, but very few labeled neurons appeared in the contralateral vCLA. A small proportion (7.0 ± 1.2%, mean ± s.e.m.) of the labeled soma were double labeled as shown in confocal images (see Figures [3C,E](#F3){ref-type="fig"}). Because TB is not easily visualized and is not transported as efficiently as FG, this quantitative measurement of double labeled neurons probably underestimates the proportion of claustral neurons that project to both FEF and V1. ![**The ventral claustrum projects to both FEF and V1. (A--B′)** Fluorogold (FG) deposit in FEF and True Blue (TB) in V1 of the right hemisphere for the same case in Figure [2](#F2){ref-type="fig"}. **(C)** Confocal image of two faintly double-labeled neurons in the left vCLA. **(D)** Reconstruction of labeled soma in the vCLA. Yellow and blue dots are FG- and TB-labeled soma, respectively, and green dots are double-labeled neurons. Black arrows indicate areas in **(C,E)**. **(E)** Confocal image of multiple retrogradely-labeled neurons in the right CLA. Red arrowheads in **(C,E)** indicate double-labeled neurons, white arrowheads indicate TB-labeled neurons. Scale bars: 500 μm in **(A)**; 50 μm in **(C)**; 1 mm in **(D)**.](fnsys-08-00093-g0003){#F3} Nonetheless, our plotted reconstructions illustrate partial overlapping populations of FG- and TB-labeled neurons in vCLA. Double-labeled neurons dominated the center of the labeled population (see Figure [3D](#F3){ref-type="fig"}), and the presence of these neurons indicates that vCLA sends divergent projections to both FEF and V1 in the ipsilateral hemisphere, as reported previously in cats (Minciacchi et al., [@B31]). This result is similar to our previous observations indicating that the claustrum sends divergent projections to the S1 and M1 whisker regions in the ipsilateral hemisphere (Smith et al., [@B43]). The TB and FG injections also produced intermingled labeled neurons, including double-labeled cells, in several other subcortical regions. Populations of FG- and TB-labeled neurons were intermingled in the ipsilateral intralaminar nuclei (PC, CL, IAM, Pf) and bilaterally in the Re nucleus, which occupies the midline of the thalamus. Prominent labeling, including dual-labeled cells, also appeared in the lateral preoptic area. Cortico-claustro-cortical circuit connections --------------------------------------------- Tracer overlap in the claustrum was quantified for the two cases (TI15 and TI16) in which both FEF and V1 were bilaterally injected. In these cases, BDA (FEF) and FR (V1) were deposited on the left side while FG (FEF) and TB (V1) were injected on the right side (Table [1](#T1){ref-type="table"}). As shown in Figure [4B](#F4){ref-type="fig"}, labeling from all four tracers occupied a compact region in the vCLA, spanning no more than 500 μm^2^ within each coronal section. Using 50-μm^2^ bins, a bin had to contain at least four labeled varicosities and one labeled soma to be classified as terminal-soma overlap. This represents the same standard that we used previously to assess cortico-claustro-cortical connectivity (Smith and Alloway, [@B41]). ![**Projections from the left M1-FEF terminate in the right claustrum, which projects to FEF and V1 in the right hemisphere. (B)** Reconstructions of claustral labeling for the same case depicted in Figures [2](#F2){ref-type="fig"}, [3](#F3){ref-type="fig"}. BDA- and FR-labeled terminals shown as black and red dots, respectively; TB- and FG-labeled soma shown as blue- and gold-filled circles, respectively. **(A,C)** Overlap analysis in the left **(A)** and right **(C)** claustrum shows black bins, which contain at least four BDA-labeled varicosities; gold bins, which contain at least one FG-labeled soma; and white bins, which contain both an FG-labeled soma and four BDA-labeled varicosities. **(D,E)** Overlap analysis of BDA-labeled terminals and TB-labeled soma using the same threshold criteria for the bins as in **(A,C)**. Percentages represent fraction of total bins that are colored white in the claustrum of this specific section (i.e., terminal-soma overlap). Scale bars: 1 mm in **(B)**. Bin sizes: 50 μm^2^ in **(A,C--E)**.](fnsys-08-00093-g0004){#F4} Anterograde tracer injections in the left FEF produced dense terminal labeling in the right claustrum. This terminal labeling surrounded the labeled soma produced by retrograde tracer injections in the right FEF. Our overlap analysis indicated that nearly half of the labeled bins in the right claustrum contained both tracers (see Figure [4C](#F4){ref-type="fig"}). By comparison, terminal-somal overlap in the left claustrum was virtually absent owing to a paucity of labeling from either tracer (Figure [4A](#F4){ref-type="fig"}). When terminal-soma overlap across all claustral sections was calculated, the proportion of all labeled bins that contained both BDA-labeled terminals and FG-soma (i.e., terminal-somal overlap) was much larger contralateral to the FEF-BDA injection (43.3 ± 4.6%) than ipsilaterally (5.3 ± 4.3%). Hence, the FEF projects mainly to the contralateral claustrum, which then projects to the FEF in that hemisphere to create an interhemispheric cortico-claustro-cortical circuit between the FEF regions in the two hemispheres. A similar pattern was found for the connections between FEF and the contralateral V1 region. As shown by the section reconstructed in Figures [4D,E](#F4){ref-type="fig"}, terminal-somal overlap was 17.5% in the claustrum contralateral to the FEF-BDA injection but was 0% in the ipsilateral claustrum. When terminal-somal overlap was calculated for all sections through the claustrum that contained labeled bins, the proportion of bins that contained overlap was larger in the claustrum contralateral to the FEF-BDA injection (37.2 ± 3.0%) than in the ipsilateral claustrum (11.4 ± 1.2%). These findings clearly demonstrate the presence of an interhemispheric cortico-claustro-cortical circuit in which the FEF transmits information disynaptically to the contralateral V1 by means of its projections to the contralateral claustrum. Retrograde confirmation of corticoclaustral projections ------------------------------------------------------- Our anterograde tracing results indicate that V1 sends very weak projections to the claustrum, whereas FEF sends dense projections to vCLA. To confirm this finding, we inspected data from our previous study in which we injected FG into the claustrum (see Figure 9 in Smith and Alloway, [@B41]). In that case, the contralateral frontal cortex contained many retrogradely-labeled neurons in the Cg and medial AGm regions (see Figures 10, 11 in Smith and Alloway, [@B41]), but no labeled neurons were observed in the S1 barrel region of either hemisphere. In the occipital region, however, separate populations of FG-labeled neurons were found ipsilaterally (data not reported previously). As indicted by Figure [5](#F5){ref-type="fig"}, a few labeled neurons appeared in layer VI of primary visual cortex (V1) and lateral secondary visual cortex (V2l), but many more labeled neurons were observed in the medial part of the secondary visual cortex (V2m), which is consistent with previous reports (Miller and Vogt, [@B29]; Carey and Neal, [@B10]). ![**Few neurons in visual cortex project to the claustrum. (A)** Reconstruction of an FG deposit in claustrum depicted in Figure 9 of Smith and Alloway ([@B41]). **(B,C)** Nissl-stained section through primary visual (V1), medial secondary visual (V2m), and retrosplenial cortices. **(D)** Plotted location of FG-labeled neurons in an adjacent section. Inset in **(D)** indicates location of **(E)**. **(F,G)** Successive magnifications of retrogradely-labeled soma in V2m. **(H)** Digital reconstructions of FG-labeled neurons in visual cortex. Numbers indicate caudal distance from bregma. Scale bars: 250 μm in **(A,C--E)**; 1 mm in **(B,H)**; 100 μm in **(F)**; 50 μm in **(G)**.](fnsys-08-00093-g0005){#F5} Functional topography of claustral connections with motor cortex ---------------------------------------------------------------- The claustral connections with FEF in the present study were compared to the claustral connections for the M1 whisker (M1-RW, M1-Re) and M1 forepaw (M1-Fp) representations that we characterized previously (Smith and Alloway, [@B41]). Figure [6](#F6){ref-type="fig"} shows the rostrocaudal distribution of claustral labeling produced by injecting retrograde (Figure [6A](#F6){ref-type="fig"}) or anterograde (Figure [6B](#F6){ref-type="fig"}) tracers into these four motor regions (summary of injections in Table [1](#T1){ref-type="table"}). Statistical analysis revealed significant effects for injection location and hemispheric labeling for both anterograde (Injected area: *F* = 34.2; *p* \< 0.00001; Hemispheric labeling: *F* = 25.1; *p* \< 0.00001) and retrograde injections (Injected area: *F* = 10.5; *p* \< 0.00001; Hemispheric labeling: *F* = 95.1; *p* \< 0.00001). ![**Distribution of mean terminal and cell counts from tracer injections in different parts of rat motor cortex. (A)** Labeled terminal counts in the ipsilateral and contralateral claustrum from BDA and FR injections in FEF and in the rhythmic whisking (M1-RW), whisker retraction (M1-Re), and forepaw (M1-Fp) regions from a previous study (Smith and Alloway, [@B41]). **(B)** Labeled cell counts in the claustrum of both hemispheres from FG injections in the same regions. Symbols in each line graph represent the mean counts per section from three tracer injection cases; error bars represent standard error of the mean.](fnsys-08-00093-g0006){#F6} The FEF, M1-RW, and M1-Re regions all project significantly more strongly to the contralateral than to the ipsilateral claustrum (FEF, paired *t* = 2.46, *p* \< 0.05; M1-RW, paired *t* = 6.26, *p* \< 0.000001; M1-Re, paired *t* = 5.59, *p* \< 0.00001). Following retrograde tracer injections into these motor regions, however, the number of labeled neurons is much larger ipsilaterally (FEF, paired *t* = 7.34, *p* \< 0.0000001; M1-RW, paired *t* = 6.46, *p* \< 0.000001; M1-Re, paired *t* = 5.38, *p* \< 0.00001). By comparison, labeling produced by tracer injections in M1-Fp is extremely weak in both directions and is present almost entirely on the ipsilateral side (anterograde labeling, *t* = 6.04, *p* \< 0.000001; retrograde labeling, *t* = 5.60, *p* \< 0.00001). The retrograde labeling patterns observed in the claustrum in the present study were compared with three cases of retrograde labeling in the claustrum (CL01, CL05, and CL21) that were illustrated previously in Figures 1--3 of Smith and Alloway ([@B41]). These comparisons indicate that the claustrum has a distinct functional topography. As shown in Figure [7](#F7){ref-type="fig"}, each ICMS-defined and tracer-injected motor region is linked to a specific part of the claustrum. The FG injections in FEF (case TI-15) and in M1-RW (case CL21), which occupy the Cg/med-AGm region, produced retrograde labeling in the deepest parts of the vCLA. The FG injection in M1-Re (case CL05), which is centered in AGm, produced labeling in the middle of vCLA. Finally, an FG injection in M1-Fp (case CL03), which occupies AGl, revealed labeled neurons mainly in the dCLA. These data indicate that the claustrum has a topographic organization in which the medial to lateral extent of M1 cortex is represented ventral to dorsal in the claustrum. ![**Representative examples illustrating the topography of labeled neurons in the claustrum produced by tracer injections in FEF, M1-RW, M1-Re, and M1-Fp. (A)** Reconstructions of the M1 tracer injections in the current study (case TI-15) and in cases CL-03, CL-05, and CL-21 illustrated in Figures 1--3 of Smith and Alloway ([@B41]). **(B)** Reconstruction of FG-labeled neurons in the claustrum from each injection in **(A)**. Scale bars: 500 μm in **(A)**; 250 μm in **(B)**.](fnsys-08-00093-g0007){#F7} These claustrum subdivisions are defined not only by the specificity of their inputs from motor cortex, but also by their projections to different sensory regions. Comparison of the retrograde labeling in the present study with those from our previous report (Smith et al., [@B43]), indicates that vCLA projects to both FEF and V1, whereas the middle of the claustrum projects to both M1-Re and S1-Wh. Corticoclaustral projections in mice ------------------------------------ We inspected the corticoclaustral connections in the Allen Mouse Brain Connectivity Atlas ([@B1]), and focused on cases with tracer injections in S1, V1, Cg, AGm, and AGl. We examined mouse cases in which the tracers filled all cortical layers and the injection locations appeared equivalent to our injection sites as determined by the surrounding anatomical landmarks. Finally, we analyzed whether the terminal labeling patterns in the forebrain and brainstem matched the patterns seen in our rat experiments to assure functional homology with our data. We observed, for example, that Cg injections in mice produced labeling in the dorsomedial neostriatum, nucleus MD in the thalamus, dorsomedial superior colliculus, and the ocular motor complex in the midbrain. This pattern of labeling is completely consistent with the patterns that we observed when anterograde tracers were deposited in the FEF (Cg cortex) of rats. Likewise, tracer injections in AGm or AGl of mice produced subcortical labeling patterns that are consistent with our anterograde tracer injections at sites where ICMS evoked movements of the whiskers or forelimb (Alloway et al., [@B2], [@B4], [@B3]). Qualitative inspection of the injections in the S1-Wh (Experiment\#: 126908007, 127866392) region matched our previous finding that rat S1 does not project to the claustrum (Smith et al., [@B43]). Mice that received injections in V1 showed sparse labeling in the ipsilateral claustrum (Experiment\#: 113887162, 100141599), which corresponds to our findings when rat V1 region is injected. Finally, as shown in Figure [8](#F8){ref-type="fig"}, injections into Cg (Figures [8A--C](#F8){ref-type="fig"}; Experiment\# 112514202), AGm (Figures [8D--F](#F8){ref-type="fig"}; Experiment\# 141603190), and AGl (Figures [8G--I](#F8){ref-type="fig"}, Experiment\# 141602484) display patterns of interhemispheric corticoclaustral labeling that are highly similar to our results in the rat. In mice, as in rats, the majority of coronal sections containing the claustrum indicate that the AGm and Cg regions project more strongly to the contralateral than to the ipsilateral claustrum (confirming findings by Mao et al., [@B27]), whereas AGl has sparse connections with the claustrum in either hemisphere. ![**Corticoclaustral projections from Cg, AGm, and AGl in mice**. Images of AAV injections and subsequent labeling acquired from the Allen Mouse Brain Connectivity Atlas ([@B1]). Center panels show images of labeling from representative AAV tracer injections in Cg **(B)**, AGm **(E)**, and AGl **(H)**. Hyperlinks connect to the complete data sets on the Allen Institute website. In each case, labeling appears in the contralateral cortex as well as bilaterally in the striatum and claustrum. **(A,D,G)** correspond to insets of the claustrum in the left hemisphere of center panels. **(C,F,I)** likewise correspond to insets of the claustrum in the right hemisphere of center panels. Scale bars: 250 μm in **(A)**; 1 mm in **(B)**.](fnsys-08-00093-g0008){#F8} Discussion {#s4} ========== By placing different anterograde and retrograde tracers in FEF and V1 of both hemispheres, this study revealed several new findings about the functional organization of the rat claustrum. Most significantly, rat FEF sends dense projections to the contralateral claustrum, but sends relatively weak projections to the ipsilateral claustrum. The claustrum receives weak projections from ipsilateral V1 but is not innervated by the contralateral V1. When different retrograde tracers are injected into FEF and V1 of the same hemisphere, many intermingled and double-labeled neurons appear in the ipsilateral, but not the contralateral, claustrum. These results indicate that the claustrum is part of an interhemispheric circuit for transmitting information from FEF to separate visuomotor regions in the other hemisphere. Our previous work shows that the claustrum has a parallel set of circuit connections with the M1 and S1 whisker regions (Smith and Alloway, [@B41]; Smith et al., [@B43]). Collectively, these findings indicate that the claustrum has a role in the interhemispheric transmission of certain types of sensorimotor information. While the claustrum receives dense interhemispheric projections from cortical motor regions that regulate movements of the whiskers and eyes, the M1 limb regions send very weak projections to the claustrum and only within the same hemisphere. These differences in the density of corticoclaustral projections from different parts of M1 are also apparent in the Allen Mouse Brain Connectivity Atlas. A summary of these functional differences in claustral connectivity is illustrated in Figure [9](#F9){ref-type="fig"}. ![**Circuit diagram of interhemispheric sensorimotor cortico-claustro-cortical circuits in rats**. Strength of projections are indicated by line thicknesses (see legend).](fnsys-08-00093-g0009){#F9} Our last major finding is that the claustrum has a well-defined functional topography along its dorsoventral axis. The M1 forepaw region projects to the dorsal claustrum, the M1 whisker region projects to the middle claustrum, and the FEF region projects to the vCLA. Likewise, the S1 forelimb, the S1 whisker, and the V1 regions receive projections from the dorsal, middle, and vCLA, respectively. Visuomotor claustrum circuitry ------------------------------ Corticoclaustral projections from the frontal and occipital cortices differ both qualitatively and quantitatively. The FEF projects densely to the contralateral claustrum, but only weakly to the ipsilateral claustrum. Visual cortex sends some projections to the ipsilateral claustrum, but these originate mainly from V2m, which also projects to FEF and the ventral superior colliculus, regions known for controlling saccadic eye movements (Wang and Burkhalter, [@B52]; Wang et al., [@B54]). The corticoclaustral projections from both FEF and V2m originate from layer V, which is significant because this layer contains corticobulbar motor output neurons. These facts indicate that rat vCLA has a role in processing information concerned with eye movements. The lack of reciprocal projections between certain cortical areas and the claustrum provides some clues about the function of the claustrum. While FEF projects strongly to the contralateral claustrum, the claustrum projects ipsilaterally to FEF but does not send feedback projections to the contralateral FEF. Likewise, the connections between the claustrum and primary visual cortex are not reciprocal. The claustrum projects strongly to ipsilateral V1, but reciprocal projections from V1 to the claustrum are practically nil (Miller and Vogt, [@B29]; Carey and Neal, [@B10]). After placing different retrograde tracers in FEF and V1 of the same hemisphere, we observed many double-labeled neurons in the ventral part of the ipsilateral claustrum, and this indicates that identical information is transmitted from vCLA to both FEF and V1. When these divergent claustral projections to V1 and FEF are considered with the relative weakness of corticoclaustral feedback projections in the same hemisphere, the emerging circuit suggests that the claustrum is important for coordinating V1 and FEF processing in the same hemisphere. Functional topography in the claustrum -------------------------------------- Our studies demonstrate that rat claustrum has a well-defined functional topography. In a previous report we showed that the M1 forelimb region is linked to dCLA, whereas the M1 whisker region is connected to vCLA (Smith and Alloway, [@B41]). The present study extends this work by showing that visuomotor cortical areas are connected to the most ventral part of vCLA. We have observed intraclaustral connections along the rostrocaudal, but not the dorsoventral axis (Smith and Alloway, [@B41]). This anisotropic organization of intraclaustral connectivity is consistent with the segregation of unimodal responses in different subregions of the primate claustrum (Remedios et al., [@B36]). Theoretical function of interhemispheric sensorimotor claustral circuits ------------------------------------------------------------------------ We recently injected different retrograde tracers into S1 and M1, and we observed many double-labeled neurons in the claustrum (Smith et al., [@B43]). In the present study we observed many double-labeled claustral neurons after injecting different retrograde tracers into FEF and V1. These results are consistent with Type A and B claustral neurons that were previously reported in the brains of rats and cats (Minciacchi et al., [@B31]). Selective placement of different retrograde tracers in cortex of the same animals has revealed claustral neurons that innervate both ipsilateral and contralateral frontal regions (Type C neurons), and others that innervate the contralateral frontal and ipsilateral occipital regions (Type D neurons). Other studies on a variety of mammalian species have identified specific claustral regions that project to sensory and motor cortical areas, including divergent projections to the S1 and S2 cortices (Li et al., [@B26]; Sadowski et al., [@B37]; Jakubowaska-Sadowska et al., [@B21]). The presence of double-labeled neurons demonstrates that the claustrum conveys the same information to separate, but functionally-related cortical areas. While the exact nature of the information that is transmitted to FEF and V1 (or to the M1 and S1 whisker regions) remains unknown, claustral divergence provides a mechanism for ensuring simultaneous processing of the same information in separate cortical regions. Our findings in two different sensorimotor systems indicate that dense interhemispheric projections to the claustrum originate from motor regions in frontal cortex. Mounting evidence indicates that these frontal regions (Cg, AGm) in the rat are involved not only in motor control, but also in directed-attention and memory-guided orienting behaviors (Reep and Corwin, [@B35]; Erlich et al., [@B15]; Boly et al., [@B7]). Transmission of attention-related motor signals to the claustrum is supported by the fact that the several intralaminar thalamic nuclei also have connections with the claustrum. Many tracing studies have reported that the claustrum receives non-reciprocal projections from the centromedial, CL, PC, and Pf nuclei (Kaufman and Rosenquist, [@B22]; Sloniewski et al., [@B40]; Vertes et al., [@B49]; Alloway et al., [@B5]). Substantial evidence implicates these intralaminar nuclei with a critical role in attention and conscious perception, (Hudetz, [@B20]), and these connections suggest that the claustrum is involved in dispersing attention-dependent signals during the conscious state. Consistent with our past work (Smith and Alloway, [@B41]; Smith et al., [@B43]), the present study supports our hypothesis that claustral connections enable interhemispheric transmission of certain types of modality-specific information to widely-separated cortical areas. By transmitting information from the frontal cortex in one hemisphere to parietal and occipital regions in the other hemisphere, the claustrum provides an interhemispheric route that extends beyond the other callosal projections that interconnect corresponding sites in both hemispheres. Ocular saccades and whisking are rapid movements involved in the active acquisition of visual and somesthetic information from both sides of the body. These movements are purposeful, they require a conscious state, and they are dynamically modulated by sensory inputs. In addition to callosal connections between corresponding cortical areas in the two hemispheres, the claustrum provides a node for transmitting attention-dependent sensorimotor signals from one frontal region to multiple sensorimotor regions in the other hemisphere. This is especially relevant when attention is directed toward improving the acquisition and interpretation of sensory inputs that may come from a broad expanse of extra-personal space. Indeed, studies in the human visual system have indicated that callosal connections and subcortical circuits are involved in interhemispheric visuomotor integration, "promoting a unified experience of the way we perceive the visual world and prepare our actions" (Schulte and Muller-Oehring, [@B38]). In our view, the claustrum facilitates interhemispheric corticocortical transmission so that multiple sensorimotor cortical regions can work together to produce a stable global percept out of the rapidly shifting sensory information coming in from sensors on both sides of the head. Conflict of interest statement ------------------------------ The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. This work was supported by NIH grant NS37532 awarded to Kevin D. Alloway. [^1]: Edited by: Brian N. Mathur, University of Maryland School of Medicine, USA [^2]: Reviewed by: Preston E. Garraghty, Indiana University, USA; Helen Sherk, University of Washington, USA [^3]: This article was submitted to the journal Frontiers in Systems Neuroscience.
Mid
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Q: can't upvote edited post (Related to Possible bug in locking upvote on an edited question? ) Order of events: User X answered my question. Answer sounded reasonable, so I upvoted. Then I tried to use it, and got a compiler error, so I removed the upvote. Several minutes later, (>5min, I think) User X edited answer to something else. I wanted to upvote, but was locked out (can't find the error message to quote here, something like "you can't change your vote until the user edits it") I couldn't upvote until User X edited the answer again, at my request. The problem is step #5: The user did edit his answer, after I changed my initial vote. (There is a slight chance that my memory of the order of events is wrong, but I am not sure how to check this.) The specific Q/A is here: C++: constructor / initializer for array? A: I have checked the data; step 3 occured about 9 minutes after step 4 -- i.e. you removed the upvote after the edit was made. So the behavior was indeed correct.
Low
[ 0.5121951219512191, 26.25, 25 ]
If there’s one thing I know about superheroes, it’s that a little paralysis isn’t going to keep them down. Not for very long, anyway. And it’s especially true if they happen to be the night. So is the the rabbit really gone? I feel like he could come jumping out of the bushes or something at any moment …
Low
[ 0.402564102564102, 19.625, 29.125 ]
Louisa Deighton jailed for spitting at cop and urinating in police van after arrest in Sevenoaks A serial shop lifter spat at a police officer, threw water over a nurse and then urinated in a police van, a court heard. Her "disgusting" actions sparked an unusual response from Kent’s Chef Constable Alan Pughsley who wrote a victim impact statement. The letter – given to the judge but not read out loud in court – expressed his concerns about protecting his staff from such incidents. She targeted Boots in Sevenoaks High Street It followed Louisa Deighton’s attacks on two emergency workers and four police officers. The 33-year-old, from Chesterfield Close, Orpington, had been arrested for a robbery and eight thefts from the Boots store in High Street in Sevenoaks in April and May, involving £4,500 worth of cosmetics. Maidstone Crown Court heard that such was the concern by police and emergency staff that the Chief Constable took the unusual step of writing a statement. Prosecutor Iestyn Morgan said it outlined the Chief Constable's desire to protect his staff from attacks. No-one was physically injured in any of the incidents. Mr Morgan said there had been “a series of shopliftings at Boots the Chemist in High Street, Sevenoaks". Louisa Deighton had been arrested for a robbery and eight thefts from the Boots store in High Street in Sevenoaks in April and May. Picture: Google Street View (13304983) He added: “The total amount of products taken was round about £5,000 and the last of the thefts involved her being confronted by a shop worker, who recognised Deighton and approached her. “She asked Deighton to return the items and leave the store and Deighton replied that she could do what she wants and if the assistant didn’t get out of the way she would hurt her. “She then continued to take items from the shelf before leaving the store. "She was arrested in a car and taken into custody," he added.# Police arrested her in Orpington .Picture by: Martin Apps Mr Morgan said Deighton then complained of suffering withdrawal symptoms and was taken to Pembury Hospital. The heroin addict demanded special medicines but was told by the nurse she could only have codeine and threw a glass of water over the nurse. Mr Morgan said that as she was taken to a police van she tried to kick out at one officer before urinating in the van on the journey. At Tunbridge Wells she was asked to hand over her hairband but refused and spat at an officer before throwing her head towards another officer and kicked yet another officer in the groin. Deighton appeared at Maidstone Crown Court Deighton, who admitted 16 charges of robbery, assaults, damaging property and thefts, then shouted out from the dock: “I just want to say that I am sorry. "I need professional help. I also need help with my mental health." Her barrister Emin Kandola said the mother of two had “simply lost control and now accepts that that is unacceptable". She was jailed for a total of 12 months that she had taken the cosmetics in order the sell to feed her habit. Judge Julian Smith told her: “When you were confronted by the shop assistant you became belligerent and aggressive and carried on helping yourself.”
Mid
[ 0.5376344086021501, 31.25, 26.875 ]
Pages Wednesday, March 9, 2011 Ok, all you young whipper-snappers out there who know what tagging is: I've been tagged! So, you write down 7 random things about yourself? Here goes: 1. I have to wear glasses now when I read. 2. I LOVE chocolate! 3. I have red hair. 4. I just pre-ordered the movie "Tangled". 5. I don't like winter. 6. I like to stay up late. 7. I'm going to church tonight (Wed. night service) Now, I will tag someone! Ha, ha, ha!!!!!! I will tag beachbabydoll, beast'sbelle, and Liddy. Have fun!!!! ~Susan~ Wednesday, March 2, 2011 My daughter found this web site: http://www.ellowynewilde.com/. They have the most beautiful dolls I've ever seen. They average about $100.00 a piece, and I believe they are about 14 inches high. Most of you adults have probably already seen these dolls. Here is my favorite doll I saw: I think this is just beautiful!!! Here are more: She is stylish, yet modest. For the most part they are all modestly dressed, buy very stylish! They do have a creapy line of dolls that I don't agree with, but these are so beautiful! What do you think? Tuesday, March 1, 2011 It's actually an old project that I haven't started until a few days ago. This past Halloween my daughter wanted to be Alice in Wonderland for our church fall festival. She wanted her AG doll to have a matching costume too, but I never started it. Here's the pattern: The costume wasn't in the traditional colors, but it was still cute. My daughter DID want the traditional colors because the fabric store had nothing similar to what was on the pattern cover. This is what it turned out like. It really looks better on her, than on a hanger. Plus, she looked like Alice in Wonderland when she put it on. I went to Good Will in hopes of finding a white rabbit for her to hold that somebody didn't want anymore. When I arrived at the store I said a prayer, and there was this HUGE white rabbit ready to be bought. So, for $2.00 I bought it, washed it, and made the rabbit a costume just like in the movie. God was so good that day! We ended up giving it away to a little 4-year-old girl at the fall festival. But, I can't find my pictures anywhere!!!! My daughter will have to pose again in the costume before she gets bigger, but I'll never be able to have the pictures with her and the white rabbit if I can't find these pictures.
Low
[ 0.47716894977168905, 26.125, 28.625 ]
Assaultcube Port I would like to see assaultcube ported to Android. It is the best fps that can run on ancient hardware (pentium 3's!) and, done right, would be one of the most successful android games ever by launching hardcore mobile gaming This would require... The game uses openAL, I dunno how much coding that would be to convert Creating a control system that can use the buttons and keys on the phone, as well as the touch screen I decided to take a look into this, after I came across your post while searching for something else. I've been doing a lot of porting programs to Android in my spare time, and this one looks like a good candidate. The biggest initial task would be porting the graphics to OpenGL ES, which is a significantly different API than plain vanilla OpenGL. I found that Intel has done some work on this (see this article). It's not entirely what would be needed for an Android port, but it would certainly be better than starting from scratch. After getting the graphics to work, the main task would be the user interface, as you suggested. This is actually the fun part of porting to Android - where you can really start to personalize the project. So the verdict? Well, this looks like a great project. I have a couple others I'm working on at the moment, but I will definitely put this on my wish-list for when I'm looking to start another project ( assuming someone else doesn't get to it first )
High
[ 0.655813953488372, 35.25, 18.5 ]
Welcome to Top 10 Places Top 10 Places – learn about top 10 attractions in tourist destinations, such as USA, Los Angeles, Europe, Florida, California and many other places in the world. Simply navigate to your destination and see the top 10 attractions so you can pick and choose which ones to visit or you can visit them all.
Low
[ 0.35224586288416004, 18.625, 34.25 ]
package com.twitter.finagle.exp.routing import com.twitter.finagle.service.ReqRepT import com.twitter.finagle.{Service, Status} import com.twitter.util.routing.Router import com.twitter.util.{Future, Return, Throw, Time} import scala.util.control.NonFatal /** * A [[Service]] overlay for a [[Router]] of [[Service services]]. The input [[Req request]] will * attempt to match a known [[Service service endpoint]] for the underlying [[Router]]. * * If a matching service is found, then the route's service will have its [[Service.apply]] called * with the input request. * * If no matching [[Route]] is found, the [[routeNotFoundHandler]] will be called * with the input [[Req]] to allow for customizing behavior of an unmatched route. * * If a [[Future.exception]] results from either the matching service's [[Service.apply]], * the [[routeNotFoundHandler]], or any inline exceptions thrown when calling [[apply()]], * then the [[exceptionHandler]] function can be used to optionally return a * successful [[Rep response]]. * * @param router The underlying [[Router]] that this [[Service]] will be layered upon. * @param notFoundHandler The function that will be called to handle returning a [[Rep response]] * when no matching [[Route route]] is found for the input [[Req request]]. * @param exceptionHandler PartialFunction to handle returning an expected [[Rep]] type when an * exception is encountered within the [[RoutingService]] lifecycle. * @tparam Req The [[RoutingService]] service request type. * @tparam Rep The [[RoutingService]] service response type. * * @note The [[RoutingService]] maintains and reflects the lifecycle [[Status]] of the * [[router]]'s underlying [[Service]] statuses. Calling [[close]] on the [[RoutingService]] * will close the underlying [[router]], which will in turn close any * underlying [[Service services]] defined within the [[Router]]. If a [[Service]] has been * closed outside of this [[RoutingService]], the availability of this [[RoutingService]] will * be marked as [[Status.Closed]]. */ private[finagle] class RoutingService[Req, Rep]( router: Router[Req, Service[Req, Rep]], notFoundHandler: Req => Future[Rep], exceptionHandler: PartialFunction[ReqRepT[Req, Rep], Future[Rep]]) extends Service[Req, Rep] { private[this] val errorHandler: PartialFunction[ReqRepT[Req, Rep], Future[Rep]] = { exceptionHandler.orElse { case ReqRepT(_, t @ Throw(NonFatal(_))) => // TODO - increment unhandled error counter Future.const(t) } } override def apply(request: Req): Future[Rep] = try { val rep = router(request) match { case Some(svc) => svc(request) case _ => notFoundHandler(request) } rep.transform { case r @ Return(_) => Future.const(r) case t @ Throw(NonFatal(_)) => errorHandler(ReqRepT(request, t)) } } catch { case NonFatal(t) => errorHandler(ReqRepT(request, Throw(t))) } override def close(deadline: Time): Future[Unit] = router.close(deadline) override def status: Status = if (router.isClosed) { Status.Closed } else { Status.worstOf[Service[Req, Rep]](router.routes, _.status) } }
Mid
[ 0.5990990990990991, 33.25, 22.25 ]
defmodule CodeFundWeb.Endpoint do use CodeFundWeb, :endpoint socket("/socket", CodeFundWeb.UserSocket) # Serve at "/" the static files from "priv/static" directory. # # You should set gzip to true if you are running phoenix.digest # when deploying your static files in production. plug( Plug.Static, at: "/", from: :code_fund, gzip: false, only: ~w(css fonts home canvab docs theme images js theme favicon.ico robots.txt) ) # Code reloading can be explicitly enabled under the # :code_reloader configuration of your endpoint. if code_reloading? do socket("/phoenix/live_reload/socket", Phoenix.LiveReloader.Socket) plug(Phoenix.LiveReloader) plug(Phoenix.CodeReloader) end plug(Plug.RequestId) plug(Plug.Logger) plug( Plug.Parsers, parsers: [:urlencoded, :multipart, :json], pass: ["*/*"], json_decoder: Jason ) plug(Plug.MethodOverride) plug(Plug.Head) # The session will be stored in the cookie and signed, # this means its contents can be read but not tampered with. # Set :encryption_salt if you would also like to encrypt it. plug( Plug.Session, store: :cookie, key: "_code_fund_key", signing_salt: "XnAMxfYz" ) plug(CodeFundWeb.Router) @moduledoc """ Callback invoked for dynamically configuring the endpoint. It receives the endpoint configuration and checks if configuration should be loaded from the system environment. """ def init(_key, config) do if config[:load_from_system_env] do port = System.get_env("PORT") || raise "expected the PORT environment variable to be set" {:ok, Keyword.put(config, :http, [:inet6, port: port])} else {:ok, config} end end defoverridable url: 0 @spec url() :: String.t() def url() do case Mix.env() == :prod do true -> super() |> URI.parse() |> Map.put(:port, nil) |> to_string false -> super() end end end
Mid
[ 0.607843137254901, 38.75, 25 ]
A heart to know, eyes to see and ears to hear Moses concludes his recitation of blessing and curses when instructing what it means to come into the land by telling the people that only today, forty years after their birth as a people, forty years after the wandering in the desert, have they attained a “heart to know, eyes to see and ears to hear”. “The people demand social justice” has been the slogan of the “Israeli summer”. In many ways the 460,000 people in the streets on Saturday night September 3rd are the new generation coming into the land after 40 years of wandering. There is nowhere on earth that compares with the brilliantaccomplishments of the early chalutzim and the first 20 years ofbuilding the Israeli state. Between 1948 and 1952 the populationdoubled. The new state created jobs, living spaces, revived an ancientlanguage and provided a new sense of purpose for the people of both theState of Israel and the Jewish people while securing its own safety ina hostile environment. In 1967 it was clear to the world that Jewishdestiny was in Jewish hands. In the ensuing 40 years Israel continued toprotect its people, made peace with Egypt and Jordan, tried to pursuepeace with the Palestinians and again brought home one million newcitizens from the former Soviet Union and Ethiopia primarily. However,during these years some lost sight of the societal need for equity. The Kli Yakar teaches us about the phrase V’Rishta, V’Yashavta Bain reference to the land “and you will posses it and dwell in it” Itis explained that human nature is such that after one is settled intheir own land and begins to prosper it is easy to believe that thewealth and prosperity are only of one’s own doing. Some will say thatprosperity comes from God. Others may say it is from the collectiveefforts of the society. For sure, as important as individual work is increating success some elements of prosperity are due to the society as awhole. Bikkurim is the offering of thefirst fruits of success in order to support the larger society. Itcomes to teach us that our success is part of what the society hasenabled us to accomplish. Israel has been so focused on security issuesfor the past 40 years that the prosperity that was created has notbeen made available to all its citizens. The folks in the tent cities,the marchers in the streets, after 40 years, once again have the heartto know, the eyes to see and the ears to hear for a new generation. Justice, Justice, You Shall Pursue” is the English translation of the IMPJ bannerunder which members of our Israel movement marched this summer in TelAviv, Jerusalem, Haifa and other places in Israel. Our Reform IsraelMovement was present and proud. Noar Telem in Jerusalem held a Havdalahservice at the sight of the beginning of the march in front of the bigHaMashbir Department store and next to one of the tent enclaves. Morethan 200 people were present. We work for Israel in many ways. Israeltoday is under enormous political pressures. And yet our love forIsrael is not just about politics. Our vision of Zionism is reflectedin the words of the Israeli Declaration of Independence noting thatIsrael should be “based on freedom, justice and peace as envisaged bythe prophets”. To paraphrase the Torah, we have come intothe land which the Lord our God has given us as an inheritance, we havepossessed it and dwell in it, and we are offering our first fruits,our Bikkurim; to work together for a more just, equitable, andpeaceful Israel. This summer we have all attained a “heart to know,eyes to see and ears to hear”. Rabbi Daniel R. Allen,Executive Director of ARZA, has served as the CEO of the AmericanFriends of Magen David Adom and the United Israel Appeal. Allen isconsidered a leading expert on Israel and American Jewish Philanthropy. About Rabbi Daniel Allen Rabbi Daniel R. Allen is the Executive Director of ARZA, and has served as the CEO of the American Friends of Magen David Adom and the United Israel Appeal. Allen is considered a leading expert on Israel and American Jewish Philanthropy. One Response to “A heart to know, eyes to see and ears to hear” Thanks for this clear and meaningful explanation of The Israeli Summer movement. And thanks for pointing Us to the mission Israel and the Jewish People have of modelling and sharing enlightened peace, justice, freedom, equality and love to all. I pray for reconciliation within Israel, and with all of Israel’s neighbors, and all the countries and religions of this Planet. Categories Archives About RJ.org The Reform Judaism blog, RJ.org, is operated for the Reform Movement and its institutions by the Union for Reform Judaism. RJ.org is the place to get the News and Views of Reform Jews from around North America and the world. Read more.
High
[ 0.6600985221674871, 33.5, 17.25 ]
VOTE for Freedom - Go Home Microsoft There is no choice if you want a computer; YOU HAVE TO BE Microsoft's* customer, and YOU MUST PAY the amount Microsoft decides. Microsoft is fighting hard to steal YOUR Freedom. Fight back! It takes less than 5 minutes to read and sign the petition! Think about how competition has caused computer prices to decline (everything except for Microsoft prices that is). The monopolist, Microsoft, is exempt from the laws of competition. On nearly every computer, absence of real competition hurts you and EVERYONE you know. The Problem: This time around, Microsoft gets to kill two birds with one stone. If Microsoft were allowed to own Yahoo, it would also own Zimbra, and that would be the death of Zimbra as a competitor to Microsoft's Exchange Server* which was purchased by Yahoo a month before Microsoft's move to buy Yahoo. The death of Zimbra also kills, world-wide, the Linux servers needed to run Zimbra software. Linux is free software that competes against Microsoft's Windows.* A Vote for Freedom means Microsoft is not permitted to take-over Yahoo. Your help is needed to get the word to the people that will rule on this merger. Zimbra has been growing rapidly and by buying Zimbra, Yahoo became Microsoft's highly successful competitor to Exchange Server. A Microsoft/Yahoo deal would be anti-competitive. YOU are a member of this community; PROUDLY help send Microsoft home empty-handed. Please do ONE OR MORE of the steps listed below (listed from easiest to hardest):
Mid
[ 0.5654885654885651, 34, 26.125 ]
No auxiliary fees, no exam? Student cries foul after allegedly being barred from test, principal denies knowledge of incident A fifth-form student of Edith Dalton James High School in St Andrew is claiming that he was removed from an examination room yesterday because his auxiliary fees were unpaid. The student told The Gleaner that he was in his class minutes before an examination was scheduled to begin, when students who have fees outstanding were told that they would not be allowed to sit the examination. "When we got out of the class, we were there waiting to see what would happen. I left after the examination started when I saw that they wouldn't let us in," the student told The Gleaner. Ray Howell, principal of the school, said the institution tried innovative ways to collect the $7,000 auxiliary fee for each student. He said parents were asked to write commitment letters for payment before the students could sit the examination. "I tell them to put it in writing, and once they do that, I sign off on it and send it to the vice-principal," Howell said. He told The Gleaner that he was not aware of any student who was not allowed to sit the examination as a result of the non-payment of fees. GIVING A LISTENING EAR "About 20 students wrote letters themselves today (yesterday) outlining the situations at home," the principal said. "I signed off on those letters and all I required of them is their parents' cell numbers. Therefore, (there is) no child who comes to the institution who has given a case (and) we have not listened to the case," Howell said. Howell said the school faces critical financial challenges as the compliance rate for payment continues to be under 30 per cent each year. He said it is important that parents assist in ensuring the functioning of the plant. "While the ministry gives us a cost-sharing grant, it is not enough because of the increased cost for electricity, water and other school-operation activities," Howell said. In the meantime, Everton Hannam, president of the National Parent-Teacher Association, while opting not to comment on the Edith Dalton James case, said parents should enter into arrangements with the schools where auxiliary fees are a concern. "Some ways should be found to ensure that the fees are paid, but certainly not allowing the children to take the exam is backward thinking," Hannam said. Late yesterday, Education Minister Ronald Thwaites said while auxilary fees are obligatory, students should not be excluded from school activities. "No student is to be excluded from examination or any school activity because of non-payment of fees. It is a clear policy, but every student should make all effort to assist the schools with the expenses that they themselves are benefiting from," the minister said.
Mid
[ 0.632558139534883, 34, 19.75 ]
Protein tyrosine kinase in rat brain: neonatal rat brain expresses two types of pp60c-src and a novel protein tyrosine kinase. Using angiotensin I as a substrate, the activity of protein tyrosine kinase was determined in various rat tissues, and its developmental change in rat brain was investigated. The specific activity was shown to be the highest in the brain among the tissues examined in neonatal rats, while it was the highest in the spleen in adult rats. In the brain, the activity varied during development and was the highest in the first postnatal week. To identify the protein tyrosine kinase and examine its relationship with pp60c-src, which is known to be highly expressed in neuronal cells, we attempted to characterize the enzyme from neonatal and adult rat brain, using poly(Glu,Tyr) as a substrate. Neonatal brain was found to express two types of pp60c-src and a novel protein tyrosine kinase to almost the same level, while adult brain expressed pp60c-src predominantly. The neonatal type of pp60c-src and the novel enzyme were designated as pp60nc-src and N-PTK in the present study, respectively. pp60c-src, pp60nc-src, and N-PTK were purified about 660-. 370-, and 260-fold from crude homogenate of neonatal brain, respectively, by procedures including sequential column chromatography on DEAE cellulose, hydroxylapatite, Ultrogel AcA44, and poly(Glu,Tyr) Sepharose. N-PTK behaved as a molecule with apparent Mr = 50,000 on Ultrogel AcA44 gel filtration chromatography. It was not immunoprecipitated by anti-pp60c-src antiserum and did not phosphorylate IgG heavy chain of anti-pp60c-src antibody. It required mainly Mn2+ for activity and phosphorylated tyrosine-containing polyamino acids and synthetic peptides such as angiotensin II and RR-SRC peptide.(ABSTRACT TRUNCATED AT 250 WORDS)
High
[ 0.6666666666666661, 33, 16.5 ]
Q: Conversion from string to binary string in Java I have hexadecimal string of length 80bits like "12345ABCDEF78E9CD741" and need to convert into binary string. I tried the following code String Skey = "12345ABCDEF78E9CD741"; int i = Integer.parseInt(Skey, 16); String bin = Integer.toBinaryString(i); But the integer cant hold 80 bits. So how this can be done in java. A: Parse it to a BigInteger and convert that to binary BigInteger bigint = new BigInteger("12345ABCDEF78E9CD741", 16); System.out.println(bigint.toString(2)); Output: 10010001101000101101010111100110111101111011110001110100111001101011101000001
High
[ 0.706806282722513, 33.75, 14 ]
/** * Copyright (C) 2016 Hyphenate Inc. All rights reserved. * <p> * Licensed under the Apache License, Version 2.0 (the "License"); * you may not use this file except in compliance with the License. * You may obtain a copy of the License at * http://www.apache.org/licenses/LICENSE-2.0 * Unless required by applicable law or agreed to in writing, software * distributed under the License is distributed on an "AS IS" BASIS, * WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied. * See the License for the specific language governing permissions and * limitations under the License. */ package com.htmessage.fanxinht.utils; import java.text.SimpleDateFormat; import java.util.Date; import java.util.List; import java.util.regex.Pattern; import android.app.Activity; import android.app.ActivityManager; import android.app.ActivityManager.RunningTaskInfo; import android.app.AlertDialog; import android.app.ProgressDialog; import android.content.Context; import android.graphics.Rect; import android.net.ConnectivityManager; import android.net.NetworkInfo; import android.os.Build; import android.text.TextUtils; import android.util.DisplayMetrics; import android.util.Log; import android.view.View; import android.view.ViewTreeObserver; import android.widget.TextView; import android.widget.Toast; import com.alibaba.fastjson.JSONException; import com.alibaba.fastjson.JSONObject; import com.htmessage.fanxinht.HTApp; import com.htmessage.fanxinht.HTConstant; import com.htmessage.fanxinht.R; import com.htmessage.fanxinht.acitivity.addfriends.invitefriend.ContactInfo; import com.htmessage.fanxinht.acitivity.main.servicecontacts.ServiceUser; import com.htmessage.fanxinht.domain.User; import com.github.promeg.pinyinhelper.Pinyin; import com.jrmf360.rplib.JrmfRpClient; import com.jrmf360.rplib.http.model.BaseModel; import com.jrmf360.tools.http.OkHttpModelCallBack; public class CommonUtils { private static final String TAG = "CommonUtils"; private static Toast toast; private static ProgressDialog dialog; /** * check if network avalable * * @param context * @return */ public static boolean isNetWorkConnected(Context context) { if (context != null) { ConnectivityManager mConnectivityManager = (ConnectivityManager) context.getSystemService(Context.CONNECTIVITY_SERVICE); NetworkInfo mNetworkInfo = mConnectivityManager.getActiveNetworkInfo(); if (mNetworkInfo != null) { return mNetworkInfo.isAvailable() && mNetworkInfo.isConnected(); } } return false; } /** * check if sdcard exist * * @return */ public static boolean isSdcardExist() { if (android.os.Environment.getExternalStorageState().equals(android.os.Environment.MEDIA_MOUNTED)) return true; else return false; } static String getString(Context context, int resId) { return context.getResources().getString(resId); } /** * get top activity * @param context * @return */ public static String getTopActivity(Context context) { ActivityManager manager = (ActivityManager) context.getSystemService(Context.ACTIVITY_SERVICE); List<RunningTaskInfo> runningTaskInfos = manager.getRunningTasks(1); if (runningTaskInfos != null) return runningTaskInfos.get(0).topActivity.getClassName(); else return ""; } /** * set initial letter of according user's nickname( username if no nickname) * * @param * @param user */ public static void setUserInitialLetter(User user) { final String DefaultLetter = "#"; String letter = DefaultLetter; if (!TextUtils.isEmpty(user.getNick())) { letter = Pinyin.toPinyin(user.getNick().toCharArray()[0]); user.setInitialLetter(letter.toUpperCase().substring(0, 1)); if (isNumeric(user.getInitialLetter()) || !check(user.getInitialLetter())) { user.setInitialLetter("#"); } return; } if (letter == DefaultLetter && !TextUtils.isEmpty(user.getUsername())) { letter = Pinyin.toPinyin(user.getUsername().toCharArray()[0]); } user.setInitialLetter(letter.substring(0, 1)); if (isNumeric(user.getInitialLetter()) || !check(user.getInitialLetter())) { user.setInitialLetter("#"); } } /** * set initial letter of according user's nickname( username if no nickname) * * @param * @param user */ public static void setServiceInitialLetter(ServiceUser user) { final String DefaultLetter = "#"; String letter = DefaultLetter; if (!TextUtils.isEmpty(user.getNick())) { letter = Pinyin.toPinyin(user.getNick().toCharArray()[0]); user.setInitialLetter(letter.toUpperCase().substring(0, 1)); if (!check(user.getInitialLetter()) || isNumeric(user.getInitialLetter())) { user.setInitialLetter(DefaultLetter); } return; } if (letter == DefaultLetter && !TextUtils.isEmpty(user.getUsername())) { letter = Pinyin.toPinyin(user.getUsername().toCharArray()[0]); } user.setInitialLetter(letter.substring(0, 1)); if (!check(user.getInitialLetter()) || isNumeric(user.getInitialLetter())) { user.setInitialLetter(DefaultLetter); } } /** * set initial letter of according user's nickname( username if no nickname) * * @param * @param user */ public static void setContactsInfoInitialLetter(ContactInfo user) { final String DefaultLetter = "#"; String letter = DefaultLetter; if (!TextUtils.isEmpty(user.getName())) { letter = Pinyin.toPinyin(user.getName().toCharArray()[0]); user.setLetter(letter.toUpperCase().substring(0, 1)); if (isNumeric(user.getLetter()) || !check(user.getLetter())) { user.setLetter("#"); } return; } if (letter == DefaultLetter && !TextUtils.isEmpty(user.getName())) { letter = Pinyin.toPinyin(user.getName().toCharArray()[0]); } user.setLetter(letter.substring(0, 1)); if (isNumeric(user.getLetter()) || !check(user.getLetter())) { user.setLetter("#"); } } /** * set initial letter of according user's nickname( username if no nickname) * * @param * @param user */ public static void setUserTeamLetter(User user) { final String DefaultLetter = "0"; String letter = DefaultLetter; String info = user.getUserInfo(); JSONObject userJson = JSONObject.parseObject(info); String teamId = userJson.getString("teamId"); if (!TextUtils.isEmpty(teamId)) { letter = teamId; user.setInitialLetter(letter); return; } } public static String getDuration(Context context, String rel_time, String now_time) { if (TextUtils.isEmpty(now_time)) { if (!TextUtils.isEmpty(rel_time)) { String showTime = rel_time.substring(0, rel_time.lastIndexOf(":")); return showTime; } return "时间错误"; } String backStr = ""; SimpleDateFormat format = new SimpleDateFormat("yyyy-MM-dd HH:mm:ss"); Date d1 = null; Date d2 = null; try { d1 = format.parse(rel_time); d2 = format.parse(now_time); // 毫秒ms long diff = d2.getTime() - d1.getTime(); long diffMinutes = diff / (60 * 1000) % 60; long diffHours = diff / (60 * 60 * 1000) % 24; long diffDays = diff / (24 * 60 * 60 * 1000); if (diffDays != 0) { if (diffDays < 30) { if (1 < diffDays && diffDays < 2) { backStr = context.getString(R.string.yesterday); } else if (1 < diffDays && diffDays < 2) { backStr = context.getString(R.string.The_day_before_yesterday); } else { backStr = String.valueOf(diffDays) + context.getString(R.string.Days_ago); } } else { backStr = context.getString(R.string.long_long_ago); } } else if (diffHours != 0) { backStr = String.valueOf(diffHours) + context.getString(R.string.An_hour_ago); } else if (diffMinutes != 0) { backStr = String.valueOf(diffMinutes) + context.getString(R.string.minutes_ago); } else { backStr = context.getString(R.string.just); } } catch (Exception e) { e.printStackTrace(); } return backStr; } public static int getSupportSoftInputHeight(Activity activity) { Rect r = new Rect(); activity.getWindow().getDecorView().getWindowVisibleDisplayFrame(r); int screenHeight = activity.getWindow().getDecorView().getRootView().getHeight(); int softInputHeight = screenHeight - r.bottom; if (Build.VERSION.SDK_INT >= 20) { // When SDK Level >= 20 (Android L), the softInputHeight will contain the height of softButtonsBar (if has) softInputHeight = softInputHeight - getSoftButtonsBarHeight(activity); Log.d("observeSoftKeyboard---9", String.valueOf(getSoftButtonsBarHeight(activity))); } if (softInputHeight < 0) { Log.w("EmotionInputDetector", "Warning: value of softInputHeight is below zero!"); } return softInputHeight; } private static int getSoftButtonsBarHeight(Activity activity) { DisplayMetrics metrics = new DisplayMetrics(); activity.getWindowManager().getDefaultDisplay().getMetrics(metrics); int usableHeight = metrics.heightPixels; if (Build.VERSION.SDK_INT >= Build.VERSION_CODES.JELLY_BEAN_MR1) { activity.getWindowManager().getDefaultDisplay().getRealMetrics(metrics); } int realHeight = metrics.heightPixels; if (realHeight > usableHeight) { return realHeight - usableHeight; } else { return 0; } } //键盘显示监听 public static void observeSoftKeyboard(final Activity activity, final OnSoftKeyboardChangeListener listener) { final View decorView = activity.getWindow().getDecorView(); decorView.getViewTreeObserver().addOnGlobalLayoutListener(new ViewTreeObserver.OnGlobalLayoutListener() { int previousKeyboardHeight = -1; @Override public void onGlobalLayout() { Rect rect = new Rect(); decorView.getWindowVisibleDisplayFrame(rect); int displayHeight = rect.bottom - rect.top; int height = decorView.getHeight(); int keyboardHeight = height - rect.bottom; if (Build.VERSION.SDK_INT >= 20) { // When SDK Level >= 20 (Android L), the softInputHeight will contain the height of softButtonsBar (if has) keyboardHeight = keyboardHeight - getSoftButtonsBarHeight(activity); } if (previousKeyboardHeight != keyboardHeight) { boolean hide = (double) displayHeight / height > 0.8; listener.onSoftKeyBoardChange(keyboardHeight, !hide, this); } previousKeyboardHeight = height; } }); } public interface OnSoftKeyboardChangeListener { void onSoftKeyBoardChange(int softKeybardHeight, boolean visible, ViewTreeObserver.OnGlobalLayoutListener onGlobalLayoutListener); } public static User Json2User(JSONObject userJson) { User user = new User(userJson.getString(HTConstant.JSON_KEY_HXID)); user.setNick(userJson.getString(HTConstant.JSON_KEY_NICK)); user.setAvatar(userJson.getString(HTConstant.JSON_KEY_AVATAR)); user.setUserInfo(userJson.toJSONString()); CommonUtils.setUserInitialLetter(user); return user; } public static JSONObject User2Json(User user) { JSONObject jsonObject = new JSONObject(); String userInfo = user.getUserInfo(); try { if (userInfo != null) { jsonObject = JSONObject.parseObject(userInfo); } } catch (JSONException e) { Log.d("JSONUtil----->>", "User2Json error"); } return jsonObject; } public static boolean isChinese(String str) { char[] chars = str.toCharArray(); boolean isGB2312 = false; for (int i = 0; i < chars.length; i++) { byte[] bytes = ("" + chars[i]).getBytes(); if (bytes.length == 2) { int[] ints = new int[2]; ints[0] = bytes[0] & 0xff; ints[1] = bytes[1] & 0xff; if (ints[0] >= 0x81 && ints[0] <= 0xFE && ints[1] >= 0x40 && ints[1] <= 0xFE) { isGB2312 = true; break; } } } return isGB2312; } public static boolean test(String s) { char c = s.charAt(0); int i = (int) c; if ((i >= 65 && i <= 90) || (i >= 97 && i <= 122)) { return true; } else { return false; } } public static boolean check(String fstrData) { char c = fstrData.charAt(0); if (((c >= 'a' && c <= 'z') || (c >= 'A' && c <= 'Z'))) { return true; } else { return false; } } public static boolean isNumeric(String str) { Pattern pattern = Pattern.compile("[0-9]*"); return pattern.matcher(str).matches(); } /** * 短吐司 * * @param context * @param msg */ public static void showToastShort(Context context, String msg) { if (toast == null) { toast = Toast.makeText(context, msg, Toast.LENGTH_SHORT); } else { toast.setText(msg); } toast.show(); } /** * 短吐司 * * @param context * @param msg */ public static void showToastShort(Context context, int msg) { if (toast == null) { toast = Toast.makeText(context, msg, Toast.LENGTH_SHORT); } else { toast.setText(msg); } toast.show(); } /** * 长吐司 * * @param context * @param msg */ public static void showToastLong(Context context, String msg) { if (toast == null) { toast = Toast.makeText(context, msg, Toast.LENGTH_LONG); } else { toast.setText(msg); } toast.show(); } /** * 长吐司 * * @param context * @param msg */ public static void showToastLong(Context context, int msg) { if (toast == null) { toast = Toast.makeText(context, msg, Toast.LENGTH_LONG); } else { toast.setText(msg); } toast.show(); } /** * 弹窗 * * @param context * @param title * @param content * @param listener */ public static void showAlertDialog(Activity context, String title, String content, final OnDialogClickListener listener) { AlertDialog.Builder builder = new AlertDialog.Builder(context); View dialogView = View.inflate(context, R.layout.layout_alert_dialog_delete, null); TextView tv_delete_people = (TextView) dialogView.findViewById(R.id.tv_delete_people); View view_line_dialog = dialogView.findViewById(R.id.view_line_dialog); TextView tv_delete_title = (TextView) dialogView.findViewById(R.id.tv_delete_title); TextView tv_cancle = (TextView) dialogView.findViewById(R.id.tv_cancle); TextView tv_ok = (TextView) dialogView.findViewById(R.id.tv_ok); tv_delete_title.setText(title); tv_delete_people.setText(content); builder.setView(dialogView); final AlertDialog dialog = builder.show(); tv_ok.setOnClickListener(new View.OnClickListener() { @Override public void onClick(View v) { dialog.dismiss(); listener.onPriformClock(); } }); tv_cancle.setOnClickListener(new View.OnClickListener() { @Override public void onClick(View v) { dialog.dismiss(); listener.onCancleClock(); } }); } public interface OnDialogClickListener { void onPriformClock(); void onCancleClock(); } public static void showDialogNumal(Context context, String msg) { dialog = new ProgressDialog(context); dialog.setMessage(msg); dialog.show(); } public static void cencelDialog() { if (dialog != null) { dialog.dismiss(); } } /** * 更新魔方的后台信息 * @param activity * @param nick * @param avatar */ public static void upDateRedAvatarUrl(Activity activity,String nick, String avatar) { if (TextUtils.isEmpty(nick)) { nick = HTApp.getInstance().getUsername(); } if (TextUtils.isEmpty(avatar)) { avatar = HTApp.getInstance().getUserAvatar(); } JrmfRpClient.updateUserInfo(activity,HTApp.getInstance().getUsername(), HTApp.getInstance().getThirdToken(), nick, avatar, new OkHttpModelCallBack<BaseModel>() { @Override public void onSuccess(BaseModel baseModel) { boolean success = baseModel.isSuccess(); if (success) { Log.d(TAG, "----更新魔方红包信息成功"); } else { Log.d(TAG, "----更新魔方红包信息失败"); } } @Override public void onFail(String s) { Log.d(TAG, "----更新魔方红包信息失败"); } }); } public interface onUpdateListener { void success(); void failed(); } }
Low
[ 0.49896480331262905, 30.125, 30.25 ]
Early oral feeding after colorectal surgery: A mixed methods study of knowledge translation. Evidence-based guidelines recommend early oral feeding (EOF) as prescription of an unrestricted diet within 24 hours after colorectal surgery. The present study aimed to understand local postoperative feeding practices after colorectal surgery; identify barriers to EOF implementation; select, tailor and implement stakeholder engagement strategies to facilitate EOF uptake; and evaluate changes to practice. A longitudinal, mixed methods study was undertaken, guided by the knowledge-to-action framework. Phase 1 assessed the nature of the problem using postoperative diet Audits 1 and 2. In Phase 2, staff interviews identified barriers to EOF implementation. Results from Phases 1 and 2 were fed back to inform Phase 3 strategies. Knowledge uptake was monitored in Audits 3 and 4. Phase 4 evaluated outcomes from Audit 5. In Phase 1, median time to commencement of full diet was postoperative Days 4 and 3 in Audits 1 and 2, respectively. Phase 2 identified EOF barriers, including disparities in diet upgrade practices and variable understanding of hospital diets. In Phase 3, planned strategies were implemented to improve EOF (i) educational session describing local hospital diets; (ii) consultant decision to prescribe a full diet on operation notes; and (iii) educational sessions with nursing staff describing changes to EOF practice. In Phase 4, median time to commencement of full diet improved to postoperative Day 0. Patients prescribed a full diet on operation notes increased from 0% to 82%. The present study successfully identified and overcame local barriers to improve EOF practices to align with guideline recommendations.
High
[ 0.678048780487804, 34.75, 16.5 ]
Beyond the big headline, a tale of Indian magnificence This day should have been about Ajinkya Rahane’s magnificent assertion of his credentials against a team management that decided he should be benched in the first two Tests of their series against South Africa. It should have been about Virat Kohli and his continuing quest to push the boundaries of batting excellence after a series in which the Indian batsmen have been challenged like never before – against top-class pace bowlers in conditions that aid them. It should have been about Bhuvneshwar Kumar, the unsung hero of the current team, for whom being the best performer in the XI for one match is no guarantee of finding a place in the next. And who can come back despite that, and still deliver one match-turning moment after another. It should have been about M Vijay rediscovering the Monk within. After a strange dalliance with deliveries well outside offstump – the ones who he didn’t care to give a second glance to earlier – he was back at his most patient, his most serene self. All the headlines though, will focus on how play was called off 19 minutes before stumps were scheduled on Friday (January 26) because the umpires deemed the pitch might have become too dangerous with South Africa 17 for 1 chasing 241. It should have been about all the cricketers, and about the Indian batting performance overall. South Africa’s bowling attack had Kagiso Rabada, fierce of pace and endless of stamina with bundles of skill. It had Vernon Philander, who seems to take it as a personal insult if he gives the batsman a centimetre of room. It had Morne Morkel, hostile and delivering the ball from a height that made playing him naturally uncomfortable. And it had Lungi Ngidi, a young tyro who could be a predator. India’s batsmen faced up against these men, on a pitch that resembled a spitting cobra. It had fangs that would appear without warning and sting. And on this pitch, against this attack – they came through. These were the main contributors, but what of Parthiv Patel, sent in to open the innings, making 16 off 15 and not allowing the bowlers to settle into an early rhythm? What of Mohammed Shami, gleefully ransacking boundaries to deny South Africa an opening that seemed there for the taking? India got to 247 all out, but rarely has the value of 247 in a Test match been as mismatched. For those who see only the scoreboard of this match later, they will not know of the courage and skill that went into making those runs. They will not know of how Vijay showed control beyond exemplary, how Kohli rose above the surface and situation for the second time in a match, and how both of them gave India ownership of a passage that could have been their undoing. They will not know that Rahane, inexplicably left out of the first two Tests, walked out and decided that “If I perform here I will be a hero.” Rahane’s 48 was the highest score of India’s innings, and his runs came in just 68 balls. From the outset, when he walked out post lunch to join Kohli, he looked for scoring opportunities. “I was visualising when I was sitting in the dressing room,” he would reveal later. “I was thinking what my approach was going to be because only survival was not the point on this wicket because we wanted to score runs. I was actually thinking from last night what are the important shots on this wicket, and that if I get aggressive in my batting, I could put South Africa on the back foot because they were dominating with their bowling. I was just thinking about going aggressive, if the ball is there to be hit, I will play my shot and that’s it. Vijay and Virat batted out the difficult part so it was easier for me.” Given the context of the match, and the personal story of a mini-comeback after finding himself in the unfamiliar environs of outside the XI in a Test match, Rahane had some extra motivation heading into the match. “It’s definitely a very important innings for me. I was very motivated before this match. When you get an opportunity and then you find a pitch like this, your motivation level rises,” he held. “It was important for me to stay relaxed and not take any pressure when I went out to bat. And the situation was such, we were 100 for 4, I was visualising that if we can score 70-80 runs also from here, then it will be very difficult for them. And then to get 240 runs eventually was very good. But personally, I was really determined and motivated to do well. From all the pitches I’ve played on, I think this was the most challenging.” After the first innings, Cheteshwar Pujara had described the pitch as one of the most challenging he has played on. Even the South Africans have conceded the difficulty of the conditions, where any ball with your name on it might be the next one. Today should have been about Rahane’s redemption, Kohli’s class, Vijay’s serenity and Bhuvneshwar’s grit. That they were all reduced to being the side act was one of the gross injustices that cricket sometimes dishes out. Saurabh Somani is Assistant Editor at Wisden India. You can follow him on twitter @saurabh_42 About Wisden india Wisden India believes that there's still a place for intelligent writing. Ours is a combination of reportage and analysis, concise and hard-hitting. But fine writing is but one part of the package. We are excited by new media, and will be using it extensively, driven by Wisden's brand values. There will also be engagement with fans over social-networking platforms like Facebook and Twitter - including blogs, polls and fan votes on various elements of the digital offering.
Mid
[ 0.551971326164874, 38.5, 31.25 ]
1 B.R. 212 (1979) In re Stephen A. HOLLOCK, Individually and trading as S & R T.V. Electronics, Bankrupt. PIERCE-PHELPS, INC. and First Pennsylvania Banking & Trust Company, Appellees, v. Stephen A. HOLLOCK, Individually and trading as S & R T.V. Electronics, Appellant. Bankruptcy No. 76-201, Civ. No. 79-548. United States District Court, M.D. Pennsylvania. September 13, 1979. *213 Charles A. Shea III, Shea, Shea & Caputo, Wilkes-Barre, Pa., for appellant. John Q. Durkin, Nogi, O'Malley & Harris, Scranton, Pa., for appellees. MEMORANDUM AND ORDER RICHARD P. CONABOY, District Judge. Stephen A. Hollock, individually and trading as S & R T.V. Electronics, filed a Voluntary Petition in Bankruptcy on February 20, 1976. Pursuant to Rules 701 and 712, Pierce-Phelps, Inc. and First Pennsylvania Banking and Trust Company brought an adversary proceeding against Hollock to determine the dischargeability of a debt which he owed to them. A hearing on the matter was held before Bankruptcy Judge Gibbons, and he determined that the Plaintiffs Pierce-Phelps and First Pennsylvania Bank were entitled to have their debt excepted from the order of discharge. Hollock has appealed that determination to this *214 court pursuant to Bankruptcy Rule 801. Since we find that the facts as found by the Bankruptcy Judge are amply supported by the record, and do support his conclusions of law we will affirm the determination of the Bankruptcy Judge. The indebtedness which is the subject of this action is the result of a floor plan financing agreement which was entered into by Pierce-Phelps as supplier, First Pennsylvania Bank as financing agent and Hollock as dealer. The bankrupt applied for this plan in June of 1973. He submitted credit applications and financial statements in support of his application. None of these initial statements were false or misleading in any way. Hollock's application was approved, and on July 2, 1973, he executed a Dealer Floor-Plan Agreement and Signatory Authorization with First Pennsylvania. This contract granted him a secured line of credit in the amount of $20,000. Under the dealer floor-plan arrangement, Pierce-Phelps supplied equipment to Hollock, and was paid for the items delivered by the bank. When Hollock subsequently sold an item he was to forward his payment for it immediately to the bank. Pierce-Phelps employed checkers, who went to the individual dealers each month to check the inventory against their records, and determine that proper payments were being made. If the checker found that a piece of equipment was not in the inventory, and payment for it had not been forwarded to the bank, he was to collect payment before leaving the dealer. Hollock maintained his place of business in his home, and stored his equipment in his basement. During the seven months prior to December of 1974, it became increasingly difficult for the checker assigned to Hollock to perform his duties, because the cartons were stored in an inaccessible area. Hollock helped the checker by reading the serial numbers from the cartons to him, while the checker compared them to his list. After the physical count was completed, both the checker and Hollock would sign and verify the report before it went back to Pierce-Phelps. In December of 1974, Hollock informed Pierce-Phelps' credit manager that he had "cheated" on the reports that he had made with the checker. He had called model and serial numbers from empty cartons, even though some of the items had in fact been missing since July of 1974. The total value of all the missing items was determined to be $9,150.32. Section 17(a) of the Bankruptcy Act, 11 U.S.C. § 35(a), excepts certain debts from discharge in bankruptcy, including: "(2) . . . liabilities for obtaining money or property by false pretenses or false representations, or for obtaining money or property on credit or obtaining an extension or renewal of credit in reliance upon a materially false statement in writing respecting his financial condition made or published or caused to be made or published in any manner whatsoever with intent to deceive." The party seeking to declare a debt nondischargeable under this section must prove the following elements: "`(1) the debtor made the representations; (2) that at the time he knew they were false; (3) that he made them with the intention and purpose of deceiving the creditor; (4) that the creditor relied on such representations and (5) that the creditor sustained the alleged loss and damage as the proximate result of the representations having been made.'" Sweet v. Ritter Finance Co., 263 F.Supp. 540, 543 (W.D.Va.1967). Collier on Bankruptcy, 14th Edition Paragraph 17.16 p. 1641 discusses this provision: "A false representation within the meaning of clause (2) may consist of a false financial statement made to the creditor for the purpose of obtaining property on credit terms. (citing cases) Although case law had reached this result prior to the 1960 amendment, (citing cases) the addition of the following clause in § 17a(2) removed any doubt on the subject: (citing cases) `or for obtaining money or property on credit or obtaining an extension or renewal *215 of credit in reliance upon a materially false statement in writing respecting his financial condition made or published or caused to be made or published in any manner whatsoever with intent to deceive. . . .' (citing cases) But a statement which was true when given, will not constitute a false representation because of a subsequent change in the debtor's affairs, unless the statement constitutes a continuing representation because of the debtor's duty to inform the creditor of changes in his (the debtor's) status. (citing cases)." The Bankruptcy Judge, based on the above provisions of law, found that the inventory statements in question were "continuing representations" by the debtor, that the creditors relied on them to their detriment, that the debtor acknowledged that the statements were false, and made for the purpose of deceiving the creditors, and that as a result of their reliance on these representations, the creditors suffered a loss of $9,150.32. Therefore, he excepted this debt from discharge. In reviewing the determinations of a Bankruptcy Judge, the District Court must accept the Bankruptcy Judge's findings of fact unless they are clearly erroneous, giving due regard to the opportunity of the Bankruptcy Judge to judge the credibility of the witnesses. See Bankruptcy Rule 810. The clearly erroneous standard does not apply to questions of law, and the Bankruptcy Judge's legal conclusions may not be approved without our independent determination of the legal questions. In re Gilchrist, 410 F.Supp. 1070, 1075 (E.D.Pa.); 2A Collier Paragraph 39.28 at 1532-1533. The debtor's objections to the findings of the Bankruptcy Judge frame three issues for our consideration: (1) whether the misrepresentations made by the debtor were subsequent to the extension of credit, and therefore have no effect on the dischargeability of this as a pre-existing debt; (2) whether the misstatements and resulting incorrect inventory reports were "continuing representations" on which the creditor was entitled to rely; and (3) whether the creditors sustained their burden of proof. The debtor's first objection is based on the principle that the fraud necessary to except a debt from discharge must have existed when the debt was created, and that any subsequent fraudulent conduct is inconsequential. He argues that the original extension of credit here took place before any false statements were made, and that his subsequent misrepresentations therefore do not bar this debt from discharge. In support of this, the debtor relies on several cases which we find to be inapposite because they deal with debts created by a single contract, extension of credit or payment due, and allegations of fraud subsequent to the time the credit was extended.[1] No cases are cited where there is an ongoing relationship or course of dealing between the parties, as in the case at bar. Their agreement contemplated a flexible line of credit, subject to periodic evaluation, which placed on the debtor a duty to make continuing representations in the form of monthly inventory reports to keep the creditor informed of his status. Therefore, we cannot agree that this case is governed by the principle suggested by the debtor and is not subject to discharge on that basis. Debtor next contends that the inventory reports were not continuing representations made by him because they were made by employees of the creditor, and were not his statements. *216 The checkers employed by the creditors were operating according to the following instructions: "It is your important responsibility to physically determine whether or not items still being financed are on the dealer's floor. A mere checking of our list against the dealer's records is not sufficient, nor should the job be delegated to the dealer or one of his employees. . . . Our letter to the dealer, welcoming him to the Plan, has told him that you will check for us, and asked the dealer to provide you with every cooperation so that you can do your job easily and with the least possible disturbance to the dealer." The debtor contends that the checker was not acting according to his instructions when he allowed the debtor to assist him in making the inventory check, and that the creditor therefore is not entitled to rely on these reports. However, the checker's instructions do allow him to enlist the cooperation of the dealer, which in this instance is just what occurred. Copies of the forms submitted at the hearing indicated that they were signed by the debtor and the checker, and that the debtor knew that they would then be forwarded to Pierce-Phelps as a part of the floor-plan financing system. Under these circumstances, we find no error in the Bankruptcy Judge's determination that these constituted "continuing representations" of the debtor, on which the creditors were entitled to rely. The last contention of the debtor is that his creditors have failed to sustain their burden of proof. However, our examination of the record shows that the testimony offered supports the finding of the Bankruptcy Court. There was uncontradicted testimony presented to show that the debtor made false representations to the creditors by submitting false inventory reports; that he knew these reports were false when made; that he did so for the purpose of deceiving his creditors and delaying his payments and obtaining an extension of further credit; that the creditors relied on these representations, and as a result of this reliance suffered a loss in the amount of $9,150.32. The creditors did establish all the elements necessary to except a debt from discharge under Section 17(a) of the Bankruptcy Act. The determination of the Bankruptcy Judge will be affirmed. ORDER NOW, this 13th day of September, 1979, the Order of the Bankruptcy Court is hereby affirmed, and the debt owed by the bankrupt herein to the Appellees herein in the sum of $9,150.32 is excepted from the order of discharge in these proceedings. NOTES [1] See e.g. In re Schalm CCH Bankruptcy Law Reporter Paragraph 66, 811 (S.D.N.Y., 1978) Cash and letters of credit obtained by general partner from limited partners were not excepted from discharge by later false representations); In re Ducote, CCH Bankruptcy Law Reporter Paragraph 66, 691 (W.D.La., 1978) (False statement submitted to loan company after loan was approved does not except that loan from discharge); In re Langdon, CCH Bankruptcy Law Reporter Paragraph 66, 117 (S.D.N.Y.1977) (Purchaser of mobile home from bankrupt seller sought to have down payment returned as a non-dischargeable debt, and court refused, because there was no fraudulent intent alleged at the inception of the contract).
Mid
[ 0.5623582766439911, 31, 24.125 ]
Q: How to migrate gulpfile.js file content to webpack-mix.js file I bought a theme online and got a gulpfile with it, while i am using webpack-mix file. I tried a few things but couldn't solve it. Can someone tell me where to look or how to solve. Thanks! Gulpfile.js // Define variables var layout = 'layout_1', // 'layout_1', 'layout_2', 'layout_3', 'layout_4', 'layout_5' theme = 'default', // 'default' or 'material' direction = 'LTR', // 'LTR' or 'RTL' type = 'full', // 'full' or 'seed' iconset = 'icomoon'; // 'icomoon' (default), 'fontawesome', 'material' // Define plugins var gulp = require('gulp'), postcss = require('gulp-postcss'), jshint = require('gulp-jshint'), sass = require('gulp-sass'), minifyCss = require('gulp-clean-css'), concat = require('gulp-concat'), uglify = require('gulp-uglify'), rename = require('gulp-rename'), rtlcss = require('gulp-rtlcss'); // Lint gulp.task('lint', function() { return gulp .src(layout + '/' + direction + '/' + theme + '/' + type + '/assets/js/*.js') .pipe(jshint()) .pipe(jshint.reporter('default')); }); // // SCSS compilation // gulp.task('sass', function() { return gulp .src('global_assets/scss/layouts/' + layout + '/' + theme + '/compile/*.scss') .pipe(sass()) .pipe(postcss(processors)) .pipe(gulp.dest(layout + '/' + direction + '/' + theme + '/' + type + '/assets/css')) .pipe(minifyCss({ level: {1: {specialComments: 0}} })) .pipe(rename({ suffix: ".min" })) .pipe(gulp.dest(layout + '/' + direction + '/' + theme + '/' + type + '/assets/css')); }); // Listen for changes in all SCSS files and automatically re-compile gulp.task('watch', function() { gulp.watch('global_assets/scss/**/*.scss', ['sass']); }); webpack.mix.js mix.js('resources/js/app.js', 'public/js') .sass('resources/sass/app.scss', 'public/css'); I just need the basic functions migrated. Can someone help me migrate this gulpfile to webpack.mix.js file? A: My solution const mix = require('laravel-mix'), postcss = require('postcss-custom-properties'); /* |-------------------------------------------------------------------------- | Mix Asset Management |-------------------------------------------------------------------------- | | Mix provides a clean, fluent API for defining some Webpack build steps | for your Laravel application. By default, we are compiling the Sass | file for the application as well as bundling up all the JS files. | */ var layout = 'admin', theme = 'material', iconset = 'icomoon'; mix.react('resources/assets/js/app.js', 'public/js') .sass('resources/assets/scss/front.scss', 'public/css/front.css') mix.sass('resources/assets/scss/admin.scss', 'public/css/admin.css') .options({ autoprefixer: { options: { browsers: [ '>= 1%', 'last 1 major version', 'Chrome >= 45', 'Firefox >= 38', 'Edge >= 12', 'Explorer >= 10', 'iOS >= 9', 'Safari >= 9', 'Android >= 4.4', 'Opera >= 30' ], map: false } }, postCss: [postcss], purifyCss: true }); mix.sass('resources/assets/scss/shared/icons/' + iconset + '/compile/styles.scss', 'public/css/' + layout + '/icons/' + iconset) mix.disableNotifications();
Mid
[ 0.548523206751054, 32.5, 26.75 ]
[MV & Album Review] Sunmi – 'WARNING/Siren' SUNMI – 'WARNING' Ex-Wonder Girls alum Sunmi has released the mini-album 'Warning,' wrapping up the trilogy started with "Gashina." Each of these singles gives a warning to a hypothetical lover. "Siren" is the final one. This EP contains five new tracks, plus the previous singles "Gashina" and "Heroine." The album opens with the darkwave track "ADDICT." There are vocals, but it sounds for all the world like an intro track. A very edgy one. She's been flirting with dark and dangerous songs for awhile throughout her solo career, but I think this is where she finally succeeded. It's all in English, too. "Siren" is the title track, and opens suitably dark for the subject matter. The title refers to the monsters from Greek mythology who enchanted sailors with their songs and drowned them. She's cautioning a boyfriend that's she's likely to hurt them. Probably one of the best I've heard from her yet. "Curve" is more pure R&B than the previous two tracks. She's in fine form for this one too, her voice equal parts sharp and seductive. It's not the best song in this collection, but it's not bad at all. She smooths it out on "Black Pearl," another R&B inspired track. It likens a transformation in her, caused by a guy. From the sound of it, it wasn't a good relationship. Regardless of how this track was written, at least we got a good song out of it. "SecretTape" is the ending track, and it's the outlier here, starting quietly on an acoustic guitar and then suddenly shifting in power and energy (not to mention volume) to more of a dance tune. The change-up is dramatic and swift. Sunmi has talked of wanting to create her own genre and cement her identity as a solo artist. I'm not sure whether or not she succeeded, but the beginning and ending tracks certainly are original, and not often heard in K-pop. The EP is pretty awesome, bolstered by her previous hits. The fact that she had a hand in all these songs is also pretty impressive. Her own genre? They jury's still out. But it is all highly unique and all Sunmi. MV REVIEW If the song was dark, the video is ominous, but also weird. Apparently, there's a clone of Sunmi running around. This clone is the one singing the song, and she apparently exists in every room at once, and Sunmi can't even escape by leaving the house since she's stopped on her doorstep by flashing lights and the yellow tape they use to cordon off crime scenes. Sunmi dances here, too, and her movements are as bold as any boy group. She's no stranger to all this, so my expectations are high. And I really enjoyed the dance moves, particularly how she spreads her arms and the backup dancers explode away from her. The choreo is solid and arresting. This could have been played for laughs, but the lighting and the oddness of it give it a gloomier cast. And I like that. Despite the bright colors and the intensity of the vocals, the MV still manages to be unsettling. And yeah, I'd be running away from a clone of myself. A clone of Sunmi? There's no way I'd run.
Mid
[ 0.581730769230769, 30.25, 21.75 ]
CytoSport ends endorsement deal with Hernandez BOSTON (AP) - The company that makes Muscle Milk is ending its endorsement deal with Patriots tight end Aaron Hernandez. Police have searched in and around Hernandez's home in North Attleborough, Mass., after a 27-year-old semi-pro football player from Boston was found dead a mile away. The district attorney's office has not said whether Hernandez will face any charges. Benicia, Calif.-based CytoSport says in a one-sentence statement that in light of the investigation involving Hernandez, it was terminating its endorsement contract with him effective immediately. The company, which makes Muscle Milk and other nutritional supplements for athletes, did not say how much that contract was worth or what it called for Hernandez to do. (Copyright 2013 The Associated Press. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.)
Low
[ 0.376975169300225, 20.875, 34.5 ]
The increasing use of the electromagnetic spectrum and the need for more sensitive radio telescopes spurs wide interest in adaptive RFI suppression techniques, such as spatial filtering. We study the effect of spatial filtering techniques on radio astronomical image formation. Current deconvolution procedures such as CLEAN are shown to be unsuitable to spatially filtered data, and the necessary corrections are derived. To that end, we reformulate the imaging (deconvolution/calibration) process as a sequential estimation of the locations of astronomical sources. This leads to an extended CLEAN algorithm and gives estimates of the expected image quality and the amount of interference suppression that can be achieved. Some of the effects are shown in simulated images.
High
[ 0.6890756302521001, 30.75, 13.875 ]
Contents ======== 1. Introduction 2. Adenylate kinase isoform-based energetic and metabolic signaling network 2.1. Adenylate kinase isoforms in the nucleus2.2. Adenylate kinase isoforms in cell motility and nucleotide pool homeostasis2.3. Adenylate kinase localization and interacting partners 3. Adenylate kinase catalyzed β-phosphoryl transfer and cell energy economy 4. Adenylate kinase and AMP signaling: an integrated metabolic monitoring and signal ommunication system 5. AMP as universal fuel consumption and low energy signal, mediator of drug action and therapeutic agent 6. Adenylate kinase and AMP signaling networks in body energy sensing 7. Adenylate kinase never rests: from altered energetic signaling to immunodeficiency, cell motility defects, reticular dysgenesis and sensorineural deafness 8. Summary 1.. Introduction ================ Recent studies provide new evidence of the unique energetic, metabolic monitoring and signaling role played by the ubiquitous enzyme adenylate kinase which catalyzes the nucleotide phosphoryl exchange reaction 2ADP ↔ ATP + AMP, critical in cell life \[[@b1-ijms-10-01729]--[@b11-ijms-10-01729]\]. Historically, the function of adenylate kinase has been ascribed to *de novo* adenine nucleotide synthesis and cell energy economy through regulation of nucleotide ratios in different intracellular compartments and AMP-sensitive metabolic enzymes \[[@b1-ijms-10-01729],[@b12-ijms-10-01729]--[@b17-ijms-10-01729]\]. Adenylate kinase has been intensely studied, including its genetics and gene polymorphism, tissue and developmental expression, intracellular distribution and structurefunction relationship \[[@b2-ijms-10-01729],[@b3-ijms-10-01729],[@b14-ijms-10-01729],[@b16-ijms-10-01729]--[@b25-ijms-10-01729]\]. This exemplifies adenylate kinase as a model protein for nucleotide binding folds and phosphoryl transfer catalysis \[[@b19-ijms-10-01729],[@b24-ijms-10-01729],[@b25-ijms-10-01729]\]. The energetic role of adenylate kinase has gained particular significance following discovery that this enzyme facilitates transfer and utilization of γ- and β-phosphoryls in the ATP molecule through a chain of sequential reactions \[[@b1-ijms-10-01729],[@b26-ijms-10-01729]--[@b28-ijms-10-01729]\]. The adenylate kinase-catalyzed energy transfer shuttle and ligand conduction circuit concept \[[@b1-ijms-10-01729],[@b5-ijms-10-01729],[@b29-ijms-10-01729]--[@b31-ijms-10-01729]\] ([Figure 1](#f1-ijms-10-01729){ref-type="fig"}) is supported by biochemical, phosphoryl exchange measurements using ^18^Olabeling, physiological and gene-knockout studies \[[@b4-ijms-10-01729],[@b5-ijms-10-01729],[@b8-ijms-10-01729],[@b15-ijms-10-01729],[@b27-ijms-10-01729]--[@b42-ijms-10-01729]\], and is broadly used to explain energetic signaling mechanisms in heart and skeletal muscles \[[@b5-ijms-10-01729],[@b15-ijms-10-01729],[@b42-ijms-10-01729]--[@b44-ijms-10-01729]\], in hormone secretion \[[@b45-ijms-10-01729]--[@b47-ijms-10-01729]\], organ failure \[[@b4-ijms-10-01729],[@b31-ijms-10-01729],[@b48-ijms-10-01729]--[@b50-ijms-10-01729]\], tumor development \[[@b51-ijms-10-01729]--[@b53-ijms-10-01729]\], energy support of the cell nucleus \[[@b30-ijms-10-01729],[@b34-ijms-10-01729],[@b54-ijms-10-01729],[@b55-ijms-10-01729]\], as well as in sperm and cell motility \[[@b8-ijms-10-01729],[@b56-ijms-10-01729]--[@b59-ijms-10-01729]\]. Muscles of AK1 knockout mice, with one less phosphotransfer chain, display lower energetic efficiency, slower relaxation kinetics and a faster drop in contractility upon ischemia associated with compromised myocardial-vascular crosstalk, AMP and adenosine generation, and impaired metabolic signal communication to the membrane metabolic sensor - the ATP-sensitive potassium channel (K-ATP) and distorted signaling to the energy-sensing AMP-activated protein kinase (AMPK) \[[@b4-ijms-10-01729],[@b5-ijms-10-01729],[@b1-ijms-10-01729],[@b32-ijms-10-01729],[@b33-ijms-10-01729],[@b35-ijms-10-01729],[@b39-ijms-10-01729]--[@b42-ijms-10-01729]\]. The unique ability of the ^18^O-assisted ^31^P-NMR technique to monitor adenylate kinase phosphotransfer and AMP signal dynamics in intact tissues, together with measurements of phosphotransfer rates through creatine kinase and glycolytic/glycogenolytic circuits and responses of metabolic sensors provide further insights into an integrated cellular energetic, metabolic monitoring and energy sensing interface \[[@b5-ijms-10-01729],[@b30-ijms-10-01729],[@b37-ijms-10-01729],[@b44-ijms-10-01729],[@b60-ijms-10-01729]\]. Due to a unique property of the catalyzed reaction, adenylate kinase is recognized as a sensitive reporter of the cellular energy state, translating small changes in the balance between ATP and ADP into relatively large changes in AMP concentration \[[@b1-ijms-10-01729],[@b2-ijms-10-01729],[@b5-ijms-10-01729],[@b29-ijms-10-01729],[@b62-ijms-10-01729]\]. This enables enzymes and metabolic sensors that are affected by AMP to respond with higher sensitivity and fidelity to stress signals \[[@b33-ijms-10-01729],[@b35-ijms-10-01729],[@b42-ijms-10-01729],[@b52-ijms-10-01729],[@b60-ijms-10-01729]--[@b63-ijms-10-01729]\]. Recent data further indicate that adenylate kinase mediated intracellular AMP signaling is coupled with a number of AMP-responsive elements including metabolic sensors, AMPsensitive metabolic enzymes and adenosine signaling \[[@b5-ijms-10-01729],[@b30-ijms-10-01729],[@b33-ijms-10-01729],[@b42-ijms-10-01729],[@b47-ijms-10-01729],[@b61-ijms-10-01729]--[@b65-ijms-10-01729]\]. By catalyzing nucleotide exchange and AMP signaling, adenylate kinase regulates the activity of glycolytic and glycogenolytic enzymes and provides an integrative node for both pathways to respond rapidly to fluctuating energy demands \[[@b5-ijms-10-01729],[@b30-ijms-10-01729]\]. Adenylate kinase generated AMP is emerging as a potential metabolic signal whose intracellular and circulatory levels determine the balance of peripheral organ energy supply between glucose, glycogen and fat, thus regulating food intake, hormonal state, sleep, hibernation and body energy sensing in conjunction with hypothalamic AMP-activated protein kinase (AMPK), K-ATP channels and adenosine metabolic signaling cascades \[[@b4-ijms-10-01729],[@b5-ijms-10-01729],[@b30-ijms-10-01729],[@b63-ijms-10-01729]--[@b69-ijms-10-01729]\]. Thus, such integrated energetic and metabolic signaling roles place adenylate kinase as a hub within the metabolic regulatory system coordinating components of the cellular bioenergetics network. A distinct role for adenylate kinase is emerging in cell motility, differentiation and mechanoelectrical signal transduction. Adenylate kinase has been implicated in spermatozoa motility by facilitating ATP delivery from midpiece mitochondria to remote ATPases in the tail \[[@b20-ijms-10-01729]\]. It was demonstrated that through interaction with anchoring protein Oda5p adenylate kinase provides local ATP for dynein ATPase, ensuring that both high-energy phosphate bonds of ATP are efficiently utilized at the major site of power production of the microtubule motors involved in diverse cellular movements \[[@b57-ijms-10-01729],[@b70-ijms-10-01729]\]. A recent study has demonstrated that a mutation in adenylate kinase 7 (AK7) underlies a primary ciliary dyskinesia phenotype in chronic obstructive pulmonary disease \[[@b7-ijms-10-01729]\]. Moreover, van Horssen et al. \[[@b8-ijms-10-01729]\] demonstrated that cytoskeleton-based cell motility can be modulated by spatial repositioning of adenylate kinase 1 (AK1) enzymatic activity providing local ATP supply and 'on-site' fueling of the actomyosin-machinery. More significantly and unexpectedly, mutations in the mitochondrial AK2 (adenylate kinase 2) gene have been identified in individuals affected with reticular dysgenesis, the most severe form of inborn severe combined immunodeficiencies (SCID), which is associated with sensorineural deafness, a process where nucleotide signaling, cell motility and ciliary functions are involved \[[@b9-ijms-10-01729],[@b10-ijms-10-01729]\]. Knockdown of zebra fish *ak2* lead to aberrant leukocyte development, stressing the critical role of AK2, the major isoform in this type of cells, in leukocyte differentiation \[[@b10-ijms-10-01729]\]. It is increasingly recognized that systemic integration of complementary energetic and metabolic signaling networks ensures cellular energy homeostasis and an adequate response to a broad range of functional activities and stress challenges \[[@b5-ijms-10-01729],[@b44-ijms-10-01729]\]. A network and circuit view of the cellular energetic system allows for new perspectives leading to a comprehensive understanding of disease conditions associated with disturbances in energy metabolism, metabolic monitoring and signaling, and metabolic sensors response \[[@b5-ijms-10-01729],[@b71-ijms-10-01729],[@b72-ijms-10-01729]\]. The purpose of this review is to summarize recent evidence regarding the role of the adenylate kinase phosphotransfer circuit in facilitating intracellular energetic communication, metabolic monitoring and AMP signal transduction. We highlight that due to intrinsic catalytic properties adenylate kinase is able to monitor and sense cell and body energetic imbalances caused by physical activity, inadequate oxygenation or nutrient supply. By generating and transmitting metabolic signals to a number of AMP/nucleotide-sensitive cellular and extracellular components, adenylate kinase is a primary player in adjusting cellular energetics, food intake, substrate transport and vascular blood flow to direct nutrient and oxygen delivery and maintain energy homeostasis. 2.. Adenylate Kinase Isoform-Based Energetic and Metabolic Signaling Network ============================================================================ The existence of multiple isoforms of an enzyme usually relates to their different intracellular distribution and kinetic properties according to the local metabolic requirements ([Figure 2](#f2-ijms-10-01729){ref-type="fig"}) \[[@b8-ijms-10-01729],[@b13-ijms-10-01729],[@b14-ijms-10-01729],[@b51-ijms-10-01729],[@b56-ijms-10-01729],[@b57-ijms-10-01729],[@b73-ijms-10-01729]\]. Following the discovery of adenylate kinase more than six decades ago \[see [@b57-ijms-10-01729]\], three major isoforms, AK1, AK2 and AK3 have been identified, which are localized in the cytosol, mitochondrial intermembrane space and matrix, respectively \[[@b13-ijms-10-01729],[@b14-ijms-10-01729],[@b73-ijms-10-01729]\]. They differ in molecular weight, structure, kinetic properties and nucleotide specificity \[[@b19-ijms-10-01729],[@b25-ijms-10-01729],[@b74-ijms-10-01729]\]. AK1 and AK2 specifically bind AMP and favor binding to ATP over other nucleotide triphosphates, while AK3 is a GTP:AMP phosphotransferase specific for the phosphorylation of intramitochondrial AMP, but can only use GTP or ITP as a substrate \[[@b13-ijms-10-01729],[@b75-ijms-10-01729]\]. Within the AK family there are several conserved regions, including a P-loop, AMP- and MgATP/MgADP-binding domains and a lid domain \[[@b19-ijms-10-01729],[@b25-ijms-10-01729]\]. Adenylate kinase isoforms can form dimers and higher molecular order structures \[[@b76-ijms-10-01729],[@b77-ijms-10-01729]\]. Phosphorylation of adenylate kinase has not been detected; but acetylation and myristoylation, which could facilitate binding of adenylate kinase to cell membranes, mitochondria or the nucleus, have been demonstrated \[[@b56-ijms-10-01729],[@b73-ijms-10-01729],[@b78-ijms-10-01729]\]. Recently discovered glutathionylation of adenylate kinase could confer regulation of its activity by the cellular redox state \[[@b79-ijms-10-01729]\]. Different polymorphic subforms of AK1 (AK1-1 and AK1-2) and splice variants of AK2 (AK2AD) have been found, which have distinct electrophoretic mobility and kinetic properties, i.e. AK2A (26.5 kDa) and AK2B (25.6 kDa) \[[@b2-ijms-10-01729],[@b5-ijms-10-01729],[@b80-ijms-10-01729],[@b81-ijms-10-01729]\]. AK1-2 occurs only in the Caucasian populations and is common among hemophilia-A patients \[[@b81-ijms-10-01729]\]. A recent study indicates that the negative effect of smoke on birth weight is more marked in AK1-1 mothers that in AK1-2 carriers, suggesting that zygotes carrying AK1-2 allele are more protected from damaging factors \[[@b82-ijms-10-01729]\]. Interestingly, the specific activity of AK1-2 is about 3.5-times lower than that of AK1-1, whereas the Michaelis constants do not differ for the allelozymes \[[@b80-ijms-10-01729]\]. Sequence analysis showed that Glu-123 in AK1-1 is exchanged for Gln-123 in AK1-2. Mitochondrial AK2-1(A) subform was found in about 30% of bipolar manic depression syndrome (MDS) patients, but in no case of unipolar MDS or controls. Also, tissue specific adenylate kinase isoforms AK4 and AK5 have been cloned which have mitochondrial matrix and cytosolic localization respectively ([Figure 2](#f2-ijms-10-01729){ref-type="fig"}) \[[@b2-ijms-10-01729],[@b23-ijms-10-01729]\]. AK4 protein levels are increased in cultured cells exposed to hypoxia and in animal models of neurodegenerative diseases \[[@b83-ijms-10-01729]\]. Although AK4 is enzymatically inactive it retains nucleotide binding capability, interacts with the mitochondrial ADP/ATP translocator and serves stress responsive protein function promoting cell survival and proliferation \[[@b83-ijms-10-01729]\]. Both AK4 and AK3 are among hypoxia-inducible factor 1 (HIF-1) regulated genes promoting cell survival \[[@b84-ijms-10-01729],[@b85-ijms-10-01729]\]. AK5 was detected in human pancreatic beta-cells and was implicated in regulation of the K-ATP channel \[[@b47-ijms-10-01729]\], while appearance of autoantibodies to AK5 in refractory limbic encephalitis patients carries a poor prognosis \[[@b86-ijms-10-01729]\]. More recently, the existence of an additional *AK1* gene product, the p53-inducible membrane-bound myristoylated AK1β, has been reported and implicated in p53-dependent cell-cycle arrest and nucleotide exchange in the submembrane space \[[@b51-ijms-10-01729],[@b73-ijms-10-01729],[@b87-ijms-10-01729]\]. In this context, the gene encoding AK1 is down-regulated during tumor development, which could be associated with lower AK1β levels and cell cycle disturbances \[[@b88-ijms-10-01729]\]. AK1β also has been demonstrated to be associated with the nuclear envelope \[[@b73-ijms-10-01729]\] and proteomic studies have identified AK1β in epithelium microvilli \[[@b89-ijms-10-01729]\], suggesting a role in energy support of nuclear and epithelia transport processes. 2.1.. Adenylate kinase isoforms in the nucleus ---------------------------------------------- The AK6 isoform was identified to be localized to the cell nucleus where energy provision and nucleotide channeling into DNA synthesis play a critical role in processing genetic information \[[@b34-ijms-10-01729],[@b54-ijms-10-01729]\]. However, there is still controversy regarding the AK6 isoform which is also known as TAF9 RNA polymerase II possessing ATPase activity \[[@b90-ijms-10-01729]\], suggesting that other adenylate kinase isoforms (AK1 and AK5) can also subserve nuclear energetic needs ([Figure 2](#f2-ijms-10-01729){ref-type="fig"}) \[[@b13-ijms-10-01729],[@b34-ijms-10-01729],[@b73-ijms-10-01729]\]. Knockdown of AK6 slows growth and development of *C. elegans* \[[@b91-ijms-10-01729]\], while in yeast a point mutation in Fap7 gene, an analog of AK6, reduces growth on glucose \[[@b92-ijms-10-01729]\]. Another nuclear protein Rad50, a member of DNA repair RAD50/MRE11/NBS1 protein complex (RMN), which is essential for sensing and signaling from DNA double-strand breaks, in addition to ATP binding and hydrolysis bears an adenylate kinase activity required for efficient tethering between different DNA molecules \[[@b93-ijms-10-01729]\]. A mutation affecting the adenylate kinase activity of Rad50, necessary for DNA tethering also abolishes the formation of viable spores \[[@b93-ijms-10-01729]\]. Mutations in the genes that encode Nbs1 and Mre11, which are part of the RMN complex, are responsible for the human radiation sensitivity disorder, the Nijmegen breakage syndrome (NBS), and the ataxia-telangiectasia-like disorder (ATLD), which are characterized by defective checkpoint responses and high levels of chromosomal abnormalities \[[@b94-ijms-10-01729]\]. Interestingly, the Nijmegen breakage syndrome gene product, Nbs1, is required for enzymatic activities of Rad50 and whole RMN complex function, including partial unwinding of a DNA duplex and efficient cleavage of fully paired hairpins \[[@b95-ijms-10-01729]\]. Thus, adenylate kinase and adenylate kinase activity-possessing proteins play a significant role in the energetics of cell nucleus which is separated from major ATP generating processes in the cytosol. 2.2.. Adenylate kinase isoforms in cell motility and nucleotide pool homeostasis -------------------------------------------------------------------------------- The large molecular weight isoform AK7 is associated with cell motility and other processes \[[@b5-ijms-10-01729]\]. Recently, a high level of expression of the AK7 isoform has been demonstrated in bronchial epithelium and appears to be associated with ciliary function \[[@b96-ijms-10-01729]\]. AK7 is a differentiation marker of kinocilia-bearing cells \[[@b97-ijms-10-01729]\], and mutation in the AK7 gene is associated with human ciliary dyskinesia \[[@b7-ijms-10-01729]\]. In this regard, Foxj1, a forkhead transcription factor necessary for ciliogenesis, induces adenylate kinase isoforms AK5 and AK7 along with genes whose products comprise dynein arms \[[@b98-ijms-10-01729]\]. Yet to be named, a protein with adenylate kinase domains coded by chromosome 9 open reading frame 98 (C9orf98) gene is associated with cell migration and nucleotide exchange \[[@b99-ijms-10-01729]\]. In this regard, sea urchin embryo cilia and sperm flagella use high-molecular weight adenylate kinase with triplicated catalytic domains to power swim by ciliary and flagellar movement \[[@b100-ijms-10-01729]\]. Thus, multiple adenylate kinase isoforms create a phosphotransfer network to serve specific needs in different cellular compartments for energetic and metabolic signaling. Heart muscle harbors about 30 -- 40% of adenylate kinase activity in mitochondria particularly in the intermembrane space \[[@b26-ijms-10-01729],[@b74-ijms-10-01729]\]. The mitochondrial AK2 isoform has the highest affinity (lowest Km) for AMP (≤ 10 μM) among AMP metabolizing enzymes and is highly concentrated in the narrow intermembrane space \[[@b18-ijms-10-01729],[@b26-ijms-10-01729],[@b74-ijms-10-01729]\]. Virtually all the AMP reaching mitochondria is converted to ADP and channeled into oxidative phosphorylation maintaining a low cytosolic AMP concentration \[[@b21-ijms-10-01729],[@b35-ijms-10-01729],[@b41-ijms-10-01729],[@b101-ijms-10-01729]\]. In such a way, adenylate kinase tunes cytosolic AMP signals and guards the cellular adenine nucleotide pool \[[@b1-ijms-10-01729],[@b41-ijms-10-01729],[@b102-ijms-10-01729],[@b103-ijms-10-01729]\]. During intense physical activity or metabolic stress, such as ischemia, the AMP concentration rises, turning on other AMP-metabolizing enzymes such as AMPdeaminase and 5'-nucleotidase producing IMP and adenosine \[[@b60-ijms-10-01729],[@b104-ijms-10-01729]\]. In this regard, a marked elevation of mitochondrial AK2 activity has been demonstrated in hypertrophy in response to increased energy demand and the necessity to maintain the cellular adenine nucleotide pool \[[@b105-ijms-10-01729]\]. In Drosophila, AK2 is essential for survival and circadian rhythm formation and the lack of the AK2 gene causes significant insect growth suppression \[[@b2-ijms-10-01729]\]. AK2 is downregulated in Keloids disease associated with fibroproliferative dermal tumors developing as a result of deregulated wound healing \[[@b106-ijms-10-01729]\]. Expression of adenylate kinase isoforms increases in response to muscle exercise, hypoxia, and metabolic stress \[[@b107-ijms-10-01729],[@b108-ijms-10-01729]\]. Also, muscle exercise performance correlates with adenylate kinase activity, signifying that this enzyme is an integral part of cellular energetic homeostasis \[[@b108-ijms-10-01729]\]. In addition, a decreased expression and activity of AK1 has been found in a mouse model for muscular dystrophy (mdx mice) suggesting a direct relationship between lack of dystrophin and alteration of AK1 inducing energetic deficit \[[@b109-ijms-10-01729]\]. A significant increase in AK1 in obese patients could indicate an imbalance in AMP signaling in this metabolic syndrome \[[@b110-ijms-10-01729]\]. 2.3.. Adenylate kinase localization and interacting partners ------------------------------------------------------------ Although major compartments for adenylate kinase isoform localization are known based on cellular fractionation, intimate intracellular anatomy of adenylate kinase distribution has only been studied by immunocytochemistry in neuronal cells and skeletal muscle \[[@b74-ijms-10-01729],[@b111-ijms-10-01729],[@b112-ijms-10-01729]\]. In skeletal muscle myofibrils, adenylate kinase is localized in linear arrays along with creatine kinase and glycolytic enzymes \[[@b111-ijms-10-01729]\]. Similar localization of GFP-tagged AK1 was detected in neonatal cardiomyocytes \[[@b76-ijms-10-01729]\]. Such sequential arrangement of adenylate kinase molecules could provide a bidirectional phosphorelay that links ATP-generation with ATP-consumption and ATP-sensing processes \[[@b1-ijms-10-01729],[@b5-ijms-10-01729]\]. Another study using tagged proteins indicates that AK1β-EGFP is mainly localized on the plasma membrane, whereas AK1-EGFP is distributed throughout the cell except for trace amounts in the nuclear membrane and some vesicles \[[@b87-ijms-10-01729]\]. Adenylate kinase was found to co-purify and presumably interact with glycolytic enzymes and associate with myofibrils, cellular and mitochondrial membranes \[[@b21-ijms-10-01729],[@b26-ijms-10-01729],[@b33-ijms-10-01729],[@b51-ijms-10-01729],[@b73-ijms-10-01729],[@b74-ijms-10-01729],[@b78-ijms-10-01729],[@b113-ijms-10-01729]\]. Adenylate kinase was also found to be engaged in intimate functional/structural interactions with the sarcolemmal K~ATP~ channel, a major metabolic sensor \[[@b33-ijms-10-01729],[@b46-ijms-10-01729],[@b47-ijms-10-01729]\]. More recently, a phosphotransfer enzyme anchoring protein FHL2 was discovered in heart muscle \[[@b76-ijms-10-01729]\]. This protein positions adenylate kinase and other phosphotransfer enzymes close to ATP utilization sites in myofibrils ensuring that both high-energy phosphate bonds of ATP are efficiently utilized. Mutation of the FHL2 protein is associated with cardiomyopathy \[[@b76-ijms-10-01729]\]. Another adenylate kinase anchoring protein, Oda5p, anchors adenylate kinase in the proximity of the dynein arm ensuring that both high-energy phosphate bonds of ATP are efficiently utilized at the major site of power production of the microtubule motors involved in diverse cellular movements \[[@b57-ijms-10-01729],[@b70-ijms-10-01729]\]. In epididymal spermatozoa adenylate kinase AK1 interacts with sperm associated protein P25b within cholesteroland sphingolipid-enriched membrane domains \[[@b114-ijms-10-01729]\]. Such association and localization is necessary for peri-membrane space ATP homeostasis and for sperm maturation and fertilization \[[@b114-ijms-10-01729]\]. A direct interaction between adenylate kinase and several enzymes of the dNTP synthase complex, as well as nucleoside diphosphate kinase was demonstrated using protein affinity chromatography and immunoprecipitation \[[@b115-ijms-10-01729]\]. These results identified adenylate kinase as a specific component of the nuclear dNTP synthase complex, where it facilitates the survey of nucleotide ratios and the synthesis of nucleotides necessary for error-free DNA replication. Although topological positioning of specific proteins is crucial in energetics and signaling processes, the full interactome of adenylate kinase isoforms in cardiac muscle and other tissues is still unknown. In summary, molecular diversity and intracellular arrangement of adenylate kinase isoforms serve as a prototype of energetic and metabolic monitoring network where the localization of enzymes, their kinetic properties and the ability to communicate between different compartments play a critical role. 3.. Adenylate Kinase Catalyzed β-Phosphoryl Transfer and Energy Economy ======================================================================= Adenylate kinase's unique energetic function allows the utilization of the second high-energy bond of the β-phosphoryl in the ATP molecule, thereby doubling the energetic potential, a property not shared by other phosphotransfer systems \[[@b1-ijms-10-01729],[@b5-ijms-10-01729],[@b12-ijms-10-01729],[@b20-ijms-10-01729],[@b26-ijms-10-01729],[@b29-ijms-10-01729]\]. This catalytic function of adenylate kinase is particularly important in tissues with high and fluctuating energy demands, as well as those under metabolic stress \[[@b1-ijms-10-01729],[@b2-ijms-10-01729],[@b5-ijms-10-01729]\]. It is also important for the intimate energy supply to specific cellular processes such as cell ciliary, flagella or cytoskeleton based motility \[[@b8-ijms-10-01729],[@b20-ijms-10-01729],[@b29-ijms-10-01729]--[@b31-ijms-10-01729]\]. A concerted action of both cytosolic and mitochondrial adenylate kinase isoforms is required to facilitate high-energy phosphoryl delivery to cellular ATPases and feedback signal communication to mitochondrial respiration within structurally organized enzymatic modules and networks (see [Figure 1](#f1-ijms-10-01729){ref-type="fig"}) \[[@b1-ijms-10-01729],[@b26-ijms-10-01729],[@b29-ijms-10-01729],[@b31-ijms-10-01729]\]. In these networks, a series of rapidly equilibrating reactions catalyzed by adenylate kinase provide the driving force for high-energy phosphoryl flux \[[@b1-ijms-10-01729],[@b5-ijms-10-01729],[@b30-ijms-10-01729]\]. In addition, adenylate kinase coupled with creatine kinase and glycolytic pathways communicate adenine nucleotide flux changes generated by cellular ATPases to metabolic sensors \[[@b5-ijms-10-01729],[@b29-ijms-10-01729],[@b33-ijms-10-01729],[@b37-ijms-10-01729]\]. In such a way phosphotransfer reactions synchronize electrical and mechanical activities with energy supply processes, which is fundamental for optimal function of the heart \[[@b44-ijms-10-01729],[@b116-ijms-10-01729]\]. Adenylate kinase is one of principle components in the generation of metabolic oscillations by sustaining dynamic fluctuations of adenine nucleotide ratios \[[@b5-ijms-10-01729],[@b29-ijms-10-01729],[@b117-ijms-10-01729],[@b118-ijms-10-01729]\]. In this regard, the term of excitable "adenylate kinase medium" has been proposed \[[@b119-ijms-10-01729]\] to emphasize the significance of this enzyme in conveying energetic and metabolic signals \[[@b5-ijms-10-01729],[@b33-ijms-10-01729]\]. These functions render adenylate kinase essential to the integrated cellular phosphotransfer network sustaining an efficient and vibrant cell energetic economy. Further insights and key support for the current understanding of metabolic signaling networks in their full complexity have come with the development of new methodologies \[[@b1-ijms-10-01729],[@b4-ijms-10-01729],[@b15-ijms-10-01729],[@b31-ijms-10-01729],[@b44-ijms-10-01729],[@b60-ijms-10-01729]\]. Highenergy phosphoryl fluxes through adenylate kinase, captured with ^18^O-assisted ^31^P-NMR, tightly correlated with the performance of the myocardium under various conditions of stress load \[[@b120-ijms-10-01729]\]. This implicates that adenylate kinase along with other phosphotransfer reactions are indispensable routes that direct flow of high-energy phosphoryls between cellular ATPases and the ATP production machinery in mitochondria \[[@b44-ijms-10-01729]\]. Labeling studies indicate that in intact tissues the highest adenylate kinase-catalyzed β-phosphoryl phosphotransfer flux is in the kidney, which approximates 98% of γ-ATP turnover, followed by the liver (80%), the heart (15 -- 22%) and contracting (10 -- 17%) or resting (3 -- 5%) skeletal muscles suggesting an important role of adenylate kinase in tissue energy homeostasis \[[@b5-ijms-10-01729],[@b30-ijms-10-01729],[@b41-ijms-10-01729]\]. Specifically, the total adenylate kinase enzymatic capacity measured in vitro in murine heart is about 6 mM/s, while the phosphotransfer flux in vivo is between 0.2--0.3 mM/s, it increases with functional load and can reach 1 mM/s in hypoxia and is expected to rise even more in ischemia \[[@b5-ijms-10-01729]\]. For comparison, the range of phosphotransfer capacities of creatine kinase and glycolytic pathways are 6--10 mM/s and 2--3 mM/s, respectively \[[@b5-ijms-10-01729]\]. In this regard, activities of adenylate kinase isoforms and intracellular free AMP levels tightly correlate with tissue respiration rates \[[@b16-ijms-10-01729],[@b121-ijms-10-01729]\] and expression of adenylate kinase isoforms increases in response to muscle exercise, hypoxia, and metabolic stress \[[@b107-ijms-10-01729],[@b108-ijms-10-01729]\]. Indeed, adenylate kinase remains active in its ATP regenerating and transferring role as long as ADP is available and the enzyme is not inhibited by a build-up of AMP \[[@b12-ijms-10-01729],[@b13-ijms-10-01729]\]. Adenylate kinase phosphotransfer flux is markedly suppressed by high glucose in insulin secreting cells, reducing adenylate kinase-mediated AMP signaling to the K-ATP channel and AMPK, two key regulators of hormone secretion \[[@b45-ijms-10-01729],[@b122-ijms-10-01729]\]. There is a reciprocal compensatory relationship between adenylate kinase and creatine kinase phosphotransfers to safeguard cellular energy economy: reduction of creatine kinase activity promotes high-energy phosphoryl transfer through the adenylate kinase system in creatine kinase-knockout muscles or under hypoxic stress \[[@b1-ijms-10-01729],[@b15-ijms-10-01729],[@b28-ijms-10-01729],[@b36-ijms-10-01729],[@b60-ijms-10-01729]\]. The condensed mitochondrial structures and a very narrow intracristal space in the living cell poses diffusional limitations for nucleotide exchange \[[@b29-ijms-10-01729]\]. Adenylate kinase (AK2) in the intermembrane space appears necessary to conduct the ADP stimulatory signal through the adenine nucleotide translocator to matrix ATP-synthases, as well as in exporting ATP produced by oxidative phosphorylation \[[@b2-ijms-10-01729],[@b21-ijms-10-01729],[@b29-ijms-10-01729]\]. Disruption of the adenylate kinase gene impedes ATP export and mitochondria-cytosolic communication in yeast \[[@b101-ijms-10-01729]\]. Muscles of AK1 knockout mice display lower energetic efficiency, slower relaxation kinetics and can not sustain low ADP levels under a functional load despite the presence of active creatine kinase, mitochondrial oxidative phosphorylation and glycolytic/glycogenolytic ATP-regenerating pathways, indicating disruption of the coherent energetic network with blunted response to metabolic signals \[[@b15-ijms-10-01729],[@b40-ijms-10-01729]--[@b42-ijms-10-01729]\]. Genetic disruption of both cytosolic M-CK- and AK1-catalysed phosphotransfer pathways compromises intracellular metabolic communication and energetic efficiency, reducing the cellular capability to maintain total ATP turnover under functional load \[[@b39-ijms-10-01729]\]. These new methodologies and transgenic gene manipulations provide the opportunity to decipher regulatory mechanisms that underlie cardiac and skeletal muscle bioenergetic homeostasis. Taken together, studies of adenylate kinase gene-knockout models have opened new perspectives for the further understanding of how cellular energetic and metabolic signaling networks integrate with genetic, biosynthetic, membrane-electrical and receptor-mediated signal transduction events \[[@b2-ijms-10-01729],[@b5-ijms-10-01729],[@b32-ijms-10-01729],[@b33-ijms-10-01729],[@b35-ijms-10-01729],[@b39-ijms-10-01729]\]. Gene-knockout studies also revealed a remarkable plasticity of the cellular phosphotransfer system, where deficiency in an individual enzyme is compensated through the remodeling of the whole energetic network at enzymatic, architectural and genomic levels \[[@b15-ijms-10-01729],[@b36-ijms-10-01729],[@b123-ijms-10-01729],[@b124-ijms-10-01729]\]. Unexpectedly and contrary to common beliefs that adenylate kinase promotes nucleotide degradation, the AK1 deficient heart had less ability to maintain nucleotide pools under metabolic stress \[[@b32-ijms-10-01729],[@b35-ijms-10-01729]\]. Also, in failing hearts adenylate kinase activity tightly correlates with higher cellular adenine nucleotide content \[[@b49-ijms-10-01729],[@b50-ijms-10-01729]\], indicating a new function for adenylate kinase to safeguard the cellular nucleotide pool by rephosphorylating AMP back to ADP and ATP. Emphasizing the significance of intact energetic and metabolic signaling, AK1 deficiency is associated with a range of compensatory changes in glycolytic, glycogenolytic and mitochondrial metabolism and corresponding gene expression to support energy metabolism \[[@b4-ijms-10-01729],[@b15-ijms-10-01729],[@b32-ijms-10-01729],[@b35-ijms-10-01729],[@b39-ijms-10-01729],[@b123-ijms-10-01729]\]. In this regard, one of the major finding resulting from adenylate kinase and creatine kinase knockout studies was the discovery that glycolytic/glycogenolytic enzymes have the ability to provide a network capacity for transferring and distributing high-energy phosphoryls \[[@b1-ijms-10-01729],[@b5-ijms-10-01729],[@b36-ijms-10-01729]\]. The function of the adaptor protein DRAL/FHL-2, which anchors adenylate kinase, creatine kinase and glycolytic enzymes to sites of high energy consumption in myofibrils \[[@b76-ijms-10-01729]\], further highlights the significance of the topological arrangement and integration of the intracellular phosphotransfer network in matching cellular energetic needs. In summary, adenylate kinase-facilitated high energy phosphoryl transfer and coordination between cellular sites of ATP consumption and ATP generation are essential for the safeguard of the cellular nucleotide pool and energy economy. Although significant progress has been made, there are still significant unanswered questions concerning adenylate kinase physiology, especially regarding the energetic role of mitochondrial intermembrane AK2 and matrix AK3, nuclear AK6, ciliary AK7 and other tissue specific adenylate kinase isoforms. 4.. Adenylate Kinase and AMP Signaling: An Integrated Metabolic Monitoring and Signal Communication System ========================================================================================================== Growing evidence indicates the significance of metabolic monitors which directly sense cellular energy state and respond to metabolic imbalances by generating and delivering signaling molecules to metabolic sensors and effectors to produce a regulatory response \[[@b1-ijms-10-01729],[@b2-ijms-10-01729],[@b5-ijms-10-01729],[@b52-ijms-10-01729],[@b62-ijms-10-01729]\]. Central in metabolic monitoring is the enzyme adenylate kinase which constantly reads cellular adenine nucleotide balance, and, in case of disparity, generates AMP signals and facilitates their delivery to a number of AMPsensitive components, including those in the gycolytic and glycogenolytic pathways and to metabolic sensors and effectors such as K-ATP channels and AMPK, which adjust tissue energy and body hormonal state ([Figure 3](#f3-ijms-10-01729){ref-type="fig"}) \[[@b5-ijms-10-01729],[@b29-ijms-10-01729],[@b37-ijms-10-01729],[@b61-ijms-10-01729]\]. Both K-ATP channels and AMPK can regulate cellular energy balance through managing Ca^2+^ influx and by phosphorylating targeted proteins \[[@b5-ijms-10-01729],[@b44-ijms-10-01729]\]. Due to a unique property of the adenylate kinase-catalyzed reaction, a small decrease in ATP levels results in a large increase in AMP, making the latter a sensitive indicator and therefore a suitable signaling molecule of cellular energetic status \[[@b1-ijms-10-01729],[@b5-ijms-10-01729],[@b62-ijms-10-01729]\]. In recent years AMP signaling is emerging as one of the most versatile system in the regulation of diverse cellular processes \[[@b5-ijms-10-01729],[@b72-ijms-10-01729]\]. Importantly, AMP signals must be integrated and tuned to an appropriate level, since low or excess AMP signaling, due to metabolic, hormonal state or metabolic sensors mutations, are associated with disease conditions \[[@b5-ijms-10-01729],[@b29-ijms-10-01729],[@b37-ijms-10-01729],[@b61-ijms-10-01729],[@b62-ijms-10-01729],[@b72-ijms-10-01729],[@b125-ijms-10-01729]\]. As a result of adenylate kinase-mediated metabolic monitoring and AMP signaling ([Figure 3](#f3-ijms-10-01729){ref-type="fig"}), the activity of ATP generating pathways is increased while ATP-consumption is decreased. In particular, adenylate kinase phosphotransfer directly couples with K-ATP channels, facilitating the translation of metabolic signals critical in adjusting cellular excitability-dependent functions in response to demand \[[@b1-ijms-10-01729],[@b33-ijms-10-01729],[@b37-ijms-10-01729],[@b46-ijms-10-01729],[@b47-ijms-10-01729],[@b61-ijms-10-01729]\]. In the intracellular environment where diffusion is restricted, reactions tend to depend strongly on the local rather than global concentrations of metabolites \[[@b37-ijms-10-01729]\]. In this way, adenylate kinase-catalyzed AMP signal generation and nucleotide exchange in the intimate "sensing zone" of metabolic sensors regulate the dynamics and frequency of ligand switching in order to facilitate decoding of cellular information \[[@b5-ijms-10-01729],[@b30-ijms-10-01729],[@b44-ijms-10-01729]\]. Indeed, intracellular measurements using the ^18^O-assisted ^31^P NMR and mass spectrometric techniques indicate that adenylate kinase is uniquely situated to tune the magnitude of the AMP signal because its phosphotransfer displays only a fraction of total capacity, is compartmentalized and not universally at equilibrium, thus it can differentially promote both AMP signal generation and AMP rephosphorylation \[[@b1-ijms-10-01729],[@b4-ijms-10-01729],[@b28-ijms-10-01729],[@b31-ijms-10-01729],[@b36-ijms-10-01729],[@b38-ijms-10-01729],[@b45-ijms-10-01729],[@b60-ijms-10-01729],[@b120-ijms-10-01729],[@b126-ijms-10-01729]\]. In this way, adenylate kinase through negative and positive feedback loops governs adenine nucleotide and glycolytic oscillations providing a dynamic component for facilitated intracellular energetic signal communication \[[@b5-ijms-10-01729],[@b29-ijms-10-01729],[@b117-ijms-10-01729],[@b119-ijms-10-01729]\]. Moreover, through a series of spatially linked enzymatic reactions adenylate kinase facilitates propagation of nucleotide signals in the intracellular and extracellular space, thus coordinating the response of metabolic sensors and nucleotide/nucleoside receptor signaling \[[@b1-ijms-10-01729],[@b5-ijms-10-01729],[@b64-ijms-10-01729],[@b65-ijms-10-01729]\]. Therefore adenylate kinase provides sustained communication between cytosolic and nuclear processes coordinating cell energetic and genomic events \[[@b30-ijms-10-01729],[@b34-ijms-10-01729]\] and between myocardium and vasculature regulating coronary flow and oxygen delivery \[[@b4-ijms-10-01729]\]. Adenylate kinase-induced increase in AMP promotes the generation of adenosine, a powerful metabolic signaling and cardioprotective agent \[[@b60-ijms-10-01729],[@b104-ijms-10-01729]\]. AMP also triggers AMPK activation, an essential signaling module in cellular adaptation to stress \[[@b42-ijms-10-01729],[@b52-ijms-10-01729],[@b62-ijms-10-01729],[@b127-ijms-10-01729]\]. In the heart, the significance of AMPK is suggested by the findings that AMPK activity is increased in ischemia and preconditioning, and that AMPK agonists protect myocardium against ischemic injury \[[@b127-ijms-10-01729],[@b128-ijms-10-01729]\]. Hypoxia or metabolic stress increases adenylate kinase flux inducing AMP generation and downstream AMP/adenosine signaling events important in cardioprotection \[[@b1-ijms-10-01729],[@b59-ijms-10-01729],[@b63-ijms-10-01729],[@b104-ijms-10-01729]\]. Adenylate kinase deficiency compromises metabolic signal reception by metabolic sensors, such as K-ATP channels and AMPK producing a stress vulnerable phenotype \[[@b33-ijms-10-01729],[@b42-ijms-10-01729]\]. In this regard, new data suggests that hydrolysis of AMP by CD73 on graft-resident or circulating cells regulates endothelial barrier function and diminishes transendothelial leukocyte trafficking and mitigates inflammatory and immune response of cardiac transplantation via the A(2B) adenosine receptors \[[@b129-ijms-10-01729]\]. Thus, adenylate kinasemediated AMP signaling through metabolic sensors and nucleoside receptors is an integral part of cellular stress response system. Adenylate kinase does not act alone in performing cellular metabolic monitoring. Recent evidence indicates that the interaction between adenylate kinase and creatine kinase phosphorelays determines metabolic signal communication to the K-ATP channel and mediates energetic remodeling in preconditioned and failing hearts \[[@b29-ijms-10-01729],[@b33-ijms-10-01729],[@b34-ijms-10-01729],[@b37-ijms-10-01729],[@b41-ijms-10-01729],[@b44-ijms-10-01729],[@b116-ijms-10-01729]\]. Under normal conditions creatine kinase suppresses adenylate kinase phosphotransfer by scavenging cellular ADP \[[@b28-ijms-10-01729]\] and thus maintaining the K-ATP channels in the closed state with low metabolic signaling through the AK → AMP → AMPK and AK → AMP → adenosine axis \[[@b33-ijms-10-01729],[@b52-ijms-10-01729],[@b61-ijms-10-01729],[@b105-ijms-10-01729],[@b116-ijms-10-01729]\]. However, hypoxia or metabolic stress diminishes creatine kinase and increases adenylate kinase flux inducing AMP generation and downstream AMP/adenosine signaling events to adjust cellular energy balance \[[@b1-ijms-10-01729],[@b60-ijms-10-01729],[@b63-ijms-10-01729],[@b126-ijms-10-01729]\]. Indeed, deletion of the AK1 gene shifts this balance towards the creatine kinase system, compromising energetic signal communication \[[@b4-ijms-10-01729],[@b33-ijms-10-01729],[@b35-ijms-10-01729],[@b39-ijms-10-01729]\]. Accordingly, AK1 deficiency blunts metabolic signal reception by metabolic sensors, such as K-ATP channels and AMPK, compromising their ability to withstand energetic stress \[[@b33-ijms-10-01729],[@b42-ijms-10-01729]\]. Underscoring the significance of phosphotransfer redistribution in metabolic signaling is the observation that altered adenylate kinase and creatine kinase phosphotransfer enzyme activities are associated with hypertrophy, abnormal vascular tone and hypertension \[[@b105-ijms-10-01729],[@b130-ijms-10-01729],[@b131-ijms-10-01729]\]. The role of adenylate kinase in integrating signaling pathways is further indicated by the recent demonstration that AMP-stimulated AMPK regulates vascular response to hypoxia and nitric oxidedependent vasorelaxation as well as excitation of the oxygen-sensing carotid body which is critical for detection of O~2~ deficit in the bloodstream and adjustment of breathing pattern \[[@b132-ijms-10-01729]--[@b134-ijms-10-01729]\]. In addition, adenylate kinase appears to be the major phosphotransfer system in extraocular muscle, where, together with creatine kinase, it regulates precise eye movements \[[@b135-ijms-10-01729]\]. A more recent study suggests that intracellular and extracellular adenylate kinase plays an important role in nucleotide energetic signaling regulating actin assembly-disassembly involved in cell movement and chemotaxis \[[@b136-ijms-10-01729]\]. Thus, the balance between phosphotransfer systems and subsequent signaling events determine the outcome of metabolic regulation of muscle contractility, electrical activity and vascular tone. In recent years, adenylate kinase-mediated extracellular AMP and ADP signaling has gain an additional significance due to the involvement in high-density lipoprotein (HDL) endocytosis, in signaling through adenosine and AMP-specific receptors \[[@b137-ijms-10-01729]\] and through AMP and other metabolite-sensing RNA riboswitches \[[@b138-ijms-10-01729], [@b139-ijms-10-01729]\], as well as in cell differentiation, tumor suppression and regulation of vascular tone \[[@b5-ijms-10-01729],[@b30-ijms-10-01729],[@b45-ijms-10-01729],[@b51-ijms-10-01729],[@b53-ijms-10-01729],[@b55-ijms-10-01729],[@b64-ijms-10-01729],[@b65-ijms-10-01729],[@b140-ijms-10-01729],[@b141-ijms-10-01729]\]. In this regard, metabolic monitoring system in procaryotic cells utilizes RNA structures embedded at the 5′ ends of mRNAs to sense particular metabolic cues and regulate the encoded genes \[[@b142-ijms-10-01729]\]. By sensing the energy status of muscle cells and regulating gene expression, the adenylate kinase and downstream AMP signaling are critical regulators of mitochondrial itochondrial biogenesis, through the AMPK-PGC-1 signaling cascade, thereby increasing the energy transducing capacity of the cell \[[@b138-ijms-10-01729],[@b143-ijms-10-01729]\]. Moreover, adenylate kinase through AMP signaling regulates glycolytic and glycogenolytic pathways conveying information regarding increased energy demand \[[@b5-ijms-10-01729]\]. Regulation of glycogen metabolism is of primary importance in muscle energetics, including that of the heart \[[@b5-ijms-10-01729],[@b144-ijms-10-01729]\]. Particularly, defective AMP and AMPK signaling is a primary cause of imbalance in glycogen metabolism and associated disease conditions \[[@b145-ijms-10-01729]\]. Adenylate kinase metabolic monitoring plays a significant role in plant tissues \[[@b146-ijms-10-01729]\]. Modulation of plastidial adenylate kinase activity and consequently AMP and adenine nucleotide levels significantly increases starch yield and amino acid biosynthesis \[[@b147-ijms-10-01729],[@b148-ijms-10-01729]\], while overexpression of adenylate kinase in yeasts markedly increases ATP production \[[@b149-ijms-10-01729]\]. Thus, adenylate kinase by providing ATP β-phosphoryls for energetic needs and by regulating nucleotide ratios and AMP signaling adjusts the efficiency of energy metabolism, the capacity of ATP generating reactions and the activity of biosynthetic processes. Intracellular energetic and metabolic signal communication can employ several different mechanisms ranging from facilitated diffusion to ligand conduction, depending on cell type and specific compartment, structural organization and topological arrangement of enzymatic networks \[[@b29-ijms-10-01729],[@b30-ijms-10-01729]\]. While spatial heterogeneity and directionality of the enzyme-catalyzed process is not important in well mixed conditions *in vitro,* this becomes very important entity in highly organized living matter \[[@b150-ijms-10-01729]\]. The cluster organization of enzymes and the high rate of unidirectional phosphoryl exchange in phosphotransfer systems would promote ligand conduction and signal communication at cellular distances \[[@b1-ijms-10-01729],[@b29-ijms-10-01729],[@b30-ijms-10-01729]\]. Adenylate kinase facilitates mitochondria-nuclear energetic communication \[[@b34-ijms-10-01729]\] and within the nucleus, embedded into organized enzymatic complexes of nucleotide-metabolizing and phosphotransfer enzymes, is involved in maintaining proper nuclear dNTP ratios and facilitates channeling of nucleotides into DNA replication machinery \[[@b115-ijms-10-01729]\]. Imbalances in dNTP ratios affect the fidelity of DNA replication and repair leading to acquired mutations \[[@b30-ijms-10-01729],[@b115-ijms-10-01729]\]. Thus, adenylate kinase surveys nucleotide ratios necessary for error-free DNA replication, while another nuclear protein Rad50, harboring adenylate kinase activity, participates in DNA double-strand break repair \[[@b93-ijms-10-01729]\]. Despite recent advances in the metabolic signaling field, more studies are necessary to elucidate mechanisms which link adenylate kinase phosphotransfer flux, AMP signal dynamics and the response of metabolic sensors (AMPK, K-ATP), as well as the significance of AK → AMP → AMP-sensors signaling system in heart physiology, such as in shaping heart force-frequency relationship and Frank- Starling response, and cardioprotection \[[@b5-ijms-10-01729],[@b44-ijms-10-01729]\]. At the molecular level, studies of multienzyme complexes including adenylate kinase would shed light on intimate mechanisms of metabolic sensing. Co-localization of components in signal transduction cascades is critical for the directionality and specificity of the signaling response. The presence of adenylate kinase in close proximity of AMPK would facilitate metabolic signal transduction and create a favorable energetic environment for the phosphorylation of targeted proteins. The significance and downstream mechanisms by which AK → AMP → AMPK signaling axis regulate cell cycle, developmental potential, and timing of differentiation are just starting to be elucidated. Thus, although more studies are needed, adenylate kinase-mediated metabolic monitoring and downstream AMP signaling is increasingly recognized among major homeostatic mechanisms in a number of cells, critical in the regulation of diverse cellular processes and stress-response. 5.. AMP as Universal Fuel Consumption and Low Energy Signal, Mediator of Drug Action and Therapeutic Agent ========================================================================================================== Metabolic signals regulate and integrate many vital functions throughout the human body, including energy homeostasis, blood pressure, heart performance, food intake, hormonal status and brain performance \[[@b30-ijms-10-01729],[@b71-ijms-10-01729]\]. Recent evidence suggests the general importance of adenylate kinase-mediated AMP signaling in appetite, wakefulness and sleep control and in hormonal, food and antidiabetic drug actions which are coupled to alterations of cellular AMP levels and associated signaling \[[@b4-ijms-10-01729],[@b5-ijms-10-01729],[@b46-ijms-10-01729],[@b47-ijms-10-01729],[@b55-ijms-10-01729],[@b62-ijms-10-01729]--[@b70-ijms-10-01729],[@b86-ijms-10-01729],[@b138-ijms-10-01729],[@b151-ijms-10-01729]\]. AMP signaling also plays an important role in hypoxic response, immune function and taste reception \[[@b60-ijms-10-01729],[@b85-ijms-10-01729],[@b129-ijms-10-01729],[@b137-ijms-10-01729],[@b139-ijms-10-01729]\]. Adenylate kinase integrates and tunes AMP signals coming from different sources and delivers them to metabolic sensors to elicit a regulatory response ([Figure 4](#f4-ijms-10-01729){ref-type="fig"}). Reduced or increased adenylate kinase activity would distort integration of AMP signals and, depending on tissue metabolic phenotype and intensity of AMP-generating reactions, could produce both positive and negative impact on the activity of metabolic sensors \[[@b42-ijms-10-01729],[@b152-ijms-10-01729]\]. Recent evidence suggests that ingestion of fructose, a major constituent of sugar and high-fructose corn syrup, causes increase in cellular AMP and AMP/ATP ratio leading to activation of AMPK \[[@b68-ijms-10-01729], [@b153-ijms-10-01729]\]. Contrary to glucose, which usually lowers cellular AMP levels and inhibits AMPK, fructose activates hypothalamic AMPK and increases food consumption ([Figure 4](#f4-ijms-10-01729){ref-type="fig"}) \[[@b68-ijms-10-01729]\]. Compared with glucose-sweetened beverages, consumption of fructose-sweetened beverages with meals elevates postprandial plasma triglycerides and lowers 24-h insulin and leptin profiles in normal weight women \[[@b154-ijms-10-01729]\]. Fructose metabolism bypasses the rate-limiting step of the glucose pathway, and is metabolized much more quickly than glucose. Excessive fructose intake depletes cellular ATP by trapping inorganic phosphate required for ATP resynthesis, consequently inducing nucleotide degradation and increasing plasma uric acid and allantoin levels \[[@b155-ijms-10-01729]\]. These metabolic alterations induced by fructose may play an important role in the epidemic of metabolic syndrome and may contribute the development of diabetes and cardiovascular disease \[[@b156-ijms-10-01729]\]. A diet high in fructose can give rise to hyperlipidemia, insulin resistance and hypertension \[[@b157-ijms-10-01729]\]. Similarly, ethanol consumption and subsequent acetate metabolism causes AMP accumulation in liver and other tissues resulting in increased AMP and adenosine signaling and blood flow \[[@b158-ijms-10-01729],[@b159-ijms-10-01729]\]. Excess ethanol consumption can also cause nucleotide degradation and depletion of cellular adenine nucleotide pool \[[@b160-ijms-10-01729]\]. However, short term and limited exposure to fructose and ethanol could be beneficial in stimulating energy metabolism and metabolic signaling, thus "AMPing" your body \[[@b153-ijms-10-01729],[@b161-ijms-10-01729]\]. In this regard, cardioprotection induced by both fructose and ethanol preconditioning stimuli could be related to augmented AMP signaling \[[@b162-ijms-10-01729],[@b163-ijms-10-01729]\]. Normal human blood AMP levels are in the 10--20 μM range of which only a fraction is free due to binding to serum proteins \[[@b164-ijms-10-01729]\]. Intracellular and blood AMP levels are increased during physical activity and are sensitive indicators of myocardial ischemia rising within minutes after insult \[[@b165-ijms-10-01729],[@b166-ijms-10-01729]\]. Adenylate kinase isoforms provide fine tuning of intracellular, interstitial and circulating AMP levels due to different kinetic properties and localization ([Figure 5](#f5-ijms-10-01729){ref-type="fig"}). Deficiency of AK1 isoform reduces the AMP signal stress response \[[@b4-ijms-10-01729],[@b32-ijms-10-01729],[@b33-ijms-10-01729],[@b35-ijms-10-01729],[@b42-ijms-10-01729]\], however at the basal level it could result in higher AMP signaling due to compromised tune-up mechanisms \[[@b152-ijms-10-01729]\]. Circulating AMP is emerging as a molecular mediator of hibernation and constant darkness effect, switching mice from a glucoseburning, fat-storing state to a fat-burning, glucose-conserving lethargy \[[@b66-ijms-10-01729]\]. In hibernating mammals AMP originating, at least partly, from the brown fat also down-regulates the seasonally-dependent proliferation of the thymus \[[@b167-ijms-10-01729]\]. In addition, overworked brains release adenosine, usually originating from AMP, to slow cell activity and trigger sleep \[[@b168-ijms-10-01729],[@b169-ijms-10-01729]\]. These data strongly support the notion that AMP and adenosine play a key role as endogenous modulators of wakefulness and sleep which fits with our proposed role of phosphotransfer reactions in regulating brain activity and information processing \[[@b30-ijms-10-01729]\]. Available evidence suggests that growth factors, which alter cellular energy metabolism, and hormones, such as adipocyte-derived leptin and adiponectin, activate AMPK through local or temporal regulation of AMP levels \[[@b170-ijms-10-01729]--[@b172-ijms-10-01729]\]. Leptin alters muscle adenine nucleotide homeostasis (decreases ATP) and increases AMP dynamics (inferred from elevated AMP and IMP levels) followed by activation of AMPK \[[@b173-ijms-10-01729]--[@b175-ijms-10-01729]\]. This could be also due to increased expression of uncoupling proteins (UCP) - mitochondrial carriers that dissipate the electrochemical gradient across the mitochondrial inner membrane \[[@b176-ijms-10-01729],[@b177-ijms-10-01729]\]. Mild uncoupling of mitochondria shift cellular nucleotide balance and, due to the monitoring function of adenylate kinase, AMP levels would go up triggering metabolic signaling cascades \[[@b176-ijms-10-01729],[@b177-ijms-10-01729]\]. Interestingly, AMP by itself through interaction with ANT can produce uncoupling that could facilitate respiration and reduce ROS production \[[@b178-ijms-10-01729]\], which could be beneficial during ischemia reperfusion. AMP signaling plays a significant role in cellular senescence. It's been shown by proteome analysis that AK1 protein is markedly increased in senescent skeletal muscle fibers \[[@b179-ijms-10-01729]\] and that lifespan of worms can be extended by the addition of copies of the AMPK gene and by chronic activation of AMPK as is seen on calorie-restricted diets \[[@b180-ijms-10-01729]\]. Indeed, AMP/ATP ratios are several folds higher in senescent fibroblasts compared with young fibroblasts and this is accompanied by a marked elevation in AMPK activity \[[@b181-ijms-10-01729],[@b182-ijms-10-01729]\]. This could be viewed as a compensatory measure to cope with declining capacity of energy metabolism during aging. AMP and AMPK signaling is critical in cell differentiation, maintaining cell polarity and completing normal cell division as well as in induction of meiotic maturation in mammalian oocytes \[[@b183-ijms-10-01729]--[@b185-ijms-10-01729]\]. AMP directly or through AMPK plays a physiological role in modulating activity of cystic fibrosis transmembrane conductance regulator (CFTR) in polarized epithelia cells \[[@b186-ijms-10-01729],[@b187-ijms-10-01729]\]. CFTP nucleotide binding folds possess an intrinsic adenylate kinase activity which could facilitate metabolic signal reception \[[@b61-ijms-10-01729],[@b188-ijms-10-01729]\]. Thus, AMP signaling plays a critical role in altered hormonal and energetic states including cell differentiation, maintenance of polarity and senescence. AMP is important mediator of insulin and metabolic protein kinase Akt signaling. It has been proposed that protein kinase Akt mediates inhibitory effects of insulin on AMPK \[[@b189-ijms-10-01729]\]. Since Akt does not directly phosphorylate AMPK, changes in Akt activity induced by insulin can regulate AMPK through changes in cellular AMP/ATP ratio. Indeed, it was demonstrated that Akt activation reduces cellular AMP/ATP ratio causing decline in AMPK activity \[[@b190-ijms-10-01729]\]. Insulin and Akt-mediated inhibition of AMPK can be overcome by metformin, which is known to act on site I of mitochondrial respiratory chain causing increase in AMP levels \[[@b189-ijms-10-01729],[@b191-ijms-10-01729]\]. In this regard, free fatty acids, which activation generates AMP, prevents AMPK inhibition by insulin \[[@b192-ijms-10-01729]\]. Thus, insulin-Akt signaling axis can expand the range of metabolic effects through tuning up AMP signals and the activity of AMPK. Most importantly, recent studies indicate that pharmacological actions of popular antidiabetic drugs metformin and thiazolidinediones and cholesterol lowering statins are related to their ability to alter cellular AMP levels and consequently AMPK activity \[[@b151-ijms-10-01729],[@b193-ijms-10-01729]--[@b195-ijms-10-01729]\]. Time course studies revealed that troglitazone-induced increases in phosphorylated forms of AMPK and ACC are paralleled by an increase in the AMP-to-ATP ratio \[[@b193-ijms-10-01729]\]. A similar increase in AMP is seen following incubation of cells with rosiglitazone \[[@b196-ijms-10-01729]\]. Moreover, livers of rats treated with resveratrol, a constituent of red grapes and red wine, show a strong tendency for AMPK activation, as well as increase phosphorylation of two downstream indicators of its activity \[[@b197-ijms-10-01729]\]. Besides inhibiting HMG-CoA reductase, statins preserve CD39/ATPDase activity in thrombin-treated endothelial cells \[[@b198-ijms-10-01729]\]. Preservation of adenine nucleotide metabolism may directly contribute to the observed anti-thrombotic and anti-inflammatory actions of statins. In this regard, metformin, a biguanidine compound from French lilac and more recently extracts from bitter melon, a traditional Chinese medicine, activate AMPK and exerts its glucose lowering effect through mild interference with the efficiency of energy metabolism resulting in changes in intracellular nucleotide dynamics and AMP levels \[[@b151-ijms-10-01729],[@b194-ijms-10-01729],[@b199-ijms-10-01729]\]. Through activating AMP signaling metformin also improves cardiac function after ischemia in rats \[[@b200-ijms-10-01729], [@b201-ijms-10-01729]\]. Interestingly that metformin increases glucose utilization and lactate production in cells with a dominant-negative mutant form of AMPK (DN-AMPK) \[[@b202-ijms-10-01729]\], suggesting existence of AMPKindependent pathways of metabolic signaling including direct effects of AMP on other metabolic sensors and enzymes of energetic pathways. Recent interest in clinical use of adenosine as "adenosine flush" and in reperfusion therapy is also associated with AMP signaling, activation of AMPK and replenishment of cellular ATP levels \[[@b203-ijms-10-01729]--[@b205-ijms-10-01729]\]. Adenosine, besides signaling through adenosine receptors, can be taken up by cells and phosphorylated to AMP initiating metabolic signaling cascades \[[@b104-ijms-10-01729],[@b206-ijms-10-01729]\]. Subsequent conversion of AMP to ADP and ATP by reactions involving adenylate kinase and ATP synthesis in mitochondrial oxidative phosphorylation and glycolysis would replenish cellular ATP and total adenine nucleotide pool which is diminished during ischemic insult \[[@b104-ijms-10-01729],[@b206-ijms-10-01729]\]. Thus, adenosine and AMP have pleiotropic metabolic signaling and energetic effects which could be further explored in reperfusion therapy. Last but not least, AMP through interaction with taste receptors has the bitterness-suppressing quality that allows taste buds to interpret food as seeming "sweeter" \[[@b207-ijms-10-01729]\]. This makes lower-calorie food products more palatable. Recently AMP has been approved by the FDA as a 'Bitter Blocker' additive to foodstuffs (Linguagen Corp.). AMP is found in a wide range of natural foods --- including breast milk. Calcium compounds in breast milk are usually bitter and thus breast milk may be natural system using bitter-blockers. AMP also inhibits behavioral and electrophysiological responses of mice to bitter tastants \[[@b207-ijms-10-01729]\]. A number of AMP containing medications are used for nutritional supplementation and for treating dietary shortage or imbalance and disease conditions \[[@b208-ijms-10-01729]\]. Nucleotides such as AMP affect a number of immune functions, including the reversal of malnutrition and starvation-induced immunosuppression due to adenine nucleotide shortage, the enhancement of Tcell maturation and function and natural killer cell activity \[[@b208-ijms-10-01729]\]. However AMP by itself has immunosuppressive properties. In fact, mosquito and fly saliva contains AMP and adenosine as vasodilatative agents which also have immunosuppressant activity facilitating pathogen or parasite transmission \[[@b209-ijms-10-01729]\]. To this end, secreted and cell associated adenylate kinase has been identified as a virulence factor in a number of pathogens affecting nucleotide signaling and host immune defense \[[@b210-ijms-10-01729]\]. Due to immunomodulatory function, a promising therapeutic potential for the AMP analog AICAR/(ZMP) exist in the treatment of multiple sclerosis and other Th1 cell-mediated inflammatory diseases such as psoriasis and arthritis \[[@b211-ijms-10-01729]\]. Thus, AMP is emerging as pivotal metabolic signal conveying information about food consumption, hormonal and energy metabolism status, a regulator of brain activity associated with wakefulness and appetite control as well as a mediator of drug action and therapeutic agent. 6.. Adenylate Kinase and AMP Signaling Networks in Body Energy Sensing ====================================================================== Sensing body energy level and corresponding mental and physical strength is important for humans and animals and this property had key survival and evolutionary advantages \[[@b5-ijms-10-01729],[@b30-ijms-10-01729],[@b72-ijms-10-01729],[@b212-ijms-10-01729]--[@b216-ijms-10-01729]\]. Here we further advance the hypothesis that body energy sensing is mediated in part by adenylate kinase, which conveys information about the adenine nucleotide pool status and, thus the overall energy balance \[[@b5-ijms-10-01729],[@b30-ijms-10-01729]\]. The general concept has been proposed previously by H. Teagtmeyer \[[@b217-ijms-10-01729]\] that systemic metabolic communication and energy transfer arises from the interaction of a series of moiety conserved cycles operating through tissues and circulation. Phosphotransfer reactions have emerged as principle signal generators and coupling relays between cellular metabolism and metabolic sensors \[[@b5-ijms-10-01729],[@b29-ijms-10-01729],[@b30-ijms-10-01729],[@b44-ijms-10-01729],[@b218-ijms-10-01729]\]. In particular, adenylate kinase as generator and modulator of metabolic signals is a critical player integrating complex AMPK and KATP channel signaling cascades in regulation of hormone secretion, blood flow, stress response, muscle and brain functional activity \[[@b1-ijms-10-01729],[@b4-ijms-10-01729],[@b5-ijms-10-01729],[@b30-ijms-10-01729],[@b33-ijms-10-01729],[@b34-ijms-10-01729],[@b37-ijms-10-01729],[@b47-ijms-10-01729]\]. A case in point is myocardial-vascular metabolic signal communication governed by phosphotransfer redistribution, metabolic cycles and relays culminating in a metabolic sensor and functional response ([Figure 6](#f6-ijms-10-01729){ref-type="fig"}) \[[@b4-ijms-10-01729]\]. As brain function specifically depends on glucose metabolism, new spatial and network representation of glycolytic pathway \[[@b5-ijms-10-01729]\] allow for new perspectives and understanding of energetic signal communication and glucose sensing in neurons \[[@b30-ijms-10-01729],[@b212-ijms-10-01729]\]. Body energy sensing depends on information relayed and distributed to a central network of metabolic sensing neurons through hard-wired neural connections and by metabolic and hormonal signals from the periphery coming through the blood and interstitial fluids \[[@b212-ijms-10-01729],[@b214-ijms-10-01729]\]. The brain has a specialized set of neurons that integrate many of these signals and produce regulatory response. These, first described as "glucose sensing" neurons, are really broad-range cellular metabolic sensors that have transporters, metabolite-sensing kinases, ion channels, and receptors that allow them to sense and interpret signals coming from the periphery \[[@b214-ijms-10-01729]\]. Metabolic sensing neurons are integrated into a network that links them to afferent and efferent pathways involved in the control of energy homeostasis \[[@b212-ijms-10-01729]\]. Recent studies indicate that beside satiety hormonal signals, such as leptin and insulin, a myriad of metabolic inputs are generated and sensed by the brain including glucose, fructose, fatty acids and their metabolites, amino acids, Krebs cycle intermediates and nucleotides through specialized receptors and signaling cascades \[[@b212-ijms-10-01729]--[@b216-ijms-10-01729]\]. In many cases, reception or metabolism of these signals by sensing neurons results in altered intracellular ATP/AMP ratio and behavior of metabolic sensors such as AMPK, K-ATP channels and other regulators of firing activity \[[@b33-ijms-10-01729],[@b72-ijms-10-01729],[@b213-ijms-10-01729],[@b219-ijms-10-01729],[@b220-ijms-10-01729]\]. This integrated information is then used not only to guide choices the animal makes about the amount of fuels to take in from the environment but also how stored fuels should be distributed and metabolized by various peripheral tissues. Molecular defects or a raise in threshold for sensing catabolic signals from the periphery by specialized metabolic sensing neurons is one of the causes of obesity \[[@b212-ijms-10-01729]--[@b214-ijms-10-01729]\]. Metabolism sensing neurons are regulated by glucose through mechanisms requiring either the KATP channel or the Na^+^/glucose cotransporter SGLT3, which is a glucose-sensing rather than glucosetransporting molecule \[[@b212-ijms-10-01729]--[@b216-ijms-10-01729]\]. In glucose-excited neurons, the decrease in ATP and ATP-to-ADP ratio leads to activation of K-ATP channels and plasma membrane hyperpolarization, and thus reduction in neuronal firing activity. In glucose-inhibited neurons, the reduced ATP-to-ADP ratio induces closure of chloride channels and/or reduction in the activity of the Na-K pump, depolarization of the plasma membrane, activation of voltage-sensitive Ca^2+^ channels, and synaptic neurotransmitter secretion. Changes in energy expenditure are achieved by regulating hormonal status, sympathetically mediated thermogenesis and cellular energy sensors such as AMPK, which switch off ATP-consuming and activate ATP-regenerating pathways in response to cellular fuel shortage \[[@b212-ijms-10-01729]--[@b214-ijms-10-01729]\]. Recent studies show that activity of AMPK is increased in the brain in response to low levels of cellular fuels and negative energy balance and, contrary to peripheral tissues, decreased by leptin \[[@b72-ijms-10-01729],[@b213-ijms-10-01729],[@b219-ijms-10-01729]\]. Furthermore, reduced activity of AMPK in the hypothalamus reduces food intake and body weight \[[@b213-ijms-10-01729],[@b219-ijms-10-01729]\]. Circulating leptin levels give the brain input regarding energy storage so it can regulate appetite and metabolism. Although leptin is a circulating signal that reduces appetite, in general, obese people have an unusually high circulating concentration of leptin and develop leptin resistance \[[@b212-ijms-10-01729]--[@b214-ijms-10-01729]\]. Among other factors, consumption of high amounts of fructose causes leptin resistance \[[@b221-ijms-10-01729]\]. This could be due to excess of AMP signaling in the periphery induced by both leptin and fructose which is conveyed to the brain as false "low energy" signal forcing it to increase food consumption. AMP and other peripheral metabolic signals apparently can overcome inhibitory leptin signaling circuits in the hypothalamus \[[@b68-ijms-10-01729],[@b153-ijms-10-01729],[@b175-ijms-10-01729]\]. In this regard, a significant increase in adenylate kinase isoform AK1 and other phosphotransfer enzymes in obese/overweight and morbidly obese women further indicate an imbalance in metabolic signaling in this metabolic syndrome \[[@b116-ijms-10-01729]\]. Labeling studies of adenine nucleotide -phosphoryls indicate that adenylate kinase is active in the brain and that its phosphotransfer rate is increased by drugs improving cerebral circulation and memory dysfunction \[[@b222-ijms-10-01729]\]. Similarly, photic stimulation increases adenylate kinase-mediated ATP β-phosphoryl turnover in photoreceptors suggesting a role in energetics of these specialized cells \[[@b223-ijms-10-01729]\]. Other studies indicate that adenylate kinase isoforms in the brain may contribute to neuronal maturation and regeneration \[[@b23-ijms-10-01729],[@b224-ijms-10-01729]\]. Activation of melanocortin system, which is involved in regulation of appetite, metabolism and body weight, increases expression of adenylate kinase AK1 in the hypothalamus \[[@b225-ijms-10-01729]\]. AMPK, a master metabolic sensor present in hypothalamus, responds to adenylate kinase integrated AMP levels, and plays a critical role in hormonal and nutrient-derived anorexigenic and orexigenic signaling \[[@b62-ijms-10-01729],[@b72-ijms-10-01729],[@b226-ijms-10-01729]\]. Adenylate kinase AK2 is among 14 genes mapped in quantitative trait loci for body weight and abdominal fat weight \[[@b227-ijms-10-01729]\]. Recent proteome studies revealed that adenylate kinase AK2 may be an important regulator involved in the anti-lipid and antioxidant effects of tomato paste \[[@b228-ijms-10-01729]\]. The down-regulation of AK1 expression by hyperglycemia in pancreas may contribute to the defective coupling of glucose metabolism to K-ATP channel activity in type 2 diabetes \[[@b48-ijms-10-01729]\]. Information processing in the brain and energy sensing takes place not only intracellularly but also on extracellular surfaces and between different type of cells through intercellular connections \[[@b30-ijms-10-01729],[@b229-ijms-10-01729],[@b230-ijms-10-01729]\]. In fact, brain ecto-adenylate kinase is an integral part of synaptosomal ATPmetabolizing enzyme cascades regulating ATP, AMP and adenosine signaling \[[@b231-ijms-10-01729]\]. Similarly, adenylate kinase by regulating nucleotide exchange and signaling at peripheral nerve endings can convey information regarding the energy state of particular tissues, thus contributing to body energy sensing. In other cell types ecto-adenylate kinase provides a mechanism for propagation of nucleotide based signals along the cellular surface, thus coordinating multiple receptor-mediated signaling events \[[@b64-ijms-10-01729],[@b65-ijms-10-01729]\]. Extracellular AMP induces bronchoconstriction in suspected asthmatic patients and is used in disease diagnostics as a bronchial provocation test \[[@b232-ijms-10-01729]\]. Both ATP and adenosine signaling which could be modulated by adenylate kinase are critical in synaptic transmission and for normal brain function \[[@b233-ijms-10-01729]\]. Thus, the systemic adenylate kinase → AMP → AMPK signaling network represents a new modality in body energy balance. In different tissues, adenylate kinase activity depends on the nutritional and hormonal state \[[@b234-ijms-10-01729],[@b235-ijms-10-01729]\]. Adenylate kinase phosphotransfer flux is markedly suppressed by high glucose in insulin secreting cells, reducing adenylate kinase-mediated AMP signaling to the K-ATP channel and AMPK, two regulators of hormone secretion \[[@b45-ijms-10-01729],[@b122-ijms-10-01729]\]. In humans, deficiency of the AK1 isoform is associated with mental retardation, psychomotor impairment and congenital anemia \[[@b236-ijms-10-01729]\]. In this regard, a strong correlation has been observed between fasting and higher expression of the adenylate kinase AK3 isoform, UCP3 and increased activity of AMPK and fatty acid oxidation \[[@b237-ijms-10-01729]\], suggesting an interrelated signaling cascade. Although the significance of energetic and metabolic signaling is growing, little is known regarding the regulation of adenylate kinase phosphotransfer under different metabolic, hormonal and functional states, and how such regulation affects the ability of the cell to generate and respond to energetic stress-related signals. A new emerging modality in extracellular and intracellular nucleotide signaling and information processing is the cAMP → AMP → adenosine/AMPK pathway sequentially connecting cAMP- and AMP-response elements \[[@b238-ijms-10-01729]\]. In this pathway, cAMP signaling is followed by conversion of cAMP by phosphodiesterases to AMP that activates the AMP-signaling cascade \[[@b183-ijms-10-01729]\]. The role of adenylate kinase in this system is envisioned to propagate AMP metabolic signals along the membrane surface or within the cytosolic space and nuclear compartment where AMPK resides \[[@b1-ijms-10-01729],[@b5-ijms-10-01729],[@b65-ijms-10-01729],[@b239-ijms-10-01729]\]. Cosequently, production of adenosine from AMP by 5′-nucleotidase could stimulate adenosinergic signaling pathways \[[@b240-ijms-10-01729]\]. Thus, this kind of integration of cyclic nucleotide → nucleotide → nucleoside signaling provides means of coordinating diverse signaling events and facilitating information transfer from one subsystem to another. Understanding principles governing integration and synchronization of metabolic sensors with cellular metabolism is important for regulation of cellular energetic and ionic homeostasis as well as hormonal balance and food intake \[[@b37-ijms-10-01729],[@b61-ijms-10-01729],[@b241-ijms-10-01729]--[@b243-ijms-10-01729]\]. Growing evidence and increasing number of discovered metabolic signaling cascades indicate that these systems are essential in vital cellular processes integrating gene expression, metabolism and response to stress, moreover their defects are associated with diseases under a wide umbrella of "metabolic syndrome" \[[@b33-ijms-10-01729],[@b62-ijms-10-01729],[@b243-ijms-10-01729],[@b244-ijms-10-01729]\]. In this regard, recent studies indicate that metabolites linked to glucose such as succinate and alphaketoglutarate can signal through specific G-protein-coupled receptors which are also present in neurons \[[@b245-ijms-10-01729],[@b246-ijms-10-01729]\]. Glucose usually decreases adenylate kinase phosphotransfer flux and intracellular AMP levels and consequently adenosine signaling, but it can increase Krebs cycle substrate levels through anaplerosis \[[@b1-ijms-10-01729],[@b246-ijms-10-01729]\]. Succinate and alpha-ketoglutarate also have signaling function in cell nucleus regulating DNA methylation, which has been implicated in obesity \[[@b247-ijms-10-01729]\]. Taken together, emerging data indicate that coupling of "energetic" phosphotransfer enzymes with phosphoryltransfering protein kinase cascades and metabolite sensitive ion channels, transporters and receptors, comprise a unified intracellular and transcellular energetic and metabolic signal transduction matrix capable of processing, integrating and delivering cellular information regarding energy state (see [Figure 6](#f6-ijms-10-01729){ref-type="fig"}). Within this network, adenylate kinase and AMP signaling throughout the intracellular compartments, extracellular space and body fluids comprise a major metabolic monitoring and body energy sensing node, capable of transducing and distributing signals to metabolic sensors to adjust energy metabolism, fuel selection, food intake and functional response. 7.. Adenylate Kinase Never Rests: From Altered Energetic Signaling to Immunodeficiency, Cell Motility Defects, Reticular Dysgenesis and Sensorineural Deafness ============================================================================================================================================================== A thoughtful notion that "adenylate kinase never rests" was expressed by P.B. Detwiler more than a decade ago when commenting on the paper entitled "Adenine nucleoside diphosphates block adaptation of mechano-electrical transduction in hair cells" \[[@b248-ijms-10-01729]\]. In this paper P.G. Gillespie and A.J. Hudspeth demonstrated that mechano-electrical signal transduction and adaptation by hair cells depends on adenine nucleotides and adenylate kinase reaction \[[@b248-ijms-10-01729]\]. Indeed, the past decade further revealed that the dynamic behavior of the adenylate kinase reaction governs many intracellular and extracellular nucleotide signaling processes and that adenylate kinase mutations cause severe human disease phenotypes \[[@b1-ijms-10-01729],[@b2-ijms-10-01729],[@b8-ijms-10-01729]--[@b11-ijms-10-01729],[@b22-ijms-10-01729],[@b30-ijms-10-01729],[@b102-ijms-10-01729]\]. Adenylate kinase in conjunction with other phosphotransfer rections is involved in metabolic signaling to membrane ion channels regulating cell ionic balance and electrical activity, and in energy supply to distant ATPases powering spermatozoa and other cell motility related processes \[[@b20-ijms-10-01729],[@b29-ijms-10-01729],[@b31-ijms-10-01729],[@b33-ijms-10-01729],[@b44-ijms-10-01729],[@b47-ijms-10-01729]\]. The large molecular weight isoform AK7 is unusual in the adenylate kinase family; it contains a Dpy-30 motif involved in protein dimerization and is associated with cell motility and other processes \[[@b2-ijms-10-01729],[@b5-ijms-10-01729],[@b96-ijms-10-01729]\]. Mutations in the evolutionarily conserved Ak7 gene results in animals presenting with pathological signs characteristic of primary ciliary dyskinesia (PCD), including ultrastructural ciliary defects and decreased ciliary beat frequency in respiratory epithelium \[[@b7-ijms-10-01729]\]. Ak7 appears to be a marker for cilia with (9 + 2) microtubular organization critical in motility, morphogenesis, cell division and immune response \[[@b7-ijms-10-01729],[@b97-ijms-10-01729]\]. In humans PCD is a genetically and phenotypically heterogeneous disorder, characterized by progressive development of bronchiectasis, inflammation, and features characteristic of chronic obstructive pulmonary disease \[[@b7-ijms-10-01729]\]. Thus, these results suggest that mutations of the human Ak7 gene may underlie a subset of genetically uncharacterized PCD cases. More recently, the elegant work from B. Wieringa's laboratory examining the adenylate kinase spatial positioning within a cell by utilizing different artificial location tags, demonstrate that cytoskeleton-based cell motility can be modulated by spatial repositioning of adenylate kinase enzymatic activity to provide local ATP supply and ADP scavenging capacity \[[@b8-ijms-10-01729]\]. These results are corroborated by the use of another heterodimer-inducing approach for transient translocation of AK1 to the specific cellular sites under conditions of constant global AK1 activity in the cell \[[@b8-ijms-10-01729]\]. Thus, adenylate kinase functions as a coupling factor between local ATP supply and regulation of actomyosin and other molecular motor behavior, which is central to cell shape changes and cell motility. Similarly, creatine kinase--mediated ATP supply fuels actin-based events in phagocytosis and is required for thrombin receptor signaling to the cytoskeleton \[[@b249-ijms-10-01729],[@b250-ijms-10-01729]\]. In this regard, the dynamics of actin and myosin in brain presynaptic and postsynaptic regions play a critical role in brain activity and memory formation, and consume the major fraction of the total energy in neurons \[[@b251-ijms-10-01729],[@b252-ijms-10-01729]\]. It remains to be determined whether adenylate kinase provides energy support for motor proteins involved in neuronal trafficking and memory consolidation. Interestingly in humans, genetic adenylate kinase deficiency or losses of adenylate kinase from the brain after surgery are associated with compromise intellectual function \[[@b253-ijms-10-01729],[@b254-ijms-10-01729]\]. Conversion of mechanical stimuli to electrical signals in stereocilia of inner ear hair cells is associated with Ca^2+^ dynamics and movement of myosin motors, similar to many mechanoelectrical and ciliary motility systems \[[@b7-ijms-10-01729],[@b248-ijms-10-01729]\]. The energy supply and nucleotide-based signaling coordinating behavior of such systems is provided by phosphotransfer enzymes including adenylate kinase \[[@b1-ijms-10-01729],[@b8-ijms-10-01729],[@b29-ijms-10-01729],[@b30-ijms-10-01729]\]. It was demonstrated that the creatine kinase circuit is essential for high-sensitivity hearing as demonstrated by hearing loss in creatine kinase knockout mice \[[@b255-ijms-10-01729]\]. Recently biallelic mutations in mitochondrial adenylate kinase AK2 gene have been identified in individuals affected with reticular dysgenesis \[[@b9-ijms-10-01729]\]. Human reticular dysgenesis is the most severe form of inborn severe combined immunodeficiencies (SCID) associated with sensorineural deafness. This disease is characterized by the absence of granulocytes and almost complete deficiency of lymphocytes in peripheral blood. Mutations in AK2 gene result in absent or strong decrease in AK2 protein expression \[[@b9-ijms-10-01729]\]. Restoration of AK2 expression in the bone marrow cells of individuals with reticular dysgenesis overcomes neutrophil differentiation arrest, underlining its specific requirement in the development of a restricted set of hematopoietic lineages. Moreover, AK2 is specifically expressed in the stria vascularis region of the inner ear, which may provide an explanation of the sensorineural deafness in these individuals \[[@b9-ijms-10-01729]\]. Interestingly, immunohistochemistry indicate that AK2 is present within the lumen of the stria vascularis capillaries suggesting that it could be functioning as an ecto-enzyme, however more detailed studies at the cellular level are required and different AK2 and other AK isoform antibodies should be tested. Since almost all cells contain mitochondria and intermembrane AK2, the negative result of intracellular AK2 immunohistochemistry could be related to inaccessibility of intermembrane proteins to antibodies. It is known that ecto-adenylate kinase plays an important role in extracellular nucleotide signaling; however it is unusual to detect a mitochondrial isoform outside the cell \[[@b64-ijms-10-01729],[@b65-ijms-10-01729]\]. An intriguing possibility exist that beside nucleotide signaling, mucosa embedded AK2 has specific mechanometabolic signal transduction functions and behavior similar to that described in smart hydrogels containing adenylate kinase \[[@b256-ijms-10-01729]\]. A recent proteome study indicates adenylate kinase is present in the extracellular mucus \[[@b257-ijms-10-01729]\]. However, whether the adenylate kinase system due to mutation of AK2 is altered in primary mechanoelectrical signal transducing hair cells which have abundant mitochondria should be determined. Our data indicate that both AK1 and AK2 associate with mitotic spindle, which have microtubular organization (9 + 2) similar to cilia, apparently to power cell division cycle and chromosome disjunction. Previous studies have shown that disruption of analogous adenylate kinase Aky2 gene in yeast coding mitochondrial intermembrane and partially cytosolic AKY2 protein halts ATP export from mitochondria \[[@b99-ijms-10-01729]\]. Thus, AK2 isoform, usually confined within mitochondrial intermembrane space, may have important extramitochondrial functions. That the gene encoding the mitochondrial energy metabolism related enzyme adenylate kinase 2 (AK2) is mutated in individuals with reticular dysgenesis is supported by simultaneously published independent evidence \[[@b10-ijms-10-01729]\]. Knockdown of zebrafish ak2 gene leads to aberrant leukocyte development, stressing the evolutionarily conserved role of AK2 in leukocyte differentiation \[[@b10-ijms-10-01729]\]. Mononuclear cells obtained from bone marrow of healthy donors lacked AK1, whereas AK2 was readily detectable. These results indicate that leukocytes may be susceptible to defects caused by the lack of AK2, as they do not express AK1 in sufficient amounts to compensate for AK2 functional deficits. Previous studies have linked AK1 mutations to severe nonspherocytic hemolytic anemia and associated with mental retardation and psychomotor impairment \[[@b3-ijms-10-01729],[@b236-ijms-10-01729]\]. In this regard, the deficiency of another metabolic enzyme adenosine deaminase (ADA) accounts for approximately 17% of all SCIDs and 50% of all autosomal recessive SCIDs \[[@b258-ijms-10-01729]\]. The metabolic basis of this immunodeficiency is likely related to accumulation of the ADA substrates adenosine and 2′-deoxyadenosine that kill T and B cells through mechanisms involving accumulation of dATP and induction of apoptosis \[[@b258-ijms-10-01729]\]. Whether nucleotide metabolism is altered in AK2 mutant cells remains to be determined. Taken together, these observations suggest that reticular dysgenesis is the first example of a human immunodeficiency syndrome that is causally linked to the defective phosphotransfer enzyme involved in nucleotide signaling and mitochondrial energy metabolism. In this regard, absence or reduction of AK2 protein would interfere with mitochondrial bioenergetics and mitochondria-nucleus energetic signal communication that could compromise implementation of leukocyte developmental program \[[@b9-ijms-10-01729],[@b30-ijms-10-01729],[@b34-ijms-10-01729]\]. Evolvement of mitochondrial network and establishment of metabolic circuits are part of developmental programming and execution of cell differentiation sequences \[[@b259-ijms-10-01729],[@b260-ijms-10-01729]\]. A recent study indicates that energy demand signaling gradients arising in the cell would allow propagation of information on local energy consumption over distances, through nucleotide-based signaling conveying positional information to mitochondria \[[@b261-ijms-10-01729]\]. In such way, responding to energy demand gradients, mitochondria can pattern the cytoplasm over length scales that are suited to provide an energy supply continuum and convey morphogenetic information in large cells and tissues \[[@b259-ijms-10-01729],[@b261-ijms-10-01729]\]. Thus, AK2 deficiency can disrupt the flow of developmental information governing cell differentiation. Adenylate kinase supports energetics and motility of flagella containing parasites and secreted adenylate kinase is a major virulence factor in a number of pathogenic bacteria \[[@b5-ijms-10-01729],[@b20-ijms-10-01729],[@b56-ijms-10-01729],[@b57-ijms-10-01729],[@b210-ijms-10-01729]\]. Recently, a novel myristoylated AK2 isoform has been discovered in P. falciparum causing severe tropical malaria \[[@b11-ijms-10-01729]\]. This modification significantly enhances the stability of the kinase and apparently could be used for targeting the enzyme to membranes or other specific cellular sites, similar to AK1, another myristoylated adenylate kinase isoform \[[@b11-ijms-10-01729],[@b51-ijms-10-01729]\]. The association of myristoylated AK2 with the disease causing clone could be used as a therapeutic target to fight malaria. A large specialized network of six adenylate kinase isoforms exists in a unicellular flagellated parasite Trypanosoma cruzi, the causative agent of Chagas' disease \[[@b59-ijms-10-01729]\]. This parasite apparently has developed a sophisticated phosphotransfer network where adenylate kinase acts in concert with arginine kinase and nucleoside diphosphate kinase to support the invasive phenotype \[[@b262-ijms-10-01729]\]. Importantly, that mutation in the adenylate kinase gene renders pathogens avirulent \[[@b210-ijms-10-01729]\], suggesting new ways to "silence" otherwise deadly bacteria. Also, a nonstructural protein 4B (NS4B) from hepatitis C virus, which is absolutely required for viral propagation, was found to possess adenylate kinase-like activity \[[@b263-ijms-10-01729]\]. Adenylate kinase 2 is highly upregulated by INF-alpha and IL-15 stimulation in natural killer (NK) cells suggesting role in innate immune defense \[[@b264-ijms-10-01729]\]. In this regard, due to unique catalytic properties and stability adenylate kinase is used as an enzyme amplification system in ATP biosensors for detecting bacterial contaminations in food industry, defense and health care that improves sensitivity levels up to several thousands fold (Celsis, AKuScreen). A recent study demonstrates that mitochondrial AK2 is directly involved in induction of apoptosis through the formation of an AK2-FADD-caspase-10 complex and that downregulation of AK2 attenuates etoposide- or staurosporine-induced apoptosis in human cells \[[@b6-ijms-10-01729]\]. Significantly, that downregulation of cytosolic AK1 transcription with siRNA increases apoptosis in pancreatic cancer cells \[[@b265-ijms-10-01729]\]. Thus, adenylate kinase plays a significant role in making decision between life and death in cellular existence and could be a target in treatment of infectious disease and cancer. In summary, we highlight here new exciting developments regarding multi-faceted adenylate kinase biology, revealing the significance of mutations and modifications of this never resting phosphotransfer enzyme in energy support of cell motility, disease pathogenesis and regulation of cell differentiation and apoptosis. 8.. Summary =========== Metabolic signals regulate and integrate many vital functions throughout the human body, including energy homeostasis, blood pressure, heart performance, food intake, hormonal status and brain performance. Growing evidence indicate the significance of metabolic monitors which directly sense cellular energy state and respond to imbalances by generating and delivering signaling molecules to metabolic sensors to produce a regulatory response. Adenylate kinase-mediated metabolic monitoring and downstream AMP signaling (AK → AMP → AMP-sensors) plays a critical role in the regulation of diverse cellular processes and serves as a primary stress-response pathway. Due to signaling to a number of AMP/nucleoside-sensitive cellular and extracellular components, adenylate kinase senses cellular energetic imbalances caused by physical activity, inadequate oxygenation or nutrient supply, generates and transmits feedback signals to adjust cellular energetics, substrate transport and vascular blood flow to facilitate oxygen and nutrient delivery. Adenylate kinase phosphotransfer dynamics regulates many diverse intracellular and extracellular nucleotide signaling processes, including excitation-contraction coupling, hormonal secretion, cell and ciliary motility, nuclear transport, energetics of cell cycle, DNA synthesis and break repair, and developmental programming. Moreover, adenylate kinase generated and modulated cellular, interstitial and blood AMP levels are emerging as potential metabolic signals that are associated with body energy sensing, sleep, hibernation, vascular flow and food intake. AMP is a mediator of antidiabetic drug action and has growing importance as a therapeutic agent. Within integrated phosphotransfer network, adenylate kinase is essential in integration and synchronization of metabolic sensors with the dynamics of cellular metabolism which is critical for regulation of genetic, energetic, electrical and signal transduction processes determining cell viability and functional activity. As such, adenylate kinase and AMP signaling components dispersed throughout the intracellular compartments, extracellular spaces and body fluids comprise a major metabolic monitoring and body energy sensing node transducing and distributing signals to metabolic sensors, thus conveying information about body energy and fuel usage status. Moreover, evidence is mounting regarding the direct relationship between defects in adenylate kinase and AMP metabolic signaling and human diseases, such as heart failure, hypertrophic cardiomyopathy, diabetes, obesity, hemolytic anemia, reticular dysgenesis, ciliary dyskinesia, cancer and neurodegeneration. Thus, adenylate kinase, previously considered as a regular housekeeping enzyme, is a critical player in metabolic monitoring and systemic integration of different signaling pathways to ensure cellular energy homeostasis and an adequate response to a broad range of functional, environmental and stress challenges. This work was supported by grants from the National Institutes of Health, Marriott Heart Disease Research Program and Marriott Foundation. A.T. holds the Mayo Clinic Marriott Family Professorship in Cardiovascular Research. The authors thank to Dr. C. Folmes for critical reading of the manuscript and valuable suggestions. ![Adenylate kinase shuttle facilitates transfer of ATP β- and γ-phosphoryls from generation to utilization sites.\ Adenylate kinase (AK), present in mitochondrial and myofibrillar compartments, enables the transfer and makes available the energy of two high-energy phosphoryls, the β- and the γ-phosphoryls of a single ATP molecule. In this case, AMP signals feedback to mitochondrial respiration amplified by the generation of two molecules of ADP at the mitochondrial intermembrane site. Within the intracellular environment of a cardiomyocyte, the transfer of ATP and AMP between ATP-production and ATP-consumption sites may involve multiple, sequential, phosphotransfer relays that result in a flux wave propagation along clusters of adenylate kinase molecules (lower panel). Handling of substrates by "bucket-brigade" or a ligand conduction mechanism facilitates metabolic flux without apparent changes in metabolite concentrations. AK1 and AK2 -- cytosolic and mitochondrial AK isoforms, respectively. i.m. and o.m. -- inner and outer membranes, respectively. Modified from \[[@b5-ijms-10-01729]\] with permission.](ijms-10-01729f1){#f1-ijms-10-01729} ![Adenylate kinase isoform network and intracellular localization.\ Adenylate kinase isoforms are coded by separate genes, KAD1 -- KAD7, localized to different chromosomes. Corresponding proteins AK1 -- AK7 define separate adenylate kinase isoforms with different molecular weights, kinetic properties and intracellular localization. The AK1 isoform mostly consists of the ADK domain which is characteristic for the whole protein family. The AK1β splice variant has an additional myristoylation domain that targets the protein to the plasma membrane. The proteins Rad50 and C9orf98 with ADK domains and activity have specific cellular functions. The AK2, AK3 and AK4 isoforms have a flexible lid domain which closes over the site of phosphoryl transfer upon ATP binding to prevent water accessibility. A short form of the lid domain exists also in AK1, AK5 and AK6. Within the network adenylate kinase proteins distribute high-energy phosphoryls (\~ P) and communicate AMP signals.](ijms-10-01729f2){#f2-ijms-10-01729} ![Adenylate kinase metabolic monitoring system.\ Adenylate kinase reads the cellular energy state, generates, tunes and communicates AMP signals to metabolic sensors. In such way adenylate kinase conveys information about the adenine nucleotide pool status and, thus, the overall energy balance. In response to AMP signals metabolic sensors reduce ATP-consuming and activate ATP-generating pathways to adjust energy metabolism, functional activity and increase fuel and oxygen supply.](ijms-10-01729f3){#f3-ijms-10-01729} ![AMPing up and down --- integration cellular AMP signals by adenylate kinase.\ Adenylate kinase integrates AMP metabolic signals produced or downregulated during exercise, stress response, food consumption and during changes in hormonal balance or mitochondrial coupling state. Adenylate kinase relays deliver AMP signals to metabolic sensors and by catalyzing nucleotide exchange in the intimate "sensing zone" of metabolic sensors facilitate decoding of cellular information.](ijms-10-01729f4){#f4-ijms-10-01729} ![Regulation of intracellular AMP levels.\ Cytosolic adenylate kinase (AK1) is the major AMP generator while mitochondrial AK2 isoform, due to low Km(AMP), is the major AMP sequestration and tune-up mechanism. AMP is also generated during free fatty and amino acid activation, during adenosine rephosphorylation by adenosine kinase (ADK), during IMP reamination and by cyclic nucleotide phosphodiseterase (PDE). Oxygen deprivation and intense muscle contraction increase AMP removal through adenosine and IMP pathways catalyzed by 5'-nucleotidase (5'-NT) and AMP-deaminase (AMPD). Defects in mitochondria metabolism would reduce AMP tuning capacity of AK2 and, in fact, can reverse reaction towards AMP generation. The metabolically active AMP pool, estimated about 10--20%, is in dynamic equilibrium with bound and/or compartmentalized AMP \[[@b1-ijms-10-01729],[@b5-ijms-10-01729]\].](ijms-10-01729f5){#f5-ijms-10-01729} ![Myocardial-vascular metabolic signaling as a paradigm of global energy sensing.\ Metabolic signal transduction cascades initiated by phosphotransfer redistribution between adenylate kinase (AK) and creatine kinase (CK) govern AMP/adenosine (Ado) cycle and the response of metabolic sensors (ATP-sensitive potassium channel, K-ATP and AMP-activated protein kinase, AMPK). Hypoxia or metabolic stress diminishes CK and increases AK flux inducing AMP generation and subsequent AMP/adenosine signaling events. Adenosine/AMP signals delivered to vascular tissue through intercellular and paracellular pathways induce signaling through A(2A) adenosine receptors, AMPK and K-ATP channels. AMPK activates eNOS inducing NO/cGMP signaling and could regulate K-ATP channels. Collectively, A(2A)AR, AMPK, eNOS and K-ATP signaling converge on contractile protein, Ca^2+^ and membrane potential regulation, critical determinants of vascular tone. Dipyridamole, an adenosine uptake inhibitor, disrupts Ado- AMP cycle and tuning of adenosine signals, thus potentiating vascular response. Modified from \[[@b4-ijms-10-01729]\] with permission.](ijms-10-01729f6){#f6-ijms-10-01729}
Mid
[ 0.640350877192982, 36.5, 20.5 ]
So we could imagine encountering being a handful of sympathizers among them. But we were surprised to find the lengths to which a man identifying himself as a representative for Greece's mainstream New Democracy party went to explain the appeal of a party many describe as neo-Nazi. Petros Galatoulas is also the general secretary of the Federation of the Hellenic Societies in Greater New York, which is based out of the cultural center. Behind the 57-year-old's desk are photos of himself with former Chicagoy Mayor Richard M. Daley (that's the younger one) and other dignitaries. Although his English is solid, he wanted me to make sure I was absolutely clear on what he was saying, so he phoned up friend and Federation member Francis Papadopoulos to translate for him. I asked him how a neo-Nazi party could possibly have any support in Greece, especially given that in less than 24 hours after my visit, the Federation would be celebrating "Oxi Day," which marks Greece's refusal to allow Axis powers to occupy their country. "I am against them — we don't support them," he said. "I don't like this [Nazi imitation]. It's five or six people, crazy people." However, he indicated Golden Dawn had sympathy throughout Greece. In many regions, the party has become a sort of defacto police force as actual law enforcement, who've been victims of austerity cuts. "People didn't know where else to turn," he said. Both Galatoulas and Papadopoulos also said that immigration was a serious problem, with foreign nationals exacerbating the country's labor problem by taking jobs and undercutting wages. "It's the same system in America: if they are illegal they need to be deported," Papadopolous said. It was clear Golden Dawn remains an extremely controversial subject — the tension in the room immediately increased as soon as I brought up the subject. Galatoulas never addressed the initial rumor about the fundraiser.
Mid
[ 0.5732484076433121, 33.75, 25.125 ]
There are several reasons for Cain’s rise — not least among them the sad state of GOP presidential field for 2012. But I’ll focus on just two: (1) Herman Cain understands how white conservatives think, and (2) knows just what they want to hear from someone like him. Cain has cleaved to, and returned again and again to a longstanding conservative belief when it comes to African Americans and other people of color who don’t vote Republican: Those colored folks just don’t know what’s good for ’em. It’s a simple answer, as I wrote in 2005. It occurred to me that I’d heard the kind of stuff before, most recently in the comments resulting from a brouhaha that recently broke out about the portrayal of certain black Republicans. It’s the same basic rhetoric I’ve heard in just about every discussion I’ve been involved in over why there aren’t more black republicans. My point has always been that Republicans — like other predominantly white organizations — spend more time asking why more black people aren’t joining them than they do asking themselves why they aren’t attracting more black supporters. In other words, they avoid the reality that the reason they don’t attract more Black supporters is because they don’t address — and aren’t seen as addressing — the needs and concerns of many in Black communities. The analysis never gets further than that because it would probably undermine their current base of power. So every discussion I’ve had ends up with the other side’s argument boiling down to this: the reason more blacks don’t support the Republican party is because they don’t know what’s good for them. That’s the nice way of putting it. The more blunt way of putting it would be much closer to the way the conservative blogger above put it. Because they are dumb. The Blacks who don’t vote Republican are dumb… (This phenomenon isn’t limited to race, by the way. The same can apply to any predominantly homogenous organization that seeks to diversify its ranks, fails to do so, and then wonders why. Nor are liberals or progressives immune. We should this in mind when we wonder why we don’t have more support among white working-class Americans, many of whom joined the ranks of the birthers and tea partiers.) It’s an easy out, because it doesn’t require Republicans to address their own agenda, let alone change it. It’s easier to ask “Why don’t more Blacks vote Republican?” and answer “Because they don’t know any better,” “Because they don’t know what’s good for them,” or “Because they’re brainwashed.” Case closed. It’s easy, because you don’t need to do anything else, except perhaps bemoan their failure to “wise up” and “join us.” There’s no work and no change required on your part. Self examination, on the other hand, is hard. It’s harder to ask “How are we failing to address the concerns of fill-in-the-group effectively, so that they will naturally want to join us?”, because the answer may challenge and require you to change some of your assumptions. You have to put yourself in the position of the “Other,” and then work harder to find ways to address their concerns in the context of your values. It’s even harder because failure is then your fault — not theirs. As Anson Asaka points out, if Republicans asked themselves the second question, they’d have to consider that maybe African Americans have some good reasons for not voting Republican. African Americans are not brainwashed. The majority of black people support the Democratic Party because it is their interest to do so, at this point in time. Democratic administrations enacted major civil rights legislation ending Jim Crow. Democrats supported and continue to support affirmative action. Democratic presidents have appointed judges and Attorney Generals who have defended civil rights. The opposite is true for Republican administrations. The Democrats were the first major political party to nominate an African American for President. The Democrats were the first party to appoint an African American as a Supreme Court justice. Most black elected officials are Democrats. Many African Americans hold key positions and wield substantial influence in the Democratic Party. That is not true with respect to the Republican Party. In response to the enactment of civil rights legislation, Dixiecrats left the Democratic Party and fled to the Republican Party. To win over Southern segregationists, the Republican Party adopted the Southern strategy and became hostile to civil rights, workers rights and welfare. Instead of being the Party of Lincoln, the Republican Party became the party of Strom Thurman and Jesse Helms. In effect, the Republican Party became the new White Citizens’ Council. It is no coincidence that Republicans are at the front line defending symbols of the racist Confederate past. So far, only one of Perry’s GOP rivals has commented on N-WordheadGate: Herman Cain. Asked yesterday about the story, Cain, the only black Republican in the race, lashed out at Perry. “Since Governor Perry has been going there for years to hunt, I think that it shows a lack of sensitivity for a long time of not taking that word off of that rock and renaming the place,” Cain said on This Week. On Fox News Sunday, Cain added that there “isn’t a more vile, negative word than the N-word and for him to leave it there as long as he did before, I hear, that they finally painted over it, is just plain insensitive to a lot of black people in this country.” Cain’s reaction is certainly understandable. Anyone could find the revelations offensive, and Cain is a black man who grew up in the segregated South. And yet, as Michael Tomasky points out today, it’s Cain, not Perry, who could be damaged the most by this story. To understand why, you have to consider that there are two things Republicans hate more than anything. One is being accused of racism, which has happened with increasing frequency since President Obama became president, and, if you ask Republicans, is never, ever justified. Two is unfair treatment by the allegedly biased mainstream media. So among Republicans, the widespread response to the Post story was not, “wow, Rick Perry messed up.” It was, “the liberal media is smearing another Republican as a racist!” It’s in this context that the backlash has occurred. Cain wasn’t expressing reasonable grievances — he was “piling on” and legitimizing a sleazy political attack. The Daily Caller’s Matt Lewis writes this morning, “Cain’s comments were — at best — premature — and at worst, highly irresponsible. It was a cheap shot, and, perhaps a signal that Cain is willing to play the race card against a fellow Republican when it benefits him.” Over at the conservative blog Red State, Eric Erickson says the story is “a slander Herman Cain is picking up and running with as a way to get into second place.” Cain held his tongue when the audience booed a gay soldier at a republican debate. But he was the only Republican candidate to criticize Rick Perry over (a) the name of his hunting camp and (b) his failure to change it. Big mistake. “Niggerhead” itself did little to harm Perry’s standing among GOP voters. (Immigration and Perry’s beyond-inept debate performance did that.) Calling Perry out over “Niggerhead” did a good deal of damage to Herman Cain. Bet he won’t do that again. The context of Cain’s remark and the backlash against it might also explain why Cain in particular has drawn little African American support, and why his candidacy would probably not boost the number of Blacks voting Republican. Flip the context, and what many African Americans see in Cain is the same thing they see when the look at the likes of Clarence Thomas — a Black man who has lived long enough, and is old enough that he ought to know better. Because they know better, and know that he really knows better, most respond to Cain with a familiar two-word dismissal: “Negro, please.” …Some blacks like Cain have gotten a small piece of the economic pie, and have markedly increased their political reach and standing. This makes it even easier to buy Cain’s line and to get mad at those that don’t and accuse them of screaming racism whenever anything goes wrong. However, Cain knows but would never dare publicly admit the tormenting facts that countless studies, surveys, reports, and investigations, lawsuits, and court challenges, and the mountains of EEOC complaints have irrefutably documented. Blacks are still two and three times more likely to be unemployed than whites, trapped in segregated neighborhoods, and have their kids will attend disgracefully failing, mostly segregated public schools. Young Black males and females are far more likely to be murdered, suffer HIV/AIDS affliction, to be racially profiled by police, imprisoned, placed on probation or parole, permanently barred in many states from voting because of felony convictions, much more likely to receive the death penalty especially if their victims are white, and more likely to be victims of racially motivated violence than whites. Research studies show that whites with a felony record are more likely to be hired in some places than college educated blacks. Cain would never purse his lips to acknowledge the stark fact that middle-class blacks, like himself, who reaped the biggest gains from the civil rights struggles, often find the new suburban neighborhoods they move to re-segregated and soon look like the old neighborhoods they fled. They are ignored by cab drivers, followed by clerks in stores, left fuming at restaurants because of poor or no service, find that more and more of their sons and daughters are cut out of scholarships and student support programs at universities because of the demolition of affirmative action, and denied bank loans for their businesses and homes. Cain could easily find himself being by passed by a fearful cab driver while on his way to an important business meeting who didn’t watch Fox News and know who Cain was. In fact just a week before Cain cavalierly blew off the corrosive and shackling bars of racism that still shackle millions of blacks as “no big deal” Cain huffed at the revelation of his GOP presidential rival Rick Perry’s “Niggerhead” rock. Cain quickly corrected his memory lapse and got back on script and shrugged it off as much ado about nothing. What Hermain Cain is doing is nothing new. It was a method of survival for generations of our ancestors, because knowing how some white people thought, telling them what they want to hear, and allowing them to believe what they wanted or needed to believe — about you, and about themselves — could make the difference between life and death. It could mean the difference between a job and survival, or no job (as recently illustrated on the big screen in The Help. At other times, papering over uncomfortable truths helped maintain the appearance of peace and order, and sustain relationships that at least looked happy on the surface. Millions of our ancestors learned these lessons and passed them down to their children. Those lessons came down through the generations, and are still learned today, because they are still necessary today. It is also, and always has been, a way to get ahead, to “get over”, by using what you know to gain an advantage. Cain has certainly done that, going an an little known candidate to one whose name appears regularly in the media. He’s done so based in part on his strengths — he’s an effective speaker, with a simple message message that the GOP base loves — and in part on what he understands about conservatives and why it makes him useful to Republicans. Of course, this isn’t the first time that Cain has attacked Obama for his blackness, or lack thereof. At the beginning of this year, he told a group of Republicans that “they”—the liberal media—are “scared” that a “real black man might run against Barack Obama.” Likewise, in an interview with New York Magazine this summer, Cain doubled-down on his remarks, telling the magazine that Obama is not a “strong black man” in terms that he identifies with. That Cain presents himself as more blackity-black than Barack Obama is just part of his persona. What’s striking about it all is his choice of audience. With the exception of his interview with New York Magazine, Cain saves these remarks for white, Republican audiences. I’d be shocked if this wasn’t deliberate. Conservatives hate accusations of racism and are more vocal about those than they are actual instances of discrimination against racial minorities. With his upbringing in the segregated South and an accent that shows it, Herman Cain stands as the perfect weapon against anyone who questions the racial egalitarianism of conservatives. To borrow a line I used yesterday, Cain offers “absolution from racial guilt and a unique chance to turn the tables on liberals who accuse the right of racism.” Herman Cain is a great speaker, but that’s the reason he received a standing ovation from the crowd at the Values Voter Summit, after denying any anger over Jim Crow. Indeed, this quote—from an attendee at the summit—says it all, “I don’t give him a chance, but it would be interesting. At least, no one would call him a racist.” Cain learned a valuable lesson when he dared criticize Rick Perry’s “insensitivity” in failing for decades to change the name of his hunting camp to something less offensive than “Niggerhead.” It’s an old lesson, and simple one: “Remember your place, boy.” It may be the key to his future success in the GOP, if he remembers the narrow role he is allowed to play, and sticks to the script. Herman Cain knows the rules, and has always known them. His temporary lapse over “Niggerhead” was merely a refresher course, to remind him of what he already knows. For example, he may be leading the Republican pack at the moment, but we will not see Herman Cain on the stage at the end of the GOP convention, thanking his party for its faith in him and promising victory in November, and Herman Cain knows it. Not even if he wins every primary and leads Mitt Romney in every poll from now until the last primary, will Herman Cain be the Republican nominee. Cain may be leading the pack now, in part because he’s also got a tax message that resonates deeply with the GOP base, even if it makes the Republican establishment nervous. But Cain said himself that the last debate looked like he and Romney were the top two candidates. In another party, it might be so. But it won’t be so in the GOP. No matter how many polls he wins, Cain will never be more than a “second tier” GOP candidate. Period. And he knows it. They may not like Romney. They may not even want to elect him. But as much as conservatives like Herman Cain, they don’t want to elect him even more than they don’t want to elect Romney. Cain may be the right’s new “Black Friend,” and a great guy, but Romney — even Perry — is “acceptable” to Republicans as president in a way that a Herman Cain won’t be for a very long time to come. Maybe Cain understands that, and isn’t running for the top of the ticket anyway. If he’s very, very lucky, and remembers his lessons well, we could witness him accepting the number 2 spot, where his job will be to support the ideas of the guy at the top of the ticket. You know, one of the white guys he’s beating out right now. (Take your pick.) And if that day comes, Herman Cain will say it’s not about race. He’ll continue to say that throughout his term as VP, every time the media asks him. You know, as part of a news article about Vice President Cain hunting with President Perry — at “Niggerhead,” of course. About Terrance Heath Terrance Heath is the Online Producer at Campaign for America's Future. He has consulted on blogging and social media consultant for a number of organizations and agencies. He is a prominent activist on LGBT and HIV/AIDS issues.
Low
[ 0.515086206896551, 29.875, 28.125 ]
Middle-School Course on Islam Draws Controversy A middle school course on Islam that is being taught in California has become a point of controversy. One parent has filed a complaint against the San Luis Obispo school district, claiming that the schools do not give as much instruction time for teaching other religions, The Washington Times reported. In that district, students pretended they were warriors fighting forIslam. In a second school district, the Excelsior School in the Byron UnionSchool District near Oakland, about 125 seventh-graders read verses fromthe Quran, studied Islamic proverbs and dressed up in Muslim robes, thecourse description handouts said. "From the beginning, you and your classmates will become Muslims," the handout reads. "Dressing as a Muslim and trying to be involved will increase your learning and enjoyment." Peggy Green, superintendent of the Byron Union School District, toldthe newspaper that her schools are not promoting the faith, but solelyteaching about Islam. She said students could get extra credit if theydressed up as a Muslim. Ken Connor, president of the Washington-based Family ResearchCouncil, thinks the classes are unfair. "This reflects a terrible double standard," he told the newspaper. "Anything that smacks of Christianity is systematically excluded in the classroom, but everything else like Wicca to Islam is welcomed." The American Center for Law and Justice, has sent a letter to ByronUnion School District insisting that school officials allow students toopt out of the course on Islam. "While it is appropriate to teach about various religions--including the teachings of Islam, Judaism, and Christianity--it is not appropriate for a public school to require students to attend a coursethat violates their religious beliefs," said Jay Sekulow, chief counsel for the conservative law firm based in Virginia Beach, Va.
Mid
[ 0.569138276553106, 35.5, 26.875 ]
The invention relates to a fixture for an electronic flash, and more particularly, to such fixture including a connection terminal utilized for synchronized flashlight illumination and another connection terminal which is used to transmit an electrical signal indicative of the completion of a charging operation or the completion of a flashlight illumination of an electronic flash to a camera on which it is mounted, and enabling an electronic flash to be detachably mounted on a hot shoe of the camera. Such an electronic flash will be referred to hereafter as "of the kind specified." A conventional fixture for an electronic flash is illustrated in FIGS. 1 and 2. Referring to these Figures, there is shown electronic flash 1 having fixture 2 which is provided on the bottom surface thereof. Fixture 2 has connection member 3 in the form of a square plate which is adapted to be fitted into guide groove 8 formed in hot shoe 7 (see FIG. 2) that is provided on the top surface of a camera. Subsequently, fixing knob 4 may be turned to secure connection member 3 to shoe 7, thus mounting electronic flash 1 on the camera. It will be seen that a plurality of connection terminals are provided on bottom surface 3a of connection member 3, including centrally located terminal 5 which is used to permit a synchronized flashlight illumination, and connection terminals 6a, 6b located on the opposite sides thereof and which are used to transmit an electrical signal to the camera which is indicative of the completion of a charging operation or the completion of a flashlight illumination of the electronic flash. These terminals are provided in the form of retractable dowels. Hot shoe 7 includes an inner bottom surface 7a which is adapted to be engaged by bottom surface 3a of connection member 3. Three connection terminals 10, 11a, 11b are disposed in a layout corresponding to terminals 5, 6a, 6b. It is to be understood that terminals 10, 11a, 11b are electrically insulated from each other by forming part of bottom wall of hot shoe 7 with insulating member 9, and remain exposed. As indicated by an arrow a, connection member 3 of the electronic flash is inserted into guide groove 8 from the rear side. FIG. 3 shows hot shoe 12 of a more usual camera which has single connection terminal 14 alone that is used for providing a synchronized flashlight illumination. Only region 13 of the bottom surface of hot shoe 12 is electrically insulated by an insulating member while the remainder is formed by an electrically conductive member such as metal, so that when electronic flash 1 having fixture 2 is mounted on such hot shoe 12, the conductive material of the bottom surface of shoe 12 will short-circuit connection terminals 6a, 6b, causing a malfunctioning or possibly destroying the function of electronic flash 1. It will be understood that the same difficulty occurs also when electronic flash 1 is mounted on a usual accessory shoe which has no synchronized flashlight terminal.
Mid
[ 0.6052009456264771, 32, 20.875 ]
There are many ways to go about building a winning NHL roster, and the most successful teams use all the tools at their disposal: signing free agents, trading with other squads and drafting players. Of the three main roster-building tools, the draft gives teams the most control over their own destiny. Whereas top free agents can say yea or nay to any particular offer (and tend to favour markets that offer the more attractive mixes of size, competitiveness and tax treatment), and trades require another willing and self-interested partner, teams typically get what they want at the draft. There are certain players available to be chosen, teams make their selections. Fin. Of course, teams' advantages differ at the draft based on where they finished in the standings the previous season and where the lottery balls fall. But in no way is that the be-all, end-all factor in determining what is a good and bad-drafting team. Success at the draft came up in a piece I...
High
[ 0.6621621621621621, 36.75, 18.75 ]
BRUSSELS (Reuters) - European Union farm ministers fell short of a consensus agreement on Monday to allow imports of five genetically modified (GMO) products, paving the way for default approval by legal rubberstamp, EU officials said. The products were four insect-resistant GMO maize types, including three hybrids developed by U.S. biotech company Monsanto Co from existing GMOs. The other maize, GA21, is marketed by Swiss agrochemicals company Syngenta. The other GMO product was a potato made by German chemicals group BASF known as Amflora and engineered to produce high amounts of starch for use in industrial processing but whose by-products can also be used in animal feed. ADVERTISEMENT None of the five GMOs is intended for growing in the 27-country EU's fields but for use in food and animal feed. "There was no qualified majority either for or against any of the proposals on GMOs," one official said. Under the EU's complex weighted voting system, countries have different influence in a decision and must reach a consensus majority. The applications for EU approval now return to the European Commission, the EU's executive arm, most probably for a default approval with a few weeks or possibly longer. EU law provides for rubberstamp GMO authorizations when ministers are unable to agree after a certain time. Since 2004, the Commission has authorized a string of GMOs -- nearly all maize types -- in this way, outraging green groups. For the three maize hybrids, developed from Monsanto's existing MON863, MON810 and NK603 product lines for general use in food and animal feed, 11 countries voted against approval and five abstained, officials said. The other GMO maize under discussion was GA21, originally a Monsanto product but now owned by Syngenta, one of the world's largest producers of GMO seeds. Ten countries voted against and six abstained. EU approval of GA21 maize is of particular interest to Spanish grain traders, since the modified strain may only now be imported into EU markets in processed form. Syngenta's request for EU approval, if granted, would allow GA21 imports as grain. The high-starch potato attracted a higher number of negative votes -- 14 countries. While BASF has filed a separate EU approval request for its high-starch potato to be cultivated, ministers dealt only with an application for by-products from the potato's starch extraction process to be used in feed.
Mid
[ 0.5400943396226411, 28.625, 24.375 ]
Something’s WRONG with MY LITTLE PONY: Friendship is magic As it turns out, I’m a “Brony”… I watch My little Pony: Friendship is magic. I likes it. But there’s something just a little WRONG here somewhere… Wonder what it could be? and will it CORRUPT THE CHILDREN?! “Twilight Sparkle, a talented but introverted student of Princess Celestia, is sent to Ponyville in the hopes that she will open up and make some friends. There, she meets fellow ponies Pinkie Pie, Applejack, Rainbow Dash, Rarity, and Fluttershy. However, she is too focused on researching and preventing a prophecy, involving an evil pony who was sealed within the moon and would return during the “longest day of the thousandth year”. From the TV series “My Little Pony: Friendship is Magic”, the 2010 reboot of the perennial Hasbro franchise as masterminded by Lauren Faust. (of the Powerpuff girls and more)
Low
[ 0.519750519750519, 31.25, 28.875 ]
WALLABIES superstar David Pocock is considering taking a year off from rugby to study in England for 12 months, while Queensland flanker Liam Gill is poised to join French glamour club Toulon, putting Australia’s backrow stocks in disarray. Pocock’s shock potential break from the game in 2017 would have huge ramifications for the Wallabies and Brumbies, given he was the nation’s best player at last year’s World Cup. The ARU is working feverishly to keep Pocock in Australia, but the final decision will rest with the 27-year-old backrower. Renowned as much for his off-field endeavours as his on-field brilliance, Pocock is hardly an orthodox athlete and this latest news epitomises his approach to life and sport. Pocock had two seasons completely ruined by successive knee injuries, yet came back last year to carry the Wallabies to the World Cup final and establish himself as a world-class No.8. But despite his form and claims to the Wallabies No.8 jersey, Pocock has a desire to take a complete break from rugby once his ARU contract expires on December 31 and turn his attention to intellectual pursuits. The Daily Telegraph can reveal that as part of ongoing negotiations with the ARU and Brumbies, Pocock has asked for a 12-month sabbatical in 2017 to study, and then return in 2018 with a view to playing at the 2019 World Cup in Japan. The Brumbies are desperate for Pocock to stay, but will not grant him a one-year absence. “It creates all sorts of problems if Poey takes a break,” Brumbies chief executive Michael Jones said. “My preferred solution, and our offer to him, doesn’t allow a break. “There is still a fair bit of water to go under the bridge.” Adding to the intrigue is Gill’s impending departure from Queensland Reds at the end of this season to join Toulon, who have on their roster several other notable Australians including Quade Cooper, Matt Giteau, Drew Mitchell and James O’Connor. Pocock is now also being linked to the Reds as a potential replacement for Gill. Queensland snuck under the radar to poach Brumbies captain Stephen Moore on a three-year deal starting from 2017, and Moore’s influence could be vital in the Reds’ bid to lure Pocock back to Brisbane where he played his junior rugby. Gill said it was a tough call to make but that he would use it to help fuel his final season at the Reds. “It was a very difficult decision, but I felt the time was right to challenge myself and play rugby in a different environment,” Gill said. “I feel I have done as much as I can in Australian rugby and now look to enjoy a new opportunity. “It’s really difficult to leave the Reds, but I’m excited by the opportunity this current group has for the season. This news just gives me even more drive to repay the faith of the QRU and the support of our fans.” Executive General Manager – Reds, Daniel Herbert said: “It’s disappointing to be losing Liam to an overseas club, but we understand he has weighed up his options and decided this was too good an opportunity to refuse. “Liam is a talented player and someone who has made a great contribution to the Reds over the past six years after graduating from our elite pathways system. He has international aspirations but plays in a position in which Australia have significant depth and he felt he would have limited Wallaby opportunities. “Whilst we are disappointed to see him go there are limitations to what we are currently able to do if players garner overseas interest and aren’t in the top band of Wallabies. We hoped a flexible contract would encourage Liam to stay in Queensland and Australia but in the end he felt this was his best option all things considered. “We know his focus will remain on the Reds while he is still at Ballymore and hope his final year with us is a successful one.” At just 23, Gill has played 15 Tests for the Wallabies but in recent times has fallen down the pecking order to Pocock, Michael Hooper and Sean McMahon for national selection, and was not given any ARU top-up money when he re-signed with the Reds for the 2016 season. It’s believed Toulon’s deal dwarfs those offered to Gill by Australian Super Rugby clubs including the Reds and Western Force, and he will depart at the conclusion of this Super season. Pocock, meanwhile, is keen to study at either of England’s most famous universities - Oxford or Cambridge - but his chosen field is unclear. Pocock’s website says he is currently studying a Bachelor of Ecological Agricultural Systems. Never one to walk a traditional path, Pocock has been globally lauded for his strong advocacy of environmental and human rights issues.
Low
[ 0.507726269315673, 28.75, 27.875 ]
Chronic interstitial lung diseases in children. Interstitial lung diseases (ILDs) in children constitute a heterogeneous group of rare diseases that have been described and classified according to experiences and research in adults. However, pediatric pulmonologists have observed that the clinical spectrum is broader in children than in adults, and that many of these disorders have different courses and treatment responses. In addition, probably due to the various stages of lung development and maturation, new clinical forms have been described, particularly in infants. This has broadened the classification of ILDs in this age bracket. The understanding that neither the usual definition nor the standard classification of these disorders entirely apply to children has prompted multicenter studies designed to increase knowledge of these disorders, as well as to standardize diagnostic and therapeutic strategies. We have reviewed the conceptualization of ILDs in children, taking into consideration the particularities of this group of patients when using the criteria for the classification of these diseases in adults. We have also made a historical review of several multicenter studies in order to further understanding of the problem. We have emphasized the differences in the clinical presentation, in an attempt to highlight knowledge of newly described entities in young children. We underscore the need to standardize management of laboratory and radiological routines, as well as of lung biopsy processing, taking such knowledge into account. It is important to bear in mind that, among the recently described disorders, genetic surfactant dysfunction, which is often classified as an idiopathic disease in adults, should be included in the differential diagnosis of ILDs.
High
[ 0.686419753086419, 34.75, 15.875 ]
Data is available at the NIH funded Systems Biology Center website: <http://stmc.health.unm.edu/tools-and-data/> under the Dowload Data Here link after Letendre K. et al. reference. Also available for download from: <https://www.dropbox.com/sh/bmab4vnrdxn7ond/AAAluhRS9jor1v46C_c_76bQa?dl=0> Introduction {#sec001} ============ Search has been extensively studied in biology, particularly in ecology, to understand how animals search for food, mates and prey. The pattern of movement by searching agents affects search efficiency in a variety of biological contexts \[[@pcbi.1004818.ref001]--[@pcbi.1004818.ref003]\]. Optimal foraging theory suggests that animals, including social animals such as ants and bees, have evolved strategies to individually or collectively maximize food intake in minimal time \[[@pcbi.1004818.ref004]\]. Similar to foraging animals, T cells of the immune system search for targets to mount an immune response. T cells are a critical immune effector, required to clear viral infections and to help B cells produce antibody. In order to initiate an effective immune response, naïve T cells must encounter and sample dendritic cells (DCs) bearing cognate antigen in lymph nodes (LNs). In the absence of infection, T cells continuously enter and exit LNs interacting with DCs. Upon infection, DCs present cognate antigen and provide stimulatory signals leading to T cell activation. T cell-DC interactions are required for naïve T cells to survive, activate and eventually clear infection as well as maintain immune memory \[[@pcbi.1004818.ref005]--[@pcbi.1004818.ref007]\]. T cell activation is promoted by repeated sampling of nearby DCs \[[@pcbi.1004818.ref008]\], while at the same time T cells explore the entire population of DCs for rare antigen indicative of infection. This presents T cells with an optimization problem in which T cells must balance *thoroughness* and *extent* of search. This requires that many T cells search across a broad *extent*, contacting many DCs quickly, a process similar to optimal foraging in animals. Simultaneously, T cell search is sometimes *thorough*, repeatedly sampling in a small area \[[@pcbi.1004818.ref008]\]. Both of these factors contribute to the overall rate at which T cells encounter DCs within LNs, which is a critical component of organismal fitness impacting the overall timing of the immune response. Relatively little quantitative analysis has been done to describe how T cells move in LNs or how that movement affects the rate at which T cells encounter DCs. Initial studies to understand the type of T cell motion in LNs from pioneering two-photon imaging of naïve T cells suggested that T cells move using a simple diffusive random walk, analogous to Brownian motion of molecules \[[@pcbi.1004818.ref009],[@pcbi.1004818.ref010]\]. Following these studies, computational modeling of T-DC interactions have often used simple diffusive random walks to represent T cell behavior \[[@pcbi.1004818.ref011],[@pcbi.1004818.ref012]\]. However, subsequent studies have not precisely described T cell motion in LNs, so it is unclear whether diffusive random walks are appropriate models for T cell movement. Optimal random search strategies have been extensively studied in ecology, and ecological models of movement may be useful for characterizing T cell motility and search efficiency. Brownian motion, Lévy walks, and correlated random walks (CRWs, also called persistent random walks), have been proposed as idealized biological search models \[[@pcbi.1004818.ref013]\], but careful quantitative analysis is required to understand how well search models characterize T cell motility and search efficiency \[[@pcbi.1004818.ref014]\]. Brownian motion is often referred to as a simple random walk and is characterized by movement with uniformly distributed turning angles and small fixed step sizes relative to the time resolution of observation \[[@pcbi.1004818.ref010],[@pcbi.1004818.ref015]--[@pcbi.1004818.ref018]\]. Qualitative similarities between Brownian motion and the movement of microorganisms resulted in simple random motion being used as a dominant model of cell motion \[[@pcbi.1004818.ref019]\]. Brownian motion results in diffusive movement in which distance travelled is proportional to the square root of time. In two dimensions this results in a normal distribution of speeds, and in three dimensions it results in a Maxwell distribution of speeds \[[@pcbi.1004818.ref020]\]. Lévy walks exist between ballistic (or straight directional) motion at one extreme and Brownian motion at the other. In contrast to Brownian motion, the step lengths of Lévy searchers fit a power law distribution with most step lengths being small, but with a heavy-tail, that is, a decreasing probability of larger steps and a non-zero probability of steps of any length \[[@pcbi.1004818.ref002],[@pcbi.1004818.ref013]\]. Lévy walks have been used to model animal movement, for example, in albatross, ant, aphid and human foraging, and more recently, T cells in the brain \[[@pcbi.1004818.ref002],[@pcbi.1004818.ref021]--[@pcbi.1004818.ref024]\]. Both Brownian and Lévy walks assume that the direction of search at each step is drawn from a uniform distribution and is independent of previous steps (i.e. is isotropic and Markovian). CRWs on the other hand use fundamentally different mechanisms to model similar patterns of motion that tend to persist in direction over time. CRWs depend on the distribution of turning angles between successive steps leading to directional persistence. In search modelled by CRWs, the current direction of motion probabilistically influences future step directions \[[@pcbi.1004818.ref013]\]. On relatively short time scales, Lévy walks and CRW may be difficult to distinguish since they both produce superdiffusive motion \[[@pcbi.1004818.ref025]\], that is, displacement that increases faster than the square root of time. Compared to diffusive movement, superdiffusion increases search *extent* and decreases search *thoroughness*. Despite the fact that many search strategies are well-characterized, there has been no systematic analysis of T cell motion in LNs. The lack of clarity in empirical studies has led to T cell motility being modelled using Brownian motion \[[@pcbi.1004818.ref018]\], Lévy walks \[[@pcbi.1004818.ref024]\], and correlated random walks (CRW) \[[@pcbi.1004818.ref008],[@pcbi.1004818.ref026]\], or a combination of movement patterns \[[@pcbi.1004818.ref027]\]. Recently, Harris et al. showed that the movement of T cells in *Toxoplasma gondii* infected brain tissue fits a Lévy walk resulting in superdiffusion and efficient detection of protozoan targets \[[@pcbi.1004818.ref024]\]. It is not clear if Lévy movement has not previously been found in LN because such movement does not occur there, or simply because it had not been looked for. The lack of precise quantitative understanding of T cell motion in LNs leads to inconsistent models and limits our ability to determine how T cell motility affects the efficiency with which T cells encounter DCs. In this study, we analyze T cell search behavior in LNs using two-photon microscopy. We begin our analysis with traditional statistical methods that describe the velocities, step lengths, displacement, and turning angles taken by naïve T cells searching for DCs. We then extend these analyses to more accurately and comprehensively describe motility patterns, including using maximum likelihood estimates (MLE) to fit experimental data. Our study statistically analyzes T cell search strategies in LNs, and uses multiple efficiency metrics that measure the spatial thoroughness and extent of T cell search. We then directly quantify the contribution of different types of motion to the efficiency of T cell search. Additionally, by comparing T cell movement to the patterns generated by null models of random motion, interesting non-random interactions between T cells and their environment become apparent, suggesting that T cells adapt movement in response to environmental cues. Our null models reveal hot spots that are visited more frequently than can be explained by chance. Our results suggest that even a precise characterization of T cell movement based on the assumption of random movement does not fully capture the complexity of T cell movement in the LN environment. Results {#sec002} ======= Movement of naïve T cells in lymph nodes is superdiffusive, not Brownian {#sec003} ------------------------------------------------------------------------ Two photon microscopy (2PM) has been used extensively to study the movement of T cells in intact lymph nodes \[[@pcbi.1004818.ref015],[@pcbi.1004818.ref016],[@pcbi.1004818.ref018],[@pcbi.1004818.ref028],[@pcbi.1004818.ref029]\]. We isolate bulk primary T cells from LNs of naïve C57Bl/6 animals, fluorescently label T cells with dyes, reintroduce labeled T cells into recipient mice, and then use 2PM to image labeled T cells in intact explanted LNs of recipients (see [Materials and Methods](#sec009){ref-type="sec"} for further details). We track cells for up to 10 minutes and include all motile cells in observation windows. We eliminate tracks with total track length shorter than 17μm or that show squared displacement less than 300μm^2^ (= 17μm x 17μm) as described previously by Letendre et al. \[[@pcbi.1004818.ref030]\]. The data analyzed here are from 5,891 individual T cell tracks from 41 fields from 12 experiments. We group those 41 fields into 7 datasets, each dataset containing fields imaged using frame rates within one second of each other. This allows us to combine data across fields when performing analyses, such as velocity autocorrelation, that depend on the frame rate. We observe T cell velocities and motility coefficients largely in agreement with those previously published \[[@pcbi.1004818.ref009],[@pcbi.1004818.ref016],[@pcbi.1004818.ref030],[@pcbi.1004818.ref031]\]. We calculate the diffusion coefficient using the unweighted average method \[[@pcbi.1004818.ref032],[@pcbi.1004818.ref033]\]. T cells move with a mean speed with 95% confidence interval = 5.81 ±0.024 μm/min, median speed = 4.22 μm/min, motility coefficient, D = 19.2±0.534 μm^3^/min, calculated from a linear fit MSD of 5,185 tracks (out of 5,891 tracks filtered for *r*^*2*^ \> 0.8). The motility coefficient is calculated using a linear model fit to the first 25% of each displacement curve and for positions not exceeding the 10 min track time. Displacement is commonly used as a first step to assess whether movement is consistent with a Lévy walk or Brownian motion (sample tracks in [S1 Fig](#pcbi.1004818.s002){ref-type="supplementary-material"})\[[@pcbi.1004818.ref024],[@pcbi.1004818.ref031]\]. We determine the displacement of individual T cells over time. [Fig 1A](#pcbi.1004818.g001){ref-type="fig"} shows the mean squared displacement (MSD) of one of the 7 datasets, as well example tracks with lower ([Fig 1B](#pcbi.1004818.g001){ref-type="fig"}) and higher ([Fig 1C](#pcbi.1004818.g001){ref-type="fig"}) *r*^*2*^ values. We then calculate the linear fit to the log-log-transformed data. Logarithmically transforming data before applying a linear regression is a common way to measure the exponent of a power-law relationship between dependent and independent variables \[[@pcbi.1004818.ref034]\]. Log-log-transformed Lévy walks produce displacement exponents, *α*, between 1 and 2 \[[@pcbi.1004818.ref035]\]. We calculate the distribution of *α* for all T cell tracks and find that 56% of T cells have a displacement exponent *α* falling in the expected window for a Lévy walk ([Fig 1D](#pcbi.1004818.g001){ref-type="fig"}). Only 28.3% of cell tracks are subdiffusive (*α* \< 1), and the remaining tracks (15.6%) have a best-fit displacement exponent indicative of accelerating motion (*α* \> 2). Because low *r*^2^ values of linear fits to log-log-transformed data may indicate that the data are not well-described by any displacement exponent, we repeat the analysis on data sets restricted to *r*^2^ values \> 0.5, which discards 33% of all tracks, and *r*^2^ \> 0.75, discarding 50% of all tracks (see [S2 Fig](#pcbi.1004818.s003){ref-type="supplementary-material"} for figures with different *r*^2^ filters). Increasing *r*^2^ filtering decreases the fraction of cells in the subdiffusive window, but the qualitative message remains the same: T cells demonstrate heterogeneous behavior, with some displacements consistent with subdiffusive, Brownian, ballistic and even accelerating motion, but the majority of T cells are superdiffusive but sub-ballistic. [Fig 1D](#pcbi.1004818.g001){ref-type="fig"} shows the histogram of *α* for tracks with an *r*^2^ \> 0.8, other *r*^2^ thresholds are shown in [S2 Fig](#pcbi.1004818.s003){ref-type="supplementary-material"}, including all tracks with no filtering in [S2A Fig](#pcbi.1004818.s003){ref-type="supplementary-material"}. ![T cells move in lymph nodes with some features of a Lévy walk.\ Lévy walks are characterized by particular power law exponents of mean squared displacement (MSD) and step length distribution. (A, bottom) Observed T cell MSD vs. time. The dashed line is the linear regression with slope *α* = 1.41 indicating superdiffusion. (A, top) The number of data points in the MSD calculation. (B) Example displacements for a single T cell track with *r*^2^ = 0.52, and (C) with *r*^2^ = 0.93. (D) Histogram of *α* for individual tracks with *r*^2^ \> 0.8 (see [S2 Fig](#pcbi.1004818.s003){ref-type="supplementary-material"} for other *r*^2^ thresholds) with labels indicating the range of values of *α* consistent with Brownian, Lévy and ballistic motion. (E) Empirical complementary cumulative distribution function (CCDF) of all 145,731 step lengths for all 5,077 cells. The *x*-axis is all possible distances less than the maximum observed, the *y*-axis is the probability that an observed step length exceeds a particular value of x. The dashed line (offset for clarity) with slope 4.05 is the best fit to the power law tail of the CCDF which includes only 6.15% of the steps \[[@pcbi.1004818.ref036]\]. The line with slope 1.19 is the best fit to all data. (F,G) Examples of step length distributions and MLE fits for tracks with 49% and 93% of the track in the tail. (H) Percentage of tracks in the Lévy region for *μ* and *α* power law exponents and their intersection. Data are included when the *r*^2^ \> 0.5 for *α* and at least 50% (left histogram) or 70% (right histogram) of the track steps are retained in fitting the power law tail.](pcbi.1004818.g001){#pcbi.1004818.g001} Naïve T cell movement in LNs is not consistent with a Lévy walk {#sec004} --------------------------------------------------------------- While displacement analysis suggests many T cells are consistent with a Lévy walk, another defining feature of Lévy walks is that the inverse power law complementary cumulative distribution function (CCDF) for step lengths has an exponent, *μ*, between 1 and 3. Therefore, we analyzed T cell step lengths for the *μ* exponent. We define a *step* to be the resultant of a velocity subsequence in which each T cell velocity vector deviates by no more than 15° from the previous vector and a *step length* is the distance covered by a step. [Fig 1E](#pcbi.1004818.g001){ref-type="fig"} shows that a power law fit to the population of T cell step lengths is only valid if almost 94% of the data are excluded from the analysis (see [Materials and Methods](#sec009){ref-type="sec"}: Distribution fitting). The resulting best-fit *μ* exponent for the remaining 6% of the power law tail is 4.05 ([Fig 1E](#pcbi.1004818.g001){ref-type="fig"}). The curvilinearity, the poor fit, as well as the *μ* value all indicate that a Lévy walk is not a good description of T cell motility. On average 51% of data must be excluded in order to obtain a maximum likelihood estimated (MLE) power law fit (see [Fig 1F and 1G](#pcbi.1004818.g001){ref-type="fig"} for example tracks with low and high percentage of steps in the power law tail; see [S3A and S3D Fig](#pcbi.1004818.s004){ref-type="supplementary-material"} for histograms of *μ* using other goodness of fit (GoF) threshold values; and see [S2](#pcbi.1004818.s003){ref-type="supplementary-material"} and [S3](#pcbi.1004818.s004){ref-type="supplementary-material"} Figs for additional analysis.) We determined the number of tracks that fit both 1\< *μ* \<3 and 1\< *α* \<2 parameters. Setting our GoF filtering criteria to require that at least 70% of the data per track is retained in calculating the exponent *μ* ([Fig 1F](#pcbi.1004818.g001){ref-type="fig"}), and the *r*^2^ statistic for the power law exponent *α* is at least 0.7, we find that only 5.5% of all T cell tracks fit both criteria for Lévy walk ([Fig 1H](#pcbi.1004818.g001){ref-type="fig"}). We note that the tracks excluded when filtering by *r*^2^ and those filtered by the percent of track in the power law tail both tend to be subdiffusive. For any filtering criteria the vast majority of T cell tracks are not Lévy walks ([S3E Fig](#pcbi.1004818.s004){ref-type="supplementary-material"}). To further analyze T cell motion, we quantify speeds (T cell displacement between consecutive frames multiplied by the frame rate) of all T cell tracks ([Fig 2A and 2C](#pcbi.1004818.g002){ref-type="fig"}) and find that in LNs T cell speeds range from 6.5×10^−4^ μm/s to 0.9 μm/s ([Fig 2A](#pcbi.1004818.g002){ref-type="fig"}). We fit experimentally derived speeds ([Fig 2A](#pcbi.1004818.g002){ref-type="fig"}) and step lengths ([Fig 2B](#pcbi.1004818.g002){ref-type="fig"}) to idealized probability distributions. We use parametric distributions because they are associated with well-known generative processes; for example, the Gaussian distribution is produced by the cumulative effect of additive processes, the lognormal distribution is often associated with multiplicative or branching processes \[[@pcbi.1004818.ref037]\], and the Maxwell distribution is a product of Brownian motion in three dimensions. We use likelihood measures to rank how well different distributions explain the observed data (Tables [1](#pcbi.1004818.t001){ref-type="table"} and [2](#pcbi.1004818.t002){ref-type="table"}). ![Distributions of T cell speed and step lengths with MLE fits.\ For (A) speed and (C) step length the lognormal function is the best fit (see Tables [1](#pcbi.1004818.t001){ref-type="table"} and [2](#pcbi.1004818.t002){ref-type="table"} for likelihood values and model parameters). Fits for normalized speed (B) and normalized step lengths (D) are divided by the mean speed or step length of the track from which they are drawn. (E) Histogram of all 149,592 observed turning angles. The green line is the maximum likelihood estimation of the gamma distribution used to model turning angles in the efficiency simulation. (F) Turning angle autocorrelation for 23,169 vectors from the 537 T cell tracks observed in one dataset. The correlation in movement direction decays until reaching zero at approximately 240 s.](pcbi.1004818.g002){#pcbi.1004818.g002} 10.1371/journal.pcbi.1004818.t001 ###### MLE fits to step lengths and normalized step lengths (N = 145,731 steps). Negative log-likelihood measures the relative ability of candidate models to explain the observed data (For additional fits tested, see [S1](#pcbi.1004818.s016){ref-type="supplementary-material"} and [S2](#pcbi.1004818.s017){ref-type="supplementary-material"} Tables). The corrected Akaike information criterion (AICc) and Bayesian information criterion (BIC) ([S2 Table](#pcbi.1004818.s017){ref-type="supplementary-material"}) confirm that order of fit quality is not due to the number of model parameters. The most negative log likelihood and AICc scores are the best fits; in this case that is the smallest positive score for the lognormal distribution. The last column lists the distribution parameters that were selected by MLE. See [S1](#pcbi.1004818.s016){ref-type="supplementary-material"} and [S2](#pcbi.1004818.s017){ref-type="supplementary-material"} Tables for other distribution fits and goodness of fit statistics. ![](pcbi.1004818.t001){#pcbi.1004818.t001g} ------------------------------------------------------------------ ------------------------------- ------------ ----------------- ---------------- **Step lengths** Distribution Negative log Likelihood×10^5^ AICc×10^5^ MLE Parameters **Lognormal** **2.65** **5.29** **μ = 0.4818** **σ = 0.9192** Gaussian 3.36 6.72 μ = 2.3895 σ = 2.4229 Maxwell 4.02 8.04 a = 3.8497 Power Law (Levy) 4.58 9.16 α = 1.1921 **Normalized Step lengths (step length/track mean step length)** **Lognormal** **1.20** **2.40** **μ = -0.2217** **σ = 0.6896** Gaussian 1.61 3.23 μ = 1 σ = 0.7324 Maxwell 1.69 3.37 a = 0.5117 Power Law (Levy) 3.32 6.63 α = 1.2245 ------------------------------------------------------------------ ------------------------------- ------------ ----------------- ---------------- 10.1371/journal.pcbi.1004818.t002 ###### MLE fits to speeds and normalized speeds (N = 159,746). The lognormal distribution has the most negative log-likelihoods and AICc score and therefore is the best fit. The parameters selected by MLE are shown for each distribution. See [S1](#pcbi.1004818.s016){ref-type="supplementary-material"} and [S2](#pcbi.1004818.s017){ref-type="supplementary-material"} Tables for other distribution fits and goodness of fit statistics. ![](pcbi.1004818.t002){#pcbi.1004818.t002g} -------------------------------------------- ------------------------------- ------------ ----------------- ---------------- **Speeds** Distribution Negative log Likelihood×10^5^ AICc×10^5^ MLE Parameters **Lognormal** **-1.84** **-3.68** **μ = -2.5027** **σ = 0.9329** Gaussian -1.61 -3.23 μ = 0.1161 σ = 0.0881 Maxwell -1.12 -2.24 a = 0.0071 Power Law (Levy) 0.122 0.245 μ = 1.2069 Normalized Speeds (speed/track mean speed) **Lognormal** **1.22** **2.45** **μ = -0.1669** **σ = 0.6154** Gaussian 1.37 2.74 μ = 1 σ = 0.5706 Maxwell 1.32 2.65 a = 0.4414 Power Law (Levy) 3.58 7.16 μ = 1.2446 -------------------------------------------- ------------------------------- ------------ ----------------- ---------------- The distribution of T cell step lengths and speeds is more consistent with a lognormal distribution than with Brownian motion (defined by a Gaussian or Maxwell distribution) or a Lévy walk (defined by a power law distribution of speeds \[[@pcbi.1004818.ref038]\]) as shown by the higher values in the MLE for power law fits in Tables [1](#pcbi.1004818.t001){ref-type="table"} and [2](#pcbi.1004818.t002){ref-type="table"}. The variance of observed T cell speeds and lengths is high, and the distributions have a heavier tail (greater right skew) than both Gaussian and Maxwell distributions. The power law probability distribution over-represents both very small steps and very large steps compared to observed T cells. The lognormal distribution shows the best statistical fit for both speed and step lengths. The gamma distribution also fits the observed speeds very well ([S1](#pcbi.1004818.s016){ref-type="supplementary-material"} and [S2](#pcbi.1004818.s017){ref-type="supplementary-material"} Tables, [S4 Fig](#pcbi.1004818.s005){ref-type="supplementary-material"}). However since gamma and lognormal are often used to model the same phenomena, we present only lognormal here \[[@pcbi.1004818.ref039]\]. It is possible that the right skew in the speed distribution arises from the variance between track mean speeds rather than from speed variance within tracks \[[@pcbi.1004818.ref022]\]. To test for this possibility, we divide each speed drawn from within a cell track by the cell mean speed (called "normalized") and ask whether the distribution becomes less heavy-tailed. We find that both normalized speed and step length distributions are still best fit by a lognormal distribution (compare [Fig 2A](#pcbi.1004818.g002){ref-type="fig"} with [Fig 2C, 2B and 2D](#pcbi.1004818.g002){ref-type="fig"} and the normalized vs. raw lengths and speeds in Tables [1](#pcbi.1004818.t001){ref-type="table"} and [2](#pcbi.1004818.t002){ref-type="table"}), but the right skew is decreased. Our observations indicate that the heavy-tailed lognormal distribution is not simply due to distinct populations moving at different mean speeds, though heterogeneity in speed within the population is a factor. Both Brownian motion and Lévy walks assume that the angle of each turn is drawn from a uniform random distribution. We analyze the turning angles of each T cell at each time step and find that T cell turning angles are not uniform, and that there is a bias toward turning angles of less than 90° ([Fig 2E](#pcbi.1004818.g002){ref-type="fig"}). The non-uniform distribution of turning angles suggests that T cells may move according to a CRW. We fit distributions to turning angles using MLE and find the gamma distribution to be the best fit, although it cannot capture all of the variation in the bi-modal distribution ([Fig 2E](#pcbi.1004818.g002){ref-type="fig"} green-dotted line). We then performed an autocorrelation analysis of directions over time to determine whether there is a dependency between the direction of T cells at one time step and the previous time steps ([Fig 2F](#pcbi.1004818.g002){ref-type="fig"}). We find that T cells show turning angle autocorrelation consistent with a CRW (indicated by positive values in [Fig 2F](#pcbi.1004818.g002){ref-type="fig"}). The correlation persists for approximately 4 minutes. Our cross-correlation analysis shows no drift in the observation fields (Materials and Methods: Equation 2). T cells balance search for unique individual targets and interactions with multiple targets {#sec005} ------------------------------------------------------------------------------------------- A key function of naïve T cell search within LNs is to find and interact with antigen bearing DCs. To determine whether different types of search can affect T cell interaction with DCs, we use an agent-based model, using biologically informed parameters, to assess the degree to which different modes of random search predict the observed pattern of T cell search efficiency (i.e., the number of DCs encountered per unit time). We reproduce features of T cell movement by creating search tracks using the best distribution fit to speeds ([Table 2](#pcbi.1004818.t002){ref-type="table"}) and turning angles, limited by the total distance covered and time observed for empirical T cell tracks. We run simulations with DC targets placed with 3 different degrees of clustering: highly clustered (DC centers placed in 10μm radius spheres), moderately clustered (in 20μm radius spheres) to more evenly dispersed (in 40μm radius spheres) ([S5 Fig](#pcbi.1004818.s006){ref-type="supplementary-material"}). We confirm that these DC placements result in a range of clusteredness according to the Hopkins aggregation statistic that ranges from 0.44 for dispersed clusters (close to the 0.5 value expected for a uniform distribution) to 0.2 for compact clusters. We confirm that Brownian motion in our simulations results in diffusive movement ([S6 Fig](#pcbi.1004818.s007){ref-type="supplementary-material"}). We then compare efficiency of modelled search with observed T cell tracks from the experimental data across this range of DC cluster sizes. We calculate efficiency of T cell search in two ways. First, we determine how many unique "DC" targets were encountered by each T cell in a specific period of time. Previous studies suggest that naïve T cells have no *a priori* information about the location of DCs in LNs \[[@pcbi.1004818.ref011],[@pcbi.1004818.ref012]\]. Second, we determine how many total DC target encounters occur in the specified time. Total contacts count repeated contact with the same DC while unique contacts counts only one contact per DC. Total contacts are important for T cell activation and potentially survival while unique contacts are a measure of how long it may take T cells to find rare DCs presenting cognate antigen. The simulation addresses two questions: do statistical descriptions of T cell movement produce search efficiencies that are similar to those of observed T cells; and, how do the relative efficiencies of the idealized models compare to each other and experimentally observed T cells. Not surprisingly, the efficiency of observed T cells show a much wider range of variability compared with idealized models ([Fig 3A](#pcbi.1004818.g003){ref-type="fig"}), and we find clear differences in search efficiency between observed T cells and some idealized models. Brownian searchers are approximately 40% less efficient than observed T cells for unique DC contact ([Fig 3A and 3B](#pcbi.1004818.g003){ref-type="fig"} and [Table 3](#pcbi.1004818.t003){ref-type="table"}). In contrast, the power law (Lévy) fit was 30% *more* efficient than observed T cell tracks, and as expected, more efficient than any other model for unique contacts with DCs. We also modelled a correlated random walk (CRW) as well as a CRW with a lognormal distribution of step lengths (a lognormal modulated CRW, LogMCRW). We show that the idealized search that most closely fits the observed efficiency of experimentally derived T cell search in LNs is the LogMCRW ([Fig 3B](#pcbi.1004818.g003){ref-type="fig"}), in keeping with CCDF fits ([Fig 2](#pcbi.1004818.g002){ref-type="fig"}). Efficiency is not dependent on placement of DC targets in the model: efficiency measures remain similar across multiple target distributions and degrees of clustering ([Table 3](#pcbi.1004818.t003){ref-type="table"}). Thus, LogMCRW is not only the best description of the step length distribution, but also the best efficiency match for unique contact T cell search in LNs. ![T cell search balances unique and total contacts with targets.\ Interquartile boxplots show search efficiency for DCs in 10 μm radius clusters. Panels (A) and (B) show *unique contact* efficiency; (C) and (D) show *total contact* efficiency. (A) and (C) show 1000 efficiency samples for each of the 41 fields. (B) and (D) compare the percent change in median search efficiency for each candidate search model relative to observed T cell search (indicated by the line at 0). See Tables [3](#pcbi.1004818.t003){ref-type="table"} and [4](#pcbi.1004818.t004){ref-type="table"} for other target distributions and significance values. Outliers are not shown for clarity.](pcbi.1004818.g003){#pcbi.1004818.g003} 10.1371/journal.pcbi.1004818.t003 ###### Percent change of each idealized search strategy for unique contacts compared to the empirical search strategy across 3 different target distributions. Table entries are percent change in median search efficiency from observed ± 95% confidence interval. Two p-values are shown: the first indicates the significance of the change in *median* efficiency between the observed and idealized runs (N = 10 runs, each run consists of 4,100 samples, [Fig 3B](#pcbi.1004818.g003){ref-type="fig"}). The second p-value tests whether *all* raw efficiency values differ between observed and idealized runs (N = 41,000, [Fig 3A](#pcbi.1004818.g003){ref-type="fig"}). All p-values are calculated using the Mann-Whitney U test. The values in parentheses are the Hopkins aggregation statistic. All search strategies are statistically different from observations except LogMCRW in the most diffuse 40 μm DC clusters (in bold). ![](pcbi.1004818.t003){#pcbi.1004818.t003g} Search Strategy ------------------ --------------------- --------------------- --------------------- --------------------- ---------------------- --------------------- **10 μm (0.2)** -41.88 ± 0.82 -28.11 ± 1.09 -15.91 ± 1.69 -12.98 ± 0.99 -7.35 ± 1.92 27.63 ± 5.44 p \< 10^−4^, 10^−4^ p \< 10^−4^, 10^−4^ p \< 10^−4^, 10^−4^ p \< 10^−4^, 10^−4^ p \< 10^−4^, 10^−4^ p \< 10^−4^, 10^−4^ **20 μm (0.32)** -39.828 ± 0.64 -25.87 ± 0.70 -13.39 ± 1.62 -9.926 ± 1.37 -3.98 ± 1.94 34.17 ± 8.49 p \< 10^−4^, 10^−4^ p \< 10^−4^, 10^−4^ p \< 10^−4^, 10^−4^ p \< 10^−4^, 10^−4^ p \< 10^−3^, 10^−4^ p \< 10^−4^, 10^−4^ **40 μm (0.44)** -41.88 ± 0.81 -22.75 ± 0.55 -9.621 ± 1.97 -4.798 ± 1.37 -0.218 ± 2.17 36.02 ± 6.41 p \< 10^−4^, 10^−4^ p \< 10^−4^, 10^−4^ p \< 10^−4^, 10^−4^ p \< 10^−3^, 10^−3^ p = **0.85**, 10^−4^ p \< 10^−4^, 10^−4^ Our simulation of unique target search also gives a quantitative estimate of the contribution of different types of T cell movement to search efficiency ([Table 3](#pcbi.1004818.t003){ref-type="table"}). Correlation in angles of T cells increases the search efficiency by \~10% (from -42% for Brownian without correlation to -28% for CRW; -17% for lognormal to -7% for LogMCRW). The heavy-tailed step lengths contributed a 20% increase in efficiency (-42% Brownian to -17% lognormal). These results show that T cell motion is a complex mix of multiple motility parameters that contribute to overall T cell search efficiency. In addition to unique antigen search, multiple DC contacts by T cells contribute to T cell activation and may also be required for survival \[[@pcbi.1004818.ref041]--[@pcbi.1004818.ref043]\]. Interestingly, we find that the efficiency of total contacts is reversed from that seen for unique contacts (compare [Fig 3B and 3D](#pcbi.1004818.g003){ref-type="fig"}, [Table 4](#pcbi.1004818.t004){ref-type="table"}). Brownian searchers made the greatest number of total contacts, while power law (Lévy) searchers made the fewest total contacts ([Fig 3D](#pcbi.1004818.g003){ref-type="fig"}). Brownian searchers tend to resample the same locality and are therefore more thorough in their search at the cost of reduced search extent. In contrast, superdiffusive heavy-tailed searchers leave DC clusters more quickly and their total contact rate falls, increasing extent at the cost of thoroughness. Again, LogMCRW is closer to observed data than the other simulated patterns, and it successfully balances total contact rate with exploration of new DC clusters ([Fig 3D](#pcbi.1004818.g003){ref-type="fig"}). 10.1371/journal.pcbi.1004818.t004 ###### Percent change of each simulated search strategy for total contacts compared to the empirical search strategy across 3 different target distributions. Table entry format is identical to [Table 3](#pcbi.1004818.t003){ref-type="table"}. These values correspond to [Fig 3C and 3D](#pcbi.1004818.g003){ref-type="fig"}. Brownian motion, bootstrap and LogMCRW are not significantly different from the observed distribution of efficiencies when targets are more clustered (in bold), but power law search underestimates the efficiency of search for total contacts. ![](pcbi.1004818.t004){#pcbi.1004818.t004g} Search Strategy -------------- ----------------------- --------------------- --------------------- ---------------------- ----------------------- --------------------- 10 μm (0.2) 8.7 ± 1.16 12.94 ± 1.34 7.24 ± 3.25 0.73 ± 2.59 8.4 ± 3.66 -28.66 ± 2.43 p \< 10^−4^, **0.29** p \< 10^−4^, 10^−3^ p \< 0.01, 0.05 p = **0.63**, 10^−4^ p \< 10^−3^, **0.73** p \< 10^−4^, 10^−4^ 20 μm (0.32) 12.71 ± 1.52 15.67 ± 1.54 9.22 ± 2.72 2.29 ± 2.72 12.18 ± 2.64 -26.27 ± 4.14 p \< 10^−4^, **0.87** p \< 10^−4^, 10^−4^ p \< 0.05, 0.05 p = **0.19**, 10^−4^ p \< 10^−4^, **0.8** p \< 10^−4^, 10^−4^ 40 μm (0.44) 17.71 ± 1.86 20.89 ± 1.58 13.07 ± 3.24 4.52 ± 2.51 16.31 ± 2.69 -24.08 ± 4.4 p \< 10^−4^, 10^−4^ p \< 10^−4^, 10^−4^ p \< 10^−4^, 10^−4^ p \< 0.05, 10^−4^ p \< 10^−4^, 10^−4^ p \< 10^−4^, 10^−4^ We also performed a statistical bootstrap analysis in which search tracks were generated by sampling uniformly from all observed track speeds and turning angles \[[@pcbi.1004818.ref041]\]. While the efficiency of total contacts for bootstrap tracks is statistically indistinguishable from observed T cells, bootstrap tracks are 12% less efficient than observed cells in unique contacts ([Fig 3B](#pcbi.1004818.g003){ref-type="fig"} and [Table 3](#pcbi.1004818.t003){ref-type="table"}). Thus, individual T cell tracks confer efficiency for unique DC target search that is lost when the steps within a track are randomized, suggesting that there is underlying heterogeneity in T cell tracks that increases T cell search efficiency. Naïve T cells show heterogeneity in movement patterns {#sec006} ----------------------------------------------------- To assess potential variation in T cell motility, we analyzed differences in speeds across individual T cell tracks. We find that the distribution of speeds is highly skewed for cells with lower mean speeds, but there is less skew for cells with high mean speeds ([Fig 4A](#pcbi.1004818.g004){ref-type="fig"}). The fastest cells (mean speeds \>15 μm/min, [Fig 4D](#pcbi.1004818.g004){ref-type="fig"}) produce more symmetric speed distributions as demonstrated by the low skew and kurtosis. Also, distribution fitting of speeds shows that the speeds are now best fit by Gaussian and Maxwell distributions ([Table 5](#pcbi.1004818.t005){ref-type="table"}). In contrast, slow cells (mean speed \<5 μm/min, [Fig 4C](#pcbi.1004818.g004){ref-type="fig"}) have a heavier tailed distribution of speeds as shown by skew and kurtosis with lognormal remaining the best fit ([Table 5](#pcbi.1004818.t005){ref-type="table"}). This is not due to the number of data points available at high speeds, as skew decreased even at the speeds with the highest number of data points ([Fig 4B](#pcbi.1004818.g004){ref-type="fig"}). However, "slow" and "fast" are not discrete populations, as a mixed Gaussian cluster analysis shows no evidence of discrete populations defined by mean speed and variance ([S7 Fig](#pcbi.1004818.s008){ref-type="supplementary-material"}). These results suggest that T cells exhibit a continuum of movement patterns within LNs, leading to different types of searches: slow moving cells show a heavy-tailed distribution while faster moving cells are more Brownian. ![T cells moving at different speeds show different movement patterns.\ (A) Skew of step length distribution as a function of track mean speed and (C) the number of data points as a function of track mean speed. Tracks with mean track speeds (MTS) less than 5μm/min (B) and greater than 15μm/min (D) were selected to illustrate different MLE model fits for fast and slow tracks (for fits see [Table 5](#pcbi.1004818.t005){ref-type="table"}).](pcbi.1004818.g004){#pcbi.1004818.g004} 10.1371/journal.pcbi.1004818.t005 ###### Best fit likelihood and MLE estimated parameters for the fastest and slowest cells. The Gaussian distribution better fits tracks with mean speed \> 15 μm/min while lognormal better fits tracks with mean speed \< 5 μm/min. The step speed distribution for fast tracks has a shorter and lighter tail than the sample of tracks with slower mean speeds. Best negative loglikelihood scores are in bold. For tracks with mean speed of \< 5 um/min, skew is 2.37 and kurtosis 13.3; for tracks with mean speed \> 15 um/min, skew is 0.52 and kurtosis 3.98. ![](pcbi.1004818.t005){#pcbi.1004818.t005g} Mean Speed \< 5 μm/min Mean Speed \> 15 μm/min --------------- ------------------------ ------------------------- ----------- ----------- ----------- ------------ **Lognormal** **-1.09** **-3.35** **0.826** -2.60 -1.35 0.387 **Gaussian** -0.918 0.0482 0.0407 **-2.73** **0.277** **0.0958** Maxwell -0.789 0.0013 -2.66 0.0286 Power Law -0.492 1.25 2.018 1.35 "Hotspots" in the LN environment show differing patterns of T cell motion {#sec007} ------------------------------------------------------------------------- The variation in movement shown in [Fig 4](#pcbi.1004818.g004){ref-type="fig"} suggests that T cells may alter their search pattern in response to environmental cues. Our previous work shows that altering movement in response to environmental cues can enhance search efficiency \[[@pcbi.1004818.ref044],[@pcbi.1004818.ref045]\]. Extending our previous work in \[[@pcbi.1004818.ref046]\], we analyze T cells in LN to identify whether T cells movement changes within local microenvironments of the LN. To do this, we identify whether there are locations in the LN that are visited by T cells more frequently than predicted by a null model. We analyzed each observation field separately; each field was discretized into cubes of 20μm per side, which is approximately twice the diameter of a naïve T cell. We used the LogMCRW simulation we described earlier as a null model (for details of null model see [Materials and Methods](#sec009){ref-type="sec"}, [S11 Fig](#pcbi.1004818.s012){ref-type="supplementary-material"}). We identified spots that were visited by T cells in the simulation null model and then identified spots that were visited by T cells from actual experimental data. We found that experimental T cells visited certain spots at significantly higher frequency than the null model (see [S11 Fig](#pcbi.1004818.s012){ref-type="supplementary-material"} \[[@pcbi.1004818.ref047]\]). Spots that were visited at a frequency 2σ higher than the null model were called "hotspots" (examples shown in [S12 Fig](#pcbi.1004818.s013){ref-type="supplementary-material"}). Hotspots were observed in 37 of the 41 observation fields. The null model results in only 2.73% of visited locations being hotspots (as expected given that we identify hotspots as those visited 2 standard deviations above the mean, [S11 Fig](#pcbi.1004818.s012){ref-type="supplementary-material"}); in contrast, in empirical observations, 10.51% of locations from observed experimental data are hotspots. We also find that our null simulation predicts 32% tracks will visit hotspots but our observed tracks show that 51% of observed tracks visit hotspots. These data all support the hypothesis that hotspots exist in empirical observations. We define *hot tracks* to be T cell tracks that intersect with hotspots and *cold tracks* to be those that do not. Hot tracks have median speeds that are significantly higher than cold tracks with hot track speed at 7.27 μm/min and cold tracks at 4.25 μm/min (median speed is 37.4% greater for hot tracks than for cold, p-values \<\< 10^−3^ Mann-Whitney U test). We also find that the step length distributions of hot tracks have a significantly lower skew and kurtosis compared to cold tracks ([Table 6](#pcbi.1004818.t006){ref-type="table"}), indicative of more Gaussian distributions in hot tracks. Furthermore, though the step lengths of hot tracks and cold tracks are both best fit by lognormal PDFs, the Gaussian and Maxwell distributions are nearly as good for hot tracks ([Fig 5A and 5B](#pcbi.1004818.g005){ref-type="fig"} and [Table 6](#pcbi.1004818.t006){ref-type="table"}). These results show that T cells that visit hotspots exhibit different, and more Brownian movement, suggesting that they search more thoroughly than T cells that do not visit hotspots. ![T cells visiting hotspots show a different distribution of speeds than T cells that do not visit hotspots.\ Cold tracks (A) have a speed distribution that is more peaked at low speeds with a more skewed, heavy-tailed distribution compared to hot tracks (B). For fits, see [Table 6](#pcbi.1004818.t006){ref-type="table"}. (C) Visit frequency, or number of observations of hot tracks in hot vs. cold spots. Hot tracks were observed to visit hotspots more than cold spots. The graph shows the distribution of average number of visits by hot tracks to hotspots versus cold spots. Interquartile box plot of the distribution with the red line indicating the median number of visits. Outliers are not shown. \*\*\*\* indicates p\<\<10^−3^ using Mann-Whitney U test.](pcbi.1004818.g005){#pcbi.1004818.g005} 10.1371/journal.pcbi.1004818.t006 ###### Hot and cold track step lengths show different MLE distribution fits. Hot tracks tend to be faster than cold tracks and more Brownian in their movement pattern. The high kurtosis and skew is due to a long tail in the distribution of step lengths belonging to tracks that do not visit hotspots. For hot tracks, skew is 1.45 and kurtosis 6.74; for cold tracks skew is 11.12 and kurtosis 136. ![](pcbi.1004818.t006){#pcbi.1004818.t006g} Hot Tracks Cold Tracks ----------- ------------ ------------- ------- ------ ------- ----------- Lognormal 1.29 0.671 0.752 1.85 0.819 **0.583** Gaussian 1.405 2.504 1.72 4.22 4.53 **22.3** Maxwell 1.48 3.077 8.24 171 Power Law 2.96 2.65 1.21 The presence of hotspots suggests that a microenvironment within the LN might modify T cell behavior. To show T cell adaptation within LNs, we ask whether hot tracks (T cells that have visited hotspots) behave differently in hotspots versus other locations within the LN (cold spots). We find that T cells from hot tracks spend more time in hotspots than in other locations (cold spots), with T cells spending a median of 5.36 time steps in hotspots compared to 4.5 in cold spots (p-values \<\< 10^−3^ Mann-Whitney U test, [Fig 5C](#pcbi.1004818.g005){ref-type="fig"}). T cells that visit hotspots are found in those hotspots between 13.3% and 23.2% (95% confidence interval) more often than they are in other LN locations, i.e. cold spots. Thus, hotspots are visited by more T cells than can be explained by chance, the T cells that visit those hotspots move differently than those that don't, and T cells spend more time in hotspots than in other locations; all suggesting that T cell movement changes in response to the LN environment. Discussion {#sec008} ========== T cell activation depends on interactions between T cells and antigen-bearing DCs in secondary lymphoid organs including LNs \[[@pcbi.1004818.ref009],[@pcbi.1004818.ref017]\]. In this study, we quantify the movement of T cells within LNs, and how efficiently they encounter DC targets (in terms of both unique and total contacts). We use quantitative analysis and computer simulations to show that a search strategy that employs both correlations in successive turning angles and a lognormal distribution of speeds is most representative of observed T cell motion, which we call a LogMCRW. However, T cell motion does not perfectly fit any simple parametric model, and different types of motility are observed depending on where the T cell is and how fast the T cell moves. Accurate characterization of T cell movement is important because motility determines the timing of other immune processes downstream of T cell activation. Several groups have published models of how T cells interact with DCs in LNs. Mirsky at al. \[[@pcbi.1004818.ref048]\] provide a review. Recent data also suggests that motility can affect both T cell recirculation \[[@pcbi.1004818.ref049]\] and T cell dwell time leading to activation especially when detecting rare antigen \[[@pcbi.1004818.ref008],[@pcbi.1004818.ref041]\]. Different studies employ different models of T cell motion due to the lack of precise understanding of how T cells move. For example, some models assumed Brownian movement while another assumed a CRW with a Gaussian distribution of steps and speeds, and yet another uses tracks bootstrapped from empirical data \[[@pcbi.1004818.ref018],[@pcbi.1004818.ref026],[@pcbi.1004818.ref040],[@pcbi.1004818.ref041]\]. Our results show that the LogMCRW pattern of motion not only fits the experimental data, but also most faithfully reproduces the modelled search efficiency of observed T cell movement. We use an agent-based model to compare empirical T cell movement to idealized simulations. These simulations demonstrate that simulated Lévy walks overestimate real T cell search efficiency (for unique DC contacts) while the Brownian walk, CRW, and bootstrap tracks underestimate it. The reverse is true for total contacts. A lognormal distribution of steps combined with correlation among steps (LogMCRW) best represents empirical T cell search efficiency for total and unique contacts. We identify and quantify three mechanisms that increase T cell search efficiency for unique targets: 1) heavy-tailed step lengths (comparing lognormal versus Brownian search accounts for 20%); 2) directional correlation (comparing lognormal vs. LogMCRW accounts for 10%); and heterogeneity among T cells (comparing bootstrap to observed accounts for 10%) ([Fig 4](#pcbi.1004818.g004){ref-type="fig"} and [Table 3](#pcbi.1004818.t003){ref-type="table"}). Thus, computational models allow us to quantify the contribution of a variety of factors to T cell search efficiency. In our study, we thoroughly analyze the motility of naïve T cells in LNs in the absence of antigenic stimulation. Our results largely agree with a recent study by Banigan et al. also showing persistent directional movement for 3--4 minutes by naïve T cells \[[@pcbi.1004818.ref027]\]. T cells have previously been shown to move in "streams", which may correspond to the persistence in movement. Persistence may also reflect cells following a path of least resistance or intrinsic regulation of cell movement, for example, the time required to form a leading edge. In contrast to Banigan, we find a lognormal distribution of T cell steps and show that the heavy tailed distribution of step lengths is important for search efficiency. Banigan et al. also suggested that modeling T cell movement using 2 subpopulations may be a more faithful reproduction of T cell movement in LN \[[@pcbi.1004818.ref027]\]. Our data does not support the existence of 2 subpopulations of T cells. Rather, we find that there may be subregions (hotspots) within the LN that leads to differences in T cell search behavior. T cell motion near hotspots is less directionally persistent and more Brownian ([Fig 5](#pcbi.1004818.g005){ref-type="fig"}). These results demonstrate that T cells react to their environment, and more specifically, they suggest that T cells that visit hotspots stay longer and thus search more thoroughly at those hotspots. The identity of hotspots remains to be determined. It is possible that hotspots are locations of DCs or high endothelial venules from which T cells enter the LN. T cells that search areas with DCs more thoroughly may have more repeated contacts with the same DC as well as contacts with more DCs within the same area, enhancing the potential for productive T cell interaction with DCs presenting cognate antigen. One potential mechanism for hotspots is chemokine production by DCs, although there is no direct experimental evidence for this. Another possibility is that hotspots may reflect an underlying structure such as the fibroblastic reticular cells that may form a network that guides T cell movement \[[@pcbi.1004818.ref050]\]. However, the distribution of our hotspots does not obviously reflect any network structure. Others have tested the potential role of a network on T cell search efficiency \[[@pcbi.1004818.ref011],[@pcbi.1004818.ref051]\] and found that the presence of a network has little impact on T cell search efficiency. Upon activation by cognate antigen, T cell motility within the LN changes, T cells slow down over a period of several hours and begin to form long lived interactions with DCs, essentially ending the "search" phase \[[@pcbi.1004818.ref016],[@pcbi.1004818.ref017]\]. Effector T cells then exit the LN and enter peripheral sites of inflammation. Effector T cell motion in the brains of *Toxoplasma gondii* infected animals was shown to be a generalized Lévy walk based on displacement analysis \[[@pcbi.1004818.ref024]\]. This differs from our findings that T cells in LNs do not fit a Lévy walk. The difference between our findings and those of Harris et al. may result from intrinsic differences between naïve and effector states. Another possibility is that differences between the tissues that the T cell resides in, for example, the LN for naïve T cells or the brain for effector T cells, contain structural and chemical variability leading to different motility. As expected, our simulation shows that Lévy searchers are efficient at finding rare targets, but Brownian motion is more efficient when measuring total contacts. These results show that biological context may be important for T cell search efficiency: in the search for rare and unique antigens, the heavy-tailed search is more efficient. However, in situations where high numbers of DC contacts may be important for T cell activation and potentially survival, Brownian motion has an advantage. The observed T cell motion appears to combine the best properties of each, utilizing multiple modes of motility to achieve efficiency in different contexts. Previous studies have used modeling to reproduce experimental results, and we use this approach to show that the LogMCRW statistical model captures immunologically important properties of T cell search. Similar to empirically observed T cell movement, combining multiple features of random search in the LogMCRW balances search over a wide spatial extent to find unique targets, with thorough search that allows repeated contacts within a cluster. In addition, we extend our use of modeling to identify novel features of the biology underlying T cell movement in LNs. Because the LogMCRW is a good estimate of search efficiency, it also provides a useful null model with which observed T cell motion can be compared, revealing that T cells move differently in different locations in the LN. Thus the statistical model and search efficiency simulations not only characterize cell movement and provide estimates of search efficiency, they can also be used to reveal the complexity of T cell motility. Indeed, comparison to our null model reveals non-random T cell movement which may indicate change in response to some feature of the LN. We find that T cells respond differently to specific microenvironments within the lymph nodes, which we call hotspots. The presence of hotspots suggest that, like foraging animals, T cells may respond to features of their environment in order to guide their search \[[@pcbi.1004818.ref052],[@pcbi.1004818.ref053]\]. Prior work has characterized the movement of foraging animals using both CRW and Lévy walks. Lévy walks in particular have been suggested as optimal to maximize foraging rate \[[@pcbi.1004818.ref002],[@pcbi.1004818.ref016]\]. Our work suggests that in order to balance maximizing repeated (total) contacts with maximizing new (unique) contacts, the LogMCRW may be more effective. More generally, walks with heavy tailed step length distributions and correlation among turning angles may be most effective at balancing the thoroughness and extent of search. In foraging animals as well as searching T cells, natural selection may opt for movement that is effective in a variety of circumstances, even if that movement is difficult to describe analytically. T cells provide a unique window into biological search strategies because so many searchers can be visualized rapidly in relatively intact natural conditions. Such movement patterns can be included in agent-based models, even if they are not easy to present in closed form equations. Our data suggests that the LogMCRW strategy might be a better approach than either Brownian or Lévy walk in situations that need to balance repeated contacts with already-found targets and discovery of new items. Additionally, T search for patchily distributed DCs \[[@pcbi.1004818.ref016]\] in the LN may demonstrate response to cues, similar to other collective foragers such as ants collecting patchily distributed resources in natural habitats \[[@pcbi.1004818.ref054]\]. In contrast to previous assumptions about simple random motion, our analysis shows that T cell movement in lymph nodes is complex, and involves correlation, variation in step lengths, and heterogeneity in response to local environments. The deviation from idealized models reflects the immunological need to balance the spatial extent and local thoroughness of search. The complex movements of T cells in LN provide a window into biological search strategies and how natural selection may balance multiple objectives in a variety of biological contexts. Materials and Methods {#sec009} ===================== Ethics statement {#sec010} ---------------- The protocol was approved by the IACUC at the University of New Mexico (protocol \# 10--100487). The breeding and maintenance of mice used in this research conform to the principles outlined by the Animal Welfare Act of the National Institutes of Health. All efforts were made to minimize suffering with use of ketamine and xylazine when appropriate. Euthanasia was performed by isofluorane overdose. Mice {#sec011} ---- C57BL/6 mice were from Jackson Laboratories (Bar Harbor, ME). All mice were bred and/or maintained in a specific pathogen-free condition in barrier facilities (Albuquerque, NM) and conform to the principles outlined by the Animal Welfare Act and the National Institutes of Health guidelines. T cell observations using two-photon microscopy {#sec012} ----------------------------------------------- Lymph nodes were prepared according to the protocol described previously \[[@pcbi.1004818.ref030],[@pcbi.1004818.ref055]--[@pcbi.1004818.ref057]\]. T cells were purified by nylon wool or by negative selection using the pan-T cell kit (Miltenyi Biotec) as previously described by Cannon et al. \[[@pcbi.1004818.ref028]\] and purified T cells labeled with either 1μM CFSE (Invitrogen) or 5 μM CMTMR (Invitrogen, Carlsbad, CA). 5 to 10×10^6^ labeled T cells were injected I.V. into recipient mice and inguinal lymph nodes were removed 15--18 hours later and imaged using two photon-imaging. Imaging experiments were performed using either a workstation with a Bio-Rad Radiance 2000 scanner mounted on an Olympus upright microscope with a chamber at 37°C or a 2-photon microscope in the Fluorescence Microscopy Facility in the UNM Cancer Center with a mode locked Ti:Sapphire infrared laser (Coherent Ultra II; tunable from 680--1080 nm; avg. power 3.5 W) for multiphoton fluorescence excitation on a Zeiss Axiovert 200 stand. For the Bio-Rad 2P, explanted lymph nodes were placed on a glass coverslip in the chamber. The sample is perfused with a 37°C solution of DMEM (phenol red free, Gibco) bubbled with 95% O~2~ and 5% CO~2~. T cell motility within a lymph node was monitored in the T cell area at a minimum of 50--70μm below the surface of the node. For the Zeiss 2P, the microscope stand is a Zeiss Axiovert 200 with motorized XY stage and IR-corrected long working distance objectives (25X:multi-immersion and 40X:water immersion) and image acquisition via a Zeiss LSM510 scanhead. Ex-vivo tissue and organs are maintained during microscopic observation in a stage microincubator system (LCI-Live Cell Imaging) equipped with heating, humidity, CO~2~ atmosphere and perfusion. Explanted lymph nodes were placed on a glass coverslip in the chamber. The sample is perfused with a 37°C solution of DMEM (phenol red free, Gibco) bubbled with 95% O~2~ and 5% CO~2~. For 4D analysis of T cell motility, multiple stacks in the z-axis (z step = 3 μm) were acquired every 15--20 s (depending on the number of z stacks acquired) for 15--40 min, with an overall field thickness of 40--60 μm. Cell motility was analyzed with Imaris software (version 6; Bitplane). Tracks that lasted fewer than 3 time steps (duration filter in Imaris) were not taken into account in the analysis. Length filter (threshold of 17 μm = 3 times the diameter of the cell) Displacement^2^ filter (threshold of 300 μm^2^ = 17 μm X 17 μm) were also used to discard tracks of non-motile cells. Videos were made by projecting the 4D information along the z-axis in a single plane. The observation area covers approximately two thirds of the T cell zone of the lymph node. Cell motility was analyzed with Imaris 6.0 (Bitplane AG, Zurich, Switzerland). The point sequences generated by Imaris were used to create position vectors joining adjacent cell locations (sample tracks [S1 Fig](#pcbi.1004818.s002){ref-type="supplementary-material"}). The Euclidean norm for each vector was calculated and divided by the time resolution to produce speeds. Distribution fitting {#sec013} -------------------- Following Fisher \[[@pcbi.1004818.ref058]\] we use maximum likelihood estimation (MLE) to parameterize candidate PDFs. We fit probability model parameters using cumulative distribution functions (CDF), rather than by binning data which has been shown to bias conclusions about random walk distributions \[[@pcbi.1004818.ref059]\]. We define a *step* as a vector of T cell motion that does not deviate beyond 15° from the original direction (see [S8 Fig](#pcbi.1004818.s009){ref-type="supplementary-material"} for analysis of threshold dependency). Five PDF models (lognormal, Maxwell, Gaussian, exponential, and power law) for step length and speed were selected for analysis based on a combination of their negative log-likelihood scores, their importance in other biological processes, and their previous use in modeling T cell movement. Our selection of the relative goodness of fit (GoF) of each candidate PDF to empirical data was evaluated using likelihood functions, Anderson-Darling (AD), Bayesian information criterion (BIC), corrected Akaiki Information Criterion (AICc), and the Kolmogorov-Smirnov (KS) test. Following Clauset, Shalizi, and Newman \[[@pcbi.1004818.ref036]\], we fit power laws using MLE and with the power law PDF: $P\left( x \right) = \frac{\mu - 1}{x_{\text{min}}}\left( \frac{x}{x_{\text{min}}} \right)^{\mu}$ where *x*~min~ is the smallest observed value, *P*(*x*) is the probability of *x* occurring, and *μ* is the estimated parameter. We used the *x*~min~ value with the best KS score of all possible choices as an estimator of the beginning of a power law tail. The percentage of positions in a track in the power law tail gives us a measure of the quality of the power law fit. Using this measure we show that a power law fit to the population of observed steps excludes 94% of the data ([Fig 1F and 1H](#pcbi.1004818.g001){ref-type="fig"}). Autocorrelation and cross-correlations {#sec014} -------------------------------------- Velocity autocorrelations were calculated following \[[@pcbi.1004818.ref060]\] and \[[@pcbi.1004818.ref061]\]. The autocorrelation function is the ensemble mean for the *n-1* possible delay times given the *n* vectors defining a T cell track. The result is a measure of how much T cell direction depends on previous directions as a function of time delay. Our use of autocorrelation is distinct from the analysis of periodic velocity vector magnitudes by Beltman et al. \[[@pcbi.1004818.ref040]\], but the similar to that done in Banigan et al. \[[@pcbi.1004818.ref027]\]. Letting *v*(*p*~*k*~(*t*)) be the unit velocity vector at time *t* belonging to the *k*^*th*^ path, we defined the cross-correlation function, C~cross~, to be: C~cross~(*p*) = ⟨*v*(*p*~*k*~(*t*)) ∙ *v*(*p*~*m*~(*t*))⟩, ∀*k*, *m* where *p*~*k*~ and *p*~*m*~ are T cells paths. This measures the step angle dependence between T cell paths at the same moment in time, that is, a measure of drift due to global effects on the observation field. Mean squared displacement {#sec015} ------------------------- Mean squared displacement (MSD) coefficients, commonly called the *α* exponent \[[@pcbi.1004818.ref001],[@pcbi.1004818.ref013],[@pcbi.1004818.ref021]\], were calculated using least-squares polynomial fit by numerically solving the associated Vandermonde matrix \[[@pcbi.1004818.ref062]\] and fit quality assessed with the *r*^2^ measure. Parametric and linear fits were also made to mean displacement. In [Fig 1A](#pcbi.1004818.g001){ref-type="fig"} we present only the first 10 minutes of observation (as was done in \[[@pcbi.1004818.ref016],[@pcbi.1004818.ref063],[@pcbi.1004818.ref064]\]) at which point the curve reaches its first stationary inflection which in \[[@pcbi.1004818.ref061]\] is indicative of unconstrained motion and therefore appropriate for determining *α*. In addition, in this study few tracks persist beyond 10 minutes and so the MSD signal also becomes dominated by noise ([Fig 1A](#pcbi.1004818.g001){ref-type="fig"} top). Heterogeneity {#sec016} ------------- We tested for heterogeneity by comparing track speed skew ([Fig 4](#pcbi.1004818.g004){ref-type="fig"}) and AIC evidence ratios as a function of mean speed. The sample skew of the distribution of speeds was calculated using the method of moments applied to a mean speed sliding window of width 0.125 μm/s progressing in 0.1 μm/s increments. Search efficiency simulation {#sec017} ---------------------------- The simulation to test T-DC interaction efficiency was implemented as a continuous (floating-point) 3D model written in C++. Boost libraries \[[@pcbi.1004818.ref065]\] were used to generate variates drawn from model PDFs. Because the clustering and density of targets can influence which movement types are most efficient, we replicated the estimated density of DCs and varied the degree of clustering in our simulations. We use LN DC density of 2--5% as determined in \[[@pcbi.1004818.ref043]\] to calculate a target DC density of 3.17×10^−5^ targets/μm^3^. Our observed fields have an average volume of 6.3×10^6^ μm^3^. We scale the number of targets as a function of field volume in order to maintain the same target density between simulation fields. DCs were clustered into groups of 10 and were uniformly distributed within spheres defining a cluster. By varying the sphere radius, we controlled the degree of clustering from uniform to highly clustered. A 3D version of the Hopkins statistic \[[@pcbi.1004818.ref066]\] was used to measure the resulting non-uniformity of target placement (Tables [3](#pcbi.1004818.t003){ref-type="table"} and [4](#pcbi.1004818.t004){ref-type="table"}). In the Hopkins statistic scores range from 0 to 0.5 where 0 is highly clustered and 0.5 indicates no clustering ([S5 Fig](#pcbi.1004818.s006){ref-type="supplementary-material"}). T cell tracks were observed and recorded as 3D coordinate sequences within a bounding box defined by the visible section of the *ex vivo* lymph node. Idealized models (Brownian, CRW, Power Law, etc.) of search were parameterized by the speeds and turning angles estimated from observation (see [Distribution fitting](#sec013){ref-type="sec"}). Searchers in the idealized model start at the same initial positions as the observed T cells, and exist in a volume equal to the observed field volume. Candidate search patterns were generated for each of the 41 observation fields. Our efficiency measure is the number of targets found divided by the sum of the time used by searchers. Since we modelled walks rather than flights (i.e. speeds are finite) the sum of D(*k*) for all simulated tracks *k* was limited to the total distance travelled by observed T cells. Therefore the average velocity of the population of searchers is kept within the observed range. Based on an assumed radii of 5 μm for DCs and T cells, targets were marked as discovered if a searcher track passed within 10 μm of a target point. We define two versions of the efficiency measure, one that increments its output value only when a target was not previously detected by that searcher, and another that increments for all targets found. These two versions allow us to record unique contacts and total contacts ([Fig 3](#pcbi.1004818.g003){ref-type="fig"}). The simulation measures the target encounter rate and determines, using the Mann-Whiney test, whether the candidate search models' search efficiency is significantly different from that observed in T cells. We use the Mann-Whitney test because the observed and simulated distribution of efficiencies is non-Gaussian. Simulations were replicated 100 times per field, producing 4,100 efficiency data points for each search model. The entire process was repeated 10 times in order to generate confidence intervals for the simulation; in all this results in 41,000 efficiency samples. Identifying hotspots and hot tracks {#sec018} ----------------------------------- In order to test whether the environment within LNs influences T cell movement we extend an analysis begun in \[[@pcbi.1004818.ref046]\]. Fields were discretized into 8000 μm^3^ cubes (the length of a cube is 20 μm, approximately twice the diameter of a T cell). We use the LogMCRW simulation as a null model and record the number of times a location is visited by unique T cells in simulation (repeated 10 times). We use a 2σ (two-standard deviation) threshold for determining which locations are visited more frequently in the observed fields than expected and call these hotspots. This is repeated for each of the 41 individual observational fields. All other visited locations are called cold spots. A comparison of the number of hotspots in simulation and in the observed data gives an indication of how much behavior is not captured by the simulation. We define hot tracks to be T cell tracks that visit hotspots and cold tracks to be T cell tracks that do not. We also examine the number of visits by hot tracks to cold spots and hotspots. We also examine the distribution of step lengths and speeds for hot and cold tracks. For additional information on methods, see supplementary materials and methods ([S1 Text](#pcbi.1004818.s001){ref-type="supplementary-material"}). Supporting Information {#sec019} ====================== ###### Supplemental Methods. (DOCX) ###### Click here for additional data file. ###### Example of individual T cell tracks. (TIF) ###### Click here for additional data file. ###### Histogram of mean squared displacement exponents with varying *r*^2^ filters. As the linear regression slopes are filtered by the *r*^2^ statistic, the histogram narrows but maintains its mean value. (A) *r*^2^ \> 0, 3.5% of tracks filtered, (B) *r*^2^ \> 0.25, 21% filtered, (C) *r*^2^ \> 0.5, 33%, (D) *r*^2^ \> 0.75, 50%, and *r*^2^ \> 0.9, 69% of tracks filtered out. (E) *r*^2^ \> 0.8 with regions of interest marked. (TIF) ###### Click here for additional data file. ###### **Histogram of power law exponents fit to the CCDF of step length for tracks with varying percentages of their steps in the power law tail: (A) all tracks, (B) tracks with at least 50%, (C) 70%, and (D) 90% of steps in the power law tail.** An increasing fraction of steps in the tail results in *μ* values being more likely to be between 1 and 3 but as a total fraction of all tracks those well fit by a power law falls rapidly, for (A) 35%, (C) 31%, (D) 24%, and (E) 7% of total tracks are represented. (E) Fraction of Tracks with Lévy characteristics. Power law exponents, *μ*, for step length and *α*, for displacement. Tracks are grouped by fit quality (GoF). Retained percentage refers to the amount of data discarded in order to obtain a power law fit (see [methods](#sec009){ref-type="sec"} for *μ* fitting). Displacement *α*, values are filtered by *r*^2^. (TIF) ###### Click here for additional data file. ###### Weibull probability plot. The gamma probability distribution has comparable negative log-likelihood scores to the lognormal distribution (speeds shown here). The lognormal model overestimates the probability of high speeds at the tail of the distribution while the gamma distribution over estimates the probability of very low speeds. (TIF) ###### Click here for additional data file. ###### Sample DC target cluster distributions in simulation. Panel A: 20 μm radius clusters with Hopkins index = 0.2. Panel B: 20 μm radius clusters with Hopkins index = 0.32. Panel C: 40 μm radius clusters with Hopkins index = 0.44. (TIF) ###### Click here for additional data file. ###### Mean squared displacement for simulated search models. Numbers in color indicate the slope of the mean-squared linear fit to the log-log transformed displacement curve. As expected, Brownian motion has a slope close to one, as does the lognormal step distribution model. All other models produce superdiffusive motion. (TIF) ###### Click here for additional data file. ###### We found no evidence of distinct subpopulations defined by variance and mean speed. An expectation maximization Gaussian mixture model finds that clustering tracks according to track speed and track variance results in a single grouping. The color bar and contour map indicate the height of the best-fit Gaussian model. Increasing the number of Gaussians to fit incrementally up to 16 does not reveal any natural clusters. This figure supports the skew plot [Fig 4C](#pcbi.1004818.g004){ref-type="fig"}. Example field (1 of 41). (TIF) ###### Click here for additional data file. ###### The dependency between the angle used to calculate steps from T cell positions and the number of steps resulting. For example at threshold of 180° all steps in each track are combined and the resulting number of steps in the population is small. The influence of the angle threshold on the number of combined positions is smooth. No natural choice of threshold angle is apparent. (TIF) ###### Click here for additional data file. ###### As the number of data points in tracks lasting more than 10 minutes drops, MSD becomes dominated by noise. As a result we perform linear regression only on the first 10 minutes of each track (green line). (1 of 7 datasets). (TIF) ###### Click here for additional data file. ###### Visualization of search tracks. Dark green targets are undiscovered. Targets become cyan if they are within the search volume of a T cell track (detected). In this example targets are grouped into clusters of 10 with radius 10 μm. Each T cell track is assigned a random color to help distinguish them from one another. Example field (1 of 41). (TIF) ###### Click here for additional data file. ###### Distribution of hotspot visitor counts. Spot counts for (A) simulated locations over 10 repetitions, and (B) observed locations. Example plot of observed field and the corresponding simulation (1 of 41). The red lines correspond to the hotspot threshold for this field (μ+2σ of the simulated location visitor counts). For this field the threshold is 4.047. Of the 498 locations in the simulated field 17 (3.41%) are hotspots (mean of 10 simulations). The observed field had 621 locations, of which 78 (12.5%) are hotspots, an increase of 258% over simulation. (TIF) ###### Click here for additional data file. ###### Visualization of hotspots and hot tracks in 4 of 41 observed fields. Hotspots are indicated by black rectangles where the area is proportional to the number of unique visitors. Hot tracks are displayed in color with each color corresponding to a track. Tracks that do not visit a hot spot are shown in grey with the shades corresponding to individual tracks. Plots are a projection of a 3D space into the xy-plane. Overlapping hotspots indicate distinct z-coordinates. (TIF) ###### Click here for additional data file. ###### A potential source of error is the dependence of the observed speed on the frame rate of observation. We test whether this confounding factor exists in our experiments by fitting a linear model to the mean speed for each of our seven binned microscope video frame rates vs the observed mean speed. Our frame delays range from 13 s to 20.7 s. The slope of the best MLE fit is 0.0013. The p-value is 0.66 and the *r*^2^ is 0.041. Together this suggests there is no relationship between frame rates and observed speed and that the observed speeds are not artifacts of the measuring rate. (TIF) ###### Click here for additional data file. ###### Video of the simulation in progress. The video shows four instances of the efficiency simulation 1) An observed field, 2) Brownian motion simulation, 3) Power Law simulation, and 4) LogMCRW. Individual T cell tracks are variously colored according to track. Target DCs are green initially and turn cyan when encountered by a T cell. (MP4) ###### Click here for additional data file. ###### Extended step fit statistics. Table shows the Akaike information criterion evidence ratio (AIC E), applied to first 7 rows only; the corrected Akaike information criterion (AICc); negative log-likelihood (nlogl), Kolmogorov-Smirnov (KS), Anderson-Darling (AD), chi-squared (χ2), and Bayesian information criterion (BIC). Score ranking is in parentheses. Differences in BIC and AICc scores are less than 1:103 of the AICc score. (DOCX) ###### Click here for additional data file. ###### Extended speed fit statistics. Table shows the Akaike information criterion evidence ratio (AIC E), applied to first 7 rows only; the corrected Akaike information criterion (AICc); negative log-likelihood (nlogl), Kolmogorov-Smirnov (KS), Anderson-Darling (AD), chi-squared (χ2), and Bayesian information criterion (BIC). Score ranking is in parentheses. Differences in BIC and AICc scores are less than 1:103 of the AICc score. (DOCX) ###### Click here for additional data file. ###### Maximum likelihood estimated parameters and associated likelihood scores for steps calculated using a 30° threshold. The lognormal probability distribution is still the best fit when steps are calculated using a 30° rather than 15° threshold. Compare to [Table 1](#pcbi.1004818.t001){ref-type="table"} in the main text. (DOCX) ###### Click here for additional data file. Thanks to François Asperti-Boursin for data collection, T cell tracking, Imaris analysis and discussion. Thanks to Christian Gunning, Helen Wearing, David Ackley, Vasudev Kenkre, Stephanie Forrest, Aaron Neumann, Deborah Gordon, Brianna Mulligan, and Grant Lythe for helpful discussion and reviews of this paper. Thanks to Genevieve Phillips and Becky Lee of the UNM Cancer Center Fluorescence Microscopy Facility as well as John Connor and Denis Bragin of the BRAIN Imaging Center for help with 2-photon microscopy. [^1]: The authors have declared that no competing interests exist. [^2]: Conceived and designed the experiments: GMF JLC MEM. Performed the experiments: GMF JLC. Analyzed the data: GMF KAL JLC MEM. Wrote the paper: GMF MEM JLC.
Mid
[ 0.6247191011235951, 34.75, 20.875 ]
By now, you’ve heard the praise, the fervor, and the cries of sore losers everywhere. But the hype for this one really is deserved. Cuphead is a magnificent blend of gameplay taken from Contra, Gradius, and even some Mega Man for good measure. And while many games have done so, Cuphead is one of the ones that stands out from the crowd. If you haven’t already bought, and downloaded this game to your Xbox One or Computer you really ought to. But if you need more details before doing so, read on. GENERATIONS: The animation on display will even amaze your Great Grandparents. Cuphead is the result of a couple of high-risk takers. Studio MDHR started out with a vision: An action game that truly feels like playing a late 1930’s cartoon. Early on they discovered that making that vision a reality was going to be far more time-consuming, and expensive than originally thought. They ended up quitting their jobs, and re-mortgaging their homes just to be able to bring this title to market. My hope is that this risk has paid off. Because the finished product is nothing short of amazing. Cuphead very likely has the best animation of any video game ever made thus far. Studio MDHR painstakingly made every background in the game by matte painting it. Every frame of animation was hand drawn on a cell before being scanned into a computer to be inked, and colored. As a result the game delivers on the core promise of looking, and feeling like a 1930’s animated short. The character designs are breathtaking. All of the hallmarks of vintage cartoons are here. The angled pupils, exaggerated movement, and pretty much everything you can recall from old Popeye, and Betty Boop serials are here. Studio MDHR even went as far as hiring an actual big band jazz ensemble to write, and perform the score for Cuphead. So not only does it look like an 80-year-old cartoon, it also sounds like an 80-year-old cartoon. Just seeing the game in action alone would be worth the price of admission. There is such a wealth of talent on display through the entire game that it’s honestly something that has to be experienced. In the realm of audio, and visual experiences Cuphead is nearly in a class all by itself. But what about the game play? Well, it’s a fairly solid, and enjoyable experience. The game starts out with a very clever tutorial, and a classic story book introduction. Cuphead, and his brother Mugman go against their guardian’s wishes when they visit a casino. Unfortunately, the Casino is owned by the Devil, and he rigs the game at the Craps table to claim the souls of our heroes. But they plead for their lives so he tells them he’ll forgive their debt if they go get the soul contracts of the others in the town. So that’s the set up for just why Cuphead, and Mugman are off on their adventure. The game places you on an overhead view of a map, where you move the characters around, and choose a stage, or talk to an NPC. There are three maps, and you’ll need to complete every stage to move onto the next one. Each map also has a shop in it where you can use coins to upgrade your abilities. There are three main types of stage on display here. You’ll have Run n’ Gun stages. These play like you’d expect, taking homage from games like Contra, and Metal Slug. So you’ll have to fire where you’re going. You can’t shoot backwards while moving forward. The game play is not a twin stick style, rather a more traditional one. In these stages you’ll find the aforementioned coins. So you’ll certainly need to play these if you want any hope of buffing up your character. Some of the items in the shops will give you a new style of weapon, or extra hits on your health meter. But any item you choose will have a side effect to balance things out. For instance, buying extra health comes at the cost of weakening your attacks slightly. But there are a wide variety of things to check out here. So you can swap out items for others after you’ve paid for them, and see what load out works best for you. There are shmup levels too, these generally play like the third type of stage I’ll get to in a moment. The difference being here, you’ll be piloting a plane, and fighting a multifaceted battle against a boss character. With the shmup mechanics here, the game feels a lot more like the memorable moments in old horizontal shooters like Thunder Force III, R-Type, Gradius, or Life Force rather than the more contemporary bullet hell shooter. Just because there aren’t zillions of things to avoid doesn’t mean there isn’t anything to avoid. These encounters throw plenty enough at you, and you’ll have to memorize attack patterns to survive. You can also shrink your plane so if you get into a situation you don’t think is avoidable, it may just be your ace in the hole. Finally, there are the Boss stages. In these you’ll use the Run n’ Gun mechanics in a multifaceted battle against a boss character. These fights feel closer to the classic NES Mega Man boss fights. than the ones in the old Run n’ Guns. One boss in particular will give you memories of storming Dr. Wily’s castle in Mega Man II. All of these bosses however will require you to learn patterns, and expert timing to get through them in one piece. Since most of the stages in the game are Boss stages you can expect to lose many, many times when you first attempt them. There are also a couple of side challenges where you’ll free ghosts by parrying other ghosts. You should honestly do these because the parry is a mechanic Cuphead uses to beef up your super meter. When you fill up the meter you can do a very devastating attack which is especially handy in boss battles. Anything colored pink in the game can be parried, and these challenges are the perfect way to master this mechanic. Most of the stages in the game have an easy mode in addition to a regular tough as nails mode. You’ll need to beat the harder difficulty on bosses to get the contracts, needed to finish the story. But playing the stages on Easy will let you progress, and see what future stages have to offer. You can also go back to any stage you beat previously to replay it. Cuphead definitely has a high level of challenge. But the challenge is generally very fair. You’ll die hundreds of times over. But upon your expletive laden loss you’ll understand that your last death was your own fault. You jumped when you meant to shoot. Or you didn’t plan for a moving platform properly. Or you weren’t patient enough. Or you panicked, and walked into that projectile. Cuphead isn’t impossible though. Those who absolutely love old platformers, shmups, and classic action games from the days of Atari, Sega, Nintendo, and Commodore platforms will likely pick things up a bit faster. But that doesn’t mean someone newer to this type of experience cannot persevere. It’s the kind of game that requires patience, and practice to excel in. For some players it may take more time, and patience than others. But everything in the game is so captivating it’s worth checking out. There are a couple of very minor issues I have with the game though. The most alarming are a few rare bugs. Admittedly these are rare, and in time they’ll probably be fixed. But they’re still a nuisance when they happen. One of them will glitch a low-level enemies’ health to a point it takes no damage. When this happens you can try to just skip past it. But that might mean you take damage in the process, and impede your ability to clear the level. Exiting the stage, and re-entering it usually fixes it in the interim, but that is also a nuisance. The other bug I’ve run into is an inexplicable performance hit, where the game will suddenly drop frames, and run ridiculously choppy for around 60 seconds before going back to normal. It’s especially annoying in boss fights. Closing the game, and re-starting the application again, fixes it in the interim. But it can be pretty annoying. I also wish there could have been a few more action stages over boss rush stages to add to the variety. Nevertheless, I can wholeheartedly recommend Cuphead to just about anybody who is even remotely interested in it. The animation, and soundtrack alone are worth the price of admission. Even for all of the complaints some may have with the level of challenge, the experience easily overshadows that. This is a game that is a wonder to behold. And while old-school arcade challenge may not be your Cuphead of tea, (I know, that’s a terrible joke.) Cuphead is still one of the most entertaining experiences you’ll likely have this year. If you relish a challenge, and love classic cartoons you should buy this for your computer or Xbox One if you haven’t already. You may want to look into this game even if you normally don’t care for this sort of fare. The amount of talent, and dedication on display is nothing short of captivating. Here’s hoping Cuphead was a successful enough endeavor for a follow-up, or another game using the same wonderful artists, and animators. I know I’ve repeated myself a lot in this review, and I probably sound a bit redundant. But win or lose, Cuphead is one experience you just may want to roll the dice on. (I think I did better on that one.) Anyway, as we all know, knockoffs are nothing new. We see them in everything. Everyday household items. Appliances, and of course creative media. Including obviously, video games. Over the last thirty or more years we’ve seen Pac-Man clones. Space Invaders clones. Super Mario Brothers clones. Street Fighter clones. Doom clones. Basically, one could spend a lifetime talking about the concept alone before even getting to the examples. Some of which I’ve already reviewed. Many knockoffs aren’t worth a second thought. But as Mortal Kombat, Saints Row, and others have taught us, sometimes they are. Taking a proven formula, and putting their own spin on it. PROS: Nice graphics. Decent mechanics. Controls well. CONS: Saves can’t be brought to another system. Unbalanced. CAPTAIN PLANET: He’s our hero! Going to take pollution, down to zero! Cartoon Network Punch Time Explosion XL does just that. This time the target is Super Smash Bros. The SSB series looks like it can easily be copied at face value. The core concept of keeping combatants off of your hill or out of your ring seems simple. You have a cast of characters who are unique, yet share a simplified movement set. Moving beyond that, Smash has also employed campaigns in past games. Such as Melee’s Adventure Mode, or Brawl’s Subspace Emissary Mode. Smash has a ton of different items you could add in for random fun. Or assist trophies, that enable NPCs to help you win. Nintendo’s series even has a lot of individual mini game challenges throughout the series from target smashing, to sandbag beating. All with mechanics that hyper-competitive players find quite deep. Today, the series has hardcore fans, and countless tournaments where the best players win enough cash to live on. It’s one of the most watched series on Twitch. Its reputation has reached the heights of games like Street Fighter, and Tekken. To say that CNPTEXL has some lofty goals is an understatement. Does it get anywhere near the pedigree of Nintendo’s mascot party fighter? No. But is it a bad game? Shockingly, the answer is also no. This game takes Nintendo’s approach to mascots, and applies it to Time Warner’s Cartoon Network. The game was published a bit before the channel’s power houses Adventure Time, and Regular Show. So you won’t be playing as Benson or throwing down with Finn. However the game’s roster does go pretty far back to the channels early days. Dexter’s Lab, The Power Puff Girls, Samurai Jack, and Johnny Bravo all make appearances with many of their characters. Some of the later hits like Ben 10 & The Grim Adventures of Billy, and Mandy are here. And even some of the lesser known shows are represented. The game has a campaign mode in the vein of Super Smash Bros. Brawl’s Subspace Emissary mode. The story is told by a narrator (Voiced by Space Ghost’s George Lowe), which follows the convergence of all of Cartoon Network’s shows. This follows a formula similar to Brawl’s. You will go through side scrolling platformer stages with brawler elements. Depending on the stage, you can use a certain number of characters. When you get to the end of the campaign it is revealed that the narrator’s TV remote has gone rogue, and is responsible for the merging of the realities. Of course, this remote is the final boss. Along the way you’ll also unlock characters for you to use in the other mode. Again, much like the Subspace Emissary. The difference is that you use currency to do it. CNPTEXL has a Store option where you will find not only the bonus characters, but stages, alternate costumes, and clips from the various Cartoon Network shows. Clearing the game or playing enough in the other modes will give you points that can be used to unlock them. Once unlocked, the characters, and stages can be used in the Story mode or the Battle mode. There is a vault where the unlocked clips can be viewed, along with the character models. It works kind of like a cut down version of Smash’s trophy room. You can get info on the characters, what shows they belong to, and their original appearances. It isn’t nearly as deep as what you will find in Nintendo’s games, but it still gives you something to look forward to if you are a fan of the CN shows. The clips are DVD quality, and most of the clips are from some of the better shows’ moments. The meat of the game is in its multiplayer. Battle mode is up to four players, and also allows you to use a variety of controllers. If you’re playing the Wii version you can use the Wiimote, and Nunchuck. Or you can opt for either a Classic Controller or a Gamecube Controller. As I’ve mentioned before, the core concept of CNPTEXL is the same as the Nintendo franchise it cribs from. Each of the game’s 26 stages will see players trying to keep each other off of the arena. You do this by attacking one another, to build up damage. The more damage you take, the farther you are knocked back with each successful hit. Each stage has a knockout zone around it. Going beyond it, or being unable to otherwise make it back to the arena results in a death. The object of course is to be the last one with any lives left. The game plays as one would expect. There is a primary attack button, a special move button, a shield button, and a button for your finishers. Each of the main three buttons can be combined with directions. So as in Smash, you can get different moves based upon what direction is used with each. It also has smash attacks of its own. So pressing a direction with the attack button at the same time will dish out more knock back. The shield also allows you to roll out-of-the-way, and perform parries as in Smash. Many of the tactics employed in Smash like edge guarding can also work here. Even holding the shield for too long will break it, leaving you open to punishment. The finisher button is novel too in that you don’t have to chase down a smash ball. The one thing this game does to carve itself out a niche is the use of a gem system. Beating up on your opponent will cause them to drop gems. Collect enough of them, and you can use your finisher. Most of the finishers are pretty cool, and have anime inspired animations leading up to the attack. In addition to the primary battle mode, there are a handful of variants. Choosing a custom match is similar to the way custom matches in Smash games work. You can turn assist trophies on or off, set the frequency of items, and set the time limit or number of lives. It does not let you go over each individual item however. Beyond the custom mode, there is a mode called Drones where the game will throw a bunch of NPC enemies into the match. Instead of scoring you on stock or knockouts, it instead scores you on whoever defeated the most computer controlled combatants. There is also a variant called PTE mode, where you collect energy orbs. Think of it like the coin mode in the Smash series. Finally, there’s the arcade mode. This plays like the arcade mode in Smash. The game puts you in a ladder, against other combatants, and you’ll get a different ending for each character you beat the mode with. As far as the look, and sound of the game go, the visuals are pretty nice, while the sound isn’t. All of the characters models look pretty good considering Papaya’s probable budget constraints. Backgrounds aren’t very detailed. Muddy textures cover most of the background objects, and small details are lost in the shuffle. Although one has to be impressed with some of the destruction, and transition that goes on in certain stages. Again, the finishing moves are actually pretty impressive. Especially if you’re a fan of some of these old shows. Audio is lackluster however. Aside from the voice samples, and quality during the unlockable clips, there isn’t much to recommend. Music isn’t all that memorable, and none of the effects will really wow you. Despite all of the similarities with Nintendo’s games it still doesn’t hold a candle to Super Smash Bros. That’s the biggest trouble with Cartoon Network Punch Time Explosion XL. The roster isn’t as large, and as great as many of these shows were, it simply isn’t as fun to pick up Johnny Bravo, as it is to pick up Donkey Kong. What’s worse is that the roster you do get isn’t really all that balanced. There are a handful of characters you’ll stick with if you do decide to play this with friends even remotely regularly. While every fighting game ends up with one or two characters that have more versatility, the best fighters still make everyone viable. This game really doesn’t. It was clearly made to be a Smash clone for people on a budget. Or at least for Cartoon Network fans who couldn’t get enough Smash-like experiences. Unfortunately while it does succeed on those merits, it won’t succeed in keeping you away from Nintendo’s franchise for very long. The fact you can’t unlock everything on your own, and bring it to a friend’s is disheartening too. Especially since, at least on the Wii, you can back up your save file to an SD card. Still, if you do like some of these classic cartoons, you might want to check the game out anyway. It is by no means a terrible game, and it is a fun ride as far as licensed games go. But you aren’t going to drop Super Smash Bros. for this. Nor are you going to fool yourself into thinking you’re playing Super Smash Bros. if you pick it up on the Xbox 360 or PlayStation 3. It’s average. But sometimes that’s enough. This year was packed with a large amount of guests, activities, and panels. So many in fact, that it was impossible to see everything between the variety, and overlap. Still, I just like to recap my convention experiences. I always have a lot of fun, getting to go to panels, talking with other fans, and taking in a really great meal. Some of the highlights for me over the weekend began almost immediately upon arrival. One of the first events I attended was an Epic Rap Battles Of History event. Some of the most notable episodes were played on a screen. After each one of them the hosts of the event, and the fans in attendance debated which characters won. Historical Accuracy, the number of good insults, rhythmic flow, were all factors in picking a winner. A large number of attendees loved the He-Man costume I roamed about the convention center in. I probably stopped every 15 minutes or so, so that someone could take a snapshot. It was more over than my Dr.Insano cosplay from last year, and that had gone very well. But there were far many more impressive costumes than mine. One of the best moments was when Alan Oppenheimer’s booth assistant saw me coming down the aisle. Then proceeded to put her head face down on her arm on top of her table, and laugh. But both Mr. Oppenheimer, and his assistant were very kind, hospitable, and friendly. Of course Masters Of The Universe was a huge part of my childhood. So meeting the guy who provided the voices of many of its most iconic characters like Man At Arms, and Skeletor was a really awesome moment for me. I also got to see Alan Oppenheimer, and Noah Hathaway talk about their time working together on The Never Ending Story, and other projects in a panel together. Like many of the various panels I attended it was pretty informative. Noah talked in-depth about how the scene where Artax dies in a swamp was done, taking several shoots on a giant sound stage. The stage had a lowering platform for the horse to simulate sinking, and was covered in mud. The set designers also brought in the trees, and other props for the scene. He also talked about leaving, and returning to acting, as well as the fun of nitpicking movies. Alan also talked a lot about voice acting, and the importance of being able to visualize a voice for a character. He also talked about using traditional acting techniques in voice acting. Notably, how much of acting is actually listening to the other performers in any given scene. Like last year’s ConnectiCon, Doug Walker was in three panels. Doug is best known for his long running Nostalgia Critic web show. The first panel was on Friday, and it focused on how to better debate movies with other people by listening. The set up, was that each of the attendees in line would bring up a movie they loved that the internet at large seemed to hate, or vice versa, and why. The point of the exercise was to show how much you could learn about someone in just hearing why they did or didn’t like a movie. It also made for the argument that you can have a strong opinion about a film, and still remember that that’s ultimately what it is: An opinion. Often times we can forget that when we talk about pop culture. We may have all of the evidence in the world that a movie is bad, and justify our opinion. But someone else is going to like it anyway, and it doesn’t make them terrible for doing so. In fact, really listening to someone’s opposing point of view may bring out some interesting things you may not have considered. Doug was also part of a web series roundtable panel with Marble Hornets, internet comedian Uncle Yo, and Signal Crash. This Q&A session was geared more toward production of content. Advice was given to creative people in attendance. What kinds of techniques to use in any given craft. What avenues to take in furthering a goal. But there was also the rather frank theme of doing what one loves because they love to do it above all else. Not only from Doug Walker, but from all of the members of the panel. It was an encouraging panel that acknowledged challenges, acknowledged that there will be rejections, and failures. But it also left a theme of persistence, and sense of pride in whatever our passions are. Whether we ever get to do them professionally or not. Of course there was also the That Guy With The Glasses panel in which Doug, and Rob Walker fielded questions of all kinds. As in the roundtable, some of the questions were about production, promotion, and professionally furthering one’s creative output into a business. Others were about the content of the TGWTG flagship series. Then there were other moments that came out of left field. One fan brought in a script, and wanted the Walkers to produce. They couldn’t do that, but they did recite the first page in the voices of Chester A. Bum, and Jeff Goldblum. At one point during the panel the Nostalgia Chick herself; Lindsay Ellis showed up with the rest of Chez Apocalypse. Posing as a con goer, Lindsay asked Doug when Nella (of Chez Apocalypse) would be getting top billing in lieu of the Nostalgia Chick. Fans cheered as Lindsay, Nella, and Elisa would celebrate the run in during their exit. Chez Apocalypse were also part of another panel with other internet media creators including members of Steam Funk Studios, and Overclock Remix. Similar to some of the other panels, it was a Q&A session filled with some insight into the guests’ creative processes, how they keep things fresh, and how they handle criticism. There was also a lot of advice given to the audience at hand. The biggest piece being perseverance. Being able to see where one began, and the level of improvement over time as a driver to keep going. Actor Walter Jones was also at ConnectiCon. Most know him as the Black Ranger from the original Mighty Morphin Power Rangers show. He talked about his life growing up in Detroit, Michigan. His early days working as an entertainer on cruise ships, and of course his time on Power Rangers. He joked about how difficult the helmets were to see out of at times. He described some of the impressive stunts he did during shoots only to have parts lost during edits. He was also asked if he had seen himself as a role model for African-American children by someone in attendance. He told the audience that he saw himself as a role model for all of the children watching the show, and that nobody in the cast risked doing anything to jeopardize that. When asked if he would ever return to Power Rangers, he said it would be an option provided it would be backed by The Writers Guild Of America. The original show wasn’t, and it was the main reason he left after the Mighty Morphin era of the series ended. Another person asked if he still talks with the rest of the cast, and he replied that he did from time to time when schedules line up. He added that he actually knows some of the cast members from other iterations of the series. It was an intriguing panel even if you weren’t a Power Rangers fan. I also found my way into a Cosplay Court event during the convention. Hosted by Steam Funk, it played a lot like a small claims court show like The People’s Court. The spin on it was that everyone in the room had to play in their cosplay character. Audience members were chosen for the character on trial, prosecution, defense, and even the witnesses. In one case I was called to the stand as He-Man, and was cross-examined by a cosplayer who was The Mad Hatter from American McGee’s Alice. In one case a Mario cosplayer was on trial for the extermination of the Koopa race, as well as the Mushroom Kingdom’s citizens. Another case was against Frozen’s Elsa, and of course there were many Disney themed cosplayers involved. Including a pretty good Ursula of The Little Mermaid fame. Voice actors Maurice La Marche, and Rob Paulsen also had two events. I managed to get into the second one. It was a Pinky & The Brain Q&A, and it was certainly one of the highlights of the convention for me. Nearly the entire session was done in character. Both actors talked about many of the shows they’ve done over the years, in addition to a lot of the cartoons that inspired them. There were some zany moments too. One member of the audience wanted Maurice to determine if a photo of his daughter looked more like him or his ex-wife. There was another point when someone had asked P&B which fan was the worst they had experienced. Maurice pointed into the front of the crowd saying “That guy right there.” to which the crowd erupted in laughter as it was revealed to be Doug Walker. Doug pretended to fail to be conspicuous while walking to an exit that turned out to be a hall filled with chairs. He then sheepishly walked back to his chair. Later in the panel, the two actors actually listed Doug in a list of some of the most pleasant entertainers they’ve known over the years. A list that included names like JonLovitz, and Steven Spielberg. I was also lucky enough to catch a Voice Actor roundtable near the end of the final day of the convention. Lauren Landa, (Dead or Alive 5, Attack On Titan) Danielle McRae (League Of Legends, Skullgirls), Chris Cason (Dragonball Z), Brittany Lauda (Prince Adventures) were on hand to make for a nice sendoff. All of the guests were laid back, very friendly, and were funny. As with all of the previous panels fans asked the panelists what some of their favorite works were. What some of their dream roles would be, and some of the things voice acting entails. Speaking of interesting people, I do want to give a shout out to Jenisaur, a blogger who introduced herself to me at the convention. She writes over at http://www.sub-cultured.com/ about all kinds of things. Comics. Conventions. Novels. You name it. If it sounds interesting to you, check it out. There were a lot of other panels, and events I missed that I would have loved to have seen. But you can only get out to so many over the three days. I would have loved to have made it out to the Jennifer Hale panel. She has done so many interesting video game, and animated television roles over the years. I also missed seeing Ellen McLain, the voice of GLaDOS from the Portal series. Her husband John Patrick Lowrie was there with her, and he’s done voice work for Half-Life 2. Hearing a bit about voice work for Valve would have really been a blast for me, and sadly I had to miss them. TV’s Diedrich Bader was there too. I also had to miss his panel. I did get to see him for a split second roaming the dealer’s room, and shared a very brief “Hello”. I loved seeing him on The Drew Carey Show back in the day, and his role in Office Space was pretty great. Apparently he has done a myriad of cameos, and voice work that I never knew about. Alas, another interesting panel I missed out on. Others I missed? TeamFourStar was there. There was a Cards Against Humanity panel. There’s just so much to do, and so little time. But I suppose that’s a testament to just how much there is to do every year. Cosplay death match, creative workshops, heavily discounted movies at the theatre across the street. Video game tournaments. Table top game tournaments. Japanese import rhythm arcade machines. Swag. Obviously the panels. It really is a great time, and I love it when I attend it. I can’t wait to see what next year brings. Plus there’s always City Steam Innocence IPA waiting for me a mere two blocks away.
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This story made me smile! Here's the full story!! Garvin Teens battling chronic illness got the chance to experience all the glitz and glamour of prom night, thanks to a Florida hospital that was determined to help their patients experience all the normal milestones of growing up. Load Error 17-year-old Ruby Troche, who was diagnosed with gastroparesis, was one of the many extended-stay patients at the Arnold Palmer Children’s Hospital in Orlando in attendance. “I missed most of the major high school events that go on in my high school because I’m here most of the time,” Ruby told InsideEdition.com. “It gave me the chance to socialize with everyone else and feel comfortable knowing that people there had similar medical experiences as me.” According to event coordinator Amanda Harris, the hospital brought in DJs, set up a dance floor and rented a photo booth for the big day. “Just because you’re feeling sick doesn’t mean that you don’t get to do the things all your friends get to do,” said Harris, according to the hospital. “It’s just like a prom that you would see at any high school.” Patients who were in the hospital in the last year were invited to attend, and allowed to bring a date. Parents were invited to a special dinner on the other side of the hospital, where they could be present while giving the teens their privacy. Ruby explained she was diagnosed with the condition more than a year ago, and would frequently be admitted into the children’s hospital for stays of up to two months at a time. Like many other patients, she missed most high school events or did not know her classmates well enough to participate in the ones she could attend. She said it’s always been her dream to go to prom, and even though she’s not sure whether she would make it to her own, Ruby said she’s glad to have participated in the hospital’s celebration. “I could feel the happiness and joy in the air, everyone was excited to be there,” Ruby said. “Having this happen just made me really happy I got to experience it with all the people I see most of the time in the hospital.” I have the 14.5 WSM and was going to give to my dad but he surprised me by saying he was satisfied with his Weber kettle and roti! I still haven't decided if I will keep wsm and use grate or sell it and find another way to get grate. Remember you own a Akorn you can use Kingsford or something close to that to use in the Akorn! I use both lump and briquettes but find in my Akorn the briqs work best and get a constant long burn!! Garvin White Chocolate Mousse Servings: 1 INGREDIENTS 8 egg yolks ¼ cup sugar 1½ cups heavy cream (for the eggs) 1½ cups white chocolate (over 30% cocoa butter) 2 cups heavy cream, chilled (for whipping) PREPARATION In a large bowl, beat the egg yolks with a hand mixer until frothy and airy, then mix in the sugar slowly. Beat until lemon-colored and fluffy. Heat the cream in a pot over medium heat until steaming but not boiling, then slowly mix in half of the cream with the eggs – being sure to not cook the eggs by pouring too much cream inside before it’s mixed. Pour the warm creamy egg mixture into the pot with the rest of the cream and cook over low heat, stirring constantly until the mixture has thickened enough to coat the back of a spoon without dripping off too much. Mix in the white chocolate until smooth, then transfer the mix to a bowl and press cling film into the surface to prevent a skin from forming. Chill completely. Once the white chocolate mixture is set, beat the cold cream in a large bowl until stiff peaks. Be careful not to overmix, it’s safer to undermix than the over mix. Carefully fold in the white chocolate mixture into the cream, a little at a time, until folded in completely. Set aside for later use. Mirror Glaze Servings: 1 INGREDIENTS 300 milliliters water 1½ cups sugar 1 14-ounce can sweetened condensed milk 15 gelatin sheets 26 ounces white chocolate, chopped (over 30% cocoa butter) Gel food coloring of choice PREPARATION Boil the water, sugar, and condensed milk in a pot for 1 minute, then remove from heat. Bloom the gelatin in 8 cups of cold water for 5 minutes, then wring the gelatin sheets of excess water and mix into the sugar mixture. Pour the liquid over the chocolate, letting it sit for 2-3 minutes to allow the chocolate to soften. Using an immersion blender, carefully blend the chocolate and the liquid, making sure that you are not blending in air bubbles by lifting up the blender too high. It’s okay to go slow, just make sure it’s all blended with as little bubbles as possible, which will show up in the final product. Sieve the mix into a large jug or vertical container to remove any excess bubbles. If there are still bubbles, continue to sieve back and forth. A trick to remove air bubbles from the surface is to manually pop them with a toothpick or to press cling film into the surface and remove the bubbles. Separate the glaze into different containers and color them to your desire. We used red and white for this cake. Blend the coloring with the glaze until the color is distributed evenly, then cover each container with the cling film, pressing the film into the glaze to ensure that there is no skin when you are ready to use the glaze. When you are ready to use the glaze, make sure each one is around 90-96°F, then pour the colored glazes back into one container. Swirl them if you’d like, then glaze your cake! Mirror Glaze Cake Servings: 8-10 INGREDIENTS 1 recipe White Chocolate Mousse 18 ounces strawberry jam, seedless 2 round vanilla cakes, prepared with box instructions and trimmed to 1 cm thick 1 recipe Mirror Glaze PREPARATION Spread the jam evenly into the bottom of a round 8-inch cake pan, then place one of the cake rounds on top. Freeze completely. In a 9-inch by 3-inch silicone round cake mold, pour ⅔ of the chocolate mousse then tap the mold on the table to release any air bubbles. Place the frozen cake & jam disc on top of the mousse, jam-side down. Press the cake down slightly, then cover it with the rest of the mousse. Place the 2nd cake round on top, pressing down until the mousse rises to the level of the cake. Carefully transfer to a freezer and freeze overnight. It is vital that the cake is 100% frozen through. Place a can on top of a baking sheet, then carefully unmold the cake onto the can. Make sure to work quickly and that the glaze is already prepared. When the mirror glaze i Garvin
Low
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Q: How to insert and update bulk data From one DB to another There are two DBs on different servers. I want to run a procedure once a day so that I can get updated records. If it already exists then it should update, else insert a new row. So far I did it like this: if not exists (Select emp_id From DB1.dbo.Emp_Master where emp_code = (Select pk_emp_code From DB2) Begin INSERT INTO DB1.dbo.Emp_Master(emp_code,emp_name,emp_dept ,emp_desg ,emp_mob ,email_id,emp_dob,emp_doj) Select pk_emp_code,first_name+ '' +last_name,dept.dept_desc, desg.desig_desc,office_phone,email,REPLACE(CONVERT(NVARCHAR,CAST(dob AS DATETIME), 6), ' ', '-') , REPLACE(CONVERT(NVARCHAR,CAST(doj AS DATETIME), 6), ' ', '-') From DB2 Select 1 END ELSE BEGIN UPDATE DB1.dbo.Emp_Master SET emp_name=first_name+ '' + last_name,emp_dept=dept.dept_desc,emp_desg=desg.desig_desc, email_id=email,emp_mob=office_phone,emp_dob=REPLACE(CONVERT(NVARCHAR,CAST(dob AS DATETIME), 6), ' ', '-'), emp_doj=REPLACE(CONVERT(NVARCHAR,CAST(doj AS DATETIME), 6), ' ', '-') FROM [DB2] where emp_code =pk_emp_code Select 2 END I am getting error SubQuery return more than one value What's gone wrong? A: It's this part that returns the error (inside your IF NOT EXISTS): Select emp_id From DB1.dbo.Emp_Master where emp_code = (Select pk_emp_code From DB2) There is no correlation between the inner and outer query. A possible rewrite is along these lines: Select emp_id From DB1.dbo.Emp_Master where emp_code IN (Select pk_emp_code From DB2) Moreover, the check you're doing at the very beginning of your code will skip inserting all the rows if any of them matches. I suppose that what you want to do here is an upsert (if matched updated, if not matched insert). You can do it with the MERGE statement or with something like this: IF OBJECT_ID('tempdb..#updatedRows') IS NOT NULL DROP TABLE #updatedRows; CREATE TABLE #updatedRows ( emp_code int PRIMARY KEY CLUSTERED ); UPDATE DB1.dbo.Emp_Master SET emp_name = first_name+ '' + last_name, emp_dept = dept.dept_desc, emp_desg = desg.desig_desc, email_id = email, emp_mob = office_phone, emp_dob = REPLACE(CONVERT(NVARCHAR,CAST(dob AS DATETIME), 6), ' ', '-'), emp_doj = REPLACE(CONVERT(NVARCHAR,CAST(doj AS DATETIME), 6), ' ', '-') OUTPUT INSERTED.emp_code INTO #updatedRows FROM [DB2] WHERE emp_code = pk_emp_code; INSERT INTO DB1.dbo.Emp_Master( emp_code, emp_name, emp_dept, emp_desg, emp_mob, email_id, emp_dob, emp_doj ) SELECT pk_emp_code, first_name + '' + last_name, dept.dept_desc, desg.desig_desc, office_phone, email, REPLACE(CONVERT(NVARCHAR,CAST(dob AS DATETIME), 6), ' ', '-') , REPLACE(CONVERT(NVARCHAR,CAST(doj AS DATETIME), 6), ' ', '-') FROM DB2 WHERE pk_emp_code NOT IN ( SELECT emp_code FROM #updatedRows );
Mid
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Visualizing Decision Trees with Python (Scikit-learn, Graphviz, Matplotlib) Learn about how to visualize decision trees using matplotlib and Graphviz Image from my Understanding Decision Trees for Classification (Python) Tutorial. Decision trees are a popular supervised learning method for a variety of reasons. Benefits of decision trees include that they can be used for both regression and classification, they don’t require feature scaling, and they are relatively easy to interpret as you can visualize decision trees. This is not only a powerful way to understand your model, but also to communicate how your model works. Consequently, it would help to know how to make a visualization based on your model. This tutorial covers: How to Fit a Decision Tree Model using Scikit-Learn How to Visualize Decision Trees using Matplotlib How to Visualize Decision Trees using Graphviz (what is Graphviz, how to install it on Mac and Windows, and how to use it to visualize decision trees) How to Visualize Individual Decision Trees from Bagged Trees or Random Forests As always, the code used in this tutorial is available on my GitHub. With that, let’s get started! How to Fit a Decision Tree Model using Scikit-Learn In order to visualize decision trees, we need first need to fit a decision tree model using scikit-learn. If this section is not clear, I encourage you to read my Understanding Decision Trees for Classification (Python) tutorial as I go into a lot of detail on how decision trees work and how to use them. Import Libraries The following import statements are what we will use for this section of the tutorial. import matplotlib.pyplot as plt from sklearn.datasets import load_iris from sklearn.datasets import load_breast_cancer from sklearn.tree import DecisionTreeClassifier from sklearn.ensemble import RandomForestClassifier from sklearn.model_selection import train_test_split import pandas as pd import numpy as np from sklearn import tree Load the Dataset The Iris dataset is one of datasets scikit-learn comes with that do not require the downloading of any file from some external website. The code below loads the iris dataset. import pandas as pd from sklearn.datasets import load_irisdata = load_iris() df = pd.DataFrame(data.data, columns=data.feature_names) df['target'] = data.target Original Pandas df (features + target) Splitting Data into Training and Test Sets The code below puts 75% of the data into a training set and 25% of the data into a test set. X_train, X_test, Y_train, Y_test = train_test_split(df[data.feature_names], df['target'], random_state=0) The colors in the image indicate which variable (X_train, X_test, Y_train, Y_test) the data from the dataframe df went to for a particular train test split. Image by Michael Galarnyk. Scikit-learn 4-Step Modeling Pattern # Step 1: Import the model you want to use # This was already imported earlier in the notebook so commenting out #from sklearn.tree import DecisionTreeClassifier # Step 2: Make an instance of the Model clf = DecisionTreeClassifier(max_depth = 2, random_state = 0) # Step 3: Train the model on the data clf.fit(X_train, Y_train) # Step 4: Predict labels of unseen (test) data # Not doing this step in the tutorial # clf.predict(X_test) How to Visualize Decision Trees using Matplotlib As of scikit-learn version 21.0 (roughly May 2019), Decision Trees can now be plotted with matplotlib using scikit-learn’s tree.plot_tree without relying on the dot library which is a hard-to-install dependency which we will cover later on in the blog post. The code below plots a decision tree using scikit-learn. tree.plot_tree(clf); This is not the most interpretable tree yet. In addition to adding the code to allow you to save your image, the code below tries to make the decision tree more interpretable by adding in feature and class names (as well as setting filled = True ). fn=['sepal length (cm)','sepal width (cm)','petal length (cm)','petal width (cm)'] cn=['setosa', 'versicolor', 'virginica'] fig, axes = plt.subplots(nrows = 1,ncols = 1,figsize = (4,4), dpi=300) tree.plot_tree(clf, feature_names = fn, class_names=cn, filled = True); fig.savefig('imagename.png') How to Visualize Decision Trees using Graphviz Decision Tree produced through Graphviz. Note that I edited the file to have text colors correspond to whether they are leaf/terminal nodes or decision nodes using a text editor. Graphviz is open source graph visualization software. Graph visualization is a way of representing structural information as diagrams of abstract graphs and networks. In data science, one use of Graphviz is to visualize decision trees. I should note that the reason why I am going over Graphviz after covering Matplotlib is that getting this to work can be difficult. The first part of this process involves creating a dot file. A dot file is a Graphviz representation of a decision tree. The problem is that using Graphviz to convert the dot file into an image file (png, jpg, etc) can be difficult. There are a couple ways to do this including: installing python-graphviz though Anaconda, installing Graphviz through Homebrew (Mac), installing Graphviz executables from the official site (Windows), and using an online converter on the contents of your dot file to convert it into an image. Creating the dot file is usually not a problem. Converting the dot file to a png file can be difficult. Export your model to a dot file The code below code will work on any operating system as python generates the dot file and exports it as a file named tree.dot . tree.export_graphviz(clf, out_file="tree.dot", feature_names = fn, class_names=cn, filled = True) Installing and Using Graphviz Converting the dot file into an image file (png, jpg, etc) typically requires the installation of Graphviz which depends on your operating system and a host of other things. The goal of this section is to help people try and solve the common issue of getting the following error. dot: command not found . dot: command not found How to Install and Use on Mac through Anaconda To be able to install Graphviz on your Mac through this method, you first need to have Anaconda installed (If you don’t have Anaconda installed, you can learn how to install it here). Open a terminal. You can do this by clicking on the Spotlight magnifying glass at the top right of the screen, type terminal and then click on the Terminal icon. Type the command below to install Graphviz. conda install python-graphviz After that, you should be able to use the dot command below to convert the dot file into a png file. dot -Tpng tree.dot -o tree.png How to Install and Use on Mac through Homebrew If you don’t have Anaconda or just want another way of installing Graphviz on your Mac, you can use Homebrew. I previously wrote an article on how to install Homebrew and use it to convert a dot file into an image file here (see the Homebrew to Help Visualize Decision Trees section of the tutorial). How to Install and Use on Windows through Anaconda This is the method I prefer on Windows. To be able to install Graphviz on your Windows through this method, you first need to have Anaconda installed (If you don’t have Anaconda installed, you can learn how to install it here). Open a terminal/command prompt and enter the command below to install Graphviz. conda install python-graphviz After that, you should be able to use the dot command below to convert the dot file into a png file. dot -Tpng tree.dot -o tree.png Windows installing of Graphviz through conda. This should fix the ‘dot’ is not recognized as an internal or external command, operable program or batch file issue. How to Install and Use on Windows through Graphviz Executable If you don’t have Anaconda or just want another way of installing Graphviz on your Windows, you can use the following link to download and install it. If you aren’t familiar with altering the PATH variable and want to use dot on the command line, I encourage other approaches. There are many Stackoverflow questions based on this particular issue. How to Use an Online Converter to Visualize your Decision Trees If all else fails or you simply don’t want to install anything, you can use an online converter. In the image below, I opened the file with Sublime Text (though there are many different programs that can open/read a dot file) and copied the content of the file. Copying the contents of a dot file In the image below, I pasted the content from the dot file onto the left side of the online converter. You can then choose what format you want and then save the image on the right side of the screen. Save visualization to computer Keep in mind that there are other online converters that can help accomplish the same task. How to Visualize Individual Decision Trees from Bagged Trees or Random Forests A weakness of decision trees is that they don’t tend to have the best predictive accuracy. This is partially because of high variance, meaning that different splits in the training data can lead to very different trees. The image above could be a diagram for Bagged Trees or Random Forests models which are ensemble methods. This means using multiple learning algorithms to obtain a better predictive performance than could be obtained from any of the constituent learning algorithms alone. In this case, many trees protect each other from their individual errors. How exactly Bagged Trees and Random Forests models work is a subject for another blog, but what is important to note is that for each both models we grow N trees where N is the number of decision trees a user specifies. Consequently after you fit a model, it would be nice to look at the individual decision trees that make up your model. Fit a Random Forest Model using Scikit-Learn In order to visualize individual decision trees, we need first need to fit a Bagged Trees or Random Forest model using scikit-learn (the code below fits a Random Forest model). # Load the Breast Cancer (Diagnostic) Dataset data = load_breast_cancer() df = pd.DataFrame(data.data, columns=data.feature_names) df['target'] = data.target # Arrange Data into Features Matrix and Target Vector X = df.loc[:, df.columns != 'target'] y = df.loc[:, 'target'].values # Split the data into training and testing sets X_train, X_test, Y_train, Y_test = train_test_split(X, y, random_state=0) # Random Forests in `scikit-learn` (with N = 100) rf = RandomForestClassifier(n_estimators=100, random_state=0) rf.fit(X_train, Y_train) Visualizing your Estimators You can now view all the individual trees from the fitted model. In this section, I will visualize all the decision trees using matplotlib. rf.estimators_ In this example, notice how we have 100 estimators. You can now visualize individual trees. The code below visualizes the first decision tree. fn=data.feature_names cn=data.target_names fig, axes = plt.subplots(nrows = 1,ncols = 1,figsize = (4,4), dpi=800) tree.plot_tree(rf.estimators_[0], feature_names = fn, class_names=cn, filled = True); fig.savefig('rf_individualtree.png') Note that individual trees in Random Forest and Bagged trees are grow deep You can try to use matplotlib subplots to visualize as many of the trees as you like. The code below visualizes the first 5 decision trees. I personally don’t prefer this method as it is even harder to read. # This may not the best way to view each estimator as it is small fn=data.feature_names cn=data.target_names fig, axes = plt.subplots(nrows = 1,ncols = 5,figsize = (10,2), dpi=3000) for index in range(0, 5): tree.plot_tree(rf.estimators_[index], feature_names = fn, class_names=cn, filled = True, ax = axes[index]); axes[index].set_title('Estimator: ' + str(index), fontsize = 11) fig.savefig('rf_5trees.png') Create Images for each of the Decision Trees (estimators) Keep in mind that if for some reason you want images for all your estimators (decision trees), you can do so using the code on my GitHub. If you just want to see each of the 100 estimators for the Random Forest model fit in this tutorial without running the code, you can look at the video below. Concluding Remarks This tutorial covered how to visualize decision trees using Graphviz and Matplotlib. Note that the way to visualize decision trees using Matplotlib is a newer method so it might change or be improved upon in the future. Graphviz is currently more flexible as you can always modify your dot files to make them more visually appealing like I did using the dot language or even just alter the orientation of your decision tree. One thing we didn’t cover was how to use dtreeviz which is another library that can visualize decision trees. There is an excellent post on it here. Image from produced by dtreeviz library. If you have any questions or thoughts on the tutorial, feel free to reach out in the comments below or through Twitter. If you want to learn more about how to utilize Pandas, Matplotlib, or Seaborn libraries, please consider taking my Python for Data Visualization LinkedIn Learning course.
High
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import ma = require('azure-pipelines-task-lib/mock-answer'); import tmrm = require('azure-pipelines-task-lib/mock-run'); import path = require('path'); let taskPath = path.join(__dirname, '..','index.js'); let tmr: tmrm.TaskMockRunner = new tmrm.TaskMockRunner(taskPath); tmr.setInput('googleEndpoint', 'b2a89421-36e7-4bff-b7af-01f3c8796ece'); tmr.setInput('accountId', 'dummyAccountId'); tmr.setInput('webPropertyId', 'dummyWebPropertyId'); tmr.setInput('profileId', 'dummyProfileId'); tmr.setInput('experimentName', 'dummyExperimentName'); tmr.setInput('action', 'UpdateExperiment'); tmr.setInput('trafficCoverage', '0.21'); tmr.setInput('equalWeighting', 'True'); tmr.setInput('jsonFile', '0'); //process.env["AZURE_HTTP_USER_AGENT"] = "TFS_useragent"; process.env["ENDPOINT_AUTH_PARAMETER_b2a89421-36e7-4bff-b7af-01f3c8796ece_Issuer"] = "incorrectIssuer"; process.env["ENDPOINT_AUTH_PARAMETER_b2a89421-36e7-4bff-b7af-01f3c8796ece_Audience"] = "correctAudience"; process.env["ENDPOINT_AUTH_PARAMETER_b2a89421-36e7-4bff-b7af-01f3c8796ece_Scope"] = "dummyScope"; process.env["ENDPOINT_AUTH_PARAMETER_b2a89421-36e7-4bff-b7af-01f3c8796ece_PrivateKey"] = "dummyPrivateKey"; var tl = require('azure-pipelines-task-lib/mock-task'); tmr.registerMock('azure-pipelines-task-lib/toolrunner', require('azure-pipelines-task-lib/mock-toolrunner')); tmr.registerMock('azure-pipelines-task-lib/task', "azure-pipelines-task-lib/mock-task"); tmr.registerMock('./../models/GoogleAnalyticsUtils', require("./../models/MockGoogleAnalyticsUtils")); tmr.run();
Mid
[ 0.560157790927021, 35.5, 27.875 ]
Q: Ungrouped back references with biblatex I am writing a report with Overleaf and biblatex for citation management. I have enabled backref, but would like the page numbers in the backref to be ungrouped as follows (ideally without disrupting the grouping of citations in the text): A MWE is shown below: \documentclass{article} \usepackage[utf8]{inputenc} \usepackage[svgnames]{xcolor} \usepackage[ backend=biber, style=nature, backref]{biblatex} \usepackage{hyperref} \hypersetup{ colorlinks=true, citecolor={blue}, citebordercolor={blue}, } %This part is to colorize the brackets% \DeclareCiteCommand{\cite}[\color{blue}\mkbibbrackets] {\usebibmacro{cite:init}% \usebibmacro{prenote}} {\usebibmacro{citeindex}% \usebibmacro{cite:comp}} {} {\usebibmacro{cite:dump}% \usebibmacro{postnote}} \newrobustcmd{\mkbibcoloursuperscript}[2]{% \unspace\allowhyphens\textsuperscript{% \begingroup \protected\long\def\mkbibsuperscript##1{% \blx@warning{Nested superscript}% \mkbibbrackets{##1}}% \color{#1}% #2\endgroup}} %This part is to put brackets around the supercitation% \DeclareCiteCommand{\supercite}[\mkbibcoloursuperscript{blue}] {\usebibmacro{cite:init}% \let\multicitedelim=\supercitedelim \iffieldundef{prenote} {} {\BibliographyWarning{Ignoring prenote argument}}% \iffieldundef{postnote} {} {\BibliographyWarning{Ignoring postnote argument}}% \bibopenbracket}% {\usebibmacro{citeindex}% \usebibmacro{cite:comp}} {} {\usebibmacro{cite:dump}\bibclosebracket} \addbibresource{biblatex-examples.bib} \begin{document} Test.\cite{sigfridsson} \clearpage Test.\cite{sigfridsson} \clearpage Test.\cite{sigfridsson} \clearpage Test.\cite{sigfridsson} \clearpage Test.\cite{sigfridsson} \printbibliography[ heading=bibintoc, title={Bibliography} ] \end{document} A: The formatting of the backreferences are controlled by the backrefstyle option. If you set it to backrefstyle=none,, biblatex will not attempt to compress the page ranges. \documentclass{article} \usepackage[utf8]{inputenc} \usepackage[svgnames]{xcolor} \usepackage[backend=biber, style=nature, backref=true, backrefstyle=none, ]{biblatex} \usepackage{hyperref} \hypersetup{ colorlinks=true, citecolor={blue}, citebordercolor={blue}, } %This part is to colorize the brackets \DeclareCiteCommand{\cite}[\color{blue}\mkbibbrackets] {\usebibmacro{cite:init}% \usebibmacro{prenote}} {\usebibmacro{citeindex}% \usebibmacro{cite:comp}} {} {\usebibmacro{cite:dump}% \usebibmacro{postnote}} \newrobustcmd{\mkbibcoloursuperscript}[2]{% \unspace\allowhyphens\textsuperscript{% \begingroup \protected\long\def\mkbibsuperscript##1{% \blx@warning{Nested superscript}% \mkbibbrackets{##1}}% \color{#1}% #2\endgroup}} %This part is to put brackets around the supercitation \DeclareCiteCommand{\supercite}[\mkbibcoloursuperscript{blue}] {\usebibmacro{cite:init}% \let\multicitedelim=\supercitedelim \iffieldundef{prenote} {} {\BibliographyWarning{Ignoring prenote argument}}% \iffieldundef{postnote} {} {\BibliographyWarning{Ignoring postnote argument}}% \bibopenbracket}% {\usebibmacro{citeindex}% \usebibmacro{cite:comp}} {} {\usebibmacro{cite:dump}\bibclosebracket} \addbibresource{biblatex-examples.bib} \begin{document} Test.\cite{sigfridsson} \clearpage Test.\cite{sigfridsson} \clearpage Test.\cite{sigfridsson} \clearpage Test.\cite{sigfridsson} \clearpage Test.\cite{sigfridsson} \printbibliography[ heading=bibintoc, title={Bibliography} ] \end{document}
Mid
[ 0.593350383631713, 29, 19.875 ]
PLYMOUTH MEETING, Pa. - Down four runs before even coming to bat for the first time, Villanova (13-3) spent the entire game battling back a few runs at a time but ultimately came up short by the smallest of margins in an 11-10 loss to Marist (9-7) on Saturday afternoon at the Villanova Ballpark at Plymouth in the second game of the Big Five Baseball Bash. The loss snapped a six-game winning streak for the Wildcats, who had rallied in the ninth inning to win each of their last two games before today. It came as no surprise after the last two ninth-inning rallies that Villanova would go down swinging today against a worthy Red Foxes team. The Wildcats trailed 11-8 going to the bottom of the ninth inning, had two of the first three batters retired in their final at-bat and still managed to plate two runs while getting the tying and potential winning runs on base. With runners at first and second with two outs, however, a groundball in the infield ended a marathon affair that took three hours and 35 minutes to complete and featured seven different pitchers combine to throw 357 pitches between the two teams. The offensive production was nothing new for Villanova, especially at the top of the lineup. The first four spots in the batting order produced 11 hits, nine runs scored and seven RBI on the day for the Wildcats, with Matt Szczur (Erma, N.J.) and Justin Bencsko (Pompton Plains, N.J.) getting three hits apiece. Szczur scored four runs, drove in one, walked once and stole two bases to spark the team's offense. He singled with one out and nobody on in the ninth to start an eventual two-run rally, which was capped off by Adam Nelson (St. Joseph, Mo.) sliding a two-run single through the left side to pull Villanova to within one run for the first time since the second inning. Even with a high-scoring affair and the potential for another late comeback, runs were much easier to come early on in the game. Marist built a quick 4-0 lead in a messy top of the first inning that featured two errors in the field and just one earned run, but the Red Foxes quickly fell victim to the same type of defense when an error of their own helped the Wildcats answer back with three runs in the bottom of the first inning. Both teams scored twice in the second inning to put the Marist lead at 6-5, but the Red Foxes added three runs in the top of the third for a 9-5 advantage. In the middle innings, Villanova trailed 11-6 after surrendering two more runs in the top of the sixth inning, but once again struck for two runs of their own in the bottom half to narrow the gap to 11-8. The Wildcat bullpen effectively quieted down the Red Foxes late in the game, as Marist managed just two hits after the third inning. Jerry Battipaglia (Katonah, N.Y.) entered the game with a runner at first base and nobody out in the top of the seventh and went the rest of the way for Villanova. He retired nine of the 10 batters he faced, including the last seven, and struck out four over his three innings of work. Before him, Julian Diaz (Trenton, N.J.) allowed two runs on two hits in 3 1/3 innings of work. Dain Hall (Barrington, Ill.) finished the day 2-for-4 with a pair of walks and three runs scored, while Chris Johnson (Shrewsbury, N.J.) went 2-for-3 with three RBI and a walk. The Wildcats outhit Marist by a margin of 15-11 and drew nine walks while issuing just two. Kevin Wager (Chester, Va.) and David Koczirka (Thornton, Pa.) each had two hits and drove in a run. It looked like it was going to be a trademark offensive day for Villanova when Szczur led off the home half of the first inning with a single and then stole second base. Bencsko struck out, but was safe at first anyway on a passed ball that allowed moved Szczur up to third. After Szczur scored and Bencsko moved into scoring position on a throwing error committed during a failed pickoff attempt at first base, Johnson hit a two-run double to have the Wildcats right back into the thick of things. Bencsko and Hall each singled to start the bottom of the sixth inning and Villanova wound up with two runs in the frame on an RBI single by Johnson and a sacrifice fly by Wager. During the inning, however, Marist turned to freshman Dan Zlotnick to try to register the final 12 outs of the contest. Zlotnick pitched well into the ninth inning before tiring and wound up allowing two earned runs on five hits in 3 2/3 innings pitched. He walked three and struck out five and Jake Rifkin got the final groundball for his first save. Offensively, Richard Curylo had three hits and three runs scored at the top of the order for the Red Foxes, including a two-run inside-the-park home run in the top of the third inning. Bryce Nugent hit a two-run home run off Diaz in the top of the sixth inning. Marist got at least one hit from eight of the nine spots in the lineup and put up 11 runs one day after it scored 21 times in a win over Temple. The day was over early for both starting pitchers, though both the Wildcats Kyle Helisek (Cranberry Township, Pa.) and the Red Foxes B.J. Martin were at times a victim of the defense behind them. Helisek (2-1, 2.18 ERA) was touched for nine hits and nine runs in 2 2/3 innings, with four of those runs being earned. He walked one and did not have a strikeout in his first outing in 15 days due to last week's rainouts. Martin gave up seven hits and six runs (five earned) in three-plus innings. The winning pitcher for the Red Foxes was Brendan Chapin (1-3, 7.71 ERA), who allowed two runs on three hits in two innings of work. Villanova will host Youngstown State on Sunday at 12:15 p.m. in the final game of this weekend's local tournament. NOTES: Bencsko (.551) and Szczur (.500) are both hitting at least .500 through the first 16 games of the season for the Wildcats ... Bencsko stole his BIG EAST-leading 16th base of the season during the game, but was also caught for the first time all year ... Villanova stranded 14 runners on base despite going 6-for-17 (.353) with runners in scoring position ... The Wildcats have an outstanding .976 team fielding percentage this season and the four errors committed today matched the combined total of miscues from the previous seven games ... Before allowing two home runs today, Villanova had gone six straight games without allowing a long ball since their previous loss, an 8-7 setback to Western Michigan ... The Wildcats have hit just one home run on the season, which came in the fourth game of the year against Purdue ... Today was the third straight game with three hits for Szczur, who is batting .609 (14-23) over his last five contests. Live Broadcast | Live Audio | Live Stats | Game NotesA new location and a relatively unfamiliar opponent awaits Villanova (22-25, 7-8 BIG EAST) in the final series of the regular season, as the Wildcats travel to Creighton (27-17, 10-4 BIG EAST) for a three-game set at TD Ameritrade Park. The team arrived in Omaha on Wednesday evening and is set to play the series opener today at 12:30 p.m. Central time. Friday's game gets underway at 6:30 p.m. and Saturday's contest is slated for 1 p.m.
Mid
[ 0.5393700787401571, 34.25, 29.25 ]
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Low
[ 0.515981735159817, 28.25, 26.5 ]
Outrageous skate video introduced the world to Bam Margera, the insane, parent hassling daredevil that would gain fame for risking life and limb on MTV's Jackass series. Includes a very ... See full summary »
Low
[ 0.41686746987951806, 21.625, 30.25 ]
Q: に vs で again: 前に vs 後で Following the current trend of pitting the particles に and で against each other, here is another question that does the same but from another type of usage and perspective. When we want to say "do X before Y", we use "Y 前に X": 食べる前に「いただきます」と言う。 On the other hand, when we want to say "do X after Y", we use "Y 後で X": 食べた後で「ごちそうさまでした」と言う。 What is the simplest explanation to explain the differences between 前 and 後 that make 前 goes with に while 後 goes with で in the two situations above? A: で derives from に+て, and て roughly corresponds to the present/past participles (-ing, -en) in Western languages. Kuno (1973) notices that て implies temporal order. So when you have 走ってころんだ '(By) running, I fell', running has to precede falling; it cannot be the other way around. This much is the general consensus. Notice that the usage of で in the question involves temporal notions rather than locations. Now, I found an interesting explanation here: Q14 that connects the facts mentioned above. According to this, when you have an expression A [temporal noun] で B, the て that is included in で obeys the temporal restriction mentioned above; that is, what is expressed by A [temporal noun] has to precede B. Going in the other temporal order is not allowed. Therefore, expressions like 食べた後で「いただきます」と言う。 [Temporal order: 食べた => 言う] are grammatical but × 食べる前で「いただきます」と言う。 [Temporal order: 食べる <= 言う] × 食べるよりも先で「いただきます」と言う。 [Temporal order: 食べる <= 言う] are not. に can be used by all the examples above: 食べた後に「いただきます」と言う。 食べる前に「いただきます」と言う。 食べるよりも先に「いただきます」と言う。 If there is preference of 食べた後で「いただきます」と言う over 食べた後に「いただきます」と言う, then some kind of slight difference in meaning like what phirru mentions in the comment may be playing a role here. A: In 後でする the focus is that you will do whatever you were doing, just later; whereas in 後にする the focus is that you will postpone whatever you are supposed to do until later. Treating で as the "instrumental" particle, this way, "後でする" would mean "to do (whatever), by using the time after now" And "後にする" would mean "to do (whatever), at a point of time after now" So "前に" would be "at a time before now", and "前で" would be impossible since you cannot use a time before now. Alternatively, treating で as the verb-conjunctive form of the copula だ, ”後でする” would mean "It is afterwards, and do it" This also shows the impossibility of 前で which would translate strangely into "It is now before and..." which is temporally impossible for the past to exist in the present. A: If you want a very simple answer, then you can look at the meaning of ni and de, again: ni means things are separate and interacting. de means that things are contiguous and acting in a similar manner (i.e., to the same ends). I think I answered a question you asked about them earlier to tell you that に and で could be compared to an English analogue of 'each other' and 'themselves'. Anyway... 後で is used because after the past happens, it is included as a part of a continuing timeline 'themselves'. 前に is used because the prior event interacts with the future event through time or the doer or whatever 'each other'. So, 'ホニャホニャの後でいく' = 'With/'contingent on' whatever's happening, I will do it.' 'ホニャホニャ前にいく' means, 'Whatever happened, and my going before that is related somehow'. And to reiterate one more time: '後で' means: 'the future comes only with complete a specific past' and '前に' means: 'the future seems to interacts with a past'.
Mid
[ 0.610778443113772, 12.75, 8.125 ]
LONG LAKE, N.Y. -- A Buffalo man has drowned in an Adirondack Mountains river after he was swept down the rocky Buttermilk Falls and pinned by the current, police said Sunday. Nicolas M. Padilla, 20, lost his footing Saturday as he and a friend were climbing up the rocks at the side of the falls after going for a swim in slower moving pools of water, state police said. The two "began to traverse the river's current near the crest of the water fall. Padilla lost his footing and the current swept him over the waterfall where he became lodge below the surface of the river and drown," state police said in a statement. Hamilton County Coroner, Virginia Jennings pronounced Padilla dead at the scene. Troopers said it took emergency responders about three hours to pull Padilla's body from the Raquette River in Long Lake. The town of 711 people sits in the vast Adirondack Park, about halfway between Albany and Montreal. It's about 110 miles north of Schenectady and 130 miles northeast of Syracuse. State police said their investigation is continuing.
Mid
[ 0.5549348230912471, 37.25, 29.875 ]
Brain-enhancing technologies like Elon Musk’s neural lace and neural activity transference have raised both excitement and concern about the possibility of uploading human consciousness to the cloud. Doing so would, in theory, free us from Shakespeare’s mortal coil, allowing us to exist indefinitely in digitized form. This idea presupposes that our bodies and consciousness can be separated, which, if you ask neuroscientist Anil Seth, Ph.D., is bunk. In a TED Talk in Vancouver on Wednesday, Seth, a co-director of the Sackler Centre for Consciousness Science and professor at the University of Sussex, explained why doing so was impossible. “What it means to be me cannot be reduced to — or uploaded to — a software program running on a robot, however smart or sophisticated,” Seth said. Our conscious experiences “are shaped at all levels,” he continued, referring to the idea that consciousness does not exist solely in the mind. Anil Seth Bret Hartman / TED Seth’s work has shown compelling evidence that consciousness doesn’t just consist of information about the world traveling via our senses as signals into our brains. Instead, he’s found that consciousness is a two-way street, in which the brain constantly uses those incoming signals to make guesses about what is actually out there. The end result of that interplay between reality and the brain, he says, is the conscious experience of perception. “What we perceive is [the brain’s] best guess of what’s out there in the world,” he said, explaining that these guesses are constantly in flux. To illustrate, he played for the crowd a high-pitched series of electronic beeps, which wavered in tone like a robotic bird’s warble. When they couldn’t identify what it was, he played it again. Still, it just sounded like a bunch of beeps. Then, he played a recording of a mechanized voice saying “I think Brexit is a really terrible idea” with natural human intonation. When he played the exact same robotic warble again, everyone could suddenly hear the words within the sounds. This and the other sensory illusions he used as examples were meant to illustrate what he calls the “controlled hallucinations” that make up our conscious experience; in this case, people hallucinated the words in the sounds because their brain’s predictive ability had changed. “We don’t passively see the world,” he said, “we actively generate it.” And because our bodies are complicit in the generation of our conscious experience, it’s impossible to upload consciousness to some external place without somehow taking the body with it. While his theories may be reassuring to anyone who fears that their digitized consciousness may be as susceptible to cloud hackers as nude celebrity photos, they may cause some anxiety about the nature of reality. If an individual’s experience of consciousness is particular to their own body’s interaction with what’s actually out there, then will anyone ever know what reality truly, objectively is? Seth suggests that it doesn’t matter because the most important experience of consciousness is the one we all share. “[When] we agree about our hallucinations, we call that reality,” he said.
Mid
[ 0.6497461928934011, 32, 17.25 ]
2009 ND 148 Sarmed A. Abdullah, M.D., Plaintiff and Appellant v. State of North Dakota, d/b/a University of North Dakota, and Dr. David J. Theige, individually, Defendants and Appellees No. 20080254. Supreme Court of North Dakota. Filed July 29, 2009. Paul Henry Myerchin (argued) and Clark Jay Bormann (appeared), P.O. Box 995, Bismarck, N.D. 58502-0995, for plaintiff and appellant. Tag Christian Anderson (argued), Special Assistant Attorney General, Risk Management Division, 1600 East Century Avenue, Suite 4, Bismarck, N.D. 58503, and Kirsten Renata Franzen (on brief), Assistant Attorney General, North Dakota Office of Attorney General, 500 North 9th Street, Bismarck, N.D. 58501, for defendants and appellees. Opinion of the Court by Maring, Justice. Maring, Justice. [¶ 1] Sarmed Abdullah, M.D., appeals from a summary judgment dismissing his action against the State of North Dakota, doing business as the University of North Dakota, and against Dr. David Theige, the director of the residency program at the University's School of Medicine and Health Sciences, stemming from Abdullah's dismissal from the internal medicine residency program at the University's School of Medicine for "incompetence in the area of [p]rofessionalism." Abdullah argues his dismissal from the residency program was arbitrary and capricious, and he asserts the district court erred in granting summary judgment because there are genuine issues of material fact on each of his claims. We affirm. I [¶ 2] Abdullah graduated from the Damascus University School of Medicine in Syria in 1999. In July 2001, he began a residency training program with the Medical College of Wisconsin, which included three rotations. As a result of evaluations in those rotations, the school offered him three options: (1) resign from the residency program; (2) accept probation and a remediation plan; or (3) take a leave of absence from the program and find another residency program. Abdullah decided to take a leave of absence and enrolled in a Post Graduate Year 1 internal medicine residency program at East Tennessee State University from August 2003 through September 2004. [¶ 3] On October 1, 2004, Abdullah began an internal medicine residency program at the University's School of Medicine for his Post Graduate Year 2. Abdullah's application to the University's residency program listed the Medical College of Wisconsin under "CONTINUING MEDICAL EDUCATION (CME) Courses in Internal Medicine," rather than under a "Residency" section. In April 2005, Abdullah executed a "resident contract" with the University for a training program in internal medicine at the Post Graduate Year 3 level, which ran from October 1, 2005, through September 30, 2006. The "residence contract" provided that "appropriate certification [would] be provided upon satisfactory completion of the education and training program," and "[u]nsatisfactory or persistently less than satisfactory resident evaluation can result in required remedial activities, temporary suspension from duties, or termination of employment and residency education." The contract also said the "resident [could] be terminated for unsatisfactory or persistently less than satisfactory performance of duties as determined by supervising faculty or for failure to progress in medical knowledge and skills." [¶ 4] In a June 28, 2006, letter to Abdullah, Theige, the director of the residency program, informed Abdullah that his "recent behavior and correspondence ha[d] made [Theige] very concerned about [Abdullah's] personal well-being and mental health," and Theige informed Abdullah that he had been placed on an "emergency leave of absence from the residency program, pending a psychiatric evaluation." Abdullah subsequently returned to the program on August 1, 2006, but his scheduled completion date for his residency training was extended to October 20, 2006. [¶ 5] In an October 12, 2006, letter to Abdullah, Theige informed Abdullah that he was temporarily suspended from the residency program, pending a psychiatric examination, for concerns about his "professional behavior." In an October 23, 2006, letter to Abdullah, Theige summarized Abdullah's status with the residency program, including professionalism concerns about Abdullah's failure to disclose his residency at the Medical College of Wisconsin and the circumstances of his departure from that program, Abdullah's conduct regarding authorship of a research manuscript with Dr. William Newman, and Abdullah's conduct regarding a home visit with a patient: On June 22, 2006, I received an email from you telling me that you did not intend to finish our program "if after July, 2006 my GI Fellowship contract in Mayo Clinic is not on the desk." I sent you a reply indicating my bewilderment, and asked to meet with you the next day. I later found out that you had just learned of your failure to match with a GI fellowship program. I am also aware that you were just finishing a rotation as the night float resident. The next morning, I came to work and discovered a handwritten note from you on my desk requesting my "testimony about [Abdullah] to the Chief Justice of the United States John Roberts in the US Supreme Court in Washington D.C. for the attached application. Your cooperation—not obstruction—of Justice will be appreciated." The note was attached to a typewritten 2-page "Personal Statement to the Supreme Court of the United States" which I found to be almost incoherent. At that point, I learned that you had left town that morning to begin a vacation. I met with you in my office on June 28, 2006. At that time, you appeared to be calm, coherent, and reasonable, but I placed you on an emergency medical leave from the program pending a psychiatric evaluation. In addition to the question of your mental health, I was also concerned about part of the content of your "Personal Statement to the Supreme Court." In that document, you mentioned that you had been a resident at the Medical College of Wisconsin in the summer of 2001. I was not previously aware of this. In your curriculum vitae included with your application to our program, you did list your preliminary residency in internal medicine at East Tennessee State University. An experience at the Medical College of Wisconsin was listed only in small print under the heading "Continuing Medical Education (CME) courses in Internal Medicine." We verified, with your cooperation, that you had been a resident at MCW, and that you resigned. You underwent an extensive psychiatric evaluation at the University of Pittsburgh in July 2006. I received a letter from your psychiatrist on July 18, 2006. The psychiatrist wrote that your psychiatric symptoms were contextual and related to sleep deprivation. He indicated that with treatment of the sleep disturbance, you could return to work after July 21, 2006. Our Resident Evaluation and Advancement Committee reviewed this matter on July 25, 2006. The committee recommended that you should be reinstated to the program after completing a meeting with the program director, but that concerns about your professionalism should be noted and reported in the future when requests for verification of training are received. I met with you on July 27, 2006. You were reinstated to the program as of August 1, 2006. Your anticipated completion date for the program was postponed to October 20, 2006 because of your recent medical leave. On September 28, 2006, Dr. William Newman sent me a letter expressing his concern about your professional behavior related to your joint research effort. Over the next several days, I received additional correspondence from other faculty and staff expressing concerns about your behavior. One of the concerns was that you initiated a home visit with a patient without appropriate attending physician supervision and that you contacted a physician at the Mayo Clinic on this patient's behalf, but that you did not appropriately identify yourself as a resident physician. Finally, on October 12, 2006, a staff member . . . reported that she was very frightened by your behavior and that she felt unsafe. I met with you later that morning and suspended you from the program pending a psychiatric evaluation. After I receive a report from your psychiatrist, this matter will be referred to the Resident Evaluation and Advancement Committee. One of the serious issues to be considered is the matter of my evaluation of your performance in each core competency, but especially in professionalism. In order to receive credit for the final year of training and successfully complete our program, a third-year resident must be given satisfactory ratings in each competency area. My rating of your performance in professionalism will be determined after appropriate review of the matters outlined above. [¶ 6] In a November 6, 2006, letter to Abdullah, Theige informed Abdullah that the University's Resident Evaluation and Advancement Committee had reviewed Abdullah's status and recommended dismissing Abdullah from the residency program. In that letter, Theige informed Abdullah of his dismissal from the residency program. [¶ 7] Abdullah appealed the dismissal to a Resident Fair Process and Grievance Hearing Panel, which resulted in an evidentiary hearing before a panel of five doctors. The Hearing Panel affirmed the decision to dismiss Abdullah from the residency program for "incompetence in the area of [p]rofessionalism," finding: l) The reference to three months in the Medical College of Wisconsin residency on the CV Dr. Abdullah submitted with his UND . . . application appears following a section on Continuing Medical Education credit and not in the section with his East Tennessee State University residency year. He denies this was an attempt to conceal this residency affiliation. On his Application for Residents for the VA, signed 4-26-04, he listed it clearly under previous residencies, however, he checked a "No" response to a question "Within the last five years have you resigned or retired from a position after being notified you would be disciplined or discharged, or after questions about your clinical competence were raised?" The letter from Dr. Olds [at the Medical College of Wisconsin] to Dr. Abdullah . . . clearly indicates that he was already on probation and that he was offered resignation as an alternative to accepting continuing probation and remediation. 2) The research manuscript in question describes both phase I and phase II projects. Dr. Newman was identified by all evidence and testimony as the mentor for the phase I, or initial, project, for which he was listed as the principle investigator in the submission to the Institutional Review Board. In testimony, Dr. Abdullah described the addition of the phase II component with Dr. Santoro as mentor. He submitted the manuscript to the Mayo Clinic Proceedings without either mentor listed as co-author, instead providing an acknowledgement for each. Dr. Stephanie Borchardt, research coordinator at the VA, had suggested the acknowledgement for Dr. Newman, as a minimum, after judging it to be unprofessional not to include Dr. Newman as an author. Dr. Newman was not presented a draft or any other copy of the manuscript before its submission and finally obtained an earlier copy, not the version submitted, by petitioning for it under the Freedom of Information Act to Dr. Borchardt. Dr. Abdullah did not present his findings or final write-up at a residency Research Committee meeting as required by the Program's Resident Research Requirement. 3) The visit to a former patient's home was conducted for reasons that are inconsistently explained by [Abdullah], both from his documentation at the time of the event and from his testimony at this hearing. He described it as having occurred both as a medical or community outreach activity and as an effort to obtain consent from the patient to use his records as the basis for a case report. Such a home visit, for any reason, by a resident in the program has never been done and is not a part of the training experience, nor was this visit approved or supervised by anyone in the program. The special license granted to residents by the State of North Dakota does not allow for any professional activities outside the scope of resident duties or supervision. [Abdullah] also moved to take over the care of this patient by scheduling him for an office visit without conferring first with either the patient's current primary care physician or discussing it with a clinic supervisor or administrator. He also failed to properly identify himself as a resident when he contacted a physician at Mayo Clinic seeking information pertaining to this patient. . . . . 1) The Hearing Panel concluded that Dr. Abdullah deliberately misrepresented his academic and employment history to avoid revealing the circumstances of his having left the Medical College of Wisconsin Internal Medicine Residency under disciplinary proceedings, and that this constitutes a substantial act of unethical and unprofessional conduct. Although the location of the reference to the Medical College of Wisconsin residency on the CV Dr. Abdullah submitted with his UND . . . application, combined with his testimony, leave it unclear whether this was a knowing and deliberate misrepresentation, the response on his VA application to the question regarding resignation under disciplinary conditions or questions of competence provides clear evidence of his intent to hide this fact. 2) The Panel concluded that Dr. Abdullah was unethical and unprofessional in his attempt to bar or remove a principle investigator, Dr. Newman, from work and publication over which the investigator rightfully had jurisdiction, and in deliberately submitting for publication a manuscript in violation of the program's requirements concerning resident research. 3) The Panel concluded that Dr. Abdullah's conduct concerning a home visit to a former patient and conduct concerning the patient involved in that visit was unethical and unprofessional. The visit itself was unprecedented by a resident in this program, unapproved, unsupervised and outside the scope of his resident duties and resident licensure. Seeking a patient's consent for publication by visiting him in his home is a highly irregular and troublesome approach, showing disregard for the ethical implications of the means by which to obtain consent from patients. During and following that visit he attempted to take over care of the patient, inappropriately intervened by trying to gather medical information on a patient for whom someone else had primary clinical responsibility, and failed to identify himself properly to a Mayo Clinic physician. Abdullah appealed the Hearing Panel's decision to the Dean of the University's School of Medicine, who upheld the Hearing Panel's decision to dismiss him from the residency program. [¶ 8] Abdullah then sued the University and Theige individually in district court, alleging: (1) the University breached its residency contract with Abdullah; (2) Theige intentionally interfered with Abdullah's prospective business opportunity; (3) the University and Theige arbitrarily, capriciously, and wrongfully dismissed Abdullah from the residency program, which violated his substantive due process rights under 42 U.S.C. § 1983; and (4) the University arbitrarily and capriciously dismissed Abdullah from the residency program in violation of Title I of the Americans with Disabilities Act of 1990, ["ADA"] 42 U.S.C. § 12102 et seq., and the North Dakota Human Rights Act, N.D.C.C. ch. 14-02.4. Abdullah sought damages and certification of successful completion of his third year of the residency program. The district court granted summary judgment for the University and Theige. II [¶ 9] The district court decided this case in the posture of summary judgment, which is a procedure for promptly resolving a controversy on the merits without a trial if either party is entitled to judgment as a matter of law, and if no dispute exists as to either the material facts or the inferences to be drawn from undisputed facts, or if resolving disputed facts would not alter the result. ACUITY v. Burd & Smith Constr., Inc., 2006 ND 187, ¶ 6, 721 N.W.2d 33. A district court's decision on a motion for summary judgment is a question of law that we review de novo on the record. Riemers v. Grand Forks Herald, 2004 ND 192, ¶ 4, 688 N.W.2d 167. The party moving for summary judgment must show there are no genuine issues of material fact and the case is appropriate for judgment as a matter of law. Green v. Mid Dakota Clinic, 2004 ND 12, ¶ 5, 673 N.W.2d 257. A party resisting a motion for summary judgment cannot merely rely on the pleadings or other unsupported conclusory allegations, but must present competent admissible evidence by affidavit or other comparable means which raises an issue of material fact. Beckler v. Bismarck Pub. Sch. Dist., 2006 ND 58, ¶ 7, 711 N.W.2d 172. "In summary judgment proceedings, neither the trial court nor the appellate court has any obligation, duty, or responsibility to search the record for evidence opposing the motion for summary judgment." Fish v. Dockter, 2003 ND 185, ¶ 15, 671 N.W.2d 819 (quoting Anderson v. Meyer Broadcasting Co., 2001 ND 125, ¶ 14, 630 N.W.2d 46). "The opposing party must also explain the connection between the factual assertions and the legal theories in the case, and cannot leave to the court the chore of divining what facts are relevant or why facts are relevant, let alone material, to the claim for relief." Fish, at ¶ 15 (quoting Anderson, at ¶ 14). III [¶ 10] Abdullah argues his dismissal from the residency program was arbitrary and capricious and the district court erred in granting summary judgment because there are genuine issues of material fact on each of his claims. He argues the professionalism issue was a pretext for mental health problems and his dismissal was arbitrary and capricious. He claims he did not misrepresent his reasons for leaving the Medical College of Wisconsin, he did not violate the University's standards for authorship for a research article, and he did not provide medical services to a patient in a home visit. A [¶ 11] Abdullah argues there are disputed issues of material fact about whether the University breached its contractual obligation to certify his graduation from the residency program. He claims he was dismissed for a disciplinary matter and not for academic reasons and, even if his dismissal was for academic reasons, the University did not act in good faith and its reasons for dismissal were arbitrary and capricious. [¶ 12] In rejecting Abdullah's breach of contract claim, the district court said there was no provision in the residency contract that required the University to graduate a resident and the contract gave the University vast discretion for academic decisions. The court said a reasonable person could find Abdullah engaged in unprofessional conduct during the residency program, which meant he failed to satisfactorily perform in the core competency area of professionalism. [¶ 13] Our analysis of Abdullah's breach of contract claim requires consideration of the scope of judicial analysis of the decision to dismiss Abdullah from the residency program. We have said the prima facie elements of a breach of contract action are the existence of a contract, a breach of the contract, and damages flowing from the breach of contract. Van Sickle v. Hallmark & Associates, 2008 ND 12, ¶ 11, 744 N.W.2d 532. A breach of contract occurs when there is nonperformance of a contractual duty. Id. Whether a contract has been substantially performed and whether a party has breached a contract generally are questions of fact. Wachter v. Gratech Co. Ltd., 2000 ND 62, ¶ 17, 608 N.W.2d 279. [¶ 14] In Thompson v. Associated Potato Growers, Inc., 2000 ND 95, ¶ 20, 610 N.W.2d 53 (quoting Cotran v. Rollins Hudig Hall Int'l, Inc., 948 P.2d 412, 422 (Cal. 1998)), we held a private employer's decision to terminate an employee for cause was subject to judicial analysis under an objective good-faith standard, in which: an employer is justified in terminating an employee for good cause for "fair and honest reasons, regulated by good faith on the part of the employer, that are not trivial, arbitrary or capricious, unrelated to business needs or goals, or pretextual. A reasoned conclusion, in short, supported by substantial evidence gathered through an adequate investigation that includes notice of the claimed misconduct and a chance for the employee to respond." [¶ 15] In Peterson v. North Dakota Univ. Sys., 2004 ND 82, ¶¶ 11-1 8, 678 N.W.2d 163, we considered the standard for judicial analysis of a tenured university instructor's breach of contract action against the State. We concluded that in a breach of contract action involving the Board of Higher Education's dismissal of a contract employee, judicial analysis of the substantive decision to terminate the employee was limited to deciding whether a reasoning mind could have reached the same conclusion on the evidence presented. Id. at ¶ 18. See also Ellis v. North Dakota State Univ., 2009 ND 59, ¶ 42, 764 N.W.2d 192 (applying Peterson to termination action brought under Human Right's Act). In Peterson, at ¶ 24, we affirmed a summary judgment dismissal of the tenured university instructor's breach of contract action: Viewing the facts and reasonable inferences in a light most favorable to Peterson, we conclude she has not raised a genuine or material issue of fact showing a reasoning mind could not have concluded there was adequate cause to dismiss her. Rather, the record reflects that different committees, boards, or persons placed different weight on the evidence presented. Peterson contracted for the procedures afforded to her. A breach of Peterson's employment contract does not occur merely because she disagrees with the substantive result of those procedures. The mere fact that different opinions could be reached based on the facts is not sufficient to establish the Board breached her employment contract. There was sufficient evidence in the record for a reasoning mind to conclude clear and convincing evidence existed to dismiss Peterson for cause. Accordingly, we affirm the summary judgment dismissing Peterson's breach of contract claim. [¶ 16] A common thread in Thompson and Peterson is that, in a breach of contract action, we afford a high degree of deference to an employer's decision to terminate an employee's employment for cause. Here, Abdullah was dismissed from the residency training program at a public educational institution for proffered reasons involving professionalism and academic performance. "Courts are particularly ill-equipped to evaluate academic performance." Board of Curators of Univ. of Missouri v. Horowitz, 435 U.S. 78, 92 (1978). "Academic evaluations of a student, in contrast to disciplinary determinations, bear little resemblance to the judicial and administrative factfinding proceedings . . . which . . . traditionally attached a full-hearing requirement." Id. at 89. "[T]he determination whether to dismiss a student for academic reasons requires an expert evaluation of cumulative information and is not readily adapted to the procedural tools of judicial or administrative decisionmaking." Id. at 90. [¶ 17] In Regents of University of Michigan v. Ewing, 474 U.S. 214, 225-27 (1985) (citations and footnotes omitted), the United States Supreme Court discussed a court's "narrow avenue for judicial review" of an academic decision to dismiss a student from a medical school program in the context of a substantive due process claim: When judges are asked to review the substance of a genuinely academic decision, such as this one, they should show great respect for the faculty's professional judgment. Plainly, they may not override it unless it is such a substantial departure from accepted academic norms as to demonstrate that the person or committee responsible did not actually exercise professional judgment. . . . . Considerations of profound importance counsel restrained judicial review of the substance of academic decisions. As JUSTICE WHITE has explained: "Although the Court regularly proceeds on the assumption that the Due Process Clause has more than a procedural dimension, we must always bear in mind that the substantive content of the Clause is suggested neither by its language nor by preconstitutional history; that content is nothing more than the accumulated product of judicial interpretation of the Fifth and Fourteenth Amendments. This is . . . only to underline Mr. Justice Black's constant reminder to his colleagues that the Court has no license to invalidate legislation which it thinks merely arbitrary or unreasonable." Added to our concern for lack of standards is a reluctance to trench on the prerogatives of state and local educational institutions and our responsibility to safeguard their academic freedom, "a special concern of the First Amendment." If a "federal court is not the appropriate forum in which to review the multitude of personnel decisions that are made daily by public agencies," far less is it suited to evaluate the substance of the multitude of academic decisions that are made daily by faculty members of public educational institutions-decisions that require "an expert evaluation of cumulative information and [are] not readily adapted to the procedural tools of judicial or administrative decisionmaking." [¶ 18] Other courts have held that an academic decision to dismiss a resident from a residency program is entitled to deference. See Bell v. Ohio State University, 351 F.3d 240, 249-52 (6th Cir. 2003) (stating no basis for finding medical student's interest in continuing medical education was protected by substantive due process and court's review of academic decision must show great respect for faculty's professional judgment); Gupta v. New Britain Gen. Hosp., 687 A.2d 111, 117-22 (Conn. 1996) (residency agreement between physician and hospital created educational, rather than employment, relationship and decision to dismiss resident from program for poor clinical performance was academic decision entitled to deference). [¶ 19] We conclude the deferential standard from Peterson is applicable to the decision to dismiss Abdullah from the residency program. The decision to dismiss Abdullah was made after he was afforded procedural safeguards, and the record of the proceedings before the Resident Fair Process and Grievance Hearing Panel includes evidence that the substantive decision to dismiss him from the residency program was not a substantial departure from accepted academic norms. Although Abdullah claims the dismissal was arbitrary and capricious and not in good faith, there is sufficient evidence in the record for a reasoning mind to conclude Abdullah was dismissed for incompetence in the area of professionalism. A determination of qualifications and educational experience to practice medicine involves expert evaluation of cumulative information. See Horowitz, 435 U.S. at 90. See also Singha v. North Dakota State Bd. of Med. Exam'rs, 1998 ND 42, ¶ 32, 574 N.W.2d 838. The district court applied deference to the substantive decision to dismiss Abdullah, concluding the dismissal was an academic decision based on professionalism, and decided a reasonable person could find Abdullah engaged in unprofessional conduct during the residency program. See Peterson, 2004 ND 82, ¶ 24, 678 N.W.2d 163. Although Abdullah claims he was dismissed from the residency program for disciplinary reasons and not academic reasons, in the context of the deference accorded the educational institution's decision and the evidence presented at the proceedings before the Hearing Panel, we conclude the district court did not err in granting summary judgment on Abdullah's breach of contract claim. B [¶ 20] Abdullah claims he had a prospective employment contract with another hospital after graduation, and the district court erred in granting Theige summary judgment in his individual capacity on Abdullah's claim for intentional interference with a business opportunity. Abdullah argues Theige acted recklessly and willfully, which coupled with the slanderous per se nature of Theige's allegations, precludes summary judgment. [¶ 21] In rejecting Abdullah's claim for tortious interference with a business relationship, the district court decided Abdullah failed to establish a predicate independent tort of slander necessary for that claim. [¶ 22] In Trade'N Post, L.L.C. v. World Duty Free Americas, Inc., 2001 ND 116, ¶ 35, 628 N.W.2d 707, we recognized a common law action for unlawful interference with a business relationship. We held a plaintiff must prove the following elements to prevail in a claim for unlawful interference with a business relationship: (1) the existence of a valid business relationship or expectancy; (2) knowledge by the interferer of the relationship or expectancy; (3) an independently tortious or otherwise unlawful act of interference by the interferer; (4) proof that the interference caused the harm sustained; and (5) actual damages to the party whose relationship or expectancy was disrupted. Id. at ¶ 36. [¶ 23] Although Abdullah's complaint does not specifically identify an independent tort to support his claim for unlawful interference with a business opportunity, he asserts statements by Theige were slanderous per se. However, he has not specified which statements by Theige were slanderous per se. Abdullah's amended complaint alleges "Theige acted recklessly or grossly negligently, with malfeasance, willfully and wantonly" in interfering with Abdullah's employment opportunity with another hospital after his scheduled graduation and Theige's actions included "a wrongful suspension from the program only eight (8) days prior to completion, issuance of an informal dismissal from the program in a letter dated November 6, 2006, asserted [Abdullah] failed to disclose authorship, which was erroneous, and failure to disclose in a timely fashion the evidence relied upon for the administrative hearing." In the district court, Abdullah argued Theige told the Hearing Panel that Abdullah was dishonest. However, Abdullah has not marshaled any other specific facts or legal authority to support the existence of an independent tort. [¶ 24] Under N.D.C.C. § 32-12.2-02(3)(b) and (d), a state employee may not be held liable for claims based upon a discretionary function, regardless of whether the discretion is abused, and a state employee may not be held liable for a decision resulting from a quasi-judicial act. A state employee may not be held liable in the employee's individual capacity for acts occurring within the scope of the employee's employment. N.D.C.C. § 32-12.2-03(3). See Nelson v. Gillette, 1997 ND 205, ¶¶ 13-20, 571 N.W.2d 332 (discussing scope of employment in context of action against political subdivision and social worker). Here, Abdullah does not dispute that Theige was acting within the scope of his employment as the director of the residency program at the UND School of Medicine, and we conclude Theige is immune from liability in his individual capacity under N.D.C.C. §§ 32-12.2-02(3)(b) and (d) and 32-12.2-03(3). See Lawrence v. Roberdeau, 2003 ND 124, ¶¶ 13-1 4, 665 N.W.2d 719 (testimony at judicial hearing governed by witness immunity). We conclude the district court did not err in granting summary judgment on Abdullah's claim for interference with a business opportunity. C [¶ 25] Abdullah argues the district court erred in granting summary judgment on his substantive due process claim under 42 U.S.C. § 1983. He asserts there are genuine issues of material fact about whether the actions by the University and Theige were unreasonable or arbitrary. The University and Theige argue Abdullah failed to demonstrate a violation of a clearly established law, because the right to attend a public school is not a fundamental right for purposes of substantive due process. [¶ 26] In rejecting Abdullah's substantive due process claim, the district court said Abdullah had no substantive right to continued education. The court explained that even if Abdullah had a substantive due process right to continuing education in the residency program, he failed to establish he was arbitrarily and capriciously dismissed from the program and a reasonable person could conclude he was properly dismissed from the program because of professionalism concerns. [¶ 27] In Washington v. Glucksberg, 521 U.S. 702, 719-21 (1997) (citations omitted), the United States Supreme Court explained parameters for the analysis of a substantive due process claim in the context of rejecting a substantive due process right to assisted suicide: The Due Process Clause guarantees more than fair process, and the "liberty" it protects includes more than the absence of physical restraint. The Clause also provides heightened protection against government interference with certain fundamental rights and liberty interests. In a long line of cases, we have held that, in addition to the specific freedoms protected by the Bill of Rights, the "liberty" specially protected by the Due Process Clause includes the rights to marry, to have children, to direct the education and upbringing of one's children, to marital privacy, to use contraception, to bodily integrity, and to abortion. We have also assumed, and strongly suggested, that the Due Process Clause protects the traditional right to refuse unwanted lifesaving medical treatment. But we "ha[ve] always been reluctant to expand the concept of substantive due process because guideposts for responsible decisionmaking in this unchartered area are scarce and open-ended." By extending constitutional protection to an asserted right or liberty interest, we, to a great extent, place the matter outside the arena of public debate and legislative action. We must therefore "exercise the utmost care whenever we are asked to break new ground in this field," lest the liberty protected by the Due Process Clause be subtly transformed into the policy preferences of the Members of this Court. Our established method of substantive-due-process analysis has two primary features: First, we have regularly observed that the Due Process Clause specially protects those fundamental rights and liberties which are, objectively," deeply rooted in this Nation's history and tradition, and "implicit in the concept of ordered liberty," such that "neither liberty nor justice would exist if they were sacrificed." Second, we have required in substantive-due-process cases a "careful description" of the asserted fundamental liberty interest. Our Nation's history, legal traditions, and practices thus provide the crucial "guideposts for responsible decisionmaking," that direct and restrain our exposition of the Due Process Clause. As we stated recently . . . the Fourteenth Amendment "forbids the government to infringe . . . `fundamental' liberty interests at all, no matter what process is provided, unless the infringement is narrowly tailored to serve a compelling state interest." [¶ 28] In two cases, the United States Supreme Court has assumed the existence of a substantive due process right in the context of academic dismissals from a state educational institution, but the Court has held that even if students' assumed property interest gave rise to a substantive due process right, the dismissals were not arbitrary and capricious. See Ewing, 474 U.S. at 222-23; Horowitz, 435 U.S. at 91-92. In Bell, however, the Sixth Circuit Court of Appeals rejected a claim that substantive due process protects a medical student's interest in continuing education. 351 F.3d at 251. After stating that the interests protected by substantive due process are much narrower than those protected by procedural due process, the court explained: Where . . . there is no equal protection violation, we can see no basis for finding that a medical student's interest in continuing her medical school education is protected by substantive due process (stressing, in the public university context, the similarity of equal protection and substantive due process). Certainly the contention that the medical college's actions were arbitrary or capricious cannot be sufficient; otherwise judicial review for compliance with substantive due process would become the equivalent of a typical state or federal Administrative Procedure Act. 351 F.3d at 251 (footnote and citations omitted). [¶ 29] We agree with the rationale of Bell and conclude Abdullah has not demonstrated that he has a substantive due process right to graduate from a public medical school. See C.D. v. Discroll, 82 F.3d 383, 387-88 (11th Cir. Ct. App. 1996) (student's suspension for fighting did not violate substantive due process; right to attend public schools is a state created right rather than a fundamental right for purposes of substantive due process). We conclude the district court did not err in granting summary judgment on Abdullah's substantive due process claim. D [¶ 30] Abdullah argues the district court erred in granting summary judgment on his claim for a violation of the ADA. The University and Theige respond that sovereign immunity bars Abdullah's claim for money damages under Title I of the ADA and that Abdullah failed to address the legal elements for a disability claim. [¶ 31] In rejecting Abdullah's claim for violation of the ADA, the district court said Abdullah had failed to present any facts to show that the University regarded his bouts with sleep deprivation as a disability and that the University dismissed Abdullah from the residency program because of that perceived disability. Rather, the district court concluded the evidence was clear the University dismissed Abdullah for professionalism concerns, which the court said a reasoning mind could find reasonable. [¶ 32] In the district court and this Court, Abdullah essentially concedes Board of Trustees of Univ. of Alabama v. Garrett, 531 U.S. 356 (2001), supports the University's position, but, without citing any other authority to support his ADA claim, Abdullah asserts he could amend his complaint to correct the "technicality." Abdullah has not moved to amend his complaint. Moreover, "[i]n summary judgment proceedings, neither the trial court nor the appellate court has any obligation, duty, or responsibility to search the record for evidence opposing the motion for summary judgment." Fish, 2003 ND 185, ¶ 15, 671 N.W.2d 819 (quoting Anderson, 2001 ND 125, ¶ 14, 630 N.W.2d 46). "The opposing party must also explain the connection between the factual assertions and the legal theories in the case, and cannot leave to the court the chore of divining what facts are relevant or why facts are relevant, let alone material, to the claim for relief." Fish, at ¶ 15 (quoting Anderson, at ¶ 14). [¶ 33] Abdullah has not identified facts to support an ADA claim or to identify a disability under the relevant statutes, or how those factual assertions may be relevant to his legal theory. We agree with the district court that Abdullah has failed to provide any facts to show that the University regarded his bout with sleep deprivation as a disability and that the University dismissed Abdullah from the residency program because of that perceived disability. The evidence before the Hearing Panel establishes that the decision to dismiss Abdullah was not based on his perceived mental health, but was based on his lack of professionalism. On this record we conclude the district court did not err in granting summary judgment on Abdullah's ADA claim. IV [¶ 34] We affirm the summary judgment. [¶ 35] Mary Muehlen Maring Carol Ronning Kapsner Ronald E. Goodman, S.J. Kirk Smith, S.J. Gerald W. VandeWalle, C.J. [¶ 36] The Honorable Ronald E. Goodman, S.J., and the Honorable Kirk Smith, S.J., sitting in place of Sandstrom, J., and Crothers, J., disqualified.
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Kenneth Kaiser The former head of the Boston FBI office has agreed to plead guilty to an ethics charge in an agreement that includes a recommendation from prosecutors that he serve no prison time and pay a $15,000 fine.
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Q: Thumbnail limit max ''6'' images I'm using Drupal 7 and create a module for my content thumbnail images frontpage display. Working this: if(count($p_detail->field_slide) > 0){ $output .= '<div class="right">'; $output .= '<ul class="thumbs">'; $i=1; foreach($p_detail->field_slide['und'] as $thumb): $img_path = $thumb['uri']; $img_url = image_style_url('tmb_240x117', $img_path); $img_file = '<img src="'.$img_url.'" alt="'.$p_detail->title.'" />'; $output .= '<li> <a href="'.$p_url.'"> '.$img_file.' <div class="shadow"></div> <div class="hoverimg"></div> </a> <div class="img_no">0'.$i.'</div> </li>'; $i++; endforeach; $output .= '</ul>'; $output .= '</div>'; } This codes is working. But i want show max thumbnails 6 images. For example, have got 20 images, show only first 6 images. If 2 images, only thumbnails 2 images. How can i do this? A: You could just add this line below your foreach: foreach($p_detail->field_slide['und'] as $thumb): if($i>6) { break; } $img_path = $thumb['uri']; This will just end the foreach loop after 6 images has been printed.
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Q: Tensorflow mIOU and pixel accuracy bug? Let's say I started training a tensorflow model from scratch with 1000 training steps. I get the following result at the completion of training. Now, lets say I want to train for 2000 training steps from the previously saved checkpoint. I get the mIOU and pixel_accuracy = 1.0. I am using '''TensorFlow v1.13.1'''. How can I fix this bug or problem ? A: The problem was with my data-set. I was assigning background_tag=1, class_one=2, class_two=3. After modifying ground truth images python PIL everything worked normally.
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Like this: A new WordPress theme has been implemented as part of the re-branding process. Blog posting will continue as it normally does, so there are no worries there. Things are looking pretty funky though, so while the regular blog activities are taking place I will be optimizing each post so that it fits normally. Cheers! Like this: He retreated back into his room, locking the door and sliding the dresser in front of it. Writing and photography by Penny C. Jared poked his head out into the hallway cautiously. It was brightly lit, almost blinding his eyes,but he could see nothing. On the other hand he could hear something walking across the linoleum flooring. A great many somethings. He retreated back into his room, locking the door and sliding the dresser in front of it. It was time to review his escape since the hallway was no longer a viable route. Like this: Old Beardless stood, watching the girl at the table nearby. She knew what he was up to, but there was little he could do about it. If he moved an inch everyone would know what he was up to (or assume that they did). That was just another stroke of bad luck on his part. Ever since he had killed the last one his life had been nothing but a series of mishaps. Old Beardless continued the ruse with a sigh. This is so damn boring, he thought to himself. It wouldn’t be long before she slipped up. Like this: When he had touched down on the surface of Mars Carlson took out a book-shaped bundle. Writing and photography by P. L Cobb Up, up, up. Carlson ascended into the heavens, passing clouds, passing through the ozone layer. Someone must have seen him on his journey upwards; he wasn’t travelling very fast. That thought quickly turned to other, more important things as the vacuum of space pulled at him. Carlson let out a sigh, knowing that it was his own spell that protected him from a sudden and brutal death. Continue reading → Like this: I had done it again: I had lost my keys in the dark. When and where had they fallen? I was at a loss. With hands curled up into fists I pounded on the door to my home. My roommate was normally there. Just not tonight. “Shit!” I swore under my breath. I peeked into the living room window, or tried. Everything in the inside was dark from my vantage-point, so there was no luck there. I was about to turn around when I heard a tinkling sound. It was the tinkling of spurs, the type you found on cowboy boots. When I looked it was just me and the street lamps. I looked everywhere for the source of the noise, but came up with nothing; all the while the sound started to increase in intensity. It sounded like someone rushing up towards me. My heart began to pound. Aural hallucinations! I thought frantically to myself. That’s all. No need to worry! That didn’t stop the sound from getting closer though. And there was no convenient off button . . . Behind you! I swung around just in time to see a dead man sitting atop a horse–a wraith-like cowboy rushing up towards me–death with a revolver in place of his scythe. The skeletal figure took one shot at me. Like this: Story and photography by Penny C. Chrystopher. I am now Chrystopher, he told himself once more. It had been a long time since he had done this . . . Reflect upon himself. Chrystopher promised a new beginning. That was his hope. He still couldn’t trust himself not to fall back into old habits–to fall back into his darker self. When everything was young he had been different; he swore that he had never been so evil. He had simply grown into it. He hated that, but it was the truth. “I hate myself,” he murmured. Chrystopher wasn’t trying to be hard on himself, just honest. Again with that? a part of him said in derision. Just forget it; it’s futile and you know this. Don’t disappoint yourself! Perhaps that part of him was right? “It probably is,” he reminded himself. It was him, after all. At that thought he allowed himself a deep chuckle. “I was such a bastard!” You still are! the cynical voice replied. That part of him was his darker self. Chrystopher didn’t have to like it, but that part of him would always be with him; he was better off accepting that now. Memories of the past flooded him with regret. Sometimes he wondered what his life would have been like had he woken up to himself sooner? Would the king out of darkness still have his wife? Would his son still have aligned himself with the opposing faction, and would he still have disowned and exiled him? Would he have absconded his duties as a father, and would he have allowed his mistress to terrorize his children? Would his youngest daughter be alive today? When Marianna left he had hated her for it; she was unhappy, and because of that had left him and their children. Da’Kiri–his old self–had fallen into madness. That had been so long ago, he wouldn’t be surprised if she had passed into oblivion.
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Related Stories Pic River First Nation has submitted a proposal to build a hydroelectric facility in Pukaskwa National Park. It would be at Chigamiwinigum Falls on White River, a site located within the First Nation's traditional territory. The First Nation has extensive experience in this area, according to Byron LeClair, Pic River's director of energy project development "I think that our 25 years of experience — in terms of developing, owning and operating these types of facilities — shows that we're capable of developing these projects with minimal impact to the environment." Byron LeClair is the father of Jaret LeCalir, one of the four young men killed in a car crash two years ago. (Supplied) LeClair said the Pukaskwa facility would produce enough electricity for more than 12,000 homes every year. Added to the Pic River Energy portfolio, this would push the community's supply of electricity to about 33,000 Ontario homes. The project would cost in excess of a $100 million and be Pic River's largest project to date. Compatible project? The development would be a natural fit for the First Nation, he said. "We have history, in terms of being able to balance a commercial need to generate renewable energy against preserving park values, and ... from our perspective, we don't see renewable energy and the national park mandate as being incompatible." A spokesperson for Parks Canada confirmed that officials from Pukaskwa Park met with Pic River First Nation on Wednesday. LeClair said they hope to complete the environmental assessment as soon as possible, and look forward to new construction taking place in 2018.
Mid
[ 0.637254901960784, 32.5, 18.5 ]
/* Unix SMB/CIFS implementation. Inter-process communication and named pipe handling Copyright (C) Andrew Tridgell 1992-1998 SMB Version handling Copyright (C) John H Terpstra 1995-1998 This program is free software; you can redistribute it and/or modify it under the terms of the GNU General Public License as published by the Free Software Foundation; either version 2 of the License, or (at your option) any later version. This program is distributed in the hope that it will be useful, but WITHOUT ANY WARRANTY; without even the implied warranty of MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE. See the GNU General Public License for more details. You should have received a copy of the GNU General Public License along with this program; if not, write to the Free Software Foundation, Inc., 675 Mass Ave, Cambridge, MA 02139, USA. */ /* This file handles the named pipe and mailslot calls in the SMBtrans protocol */ #include "includes.h" extern int max_send; #define NERR_notsupported 50 extern int smb_read_error; /******************************************************************* copies parameters and data, as needed, into the smb buffer *both* the data and params sections should be aligned. this is fudged in the rpc pipes by at present, only the data section is. this may be a possible cause of some of the ipc problems being experienced. lkcl26dec97 ******************************************************************/ static void copy_trans_params_and_data(char *outbuf, int align, char *rparam, int param_offset, int param_len, char *rdata, int data_offset, int data_len) { char *copy_into = smb_buf(outbuf)+1; if(param_len < 0) param_len = 0; if(data_len < 0) data_len = 0; DEBUG(5,("copy_trans_params_and_data: params[%d..%d] data[%d..%d]\n", param_offset, param_offset + param_len, data_offset , data_offset + data_len)); if (param_len) memcpy(copy_into, &rparam[param_offset], param_len); copy_into += param_len + align; if (data_len ) memcpy(copy_into, &rdata[data_offset], data_len); } /**************************************************************************** Send a trans reply. ****************************************************************************/ void send_trans_reply(char *outbuf, char *rparam, int rparam_len, char *rdata, int rdata_len, BOOL buffer_too_large) { int this_ldata,this_lparam; int tot_data_sent = 0; int tot_param_sent = 0; int align; int ldata = rdata ? rdata_len : 0; int lparam = rparam ? rparam_len : 0; if (buffer_too_large) DEBUG(5,("send_trans_reply: buffer %d too large\n", ldata )); this_lparam = MIN(lparam,max_send - 500); /* hack */ this_ldata = MIN(ldata,max_send - (500+this_lparam)); align = ((this_lparam)%4); if (buffer_too_large) { ERROR_BOTH(STATUS_BUFFER_OVERFLOW,ERRDOS,ERRmoredata); } set_message(outbuf,10,1+align+this_ldata+this_lparam,True); copy_trans_params_and_data(outbuf, align, rparam, tot_param_sent, this_lparam, rdata, tot_data_sent, this_ldata); SSVAL(outbuf,smb_vwv0,lparam); SSVAL(outbuf,smb_vwv1,ldata); SSVAL(outbuf,smb_vwv3,this_lparam); SSVAL(outbuf,smb_vwv4,smb_offset(smb_buf(outbuf)+1,outbuf)); SSVAL(outbuf,smb_vwv5,0); SSVAL(outbuf,smb_vwv6,this_ldata); SSVAL(outbuf,smb_vwv7,smb_offset(smb_buf(outbuf)+1+this_lparam+align,outbuf)); SSVAL(outbuf,smb_vwv8,0); SSVAL(outbuf,smb_vwv9,0); show_msg(outbuf); if (!send_smb(smbd_server_fd(),outbuf)) exit_server_cleanly("send_trans_reply: send_smb failed."); tot_data_sent = this_ldata; tot_param_sent = this_lparam; while (tot_data_sent < ldata || tot_param_sent < lparam) { this_lparam = MIN(lparam-tot_param_sent, max_send - 500); /* hack */ this_ldata = MIN(ldata -tot_data_sent, max_send - (500+this_lparam)); if(this_lparam < 0) this_lparam = 0; if(this_ldata < 0) this_ldata = 0; align = (this_lparam%4); set_message(outbuf,10,1+this_ldata+this_lparam+align,False); copy_trans_params_and_data(outbuf, align, rparam, tot_param_sent, this_lparam, rdata, tot_data_sent, this_ldata); SSVAL(outbuf,smb_vwv3,this_lparam); SSVAL(outbuf,smb_vwv4,smb_offset(smb_buf(outbuf)+1,outbuf)); SSVAL(outbuf,smb_vwv5,tot_param_sent); SSVAL(outbuf,smb_vwv6,this_ldata); SSVAL(outbuf,smb_vwv7,smb_offset(smb_buf(outbuf)+1+this_lparam+align,outbuf)); SSVAL(outbuf,smb_vwv8,tot_data_sent); SSVAL(outbuf,smb_vwv9,0); show_msg(outbuf); if (!send_smb(smbd_server_fd(),outbuf)) exit_server_cleanly("send_trans_reply: send_smb failed."); tot_data_sent += this_ldata; tot_param_sent += this_lparam; } } /**************************************************************************** Start the first part of an RPC reply which began with an SMBtrans request. ****************************************************************************/ static BOOL api_rpc_trans_reply(char *outbuf, smb_np_struct *p) { BOOL is_data_outstanding; char *rdata = (char *)SMB_MALLOC(p->max_trans_reply); int data_len; if(rdata == NULL) { DEBUG(0,("api_rpc_trans_reply: malloc fail.\n")); return False; } if((data_len = read_from_pipe( p, rdata, p->max_trans_reply, &is_data_outstanding)) < 0) { SAFE_FREE(rdata); return False; } send_trans_reply(outbuf, NULL, 0, rdata, data_len, is_data_outstanding); SAFE_FREE(rdata); return True; } /**************************************************************************** WaitNamedPipeHandleState ****************************************************************************/ static BOOL api_WNPHS(char *outbuf, smb_np_struct *p, char *param, int param_len) { uint16 priority; if (!param || param_len < 2) return False; priority = SVAL(param,0); DEBUG(4,("WaitNamedPipeHandleState priority %x\n", priority)); if (wait_rpc_pipe_hnd_state(p, priority)) { /* now send the reply */ send_trans_reply(outbuf, NULL, 0, NULL, 0, False); return True; } return False; } /**************************************************************************** SetNamedPipeHandleState ****************************************************************************/ static BOOL api_SNPHS(char *outbuf, smb_np_struct *p, char *param, int param_len) { uint16 id; if (!param || param_len < 2) return False; id = SVAL(param,0); DEBUG(4,("SetNamedPipeHandleState to code %x\n", id)); if (set_rpc_pipe_hnd_state(p, id)) { /* now send the reply */ send_trans_reply(outbuf, NULL, 0, NULL, 0, False); return True; } return False; } /**************************************************************************** When no reply is generated, indicate unsupported. ****************************************************************************/ static BOOL api_no_reply(char *outbuf, int max_rdata_len) { char rparam[4]; /* unsupported */ SSVAL(rparam,0,NERR_notsupported); SSVAL(rparam,2,0); /* converter word */ DEBUG(3,("Unsupported API fd command\n")); /* now send the reply */ send_trans_reply(outbuf, rparam, 4, NULL, 0, False); return -1; } /**************************************************************************** Handle remote api calls delivered to a named pipe already opened. ****************************************************************************/ static int api_fd_reply(connection_struct *conn,uint16 vuid,char *outbuf, uint16 *setup,char *data,char *params, int suwcnt,int tdscnt,int tpscnt,int mdrcnt,int mprcnt) { BOOL reply = False; smb_np_struct *p = NULL; int pnum; int subcommand; DEBUG(5,("api_fd_reply\n")); /* First find out the name of this file. */ if (suwcnt != 2) { DEBUG(0,("Unexpected named pipe transaction.\n")); return ERROR_NT(NT_STATUS_INVALID_PARAMETER); } /* Get the file handle and hence the file name. */ /* * NB. The setup array has already been transformed * via SVAL and so is in gost byte order. */ pnum = ((int)setup[1]) & 0xFFFF; subcommand = ((int)setup[0]) & 0xFFFF; if(!(p = get_rpc_pipe(pnum))) { if (subcommand == TRANSACT_WAITNAMEDPIPEHANDLESTATE) { /* Win9x does this call with a unicode pipe name, not a pnum. */ /* Just return success for now... */ DEBUG(3,("Got TRANSACT_WAITNAMEDPIPEHANDLESTATE on text pipe name\n")); send_trans_reply(outbuf, NULL, 0, NULL, 0, False); return -1; } DEBUG(1,("api_fd_reply: INVALID PIPE HANDLE: %x\n", pnum)); return ERROR_NT(NT_STATUS_INVALID_HANDLE); } if (vuid != p->vuid) { DEBUG(1, ("Got pipe request (pnum %x) using invalid VUID %d, " "expected %d\n", pnum, vuid, p->vuid)); return ERROR_NT(NT_STATUS_INVALID_HANDLE); } DEBUG(3,("Got API command 0x%x on pipe \"%s\" (pnum %x)\n", subcommand, p->name, pnum)); /* record maximum data length that can be transmitted in an SMBtrans */ p->max_trans_reply = mdrcnt; DEBUG(10,("api_fd_reply: p:%p max_trans_reply: %d\n", p, p->max_trans_reply)); switch (subcommand) { case TRANSACT_DCERPCCMD: /* dce/rpc command */ reply = write_to_pipe(p, data, tdscnt); if (reply) reply = api_rpc_trans_reply(outbuf, p); break; case TRANSACT_WAITNAMEDPIPEHANDLESTATE: /* Wait Named Pipe Handle state */ reply = api_WNPHS(outbuf, p, params, tpscnt); break; case TRANSACT_SETNAMEDPIPEHANDLESTATE: /* Set Named Pipe Handle state */ reply = api_SNPHS(outbuf, p, params, tpscnt); break; default: return ERROR_NT(NT_STATUS_INVALID_PARAMETER); } if (!reply) return api_no_reply(outbuf, mdrcnt); return -1; } /**************************************************************************** handle named pipe commands ****************************************************************************/ static int named_pipe(connection_struct *conn,uint16 vuid, char *outbuf,char *name, uint16 *setup,char *data,char *params, int suwcnt,int tdscnt,int tpscnt, int msrcnt,int mdrcnt,int mprcnt) { DEBUG(3,("named pipe command on <%s> name\n", name)); if (strequal(name,"LANMAN")) return api_reply(conn,vuid,outbuf,data,params,tdscnt,tpscnt,mdrcnt,mprcnt); if (strequal(name,"WKSSVC") || strequal(name,"SRVSVC") || strequal(name,"WINREG") || strequal(name,"SAMR") || strequal(name,"LSARPC")) { DEBUG(4,("named pipe command from Win95 (wow!)\n")); return api_fd_reply(conn,vuid,outbuf,setup,data,params,suwcnt,tdscnt,tpscnt,mdrcnt,mprcnt); } if (strlen(name) < 1) return api_fd_reply(conn,vuid,outbuf,setup,data,params,suwcnt,tdscnt,tpscnt,mdrcnt,mprcnt); if (setup) DEBUG(3,("unknown named pipe: setup 0x%X setup1=%d\n", (int)setup[0],(int)setup[1])); return 0; } static NTSTATUS handle_trans(connection_struct *conn, struct trans_state *state, char *outbuf, int *outsize) { char *local_machine_name; int name_offset = 0; DEBUG(3,("trans <%s> data=%u params=%u setup=%u\n", state->name,(unsigned int)state->total_data,(unsigned int)state->total_param, (unsigned int)state->setup_count)); /* * WinCE wierdness.... */ local_machine_name = talloc_asprintf(state, "\\%s\\", get_local_machine_name()); if (local_machine_name == NULL) { return NT_STATUS_NO_MEMORY; } if (strnequal(state->name, local_machine_name, strlen(local_machine_name))) { name_offset = strlen(local_machine_name)-1; } if (!strnequal(&state->name[name_offset], "\\PIPE", strlen("\\PIPE"))) { return NT_STATUS_NOT_SUPPORTED; } name_offset += strlen("\\PIPE"); /* Win9x weirdness. When talking to a unicode server Win9x only sends \PIPE instead of \PIPE\ */ if (state->name[name_offset] == '\\') name_offset++; DEBUG(5,("calling named_pipe\n")); *outsize = named_pipe(conn, state->vuid, outbuf, state->name+name_offset, state->setup,state->data, state->param, state->setup_count,state->total_data, state->total_param, state->max_setup_return, state->max_data_return, state->max_param_return); if (*outsize == 0) { return NT_STATUS_NOT_SUPPORTED; } if (state->close_on_completion) close_cnum(conn,state->vuid); return NT_STATUS_OK; } /**************************************************************************** Reply to a SMBtrans. ****************************************************************************/ int reply_trans(connection_struct *conn, char *inbuf,char *outbuf, int size, int bufsize) { int outsize = 0; unsigned int dsoff = SVAL(inbuf, smb_dsoff); unsigned int dscnt = SVAL(inbuf, smb_dscnt); unsigned int psoff = SVAL(inbuf, smb_psoff); unsigned int pscnt = SVAL(inbuf, smb_pscnt); unsigned int av_size = size-4; struct trans_state *state; NTSTATUS result; START_PROFILE(SMBtrans); result = allow_new_trans(conn->pending_trans, SVAL(inbuf, smb_mid)); if (!NT_STATUS_IS_OK(result)) { DEBUG(2, ("Got invalid trans request: %s\n", nt_errstr(result))); END_PROFILE(SMBtrans); return ERROR_NT(result); } if ((state = TALLOC_P(conn->mem_ctx, struct trans_state)) == NULL) { DEBUG(0, ("talloc failed\n")); END_PROFILE(SMBtrans); return ERROR_NT(NT_STATUS_NO_MEMORY); } state->cmd = SMBtrans; state->mid = SVAL(inbuf, smb_mid); state->vuid = SVAL(inbuf, smb_uid); state->setup_count = CVAL(inbuf, smb_suwcnt); state->setup = NULL; state->total_param = SVAL(inbuf, smb_tpscnt); state->param = NULL; state->total_data = SVAL(inbuf, smb_tdscnt); state->data = NULL; state->max_param_return = SVAL(inbuf, smb_mprcnt); state->max_data_return = SVAL(inbuf, smb_mdrcnt); state->max_setup_return = CVAL(inbuf, smb_msrcnt); state->close_on_completion = BITSETW(inbuf+smb_vwv5,0); state->one_way = BITSETW(inbuf+smb_vwv5,1); memset(state->name, '\0',sizeof(state->name)); srvstr_pull_buf(inbuf, state->name, smb_buf(inbuf), sizeof(state->name), STR_TERMINATE); if ((dscnt > state->total_data) || (pscnt > state->total_param)) goto bad_param; if (state->total_data) { /* Can't use talloc here, the core routines do realloc on the * params and data. Out of paranoia, 100 bytes too many. */ state->data = (char *)SMB_MALLOC(state->total_data+100); if (state->data == NULL) { DEBUG(0,("reply_trans: data malloc fail for %u " "bytes !\n", (unsigned int)state->total_data)); TALLOC_FREE(state); END_PROFILE(SMBtrans); return(ERROR_DOS(ERRDOS,ERRnomem)); } /* null-terminate the slack space */ memset(&state->data[state->total_data], 0, 100); if (dscnt > state->total_data || dsoff+dscnt < dsoff) { goto bad_param; } if (dsoff > av_size || dscnt > av_size || dsoff+dscnt > av_size) { goto bad_param; } memcpy(state->data,smb_base(inbuf)+dsoff,dscnt); } if (state->total_param) { /* Can't use talloc here, the core routines do realloc on the * params and data. Out of paranoia, 100 bytes too many */ state->param = (char *)SMB_MALLOC(state->total_param+100); if (state->param == NULL) { DEBUG(0,("reply_trans: param malloc fail for %u " "bytes !\n", (unsigned int)state->total_param)); SAFE_FREE(state->data); TALLOC_FREE(state); END_PROFILE(SMBtrans); return(ERROR_DOS(ERRDOS,ERRnomem)); } /* null-terminate the slack space */ memset(&state->param[state->total_param], 0, 100); if (pscnt > state->total_param || psoff+pscnt < psoff) { goto bad_param; } if (psoff > av_size || pscnt > av_size || psoff+pscnt > av_size) { goto bad_param; } memcpy(state->param,smb_base(inbuf)+psoff,pscnt); } state->received_data = dscnt; state->received_param = pscnt; if (state->setup_count) { unsigned int i; if((state->setup = TALLOC_ARRAY( state, uint16, state->setup_count)) == NULL) { DEBUG(0,("reply_trans: setup malloc fail for %u " "bytes !\n", (unsigned int) (state->setup_count * sizeof(uint16)))); TALLOC_FREE(state); END_PROFILE(SMBtrans); return(ERROR_DOS(ERRDOS,ERRnomem)); } if (inbuf+smb_vwv14+(state->setup_count*SIZEOFWORD) > inbuf + size) goto bad_param; if ((smb_vwv14+(state->setup_count*SIZEOFWORD) < smb_vwv14) || (smb_vwv14+(state->setup_count*SIZEOFWORD) < (state->setup_count*SIZEOFWORD))) goto bad_param; for (i=0;i<state->setup_count;i++) state->setup[i] = SVAL(inbuf,smb_vwv14+i*SIZEOFWORD); } state->received_param = pscnt; if ((state->received_param == state->total_param) && (state->received_data == state->total_data)) { result = handle_trans(conn, state, outbuf, &outsize); SAFE_FREE(state->data); SAFE_FREE(state->param); TALLOC_FREE(state); if (!NT_STATUS_IS_OK(result)) { END_PROFILE(SMBtrans); return ERROR_NT(result); } if (outsize == 0) { END_PROFILE(SMBtrans); return ERROR_NT(NT_STATUS_INTERNAL_ERROR); } END_PROFILE(SMBtrans); return outsize; } DLIST_ADD(conn->pending_trans, state); /* We need to send an interim response then receive the rest of the parameter/data bytes */ outsize = set_message(outbuf,0,0,True); show_msg(outbuf); END_PROFILE(SMBtrans); return outsize; bad_param: DEBUG(0,("reply_trans: invalid trans parameters\n")); SAFE_FREE(state->data); SAFE_FREE(state->param); TALLOC_FREE(state); END_PROFILE(SMBtrans); return ERROR_NT(NT_STATUS_INVALID_PARAMETER); } /**************************************************************************** Reply to a secondary SMBtrans. ****************************************************************************/ int reply_transs(connection_struct *conn, char *inbuf,char *outbuf, int size, int bufsize) { int outsize = 0; unsigned int pcnt,poff,dcnt,doff,pdisp,ddisp; unsigned int av_size = size-4; struct trans_state *state; NTSTATUS result; START_PROFILE(SMBtranss); show_msg(inbuf); for (state = conn->pending_trans; state != NULL; state = state->next) { if (state->mid == SVAL(inbuf,smb_mid)) { break; } } if ((state == NULL) || (state->cmd != SMBtrans)) { END_PROFILE(SMBtranss); return ERROR_NT(NT_STATUS_INVALID_PARAMETER); } /* Revise total_params and total_data in case they have changed * downwards */ if (SVAL(inbuf, smb_vwv0) < state->total_param) state->total_param = SVAL(inbuf,smb_vwv0); if (SVAL(inbuf, smb_vwv1) < state->total_data) state->total_data = SVAL(inbuf,smb_vwv1); pcnt = SVAL(inbuf, smb_spscnt); poff = SVAL(inbuf, smb_spsoff); pdisp = SVAL(inbuf, smb_spsdisp); dcnt = SVAL(inbuf, smb_sdscnt); doff = SVAL(inbuf, smb_sdsoff); ddisp = SVAL(inbuf, smb_sdsdisp); state->received_param += pcnt; state->received_data += dcnt; if ((state->received_data > state->total_data) || (state->received_param > state->total_param)) goto bad_param; if (pcnt) { if (pdisp > state->total_param || pcnt > state->total_param || pdisp+pcnt > state->total_param || pdisp+pcnt < pdisp) { goto bad_param; } if (poff > av_size || pcnt > av_size || poff+pcnt > av_size || poff+pcnt < poff) { goto bad_param; } memcpy(state->param+pdisp,smb_base(inbuf)+poff, pcnt); } if (dcnt) { if (ddisp > state->total_data || dcnt > state->total_data || ddisp+dcnt > state->total_data || ddisp+dcnt < ddisp) { goto bad_param; } if (doff > av_size || dcnt > av_size || doff+dcnt > av_size || doff+dcnt < doff) { goto bad_param; } memcpy(state->data+ddisp, smb_base(inbuf)+doff, dcnt); } if ((state->received_param < state->total_param) || (state->received_data < state->total_data)) { END_PROFILE(SMBtranss); return -1; } /* construct_reply_common has done us the favor to pre-fill the * command field with SMBtranss which is wrong :-) */ SCVAL(outbuf,smb_com,SMBtrans); result = handle_trans(conn, state, outbuf, &outsize); DLIST_REMOVE(conn->pending_trans, state); SAFE_FREE(state->data); SAFE_FREE(state->param); TALLOC_FREE(state); if ((outsize == 0) || !NT_STATUS_IS_OK(result)) { END_PROFILE(SMBtranss); return(ERROR_DOS(ERRSRV,ERRnosupport)); } END_PROFILE(SMBtranss); return(outsize); bad_param: DEBUG(0,("reply_transs: invalid trans parameters\n")); DLIST_REMOVE(conn->pending_trans, state); SAFE_FREE(state->data); SAFE_FREE(state->param); TALLOC_FREE(state); END_PROFILE(SMBtranss); return ERROR_NT(NT_STATUS_INVALID_PARAMETER); }
Mid
[ 0.581497797356828, 33, 23.75 ]
No word on what those actual words are, but no doubt they're said with poise and confidence - judging by the photos the royals posted this week which show a very happy and grown up young lady on her first day of school. Since her nanny, Maria Turrion Borrallo, is from Spain, she has picked up some Spanish phrases from her. It makes sense that the pint-sized prince and princess are learning to speak Spanish, in particular. A year ago the Duchess apparently told a member of the public that Borrallo is trying to teach Charlotte Spanish, whilst George can already count up to ten in the language. She may have just started nursery school but already Princess Charlotte, 2, has a certain royal charm. and a good command of Spanish! Newton took a hard hit in the fourth quarter in which he claimed his helmet came down over his eyes and hurt his right eye. Yet, a few yards from the sideline, he stopped and collapsed to the ground, going on all fours and staring at the ground. Gruden is scheduled to work the network's playoff game Saturday in Kansas City between the Chiefs and Tennessee Titans . Oakland had previously traded Gruden to Tampa Bay for four draft picks after Gruden spent four seasons with the team. The founder of Fidei Polytechnic, Gboko, the first private polytechnic in Northern Nigeria was in April 2017. The post FFK takes another swipe at Buhari's board appointments appeared first on Vanguard News . The fact that no Republicans have signed on to the resolution likely means it would be defeated in a floor vote. The FCC's recent repeal of net neutrality rules is going to get a second look, thanks to Senate Democrats. Even when consumers place coffee cups in recycling bins, there's now no way for recycling plants to recycle them. Creagh said coffee shops have been "pulling the wool" over customers' eyes by saying their cups are recyclable. It comes a day after Chinese customs data was revealed claiming Beijing exported no oil products to North Korea in November. Trump's key to North Korea, however, has always been China and his personal relationship with Xi. We're already watching next Tuesday ... another weather system and drop in temps could bring more snow chances to the Mid-South. "But as of right now, there could be snow out in Pittsburgh, and some could be lingering into Sunday ", Evanego said. Tom Huddlestone had a 50th minute shot deflect wide for a corner, before Carson was forced to save from Mata at the other end. Marcus Olsson had Derby's first chance in the 22nd minute, and Sergio Romero had to be alert to tip over the crossbar. This will be Brown's second major film after Legendary and Warner Bros.'s Godzilla: King of Monsters which will release in 2019. Even so, the idea of Millie Bobby Brown solving crimes in 1880s England is definitely enough to get us excited. The American Red Cross is issuing an urgent call for blood and platelet donors Monday to help tackle a winter blood shortage . Eligible donors with types O, A negative and B negative blood are urged to make a Power Red donation, where available. Razer's New Laptop Uses Their Upcoming Phone To Power It It sports a 13.3-inch display , with a Quad HD resolution and a 120Hz refresh rate which is also available on the Razer Phone . The Razer Phone docks easily into Project Linda and connects with a simple key press, seamlessly integrating the devices. MI couple wanted in death of 4-year-old arrested in Georgia WDIV reported that the girl's January 1 death was not the first time police have been called to the couple's mobile home. Brad Fields, 28, faces murder, child abuse and torture charges in the death of Gabrielle Barrett on January 1, 2018. Fired Google engineer's suit claims reverse discrimination The company is 69% male and 56% white, although Google does not report how many describe themselves as "conservative". Google terminated Damore for the memo, saying it was contrary to the company's basic values and code of conduct. Samsung The Wall unveiled as the future of TV The advancements include easier sharing and connectivity, simpler controls for the television, and syncing with other devices. Samsung claims, "The Q9S incorporates AI technology to deliver clear and pristine 8K resolution for any type of content". Packers hire Brian Gutekunst as general manager Wolf's son Eliot Wolf was probably the most likely candidate for the job, but it ultimately went to Gutekunst. He was promoted to director of of college scouting in 2012 and director of player personnel in March of 2016. Fire at Home of Roy Moore Accuser Being Investigated for Arson He lost the special election to Democrat Doug Jones on December 12, turning Alabama blue from red for the first time in 25 years. Multiple neighbors witnessed a young man known for public intoxication walking around the house during the time of the fire. New Year's Eve weather update Cold temperatures are expected to continue into New Year's Day, with a high of around 15 degrees and a low of around 3 degrees. The combination of cold air and wind will drive wind chill readings down to below zero into Monday morning. Anand surprises himself with World Rapid title triumph One thing is certain; chess fans all around the world will have their eyes firmly on the next phase of the tournament. My last two rapid tournaments have been nothing short of disasters. "I came here in a pessimistic frame of mind".
Mid
[ 0.563706563706563, 36.5, 28.25 ]
Correction: Polyoxometalate-coupled MXene nanohybrid via poly(ionic liquid) linkers and its electrode for enhanced supercapacitive performance. Correction for 'Polyoxometalate-coupled MXene nanohybrid via poly(ionic liquid) linkers and its electrode for enhanced supercapacitive performance' by Shu Chen et al., Nanoscale, 2018, DOI: 10.1039/c8nr05760e.
High
[ 0.6830680173661361, 29.5, 13.6875 ]
5 Things to Know Before Hiking Rainbow Mountain At 5,200 meters altitude and boasting Instagram-worthy landscapes, Rainbow Mountain (or monte de siete colores) is without a doubt a bucket list item for thousands of people around the globe. The colorful mountain was definitely a must-do item for me during my time in Peru, and boy was it a crazy day! Here are five things every traveler should know before hiking Rainbow Mountain. 1. Altitude As mentioned above, Rainbow Mountain sits at an altitude of over 3 miles above sea-level! Even as a native of Denver, Colorado (mile-high city!) the tremendous altitude had a dizzying affect when hiking the trail. Always remember to drink coca tea throughout your time in Cuzco which is available almost everywhere. The coca leaves help counter symptoms of altitude sickness, as well as drinking plenty of water! 2. Weather Rainbow Mountain can be a bit of a treacherous hike, but even more so in the rain. The day I went happened to be good weather, and it was still ridiculously cold at the summit so make sure to dress in several warm layers. If it is raining, I DO NOT recommend hiking this trail. Several other articles have been written about the dangers of this hike during rainy weather – mainly addressing the fact that the actual trail turns into a mud slick and hikers get injured. Keep in mind that tour companies do not get paid if tours get canceled, so they will never cancel tours due to weather (even though there are safety concerns). freezing my ass off on the trail 3. Getting There How long does a day trip to Rainbow Mountain actually take? To be honest ALL DAY and a very long day at that. Tours generally head out at 3:30 am or 5 am depending on the company and the drive itself is 3 hours of curvaceous mountain roads. When you add in a bathroom stop and a breakfast stop, the journey to the trail head can very well be nearly five hours. The trail is supposed to take two hours to summit and another hour to get down. Keep in mind that this estimate varies greatly. On my tour, a trio from Mexico had two of their members injured their ankles but they decided to summit anyway which caused the rest of the group to wait in the vans for over an hour. The long road home will land you back in Cusco well after nightfall. Rainbow Mountain trailhead 4. The Hike As I mentioned before, I am from Colorado – a state where natives frequently summit 14,000 ft. peaks just for fun. That being said, I didn’t find the Rainbow Mountain hike to be particularly hard, but I might be alone in that sentiment. A Peruvian friend I made on the bus barely made it to the top, had to make frequent stops, and eventually sequestered me into agreeing to rent horses for the second half. Yes, you can rent a horse with a guide to lead you up the trail, but keep in mind that they cost more at and around the trailhead than they do further up the way. By the time my friend couldn’t take the hike anymore, we were about halfway up and the horses only cost $10 as opposed to $25. It’s a nice way to switch up the trail if you are feeling winded by the time you really start gaining altitude! Certain areas of the trail are very slick due to mud, especially if it has rained recently. Keep a close eye out and watch your footing. There are snacks, drinks, and candy bars for sale at the area just below the summit, but it’s much cheaper to pack your own. Make sure to pack plenty of snacks, extra socks, and gloves. It’s windy at the top! a horse and guide for rent on the trail 5. Photo Opps When I say that Rainbow Mountain has exploded with tourism in the last four years, I mean EXPLODED. This once quiet area of the Andean terrain now welcomes thousands of travelers daily, so don’t be surprised to have to wait your turn to snap your perfect photo. The summit will be quite crowded when you reach it, and it takes a decent amount of trial and error to grab a shot without other people in it. Bear in mind that the summit is icy cold as well, which discourages many trekkers from waiting it out to get the photos they want. Make sure you are warm and ready before you take on that last incline! crowds of tourists at the summit Want more travel tips and updates? Don’t forget to subscribe to the blog and follow me on Instagram! Share this: Like this: Post navigation About Nat Hi, I’m Natalie West and I am an international traveler! Welcome to my blog – dedicated to empowering women to travel more, live out our biggest dreams, and to be the best versions of ourselves! I have traveled to fifteen countries with more to come! A Denver, CO native, I currently live in Spain with my Nicaraguan boyfriend and am excited to explore the rest of Europe!
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922 So.2d 338 (2006) Andrew TYSON, Appellant, v. STATE of Florida, Appellee. No. 5D05-1599. District Court of Appeal of Florida, Fifth District. February 24, 2006. James S. Purdy, Public Defender, and Brynn Newton, Assistant Public Defender, Daytona Beach, for Appellant. Charles J. Crist, Jr., Attorney General, Tallahassee, and Lamya A. Henry, Assistant Attorney General, Daytona Beach, for Appellee. *339 PALMER, J. Andrew Tyson (defendant) appeals his judgment and sentence which were entered by the trial court after the defendant entered a plea of nolo contendere, but reserved his right to appeal the trial court's earlier order denying his motion to suppress. Concluding that the motion to suppress should have been granted, we reverse. In McMaster v. State, 780 So.2d 1026, 1028 (Fla. 5th DCA 2001), this court set out the standard of review applicable to a trial court's suppression order as follows: A trial court's ruling on a motion to suppress comes to this court clothed with a presumption of correctness, and we must interpret the evidence and reasonable inferences in a manner most favorable to affirming that decision. San Martin v. State, 717 So.2d 462, 469 (Fla.1998), cert. denied, 526 U.S. 1071, 119 S.Ct. 1468, 143 L.Ed.2d 553 (1999); Warren v. State, 701 So.2d 404 (Fla. 1st DCA 1997). Appellate review of a motion to suppress can present mixed questions of law and fact. Lester v. State, 754 So.2d 746 (Fla. 1st DCA 2000). The findings of fact made by the trial court are reviewed pursuant to the substantial competent evidence standard. Ikner v. State, 756 So.2d 1116 (Fla. 1st DCA 2000); Warren. The trial court's application of the law is reviewed pursuant to the de novo standard. Ikner; State v. Ramos, 775 [755] So.2d 836 (Fla. 5th DCA 2000); Warren. Id. The defendant was a passenger in a car which was the subject of a valid traffic stop. The deputy asked the vehicle's two occupants to get out of the car and then asked if either of them had drugs, weapons, or other contraband. The defendant answered: "No." At that time the deputy asked if he was "good for a search." On direct examination, the deputy said that the defendant answered, "yes." Upon searching the defendant's person, the deputy found cocaine powder in the defendant's pocket. On cross-examination, the deputy was asked: "So, he didn't say that you could go ahead and search him then, did he?" The deputy answered: "I guess no, he didn't say `sure'." Then, on redirect examination, the deputy told the prosecutor he did not know what the defendant's specific reply had been, adding: "I don't know that he replied." The deputy added that, had the defendant answered no, a search would not have been conducted. The trial judge denied the defendant's motion to suppress concluding that the deputy's testimony proved that he received consent to search from the defendant. The defendant thereafter entered a plea of nolo contendere to the charge of cocaine possession, reserving his right to appeal trial court's ruling, which the parties agreed was dispositive. The defendant does not contest the validity of the vehicle stop. Instead, he challenges the trial court's determination that he validly consented to a search of his person. The defendant argues that the State failed to carry its burden of showing that he consented to being searched, claiming that the deputy's testimony was, at best, ambiguous as to whether consent for the search had been obtained. We agree. A search conducted pursuant to consent which is freely and voluntarily given will be considered lawful. Jorgenson v. State, 714 So.2d 423, 426 (Fla.1998). Whether consent is voluntary is a question of fact to be determined from the totality of the circumstances. Id. The State carries the burden of proving a voluntary, consensual search by a preponderance of the evidence. Id. See also Bumper v. North Carolina, 391 U.S. 543, 88 S.Ct. *340 1788, 20 L.Ed.2d 797 (1968); Smith v. State, 753 So.2d 713 (Fla. 2d DCA 2000). The failure to object to a search does not equal consent to a search. While consent need not be expressed in a particular form it is not established by a showing of acquiescence to a police officer's authority. Phuagnong v. State, 714 So.2d 527 (Fla. 1st DCA 1998). Here, the deputy's testimony suggests that the deputy was not necessarily seeking affirmative assent to conduct a search, but rather, that he would conduct a search unless the defendant affirmatively told him not to do so. The essence of a consensual search is more than simply an acquiescence to police authority. See Minter-Smith v. State, 864 So.2d 1141 (Fla. 1st DCA 2003). Given the deputy's ultimate testimony that he could not say that the defendant replied when asked if he could be searched, and the absence of any other evidence indicating affirmative consent by the defendant to be searched, all the State proved here was that the defendant acquiesced to the deputy's authority. This showing was insufficient to prove consent. Judgment and Sentence REVERSED. SAWAYA, J., concurs. PLEUS, C.J., dissents, with opinion. PLEUS, C.J., dissenting. I respectfully dissent. The majority correctly notes that whether the consent to a search is voluntary is a question of fact to be determined from the totality of the circumstances. We must interpret the evidence and reasonable inferences in a manner most favorable to affirming. The trial judge heard the evidence, saw the witnesses and listened to the answers of the deputy sheriff. She determined there was a voluntary consent to a search. The defendant was asked if he was "good for a search." He answered, "Yes." The majority suggests that the deputy's testimony shows the deputy was not seeking affirmative assent to conduct a search. This conclusion ignores and violates the well established principle that it is not the task of an appellate court to interpret the evidence. That task is for the trial judge. Further, the majority has failed to resolve inferences in a manner most favorable to affirming. I would affirm.
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Chicago April 21, 2006|By From news services. Man gets 5 years for sword attack An Arlington Heights man, accused of slashing his wife's friend with a samurai-type sword during an argument last year, was sentenced to 5 years in prison Thursday after pleading guilty to an aggravated battery charge. Stephen Shult, 39, entered the plea during a hearing in the Rolling Meadows branch of Cook County Circuit Court. In exchange for the guilty plea, prosecutors agreed to drop a more serious charge of attempted murder. Girl, 11, hurt in shooting An 11-year-old girl was seriously wounded in a drive-by shooting Thursday night on Chicago's Far South Side, police said. The girl was shot in the abdomen about 8:15 p.m. in the 11400 block of South Prairie Avenue, Sgt. Eugene Mullins said. She was rushed to University of Chicago Hospitals in serious condition, Mullins said. A captain at the Calumet District said police believe the shots were fired from a vehicle, but she could not provide a description of the shooter. Police seek robbery suspect Chicago police are searching for a man who they say robbed three businesses in the 4800 to 5100 blocks of South Archer Avenue between April 11 and Tuesday. The man entered each business carrying a black duffel bag and demanded money from the cashier, police said. Although he wielded a revolver in every robbery, police said, there were no injuries. Call 312-747-8382 with information. Sexual assault added to father's murder charges A DuPage County grand jury on Thursday indicted the father of an 8-year-old girl on sexual assault charges in addition to murder charges that accuse him of stabbing her in the neck and plunging her head in a toilet. The indictment charges Neil Lofquist with 21 counts of first-degree murder and two counts of predatory criminal sexual assault in the death of Lauren Lofquist. Activists call for moratorium on arrests Immigrant rights activists gathered in the Loop on Thursday to call for the release of undocumented workers arrested in raids that netted 26 people on the Southwest Side and nearly 1,200 nationwide. The arrested workers later were released on recognizance bonds. The activists also called for a moratorium on arrests by U.S. Immigration and Customs Enforcement agents like the ones that took place Wednesday at IFCO Systems, near Pilsen.
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Early antidepressant efficacy modulation by glutamatergic gene variants in the STAR*D. The glutamatergic system has been suggested as a modulator of rapid antidepressant response. Thus, 44 glutamatergic genes were selected according to the literature and investigated in 1541 major depressive patients from the STAR*D genome wide dataset. Outcomes of interest were early response (2nd week) and late response (from the 4th to the 14th week) compared to non-response and stability of response through the STAR*D level 1. A complete agglomerative clustering, based on pairwise identity-by-state (IBS) matrix, was applied in order to control for genetic admixture. A chi-square test was employed as exploratory analysis and a logistic regression was employed to corroborate SNPs associated to the outcomes at p<0.001. Covariates were selected accordingly to their impact on phenotypes. A Bonferroni correction was applied. PLINK served for the analysis. About 1995 SNPs were available after quality control. Our results suggested that the rs1083801 within the GRM7 (glutamate receptor, metabotropic 7) gene was associated to early response under a recessive model (GG genotype observed in 14.34% of early responders vs 5.25% of late responders, OR=0.33, 95% CI=0.21-0.54, p=6.41e-06. GG genotype observed in 5.34% of non-responders, OR=0.33, 95% CI=0.20-0.56, p=4.07e-05). The result was confirmed in the white non-Hispanic group (GG genotype observed in 17.46% of early responders vs 5.81% of the rest of the sample, OR=0.29, 95% CI=0.18-0.46, p=2.04e-07). No marker predicted the stability of response. Glutamatergic genes may be useful markers of early antidepressant efficacy. This result may be relevant in further understanding the pathophysiology of the drug induced antidepressant effect.
High
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The Last Blog Post! This is my last blog post –for the foreseeable future. It is dated 7/31/2011 at 11:59PM. What happens tomorrow? A new life, of course! As... Simple Log Review Checklist Released! Today, many people are looking for very simple solutions to big and complex problems – and the area of logging and log management is no exc... Why No Open Source SIEM, EVER? Here is a perfect weekend post – on SIEM :-) Ok, all this Google web traffic of people searching for “ open source SIEM ” (sometimes “ ope... Monthly Blog Round-Up – May 2017 Here is my next monthly "Security Warrior" blog round-up of top 5 popular posts/topics this month: “New SIEM Whitepaper on Use C...
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