document_title: Cake

question_text: when did the first cake mix come out

question_tokens: when did the first cake mix come out

text: Cake

text: History

text: The term "cake" has a long history. The word itself is of Viking origin, from the Old Norse word "kaka".[2]

text: The ancient Greeks called cake πλακοῦς (plakous), which was derived from the word for "flat", πλακόεις (plakoeis). It was baked using flour mixed with eggs, milk, nuts and honey. They also had a cake called "satura", which was a flat heavy cake. During the Roman period, the name for cake became "placenta" which was derived from the Greek term. A placenta was baked on a pastry base or inside a pastry case.[3]

text: The Greeks invented beer as a leavener, frying fritters in olive oil, and cheesecakes using goat's milk.[4] In ancient Rome, basic bread dough was sometimes enriched with butter, eggs, and honey, which produced a sweet and cake-like baked good.[5] Latin poet Ovid refers his and his brother's birthday party and cake in his first book of exile, Tristia.[6]

text: Early cakes in England were also essentially bread: the most obvious differences between a "cake" and "bread" were the round, flat shape of the cakes, and the cooking method, which turned cakes over once while cooking, while bread was left upright throughout the baking process.[5]

text: Sponge cakes, leavened with beaten eggs, originated during the Renaissance, possibly in Spain.[7]

text: Cake mixes

text: During the Great Depression, there was a surplus of molasses and the need to provide easily made food to millions of economically depressed people in the United States.[8] One company patented a cake-bread mix in order to deal with this economic situation, and thereby established the first line of cake in a box. In so doing, cake as it is known today became a mass-produced good rather than a home- or bakery-made specialty.

text: Later, during the post-war boom, other American companies (notably General Mills) developed this idea further, marketing cake mix on the principle of convenience, especially to housewives. When sales dropped heavily in the 1950s, marketers discovered that the cake in a box rendered the cake-making function of housewives relatively dispiriting. This was a time when women, retired from the war-time labor force, and in a critical ideological period in American history, were confined to the domestic sphere and oriented towards the freshly blossoming consumerism in the US.[9] In order to compensate for this situation, the marketing psychologist Ernest Dichter ushered in the solution to the cake mix problem: frosting.[10] Since making the cake was so simple, housewives and other in-home cake makers could expend their creative energy on cake decorating inspired by, among other things, photographs in magazines of elaborately decorated cakes.

text: Ever since, cake in a box has become a staple of supermarkets, and is complemented with frosting in a can.

text: Varieties

text: Cakes are broadly divided into several categories, based primarily on ingredients and mixing techniques.

text: Although clear examples of the difference between cake and bread are easy to find, the precise classification has always been elusive.[5] For example, banana bread may be properly considered either a quick bread or a cake.

text:
Butter cakes are made from creamed butter, sugar, eggs, and flour. They rely on the combination of butter and sugar beaten for an extended time to incorporate air into the batter.[11] A classic pound cake is made with a pound each of butter, sugar, eggs, and flour. Baking powder is in many butter cakes, such as Victoria sponge.[12] The ingredients are sometimes mixed without creaming the butter, using recipes for simple and quick cakes.
Sponge cakes (or foam cakes) are made from whipped eggs, sugar, and flour. They rely primarily on trapped air in a protein matrix (generally of beaten eggs) to provide leavening, sometimes with a bit of baking powder or other chemical leaven added as insurance. Sponge cakes are thought to be the oldest cakes made without yeast. An angel food cake is a white sponge cake that uses only the whites of the eggs and is traditionally baked in a tube pan. The French Génoise is a sponge cake that includes clarified butter. Highly decorated sponge cakes with lavish toppings are sometimes called gateau; the French word for cake.
Chiffon cakes are sponge cakes with vegetable oil, which adds moistness.[13]
Chocolate cakes are butter cakes, sponge cakes, or other cakes flavored with melted chocolate or cocoa powder.[14] German chocolate cake is a variety of chocolate cake. Fudge cakes are chocolate cakes that contains fudge.
Coffee cake is generally thought of as a cake to serve with coffee or tea at breakfast or at a coffee break. Some types use yeast as a leavening agent while others use baking soda or baking powder. These cakes often have a crumb topping called streusel or a light glaze drizzle.
Baked flourless cakes include baked cheesecakes and flourless chocolate cakes.  Cheesecakes, despite their name, aren't really cakes at all. Cheesecakes are in fact custard pies, with a filling made mostly of some form of cheese (often cream cheese, mascarpone, ricotta, or the like), and have very little flour added, although a flour-based or graham cracker crust may be used. Cheesecakes are also very old, with evidence of honey-sweetened cakes dating back to ancient Greece.
Butter or oil layer cakes include most of the traditional cakes used as birthday cakes, etc., and those sold as packaged cakes. Baking powder or bicarbonate of soda are used to provide both lift and a moist texture. Many flavorings and ingredients may be added; examples include devil's food cake, carrot cake, and banana bread.
Yeast cakes are the oldest and are very similar to yeast breads. Such cakes are often very traditional in form, and include such pastries as babka and stollen. Birthday cake

text: Some varieties of cake are widely available in the form of cake mixes, wherein some of the ingredients (usually flour, sugar, flavoring, baking powder, and sometimes some form of fat) are premixed, and the cook needs add only a few extra ingredients, usually eggs, water, and sometimes vegetable oil or butter. While the diversity of represented styles is limited, cake mixes do provide an easy and readily available homemade option for cooks who are not accomplished bakers.

text:
Cake varieties

Gooey butter cake

German chocolate cake

A strawberry cake prepared as a layer cake

Chocolate Cake pops with sprinkles. A cake pop is a cake styled as a lollipop.

Malay steamed sponge cake

strawberry mousse cake

Carrot Cake

text: Special-purpose cakes

text: Cakes may be classified according to the occasion for which they are intended. For example, wedding cakes, birthday cakes, cakes for first communion, Christmas cakes, Halloween cakes, and Passover plava (a type of sponge cake sometimes made with matzo meal) are all identified primarily according to the celebration they are intended to accompany. The cutting of a wedding cake constitutes a social ceremony in some cultures. The Ancient Roman marriage ritual of confarreatio originated in the sharing of a cake.

text: Particular types of cake may be associated with particular festivals, such as stollen or chocolate log (at Christmas), babka and simnel cake (at Easter), or mooncake. There has been a long tradition of decorating an iced cake at Christmas time; other cakes associated with Christmas include chocolate log and mince pies.

text: A Lancashire Courting Cake is a fruit-filled cake baked by a fiancée for her betrothed. The cake has been described as "somewhere between a firm sponge – with a greater proportion of flour to fat and eggs than a Victoria sponge cake – and a shortbread base and was proof of the bride-to-be's baking skills".  Traditionally it is a two-layer cake filled and topped with strawberries or raspberries and whipped cream.[15]

text:
A decorated birthday cake

A Halloween cake shaped like a pumpkin

Wedding cakes at a bridal show

text: Shapes

text: Cakes are frequently described according to their physical form. Cakes may be small and intended for individual consumption. Larger cakes may be made with the intention of being sliced and served as part of a meal or social function. Common shapes include:

text:
Bundt cakes
Cake balls
Conical, such as the Kransekake
Cupcakes and madeleines, which are both sized for a single person
Layer cakes, frequently baked in a springform pan and decorated
Sheet cakes, simple, flat, rectangular cakes baked in sheet pans
Swiss rolls

text:
Cakes by shape

A plate of white chocolate cake balls

The kransekage is an example of a conical cake

Dobos torte is an older form of layer cake.

A sheet cake

text: Cake flour

text: Special cake flour with a high starch-to-gluten ratio is made from fine-textured, soft, low-protein wheat. It is strongly bleached, and compared to all-purpose flour, cake flour tends to result in cakes with a lighter, less dense texture.[16] Therefore, it is frequently specified or preferred in cakes meant to be soft, light, and/or bright white, such as angel food cake. However, if cake flour is called for, a substitute can be made by replacing a small percentage of all-purpose flour with cornstarch or removing two tablespoons from each cup of all-purpose flour.[17][18][19] Some recipes explicitly specify or permit all-purpose flour, notably where a firmer or denser cake texture is desired.

text: Cooking

text: A cake can fall, whereby parts of it sink or flatten, when baked at a temperature that is too low or too hot,[20][21] when it has been underbaked[21] and when placed in an oven that is too hot at the beginning of the baking process.[22] The use of excessive amounts of sugar, flour, fat or leavening can also cause a cake to fall.[22][23] A cake can also fall when subjected to cool air that enters an oven when the oven door is opened during the cooking process.[24]

text: Cake decorating

text: A finished cake is often enhanced by covering it with icing, or frosting, and toppings such as sprinkles, which are also known as "jimmies" in certain parts of the United States and "hundreds and thousands" in the United Kingdom. Frosting is usually made from powdered (icing) sugar, sometimes a fat of some sort, milk or cream, and often flavorings such as vanilla extract or cocoa powder. Some decorators use a rolled fondant icing. Commercial bakeries tend to use lard for the fat, and often whip the lard to introduce air bubbles. This makes the icing light and spreadable. Home bakers either use lard, butter, margarine, or some combination thereof. Sprinkles are small firm pieces of sugar and oils that are colored with food coloring. In the late 20th century, new cake decorating products became available to the public. These include several specialized sprinkles and even methods to print pictures and transfer the image onto a cake.

text: Special tools are needed for more complex cake decorating, such as piping bags and various piping tips, syringes and embossing mats. To use a piping bag or syringe, a piping tip is attached to the bag or syringe using a coupler. The bag or syringe is partially filled with icing which is sometimes colored. Using different piping tips and various techniques, a cake decorator can make many different designs. Basic decorating tips include open star, closed star, basketweave, round, drop flower, leaf, multi, petal, and specialty tips. An embossing mat is used to create embossed effects. A cake turntable that cakes are spun upon may be used in cake decoration.

text:
Royal icing, marzipan (or a less sweet version, known as almond paste), fondant icing
(also known as sugarpaste), and buttercream are used as covering icings and to create decorations. Floral sugarcraft or wired sugar flowers are an important part of cake decoration. Cakes for special occasions, such as wedding cakes, are traditionally rich fruit cakes or occasionally Madeira cakes, that are covered with marzipan and iced using royal icing or sugar-paste. They are finished with piped borders (made with royal icing) and adorned with a piped message, wired sugar flowers, hand-formed fondant flowers, marzipan fruit, piped flowers, or crystallized fruits or flowers such as grapes or violets.

text:
Decorated cakes

A large cake garnished with strawberries

A slice of strawberry cake with garnishing of strawberry

Chocolate layer cake with chocolate frosting and shaved chocolate topping

A chocolate cake decorated with icing, strawberries, and silvery sugar beads or Dragées

Birthday cake in shape of Lace monitor with egg in mouth

Birthday cake Iced with gem toppings.


document_title: The Good Doctor (TV series)

question_text: who plays dr marcus andrews wife on the good doctor

root

text: The Good Doctor (TV series)

text: Premise[edit]

text: The series follows Shaun Murphy, a young surgeon with autism and savant syndrome from the mid-size city of Casper, Wyoming, where he had a troubled childhood. He relocates to San Jose, California, to work at the prestigious San Jose St. Bonaventure Hospital.[2]

tag: p

text: Cast and characters[edit]

text: Main[edit]

text:
Freddie Highmore as Shaun Murphy: A surgical resident with autism and savant syndrome.[3] His savant abilities include near-photographic recall and the ability to note minute details and changes. He is portrayed in flashbacks to his teen years by Graham Verchere.[4]
Nicholas Gonzalez as Neil Melendez: Attending Cardiothoracic surgeon in charge of surgical residents.[3] He was also engaged to Jessica Preston, until season 1 episode 12.
Antonia Thomas as Claire Browne: A surgical resident who forms a special connection with Shaun.[5]
Chuku Modu as Jared Kalu: A surgical resident from a wealthy family.[6]
Beau Garrett as Jessica Preston: The hospital in-house attorney and Vice President of Risk Management. She is the granddaughter of the hospital founder and a friend of Dr. Glassman.[7]
Irene Keng as Elle McLean: A resident (appeared only in the pilot)[8][9]
Hill Harper as Marcus Andrews: Chief of surgery and board member.[8]
Richard Schiff as Aaron Glassman: President of the San Jose St. Bonaventure Hospital, who has been a mentor and good friend of Shaun since he was 14.[10][11]
Tamlyn Tomita as Allegra Aoki: Chairman and Vice President of the foundation that controls the hospital.[12]

tag: ul

text: Recurring[edit]

text:
Dylan Kingwell as Steve Murphy: Shaun's younger brother (in flashbacks).[4] He also portrays Evan Gallico, a boy in the present that resembles Shaun's brother and is suffering from stage 4 Osteosarcoma.
Paige Spara as Lea: Shaun's love interest/ former neighbor.
Eric Winter as Matt Coyle: A suave doctor who charms the hospital's staff, until he makes explicit advances towards one of them.[13]
Christina Chang as Dr. Audrey Lim
Marsha Thomason as Dr. Isabel Barnes:[14] Marcus' wife.[15]
Fiona Gubelmann as Morgan Reznick: A new resident who joins the cast for five episodes with the possibility of becoming a regular in Season 2.[16] As a resident, Morgan will turn out to be a rival for Shaun. She debuted in "She".[17]
Will Yun Lee as Adam Park: An ex-cop who decided to become a doctor in a multi-episode arc beginning in February[18]

text: Notable guests[edit]

text:
Jasika Nicole as Carly[19]
Eve Gordon as Nurse Fryday[19]
Chris D'Elia as Kenny, Shaun's new neighbor, who moves into Lea's apartment.
Graham Patrick Martin as Blake[20]

text: Episodes[edit]

text:
No.
Title
Directed by
Written by
Original air date
U.S. viewers
(millions)

1
"Burnt Food"
Seth Gordon
David Shore
September 25, 2017 (2017-09-25)
11.22[21]

On the way to begin his surgical residency at San Jose St. Bonaventure Hospital, Dr. Shaun Murphy witnesses an airport sign fall and shatter glass onto a young boy. Another doctor is first on the scene and begins applying pressure to the child's neck. Shaun tells him that he's pressing on the wrong part of the neck for a child. With his unique ability to visualize the internal body and using improvised methods and tools, Shaun is able to stabilize the boy. On the way to the hospital, Shaun notices that the boy's vitals have changed. Hospital staff are alerted to the arrival of the boy. Shaun tries to tell the doctors about the boy's vitals, stating that he needs an echo-cardiogram. The doctors disagree and begin surgery. While operating, something goes wrong and Claire Browne, a surgical resident, recalls Shaun mentioning an echo. Thanks to Shaun's diagnosis, the boy's life is saved. Meanwhile, in a hospital board meeting, Dr. Aaron Glassman, president of the hospital, tries to convince the board to hire Shaun, despite his autism. Flashbacks give us a picture of Shaun's childhood and his motivation for becoming a doctor.

2
"Mount Rushmore"
Mike Listo
David Shore
October 2, 2017 (2017-10-02)
10.93[22]

This episode's plot summary may be too long or excessively detailed. Please help improve it by removing unnecessary details and making it more concise. (January 2018) (Learn how and when to remove this template message)

Dr. Melendez is doing rounds with Dr. Browne and Dr. Kalu. Melendez calls out Shaun for arriving late on his first full day. A middle aged woman is brought into the ER with abdominal pain. Shaun immediately diagnoses a malignant tumor. Melendez assigns Browne as his number two for the surgery while giving Shaun "scut work" - all the work that residents hate doing. On the operating table, the doctors find the tumor is much bigger than expected and has encased all of her arteries. Looking at biopsy results, the residents find out that she is suffering from leiomyosarcoma, making surgery seemingly impossible. Shaun's ability to visualize the internal organs allows him to figure out that removing one of her kidneys would allow a better look, enough to view and possibly remove the mass. To Browne's dismay, Kalu suggests Shaun's idea to Melendez, getting the credit for the idea. Meanwhile, Shaun's attention to detail in his scut work gets him into trouble. Instead of releasing patients ready for discharge, Shaun rechecks them and orders additional tests. Upon learning this, Melendez assigns Nurse Freydey as Shaun's "boss" for the day. Later, after rechecking a discharged young girl's test results, Shaun races to her home. The parents are annoyed that he's bothering them after midnight and at first refuse to let him in. Shaun insists he will not leave before seeing their daughter. His diagnosis is correct and they must rush her to the hospital for surgery to save her life.

3
"Oliver"
John Dahl
William Rotko
October 9, 2017 (2017-10-09)
10.69[23]

Shaun and Claire fly to San Francisco Municipal Hospital to get a liver for a transplant patient. They can't fly back due to fog and are forced to use a police escort. Several problems arise. First, the liver's temperature rises to near the allowed maximum, forcing them to stop at a local store to cool it by submerging it in slushie. As they proceed with their journey, Shaun discovers that the liver has a clot. With only two hours of viability left, the duo decides to perform an operation en route in order to remove the clot and flush the left lobe, protecting it from the ice bath. Back at San Jose St. Bonaventure Hospital, Chuck, the recipient of the liver, is discovered to have alcohol in his system, a development that could move him to the bottom of the list. Chuck later confesses that he actually took a drink at his daughter's graduation. In order to protect its reputation and its future patients, the hospital decides to deny Chuck the liver. To their dismay, Shaun and Claire arrive back, only to find out that the liver has to be taken to another patient at another hospital.

4
"Pipes"
Steven DePaul
Thomas L. Moran
October 16, 2017 (2017-10-16)
10.60[24]

This episode's plot summary may be too long or excessively detailed. Please help improve it by removing unnecessary details and making it more concise. (January 2018) (Learn how and when to remove this template message)

Barb Allen, 22 weeks pregnant, and her husband, Mark, come to St. Bonaventure hoping that doctors can save her baby. A large non-cancerous tumor is growing so close to the fetus that for the baby to survive it must be removed. After an ultrasound, she hears from Dr. Melendez the same thing she’s heard from two other second opinions. The safest thing to do is terminate the pregnancy. Due to a medical condition that leaves her susceptible to clots, she risks having a heart attack during surgery. Barb says she’ll do anything to save the baby. Shaun interrupts offering a way to control the clotting factor pre-operatively. His suggestion is considered and surgery is scheduled. However, Melendez is angry that Shaun contradicted him in front of a patient. Complications arise when the husband changes his mind about the surgery. After a meeting with legal staff and the board, the surgery is rescheduled. However, during the procedure Barb suffers a heart attack, causing the surgery to be aborted. In recovery, Melendez explains that the baby is fine. She insists on trying the operation again. Ultimately Jared suggests stopping her heart and putting her on life support reducing the risk of a second heart attack. Surgery is successful for both mother and baby. Meanwhile, Dr. Melendez assigns Shaun and Claire case, as a punishment, to lance a boil for a patient of Dr. Andrews. 18 year old Olivia is experiencing severe pain in her genital area. After an examination, the “boil” turns out to be an abscess needing drainage. Olivia admits to being tested every month for STD's since she does pornography for a living. During the routine procedure to drain the abscess, they discover fibroid tumor wrapped around the nerve in the genital area. Surgery will mean losing feeling in her genitalia. As Dr. Andrews and Claire discuss the surgery with Olivia, Shaun rushes in with an alternative method to reconnect the vessels in a way that would leave her with no feeling in her thigh instead of her genital area. She agrees to it and the operation is successful.

5
"Point Three Percent"
Larry Teng
David Hoselton
October 23, 2017 (2017-10-23)
10.39[25]

Shaun notices a young boy with an indubitable resemblance to his deceased brother Steve, forming a bond with him. The boy's name is actually Evan and was brought to the hospital by his parents for reportedly breaking an arm; unbeknownst to Evan, he is in fact suffering from stage 4 Osteosarcoma. Shaun later suspects that he might have been misdiagnosed with cancer but indeed was suffering from Langerhans cell histiocytosis. In order not to give both Evan and his parents false hopes, Shaun decides to lie, attempting to perform a bone marrow aspiration, but he is caught red-handed by the parents. Subsequently, Evan starts coughing out blood, sending him to the OR. While on the operating table, Dr. Neil Menendez and Dr. Claire Browne discover that the cancer had metastasized, undoubtable proof that he is indeed suffering with terminal cancer. The other doctors are trying to find a prognosis of a 66-year old man, brought to the hospital by his estranged son, with an allergy causing him to have convulsions. Dr. Browne later finds out that the man is suffering from Echinococcus, a cyst form of tapeworms. Saddened by Evan's fate, which Evan has in fact known about the whole time, Shaun reads Evan the final few pages of To Kill a Mockingbird, a book of Steve's that he never finished reading before he died.

6
"Not Fake"
Michael Patrick Jann
Simran Baidwan
October 30, 2017 (2017-10-30)
10.60[26]

Shaun and the rest of the residents are working the graveyard shift when numerous casualties from a wedding bus crash come in. Among the victims are a woman with severe, visible burns, on whom Dr. Kalu tries an experimental procedure, and a young man with a damaged leg who can either have it amputated, or have an artificial bone inserted. The relative newness of the latter procedure causes a conflict between the man's parents and his soon-to-be bride.

7
"22 Steps"
David Straiton
Johanna Lee
November 13, 2017 (2017-11-13)
10.14[27]

Shaun encounters Liam, an autistic patient brought in to the hospital. Having to face prejudice from the young man's parents, Dr. Melendez defends him for the first time and acknowledges his exceptional abilities. On Dr. Glassman's directive, Claire continues her therapy sessions in order to curb her guilt over the death of a patient she inadvertently caused in the previous episode. On the other hand, Dr. Kalu gets a 73-year-old man with severe chest pains thus needing urgent medical attention and a pacemaker but his desire is to die; in order to give him hope on life, Dr. Kalu does everything he can to have him accept treatment, to no avail in which the latter finally lets him sign the DNR.

8
"Apple"
Nestor Carbonell
David Renaud
November 20, 2017 (2017-11-20)
9.97[28]

While shopping at a grocery mart for apples, a robbery takes place. With Shaun's communication limitations, he puts the lives of two customers on a first date at risk, leading to a young woman getting shot. Shaun's neighbor Lea hugs him after he admits that he made a mistake with someone getting hurt. During surgery, Dr. Lim questions Claire's ability to not let her emotions get the better of her because of a racist patient. This leads to an argument between the two with Dr. Lim ordering Claire to leave the operating room. Claire puts her emotions in check to save the life of the racist patient much to the satisfaction and delight of Dr. Lim.

9
"Intangibles"
Bronwen Hughes
Karen Struck
November 27, 2017 (2017-11-27)
9.25[29]

The team takes on the case of a young boy from the Congo who has severe congenital heart anomalies; Murphy's latest encounter with his neighbor Lea has him confused. He takes flirting lessons from Dr. Browne and notes and charts what he sees in regards to the "flirting trifecta". Meanwhile, Dr. Browne along with a lab tech search for a misplaced tissue sample from a woman with possible throat cancer.

10
"Sacrifice"
Michael Patrick Jann
Lloyd Gilyard Jr.
December 4, 2017 (2017-12-04)
9.03[30]

Shaun has reluctantly agreed to Dr. Glassman's repeated suggestions to meet with a therapist, but ultimately changes his mind after a new patient, Bobby Otto, convinces Shaun to stop letting people tell him what to do. At the end of the episode, a confrontation with Glassman in the hospital lobby leads to Shaun having a meltdown, causing him to strike Glassman in the face and run out of the hospital. Meanwhile, Claire runs into an uncomfortable situation with Dr. Matt Coyle, who makes unwanted sexual advances toward her during a patient consultation. Jared finds out and physically threatens him. As a result, Jared is fired. In later developments, after a tense dinner with Jessica, her father and Dr. Melendez, we learn that she doesn't want to have children.

11
"Islands Part One"
Bill D'Elia
Thomas L. Moran & William Rotko
January 8, 2018 (2018-01-08)
8.30[31]

Shaun and Lea embark on an impromptu road trip. Shaun drives, drinks Tequila, sings karaoke, all for the first time, and experiences his first kiss with Lea. He is devastated when Lea reveals that she plans to move to Hershey, Pennsylvania to work in her family's auto body shop. Melendez and Andrews operate on conjoined twins, one of which needs a kidney. Complications develop and the operation to separate them, planned for six months after the kidney surgery, must be done immediately. The operation goes well until it's discovered the twins have not awakened from the surgery. In an effort to get his job back, Jared apologizes to Coyle, who rejects the apology. Claire vows to ruin Coyle by finding all the other women he has harassed. Andrews calls Kalu the next day with the news that Coyle came forward, but while he's willing to give him a recommendation for other hospitals, he cannot overlook the physical assault, and will not reinstate him at St. Bonaventure. We also learn that Dr. Melendez decides it's more important to be with Jessica and that he can be a "father" in other ways.

12
"Islands Part Two"
Cherie Nowlan
Thomas L. Moran & William Rotko
January 15, 2018 (2018-01-15)
9.33[32]

Shaun returns to the hospital after his trip and gives Dr. Glassman his two weeks’ notice, intending on moving to Hershey to be with Lea. Glassman and Dr. Melendez give Murphy a recommendation, but Glassman promises to back off if Shaun stays. After a talk with Claire in which she says she will miss Shaun, he decides to stay and returns the letter to Glassman. Meanwhile, the twins suffer complications from their surgery; Katie is not getting enough blood flow to the brain, while Jenny’s heart is failing. Despite the doctors’ best efforts to save both twins, Jenny dies on the operating table. Jessica looks into previous misconduct at the hospital in which white doctors were only warned instead of fired, leading to allegations of racism by Kalu’s lawyer. Kalu gets his job back and is seen getting suited up for a shift at the hospital, but Dr. Andrews didn’t want him back as he felt using the racism card was setting them back. Finally, Jessica tells Melendez that she wants to break up because she feels like she is standing in his way of being a father.

13
"Seven Reasons"
Mike Listo
David Shore & David Hoselton
January 22, 2018 (2018-01-22)
9.61[33]

While treating a Muslim patient, Shaun senses she is lying, based on his seven reasons why people lie, and makes controversial claims. Melendez punctures the bronchus of the patient during surgery and is put under investigation after Shaun questions if his personal life is affecting his work. Jared comes to a conclusion that might explain the punctured bronchus and exonerate Melendez, while Shaun maintains his belief. In the end, Shaun's suspicion that the patient was exposed to explosive chemicals was confirmed, but for a different reason. While Claire assists in a surgery on a stroke patient, who had an aneurysm, with Dr. Lim, she learns that Coyle got a new job and a raise. They inform the patient's wife that he needs surgery or he will die. The wife refuses and Claire discovers that it is because the wife was abused and does not want her husband to survive. Claire forces her to agree to the surgery and convinces her to leave her husband. Claire meets with Kristen, another former co-worker and victim of Coyle. Finally, Shaun asks Glassman to be friends, but Glassman decides to give him his own space and not be friends, which upsets Shaun. Shaun meets his new neighbor.

14
"She"
Seth Gordon
Simran Baidwan
February 5, 2018 (2018-02-05)
9.63[34]

The four residents including the new Dr. Morgan Reznick are paired off in a competition with Reznick and Browne being paired with Melendez while Murphy and Kalu are paired up with Lim. It determines their futures at the hospital. Murphy and Kalu are faced with a gender dysphoric patient, Quinn, in which Shaun feels that people are the gender they were born with. Murphy and Kalu come to determine that Quinn has testicular cancer and find out that she has fragile bones due to being on puberty blockers. This leads to the discussion about whether or not she there should be unilateral or bilateral surgery to remove one or both testicles. The grandma accuses the parents of abuse by letting Quinn go through with the bilateral surgery, but the parents say it's their decision. While the head doctors and family are discussing whether or not to go through with the surgery, Quinn ends up with testicular torsion which requires emergency surgery. They decided to not go through with the bilateral surgery. Meanwhile, Browne and Reznick have a male patient that ended up with a superbug which is resistant to all drugs, because he took leftover drugs for the wrong purpose. The permanent damage means he needs a colostomy put in, but Claire does research on fecal microbiota transplant, which Melendez approves. With how Reznick acts, it leaves Claire feeling like she is only a team player when she needs to be. Finally, Dr. Andrews and Dr. Barnes see a fertility specialist as they want to have children. Andrews blames Barnes for waiting so long. The fertility doctor says that Andrews has a low sperm count and are referred to a urologist.

15
"Heartfelt"
Regina King
Thomas L. Moran & Johanna Lee
February 26, 2018 (2018-02-26)
7.82[35]

A female teen goes through a risky surgery to implant a sternum so she can live a normal life without being confined to her house as being in crowds, falling, or hugged could be fatal. A young male teen initially rejects the idea of having a convicted killer's liver transplanted in him, but without it he has a day to live. A former 15 year veteran cop turned doctor, Alex Park, is skeptical of the convict, Boris's, motives. After a failed attempt surgery due to Boris reacting to the anesthesia, he was ordered to stand up. Boris grabs a guard and his gun threatening to kill him. Park uses his police training to keep the situation under control all while telling him he has a choice to make. Boris kills himself so he can help the boy live. They take the body to the operating room to take organs from the dead convict. Allegra talks to Dr. Andrews about a young wealthy donor, Aidan Coulter, but Andrews says being involved with him might give people the wrong idea and that she used sex to get a big donation. Morgan tells Shaun that he needs to get an expensive tux for the black tie fundraiser in order for people to respect him. At the fundraiser, Jared tells Claire he loved her and thought maybe she would one day love him, but came to the realization that isn't true leaving the status of their relationship unknown.

16
"Pain"[36]
Allison Liddi-Brown
William L. Rotko & David Renaud
March 12, 2018 (2018-03-12)
TBD

17
"Smile"[37]
TBA
TBA
March 19, 2018 (2018-03-19)
TBD

18
"More"[20]
TBA
TBA
March 26, 2018 (2018-03-26)[37]
TBD

tag: table

text: Production[edit]

text: Development[edit]

text: In May 2014, CBS Television Studios began development on an American remake of the hit South Korean medical drama Good Doctor with Daniel Dae Kim as producer. Kim explained the appeal of adapting the series as "something that can fit into a recognizable world, with a breadth of characters that can be explored in the long run".[38] The story of a pediatric surgeon with autism was to be set in Boston and projected to air in August 2015.[39][40] However, CBS did not pick up the project and it moved to Sony Pictures Television, with a put pilot commitment from ABC in October 2016. The series is developed by David Shore, who is executive producing alongside Kim, Sebastian Lee, and David Kim.[41] ABC officially ordered the series to pilot in January 2017.[42]

text: On May 11, 2017, ABC ordered the show to series as a co-production with Sony Pictures Television and ABC Studios,[43] and it was officially picked up for a full season of 18 episodes on October 3, 2017.[44]

text: Casting[edit]

text: On February 17, 2017, Antonia Thomas was cast as Dr. Claire Browne, a strong-willed and talented doctor who forms a special connection with Shaun.[5] A week later, Freddie Highmore was cast in the lead role as Dr. Shaun Murphy, a young surgeon with autism; and Nicholas Gonzalez was cast as Dr. Neil Melendez, the boss of the surgical residents at the hospital.[3] The next month, Chuku Modu was cast as resident Dr. Jared Kalu (originally Dr. Jared Unger);[6] Hill Harper as head of surgery Dr. Marcus Andrews (originally Dr. Horace Andrews); Irene Keng as resident Dr. Elle McLean;[8] and Richard Schiff was cast as Dr. Aaron Glassman (originally Dr. Ira Glassman), the hospital president and Shaun's mentor.[10][43] Schiff was shortly followed by Beau Garrett as hospital board member Jessica Preston and a friend of Dr. Glassman.[7] In September 2017, Tamlyn Tomita was promoted to the principal cast as Allegra Aoki.[12]

text: Filming[edit]

text: Production on the pilot took place from March 21 to April 6, 2017 in Vancouver, British Columbia.[46][47] Filming for the rest of the season began on July 26, 2017, and is set to conclude on March 1, 2018.[48]

text: Music[edit]

text: Dan Romer serves as the primary composer for the series.[49]

text: Release[edit]

text: Broadcast[edit]

text: The Good Doctor began airing on September 25, 2017, on ABC in the United States,[50] and on CTV in Canada.[51] Sky Living acquired the broadcast rights for the United Kingdom and Ireland.[52] Seven Network airs the series in Australia.[53] Wowow, the largest Japanese private satellite and pay-per-view television network in Japan acquired the rights to broadcast the series beginning in April 2018.[54] In the Netherlands, the series began airing on January 29, 2018, on RTL 4 and on video-on-demand service Videoland.[55]

text: Marketing[edit]

text: A full-length trailer was released for ABC's May 2017 Upfront presentation, which /Film's Ethan Anderton described the concept as feeling like "House meets Rain Man, that just might be enough to make it interesting". However, he questioned "how long can audiences be entranced by both the brilliance of [Highmore's] character's savant skills and the difficulties that come from his autism in the workplace."[56] Daniel Fienberg of The Hollywood Reporter felt the trailer was "both kinda progressive and really dated". He added, "Too much felt on-the-nose—especially Hill Harper as the main character's detractor and Richard Schiff as his noble defender", while also commentating that "On-the-nose/premise is how you have to trailer a show like this, and maybe spaced out over 43 minutes it won't grate."[57] Ben Travers and Steve Greene for IndieWire called it "a serious trailer for a serious subject. The first glimpse of Highmore's character hints that they're toeing the line between presenting a thoughtful depiction of his condition and using his perceptive abilities as a kind of secret weapon."[58] The trailer had been viewed over 25.4 million times after a week of its release, including over 22 million views on Facebook.[59]

text: The pilot was screened at ABC's PaleyFest event on September 9, 2017.[60] The Good Doctor is included in the 35th annual PaleyFest LA. Scheduled to appear on March 22, 2018 at 7:30 pm are members of the cast: Freddie Highmore, Nicholas Gonzalez, Hill Harper, Richard Schiff, Tamlyn Tomita. David Shore (executive producer), and Daniel Dae Kim (executive producer) will also be on the panel. Additional guests will be announced at a later date.[61]

text: Reception[edit]

text: Ratings[edit]

text:
No.
Title
Air date
Rating/share
(18–49)
Viewers
(millions)
DVR
(18–49)
DVR viewers
(millions)
Total
(18–49)
Total viewers
(millions)

1
"Burnt Food"
September 25, 2017
2.2/9
11.22[21]
2.2
7.86
4.4
19.21[62]

2
"Mount Rushmore"
October 2, 2017
2.2/9
10.93[22]
2.1
7.21
4.3
18.12[63]

3
"Oliver"
October 9, 2017
2.0/7
10.69[23]
2.2
7.53
4.2
18.22[64]

4
"Pipes"
October 16, 2017
2.0/8
10.60[24]
2.1
7.34
4.1
17.96[65]

5
"Point Three Percent"
October 23, 2017
1.8/7
10.39[25]
2.0
7.10
3.8
17.50[66]

6
"Not Fake"
October 30, 2017
1.9/7
10.60[26]
2.0
6.93
3.9
17.51[67]

7
"22 Steps"
November 13, 2017
1.9/7
10.14[27]
1.9
6.92
3.8
17.14[68]

8
"Apple"
November 20, 2017
1.8/7
9.97[28]
1.8
6.98
3.6
16.99[69]

9
"Intangibles"
November 27, 2017
1.7/7
9.25[29]
1.8
6.66
3.5
15.91[70]

10
"Sacrifice"
December 4, 2017
1.6/7
9.03[30]
1.8
6.67
3.4
15.74[71]

11
"Islands Part One"
January 8, 2018
1.6/6
8.30[31]
1.8
7.10
3.4
15.40[72]

12
"Islands Part Two"
January 15, 2018
1.7/6
9.33[32]
1.8
6.66
3.5
16.00[73]

13
"Seven Reasons"
January 22, 2018
1.7/7
9.61[33]
1.9
6.91
3.6
16.53[74]

14
"She"
February 5, 2018
1.7/7
9.63[34]
1.8
7.07
3.5
16.71[75]

15
"Heartfelt"
February 26, 2018
1.3/5
7.82[35]
TBD
TBD
TBD
TBD

text: The series premiere earned a 2.2/9 rating in the 18- to 49-year-old demographic, with 11.22 million total viewers, making it the most watched Monday drama debut on ABC in 21 years, since Dangerous Minds in September 1996, and the highest rated Monday drama in the 18–49 demographic in 8.5 years, since Castle in March 2009.[76] Factoring live plus seven-day ratings, the pilot was watched by a total of 19.2 million viewers and set a record for DVR viewers with 7.9 million, surpassing the record of 7.67 million set by the pilot of Designated Survivor in 2016.[77] According to TV Guide's November 13-26 issue, the October 9 episode attracted 18.2 million viewers, beating out both NCIS and The Big Bang Theory for the most viewed primetime show that week.[78]

text: Critical response[edit]

text: The review aggregator website Rotten Tomatoes reports a 58% approval rating with an average rating of 5.49/10 based on 38 reviews. The website's consensus reads, "The Good Doctor's heavy-handed bedside manner undermines a solid lead performance, but under all the emotionally manipulative gimmickry, there's still plenty of room to improve."[79] Metacritic, which uses a weighted average, assigned a score of 53 out of 100 based on 15 critics, indicating "mixed or average reviews".[80]

text: Giving his first impression of the series' pilot for TVLine, Matt Webb Mitovich stated, "The Good Doctor boasts great DNA... [and] has the potential to be a refreshingly thought-provoking hospital drama, based on the buttons pushed in the pilot alone." He enjoyed the "warm dynamic" of Schiff and Highmore, while describing Thomas' character as "our emotional 'in' to Shaun's distinct, distant world". He noted that "it takes a while to build up momentum", but concluded that "the very final scene packs quite a punch, as Dr. Murphy unwittingly puts a colleague on notice".[81]

text: The New York Times television critic, James Poniewozik, notes in his Critic's Notebook column, that for the most part the drama is a "hospital melodrama with whiz-bang medical science, a dash of intra-staff romance and shameless sentimentality." Discussing the main characters of Dr. Aaron Glassman (Richard Schiff) and Dr. Shaun Murphy (Freddie Highmore), however, Poniewozik writes that "Mr. Schiff is convincing in the role and Mr. Highmore is striking in his." [82]

text: Speaking of Freddie Highmore's Golden Globe nomination on Monday, December 11, 2017, for his role in The Good Doctor, Laura Bradley, writing for Vanity Fair says: "... Freddie Highmore received the awards recognition that has long and unjustly eluded him..." Bradley feels that Highmore's performance has been "the central key" to the show's enormous success and while the show had lukewarm reviews, most critics have praised Highmore's work. [83]

text: Accolades[edit]

text:
Year
Award
Category
Nominee(s)
Result
Ref.

2018
Golden Globe Awards
Best Actor – Television Series Drama
Freddie Highmore
Nominated
[84]

Humanitas Prize
60-Minute Category
David Shore
Won
[85]


document_title: Alcohol dehydrogenase

question_text: where is alcohol dehydrogenase found in the body

text: Alcohol dehydrogenase

text: Evolution[edit]

text: Genetic evidence from comparisons of multiple organisms showed that a glutathione-dependent formaldehyde dehydrogenase, identical to a class III alcohol dehydrogenase (ADH-3/ADH5), is presumed to be the ancestral enzyme for the entire ADH family.[2][3][4] Early on in evolution, an effective method for eliminating both endogenous and exogenous formaldehyde was important and this capacity has conserved the ancestral ADH-3 through time. Gene duplication of ADH-3, followed by series of mutations, the other ADHs evolved.[3][4]

text: The ability to produce ethanol from sugar (which is the basis of how alcoholic beverages are made) is believed to have initially evolved in yeast. Though this feature is not adaptive from an energy point of view, by making alcohol in such high concentrations so that they would be toxic to other organisms, yeast cells could effectively eliminate their competition. Since rotting fruit can contain more than 4% of ethanol, animals eating the fruit needed a system to metabolize exogenous ethanol. This was thought to explain the conservation of ethanol active ADH in other species than yeast, though ADH-3 is now known to also have a major role in nitric oxide signaling.[5][6]

text: In humans, sequencing of the ADH1B gene (responsible for production of an alcohol dehydrogenase polypeptide) shows two variants, in which there is an SNP (single nucleotide polymorphism) that leads to either a Histidine or an Arginine residue in the enzyme catalyzing the conversion of ethanol into acetaldehyde. In the Histidine variant, the enzyme is much more effective at the aforementioned conversion.[7] The enzyme responsible for the conversion of acetaldehyde to acetate, however, remains unaffected, which leads to differential rates of substrate catalysis and causes a buildup of toxic acetaldehyde, causing cell damage.[7] In humans, various haplotypes arising from this mutation are more concentrated in regions near Eastern China, a region also known for its low alcohol tolerance and dependence.

text: A study was conducted in order to find a correlation between allelic distribution and alcoholism, and the results suggest that the allelic distribution arose along with rice cultivation in the region between 12,000 and 6,000 years ago.[8] In regions where rice was cultivated, rice was also fermented into ethanol.[8] The results of increased alcohol availability led to alcoholism and abuse by those able to acquire it, resulting in lower reproductive fitness.[8] Those with the variant allele have little tolerance for alcohol, thus lowering chance of dependence and abuse.[7][8] The hypothesis posits that those individuals with the His variant enzyme were sensitive enough to the effects of alcohol that differential reproductive success arose and the corresponding alleles were passed through the generations.

text: Classical Darwinian evolution would act to select against the detrimental form of the enzyme (Arg variant) because of the lowered reproductive success of individuals carrying the allele. The result would be a higher frequency of the allele responsible for the His-variant enzyme in regions that had been under selective pressure the longest. The distribution and frequency of the His variant follows the spread of rice cultivation to inland regions of Asia, with higher frequencies of the His variant in regions that have cultivated rice the longest.[7] The geographic distribution of the alleles seems to therefore be a result of natural selection against individuals with lower reproductive success, namely, those who carried the Arg variant allele and were more susceptible to alcoholism.[9]

text: Discovery[edit]

text: The first-ever isolated alcohol dehydrogenase (ADH) was purified in 1937 from Saccharomyces cerevisiae (brewer's yeast).[10] Many aspects of the catalytic mechanism for the horse liver ADH enzyme were investigated by Hugo Theorell and coworkers.[11] ADH was also one of the first oligomeric enzymes that had its amino acid sequence and three-dimensional structure determined.[12][13][14]

text: In early 1960, it was discovered in fruit flies of the genus Drosophila.[15]

text: Properties[edit]

text: The alcohol dehydrogenases comprise a group of several isozymes that catalyse the oxidation of primary and secondary alcohols to aldehydes and ketones, respectively, and also can catalyse the reverse reaction.[15] In mammals this is a redox (reduction/oxidation) reaction involving the coenzyme nicotinamide adenine dinucleotide (NAD+).

text: Oxidation of alcohol[edit]

text: Mechanism of action in humans[edit]

text: Steps[edit]

text:
Binding of the coenzyme NAD+
Binding of the alcohol substrate by coordination to zinc
Deprotonation of His-51
Deprotonation of nicotinamide ribose
Deprotonation of Thr-48
Deprotonation of the alcohol
Hydride transfer from the alkoxide ion to NAD+, leading to NADH and a zinc bound aldehyde or ketone
Release of the product aldehyde.

tag: ol

text: The mechanism in yeast and bacteria is the reverse of this reaction. These steps are supported through kinetic studies.[16]

text: Involved subunits[edit]

text: The substrate is coordinated to the zinc and this enzyme has two zinc atoms per subunit. One is the active site, which is involved in catalysis. In the active site, the ligands are Cys-46, Cys-174, His-67, and one water molecule. The other subunit is involved with structure. In this mechanism, the hydride from the alcohol goes to NAD+. Crystal structures indicate that the His-51 deprotonates the nicotinamide ribose, which deprotonates Ser-48. Finally, Ser-48 deprotonates the alcohol, making it an aldehyde.[16] From a mechanistic perspective, if the enzyme adds hydride to the re face of NAD+, the resulting hydrogen is incorporated into the pro-R position. Enzymes that add hydride to the re face are deemed Class A dehydrogenases.

text: Active site[edit]

text: The active site of human ADH1 (PDB:1HSO) consists of a zinc atom, His-67, Cys-174, Cys-46, Thr-48, His-51, Ile-269, Val-292, Ala-317, and Leu-319. In the commonly studied horse liver isoform, Thr-48 is a Ser, and Leu-319 is a Phe. The zinc coordinates the substrate (alcohol). The zinc is coordinated by Cys-46, Cys-174, and His-67. Leu-319, Ala-317, His-51, Ile-269 and Val-292 stabilize NAD+ by forming hydrogen bonds. His-51 and Ile-269 form hydrogen bonds with the alcohols on nicotinamide ribose. Phe-319, Ala-317 and Val-292 form hydrogen bonds with the amide on NAD+.[16]

text: Structural zinc site[edit]

text: Mammalian alcohol dehydrogenases also have a structural zinc site. This Zn ion plays a structural role and is crucial for protein stability. The structures of the catalytic and structural zinc sites in horse liver alcohol dehydrogenase (HLADH) as revealed in crystallographic structures, which has been studied computationally with quantum chemical as well as with classical molecular dynamics methods. The structural zinc site is composed of four closely spaced cysteine ligands (Cys97, Cys100, Cys103, and Cys111 in the amino acid sequence) positioned in an almost symmetric tetrahedron around the Zn ion. A recent study showed that the interaction between zinc and cysteine is governed by primarily an electrostatic contribution with an additional covalent contribution to the binding.[17]

text: Types[edit]

text: Human[edit]

text: In humans, ADH exists in multiple forms as a dimer and is encoded by at least seven different genes. There are five classes (I-V) of alcohol dehydrogenase, but the hepatic form that is used primarily in humans is class 1. Class 1 consists of α, β, and γ subunits that are encoded by the genes ADH1A, ADH1B, and ADH1C.[18] The enzyme is present at high levels in the liver and the lining of the stomach.[19] It catalyzes the oxidation of ethanol to acetaldehyde (ethanal):

text: This allows the consumption of alcoholic beverages, but its evolutionary purpose is probably the breakdown of alcohols naturally contained in foods or produced by bacteria in the digestive tract.[20]

text: Another evolutionary purpose may be metabolism of the endogenous alcohol vitamin A (retinol), which generates the hormone retinoic acid, although the function here may be primarily the elimination of toxic levels of retinol.[21][22]

text:
alcohol dehydrogenase 1A,
α polypeptide

Identifiers

Symbol
ADH1A

Alt. symbols
ADH1

Entrez
124

HUGO
249

OMIM
103700

RefSeq
NM_000667

UniProt
P07327

Other data

EC number
1.1.1.1

Locus
Chr. 4 q23

alcohol dehydrogenase 1B,
β polypeptide

Identifiers

Symbol
ADH1B

Alt. symbols
ADH2

Entrez
125

HUGO
250

OMIM
103720

RefSeq
NM_000668

UniProt
P00325

Other data

EC number
1.1.1.1

Locus
Chr. 4 q23

alcohol dehydrogenase 1C,
γ polypeptide

Identifiers

Symbol
ADH1C

Alt. symbols
ADH3

Entrez
126

HUGO
251

OMIM
103730

RefSeq
NM_000669

UniProt
P00326

Other data

EC number
1.1.1.1

Locus
Chr. 4 q23

text: Alcohol dehydrogenase is also involved in the toxicity of other types of alcohol: For instance, it oxidizes methanol to produce formaldehyde and ethylene glycol to ultimately yield glycolic and oxalic acids. Humans have at least six slightly different alcohol dehydrogenases. Each is a dimer (i.e., consists of two polypeptides), with each dimer containing two zinc ions Zn2+. One of those ions is crucial for the operation of the enzyme: It is located at the catalytic site and holds the hydroxyl group of the alcohol in place.

text: Alcohol dehydrogenase activity varies between men and women, between young and old, and among populations from different areas of the world. For example, young women are unable to process alcohol at the same rate as young men because they do not express the alcohol dehydrogenase as highly, although the inverse is true among the middle-aged.[23] The level of activity may not be dependent only on level of expression but also on allelic diversity among the population.

text: The human genes that encode class II, III, IV, and V alcohol dehydrogenases are ADH4, ADH5, ADH7, and ADH6, respectively.

text:
alcohol dehydrogenase 4
(class II), π polypeptide

Identifiers

Symbol
ADH4

Entrez
127

HUGO
252

OMIM
103740

RefSeq
NM_000670

UniProt
P08319

Other data

EC number
1.1.1.1

Locus
Chr. 4 q22

alcohol dehydrogenase 5
(class III), χ polypeptide

Identifiers

Symbol
ADH5

Entrez
128

HUGO
253

OMIM
103710

RefSeq
NM_000671

UniProt
P11766

Other data

EC number
1.1.1.1

Locus
Chr. 4 q23

alcohol dehydrogenase 6
(class V)

Identifiers

Symbol
ADH6

Entrez
130

HUGO
255

OMIM
103735

RefSeq
NM_000672

UniProt
P28332

Other data

EC number
1.1.1.1

Locus
Chr. 4 q23

alcohol dehydrogenase 7
(class IV), μ or σ polypeptide

Identifiers

Symbol
ADH7

Entrez
131

HUGO
256

OMIM
600086

RefSeq
NM_000673

UniProt
P40394

Other data

EC number
1.1.1.1

Locus
Chr. 4 q23-q24

text: Yeast and bacteria[edit]

text: Unlike humans, yeast and bacteria (except lactic acid bacteria, and E. coli in certain conditions) do not ferment glucose to lactate. Instead, they ferment it to ethanol and CO2. The overall reaction can be seen below:

text: In yeast[25] and many bacteria, alcohol dehydrogenase plays an important part in fermentation: Pyruvate resulting from glycolysis is converted to acetaldehyde and carbon dioxide, and the acetaldehyde is then reduced to ethanol by an alcohol dehydrogenase called ADH1. The purpose of this latter step is the regeneration of NAD+, so that the energy-generating glycolysis can continue. Humans exploit this process to produce alcoholic beverages, by letting yeast ferment various fruits or grains. It is interesting to note that yeast can produce and consume their own alcohol.

text: The main alcohol dehydrogenase in yeast is larger than the human one, consisting of four rather than just two subunits. It also contains zinc at its catalytic site. Together with the zinc-containing alcohol dehydrogenases of animals and humans, these enzymes from yeasts and many bacteria form the family of "long-chain"-alcohol dehydrogenases.

text: Brewer's yeast also has another alcohol dehydrogenase, ADH2, which evolved out of a duplicate version of the chromosome containing the ADH1 gene. ADH2 is used by the yeast to convert ethanol back into acetaldehyde, and it is expressed only when sugar concentration is low. Having these two enzymes allows yeast to produce alcohol when sugar is plentiful (and this alcohol then kills off competing microbes), and then continue with the oxidation of the alcohol once the sugar, and competition, is gone.[26]

text: Plants[edit]

text: In plants, ADH catalyses the same reaction as in yeast and bacteria to ensure that there is a constant supply of NAD+. Maize has two versions of ADH - ADH1 and ADH2, Arabidopsis thaliana contains only one ADH gene. The structure of Arabidopsis ADH is 47%-conserved, relative to ADH from horse liver. Structurally and functionally important residues, such as the seven residues that provide ligands for the catalytic and noncatalytic zinc atoms, however, are conserved, suggesting that the enzymes have a similar structure.[27] ADH is constitutively expressed at low levels in the roots of young plants grown on agar. If the roots lack oxygen, the expression of ADH increases significantly.[28] Its expression is also increased in response to dehydration, to low temperatures, and to abscisic acid, and it plays an important role in fruit ripening, seedlings development, and pollen development.[29] Differences in the sequences of ADH in different species have been used to create phylogenies showing how closely related different species of plants are.[30] It is an ideal gene to use due to its convenient size (2–3 kb in length with a ~1000 nucleotide coding sequence) and low copy number.[29]

text: Iron-containing[edit]

text:
Iron-containing alcohol dehydrogenase

bacillus stearothermophilus glycerol dehydrogenase complex with glycerol

Identifiers

Symbol
Fe-ADH

Pfam
PF00465

Pfam clan
CL0224

InterPro
IPR001670

PROSITE
PDOC00059

SCOP
1jqa

SUPERFAMILY
1jqa

[show]Available protein structures:

Pfam
structures

PDB
RCSB PDB; PDBe; PDBj

PDBsum
structure summary

text: A third family of alcohol dehydrogenases, unrelated to the above two, are iron-containing ones. They occur in bacteria and fungi. In comparison to enzymes the above families, these enzymes are oxygen-sensitive.[citation needed] Members of the iron-containing alcohol dehydrogenase family include:

text:
Saccharomyces cerevisiae alcohol dehydrogenase 4 (gene ADH4)[31]
Zymomonas mobilis alcohol dehydrogenase 2 (gene adhB)[32]
Escherichia coli propanediol oxidoreductase EC 1.1.1.77 (gene fucO),[33] an enzyme involved in the metabolism of fucose and which also seems to contain ferrous ion(s).
Clostridium acetobutylicum NADPH- and NADH-dependent butanol dehydrogenases EC 1.1.1.- (genes adh1, bdhA and bdhB),[34] enzymes that have activity using butanol and ethanol as substrates.
E. coli adhE,[35] an iron-dependent enzyme that harbours three different activities: alcohol dehydrogenase, acetaldehyde dehydrogenase (acetylating) EC 1.2.1.10 and pyruvate-formate-lyase deactivase.
Bacterial glycerol dehydrogenase EC 1.1.1.6 (gene gldA or dhaD).[36]
Clostridium kluyveri NAD-dependent 4-hydroxybutyrate dehydrogenase (4hbd) EC 1.1.1.61
Citrobacter freundii and Klebsiella pneumoniae 1,3-propanediol dehydrogenase EC 1.1.1.202 (gene dhaT)
Bacillus methanolicus NAD-dependent methanol dehydrogenase EC 1.1.1.244[37]
E. coli and Salmonella typhimurium ethanolamine utilization protein eutG.
E. coli hypothetical protein yiaY.

text: Other types[edit]

text: A further class of alcohol dehydrogenases belongs to quinoenzymes and requires quinoid cofactors (e.g., pyrroloquinoline quinone, PQQ) as enzyme-bound electron acceptors. A typical example for this type of enzyme is methanol dehydrogenase of methylotrophic bacteria.

text: Applications[edit]

text: In biotransformation, alcohol dehydrogenases are often used for the synthesis of enantiomerically pure stereoisomers of chiral alcohols. Often, high chemo- and enantioselectivity can be achieved. One example is the alcohol dehydrogenase from Lactobacillus brevis (LbADH), which is described to be a versatile biocatalyst.[38] The high chemospecificity has been confirmed also in the case of substrates presenting two potential redox sites. For instance cinnamaldehyde presents both aliphatic double bond and aldehyde function. Unlike conventional catalysts, alcohol dehydrogenases are able to selectively act only on the latter, yielding exclusively cinnamyl alcohol.[39]

text: In fuel cells, alcohol dehydrogenases can be used to catalyze the breakdown of fuel for an ethanol fuel cell. Scientists at Saint Louis University have used carbon-supported alcohol dehydrogenase with poly(methylene green) as an anode, with a nafion membrane, to achieve about 50 μA/cm2.[40]

text: In 1949, E. Racker defined one unit of alcohol dehydrogenase activity as the amount that causes a change in optical density of 0.001 per minute under the standard conditions of assay.[41] Recently, the international definition of enzymatic unit (E.U.) has been more common: one unit of Alcohol Dehydrogenase will convert 1.0 µmole of ethanol to acetaldehyde per minute at pH 8.8 at 25 °C.[42]

text: Clinical significance[edit]

text: Alcoholism[edit]

text: There have been studies showing that ADH may have an influence on the dependence on ethanol metabolism in alcoholics. Researchers have tentatively detected a few genes to be associated with alcoholism. If the variants of these genes encode slower metabolizing forms of ADH2 and ADH3, there is increased risk of alcoholism. The studies have found that mutations of ADH2 and ADH3 are related to alcoholism in Northeast Asian populations. However, research continues in order to identify the genes and their influence on alcoholism.[43]

text: Drug dependence[edit]

text: Drug dependence is another problem associated with ADH, which researchers think might be linked to alcoholism. One particular study suggests that drug dependence has seven ADH genes associated with it. These results may lead to treatments that target these specific genes. However, more research is necessary.[44]

text: Poisoning[edit]

text: Fomepizole, a drug that inhibits alcohol dehydrogenase, can be used in the setting of acute methanol[45] or ethylene glycol[46] toxicity. This prevents the conversion of methanol to its toxic metabolites, formic acid and formaldehyde.


document_title: 1080 (skateboarding)

question_text: who did the first 1080 on a skateboard

question_tokens: who did the first 1080 on a skateboard

text: 1080 (skateboarding)

text: The 1080 is a skateboarding stunt, performed on a vertical skateboard ramp, in which the skateboarder makes three full revolutions (1080 degrees rotation in the vertical plane) while airborne. It was first completed successfully by a 12-year-old American, Tom Schaar, on March 26, 2012.[1][2] Schaar completed the stunt on a MegaRamp at Woodward West in Tehachapi, California on his fifth attempt.[2] Red Bull described the 1080 as "the Holy Grail of all skateboard tricks."[3] Schaar has since repeated the feat, and completed a 1080 in competition while participating in the 2012 X Games Asia on April 30, 2012.[4] He won the gold medal in the Skateboard Mini MegaRamp category, the youngest person ever to have done so. At The Dew Tour Ocean City Tom landed the 1080 in Skate Mega 2.0 which resulted in him coming first.[5]

text: Tom Schaar[edit]

text: The jump was filmed by several cameras at the MegaRamp at Woodward West in Tehachapi, California. A roll-over feature was custom-built which allowed the skater to drop in on the 70-foot-tall and roll right over a 50-foot gap in the ramp, thus allowing Schaar to keep momentum going all the way through to the quarter pipe.[3] Schaar performed several 720s and a 900 while warming-up. He then attempted to perform the 1080, failing four times before successfully landing his fifth attempt,[6] being propelled 15 feet above the top of the ramp.[7]

text: Schaar commented to ESPN.com, "It was the hardest trick I've ever done, but it was easier than I thought." Several prominent skateboarders had been trying to become the first to perform the much-coveted 1080, with Shaun White thought to be the most likely to make the feat.[8] Tony Hawk tweeted in response to the video: "In the last year I've seen Shaun White try 1080s & Mitchie Brusco crash-land a few. Tom Schaar nailed it."[2]

text: Successful landings[edit]

text: 1. Tom Schaar, 30 March 2012, at MegaRamp Woodward West, Tehachapi, California (USA)[9]

text: 2. Jonathan Schwan, 29 April 2013, at MegaRamp Woodward West, Tehachapi, California (USA)[10][11]

text: 3. Mitchie Brusco, 17 May 2013, at XGames Barcelona, Spain[12]


document_title: The Dukes of Hazzard (film)

question_text: who played daisy in the dukes of hazzard movie

text: The Dukes of Hazzard (film)

text: Plot[edit]

text: Cousins Bo (Seann William Scott), Luke (Johnny Knoxville), and Daisy Duke (Jessica Simpson) run a moonshine business for their Uncle Jesse (Willie Nelson) in Hazzard County, Georgia. The cousins' primary mode of transportation is an orange 1969 Dodge Charger that the boys affectionately refer to as the "General Lee". Along the way, the family is tormented by corrupt Hazzard County Commissioner Jefferson Davis Hogg, widely known as "Boss Hogg" (Burt Reynolds), and his willing but dimwitted henchman, Sheriff Rosco P. Coltrane (M. C. Gainey).

text: After Rosco has the General Lee impounded after Bo and Luke’s attempt to runaway from a daughter of one their many moonshine customers, Billy Prickett (James Roday), a famous stock-car driver, enters Hazzard to participate in the rally. Meanwhile, Rosco plants a fake moonshine still ("'cause he's too dumb to find the real one") in Uncle Jesse's barn and seizes the Duke property in the interest of eminent domain for Boss Hogg, forcing the family to temporarily reside with neighbor and Uncle Jesse's love-interest, Pauline (Lynda Carter). Pauline informs the Dukes that Rosco seized another farm on charges so Bo and Luke investigate a local construction site and find geologic core samples with the help of bait-shop owner Sheev (Kevin Heffernan). Meanwhile, Coltrane makes arrangements to seize the General Lee as "evidence" from the local auto body shop run by the Dukes' friend Cooter Davenport (David Koechner), who instead turns the car into a hot-rod and applies a new paint job and horn, in return for finally getting payment for all the work he has done ("...'cause that's how this works...") for the boys in the past.

text: After retrieving the General Lee before Rosco can, the Dukes go to Atlanta to visit a local university geology lab, meeting up with Katie-Lynn Johnson (Nikki Griffin), a Hazzard county girl and the Dukes' love interest, and her Australian roommate Annette (Jacqui Maxwell). At the lab, they discover Boss Hogg's intentions of turning the county into a strip coalmine. They are later arrested by Atlanta Police after running from campus police. Back in Hazzard, Daisy learns, with the help of Sheriff Deputy Enos Strate (Michael Weston), that Billy Prickett has been hired by Boss Hogg to participate in the Rally as a ringer. Boss Hogg then heads to Atlanta where he informs the Duke boys, in lock-up, that they are too late to stop him and reveals that the vote on Hogg's proposition is at the same time as the rally, explaining Billy Prickett's involvement. During a transfer from detainment, Daisy helps the boys escape from the patrol car and they speed home to try to inform the townsfolk, escaping Atlanta Police, and the Georgia State Patrol after Bo out-maneuvers the city cops.

text: Upon returning home, the Dukes discover that Rosco has taken Uncle Jesse and Pauline hostage, an obvious trap for the boys, and that Billy is in on the scheme because he's ashamed of the town's low status. The two race to the farmhouse to cause a distraction to the waiting Hazzard County Sheriff's Deputies and Georgia State Troopers while Daisy and Cooter rescue Jesse and Pauline. Meanwhile, the college girls head to the rally with Sheev to inform the townsfolk about the vote on the strip-mining ordinance. Because of Sheev's armadillo hat and lack of pants, no one listens, so Bo leaves for the rally while Luke and Jesse team up to foil the county and state police who are chasing Bo, interfering with the race. Upon crossing the finish line first, before Billy, the two continue racing back and forth all the way into town, leading the townsfolk to the courthouse just in time to vote against Boss Hogg's proposed ordinance. At the courthouse, Daisy takes advantage of the governor of Georgia's presence and TV cameras to convince him into pardoning the boys, so Uncle Jesse takes the opportunity to knock out Boss Hogg and gets a pardon for assaulting a county commissioner at the same time.

text: The final scene shows a cook-out at the Dukes' house where Pauline convinces Uncle Jesse, who could not be found because he was "using the meat smoker", to get up and play the television series' main theme. Bo and Luke are romantically involved with the girls in the General Lee when they are caught by Luke's other love-interest Laurie Pullman (Alice Greczyn) from the intro of the film, who proceeds to chase them with a shotgun as they drive away.

text: During the credits, outtakes from the production of the film are shown.

text: Cast[edit]

text:
Johnny Knoxville as Luke Duke
Seann William Scott as Bo Duke
Jessica Simpson as Daisy Duke
Burt Reynolds as Boss Hogg
Willie Nelson as Uncle Jesse Duke
David Koechner as Cooter Davenport
M. C. Gainey as Sheriff Rosco P. Coltrane[1]
Michael Weston as Deputy Enos Strate
Lynda Carter as Pauline
James Roday as Billy Prickett
Kevin Heffernan as Derek "Sheev" Sheevington
Nikki Griffin as Katie-Lynn Johnson
Jacqui Maxwell as Annette
Alice Greczyn as Laurie Pullman
Junior Brown as The Balladeer (narrator)
Joe Don Baker as Governor Jim Applewhite
Barry Corbin as Bill Pullman
Randy Orton as Bo Duke (Stunt double)

text: Cameos[edit]

text: All five members of the comedy film troupe Broken Lizard make appearances in the film, classified as cameos except for Kevin Heffernan who had a larger speaking role (Sheev).

text:
Steve Lemme appears as Jimmy Pullman, the son of Bill Pullman, in an early car chase scene in which he accidentally shoots the inside of his father's truck.
Jay Chandrasekhar and Erik Stolhanske reprise their roles as "Ramathorn" and "Rabbit" from the Broken Lizard comedy, Super Troopers. The characters are now campus security officers, who give a warning to the Duke boys for driving too slowly.
Paul Soter appears as TV newsman Rick Shakely, who is reporting from the Hazzard Road Rally.
Charlie Finn, who played a dimwitted fast food employee in Super Troopers, appears as a dimwitted geology student who assists the Duke boys with the coal samples.

text:
During the bar fight scene, Indy-car driver A. J. Foyt IV appears as himself.
Bloopers roll under the ending credits, one of which features Rip Taylor interrupting the bedroom scene with Luke and the two college girls. Taylor had previously appeared with Knoxville in Jackass: The Movie.

text: Production[edit]

text: Stunts[edit]

text: Knoxville said he was initially reluctant to take on the role but was persuaded by script changes and the presence of Dan Bradley as stunt coordinator and second unit for the car chase scenes. Knoxville praised him saying "everyone in Hollywood wants Dan Bradley to shoot their car stuff".[2]

text: Locations[edit]

text: The majority of the film was shot in and around Clinton, Louisiana.

text: The street scenes are set in Atlanta but filmed in the New Orleans Central Business District, and the University scenes on the campus of Louisiana State University.

text: Reception[edit]

text: Box office[edit]

text: The film was No. 1 at the box office its opening weekend and grossed $30.7 million on 3,785 screens. It also had an adjusted-dollar rank of No. 24 all-time for August releases.[3]

text: The film eventually collected $111 million worldwide, although it was much less successful financially outside the United States.

text: Critical reception[edit]

text: Roger Ebert gave the film one star, calling it a "lame-brained, outdated wheeze" and wondered that Burt Reynolds' part in the film is "karma-wise... the second half of what Smokey and the Bandit was the first half of".[4] Ebert also named it the second worst film of the year and Richard Roeper named it the worst film of 2005.[5]

text: According to review aggregator Rotten Tomatoes, 14% of critics gave the film positive reviews, based on 168 reviews; the website's consensus called the film "A dumb, goofy and vacuous adaptation of a TV show where plot is simply an excuse to string together the car chases." The audience score on the film was "46% liked it". "Top Critics" linked by Rotten Tomatoes who gave the film a "fresh" rating (positive review) wrote for Chicago Review, USA Today, Toronto Star, New York Post, Washington Post, Slate, Entertainment Weekly, and Variety. [6] The film received an average rating of 33% on Metacritic based on 36 reviews.[7] Longtime fans of the original Dukes of Hazzard series were generally disappointed by the film.[8]

text: Awards[edit]

text: At the 26th Golden Raspberry Awards, the film received seven nominations, but didn't win any.

text:
Worst Picture - lost to Dirty Love
Worst Director (Jay Chandrasekhar) - lost to John Mallory Asher for Dirty Love
Worst Screenplay (John O'Brien) - lost to Jenny McCarthy for Dirty Love
Worst Supporting Actor (Burt Reynolds) - lost to Hayden Christensen in Star Wars: Episode III – Revenge of the Sith
Worst Supporting Actress (Jessica Simpson) - lost to Paris Hilton in House of Wax
Worst Screen Couple (Jessica Simpson & Her Daisy Dukes) - lost to Nicole Kidman and Will Ferrell in Bewitched
Worst Remake or Sequel - lost to Son of the Mask

text: At the People's Choice Awards, Simpson won the "Favorite Song from a Movie" award for her cover of Nancy Sinatra's "These Boots Are Made For Walkin'".

text: The film was nominated for two MTV Movie Awards, including Best On-Screen Team (Johnny Knoxville, Seann William Scott, & Jessica Simpson), and Sexiest Performance (Jessica Simpson).

text: Simpson won the Choice Breakout Female award for her role in the film at the Teen Choice Awards.

text: Controversy[edit]

text: Before the release of this film, Warner Bros. reportedly paid $17.5 million to the producer of Moonrunners, the movie that inspired the television series. This was soon followed by a claim from screenwriter Gy Waldron. The Hollywood Reporter reported that James Best, who portrayed Rosco P. Coltrane in the original series, filed suit in late July 2011 over royalties he was contracted to receive over spinoffs that "used his identity".[9] Ben Jones, who played Cooter Davenport in the original series, criticized the film for its emphasis on sexual content, suggesting that the original series was more family-oriented and not as sexualized.[10] He called for fans of the television series to boycott the film "unless they clean it up before the August 5th release date."

text: Some have countered that the original series also contained sexual themes, primarily Catherine Bach's (Daisy Duke) much-displayed "short shorts" (which have become so ubiquitous in American culture that skimpy blue jean cutoff shorts are now often simply called "Daisy Dukes"). In a film review, a New York Daily News entertainment columnist said the movie's sex humor is "cruder" than the TV series, but that it is "nearly identical to the TV series in... its ogling of the posterior of cousin Daisy Duke."[11]

text: Although initially he commented that he enjoyed the new style of relationship between the movie versions of Bo and Luke, John Schneider, who played Bo Duke in the original series, was later asked if he saw the film and said: "My gosh... it was terrible! It wasn’t Dukes. It was true to whatever it was; I just don’t know what that was!"[12]

text: Soundtrack[edit]

text: Jessica Simpson recorded her own version of "These Boots Are Made for Walkin'" (and added her own lyrics) for the soundtrack to the film The Dukes of Hazzard (2005). Performed from the point of view of her character in the movie, Simpson's cover was co-produced by Jimmy Jam and Terry Lewis, and was released as the soundtrack's first single in 2005. It became Simpson's fifth top-twenty single in the United States and its music video drew some controversy because of its sexual imagery.[13] Both the original Ram Jam version of "Black Betty", and the Sylvia Massy produced remake by Spiderbait appear in the film. "If You Want Blood (You've Got It)" and "Shoot to Thrill" are played by AC/DC.[14]

text: Unrated Cut[edit]

text: In 2008, an unrated cut restored changes made to get a PG-13 rating from the Motion Picture Association of America. The unrated cut was released on DVD, and included rated and unrated bonus features, including unrated deleted scenes and blooper scenes. This edition was not rated by the MPAA, but would have unquestionably been rated R for nudity, language and violent driving stunts.[15]

text: Prequel[edit]

text: A prequel to the film, titled The Dukes of Hazzard: The Beginning, was released to television on March 4, 2007 and released to DVD on March 13, 2007.