document_title: The Windmills of Your Mind

question_text: who sings the original windmills of your mind

text: The Windmills of Your Mind

text: Composition/original recording[edit]

text: In the original 1968 film The Thomas Crown Affair, the song is heard – sung by Noel Harrison – during opening credits; and, during the film, in a scene in which the character Thomas Crown flies a glider at the glider airport in Salem, New Hampshire: having edited the rough cut for this scene utilizing the Beatles track "Strawberry Fields Forever" producer/director Norman Jewison commissioned an original song be written for the glider scene which would reference the ambivalent feelings of Thomas Crown as he engages in a favorite pastime while experiencing the tension of preparing to commit a major robbery. Alan Bergman: "Michel [Legrand] played us [ie. Alan and Marilyn Bergman] seven or eight melodies. We listened to all of them and decided to wait until the next day to choose one. We three decided on the same one, a long baroque melody... The lyric we wrote was stream-of-consciousness. We felt that the song had to be a mind trip of some kind" – "The [eventual] title was [originally] a line at the end of a section... When we finished we said: "What do we call this? It's got to have a title. That line is kind of interesting.' So we restructured the song so that the line appeared again at the end. It came out of the body of the song. I think we were thinking, you know when you try to fall asleep at night and you can't turn your brain off and thoughts and memories tumble."[2]

text: Noel Harrison recorded the song after Andy Williams passed on it: according to Harrison: "It was recorded live on a huge sound stage at Paramount, with the accompanying film clips running on a giant screen and Michel blowing kisses to the orchestra."[3] Harrison took issue with the couplet "Like a tunnel that you follow to a tunnel of its own / Down a hollow to a cavern where the sun has never shone", singing the word "shone" British-style with a short vowel sound making the rhyme with "own" imperfect. Marilyn Bergman: "We said 'No, it's shone [long vowel sound].' And he said 'No, it's our language!' And we said: 'Yes, but it's our song.' So reluctantly, he sang shone [long vowel sound] and our rhyme was intact."[2] However, Harrison evidently had the last laugh; in the finally released version he sings "shone" with a short vowel. Harrison's version had a US single in the US in July 1968 soon after the premiere of the film and similarly was released in the British Isles at the time of the film's 7 February 1969 premiere in the UK and Ireland. As a result, it was a current UK release when "The Windmills of Your Mind" received an Academy Award nomination on 24 February 1969: Harrison's single debuted at #36 in the UK Top 50 dated 4 March 1969 and had risen to #15—abetted by performances by Harrison on the 27 March 1969 broadcast of TOTP and also on variety shows hosted by Rolf Harris and Scott Walker—when the song won the Academy Award on 14 April 1969, an endorsement which facilitated the Top Ten entry of Harrison's single on the UK chart dated 22 April 1969 with its chart peak of #8 effected two weeks later.[4]

text: "The Windmills of Your Mind" was performed on the Academy Awards ceremony broadcast of 14 April 1969 by José Feliciano; Noel Harrison would recall: "I was invited to sing it at the Academy Awards... but I was making a movie in England at the time, and the producer (who didn't like me) refused to let me go." The film which caused the scheduling conflict has been identified as Take a Girl Like You directed by Jonathan Miller.[3]

text: Dusty Springfield version[edit]

text: Jerry Wexler, president of Atlantic Records, heard "The Windmills of Your Mind" on the soundtrack of The Thomas Crown Affair and championed having Dusty Springfield record the song for her debut Atlantic album Dusty in Memphis, overcoming the singer's strong resistance; Springfield's friend and subsequent manager Vicki Wickham would allege: "Dusty always said she hated it because she couldn't identify with the words."[5] During the first sessions for the track at American Sound Studio in Memphis, problems with getting the proper chords down arose, and at Springfield's suggestion the song was arranged so the first three verses were sung in a slower tempo than the original film version.

text: In April 1969 the third A-side release from Dusty in Memphis was announced as "I Don't Want to Hear It Anymore" with "The Windmills of Your Mind" as B-side: however Wexler was prepared to promote "Windmills" as the A-side if it won the Oscar for Best Song, reportedly instructing mail-room clerks at Atlantic Records' New York City headquarters to listen to the Academy Awards broadcast the night of 14 April 1969; hearing "The Windmills" announced as the Best Song winner was these clerks' cue to drive a station wagon loaded with 2500 copies of a double-sided promo single of Springfield's version – identified on the label as "Academy Award Winner" – to the New York City general post office, where the copies of the single were mailed out to key radio stations across the US.[6] Although its Hot 100 debut was not effected until the 5 May 1969 issue of Billboard and then with a #99 ranking, Springfield's "The Windmills" made a rapid ascent to the Top 40 being ranked at #40 on the Hot 100 dated 24 May 1969 only to stall over the subsequent three weeks peaking at #31 on the Hot 100 dated 14 June 1969 with only one additional week of Hot 100 tenure, being ranked at #45 on the 21 June 1969 chart. On the Cash Box chart, the song rose as high as #22.[7] Local hit parades indicate that Springfield's "Windmills" had Top Ten impact in only select larger markets: Boston, Southern California, and Miami. The track did reach #3 on the Easy Listening chart in Billboard a feat matched by Springfield's third subsequent single "Brand New Me" which therefore ties with "The Windmills" as having afforded Springfield her best-ever solo showing on a Billboard chart.[8]

text: José Feliciano version[edit]

text: "The Windmills of Your Mind" was recorded by José Feliciano for his 1969 album 10 to 23,[9] and Feliciano performed the song on the Academy Awards ceremony broadcast of 14 April 1969; the song's original singer Noel Harrison would later opine of Feliciano's performance: "A wonderful musician and compelling singer, he made much too free with the beautiful melody in my humble opinion. But that's jazz."[3] It was Feliciano's version of "The Windmills" which became a hit in the Netherlands, reaching #11 on the Dutch chart in November 1969.[10] and Nr. 4 in the Turkish hit parade in April 1970.[11]

text: Other versions[edit]

text: In English[edit]

text:
All Angels on their self-titled album (2006)[12]
Ed Ames on his album The Windmills of Your Mind (1969)[13]
Tina Arena on her album Songs Of Love & Loss (2007)[14]
The Arbors on their album The Arbors (1977)
Dorothy Ashby on her album "Dorothy's Harp" (1969) - Instrumental version -[15]
Jeri Brown on her album April in Paris (1996)[16]
Anne Clark on her maxi-single The Haunted Road (1993),[17] featuring Eyeless in Gaza: track included Clark's 1996 compilation album The Nineties A Fine Collection
Petula Clark on her album Portrait of Petula (1969),[18] featured on the soundtrack of the 2012 film Killing Them Softly
The Colourfield B-side of their 1984 single "Take"; bonus track on Japanese release of the group's album Virgins and Philistines
Ray Conniff Singers on their 1969 album Jean;[19] featured in the 2015 film Focus
Randy Crawford with David Sanborn on Sanborn's album Time and the River (2015)[20]
Vic Damone on his album Over the Rainbow (1982)[21]
John Davidson on his album My Cherie Amour (1969)[22]
Skeeter Davis on her album Mary Frances (1969)[23]
Elaine Delmar on her concert album Recital At the Festival The Golden Orpheus '71 (1971)[24]
Neil Diamond on his album The Movie Album: As Time Goes By (1998)[25]
Val Doonican on his album Rocking Chair Favourites (1972)[26]
Connie Evingson on her album Stockholm Sweetnin' (2006)[27]
Laura Fygi on her album Watch What Happens When Laura Fygi Meets Michel Legrand (1997)[28]
John Gary on his album Love of a Gentle Woman (1969)[29]
Peter Grant on his album New Vintage (2006)[30]
Rigmor Gustafsson on her album On My Way to You (2006)[31]
Jacintha on her album Jacintha Goes to Hollywood (2007)[32]
Peter Jöback on his album Storybook (2004)[33]
Jack Jones on his album Jack Jones sings Michel Legrand (1971)[34]
Eliza Keil on her album Raindrops Keep Fallin' on My Head (1970)[35]
Anita Kerr Singers on their album Velvet Voices & Bold Brass (1969)[36]
Kiki and Herb on their concert album ...Will Die for You: Live at Carnegie Hall (2004);[37] mistitled "The Windmills of My Mind"
Jason Kouchak on his album Midnight Classics (2008);[38] mistitled "The Windmills of My Mind"
The King's Singers on their 1972 self-titled album[39]
Kim Kuzma on her album Acustico II (2015)[40]
Judith Lefeber on her album In My Dreams (2003)[41]
The Lettermen on their album Greatest Movie Hits (2000)[42]
Barbara Lewis on her album The Many Grooves of Barbara Lewis (1969)[43]
Abbey Lincoln on her album Over the Years (2000)[44]
Gloria Loring on her album ...And Now We Come to Distances (1969)[45]
Carmen Lundy on her album Something to Believe In (2003)[46]
The Manhattans single (c. 1970);[47] bonus track on the 2015 CD release of the group's 1971 album With These Hands
Johnny Mathis Version #1: on his album Love Theme from 'Romeo & Juliet' (1969)[48]
Version #2: with Toots Thielemans on Thielemans' album Chez Toots (1998)[49]
Chez Toots track listing reads "Les Moulins de mon cœur (The Windmills of Your Mind)": Mathis sings only the English-language lyrics
Natalia Mateo (de) on her album Heart of Darkness (2015)[50]
Jane McDonald on her album Love at the Movies (2001)[51]
Maureen McGovern Version #1: on her album Academy Award Performance – And the Envelope, Please (1975)[52]
Version #2: on her album The Music Never Ends (1997)[53]
Eva Mendes recorded for commercial (starring Mendes) for Angel perfume[54]
Nana Mouskouri on her album Falling in Love Again: Great Songs from the Movies (1993)[55]
Alison Moyet on her album Voice (2004)[56]
Jim Nabors on his album Everything is Beautiful (1970)[57]
Jerry Nelson as a "Screaming Thing" on The Muppet Show's second season premiere (1977)
Judy Page (af) on her album Time and Love (1969)[58]
Elaine Paige on her album Cinema (1984)[59]
Parenthetical Girls on their album Entanglements (2008)[60]
Billy Paul on his album Ebony Woman (1970)[61]
Pepe & Paradise on their compilation album 70s Radio Hits (2000);[62] taped performance from Yleisradio dating from 1971 or 1972
Dianne Reeves on her album When You Know (2008)[63]
Ginette Reno on her English-language album Ginette Reno (1969)[64]
Rita Reys on her album Rita Reys Sings Michel LeGrand (1972)[65]
Jimmie Rodgers on his album The Windmills of Your Mind (1969);[66] released as a single: bubbled under Hot 100 with a #123 peak
John Rowles on his album Saying Goodbyes (1971);[67] medley: "Where Do I Begin (Love Story)"/"Windmills Of Your Mind"
Sandler and Young on their album Once More With Feeling (c. 1970)[68]
The Sandpipers on their album The Wonder of You (1969)[69]
Mathilde Santing on her compilation album Matilde Matilde (1997);[70] the track is a recording of a rehearsal of Santing's performance of the song at the 1985 Knokke Festival (nl) revival
Janet Seidel on her album Comme ci comme ça (2004);[71] the track is listed as "Windmills of Your Mind"/"Moulins de mon cœur" and includes lyrics from both the English- and French-language renderings of the song.
Dinah Shore on her album Once Upon a Summertime (1975)[72]
Sharleen Spiteri on her album The Movie Songbook (2010)[73]
Sting on the soundtrack album for The Thomas Crown Affair (1999)[74]
Barbra Streisand on her album What Matters Most (2011)[75]
Swing Out Sister on their compilation album The Best of Swing Out Sister (1996);[76] taped performance from The Jeff Graham Show on Radio Luxembourg, made in 1989: the track was included on some editions of the 1989 single release "When in the World", and is also included on the 2014 compilation The Essential Swing Out Sister
Take 6 on their album The Standard (2008)[77]
Becky Taylor on her album Shine (2003)[78]
Kiri Te Kanawa on her album Magic: Kiri sings Michel Legrand (1992)[79]
Mel Tormé on his album A Time For Us (Love Theme From 'Romeo & Juliet') (1969)[80]
Grady Tate on his album Windmills of My Mind (1968)[81]
Leslie Uggams on her album On My Way to You: Songs of Alan & Marilyn Bergman (2003)[82]
Nina van Pallandt on her album Nina Alone (1970)[83]
Vanilla Fudge on their album Rock & Roll (1969);[84] B-side of single release "Lord in the Country"
Vassilikos on his album Vintage (2009)[85]
Helena Vondráčková on her album Isle of Helena (1972)[86]
Kim Weston on her album Big Brass Four Poster (1970)[87]
Susan Wong on her album 511 (2009);[88] mistitled "The Windmills of My Mind"
Edward Woodward on his album The Edward Woodward Album (1972)[89]

text: In French: "Les Moulins de mon cœur"[edit]

text: The lyrics for the French-language rendering of "The Windmills of Your Mind" were written by Eddy Marnay and this version, entitled "Les Moulins de mon cœur", was first recorded in 1968 by Marcel Amont who was resultantly afforded a minor French chart hit (peak #49).[90]

text: "Les Moulins de mon coeur" has subsequently been recorded by:

text:
Frida Boccara on her album Un jour, un enfant (1969)[91]
Richard Anthony on his album Señora la Dueña (1970)[92]
Dany Brillant on his album Histoire d'un amour (2007)[93]
Noëlle Cordier single (1969)[94]
Anne-Marie David on her concert album Live In Charleroi (2004)[95]
Natalie Dessay with Michel LeGrand on their collaborative album Entre Elle et Lui (2013)[96]
Celine Dion on her concert album Céline Dion en concert (1985); in medley "Hommage à Michel Legrand: Quand on s'aime / Brûle pas tes doigts / La Valse des lilas / Quand ça balance / Les Moulins de mon coeur"[97]
Miss Dominique on her album Une femme battante (2006)[98]
Claude François on his album Un Monde de Musique (1969)[99]
Jason Kouchak on his album Comme d'Habitude (2011)[100]
Patricia Kaas on her album "Piano Bar" (2002)[101]
Vicky Leandros single, included on her album Zoom sur Vicky (1969)[102]
Julia Migenes on her concert album Live at the Olympia (1989)[103]
Jessye Norman on her album Michel Legrand: I Was Born in Love with You (2000)[104]
Marie Denise Pelletier on her album Lesmots de Marnay (2003)[105]
Ginette Reno on her French-language album Ginette Reno (1969)[106]
Demis Roussos on his album Immortel (1995)[107]
Janet Seidel on her album Comme ci comme ça (2004);[71] the track is listed as "Windmills of Your Mind"/"Moulins de mon cœur" and includes lyrics from both the English- and French-language renderings of the song
Caterina Valente on her concert album Caterina Valente Live [London Palladium] (1975);[108] track listing reads "The Windmills of Your Mind": however it is sung completely in French
Sylvie Vartan on her album La Reine de Saba (1974);[109] the album La Reine de Saba was issued only in Japan: its tracks were all included on the 1997 box set Sylvie Vartan: Les Années RCA
Amaury Vassili on his album Canterò (2010)[110]
Vigon Bamy Jay on their album Les Soul Men (2013)[111]
Carol Welsman on her album Hold Me (2001)[112]

text: In other languages[edit]

text: In 1970 Helena Vondráčková, prior to recording "The Windmills of Your Mind" with its original English lyrics for her album Isle of Helena (1972), recorded the song as rendered in Czech: "Můžeš zůstat, můžeš jít",[113] and also Japanese: "Kaze no sasayaki".[114] Introduced on the album Ostrov Heleny Vondráčkové,[113] "Můžeš zůstat, můžeš jít" has become a signature song for Vondráčková: in 2012 when her three CD retrospective (Nejen) o lásce was issued, Vondráčková cited "Můžeš zůstat, můžeš jít" as "the song on the [anthology] dearest to [her] heart".[115] An alternate Czech rendering of "The Windmills of Your Mind": "Mlýnské kolo v srdci mém", was recorded by Hana Hegerová to serve as title cut for her 2010 album of renderings of famous French-language songs.[116]

text: "The Windmills of Your Mind" has also been rendered as:

text:
"Cirkels" (Dutch): recorded by Herman van Veen (1968),[117] Marco Bakker (nl) on his album Marco Bakker zingt romantische sfeersongs (1980),[118][119] Hans Dorrestijn with Martin van Dijk (nl) for their collaborative album Cirkels (2002).[120]
"Samanlainen onni" (Finnish): recorded by Jarkko & Laura (1968), Katri Helena (1970), Kristian (fi) on the multi-artist album Trio (1970), Tapio Heinonen (fi) on his album Julian Grimau (1971), Petri Salminen (fi) on his album Tien päällä (1997), Anneli Sari (fi) on her 1999 album Les Chansons, and Marita Taavitsainen (fi) on her album Yksi Ainoa Katse (1999).[121]
"Vinden I Min Själ" (Swedish): recorded by Lill-Babs on her album Till Mina Vänner (1979),[122] Anders Ekborg on his album Äkta Vara – 11 Sångfilmer 100% Live (2006),[123] Anita Strandell (sv) on her album Sommarbaravara (2011).[124]
"Wie sich Mühlen dreh'n im Wind" (German): recorded by Vicky Leandros on her album Ich glaub' an Dich (1969),[125] Caterina Valente on her concert album Caterina Valente Live (1969),[126] Katja Ebstein on her album ''Wunder gibt es immer wieder (1970),[127] Bibi Johns (1970).[128]
"I Mulini Dei Ricordi" (Italian): recorded by Enzo Jannacci on his album Come gli aeroplani (2001).[citation needed]
"Los molinos de tu espíritu" (Spanish): recorded by German singer Katja Ebstein on her Spanish-language album En Español (1971).[129]


document_title: List of Olympic Games host cities

question_text: where will the next summer and winter olympics be held

root

text: List of Olympic Games host cities

text: Olympic Games host cities[edit]

text:
City
Country
Continent
Summer (Olympiad)
Winter
Year
Opening Ceremony
Closing Ceremony

Athens
 Greece
Europe
S005I
—
1896
000000002018-04-06-0000April 6
000000002018-04-15-0000April 15

Paris
 France
Europe
S005II
—
1900
000000002018-05-14-0000May 14
000000002018-10-28-0000October 28

St. Louis[a]
 United States
North America
S005III
—
1904
000000002018-07-01-0000July 1
000000002018-11-23-0000November 23

London[c]
 United Kingdom
Europe
S005IV
—
1908
000000002018-04-27-0000April 27
000000002018-10-31-0000October 31

Stockholm
 Sweden
Europe
S005V
—
1912
000000002018-05-05-0000May 5
000000002018-07-22-0000July 22

Berlin
 Germany
Europe
S006VI
—
1916
Cancelled due to WWI[4]

Antwerp[d]
 Belgium
Europe
S007VII
—
1920
000000002018-04-20-0000April 20
000000002018-09-12-0000September 12[5]

Chamonix
 France
Europe
—
W001I
1924
000000002018-01-25-0000January 25
000000002018-02-04-0000February 4[6]

Paris
 France
Europe
S008VIII
—
000000002018-05-04-0000May 4
000000002018-07-27-0000July 27[7]

St. Moritz
  Switzerland
Europe
—
W002II
1928
000000002018-02-11-0000February 11
000000002018-02-19-0000February 19[8]

Amsterdam
 Netherlands
Europe
S009IX
—
000000002018-05-17-0000May 17
000000002018-08-12-0000August 12[9]

Lake Placid
 United States
North America
—
W003III
1932
000000002018-02-04-0000February 4
000000002018-02-15-0000February 15[10]

Los Angeles
 United States
North America
S010X
—
000000002018-07-30-0000July 30
000000002018-08-14-0000August 14[11]

Garmisch-Partenkirchen
 Nazi Germany
Europe
—
W004IV
1936
000000002018-02-06-0000February 6
000000002018-02-16-0000February 16[12]

Berlin
 Nazi Germany
Europe
S011XI
—
000000002018-08-01-0000August 1
000000002018-08-16-0000August 16[13]

Sapporo
Garmisch-Partenkirchen[e]
 Empire of Japan
 Nazi Germany
Asia
Europe
—
W005aV
1940
Cancelled due to WWII[4]

Tokyo
Helsinki[f]
 Empire of Japan
 Finland
Asia
Europe
S012XII
—

Cortina d'Ampezzo
 Italy
Europe
—
W005bV
1944

London
 United Kingdom
Europe
S013XIII
—

St. Moritz
  Switzerland
Europe
—
W005cV
1948
000000002018-01-30-0000January 30
000000002018-02-08-0000February 8

London
 United Kingdom
Europe
S014XIV
—
000000002018-07-29-0000July 29
000000002018-08-14-0000August 14

Oslo
 Norway
Europe
—
W006VI
1952
000000002018-02-14-0000February 14
000000002018-02-25-0000February 25

Helsinki
 Finland
Europe
S015XV
—
000000002018-07-19-0000July 19
000000002018-08-03-0000August 3

Cortina d'Ampezzo
 Italy
Europe
—
W007VII
1956
000000002018-01-26-0000January 26
000000002018-02-05-0000February 5

Melbourne
Stockholm[g]
 Australia
 Sweden
Oceania
Europe
S016XVI
—
000000002018-11-22-0000November 22
000000002018-06-10-0000June 10
000000002018-12-08-0000December 8
000000002018-06-17-0000June 17

Squaw Valley
 United States
North America
—
W008VIII
1960
000000002018-02-18-0000February 18
000000002018-02-28-0000February 28

Rome
 Italy
Europe
S017XVII
—
000000002018-08-25-0000August 25
000000002018-09-11-0000September 11

Innsbruck
 Austria
Europe
—
W009IX
1964
000000002018-01-29-0000January 29
000000002018-02-09-0000February 9

Tokyo
 Japan
Asia
S018XVIII
—
000000002018-10-10-0000October 10
000000002018-10-24-0000October 24

Grenoble
 France
Europe
—
W010X
1968
000000002018-02-06-0000February 6
000000002018-02-18-0000February 18

Mexico City
 Mexico
North America
S019XIX
—
000000002018-10-12-0000October 12
000000002018-10-27-0000October 27

Sapporo
 Japan
Asia
—
W011XI
1972
000000002018-02-03-0000February 3
000000002018-02-13-0000February 13

Munich
 West Germany
Europe
S020XX
—
000000002018-08-26-0000August 26
000000002018-09-11-0000September 11

Innsbruck
 Austria
Europe
—
W012XII
1976
000000002018-02-04-0000February 4
000000002018-02-15-0000February 15

Montreal
 Canada
North America
S021XXI
—
000000002018-07-17-0000July 17
000000002018-08-01-0000August 1

Lake Placid
 United States
North America
—
W013XIII
1980
000000002018-02-12-0000February 12
000000002018-02-24-0000February 24

Moscow
 Soviet Union
Europe[h]
S022XXII
—
000000002018-07-19-0000July 19
000000002018-08-03-0000August 3

Sarajevo
 Yugoslavia
Europe
—
W014XIV
1984
000000002018-02-07-0000February 7
000000002018-02-19-0000February 19

Los Angeles
 United States
North America
S023XXIII
—
000000002018-07-28-0000July 28
000000002018-08-12-0000August 12

Calgary
 Canada
North America
—
W015XV
1988
000000002018-02-13-0000February 13
000000002018-02-28-0000February 28

Seoul
 South Korea
Asia
S024XXIV
—
000000002018-09-17-0000September 17
000000002018-10-02-0000October 2

Albertville
 France
Europe
—
W016XVI
1992
000000002018-02-08-0000February 8
000000002018-02-23-0000February 23

Barcelona
 Spain
Europe
S025XXV
—
000000002018-07-25-0000July 25
000000002018-08-09-0000August 9

Lillehammer
 Norway
Europe
—
W017XVII
1994
000000002018-02-12-0000February 12
000000002018-02-27-0000February 27

Atlanta
 United States
North America
S026XXVI
—
1996
000000002018-07-19-0000July 19
000000002018-08-04-0000August 4

Nagano
 Japan
Asia
—
W018XVIII
1998
000000002018-02-07-0000February 7
000000002018-02-22-0000February 22

Sydney
 Australia
Oceania
S027XXVII
—
2000
000000002018-09-15-0000September 15
000000002018-10-01-0000October 1

Salt Lake City
 United States
North America
—
W019XIX
2002
000000002018-02-08-0000February 8
000000002018-02-24-0000February 24

Athens
 Greece
Europe
S028XXVIII
—
2004
000000002018-08-13-0000August 13
000000002018-08-29-0000August 29

Torino
 Italy
Europe
—
W020XX
2006
000000002018-02-10-0000February 10
000000002018-02-26-0000February 26

Beijing[i]
 China
Asia
S029XXIX
—
2008
000000002018-08-08-0000August 8
000000002018-08-24-0000August 24

Vancouver
 Canada
North America
—
W021XXI
2010
000000002018-02-12-0000February 12
000000002018-02-28-0000February 28

London
 United Kingdom
Europe
S030XXX
—
2012
000000002018-07-27-0000July 27
000000002018-08-12-0000August 12

Sochi
 Russia
Europe[h]
—
W022XXII
2014
000000002018-02-07-0000February 7
000000002018-02-23-0000February 23

Rio de Janeiro
 Brazil
South America
S031XXXI
—
2016
000000002018-08-05-0000August 5
000000002018-08-21-0000August 21

Pyeongchang
 South Korea
Asia
—
W023XXIII
2018
000000002018-02-09-0000February 9
000000002018-02-25-0000February 25

Tokyo
 Japan
Asia
S032XXXII
—
2020
000000002018-07-24-0000July 24
000000002018-08-09-0000August 9

Beijing
 China
Asia
—
W024XXIV
2022
000000002018-02-04-0000February 4
000000002018-02-20-0000February 20

Paris
 France
Europe
S033XXXIII
—
2024
000000002018-07-26-0000July 26
000000002018-08-11-0000August 11

TBD
TBD

—
W025XXV
2026
(TBD)

Los Angeles
 United States
North America
S034XXXIV
—
2028
000000002018-07-21-0000July 21
000000002018-08-06-0000August 6

TBD
TBD

—
W026XXVI
2030
(TBD)

tag: table

text: Host cities for multiple Summer and Winter Olympic Games[edit]

text:
List of cities that hosted multiple editions of the Olympic Games

City
Country
Continent
Summer Olympics
Winter Olympics
Total

London
 United Kingdom
Europe
3 (1908, 1948, 2012)
0
3

Paris
 France
Europe
3 (1900, 1924, 2024)
0

Los Angeles
 United States
North America
3 (1932, 1984, 2028)
0

Athens
 Greece
Europe
2 (1896, 2004)
0
2

Tokyo
 Japan
Asia
2 (1964, 2020)
0

Beijing
 China
Asia
1 (2008)
1 (2022)

St. Moritz
  Switzerland
Europe
0
2 (1928, 1948)

Innsbruck
 Austria
Europe
0
2 (1964, 1976)

Lake Placid
 United States
North America
0
2 (1932, 1980)

text: The 1906 Intercalated Games are not officially recognized by the IOC as an official Olympic Games.

tag: ul

text: Number of Olympic Games by country[edit]

text:
List of countries ranked by the number of times they hosted the Olympic Games

Rank
Country
Continent
Summer Olympics
Winter Olympics
Total

1
 United States
North America
5 (1904, 1932, 1984, 1996, 2028)
4 (1932, 1960, 1980, 2002)
9

2
 France
Europe
3 (1900, 1924, 2024)
3 (1924, 1968, 1992)
6

3
 Japan
Asia
2 (1940, 1964, 2020)
2 (1940, 1972, 1998)
4

4
 United Kingdom
Europe
3 (1908, 1944, 1948, 2012)
0
3

 Canada
North America
1 (1976)
2 (1988, 2010)

 Italy
Europe
1 (1960)
2 (1944, 1956, 2006)

 German Empire/ Nazi Germany/ West Germany/ Germany
Europe
2 (1916, 1936, 1972)
1 (1936, 1940)

8
 China
Asia
1 (2008)
1 (2022)
2

 South Korea
Asia
1 (1988)
1 (2018)

 Soviet Union/ Russia
Europe
1 (1980)
1 (2014)

 Greece
Europe
2 (1896, 2004)
0

 Australia
Oceania
2 (1956, 2000)
0

 Norway
Europe
0
2 (1952, 1994)

 Austria
Europe
0
2 (1964, 1976)

  Switzerland
Europe
0
2 (1928, 1940, 1948)

 Sweden
Europe
2 (1912, 1956 (equestrian events only))
0

17
 Brazil
South America
1 (2016)
0
1

 Spain
Europe
1 (1992)
0

 SFR Yugoslavia/ Bosnia and Herzegovina
Europe
0
1 (1984)

 Mexico
North America
1 (1968)
0

 Finland
Europe
1 (1940, 1952)
0

 Netherlands
Europe
1 (1928)
0

 Belgium
Europe
1 (1920)
0

text: Number of Olympic Games by continent[edit]

text:
Rank
Continent
Summer Olympics
Winter Olympics
Total

1
Europe
17 (1896, 1900, 1908, 1912, 1920, 1924, 1928, 1936, 1940, 1944, 1948, 1952, 1960, 1972, 1980, 1992, 2004, 2012, 2024)
14 (1924, 1928, 1936, 1940, 1944, 1948, 1952, 1956, 1964, 1968, 1976, 1984, 1992, 1994, 2006, 2014)
31

2
North America
7 (1904, 1932, 1968, 1976, 1984, 1996, 2028)
6 (1932, 1960, 1980, 1988, 2002, 2010)
13

3
Asia
4 (1940, 1964, 1988, 2008, 2020)
4 (1940, 1972, 1998, 2018, 2022)
8

4
Oceania
2 (1956, 2000)
0
2

5
South America
1 (2016)
0
1

6
Africa
0
0
0

text: Unsuccessful cities[edit]

text: This section does not cite any sources. Please help improve this section by adding citations to reliable sources. Unsourced material may be challenged and removed. (February 2018) (Learn how and when to remove this template message)

text:
Country
City
Bids

 United States
Detroit
7

 Hungary
Budapest
6

 Turkey
Istanbul
5

 Spain
Madrid
4

 Argentina
Buenos Aires
4

  Switzerland
Lausanne
4

 United States
Philadelphia
5

 United States
Chicago
4

 United States
Minneapolis
3

 Cuba
Havana
3

 Belgium
Brussels
3

 Azerbaijan
Baku
2

 Qatar
Doha
2

 Spain
Seville
2

 Yugoslavia
Belgrade
2

 Puerto Rico
San Juan
1

 Australia
Brisbane
1

 Slovakia
Poprad
1

 United States
Boston
1


document_title: Alabama–Ole Miss football rivalry

question_text: when did ole miss beat alabama in football

text: Alabama–Ole Miss football rivalry

text:
Alabama–Ole Miss football rivalry

Alabama Crimson Tide

Ole Miss Rebels

First meeting
October 27, 1894
Ole Miss 6, Alabama 0

Latest meeting
September 30, 2017
Alabama 66, Ole Miss 3

Next meeting
September 15, 2018 in Oxford

Statistics

Meetings total
65

All-time series
Alabama leads, 50–11–2
(53–10–2 on the field)

Largest victory
Alabama, 66−3 (2017)

Longest win streak
Alabama, 12 (1912–32)

Current win streak
Alabama, 2 (2016–present)

text: The Alabama–Ole Miss football rivalry is an American college football rivalry between the Alabama Crimson Tide and Ole Miss Rebels. They are charter members of the Southeastern Conference (SEC), and both have competed in the SEC West since 1992. Alabama has dominated the series and leads 50–11–2 (53–10–2 on the field).

tag: p

text: Notable games[edit]

text: 1964 Sugar Bowl: In the only meeting in series history played outside of Alabama or Mississippi, #8 Alabama upset #7 Ole Miss 12–7 behind four field goals by kicker Tim Davis. This Sugar Bowl, played at the end of the 1963 season, is notable for being the coldest Sugar Bowl in history, as snow plows were used to clear the Tulane Stadium field prior to the game.[1]

text: 1969: In what is often erroneously referred to as the first prime time regular season football game in history, #20 Ole Miss traveled to Legion Field in Birmingham to face #15 Alabama. A dazzling offensive shootout ensues, highlighted by the play of Ole Miss quarterback Archie Manning. Despite a 540-yard, 5 touchdown effort from Manning, Alabama emerged victorious 33–32 after a last minute touchdown pass by quarterback Scott Hunter. The game has been referred to as among the greatest in college football history.[2]

text: 1988: Ole Miss stunned #12 Alabama 22–12 in Tuscaloosa, the Rebels' first-ever road victory in the series. This game is known as "The Brick Bowl", due to a claim made by then-Alabama head coach Bill Curry that a brick was thrown through his office's window following the loss.[3]

text: 1989: Following Ole Miss' upset victory the year before, the Rebels hopped out to a 21–0 lead over #13 Alabama in Jackson, MS. The Crimson Tide then scored 62 unanswered points en route to a 62–27 victory. The 21-point comeback still stands as the largest in Alabama football history.[4]

text: 1998: This was the first overtime game in series history, with Alabama emerging victorious 20–17. It was the first overtime win in Alabama football history, as well as the first overtime loss in Ole Miss football history.

text: 2006: In 2006, Alabama beat the Rebels in an overtime thriller. In overtime, Ole Miss made a 37-yard field goal, but Alabama scored a touchdown on a pass to Le'Ron McClain to win the game 26–23.[5]

text: 2007: Alabama beat Ole Miss in Oxford by scoring 10 unanswered points to win the game 27–24, amidst controversial rulings from the officials. It was Alabama's fifth consecutive victory over the Rebels.[6]

text: 2014: In 2014, #3 Alabama came into Oxford as a 6-point favorite taking on #11 Ole Miss. Alabama led 14–3 at the half, but were held to only 3 points in the second half. Late in the fourth quarter, Ole Miss scored a go-ahead touchdown, but missed the PAT, leaving the score at 23–17. Alabama drove to Ole Miss 32 yard line, before Blake Sims threw an interception to Senquez Golson with 37 seconds left. This was Ole Miss' first victory over Alabama since 2003, snapping a 10-game losing streak in the series.[7]

text: 2015: #2 Alabama sought revenge for the previous season's defeat, but #15 Ole Miss shot out to a 30–10 lead late in the third quarter. Alabama quickly closed the gap to 30–24 less than three minutes into the fourth. Ole Miss then scored 13 unanswered to extend their lead to 43–24, but had to fight off another Crimson Tide rally to secure a 43–37 upset victory. Alabama committed 5 turnovers in this game, the most ever under head coach Nick Saban. It was the first time in school history that Ole Miss had beaten Alabama in consecutive seasons and just the second time that the Rebels had won in Tuscaloosa.[8] This would be the Crimson Tide's only loss that season as they went on to win the College Football Playoff national championship.

text: 2016: #19 Ole Miss seemed to be on track for an unprecedented third-straight win over the top-ranked Crimson Tide, leading 24–3 with less than 2:47 left to play in the first half. Alabama then scored 24 unanswered points to take a 27–24 lead midway through the third quarter. Late in the fourth quarter, the Tide had extended its lead to 48–30 before Ole Miss scored twice in rapid succession to cut the deficit to five points with just under three minutes left. Alabama was able to run out the clock, preserving a wild 48–43 victory and ending the Rebels' school record two game winning streak in the series. The 21-point comeback tied the 1989 Alabama-Ole Miss game for the largest comeback in Alabama football history.[9]

text: Game results[edit]

text:
Alabama victories
Ole Miss victories
Ties
Forfeits / Vacated wins

text:
No.
Date
Location
Winner
Score

1
October 27, 1894
Jackson, MS
Ole Miss
6–0

2
November 24, 1899
Jackson, MS
Alabama
7–5

3
October 26, 1900
Tuscaloosa, AL
Alabama
12–5

4
October 19, 1901
Tuscaloosa, AL
Alabama
41–0

5
October 12, 1907
Columbus, MS
Alabama
20–0

6
October 23, 1909
Jackson, MS
Tie
0–0

7
November 5, 1910
Greenville, MS
Ole Miss
16–0

8
November 9, 1912
Tuscaloosa, AL
Alabama
10–9

9
November 25, 1915
Birmingham, AL
Alabama
53–0

10
October 28, 1916
Tuscaloosa, AL
Alabama
27–0

11
October 27, 1917
Tuscaloosa, AL
Alabama
64–0

12
October 11, 1919
Tuscaloosa, AL
Alabama
49–0

13
October 6, 1923
Tuscaloosa, AL
Alabama
56–0

14
November 1, 1924
Montgomery, AL
Alabama
61–0

15
October 6, 1928
Tuscaloosa, AL
Alabama
27–0

16
October 5, 1929
Tuscaloosa, AL
Alabama
22–7

17
October 4, 1930
Tuscaloosa, AL
Alabama
64–0

18
October 3, 1931
Tuscaloosa, AL
Alabama
55–6

19
October 22, 1932
Tuscaloosa, AL
Alabama
24–13

20
October 7, 1933
Birmingham, AL
Tie
0–0

21
November 11, 1944
Mobile, AL
Alabama
34–6

22
January 1, 1964A
New Orleans, LA
#8 Alabama
12–7

23
October 2, 1965
Birmingham, AL
Alabama
17–16

24
October 1, 1966
Jackson, MS
#3 Alabama
17–7

25
October 7, 1967
Birmingham, AL
#9 Alabama
21–7

26
October 5, 1968
Jackson, MS
Ole Miss
10–8

27
October 4, 1969
Birmingham, AL
#15 Alabama
33–32

28
October 3, 1970
Jackson, MS
#7 Ole Miss
48–23

29
October 2, 1971
Birmingham, AL
#7 Alabama
40–6

30
October 5, 1974
Jackson, MS
#3 Alabama
35–21

31
October 4, 1975
Birmingham, AL
#9 Alabama
32–6

32
September 11, 1976
Jackson, MS
Ole Miss
10–7

33
September 10, 1977
Birmingham, AL
#6 Alabama
34–14

34
September 20, 1980
Jackson, MS
#1 Alabama
59–35

No.
Date
Location
Winner
Score

35
October 3, 1981
Tuscaloosa, AL
#11 Alabama
38–7

36
September 18, 1982
Jackson, MS
#4 Alabama
42–14

37
September 17, 1983
Tuscaloosa, AL
#12 Alabama
40–0

38
October 8, 1988
Tuscaloosa, AL
Ole Miss
22–12

39
October 7, 1989
Jackson, MS
#13 Alabama
62–27

40
October 24, 1992
Tuscaloosa, AL
#4 Alabama
31–10

41
October 23, 1993
Oxford, MS
#4 Alabama†
19–14

42
October 22, 1994
Tuscaloosa, AL
#8 Alabama
21–10

43
October 21, 1995
Oxford, MS
#21 Alabama
23–9

44
October 19, 1996
Tuscaloosa, AL
#7 Alabama
37–0

45
October 25, 1997
Oxford, MS
Alabama
29–20

46
October 10, 1998
Tuscaloosa, AL
Alabama
20–17OT

47
October 16, 1999
Oxford, MS
#11 Alabama
30–24

48
October 14, 2000
Tuscaloosa, AL
Alabama
45–7

49
October 13, 2001
Oxford, MS
Ole Miss
27–24

50
October 19, 2002
Tuscaloosa, AL
#24 Alabama
42–7

51
October 18, 2003
Oxford, MS
Ole Miss
43–28

52
September 11, 2004
Tuscaloosa, AL
Alabama
28–7

53
October 15, 2005
Oxford, MS
#6 Alabama‡
13–10

54
October 14, 2006
Tuscaloosa, AL
Alabama‡
26–23OT

55
October 13, 2007
Oxford, MS
Alabama
27–24

56
October 18, 2008
Tuscaloosa, AL
#2 Alabama
24–20

57
October 10, 2009
Oxford, MS
#3 Alabama
22–3

58
October 16, 2010
Tuscaloosa, AL
#8 Alabama
23–10

59
October 15, 2011
Oxford, MS
#2 Alabama
52–7

60
September 29, 2012
Tuscaloosa, AL
#1 Alabama
33–14

61
September 28, 2013
Tuscaloosa, AL
#1 Alabama
25–0

62
October 4, 2014
Oxford, MS
#11 Ole Miss
23–17

63
September 19, 2015
Tuscaloosa, AL
#15 Ole Miss
43–37

64
September 17, 2016
Oxford, MS
#1 Alabama
48–43

65
September 30, 2017
Tuscaloosa, AL
#1 Alabama
66–3

Series: Alabama leads 50–11–2

† Alabama forfeited as part of NCAA penalties.
‡ Alabama vacated wins as part of NCAA penalties.
A 1964 Sugar Bowl


document_title: Red blood cell

question_text: where are red blood cells made in adults

question_tokens: where are red blood cells made in adults

text: Red blood cell

text: Structure

text: Vertebrates

text: Almost all vertebrates, including all mammals and humans, have red blood cells. Red blood cells are cells present in blood in order to transport oxygen. The only known vertebrates without red blood cells are the crocodile icefish (family Channichthyidae); they live in very oxygen-rich cold water and transport oxygen freely dissolved in their blood.[8] While they no longer use hemoglobin, remnants of hemoglobin genes can be found in their genome.[9]

text: Vertebrate red blood cells consist mainly of hemoglobin, a complex metalloprotein containing heme groups whose iron atoms temporarily bind to oxygen molecules (O2) in the lungs or gills and release them throughout the body. Oxygen can easily diffuse through the red blood cell's cell membrane. Hemoglobin in the red blood cells also carries some of the waste product carbon dioxide back from the tissues; most waste carbon dioxide, however, is transported back to the pulmonary capillaries of the lungs as bicarbonate (HCO3−) dissolved in the blood plasma. Myoglobin, a compound related to hemoglobin, acts to store oxygen in muscle cells.[10]

text: The color of red blood cells is due to the heme group of hemoglobin. The blood plasma alone is straw-colored, but the red blood cells change color depending on the state of the hemoglobin: when combined with oxygen the resulting oxyhemoglobin is scarlet, and when oxygen has been released the resulting deoxyhemoglobin is of a dark red burgundy color. However, blood can appear bluish when seen through the vessel wall and skin.[11] Pulse oximetry takes advantage of the hemoglobin color change to directly measure the arterial blood oxygen saturation using colorimetric techniques. Hemoglobin also has a very high affinity for carbon monoxide, forming carboxyhemoglobin which is a very bright red in color. Flushed, confused patients with a saturation reading of 100% on pulse oximetry are sometimes found to be suffering from carbon monoxide poisoning.

text: Having oxygen-carrying proteins inside specialized cells (as opposed to oxygen carriers being dissolved in body fluid) was an important step in the evolution of vertebrates as it allows for less viscous blood, higher concentrations of oxygen, and better diffusion of oxygen from the blood to the tissues. The size of red blood cells varies widely among vertebrate species; red blood cell width is on average about 25% larger than capillary diameter, and it has been hypothesized that this improves the oxygen transfer from red blood cells to tissues.[12]

text: Mammals

text: The red blood cells of mammals are typically shaped as biconcave disks: flattened and depressed in the center, with a dumbbell-shaped cross section, and a torus-shaped rim on the edge of the disk. This distinctive biconcave shape optimises the flow properties of blood in the large vessels, such as maximization of laminar flow and minimization of platelet scatter, which suppresses their atherogenic activity in those large vessels.[13] Moreover, this shape allows for a high surface-area-to-volume (SA/V) ratio to facilitate diffusion of gases.[14] However, there are some exceptions concerning shape in the artiodactyl order (even-toed ungulates including cattle, deer, and their relatives), which displays a wide variety of bizarre red blood cell morphologies: small and highly ovaloid cells in llamas and camels (family Camelidae), tiny spherical cells in mouse deer (family Tragulidae), and cells which assume fusiform, lanceolate, crescentic, and irregularly polygonal and other angular forms in red deer and wapiti (family Cervidae). Members of this order have clearly evolved a mode of red blood cell development substantially different from the mammalian norm.[7][15] Overall, mammalian red blood cells are remarkably flexible and deformable so as to squeeze through tiny capillaries, as well as to maximize their apposing surface by assuming a cigar shape, where they efficiently release their oxygen load.[16]

text: Red blood cells in mammals are unique amongst vertebrates as they do not have nuclei when mature. Red blood cells of mammals cells have nuclei during early phases of erythropoiesis, but extrude them during development as they mature in order to provide more space for hemoglobin. The red blood cells without nuclei, called reticulocytes, go on to lose all other cellular organelles such as their mitochondria, Golgi apparatus and endoplasmic reticulum.

text: The spleen acts as a reservoir of red blood cells, but this effect is somewhat limited in humans. In some other mammals such as dogs and horses, the spleen sequesters large numbers of red blood cells which are dumped into the blood during times of exertion stress, yielding a higher oxygen transport capacity.

text: Human

text: A typical human red blood cell has a disk diameter of approximately 6.2–8.2 µm[17] and a thickness at the thickest point of 2–2.5 µm and a minimum thickness in the centre of 0.8–1 µm, being much smaller than most other human cells. These cells have an average volume of about 90 fL[18] with a surface of about 136 μm2, and can swell up to a sphere shape containing 150 fL, without membrane distension.

text: Adult humans have roughly 20–30 trillion red blood cells at any given time, constituting approximately 70% all cells by number.[19] Women have about 4–5 million red blood cells per microliter (cubic millimeter) of blood and men about 5–6 million; people living at high altitudes with low oxygen tension will have more. Red blood cells are thus much more common than the other blood particles: there are about 4,000–11,000 white blood cells and about 150,000–400,000 platelets per microliter.

text: Human red blood cells take on average 60 seconds to complete one cycle of circulation.[3][5][20]

text: The blood's red color is due to the spectral properties of the hemic iron ions in hemoglobin. Each human red blood cell contains approximately 270 million[citation needed] of these hemoglobin molecules. Each hemoglobin molecule carries four heme groups; hemoglobin constitutes about a third of the total cell volume. Hemoglobin is responsible for the transport of more than 98% of the oxygen in the body (the remaining oxygen is carried dissolved in the blood plasma). The red blood cells of an average adult human male store collectively about 2.5 grams of iron, representing about 65% of the total iron contained in the body.[21][22]

text: Microstructure

text: Nucleus

text: Red blood cells in mammals anucleate when mature, meaning that they lack a cell nucleus. In comparison, the red blood cells of other vertebrates have nuclei; the only known exceptions are salamanders of the genus Batrachoseps and fish of the genus Maurolicus.[23][24]

text: The elimination of the nucleus in vertebrate red blood cells has been offered as an explanation for the subsequent accumulation of non-coding DNA in the genome.[25] The argument runs as follows: Efficient gas transport requires red blood cells to pass through very narrow capillaries, and this constrains their size. In the absence of nuclear elimination, the accumulation of repeat sequences is constrained by the volume occupied by the nucleus, which increases with genome size.

text: Nucleated red blood cells in mammals consist of two forms: normoblasts, which are normal erythropoietic precursors to mature red blood cells, and megaloblasts, which are abnormally large precursors that occur in megaloblastic anemias.

text: Membrane composition

text: Red blood cells are deformable, flexible, are able to adhere to other cells, and are able to interface with immune cells. Their membrane plays many roles in this. These functions are highly dependent on the membrane composition. The red blood cell membrane is composed of 3 layers: the glycocalyx on the exterior, which is rich in carbohydrates; the lipid bilayer which contains many transmembrane proteins, besides its lipidic main constituents; and the membrane skeleton, a structural network of proteins located on the inner surface of the lipid bilayer. Half of the membrane mass in human and most mammalian red blood cells are proteins. The other half are lipids, namely phospholipids and cholesterol.[26]

text: Membrane lipids

text: The red blood cell cell membrane comprises a typical lipid bilayer, similar to what can be found in virtually all human cells. Simply put, this lipid bilayer is composed of cholesterol and phospholipids in equal proportions by weight. The lipid composition is important as it defines many physical properties such as membrane permeability and fluidity. Additionally, the activity of many membrane proteins is regulated by interactions with lipids in the bilayer.

text: Unlike cholesterol, which is evenly distributed between the inner and outer leaflets, the 5 major phospholipids are asymmetrically disposed, as shown below:

text: Outer monolayer

text:
Phosphatidylcholine (PC);
Sphingomyelin (SM).

text: Inner monolayer

text:
Phosphatidylethanolamine (PE);
Phosphoinositol (PI) (small amounts).
Phosphatidylserine (PS);

text: This asymmetric phospholipid distribution among the bilayer is the result of the function of several energy-dependent and energy-independent phospholipid transport proteins. Proteins called “Flippases” move phospholipids from the outer to the inner monolayer, while others called “floppases” do the opposite operation, against a concentration gradient in an energy dependent manner. Additionally, there are also “scramblase” proteins that move phospholipids in both directions at the same time, down their concentration gradients in an energy independent manner. There is still considerable debate ongoing regarding the identity of these membrane maintenance proteins in the red cell membrane.

text: The maintenance of an asymmetric phospholipid distribution in the bilayer (such as an exclusive localization of PS and PIs in the inner monolayer) is critical for the cell integrity and function due to several reasons:

text:
Macrophages recognize and phagocytose red cells that expose PS at their outer surface. Thus the confinement of PS in the inner monolayer is essential if the cell is to survive its frequent encounters with macrophages of the reticuloendothelial system, especially in the spleen.
Premature destruction of thallassemic and sickle red cells has been linked to disruptions of lipid asymmetry leading to exposure of PS on the outer monolayer.
An exposure of PS can potentiate adhesion of red cells to vascular endothelial cells, effectively preventing normal transit through the microvasculature. Thus it is important that PS is maintained only in the inner leaflet of the bilayer to ensure normal blood flow in microcirculation.
Both PS and phosphatidylinositol-4,5-bisphosphate (PIP2) can regulate membrane mechanical function, due to their interactions with skeletal proteins such as spectrin and protein 4.1R. Recent studies have shown that binding of spectrin to PS promotes membrane mechanical stability. PIP2 enhances the binding of protein band 4.1R to glycophorin C but decreases its interaction with protein band 3, and thereby may modulate the linkage of the bilayer to the membrane skeleton.

text: The presence of specialized structures named "lipid rafts" in the red blood cell membrane have been described by recent studies. These are structures enriched in cholesterol and sphingolipids associated with specific membrane proteins, namely flotillins, stomatins (band 7), G-proteins, and β-adrenergic receptors. Lipid rafts that have been implicated in cell signaling events in nonerythroid cells have been shown in erythroid cells to mediate β2-adregenic receptor signaling and increase cAMP levels, and thus regulating entry of malarial parasites into normal red cells.[27][28]

text: Membrane proteins

text: The proteins of the membrane skeleton are responsible for the deformability, flexibility and durability of the red blood cell, enabling it to squeeze through capillaries less than half the diameter of the red blood cell (7–8 μm) and recovering the discoid shape as soon as these cells stop receiving compressive forces, in a similar fashion to an object made of rubber.

text: There are currently more than 50 known membrane proteins, which can exist in a few hundred up to a million copies per red blood cell. Approximately 25 of these membrane proteins carry the various blood group antigens, such as the A, B and Rh antigens, among many others. These membrane proteins can perform a wide diversity of functions, such as transporting ions and molecules across the red cell membrane, adhesion and interaction with other cells such as endothelial cells, as signaling receptors, as well as other currently unknown functions. The blood types of humans are due to variations in surface glycoproteins of red blood cells. Disorders of the proteins in these membranes are associated with many disorders, such as hereditary spherocytosis, hereditary elliptocytosis, hereditary stomatocytosis, and paroxysmal nocturnal hemoglobinuria.[26][27]

text: The red blood cell membrane proteins organized according to their function:

text: Transport

text:
Band 3 – Anion transporter, also an important structural component of the red blood cell cell membrane, makes up to 25% of the cell membrane surface, each red cell contains approximately one million copies. Defines the Diego Blood Group;[30]
Aquaporin 1 – water transporter, defines the Colton Blood Group;
Glut1 – glucose and L-dehydroascorbic acid transporter;
Kidd antigen protein – urea transporter;
RhAG – gas transporter, probably of carbon dioxide, defines Rh Blood Group and the associated unusual blood group phenotype Rhnull;
Na+/K+ – ATPase;
Ca2+ – ATPase;
Na+ K+ 2Cl− – cotransporter;
Na+-Cl− – cotransporter;
Na-H exchanger;
K-Cl – cotransporter;
Gardos Channel.

text: Cell adhesion

text:
ICAM-4 – interacts with integrins;
BCAM – a glycoprotein that defines the Lutheran blood group and also known as Lu or laminin-binding protein.

text: Structural role – The following membrane proteins establish linkages with skeletal proteins and may play an important role in regulating cohesion between the lipid bilayer and membrane skeleton, likely enabling the red cell to maintain its favorable membrane surface area by preventing the membrane from collapsing (vesiculating).

text:
Ankyrin-based macromolecular complex – proteins linking the bilayer to the membrane skeleton through the interaction of their cytoplasmic domains with Ankyrin.

Band 3 – also assembles various glycolytic enzymes, the presumptive CO2 transporter, and carbonic anhydrase into a macromolecular complex termed a "metabolon," which may play a key role in regulating red cell metabolism and ion and gas transport function);
RhAG – also involved in transport, defines associated unusual blood group phenotype Rhmod.

Protein 4.1R-based macromolecular complex – proteins interacting with Protein 4.1R.

Protein 4.1R – weak expression of Gerbich antigens;
Glycophorin C and D – glycoprotein, defines Gerbich Blood Group;
XK – defines the Kell Blood Group and the Mcleod unusual phenotype (lack of Kx antigen and greatly reduced expression of Kell antigens);
RhD/RhCE – defines Rh Blood Group and the associated unusual blood group phenotype Rhnull;
Duffy protein – has been proposed to be associated with chemokine clearance;[31]
Adducin – interaction with band 3;
Dematin- interaction with the Glut1 glucose transporter.

text: Surface electrostatic potential

text: The zeta potential is an electrochemical property of cell surfaces that is determined by the net electrical charge of molecules exposed at the surface of cell membranes of the cell. The normal zeta potential of the red blood cell is −15.7 millivolts (mV).[32] Much of this potential appears to be contributed by the exposed sialic acid residues in the membrane: their removal results in zeta potential of −6.06 mV.

text: Function

text: Secondary functions

text: When red blood cells undergo shear stress in constricted vessels, they release ATP, which causes the vessel walls to relax and dilate so as to promote normal blood flow.[33]

text: When their hemoglobin molecules are deoxygenated, red blood cells release S-nitrosothiols, which also act to dilate blood vessels,[34] thus directing more blood to areas of the body depleted of oxygen.

text: Red blood cells can also synthesize nitric oxide enzymatically, using L-arginine as substrate, as do endothelial cells.[35] Exposure of red blood cells to physiological levels of shear stress activates nitric oxide synthase and export of nitric oxide,[36] which may contribute to the regulation of vascular tonus.

text: Red blood cells can also produce hydrogen sulfide, a signalling gas that acts to relax vessel walls. It is believed that the cardioprotective effects of garlic are due to red blood cells converting its sulfur compounds into hydrogen sulfide.[37]

text: Red blood cells also play a part in the body's immune response: when lysed by pathogens such as bacteria, their hemoglobin releases free radicals, which break down the pathogen's cell wall and membrane, killing it.[38][39]

text: Cellular processes

text: As a result of not containing mitochondria, red blood cells use none of the oxygen they transport; instead they produce the energy carrier ATP by the glycolysis of glucose and lactic acid fermentation on the resulting pyruvate.[40][41] Furthermore, the pentose phosphate pathway plays an important role in red blood cells; see glucose-6-phosphate dehydrogenase deficiency for more.

text: As red blood cells contain no nucleus, protein biosynthesis is currently assumed to be absent in these cells.

text: Because of the lack of nuclei and organelles, mature red blood cells do not contain DNA and cannot synthesize any RNA, and consequently cannot divide and have limited repair capabilities.[42] The inability to carry out protein synthesis means that no virus can evolve to target mammalian red blood cells.[43] However, infection with parvoviruses (such as human parvovirus B19) can affect erythroid precursors, as recognized by the presence of giant pronormoblasts with viral particles and inclusion bodies, thus temporarily depleting the blood of reticulocytes and causing anemia.[44]

text: Life cycle

text: Human red blood cells are produced through a process named erythropoiesis, developing from committed stem cells to mature red blood cells in about 7 days. When matured, in a healthy individual these cells live in blood circulation for about 100 to 120 days (and 80 to 90 days in a full term infant).[45] At the end of their lifespan, they are removed from circulation. In many chronic diseases, the lifespan of the red blood cells is reduced.

text: Creation

text: Erythropoiesis is the process by which new red blood cells are produced; it lasts about 7 days. Through this process red blood cells are continuously produced in the red bone marrow of large bones. (In the embryo, the liver is the main site of red blood cell production.) The production can be stimulated by the hormone erythropoietin (EPO), synthesised by the kidney. Just before and after leaving the bone marrow, the developing cells are known as reticulocytes; these constitute about 1% of circulating red blood cells.

text: Functional lifetime

text: The functional lifetime of an red blood cell is about 100–120 days, during which time the red blood cells are continually moved by the blood flow push (in arteries), pull (in veins) and a combination of the two as they squeeze through microvessels such as capillaries. They are also recycled in the bone marrow.[46]

text: Senescence

text: The aging red blood cell undergoes changes in its plasma membrane, making it susceptible to selective recognition by macrophages and subsequent phagocytosis in the mononuclear phagocyte system (spleen, liver and lymph nodes), thus removing old and defective cells and continually purging the blood. This process is termed eryptosis, red blood cell programmed cell death.[47] This process normally occurs at the same rate of production by erythropoiesis, balancing the total circulating red blood cell count. Eryptosis is increased in a wide variety of diseases including sepsis, haemolytic uremic syndrome, malaria, sickle cell anemia, beta-thalassemia, glucose-6-phosphate dehydrogenase deficiency, phosphate depletion, iron deficiency and Wilson's disease. Eryptosis can be elicited by osmotic shock, oxidative stress, energy depletion as well as a wide variety of endogenous mediators and xenobiotics. Excessive eryptosis is observed in red blood cells lacking the cGMP-dependent protein kinase type I or the AMP-activated protein kinase AMPK. Inhibitors of eryptosis include erythropoietin, nitric oxide, catecholamines and high concentrations of urea.

text: Much of the resulting breakdown products are recirculated in the body. The heme constituent of hemoglobin are broken down into iron (Fe3+) and biliverdin. The biliverdin is reduced to bilirubin, which is released into the plasma and recirculated to the liver bound to albumin. The iron is released into the plasma to be recirculated by a carrier protein called transferrin. Almost all red blood cells are removed in this manner from the circulation before they are old enough to hemolyze. Hemolyzed hemoglobin is bound to a protein in plasma called haptoglobin, which is not excreted by the kidney.[48]

text: Clinical significance

text: Disease

text: Blood diseases involving the red blood cells include:

text: Anemias (or anaemias) are diseases characterized by low oxygen transport capacity of the blood, because of low red cell count or some abnormality of the red blood cells or the hemoglobin.

text: Iron deficiency anemia is the most common anemia; it occurs when the dietary intake or absorption of iron is insufficient, and hemoglobin, which contains iron, cannot be formed

text: Sickle-cell disease is a genetic disease that results in abnormal hemoglobin molecules. When these release their oxygen load in the tissues, they become insoluble, leading to mis-shaped red blood cells. These sickle shaped red cells are less deformable and viscoelastic meaning that they have become rigid and can cause blood vessel blockage, pain, strokes, and other tissue damage.

text: Thalassemia is a genetic disease that results in the production of an abnormal ratio of hemoglobin subunits.

text: Hereditary spherocytosis syndromes are a group of inherited disorders characterized by defects in the red blood cell's cell membrane, causing the cells to be small, sphere-shaped, and fragile instead of donut-shaped and flexible. These abnormal red blood cells are destroyed by the spleen. Several other hereditary disorders of the red blood cell membrane are known.[49]

text: Pernicious anemia is an autoimmune disease wherein the body lacks intrinsic factor, required to absorb vitamin B12 from food. Vitamin B12 is needed for the production of hemoglobin.

text: Aplastic anemia is caused by the inability of the bone marrow to produce blood cells.

text: Pure red cell aplasia is caused by the inability of the bone marrow to produce only red blood cells.

text: Hemolysis is the general term for excessive breakdown of red blood cells. It can have several causes and can result in hemolytic anemia.

text: The malaria parasite spends part of its life-cycle in red blood cells, feeds on their hemoglobin and then breaks them apart, causing fever. Both sickle-cell disease and thalassemia are more common in malaria areas, because these mutations convey some protection against the parasite.

text: Polycythemias (or erythrocytoses) are diseases characterized by a surplus of red blood cells. The increased viscosity of the blood can cause a number of symptoms.

text: In polycythemia vera the increased number of red blood cells results from an abnormality in the bone marrow.

text: Several microangiopathic diseases, including disseminated intravascular coagulation and thrombotic microangiopathies, present with pathognomonic (diagnostic) red blood cell fragments called schistocytes. These pathologies generate fibrin strands that sever red blood cells as they try to move past a thrombus.

text: Transfusion

text: Red blood cells may be given as part of a blood transfusion. Blood may be donated from another person, or stored by the recipient at an earlier date. Donated blood usually requires screening to ensure that donors do not contain risk factors for the presence of blood-borne diseases, or will not suffer themselves by giving blood. Blood is usually collected and tested for common or serious Blood-borne diseases including Hepatitis B, Hepatitis C and HIV. The blood type (A, B, AB, or O) or the blood product is identified. This relates to the presence of antigens on the cell's surface. After this process, the blood is stored, and within a short duration is used. Blood can be given as a whole product or the red blood cells separated as packed red blood cells.

text: Blood is often transfused when there is known anaemia, active bleeding, or when there is an expectation of serious blood loss, such as prior to an operation. Before blood is given, a small sample of the recipient's blood is tested with the transfusion in a process known as cross-matching. In addition to the transmission of infection, certain types of transfusion reaction.

text: In 2008 it was reported that human embryonic stem cells had been successfully coaxed into becoming red blood cells in the lab. The difficult step was to induce the cells to eject their nucleus; this was achieved by growing the cells on stromal cells from the bone marrow. It is hoped that these artificial red blood cells can eventually be used for blood transfusions.[50]

text: Tests

text: Several blood tests involve red blood cells. These include a RBC count (the number of red blood cells per volume of blood), calculation of the hematocrit (percentage of blood volume occupied by red blood cells), and the erythrocyte sedimentation rate. The blood type needs to be determined to prepare for a blood transfusion or an organ transplantation.

text: Many diseases involving red blood cells are diagnosed with a blood film (or peripheral blood smear), where a thin layer of blood is smeared on a microscope slide. This may reveal abnormalities of red blood cell shape and form. When red blood cells sometimes occur as a stack, flat side next to flat side. This is known as rouleaux formation, and it occurs more often if the levels of certain serum proteins are elevated, as for instance during inflammation.

text: Separation and blood doping

text: Red blood cells can be obtained from whole blood by centrifugation, which separates the cells from the blood plasma in a process known as blood fractionation. Packed red blood cells, which are made in this way from whole blood with the plasma removed, are used in transfusion medicine.[51] During plasma donation, the red blood cells are pumped back into the body right away and only the plasma is collected.

text: Some athletes have tried to improve their performance by blood doping: first about 1 litre of their blood is extracted, then the red blood cells are isolated, frozen and stored, to be reinjected shortly before the competition. (Red blood cells can be conserved for 5 weeks at −79 °C or −110 °F) This practice is hard to detect but may endanger the human cardiovascular system which is not equipped to deal with blood of the resulting higher viscosity. Another method of blood doping involves injection with erythropoietin in order to stimulate production of red blood cells. Both practices are banned by the World Anti-Doping Agency.

text: History

text: The first person to describe red blood cells was the young Dutch biologist Jan Swammerdam, who had used an early microscope in 1658 to study the blood of a frog.[52] Unaware of this work, Anton van Leeuwenhoek provided another microscopic description in 1674, this time providing a more precise description of red blood cells, even approximating their size, "25,000 times smaller than a fine grain of sand".

text: In 1901, Karl Landsteiner published his discovery of the three main blood groups—A, B, and C (which he later renamed to O). Landsteiner described the regular patterns in which reactions occurred when serum was mixed with red blood cells, thus identifying compatible and conflicting combinations between these blood groups. A year later Alfred von Decastello and Adriano Sturli, two colleagues of Landsteiner, identified a fourth blood group—AB.

text: In 1959, by use of X-ray crystallography, Dr. Max Perutz was able to unravel the structure of hemoglobin, the red blood cell protein that carries oxygen.[53]

text: The oldest intact red blood cells ever discovered were found in Ötzi the Iceman, a natural mummy of a man who died around 3255 BCE. These cells were discovered in May 2012.[54]