document_title: Space tourism

question_text: when did the first tourist travel into space

text: Space tourism

text: Precursors[edit]

text: The Soviet space program was aggressive in broadening the pool of cosmonauts. The Soviet Intercosmos program included cosmonauts selected from Warsaw Pact member countries (Czechoslovakia, Poland, East Germany, Bulgaria, Hungary, Romania) and later from allies of the USSR (Cuba, Mongolia, Vietnam) and non-aligned countries (India, Syria, Afghanistan). Most of these cosmonauts received full training for their missions and were treated as equals, but were generally given shorter flights than Soviet cosmonauts. The European Space Agency (ESA) took advantage of the program as well.

text: The US space shuttle program included payload specialist positions which were usually filled by representatives of companies or institutions managing a specific payload on that mission. These payload specialists did not receive the same training as professional NASA astronauts and were not employed by NASA. In 1983, Ulf Merbold from ESA and Byron Lichtenberg from MIT (engineer and Air Force fighter pilot) were the first payload specialists to fly on the Space Shuttle, on mission STS-9.[6][7]

text: In 1984, Charles D. Walker became the first non-government astronaut to fly, with his employer McDonnell Douglas paying $40,000 for his flight. NASA was also eager to prove its capability to Congressional sponsors. During the 1970s, Shuttle prime contractor Rockwell International studied a $200–300 million removable cabin that could fit into the Shuttle's cargo bay. The cabin could carry up to 74 passengers into orbit for up to three days. Space Habitation Design Associates proposed, in 1983, a cabin for 72 passengers in the bay. Passengers were located in six sections, each with windows and its own loading ramp, and with seats in different configurations for launch and landing. Another proposal was based on the Spacelab habitation modules, which provided 32 seats in the payload bay in addition to those in the cockpit area. A 1985 presentation to the National Space Society stated that although flying tourists in the cabin would cost $1 to 1.5 million per passenger without government subsidy, within 15 years 30,000 people a year would pay $25,000 each to fly in space on new spacecraft. The presentation also forecast flights to lunar orbit within 30 years and visits to the lunar surface within 50 years.[8]

text: As the shuttle program expanded in the early 1980s, NASA began a Space Flight Participant program to allow citizens without scientific or governmental roles to fly. Christa McAuliffe was chosen as the first Teacher in Space in July 1985 from 11,400 applicants. 1,700 applied for the Journalist in Space program. An Artist in Space program was considered, and NASA expected that after McAuliffe's flight two to three civilians a year would fly on the shuttle. After McAuliffe was killed in the Challenger disaster in January 1986, the programs were canceled. McAuliffe's backup, Barbara Morgan, eventually got hired in 1998 as a professional astronaut and flew on STS-118 as a mission specialist.[9]:84–85 A second journalist-in-space program, in which NASA green-lighted Miles O'Brien to fly on the space shuttle, was scheduled to be announced in 2003. That program was canceled in the wake of the Columbia disaster on STS-107 and subsequent emphasis on finishing the International Space Station before retiring the space shuttle.

text: With the realities of the post-Perestroika economy in Russia, its space industry was especially starved for cash. The Tokyo Broadcasting System (TBS) offered to pay for one of its reporters to fly on a mission. For $28 million, Toyohiro Akiyama was flown in 1990 to Mir with the eighth crew and returned a week later with the seventh crew. Akiyama gave a daily TV broadcast from orbit and also performed scientific experiments for Russian and Japanese companies. However, since the cost of the flight was paid by his employer, Akiyama could be considered a business traveler rather than a tourist.

text: In 1991, British chemist Helen Sharman was selected from a pool of 13,000 applicants to be the first Briton in space.[10] The program was known as Project Juno and was a cooperative arrangement between the Soviet Union and a group of British companies. The Project Juno consortium failed to raise the funds required, and the program was almost cancelled. Reportedly Mikhail Gorbachev ordered it to proceed under Soviet expense in the interests of international relations, but in the absence of Western underwriting, less expensive experiments were substituted for those in the original plans. Sharman flew aboard Soyuz TM-12 to Mir and returned aboard Soyuz TM-11.

text: Orbital space tourism[edit]

text: At the end of the 1990s, MirCorp, a private venture that was by then in charge of the space station, began seeking potential space tourists to visit Mir in order to offset some of its maintenance costs. Dennis Tito, an American businessman and former JPL scientist, became their first candidate. When the decision to de-orbit Mir was made, Tito managed to switch his trip to the International Space Station (ISS) through a deal between MirCorp and US-based Space Adventures, Ltd., despite strong opposition from senior figures at NASA; from the beginning of the ISS expeditions, NASA stated it wasn't interested in space guests.[11] Nonetheless, Dennis Tito visited the ISS on April 28, 2001, and stayed for seven days, becoming the first "fee-paying" space tourist. He was followed in 2002 by South African computer millionaire Mark Shuttleworth. The third was Gregory Olsen in 2005, who was trained as a scientist and whose company produced specialist high-sensitivity cameras. Olsen planned to use his time on the ISS to conduct a number of experiments, in part to test his company's products. Olsen had planned an earlier flight, but had to cancel for health reasons. The Subcommittee on Space and Aeronautics Committee On Science of the House of Representatives held on June 26, 2001 reveals the shifting attitude of NASA towards paying space tourists wanting to travel to the ISS. The hearing's purpose was to, "Review the issues and opportunities for flying nonprofessional astronauts in space, the appropriate government role for supporting the nascent space tourism industry, use of the Shuttle and Space Station for Tourism, safety and training criteria for space tourists, and the potential commercial market for space tourism".[12] The subcommittee report was interested in evaluating Dennis Tito's extensive training and his experience in space as a nonprofessional astronaut.

text: By 2007, space tourism was thought to be one of the earliest markets that would emerge for commercial spaceflight.[13]:11 However, as of 2014[update] this private exchange market has not emerged to any significant extent.

text: Space Adventures is the only company that has sent paying passengers to space.[14][15] In conjunction with the Federal Space Agency of the Russian Federation and Rocket and Space Corporation Energia, Space Adventures facilitated the flights for all of the world's first private space explorers. The first three participants paid in excess of $20 million (USD) each for their 10-day visit to the ISS.

text: in February, 2003, the space shuttle Columbia disintegrated on re-entry into the Earth's atmosphere, killing all seven astronauts aboard. After this disaster, space tourism on the Russian Soyuz program was temporarily put on hold, because Soyuz vehicles became the only available transport to the ISS. On July 26, 2005, Space Shuttle Discovery (mission STS-114) marked the shuttle's return to space. Consequently, in 2006, space tourism was resumed. On September 18, 2006, an Iranian American businesswoman named Anousheh Ansari became the fourth space tourist (Soyuz TMA-9).[16]) On April 7, 2007, Charles Simonyi, an American businessman of Hungarian descent, joined their ranks (Soyuz TMA-10). Simonyi became the first repeat space tourist, paying again to fly on Soyuz TMA-14 in March–April 2009. Canadian Guy Laliberté became the next space tourist in September, 2009 aboard Soyuz TMA-16. The British singer Sarah Brightman initiated plans (costing a reported $52 million) and participated in preliminary training in early 2015, expecting to then fly (and to perform while in orbit) in September 2015, but in May 2015 she postponed the plans indefinitely.[4][17][18]

text: List of flown space tourists[edit]

text:
Space tourist
Photo
Nationality
Year
Duration of flight
Flight
Amount paid (USD)
Source of wealth

1. Dennis Tito

 United States
2001
8 days (Apr 28 – May 6)
Launch: Soyuz TM-32
Return: Soyuz TM-31
$20 million (estimated)[19]
Investment management
(Wilshire Associates)

2. Mark Shuttleworth

 South Africa
 United Kingdom
2002
11 days (April 25 – May 5)
Launch: Soyuz TM-34
Return: Soyuz TM-33
$20 million (estimated)[20]
Internet security certificates
(Thawte)

3. Gregory Olsen

 United States
2005
11 days (October 1 – 11)
Launch: Soyuz TMA-7
Return: Soyuz TMA-6
$20 million (estimated)[21]
Optoelectronic sensors
(Sensors Unlimited, Inc.)

4. Anousheh Ansari

 United States
 Iran
2006
12 days (September 18 – 29)
Launch: Soyuz TMA-9
Return: Soyuz TMA-8
$20 million (estimated)[22]
VoIP software
(Telecom Technologies, Inc.)

5. Charles Simonyi

 United States
 Hungary
2007
15 days (April 7 – 21)
Launch: Soyuz TMA-10
Return: Soyuz TMA-9
$25 million (estimated)[23]
Desktop software
(Microsoft Office)

2009
14 days (March 26 – April 8)
Launch: Soyuz TMA-14
Return: Soyuz TMA-13
$35 million (estimated)[23]

6. Richard Garriott[24]

 United States
 United Kingdom
2008
12 days (October 12 – 23)
Launch: Soyuz TMA-13
Return: Soyuz TMA-12
$30 million (estimated)[25]
Video games
(Origin Systems)

7. Guy Laliberté

 Canada
2009
11 days (September 30 – October 11)
Launch: Soyuz TMA-16
Return: Soyuz TMA-14
$40 million (estimated)[26]
Performance art
(Cirque du Soleil)

text: Proposed orbital ventures[edit]

text: This section needs to be updated. Please update this article to reflect recent events or newly available information. (December 2016)

text:
Boeing is building the CST-100 Starliner capsule as part of the CCDev program and intends to fly tourists.[citation needed] The CST-100 is planned to be launched by an Atlas V rocket.
Space Adventures Ltd. have announced that they are working on DSE-Alpha, a circumlunar mission to the moon, with the price per passenger being $100,000,000.[27]

text: Several plans have been proposed for using a space station as a hotel:

text:
American motel tycoon Robert Bigelow has acquired the designs for inflatable space habitats from the Transhab program abandoned by NASA. His company, Bigelow Aerospace, has already launched two first inflatable habitat modules. The first, named Genesis I, was launched July 12, 2006. The second test module, Genesis II, was launched June 28, 2007. Both Genesis habitats remain in orbit as of March 2012. The BA 330, an expandable habitation module with 330 cubic meters of internal space, is expected to be ready for launch by 2017. In 2004, Bigelow Aerospace established a competition called America's Space Prize, which offered a $50 million prize to the first US company to create a reusable spacecraft capable of carrying passengers to a Nautilus space station. The prize expired in January 2010 without anyone making a serious effort to win it.[28]
The Space Island Group have set out plans for their Space Island Project, and plans on having 20,000 people on their "space island" by 2020, with the number of people doubling for each decade.[29]

text: Lunar space tourism[edit]

text: In February 2017, Elon Musk announced that substantial deposits from two individuals had been received by Space X for a Moon loop flight using a free return trajectory and that this could happen as soon as late 2018.[30] Musk said that the cost of the mission would be "comparable" to that of sending an astronaut to the International Space Station, about $70 million US dollars in 2017.[31]

text: Sub-orbital space tourism[edit]

text: No suborbital space tourism has occurred yet, but since it is projected to be more affordable, many companies view it as a money-making proposition. Most are proposing vehicles that make suborbital flights peaking at an altitude of 100–160 km (62–99 mi).[32] Passengers would experience three to six minutes of weightlessness, a view of a twinkle-free starfield, and a vista of the curved Earth below. Projected costs are expected to be about $200,000 per passenger.[33]

text: Projects[edit]

text:
Blue Origin is developing the New Shepard reusable suborbital launch system specifically to enable short-duration space tourism.
On October 4, 2004, SpaceShipOne, designed by Burt Rutan of Scaled Composites, won the $10,000,000 X Prize, which was designed to be won by the first private company who could reach and surpass an altitude of 100 km (62 mi) twice within two weeks. The altitude is beyond the Kármán Line, the arbitrarily defined boundary of space.[34] The first flight was flown by Michael Melvill on June 21, 2004, to a height of 100 km (62 mi), making him the first commercial astronaut.[35] The prize-winning flight was flown by Brian Binnie, which reached a height of 112.0 km (69.6 mi), breaking the X-15 record.[36]
Virgin Galactic, headed by Sir Richard Branson's Virgin Group, hopes to be the first to offer regular suborbital spaceflights to paying passengers, aboard a fleet of five SpaceShipTwo-class spaceplanes. The first of these spaceplanes, VSS Enterprise, was intended to commence its first commercial flights in spring 2015, and tickets were on sale at a price of $200,000 (later raised to $250,000). However, the company suffered a considerable setback when the Enterprise broke up over the Mojave Desert during a test flight in October 2014. Over 700 tickets had been sold prior to the accident.[37] A second spaceplane, VSS Unity, has begun testing.[38]
XCOR Aerospace was developing a suborbital vehicle called Lynx until development was halted in May 2016.[39] The Lynx will take off from a runway under rocket power. Unlike SpaceShipOne and SpaceShipTwo, Lynx will not require a mothership. Lynx is designed for rapid turnaround, which will enable it to fly up to four times per day. Because of this rapid flight rate, Lynx has fewer seats than SpaceShipTwo, carrying only one pilot and one spaceflight participant on each flight. XCOR expect to roll out the first Lynx prototype and begin flight tests in 2015. It was hoped that Lynx would carry paying customers before the end of 2016.[40][41]

Citizens in Space, formerly the Teacher in Space Project, is a project of the United States Rocket Academy. Citizens in Space combines citizen science with citizen space exploration. The goal is to fly citizen-science experiments and citizen explorers (who travel free) who will act as payload operators on suborbital space missions. By 2012, Citizens in Space had acquired a contract for 10 suborbital flights with XCOR Aerospace and expected to acquire additional flights from XCOR and other suborbital spaceflight providers in the future. In 2012 Citizens in Space reported they had begun training three citizen astronaut candidates and would select seven additional candidates over the next 12 to 14 months.[42]
Space Expedition Corporation was preparing to use the Lynx for "Space Expedition Curaçao", a commercial flight from Hato Airport on Curaçao, and planned to start commercial flights in 2014. The costs were $95,000 each.[43][44]

Armadillo Aerospace was developing a two-seat vertical takeoff and landing (VTOL) rocket called Hyperion, which will be marketed by Space Adventures.[45] Hyperion uses a capsule similar in shape to the Gemini capsule. The vehicle will use a parachute for descent but will probably use retrorockets for final touchdown, according to remarks made by Armadillo Aerospace at the Next Generation Suborbital Researchers Conference in February 2012. The assets of Armadillo Aerospace were sold to Exos Aerospace and while SARGE is continuing to be developed, it is unclear whether Hyperion is still being developed.
EADS Astrium, a subsidiary of European aerospace giant EADS, announced its space tourism project on June 13, 2007.[46]

text: Legality[edit]

text: Under the Outer Space Treaty signed in 1967, the launch operator's nationality and the launch site's location determine which country is responsible for any damages occurred from a launch.[47]

text: After valuable resources were detected on the Moon, private companies began to formulate methods to extract the resources. Article II of the Outer Space Treaty dictates that "outer space, including the Moon and other celestial bodies, is not subject to national appropriation by claim of sovereignty, by means of use or occupation, or by any other means".[48] However, countries have the right to freely explore the Moon and any resources collected are property of that country when they return.

text: United States[edit]

text: In December 2005, the US government released a set of proposed rules for space tourism.[49] These included screening procedures and training for emergency situations, but not health requirements.

text: Under current US law, any company proposing to launch paying passengers from American soil on a suborbital rocket must receive a license from the Federal Aviation Administration's Office of Commercial Space Transportation (FAA/AST). The licensing process focuses on public safety and safety of property, and the details can be found in the Code of Federal Regulations, Title 14, Chapter III.[50] This is in accordance with the Commercial Space Launch Amendments Act passed by Congress in 2004.[51]

text: In March 2010, the New Mexico legislature passed the Spaceflight Informed Consent Act. The SICA gives legal protection to companies who provide private space flights in the case of accidental harm or death to individuals. Participants sign an Informed Consent waiver, dictating that spaceflight operators can not be held liable in the "death of a participant resulting from the inherent risks of space flight activities". Operators are however not covered in the case of gross negligence or willful misconduct.[52]

text: Environmental effects[edit]

text: A 2010 study published in Geophysical Research Letters raised concerns that the growing commercial spaceflight industry could accelerate global warming. The study, funded by NASA and The Aerospace Corporation, simulated the impact of 1,000 suborbital launches of hybrid rockets from a single location, calculating that this would release a total of 600 tonnes of black carbon into the stratosphere. They found that the resultant layer of soot particles remained relatively localised, with only 20% of the carbon straying into the southern hemisphere, thus creating a strong hemispherical asymmetry.[53] This unbalance would cause the temperature to decrease by about 0.4 °C (0.72 °F) in the tropics and subtropics, whereas the temperature at the poles would increase by between 0.2 and 1 °C (0.36 and 1.80 °F). The ozone layer would also be affected, with the tropics losing up to 1.7% of ozone cover, and the polar regions gaining 5–6%.[54] The researchers stressed that these results should not be taken as "a precise forecast of the climate response to a specific launch rate of a specific rocket type", but as a demonstration of the sensitivity of the atmosphere to the large-scale disruption that commercial space tourism could bring.[53]

text: Education and advocacy[edit]

text: Several organizations have been formed to promote the space tourism industry, including the Space Tourism Society, Space Future, and HobbySpace. UniGalactic Space Travel Magazine is a bi-monthly educational publication covering space tourism and space exploration developments in companies like SpaceX, Orbital Sciences, Virgin Galactic and organizations like NASA.

text: Classes in space tourism are currently taught at the Rochester Institute of Technology in New York,[55] and Keio University in Japan.[56]

text: Attitudes toward space tourism[edit]

text: A web-based survey suggested that over 70% of those surveyed wanted less than or equal to 2 weeks in space; in addition, 88% wanted to spacewalk (only 14% of these would do it for a 50% premium), and 21% wanted a hotel or space station.[57]

text: The concept has met with some criticism from some, including politicians, notably Günter Verheugen, vice-president of the European Commission, who said of the EADS Astrium Space Tourism Project: "It's only for the super rich, which is against my social convictions".[58]

text: Space Race television show[edit]

text: As of October 2013, NBC News and Virgin Galactic have come together to create a new reality television show titled Space Race. The show "will follow contestants as they compete to win a flight into space aboard Virgin Galactic's SpaceShipTwo rocket plane. It is not to be confused with the Children's Space TV show called "Space Racers"[59]

text: Terminology[edit]

text: Many private space travelers have objected to the term "space tourist", often pointing out that their role went beyond that of an observer, since they also carried out scientific experiments in the course of their journey. Richard Garriott additionally emphasized that his training was identical to the requirements of non-Russian Soyuz crew members, and that teachers and other non-professional astronauts chosen to fly with NASA are called astronauts. He has said that if the distinction has to be made, he would rather be called "private astronaut" than "tourist".[60] Dennis Tito has asked to be known as an "independent researcher",[citation needed] and Mark Shuttleworth described himself as a "pioneer of commercial space travel".[61] Gregory Olsen prefers "private researcher",[62] and Anousheh Ansari prefers the term "private space explorer".[16] Other space enthusiasts object to the term on similar grounds. Rick Tumlinson of the Space Frontier Foundation, for example, has said: "I hate the word tourist, and I always will ... 'Tourist' is somebody in a flowered shirt with three cameras around his neck."[63] Russian cosmonaut Maksim Surayev told the press in 2009 not to describe Guy Laliberté as a tourist: "It's become fashionable to speak of space tourists. He is not a tourist but a participant in the mission."[64]

text: "Spaceflight participant" is the official term used by NASA and the Russian Federal Space Agency to distinguish between private space travelers and career astronauts. Tito, Shuttleworth, Olsen, Ansari, and Simonyi were designated as such during their respective space flights. NASA also lists Christa McAuliffe as a spaceflight participant (although she did not pay a fee), apparently due to her non-technical duties aboard the STS-51-L flight.

text: The US Federal Aviation Administration awards the title of "Commercial Astronaut" to trained crew members of privately funded spacecraft. The only people currently holding this title are Mike Melvill and Brian Binnie, the pilots of SpaceShipOne.

text: Expected economic growth[edit]

text: A 2010 report from the Federal Aviation Administration, titled "The Economic Impact of Commercial Space Transportation on the U. S Economy in 2009", cites studies done by Futron, an aerospace and technology-consulting firm, which predict that space tourism could become a billion-dollar market within 20 years.[65] In addition, in the decade since Dennis Tito journeyed to the International Space Station, eight private citizens have paid the $20 million fee to travel to space. Space Adventures suggests that this number could increase fifteen-fold by 2020.[66] These figures do not include other private space agencies such as Virgin Galactic, which as of 2014 has sold approximately 700 tickets priced at $200,000 or $250,000 dollars each and has accepted more than $80 million in deposits.[67]


question_text: who dies in the fifth book of harry potter

root

text: Plot[edit]

text: During another summer with his Aunt Petunia and Uncle Vernon, Harry Potter and Dudley are attacked by Dementors. After using magic to save Dudley and himself, Harry is expelled from Hogwarts, but the decision is later reversed after a hearing at the Ministry of Magic. Harry is whisked off by a group of wizards (including the real Mad-Eye Moody, Professor Lupin, and several new faces, including Nymphadora Tonks, a bubbly young witch who is a Metamorphmagus [a wizard who can change his/her appearance without a potion or spell], and Kingsley Shacklebolt, a senior Auror with egalitarian views) to Number 12, Grimmauld Place, the childhood home of his godfather, Sirius Black. The building also serves as the headquarters of the Order of the Phoenix, of which Mr. and Mrs. Weasley and Sirius are also members. Ron Weasley and Hermione Granger explain that the Order of the Phoenix is a secret organisation led by Hogwarts headmaster Albus Dumbledore, dedicated to fighting Lord Voldemort and his followers, the Death Eaters. From the members of the Order, Harry and the others learn that Voldemort is seeking an object that he did not have prior to his first defeat, and assume this object to be a weapon of some sort. Harry learns that the Ministry of Magic, led by Cornelius Fudge, is refusing to acknowledge Voldemort's return because of the panic and chaos that doing so would cause, and has been running a smear campaign against him and Dumbledore.

tag: p

text: At Hogwarts, Harry learns that Dolores Umbridge, a senior employee in the Ministry of Magic, will be the new Defence Against the Dark Arts teacher. Umbridge and Harry clash, as she, like Fudge, refuses to believe that Voldemort has returned. She punishes Harry for his rebellious outbursts by having him write "I must not tell lies" with a cursed quill that carves the phrase into his skin. She also refuses to teach her students how to perform defensive spells, prompting Harry, Ron and Hermione to form their own Defence Against the Dark Arts group (with students from Gryffindor, Ravenclaw and Hufflepuff), which they call Dumbledore's Army. Many students sign up, including Neville Longbottom, Fred and George Weasley, Ginny Weasley and Luna Lovegood. Struggling to find a place to practise, Dobby the house elf tells him about the Room of Requirement and its uses. The club meet there to learn and practise defensive spells under Harry's instruction.

text: Meanwhile, Rubeus Hagrid has not yet returned from the secret mission given to him by Dumbledore at the end of the previous book, and is absent for the first part of the school year. Upon his return, Harry, Ron, and Hermione learn that his mission, which was mostly unsuccessful, was to seek out the last giants to stop them from joining Lord Voldemort. Professor Umbridge has been steadily amassing more and more power and influence at the school, and as she begins regularly inspecting Hagrid's Care of Magical Creatures lessons, it is clear that she intends to get rid of him.

text: One night, Harry has a vision through the eyes of Voldemort's snake Nagini, possessed by Voldemort, attacking Ron's father Arthur Weasley. Harry informs Professor McGonagall and Dumbledore, and Mr. Weasley is rescued. Dumbledore arranges for Harry to take Occlumency lessons with Professor Snape to protect his mind against further invasions by Voldemort.

text: Umbridge finally sacks Professor Trelawney, the Divination teacher; However, she is outraged when Professor Dumbledore undermines her power by allowing Trelawney to continue living at the school, and hires Firenze, a centaur, to take her place, in spite of Umbridge's prejudice against part-humans. Soon after, Umbridge is given a tip-off about Dumbledore's Army by Marietta Edgecombe, who in doing so unwittingly activates a curse set by Hermione which disfigures her face. Despite Dobby's warning, the gang are caught and get into trouble with Fudge. When Dumbledore takes responsibility for the illegal organisation, he is forced to leave the school and go into hiding. Dolores Umbridge becomes headmistress, and Fred and George cause pandemonium around the school in revenge.

text: During one Occlumency lesson, Snape is called away and Harry, left alone, looks into Snape's Pensieve, viewing a memory of his time as a student at Hogwarts. Harry is shocked to witness his father, James Potter, and Sirius bullying and humiliating Snape. Snape catches Harry and, enraged, refuses to continue the lessons. Distraught at this revelation of his father's character, Harry talks to Sirius and Lupin by using Floo powder through the fireplace in Umbridge's own office and learns more about his parents and their background. After helping Harry break into Umbridge's office, Fred and George then leave Hogwarts to start a joke-shop in Diagon Alley.

text: Suspecting that he will be next teacher to be sacked by Umbridge, Hagrid confesses to Harry, Ron and Hermione that he has brought his giant half-brother, Grawp, to Hogwarts, and hidden him in the Forbidden Forest, with the intention of eventually introducing him to human society. Hagrid asks the three of them to look after Grawp if he himself must leave the school. Sure enough, Umbridge leads a party of Aurors to attack Hagrid in his house one night. Hagrid overpowers them and flees the school; McGonagall, trying to disrupt the violence, is badly injured and is put in St. Mungo's Hospital.

text: On the last day of O.W.L. tests, Harry has a vision of Sirius being tortured by Voldemort in the Department of Mysteries. He tries again to illegally use Umbridge's office fireplace to communicate with the Order of the Phoenix's headquarters to make sure the vision was genuine, and is told by Kreacher the house-elf that Sirius is indeed at the Ministry, before Umbridge catches Harry and his friends in the act. Snape is summoned to provide Veritaserum in order to question Harry, but he claims to have no further stocks of the potion left. Remembering that Snape is also a member of the Order of the Phoenix, Harry gives him a cryptic warning about Sirius's fate, but Snape claims to have not understood it.

text: Umbridge decides to use the illegal Cruciatus Curse on Harry to interrogate him on Sirius's whereabouts. She also reveals she herself ordered the Dementor attack on him, intending to have him either silenced or discredited. Hermione intervenes and in order to create a distraction, convinces Umbridge that they are hiding a weapon of Dumbledore's in the Forbidden Forest. Harry and Hermione lead her into an area of the forest inhabited by centaurs, where Umbridge provokes them into taking her captive. The centaurs are furious upon learning that Hermione used them to do her bidding and turn on the pair, but Grawp arrives and clashes with the centaurs, allowing Harry and Hermione to escape.

text: Luna, Ron, Ginny, and Neville join them in the forest and all six fly to the Ministry on thestrals, expecting to find and rescue Sirius. Once in the Department of Mysteries, Harry realises that his vision was falsely planted by Voldemort; however, he finds a glass sphere that bears his and the Dark Lord's names. Death Eaters led by Lucius Malfoy attack in order to capture the sphere, which is a recording of a prophecy concerning Harry and Lord Voldemort, which is revealed to be the object Voldemort has been trying to obtain for the whole year, the Dark Lord believing that there was something he missed when he first heard the prophecy. Lucius explains that only the subjects of the prophecies, in this case Harry or Voldemort, can safely remove them from the shelves. During a heated fight Neville accidentally kicks and smashes the prophecy. Harry and his friends, soon joined by members of the Order, enter a battle with the Death Eaters, during which Bellatrix Lestrange kills Sirius and Voldemort himself arrives to kill Harry, but Dumbledore rescues him and climatically fights the Dark Lord to a stalemate. In the midst of the duel, Voldemort unsuccessfully tries to possess Harry in an attempt to get Dumbledore to kill the boy, then escapes just as Cornelius Fudge appears, finally faced with first-hand evidence that Voldemort has truly returned.

text: In his office, Dumbledore explains that Snape had understood Harry's cryptic warning, and had subsequently contacted Sirius, learning that he was still at Grimmauld Place. After Harry failed to return from the Forbidden Forest, Snape deduced where he had gone and alerted the Order of the Phoenix, allowing them to save Harry and his friends. It is revealed that during the Christmas holidays, Kreacher had interpreted a command of Sirius's as an order to leave the house, and went to Narcissa Malfoy, the wife of Lucius, and told them about Harry and Sirius's close relationship; Voldemort subsequently realised that he could lure Harry to the Department of Mysteries by tricking him into thinking that Sirius was in danger there.

text: Dumbledore then explains the prophecy: Before Harry was born, Professor Trelawney predicted that a boy with the power to defeat Voldemort would be born, would be marked as an equal by Voldemort and have powers unknown to him, and that one of the pair must kill the other, for "neither can live while the other survives". Voldemort learnt of the first part of the prophecy, and subsequently tried to murder Harry in the belief that he could prevent it from coming true, unaware that he would grant Harry power by doing so. Dumbledore tells Harry that he must stay with the Dursleys for one last summer because by taking Harry into her home, his Aunt Petunia, Lily's sister, seals the protection that Harry's mother afforded him when she died; as long as he is there, he is safe from Voldemort and his followers.

text: Harry comes to terms with the responsibility of the prophecy, but mourns for the loss of his godfather. Luna comforts him, telling him about her and her father's belief in heaven. Harry then finds an old hand-held mirror in his dormitory that was a gift from Sirius. He realises that Sirius would not want him to be depressed on the matter, and resolves to continue fighting Voldemort.

text: Publication and release[edit]

text: Potter fans waited three years between the releases of the fourth and fifth books.[2][3] Before the release of the fifth book, 200 million copies of the first four books had already been sold and translated into 55 languages in 200 countries.[4] As the series was already a global phenomenon, the book forged new pre-order records, with thousands of people queuing outside book stores on 20 June 2003 to secure their copy at midnight.[4] Despite the security, thousands of copies were stolen from an Earlestown, Merseyside warehouse on 15 June 2003.[5]

text: Critical response[edit]

text: Harry Potter and the Order of the Phoenix was met with mostly positive reviews, and received several awards. The book was cited as an American Library Association Best Book for Young Adults and as an American Library Association Notable Book, both in 2004.[6][7] It also received the Oppenheim Toy Portfolio 2004 Gold Medal along with several other awards.[8]

text: The novel was also well received by critics. Rowling was praised for her imagination by USA Today writer Deirdre Donahue.[9] Most of the negative reviewers were concerned with the violence contained in the novel and with morality issues occurring throughout the book.[10]

text: The New York Times writer John Leonard praised the novel, saying "The Order of the Phoenix starts slow, gathers speed and then skateboards, with somersaults, to its furious conclusion....As Harry gets older, Rowling gets better."[11] However, he also criticises "the one-note Draco Malfoy" and the predictable Lord Voldemort.[11]

text: Predecessors and sequels[edit]

text: Harry Potter and the Order of the Phoenix is the fifth book in the Harry Potter series.[2] The first book in the series, Harry Potter and the Philosopher's Stone was first published by Bloomsbury in 1997 with an initial print-run of 500 copies in hardback, three hundred of which were distributed to libraries. By the end of 1997 , the UK edition won a National Book Award and a gold medal in the 9 to 11 year-olds category of the Nestlé Smarties Book Prize.[12][13][14] The second novel, Harry Potter and the Chamber of Secrets, was published in the UK on 2 July 1998. Harry Potter and the Prisoner of Azkaban was published a year later in the UK on 8 July 1999 and in the US on 8 September 1999.[13][14] Harry Potter and the Goblet of Fire was published on 8 July 2000  simultaneously by Bloomsbury and Scholastic.[15] Harry Potter and the Order of the Phoenix is the longest book from the series, yet the second shortest film at 2 hours and 18 minutes.[16]

text: After the publishing of Order of the Phoenix, the sixth book of the series, Harry Potter and the Half-Blood Prince, was published on 16 July 2005, and sold 9 million copies in the first 24 hours of its worldwide release.[1][17] The seventh and final novel, Harry Potter and the Deathly Hallows, was published 21 July 2007.[18] The book sold 11 million copies within 24 hours of its release: 2.7 million copies in the UK and 8.3 million in the US.[17]

text: Adaptations[edit]

text: Film[edit]

text: In 2007, Harry Potter and the Order of the Phoenix was released in a film version directed by David Yates and written by Michael Goldenberg. The film was produced by David Heyman's company, Heyday Films, alongside David Barron. The budget was reportedly between £75 and 100 million (US$150–200 million),[19][20] and it became the unadjusted eleventh-highest-grossing film of all time, and a critical and commercial success.[21] The film opened to a worldwide 5-day opening of $333 million, third all-time, and grossed $938.4 million in total, second to Pirates of the Caribbean: At World's End for the greatest total of 2007.[22][23]

text: Video games[edit]

text: A video game adaptation of the book and film versions of Harry Potter and the Order of the Phoenix was made for Microsoft Windows, PS2, PS3, Xbox 360, PSP, Nintendo DS, Wii, Game Boy Advance and Mac OS X.[24] It was released on 25 June 2007 in the U.S., 28 June 2007 in Australia and 29 June 2007 in the UK and Europe for PlayStation 3, PSP, PlayStation 2, Windows and 3 July 2007 for most other platforms.[25] The games were published by Electronic Arts.[26]

text: The book is also depicted in the 2011 video game Lego Harry Potter: Years 5–7.

text: Translations[edit]

text: The first official foreign translation of the book appeared in Vietnamese on 21 July 2003, when the first of twenty-two instalments was released. The first official European translation appeared in Serbia and Montenegro in Serbian, by the official publisher Narodna Knjiga, in early September 2003. Other translations appeared later (e.g. in November 2003 in Dutch and German). The English-language version has topped the best-seller list in France, while in Germany and the Netherlands an unofficial distributed translation process has been started on the Internet.[27]


document_title: Ghostfacers

question_text: when do the ghostfacers first appear in supernatural

text: Ghostfacers

text: The Ghostfacers are a group of fictional characters from the television series Supernatural. Originally known as the Hell Hounds, the characters were created by Trey Callaway in Episode 1.17, entitled "Hell House".

text: Ghostfacers may also refer to:

text:
"Ghostfacers", a 2008 episode of Supernatural
Ghostfacers, a webisode series of Supernatural

tag: ul


document_title: Institutions of the European Union

question_text: where is the judicial branch of the eu located

text: Institutions of the European Union

text: History[edit]

text: Most EU institutions were created with the establishment of the European Community in 1958. Much change since then has been in the context the shifting of the power balance away from the Council and towards the Parliament. The role of the Commission has often been to mediate between the two or tip the balance.[2] However the Commission is becoming more accountable to the Parliament: in 1999 it forced the resignation of the Santer Commission[3] and forced a reshuffle of the proposed Barroso Commission in 2004.[4] The development of the institutions, with incremental changes from treaties and agreements, is testament to the evolution of the Union's structures without one clear "master plan". Some such as Tom Reid of the Washington Post said of the institutions that "nobody would have deliberately designed a government as complex and as redundant as the EU".[5]

text: Under the Treaty of Paris[edit]

text: The first institutions were created at the start of the 1950s with the creation of the ECSC, based on the Schuman declaration, between six states. The ECSC was designed to bring the markets of coal and steel, the materials needed to wage war, under the control of a supranational authority with the aim of encouraging peace and economic development. It established the first institutions. At its core was an independent executive called the "High Authority" with supranational powers over the Community. The laws made by the Authority would be observed by a Court of Justice in order to ensure they were upheld and to arbitrate.[6]

text: During the negotiations, two supervisory institutions were put forward to counterbalance the power of the High Authority. The "Common Assembly" proposed by Jean Monnet to act as a monitor, counterweight and to add democratic legitimacy was composed of 78 national parliamentarians.[7] The second was the Council of Ministers, pushed by the smaller states also to add an intergovernmental element and harmonise national policies with those of the authority.[8]

text: Establishment and changes[edit]

text: In 1957 the Treaties of Rome established two, similar, communities creating a common market (European Economic Community) and promoting atomic energy co-operation (Euratom). The three institutions shared the Court of Justice and the Parliament, however they had a separate Council and High Authority, which was called the Commission in these Communities. The reason for this is the different relationship between the Commission and Council. At the time the French government was suspicious of the supranationalism and wanted to limit the powers of the High Authority in the new Communities, giving the Council a greater role in checking the executive.[8][9][10]

text: The three communities were later merged in 1967, by the Merger Treaty, into the European Communities. The institutions were carried over from the European Economic Community (making the Commission of that community the direct ancestor of the current Commission).[9] Under the Treaties of Rome, the Common Assembly (which renamed itself the Parliamentary Assembly, and then the European Parliament) was supposed to become elected. However this was delayed by the Council until 1979. Since then it gained more powers via successive treaties.[2][7] The Maastricht Treaty also gave further powers to the Council by giving it a key role in the two new pillars of the EU which were based on intergovernmental principles.[8]

text: The 2009 Lisbon Treaty brought nearly all policy areas (including the budget) under the codecision procedure (renamed "ordinary legislative procedure"), hence increasing the power of the Parliament. The rules for the distribution of seats in the parliament were also changed to a formula system.[11][12] The High Representative merged with the European Commissioner for External Relations and joined the Commission. The appointment of the Commission President became dependent upon the last EU elections. The Council of Ministers adopted more qualified majority voting and the European Council was made a distinct institution with a permanent president. The Court of Justice had some minor renaming and adjustments. In addition, the central bank became a full institution.[11][12]

text: Overview[edit]

text:
v
t
e

text:
European Parliament
- Legislature -

European Council
- Provides impetus and direction -

Council of the European Union
- Legislature -

European Commission
- Executive -

summit of the Heads of state or government, the President of the European Council and the President of the European Commission.
gives the necessary political impetus for the development of the Union and sets its general objectives and priorities
does not legislate
based in Brussels

acts together with the Parliament as a legislature
shares with the Parliament the budgetary power
ensures coordination of the broad economic and social policy and sets out guidelines for the Common Foreign and Security Policy (CFSP)
concludes international agreements
based in Brussels

acts together with the Council as a legislature
shares with the Council the budgetary power
exerts the democratic control over the institutions including the European Commission and approves the Commission members
based in and plenary sessions in Strasbourg, primarily meets in Brussels

is the executive
submits proposals for new legislation to the Parliament and Council
implements policies
administers the budget
ensures compliance with European law ("guardian of the treaties")
negotiates international agreements
based in Brussels

tag: table

text:
Court of Justice of the European Union
- Judiciary -

European Central Bank
- Central bank -

European Court of Auditors
- Financial auditor -

ensures the uniform application and interpretation of European law
has the power to decide legal disputes between member states, the institutions, businesses and individuals
based in Luxembourg

forms together with the national central banks the European System of Central Banks and thereby determines the monetary policy of the eurozone
ensures price stability in the eurozone by controlling the money supply
based in Frankfurt

checks the proper implementation of the budget
based in Luxembourg

text: List[edit]

text: There are three political institutions which hold the executive and legislative power of the Union. The Council of the European Union represents governments, the Parliament represents citizens and the Commission represents the European interest.[14] Essentially, the Council of the European Union, Parliament or another party place a request for legislation to the Commission. The Commission then drafts this and presents it to the Parliament and the Council of the European Union, where in most cases both must give their assent. Although the exact nature of this depends upon the legislative procedure in use, once it is approved and signed by both bodies it becomes law.[15] The Commission's duty is to ensure it is implemented by dealing with the day-to-day running of the Union and taking others to Court if they fail to comply.[14] According to the 2014 edition of The Official Directory of the European Union, women account for 33% of higher-ranking officials.[16]

text: European Parliament[edit]

text: The European Parliament (EP) shares the legislative and budgetary authority of the Union with the Council of the European Union (not to be confused with the European Council). Its 751 members are elected every five years by universal suffrage and sit according to political allegiance. They represent nearly 500 million citizens (the world's second largest democratic electorate) and form the only directly elected body in the Union. Despite forming one of the two legislative chambers of the Union, it has weaker powers than the Council in some sensitive areas, and does not have legislative initiative. It does, however, have powers over the Commission which the Council does not. It has been said that its democratic nature and growing powers have made it one of the most powerful legislatures in the world.[15][17][18]

text: The Parliament's President (its speaker) is Antonio Tajani (EPP), who was elected from the Parliament's members in 2017.

text: European Council[edit]

text: The European Council is the group of heads of state or government of the EU member states. It meets four times a year to define the Union's policy agenda and give impetus to integration. The President of the European Council is the person responsible for chairing and driving forward the work of the institution, which has been described as the highest political body of the European Union.[19]

text: The current president is Donald Tusk.

text: Council of the European Union, or "Council of Ministers"[edit]

text: The Council of the European Union (informally known as the "Council of Ministers" or just "the Council") is a body holding legislative and some limited executive powers and is thus the main decision making body of the Union. Its Presidency rotates between the states every six months, but every three Presidencies now cooperate on a common programme. This body is separate from the European Council, which is a similar body, but is composed of national leaders.[20]

text: The Council is composed of twenty-eight national ministers (one per state). However the Council meets in various forms depending upon the topic. For example, if agriculture is being discussed, the Council will be composed of each national minister for agriculture. They represent their governments and are accountable to their national political systems. Votes are taken either by majority or unanimity with votes allocated according to population. In these various forms they share the legislative and budgetary power of the Parliament, and also lead the Common Foreign and Security Policy.[20]

text: The presidency has been held by Estonia since 1 July 2017.

text: Commission[edit]

text: The European Commission (EC) is the executive arm of the Union. It is a body composed of one appointee from each state, currently twenty-eight, but is designed to be independent of national interests. The body is responsible for drafting all law of the European Union and has the ability to propose new laws (bills).[21] It also deals with the day-to-day running of the Union and has the duty of upholding the law and treaties (in this role it is known as the "Guardian of the Treaties").[14]

text: The Commission is led by a President who is nominated by the Council (in practice the European Council) and approved by Parliament. The remaining 27 Commissioners are nominated by member-states, in consultation with the President, and have their portfolios assigned by the President. The Council then adopts this list of nominee-Commissioners. The Council’s adoption of the Commission is not an area which requires the decision to be unanimous, their acceptance is arrived at according to the rules for qualified majority voting. The European Parliament then interviews and casts its vote upon the Commissioners. The interviews of individual nominees are conducted separately, in contrast to Parliament’s vote of approval which must be cast on the Commission as a whole without the ability to accept or reject individual Commissioners. Once approval has been obtained from the Parliament the Commissioners can take office.[22] The current President is Jean-Claude Juncker (EPP); his commission was elected in 2014.[23][needs update]

text: Court of Justice of the European Union[edit]

text: The Court of Justice of the European Union (CJEU) is the EU's judicial branch. It is responsible for interpreting EU law and treaties. It comprises the main chamber: Court of Justice, the General Court and the Civil Service Tribunal.

text: The CJEU is located in Luxembourg.

text: European Central Bank[edit]

text: The European Central Bank (ECB) is the central bank for the eurozone (the states which have adopted the euro) and thus controls monetary policy in that area with an agenda to maintain price stability.

text: It is at the centre of the European System of Central Banks which comprises all EU national banks. The bank is governed by a board of national bank governors and a President.[11][24]

text: The ECB is located in Frankfurt.

text: The current president is Mario Draghi.

text: Court of Auditors[edit]

text: The European Court of Auditors (ECA), despite its name, has no judicial powers. It ensures that taxpayer funds from the budget of the European Union have been correctly spent. The court provides an audit report for each financial year to the Council and Parliament. The Parliament uses this to decide whether to approve the Commission's handling of the budget. The Court also gives opinions and proposals on financial legislation and anti-fraud actions.[25]

text: The Court of Auditors was set up in 1975. It was created as an independent institution due to the sensitivity of the issue of fraud in the Union (the anti-fraud agency, OLAF, is also built on its independence). It is composed of one member from each state appointed by the Council every six years. Every three years one of them is elected as the president of the court, who is currently Vítor Manuel da Silva Caldeira.[25][needs update]

text: Acts and procedures[edit]

text: There are a number of types of legislation which can be passed. The strongest is a regulation, an act or law which is directly applicable in its entirety. Then there are directives which bind members to certain goals which they must achieve. They do this through their own laws and hence have room to manoeuvre in deciding upon them. A decision is an instrument which is focused at a particular person/group and is directly applicable. Institutions may also issue recommendations and opinions which are merely non-binding declarations.[26]

text: The ordinary legislative procedure is used in nearly all policy areas and provides an equal footing between the two bodies. Under the procedure, the Commission presents a proposal to Parliament and the Council. They then send amendments to the Council which can either adopt the text with those amendments or send back a "common position". That proposal may either be approved or further amendments may be tabled by the Parliament. If the Council does not approve those, then a "Conciliation Committee" is formed. The Committee is composed of the Council members plus an equal number of MEPs who seek to agree a common position. Once a position is agreed, it has to be approved by Parliament again by an absolute majority.[15][27] There are other special procedures used in sensitive areas which reduce the power of Parliament.

text: Comparisons[edit]

text: While the EU's system of governance is largely unique, elements can be compared to other models. One general observation on the nature of the distribution of powers would be that the EU resembles the federalism of Germany. There, powers are predominantly shared (states can exercise federal powers where the federation has not already exercised them) between the levels of government, and the states participate strongly with decision making at the federal level. This is in contrast with other federations, for example the United States, where powers are clearly divided between the levels of government, and the states have little say in federal decision making.[28]

text: The EU's institutional set up is also somewhat similar to the government of Switzerland (which, although in Europe, is not an EU member state). The Swiss consensus-driven system is seen as successfully uniting a state divided by language and religion, although the EU was not directly modelled on the Swiss system despite bearing a number of similarities. The European Commission has similarities to the Swiss Federal Council in that both have all-party representation and are appointed on the basis of nationality rather than popularity. The President of the Federal Council rotates between its members each year, in a fashion similar to that of the EU's Council Presidency. Due to this system of presidency Swiss leaders, like those of the EU, are relatively unknown with national politics viewed as somewhat technocratic resulting in low voter turnout, in a similar fashion to that of the European Parliament. Other parallels include the jealously guarded powers of states, the considerable level of translation and the choice of a lesser city as the capital.[29]

text: Furthermore, executive power in the EU isn't concentrated in a single institution. It becomes clearer under the Lisbon Treaty with the division of the European Council as a distinct institution with a fixed President. This arrangement has been compared to the dual executive system found in the French republic where there is a President (the Council President) and Prime Minister (the Commission President). However, unlike the French model, the Council President does not hold formal powers such as the ability to directly appoint and sack the other, or the ability to dissolve Parliament. Hence while the Council President may have prestige, it would lack power and while the Commission President would have power, it would lack the prestige of the former.[30]

text: The nature of the European Parliament is better compared with the United States House of Representatives than with the national parliaments of the European Union. This is notable in terms of the committees being of greater size and power, political parties being very decentralised and it being separated from the executive branch (most national governments operate under a parliamentary system). A difference from all other parliaments is the absence of a Parliamentary legislative initiative. However, given that in most national parliaments initiatives not backed by the executive rarely succeed the value of this difference is in question. Equally, its independence and power means that the European Parliament has an unusually high success rate for its amendments in comparison to national parliaments; 80% average and 30% for controversial proposals.[31]

text: The composition of the council can only be compared with the quite unique and unusual composition of the German upper house, the Bundesrat. Membership of the Bundesrat is limited to members of the governments of the states of Germany and can be recalled by those governments in the same manner as the EU's Council. They retain their state role while sitting in the Bundesrat and if their term ends when they are recalled by their state governments (who are solely responsible for their appointment) or they cease to sit in their state government. Hence they also are not elected at the same time and the body as a whole cannot be dissolved like most parliaments. As government representatives, members do not vote as individual members but in state blocks, rather than political alignment, to their state governments' agreed line.[32] Each state has unequal voting powers based on population, with an absolute majority required for decisions. Likewise, the presidency rotates equally between members, though each year rather than every six months like in the EU Council.[33] However, unlike the EU's Council, the Bundesrat does not vary its composition depending on the topic being discussed.[32] They both bear similar criticisms, because of the interference, of executives in the legislative process.

text: Locations[edit]

text: The institutions are not concentrated in a single capital city: instead, their headquarters are spread across four cities, Brussels, Luxembourg, Strasbourg and Frankfurt. The current arrangement was approved in 1992 and attached to the Treaty of Amsterdam.[34] The treaty states that the Commission and Council would be based in Brussels, the Courts in Luxembourg and the Parliament in Strasbourg. However some departments of the Commission and meetings of the Council take place in Luxembourg, while the Parliament has its committees and some sessions in Brussels and its secretariat in Luxembourg. Of the new institutions, the Central Bank is based in Frankfurt[35] while the European Council is based in Brussels (but has some extraordinary meetings elsewhere).[36]

text: Brussels' hosting of institutions has made it a major centre for the EU. Together with NATO it has attracted more journalists and ambassadors than Washington D.C.[37] However the three-city agreement has been criticised, notably concerning the Parliament due to the large number of people that move between the cities. The European Green Party estimated that the arrangement costs 200 million euro and 20,268 tonnes of carbon dioxide.[38] Brussels is preferred by some due to the presence of other institutions and other groups whereas Strasbourg is supported due to its historical importance to European unity.[39]


document_title: Human iron metabolism

question_text: what part of gi tract is iron absorbed

question_tokens: what part of gi tract is iron absorbed

text: Human iron metabolism

text: Importance of iron regulation[edit]

text: Iron is an essential bioelement for most forms of life, from bacteria to mammals. Its importance lies in its ability to mediate electron transfer. In the ferrous state, iron acts as an electron donor, while in the ferric state it acts as an acceptor. Thus, iron plays a vital role in the catalysis of enzymatic reactions that involve electron transfer (reduction and oxidation, redox). Proteins can contain iron as part of different cofactors, such as iron-sulfur clusters (Fe-S) and heme groups, both of which are assembled in mitochondria.

text: Cellular respiration[edit]

text: Human cells require iron in order to obtain energy as ATP from a multi-step process known as cellular respiration, more specifically from oxidative phosphorylation at the mitochondrial cristae. Iron is present in the iron-sulfur clusters and heme groups of the electron transport chain proteins that generate a proton gradient that allows ATP synthase to synthesize ATP (chemiosmosis).

text: Heme groups are part of hemoglobin, a protein found in red blood cells that serves to transport oxygen from the lungs to the tissues. Heme groups are also present in myoglobin to store and diffuse oxygen in muscle cells.

text: Oxygen transport[edit]

text: The human body needs iron for oxygen transport. Oxygen (O2) is required for the functioning and survival of nearly all cell types. Oxygen is transported from the lungs to the rest of the body bound to the heme group of hemoglobin in erythrocytes. In muscles cells, iron binds myoglobin, which regulates its release.

text: Toxicity[edit]

text: Iron is also potentially toxic. Its ability to donate and accept electrons means that it can catalyze the conversion of hydrogen peroxide into free radicals. Free radicals can cause damage to a wide variety of cellular structures, and ultimately kill the cell.[1]

text: Iron bound to proteins or cofactors such as heme is safe. Also, there are virtually no truly free iron ions in the cell, since they readily form complexes with organic molecules. However, some of the intracellular iron is bound to low-affinity complexes, and is termed labile iron or "free" iron. Iron in such complexes can cause damage as described above.[2]

text: To prevent that kind of damage, all life forms that use iron bind the iron atoms to proteins. This binding allows cells to benefit from iron while also limiting its ability to do harm.[1][3] Typical intracellular labile iron concentrations in bacteria are 10-20 micromolar,[4] though they can be 10-fold higher in anaerobic environment,[5] where free radicals and reactive oxygen species are scarcer. In mammalian cells, intracellular labile iron concentrations are typically smaller than 1 micromolar, less than 5 percent of total cellular iron.[2]

text: Bacterial protection[edit]

text: In response to a systemic bacterial infection, the immune system initiates a process known as iron withholding. If bacteria are to survive, then they must obtain iron from their environment. Disease-causing bacteria do this in many ways, including releasing iron-binding molecules called siderophores and then reabsorbing them to recover iron, or scavenging iron from hemoglobin and transferrin. The harder they have to work to get iron, the greater a metabolic price they must pay. That means that iron-deprived bacteria reproduce more slowly. So our control of iron levels appears to be an important defense against most bacterial infections; there are some exceptions however. TB causing bacterium can reside within macrophages which are an iron rich environment and Borrelia burgdorferi utilises manganese in place of iron. People with increased amounts of iron, like people with hemochromatosis, are more susceptible to some bacterial infection.[6]

text: Although this mechanism is an elegant response to short-term bacterial infection, it can cause problems when inflammation goes on for longer. Since the liver produces hepcidin in response to inflammatory cytokines, hepcidin levels can increase as the result of non-bacterial sources of inflammation, like viral infection, cancer, auto-immune diseases or other chronic diseases. When this occurs, the sequestration of iron appears to be the major cause of the syndrome of anemia of chronic disease, in which not enough iron is available to produce enough hemoglobin-containing red blood cells.[3]

text: Body iron stores[edit]

text: Most well-nourished people in industrialized countries have 4 to 5 grams of iron in their bodies (∼38 mg iron/kg body weight for women and ∼50 mg iron/kg body for men).[7] Of this, about 6997250000000000000♠2.5 g is contained in the hemoglobin needed to carry oxygen through the blood, and most of the rest (approximately 2 grams in adult men, and somewhat less in women of childbearing age) is contained in ferritin complexes that are present in all cells, but most common in bone marrow, liver, and spleen. The liver's stores of ferritin are the primary physiologic source of reserve iron in the body. The reserves of iron in industrialized countries tend to be lower in children and women of child-bearing age than in men and in the elderly. Women who must use their stores to compensate for iron lost through menstruation, pregnancy or lactation have lower non-hemoglobin body stores, which may consist of 6996500000000000000♠500 mg, or even less.

text: Of the body's total iron content, about 6996399999999999999♠400 mg is devoted to cellular proteins that use iron for important cellular processes like storing oxygen (myoglobin) or performing energy-producing redox reactions (cytochromes). A relatively small amount (3–4 mg) circulates through the plasma, bound to transferrin.[8] Because of its toxicity, free soluble iron is kept in low concentration in the body.

text: Iron deficiency first affects the storage iron in the body, and depletion of these stores is thought to be relatively non-symptomatic, although some vague and non-specific symptoms have been associated with it. Since iron is primarily required for hemoglobin, iron deficiency anemia is the primary clinical manifestation of iron deficiency. Iron-deficient people will suffer or die from organ damage well before cells run out of the iron needed for intracellular processes like electron transport.

text: Macrophages of the reticuloendothelial system store iron as part of the process of breaking down and processing hemoglobin from engulfed red blood cells. Iron is also stored as a pigment called hemosiderin which is an ill-defined deposit of protein and iron, created by macrophages where excess iron is present, either locally or systemically for example among people with iron overload due to frequent blood cell destruction and transfusions. If the systemic iron overload is corrected, over time the hemosiderin is slowly resorbed by macrophages.

text: Mechanisms of iron regulation[edit]

text: Human iron homeostasis is regulated at two different levels. Systemic iron levels are balanced by the controlled absorption of dietary iron by enterocytes, the cells that line the interior of the intestines, and the uncontrolled loss of iron from epithelial sloughing, sweat, injuries and blood loss. In addition, systemic iron is continuously recycled. Cellular iron levels are controlled differently by different cell types due to the expression of particular iron regulatory and transport proteins.

text: Systemic iron regulation[edit]

text: Dietary iron uptake[edit]

text: The absorption of dietary iron is a variable and dynamic process. The amount of iron absorbed compared to the amount ingested is typically low, but may range from 5% to as much as 35% depending on circumstances and type of iron. The efficiency with which iron is absorbed varies depending on the source. Generally the best-absorbed forms of iron come from animal products. Absorption of dietary iron in iron salt form (as in most supplements) varies somewhat according to the body’s need for iron, and is usually between 10% and 20% of iron intake. Absorption of iron from animal products, and some plant products, is in the form of heme iron, and is more efficient, allowing absorption of from 15% to 35% of intake. Heme iron in animals is from blood and heme-containing proteins in meat and mitochondria, whereas in plants, heme iron is present in mitochondria in all cells that use oxygen for respiration.

text: Like most mineral nutrients, the majority of the iron absorbed from digested food or supplements is absorbed in the duodenum by enterocytes of the duodenal lining. These cells have special molecules that allow them to move iron into the body. To be absorbed, dietary iron can be absorbed as part of a protein such as heme protein or iron must be in its ferrous Fe2+ form. A ferric reductase enzyme on the enterocytes’ brush border, duodenal cytochrome B (Dcytb), reduces ferric Fe3+ to Fe2+.[9] A protein called divalent metal transporter 1 (DMT1), which can transport several divalent metals across the plasma membrane, then transports iron across the enterocyte’s cell membrane into the cell.

text: These intestinal lining cells can then either store the iron as ferritin, which is accomplished by Fe3+ binding to apoferritin (in which case the iron will leave the body when the cell dies and is sloughed off into feces), or the cell can release it into the body via the only known iron exporter in mammals, ferroportin. Hephaestin, a ferroxidase that can oxidize Fe2+ to Fe3+ and is found mainly in the small intestine, helps ferroportin transfer iron across the basolateral end of the intestine cells. In contrast, ferroportin is post-translationally repressed by hepcidin, a 25-amino acid peptide hormone. The body regulates iron levels by regulating each of these steps. For instance, enterocytes synthesize more Dcytb, DMT1 and ferroportin in response to iron deficiency anemia.[10] Iron absorption from diet is enhanced in the presence of vitamin C and diminished by excess calcium, zinc, or manganese.[11][citation needed]

text: The human body’s rate of iron absorption appears to respond to a variety of interdependent factors, including total iron stores, the extent to which the bone marrow is producing new red blood cells, the concentration of hemoglobin in the blood, and the oxygen content of the blood. The body also absorbs less iron during times of inflammation, in order to deprive bacteria of iron. Recent discoveries demonstrate that hepcidin regulation of ferroportin is responsible for the syndrome of anemia of chronic disease.

text: Iron recycling and loss[edit]

text: Most of the iron in the body is hoarded and recycled by the reticuloendothelial system, which breaks down aged red blood cells. In contrast to iron uptake and recycling, there is no physiologic regulatory mechanism for excreting iron. People lose a small but steady amount by gastrointestinal blood loss, sweating and by shedding cells of the skin and the mucosal lining of the gastrointestinal tract. The total amount of loss for healthy people in the developed world amounts to an estimated average of 6994100000000000000♠1 mg a day for men, and 1.5–2 mg a day for women with regular menstrual periods.[citation needed] People with gastrointestinal parasitic infections, more commonly found in developing countries, often lose more.[1] Those who cannot regulate absorption well enough get disorders of iron overload. In these diseases, the toxicity of iron starts overwhelming the body's ability to bind and store it.[12]

text: Cellular iron regulation[edit]

text: Iron import[edit]

text: Most cell types take up iron primarily through receptor-mediated endocytosis via transferrin receptor 1 (TFR1), transferrin receptor 2 (TFR2) and GAPDH. TFR1 has a 30-fold higher affinity for transferrin-bound iron than TFR2 and thus is the main player in this process.[13][14] The higher order multifunctional glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) also acts as a transferrin receptor.[15][16] Transferrin-bound ferric iron is recognized by these transferrin receptors, triggering a conformational change that causes endocytosis. Iron then enters the cytoplasm from the endosome via importer DMT1 after being reduced to its ferrous state by a STEAP family reductase.[17]

text: Alternatively, iron can enter the cell directly via plasma membrane divalent cation importers such as DMT1 and ZIP14 (Zrt-Irt-like protein 14).[18] Again, iron enters the cytoplasm in the ferrous state after being reduced in the extracellular space by a reductase such as STEAP2, STEAP3 (in erythrocytes), Dcytb (in enterocytes) and SDR2.[17]

text: The labile iron pool[edit]

text: In the cytoplasm, ferrous iron is found in a soluble, chelatable state which constitutes the labile iron pool (~0.001 mM).[19] In this pool, iron is thought to be bound to low-mass compounds such as peptides, carboxylates and phosphates, although some might be in a free, hydrated form (aqua ions).[19] Alternatively, iron ions might be bound to specialized proteins known as metallochaperones.[20] Specifically, poly-r(C)-binding proteins (PCBPs) appear to mediate transfer of free iron to ferritin (for storage) and non-heme iron enzymes (for use in catalysis).[18][21] The labile iron pool is potentially toxic due to iron's ability to generate reactive oxygen species. Iron from this pool can be taken up by mitochondria via mitoferrin to synthesize Fe-S clusters and heme groups.[17]

text: The storage iron pool[edit]

text: Iron can be stored in ferritin as ferric iron due to the ferroxidase activity of the ferritin heavy chain.[22] Dysfunctional ferritin may accumulate as hemosiderin, which can be problematic in cases of iron overload.[23] The ferritin storage iron pool is much larger than the labile iron pool, ranging in concentration from 0.7 mM to 3.6 mM.[19]

text: Iron export[edit]

text: Iron export occurs in a variety of cell types, including neurons, erythrocytes, macrophages and enterocytes. The latter two are especially important since systemic iron levels depend upon them. There is only one known iron exporter, ferroportin.[24] It transports ferrous iron out of the cell, generally aided by ceruloplasmin and/or hephaestin (mostly in enterocytes), which oxidize iron to its ferric state so it can bind ferritin in the extracellular medium.[17] Hepcidin causes the internalization of ferroportin, decreasing iron export. Besides, hepcidin seems to downregulate both TFR1 and DMT1 through an unknown mechanism.[25] Another player assisting ferroportin in effecting cellular iron export is GAPDH.[26] A specific post translationally modified isoform of GAPDH is recruited to the surface of iron loaded cells where it recruits apo-transferrin in close proximity to ferroportin so as to rapidly chelate the iron extruded.[27]

text: The expression of hepcidin, which only occurs in certain cell types such as hepatocytes, is tightly controlled at the transcriptional level and it represents the link between cellular and systemic iron homeostasis due to hepcidin's role as "gatekeeper" of iron release from enterocytes into the rest of the body.[17] Erythroblasts produce erythroferrone, a hormone which inhibits hepcidin and so increases the availability of iron needed for hemoglobin synthesis.[28]

text: Translational control of cellular iron[edit]

text: Although some control exists at the transcriptional level, the regulation of cellular iron levels is ultimately controlled at the translational level by iron-responsive element-binding proteins IRP1 and especially IRP2.[29] When iron levels are low, these proteins are able to bind to iron-responsive elements (IREs). IREs are stem loop structures in the untranslated regions (UTRs) of mRNA.[17]

text: Both ferritin and ferroportin contain an IRE in their 5' UTRs, so that under iron deficiency their translation is repressed by IRP2, preventing the unnecessary synthesis of storage protein and the detrimental export of iron. In contrast, TFR1 and some DMT1 variants contain 3' UTR IREs, which bind IRP2 under iron deficiency, stabilizing the mRNA, which guarantees the synthesis of iron importers.[17]

text: Iron-related pathology[edit]

text: Iron deficiency[edit]

text: Functional or actual iron deficiency can result from a variety of causes. These causes can be grouped into several categories:

text:
Increased demand for iron, which the diet cannot accommodate.
Increased loss of iron (usually through loss of blood).
Nutritional deficiency. This can result due to a lack of dietary iron or consumption of foods that inhibit iron absorption, including calcium, phytates and tannins. Black tea steeped for long has high tannins.
Inability to absorb iron: A common cause of iron deficiency is the widespread use of acid reducing medications, the strongest of which are proton pump inhibitors (PPIs) such as omeprazole.[citation needed]
Damage to the intestinal lining. Examples of causes of this kind of damage include surgery involving the duodenum, or diseases like Crohn's or celiac sprue which severely reduce the surface area available for absorption.
Inflammation leading to hepcidin-induced restriction on iron release from enterocytes (see above).

text: Iron overload[edit]

text: The body is able to substantially reduce the amount of iron it absorbs across the mucosa. It does not seem to be able to entirely shut down the iron transport process. Also, in situations where excess iron damages the intestinal lining itself (for instance, when children eat a large quantity of iron tablets produced for adult consumption), even more iron can enter the bloodstream and cause a potentially deadly syndrome of iron overload. Large amounts of free iron in the circulation will cause damage to critical cells in the liver, the heart and other metabolically active organs.

text: Iron toxicity results when the amount of circulating iron exceeds the amount of transferrin available to bind it, but the body is able to vigorously regulate its iron uptake. Thus, iron toxicity from ingestion is usually the result of extraordinary circumstances like iron tablet over-consumption[1][30] rather than variations in diet. The type of acute toxicity from iron ingestion causes severe mucosal damage in the gastrointestinal tract, among other problems.

text: Chronic iron toxicity is usually the result of more chronic iron overload syndromes associated with genetic diseases, repeated transfusions or other causes. In such cases the iron stores of an adult may reach 50 grams (10 times normal total body iron) or more. Classic examples of genetic iron overload includes hereditary hemochromatosis (HH) and the more severe disease juvenile hemochromatosis (JH) caused by mutations in either the gene RGMc gene, a member of a three gene repulsive guidance molecule family,[31] (also called hemojuvelin (HJV), and HFE2), Hemojuvelin, or the HAMP gene that encodes (an iron regulatory peptide). The exact mechanisms of most of the various forms of adult hemochromatosis, which make up most of the genetic iron overload disorders, remain unsolved. So while researchers have been able to identify genetic mutations causing several adult variants of hemochromatosis, they now must turn their attention to the normal function of these mutated genes.