Claude Henri Jean Chabrol (; 24 June 1930 – 12 September 2010) was a French film director and a member of the French New Wave (nouvelle vague) group of filmmakers who first came to prominence at the end of the 1950s. Like his colleagues and contemporaries Jean-Luc Godard, François Truffaut, Éric Rohmer and Jacques Rivette, Chabrol was a critic for the influential film magazine Cahiers du cinéma before beginning his career as a film maker.

Chabrol's career began with Le Beau Serge (1958), inspired by Hitchcock's Shadow of a Doubt (1943). Thrillers became something of a trademark for Chabrol, with an approach characterized by a distanced objectivity. This is especially apparent in Les Biches (1968), La Femme infidèle (1969), and Le Boucher (1970) – all featuring Stéphane Audran, who was his wife at the time.

Sometimes characterized as a "mainstream" New Wave director, Chabrol remained prolific and popular throughout his half-century career. In 1978, he cast Isabelle Huppert as the lead in Violette Nozière. On the strength of that effort, the pair went on to others including the successful Madame Bovary (1991) and La Cérémonie (1995). Film critic John Russell Taylor has stated that "there are few directors whose films are more difficult to explain or evoke on paper, if only because so much of the overall effect turns on Chabrol's sheer hedonistic relish for the medium...Some of his films become almost private jokes, made to amuse himself." James Monaco has called Chabrol "the craftsman par excellence of the New Wave, and his variations upon a theme give us an understanding of the explicitness and precision of the language of the film that we don't get from the more varied experiments in genre of Truffaut or Godard."

Life and career

Early life
Claude Henri Jean Chabrol was born on 24 June 1930 to Yves Chabrol and Madeleine Delarbre in Paris and grew up in Sardent, France, a village in the region of Creuse 400 km (240 miles) south of Paris. Chabrol said that he always thought of himself as a country person, and never as a Parisian. Both Chabrol's father and grandfather had been pharmacists, and Chabrol was expected to follow in the family business. But as a child, Chabrol was "seized by the demon of cinema" and ran a film club in a barn in Sardent between the ages of 12 and 14. It was at this time that he developed his passion for the thriller genre, detective stories and other forms of popular fiction.

Early years in Paris
After World War II, Chabrol moved to Paris to study pharmacology and literature at the Sorbonne, where he received a licence en lettres. Some biographies also state that he briefly studied law and political science at the École Libre des Sciences Politiques. While living in Paris Chabrol became involved with the postwar cine club culture and frequented Henri Langlois's Cinémathèque Française and the Ciné-Club du Quartier Latin, where he first met Éric Rohmer, Jacques Rivette, Jean-Luc Godard, François Truffaut and other future Cahiers du Cinéma journalists and French New Wave filmmakers. After graduating, Chabrol served his mandatory military service in the French Medical Corps, serving in Germany and reaching the rank of sergeant. Chabrol has said that while in the army he worked as a film projectionist. After he was discharged from the army, he joined his friends as a staff writer for Cahiers du Cinéma, who were challenging then-contemporary French films and championing the concept of Auteur theory. As a film critic, Chabrol advocated realism both morally and aesthetically, mise-en-scene, and deep focus cinematography, which he wrote "brings the spectator in closer with the image" and encourages "both a more active mental attitude on the part of the spectator and a more positive contribution on his part to the action in progress." He also wrote for Arts magazine during this period. Among Chabrol's most famous articles were "Little Themes", a study of genre films, and "The Evolution of Detective Films".

In 1955 Chabrol was briefly employed as a publicity man at the French offices of 20th Century Fox, but was told that he was "the worst press officer they'd ever seen" and was replaced by Jean-Luc Godard, who they said was even worse. In 1956 he helped finance Jacques Rivette's short film Le coup du berger, and later helped finance Rohmer's short Véronique et son cancre in 1958. Unlike all of his future New Wave contemporaries, Chabrol never made short film nor did he work as an assistant on other directors' work before making his feature film debut. In 1957 Chabrol and Eric Rohmer co-wrote Hitchcock (Paris: Éditions Universitaires, 1957), a study of the films made by director Alfred Hitchcock through the film The Wrong Man. Chabrol had said that Rohmer deserves the majority of the credit for the book, while he mainly worked on the sections pertaining to Hitchcock's early American films, Rebecca, Notorious, and Stage Fright. Chabrol had interviewed Hitchcock with François Truffaut in 1954 on the set of To Catch a Thief, where the two famously walked into a water tank after being starstruck by Hitchcock. Years later, when Chabrol and Truffaut had both become successful directors themselves, Hitchcock told Truffaut that he always thought of them when he saw "ice cubes in a glass of whiskey."

1957–1967: Early film career
The most prolific of the major New Wave directors, Chabrol averaged almost one film a year from 1958 until his death. His early films (roughly 1958–1963) are usually categorized as part of the New Wave and generally have the experimental qualities associated with the movement; while his later early films are usually categorized as being intentionally commercial and far less experimental. In the mid-sixties it was difficult for Chabrol to obtain financing for films so he made a series of commercial "potboilers" and spy spoofs, which none of the other New Wave filmmakers did.

Chabrol had married Agnès Goute in 1952 and in 1957 his wife inherited a large sum of money from relatives. In December of that year Chabrol used the money to make his feature directorial debut with Le Beau Serge. Chabrol spent three months shooting in his hometown of Sardent using a small crew and little known actors. The film's budget was $85,000. The film starred Jean-Claude Brialy as François and Gérard Blain as Serge, two childhood friends reunited when the recent medical school graduate François returns to Sardent and discovers that Serge has become an alcoholic after the stillbirth of his physically retarded first child. Despite suffering from tuberculosis, François drags Serge through a snowstorm to witness the birth of his second child, thus giving Serge a reason to live while killing himself in the process. Le Beau Serge is considered the inaugural film of the French New Wave Film movement that would peak between 1959 and 1962. Chabrol was the first of his friends to complete a feature film (although Jacques Rivette had already begun filming his first feature Paris nous appartient), and it immediately received critical praise and was a box office success. It won the Grand Prix at the Locarno Film Festival and the Prix Jean Vigo. Critics noticed similarities to Hitchcock's films, such as the motifs of doubling and re-occurrences and the "Catholic guilt transference" that Chabrol had also written about extensively in his and Rohmer's book the year earlier. Chabrol stated that he made the film as a "farewell to Catholicism", and many critics have called his first film vastly different from any of his subsequent films.

Chabrol quickly followed this success up with Les Cousins in 1958. The film is a companion piece and a reversal to Le Beau Serge in many ways, such as having the responsible student Brialy now play the decadent and insensitive Paul while the reckless Blain now plays the hard-working law student Charles. In this film, the country cousin Charles arrives in the big city of Paris to live with his corrupt cousin Paul while attending school. This was the first of many Chabrol films to include characters named Paul and Charles, and later films would often include a female named Hélène. More so than his first film, Les Cousins features many characteristics that would be seen as "Chabrolian", including the Hitchcock influence, a depiction of the French bourgeoisie, characters with ambiguous motives and a murder. It was also Chabrol's first film co-written with his longtime collaborator Paul Gégauff, of whom Chabrol once said "when I want cruelty, I go off and look for Gégauff. Paul is very good at gingering things up...He can make a character look absolutely ridiculous and hateful in two seconds flat." Les Cousins was another box office success in France and won the Golden Bear at the 9th Berlin International Film Festival.

Chabrol formed his own production company AJYM Productions (acronym based on the initials of his wife's and children's names) at the time of making Le Beau Serge.  After the success of Le Beau Serge and Les Cousins, Chabrol began funding many of the films of his friends. AJYM helped fund Eric Rohmer's feature debut The Sign of Leo, partially funded Rivette's Paris nous appartient, and Philippe de Broca's films Les Jeux de l'amour and Le farceur. He also donated excess film stock from Les Cousins to Rivette to complete Paris nous appartient. Chabrol was also a technical advisor on Jean-Luc Godard's feature debut Breathless and acted in small parts in many of his friends' and his own early films. For his support to the early careers of so many of his friends, Chabrol has been referred to as "the godfather of the French New Wave", although many film histories tend to overlook this contribution and dismiss Chabrol altogether.

After two box office hits in a row, Chabrol was given a big budget to make his first color film, À double tour (Léda) in the spring of 1959. The film stars Jean-Paul Belmondo as Laszlo and Antonella Lualdi as Léda, two outsiders of a bourgeois family who experience different results when attempting to enter that family. Chabrol adapted the script with Paul Gégauff from a novel by Stanley Ellin, and the film is known for its oedipal sex triangle and murder scenario. The film was shot on location in Aix-en-Provence with cinematographer Henri Decaë and includes choppy, hand-held camera footage that is atypical of a Chabrol film despite being present in many of the New Wave films made at the same time. The film was both a box office and critical disappointment, and critic Roy Armes criticized "Chabrol's lack of feeling for his characters and love of overacting."

In 1960 Chabrol made what is considered by many critics as his best early film, Les Bonnes Femmes. The film stars Bernadette Lafont, Clotilde Joano, Stéphane Audran and Lucile Saint-Simon as four Parisian appliance store employees who all dream of an escape from their mediocre lives, and the different outcomes for each girl. Most critics praised the film, such as Robin Wood and James Monaco. However some left-wing critics disliked Chabrol's depiction of working-class people and accused him of making fun of their lifestyles. The film was another box office disappointment for Chabrol. It was followed with two films that were also financially unsuccessful and which Chabrol has admitted to making purely for "commercial reasons". Les Godelureaux was made in 1960 and hated by Chabrol. The Third Lover (L'Œil du Malin), released in 1961, received better reviews than Chabrol's previous films, with critics pointing out that the films that Chabrol wrote without Paul Gégauff were much more compassionate and realistic than the ones with Gégauff. It was shot on location in Munich. Although she had appeared in supporting roles in several Chabrol films before, The Third Lover was the first Chabrol film in which Stéphane Audran appeared as the female lead. They later married in 1964 and worked together until the late 1970s.

In 1962 Chabrol made Ophelia, a loose adaptation of Hamlet that was another box office disappointment. Later that year he had a minor hit film with Landru, written by Françoise Sagan and starring Charles Denner, Michèle Morgan, Danielle Darrieux and Hildegard Knef. The film depicts the famous French serial killer Henri Désiré Landru, a story that had previously inspired Charlie Chaplin's film Monsieur Verdoux.

From 1964 to 1967 Chabrol made six films and one short that were critically and commercially disastrous, and this period is considered a low point of his career. Four of these films were in the then-popular genre of spy spoof films, including Le Tigre aime la chair fraiche and Le Tigre se parfume à la dynamite. Chabrol had said that "I like to get to the absolute limit of principles...In drivel like the Tiger series I really wanted to get the full extent of the drivel. They were drivel, so OK, let's get into it up to our necks." During this period a Variety headline read "Vital To Keep Making Pictures, and What Sort Not Relevant; Chabrol No 'Doctrinaire' Type." In 1965 Chabrol also contributed to the New Wave portmanteau film Six in Paris with the segment "La Muette". Chabrol co-starred with Stéphane Audran as a middle aged couple dealing with their rebellious teenage daughter. In 1964 Chabrol also directed a stage production of MacBeth for the Théâtre Récamier.

1968–1978: "Golden Era"

In 1968 Chabrol began working with film producer André Génovès and started to make more critically acclaimed films that would later be considered his "Golden Era". Most of these films revolved around themes of bourgeois characters and a murder is almost always part of the plot. Unlike his earlier films, most of these films centered around middle aged people. Chabrol often worked with the same people during this period including actors Audran and Michel Bouquet, cinematographer Jean Rabier, editor Jacques Gaillard, sound technician Guy Chichignoud, composer Pierre Jansen, set designer Guy Littaye, as well as producer Génovés and co-writer Paul Gégauff.

In 1968 Chabrol made Les Biches, one of his most acclaimed works. The film stars Stéphane Audran as the dominant and bisexual Frédérique, who finds a young protege in the bisexual Why (Jacqueline Sassard), until they both become the lover of a young architect named Paul (Jean-Louis Trintignant). Why ends up killing Frédérique, but it is unclear whether she murdered her cheating lover or the person that her lover was cheating with. The film received critical praise and was a box office hit. Chabrol followed this with a similar film The Unfaithful Wife (La Femme infidèle), in which a husband named Charles murders the lover of his cheating wife. It was later remade in 2002 by director Adrian Lyne. Chabrol finished the decade with This Man Must Die (Que la bête meure) in 1969. Based on an original story by Cecil Day-Lewis, in the film Charles (Michel Duchaussoy) plots to kill Paul (Jean Yanne) after Paul killed Charles' son in a hit and run car accident. However the film's ending is left intentionally ambiguous, and Chabrol has stated that "you'll never see a Charles kill a Paul. Never." The film was especially praised for its landscape cinematography.

In 1970 Chabrol made The Butcher (Le boucher) starring Jean Yanne and Stéphane Audran. Yanne plays Popaul, a former war hero known for his violent behavior, much like that depicted in the prehistoric cave drawings that the characters look at in their Périgord community. The French newspaper Le Figaro called it "the best French film since the liberation." After another examination of bourgeois life in The Breach (La Rupture) in 1970, Chabrol made Just Before Nightfall (Juste avant la nuit) in 1971. The film stars Michel Bouquet as an ad executive named Charles who kills his mistress but cannot handle the guilt, so he confesses his crime to her husband (François Périer) and his wife (Stéphane Audran), expecting their condemnation. To his surprise they are only compassionate and forgiving to his crime and Charles cannot find relief from the guilt of what he has done. Later in 1971 Chabrol made Ten Days' Wonder (La Décade prodigieuse), based on a novel by Ellery Queen. The film was shot in English and starred Michel Piccoli, Anthony Perkins and Orson Welles. It received poor critical reviews. He followed this with the equally disliked Dr. Popaul, starring Jean-Paul Belmondo and Mia Farrow. Critics compared the film unfavorably with Chabrol's earlier film that centered on a "Landru-like" theme. Critic Jacques Siclier said that "the novelty of Docteur Popaul comes from the offhandedness with which the criminal history is treated."

Chabrol took a slight change of pace with his 1973 film Wedding in Blood (Les Noces rouges) by making his first film with political themes. The film stars Audran and Michel Piccoli as lovers who plot to murder Audran's husband, who is the corrupt gaullist mayor of their town. To their surprise the President of France orders that no investigation be made of the mayor's death, leading the murdering couple to suspect political interest in their crime. In the spring of 1973 the French government banned the film for one month, allegedly so that it would not influence members of the jury of a controversial criminal trial. Chabrol followed this political theme with Nada, in which a group of young anarchists kidnap an American ambassador. It was Chabrol's first film to not center on the bourgeois since Le Beau Serge. Chabrol returned to more familiar ground in 1975 with A piece of pleasure (Une partie de plaisir). In this film screenwriter Paul Gégauff plays a writer with a troubled marriage that ends in tragedy. (In 1983, Gégauff was stabbed to death in real life by his second wife.) Gégauff's wife is played by his real-life first wife Danièle Gégauff (already divorced when this film was made) and his daughter is played by real life daughter Clemence Gégauff. The film received poor critical reviews, with Richard Roud calling it "rather interestingly loathsome."

Chabrol ended his Golden Period with one of his most admired and his most controversial films Violette Nozière in 1978. The film starred a young Isabelle Huppert as a real life Parisian girl from a respectable petit-bourgeois family in the 1930s. At night Violette sneaks out to pick up men and eventually contracts syphilis, which she convinces her parents must be hereditary before she kills them. The film was controversial in France but praised in other countries.

1979–2009: Later work
In the 1980s and 1990s Chabrol engaged himself with many different projects for both TV and the silver screen. His films Poulet au vinaigre (1985) and Masques (1987) were entered into the 38th Cannes Film Festival and 37th Berlin International Film Festival respectively. Madame Bovary (1991) was nominated for the Golden Globe Award for Best Foreign Language Film and for the Academy Award for Best Costume Design. It was also entered into the 17th Moscow International Film Festival. La Cérémonie (1995) is perhaps his most acclaimed film from this period, as it was nominated for numerous César Awards and was entered into the 52nd Venice International Film Festival among other. His 1999 film The Color of Lies was entered into the 49th Berlin International Film Festival.

In 1995 Chabrol was awarded the Prix René Clair from the Académie française for his body of work.

Chabrol continued directing films and TV series well into the 2000s.

Personal life

Chabrol's first marriage to Agnès Goute (1956–1962) produced a son, Matthieu Chabrol, a composer who scored most of his father's films from the early 1980s. He divorced Agnès to marry the actress Stéphane Audran, with whom he had a son, actor Thomas Chabrol. They remained married from 1964 to 1978. His third wife was Aurore Paquiss, who has been a script supervisor since the 1950s. He had four children. Chabrol was a known gourmet chef and shot 10 Days Wonder in Alsace only because he wanted to visit its restaurants. Although he acknowledges the influence of Alfred Hitchcock in his work, Chabrol has stated that "others have influenced me more. My three greatest influences were Murnau, the great silent film director...Ernst Lubitsch and Fritz Lang."

Chabrol died on 12 September 2010 of leukemia. He is buried in Pere Lachaise Cemetery in north-eastern Paris.

Filmography

As director

Le Beau Serge (1958; Prix Jean Vigo 1959)
Les Cousins (1959; Golden Bear 1959)
À double tour (1959) – based on The Key to Nicholas Street by Stanley Ellin
Les Bonnes Femmes (1960)
Les Godelureaux (1961) – based on novel of the same title by Éric Ollivier
Les Sept péchés capitaux (1962; Short)
L'Œil du Malin (1962)
Ophelia (1963) – loosely based upon Shakespeare's character
Landru (1963) – based upon the true story of Henri Désiré Landru
Les plus belles escroqueries du monde (1964; Short)
Le Tigre aime la chair fraiche (1964)
La Muette (1965; Short)
Marie-Chantal contre le docteur Kha (1965) – loosely based upon Jacques Chazot's character
Our Agent Tiger (1965)
La Ligne de démarcation (1966) – based upon the memoir by Gilbert Renault
Le Scandale (1967)
La route de Corinthe (1967) – based on novel of the same title by
Les Biches (1968) – loosely based on The Talented Mr. Ripley by Patricia HighsmithLa Femme infidèle (1969)Que la bête meure (1969) – based on The Beast Must Die by Cecil Day-LewisLe Boucher (1970)La Rupture (1970) – based on The Balloon Man by Charlotte ArmstrongJuste avant la nuit (1971) – based on The Thin Line by Edward AtiyahLa Décade prodigieuse (1971) – based on Ten Days' Wonder by Ellery QueenDr. Popaul (1972) – based on Murder at Leisure by Hubert MonteilhetLes Noces rouges (1973)Nada also known as The Nada Gang (1974) – based on Nada by Jean-Patrick ManchetteUne partie de plaisir (1975)Les innocents aux mains sales (1975) – based on The Damned Innocents by Richard NeelyLes Magiciens (1976) – based on Initiation au meurtre by Frédéric DardFolies bourgeoises (1976)Alice ou la Dernière Fugue (1977)Les Liens de sang (1978) – based on Blood Relatives by Ed McBainViolette Nozière (1978) – based upon a true French murder case in 1933Le Cheval d'orgueil (1980) – based upon an autobiography of the same title by Pêr-Jakez HeliasLes Fantômes du chapelier (1982) – based on novel of the same title by Georges SimenonLe Sang des autres (1984) – based on novel of the same title by Simone de BeauvoirPoulet au vinaigre (1985) – Cop au Vin, Chicken with VinegarInspecteur Lavardin (1986)Masques (1987)Le cri du hibou (1987) – based on The Cry of the Owl by Patricia HighsmithUne affaire de femmes (1988) – based upon the true story of Marie-Louise GiraudJours tranquilles à Clichy (1990) – based upon an Quiet Days in Clichy by Henry MillerDocteur M (1990)Madame Bovary (1991) – based on Madame Bovary by Gustave FlaubertBetty (1992) – based on novel of the same title by Georges SimenonL'Œil de Vichy (1993; Documentary)L'Enfer (1994) – adapted from the screenplay of the same title by Henri-Georges ClouzotLa Cérémonie (1995) – based on A Judgement in Stone by Ruth RendellRien ne va plus aka The Swindle (1997)Au cœur du mensonge aka The Color of Lies  (1999)Merci pour le chocolat aka Nightcap (2000; Prix Louis-Delluc 2000) – based on The Chocolate Cobweb by Charlotte ArmstrongThe Flower of Evil aka La fleur du mal (2002)La Demoiselle d'honneur (2004) – based on The Bridesmaid by Ruth RendellL'ivresse du pouvoir (2006)La Fille coupée en deux (2007)Bellamy (2009)

As actor

1956: La Sonate à Kreutzer (by Éric Rohmer)
1958: Le Beau Serge (by Claude Chabrol) – La Truffe
1959: Web of Passion (by Claude Chabrol) – Passerby (uncredited)
1960: Les Bonnes Femmes (by Claude Chabrol) – Un nageur à la piscine (uncredited)
1960: Les Jeux de l'amour (by Philippe de Broca) – Le forain
1960: Trapped by Fear (by Jacques Dupont) – Invité à la soirée (uncredited)
1961: Wise Guys (by Claude Chabrol) – Un consommateur (uncredited)
1961: Saint Tropez Blues (by Marcel Moussy) – Le réalisateur empruntant des propos de Pierre Kast
1961: Les menteurs (by Edmond T. Gréville) – Le réceptionniste de l'hôtel (uncredited)
1961: Paris Belongs to Us (by Jacques Rivette) – Un homme à la party (uncredited)
1962: Les Ennemis (by Édouard Molinaro) – Le moniteur de gymnastique (uncredited)
1962: The Seven Deadly Sins (by various directors) – Le pharmacien (segment "Avarice, L'") (uncredited)
1962: The Third Lover (by Claude Chabrol) – Man in peep show (uncredited)
1964: Les durs à cuire ou Comment supprimer son prochain sans perdre l'appétit (by Jacques Pinoteau) – Le psychiatre
1965: Six in Paris (by various directors) – The father (segment "La Muette")
1965: Marie-Chantal contre le docteur Kha (by Claude Chabrol) – Customer complaining of his fruit juice
1965: Our Agent Tiger (by Claude Chabrol) – Le médecin radiologue (uncredited)
1966: Brigitte et Brigitte (by Luc Moullet) – Le cousin obsédé de Petite Brigitte
1967: La route de Corinthe (by Claude Chabrol) – Alcibiades (uncredited)
1968: La Petite Vertu (by Serge Korber) – Le client du club 22 / Man at the bar in the night club (uncredited)
1968: Les Biches (by Claude Chabrol) – Filmmaker (uncredited)
1970: La Rupture (by Claude Chabrol) – Un passager dans le tramway (uncredited)
1970: Sortie de secours (by Roger Kahane)
1971: Aussi loin que l'amour (by Frédéric Rossif) – L'homme au poteau (uncredited)
1972: Un meurtre est un meurtre (by Étienne Périer) – Le contrôleur des wagons-lits / Railway Guard
1974: Le permis de conduire (by Jean Girault) – Le réceptionniste de l'hôtel (uncredited)
1974: La Bonne Nouvelle (Short, by André Weinfeld) – Le curé / The Priest
1976: Folies bourgeoises (by Claude Chabrol) – Le client chez l'éditeur (uncredited)
1977: Animal (by Claude Zidi) – Le metteur en scène
1978: Violette Nozière (by Claude Chabrol) – Récitant du commentaire final (uncredited)
1981: Les folies d'Élodie (by André Génovès) – Un invité au vernissage
1984: Thieves After Dark (by Samuel Fuller) – Louis Crépin dit :Tartuffe
1984: Polar (by Jacques Bral) – Théodore Lyssenko
1986: Suivez mon regard (by Jean Curtelin) – Le téléphage
1986: Je hais les acteurs (by Gérard Krawczyk) – Lieberman
1987: Sale destin (by Sylvain Madigan) – Le commissaire
1987: Jeux d'artifices (by Virginie Thévenet) – Le père de Jacques
1987: L'été en pente douce (by Gérard Krawczyk) – The priest
1988: Alouette, je te plumerai (by Pierre Zucca) – Pierre Vergne
1992: Sam suffit (by Virginie Thévenet) – M. Denis
1997: Rien ne va plus (by Claude Chabrol) – Le croupier (voice, uncredited)
1999: The Color of Lies (by Claude Chabrol) – Emmanuel Solar (voice, uncredited)
2006: Avida (by Benoît Delépine) – Le zoophile débonnaire
2008: Lucifer et moi (by Jean-Jacques Grand-Jouan) – L'homme de la rue
2010: Gainsbourg, vie héroïque (by Joann Sfar) – Le Producteur Musique de Gainsbourg
2012: Le Jour des corneilles (by Jean-Christophe Dessaint) – Le docteur (voice)
2018: The Other Side of the Wind (by Orson Welles) – Himself (final film role)

TV workHistoires insolites (1974), 5 episodesNouvelles de Henry James (1974), 2 episodes – based on stories by Henry JamesIl était un musicien (1978), 3 episodes (1978), 1 episode"Jeunesse et Spiritualité" Cyprien Katsaris (1979) Official site (1980), 2 episodes – Remake of FantômasLe système du docteur Goudron et du professeur Plume (1981) – based on The System of Doctor Tarr and Professor Fether by Edgar Allan Poe (1982) – based on Elective Affinities by Johann Wolfgang von GoetheM. le maudit (1982, short)La danse de mort (1982) – based on The Dance of Death by August StrindbergLes dossiers secrets de l'inspecteur Lavardin (1988), 2 episodesLes redoutables (2001), 1 episodeChez Maupassant (2007), 2 episodes – based on stories by Guy de MaupassantAu siècle de Maupassant: Contes et nouvelles du XIXème siècle'' (2010), 2 episodes

References

External links

Biography on newwavefilm.com
Senses of Cinema: Great Directors Critical Database
Interview with Chabrol on La Cérémonie

Surfer on the New Wave – Interview with Chabrol from 2001

1930 births
2010 deaths
Deaths from cancer in France
Deaths from leukemia
European Film Awards winners (people)
Directors of Golden Bear winners
Film directors from Paris
Burials at Père Lachaise Cemetery
English-language film directors
Film theorists
French-language film directors
German-language film directors

Claude Chabrol


Dream Evil is a Swedish heavy metal band, assembled by producer Fredrik Nordström in 1999.

History
Producer Fredrik Nordström had the ambition of creating a power metal band of his own for a long time, but had difficulty finding anyone with musical ideals similar to his own. However, while on holiday in the Greek islands during the year of 1999, Nordström met the young guitarist Gus G (from Firewind). The musicians got along quite well, despite an age difference of over a decade. Plans for a band commenced – Gus had already been planning to relocate to Gothenburg, and upon his arrival he looked up Fredrik at Studio Fredman to begin writing.

The first person asked to join the new band was Snowy Shaw (from King Diamond, Mercyful Fate and Notre Dame), but the drummer initially refused their invitation. He would later change his mind and agreed to play on the band's debut album in a session capacity.

Vocalist Niklas Isfeldt had done backing vocals for some of HammerFall's songs produced by Nordström, and since he was not involved in any major projects at the time, he agreed to take the position. He also brought along his longtime friend and Pure-X bandmate Peter Stålfors, who assumed bass guitar duties.

Up until the moment the first promotional photos were shot, the entire band had never been in the same place at the same time before. Some members did not even know each other.

The band soon got a deal with Century Media Records, and intended to name themselves Dragonslayer due to the medieval and fantastical themes of the songs written by Gus and Nordström. The label did not find the name original enough, and thus the band settled for the name Dream Evil, inspired by the Dio album of the same name.

Dream Evil's debut album was released in April 2002, and received positive feedback from the metal press. At one point the album, titled Dragonslayer, reached number one on the Japanese import charts. The band proceeded to play a series of festivals, and also supported Blind Guardian during a part of their world tour.

The band members found that they got along well as a unit despite the somewhat random manner by which they had been brought together and Snowy Shaw decided to join the band permanently. Dream Evil went on their first Japanese tour. During their stay in Japan, the band was invited by HammerFall to support their 2003 European tour. Their label manager hinted that it would be a good idea to have a new album out by then.

With little time on their hands, the band wrote the basis of several songs on the flight back to Europe, and on the day of their arrival entered the studio in order to record a new album. They took two weeks in total to record Evilized, and most songs were recorded as they had been written. It was released on 20 January, and one week later Dream Evil proceeded to tour Europe with HammerFall and the less known Masterplan.

For their third album, the band actually took time to write the songs and fine-tune them in the studio. The Book of Heavy Metal took two months to be recorded, and was released in May 2004.

Guitarist Gus G left the band in late 2004 in order to dedicate more time to Firewind, being replaced by Mark Black (then known as Mark U Black). Black had previously filled in for Gus on a few other occasions and replaced him permanently on their tour as support act for Saxon.

Niklas Isfeldt and Peter Stålfors briefly left in 2005 to be replaced by Jake E. Berg (aka Jake Steel, of Dreamland) and Tommy Larsson. However, a few months later, Niklas and Pater returned before recordings or live shows were done. At the start of 2006, Snowy Shaw abruptly quit Dream Evil. After a period of silence for several months, Dream Evil announced Pat Power (Patrik Jerksten), a co-worker of Fredrik Nordström from Studio Fredman, as Snowy's replacement.

The first album featuring the new line-up, United, was released on 13 October 2006.

Dream Evil announced on 7 December 2007 on the website that Mark Black would be leaving the band and will be replaced by Daniel Varghamne aka Dannee Demon.

On 3 March 2008 the band announced that they had begun work on a new studio album, tentatively titled In the Night. The album was released on 25 January 2010 in Europe and 26 January 2010 in North America.

On 23 July 2008 the band announced that their first live DVD/CD set, Gold Medal in Metal (Alive & Archive), was released on 25 August 2008.

On 28 December 2013 Dream Evil announced that Dannee Demon left the band and was replaced by Mark Black. Upon contact in 2015, Dream Evil informed that they were not on hiatus, just very busy with other commitments, and had eighteen tracks prepared for a future album. On 7 March 2017 the album titled Six was finally announced to be released on 26 May 2017.

Members

Current members
Fredrik Nordström – rhythm guitar (1999–present)
Niklas Isfeldt – vocals (1999–present (small hiatus in 2005))
Peter Stålfors – bass guitar (1999–present (small hiatus in 2005))
Markus Fristedt – lead guitar (2004–2007, 2013–present)
Sören Fardvik – drums (2019-present)

Former members
Snowy Shaw – drums (1999–2006)
Gus G – lead guitar (1999–2004)
Daniel Varghamne – lead guitar (2007–2013)
Jake E. Berg – vocals (2005)
Tommy Larsson – bass guitar (2005, died in 2020)
Pat Power – drums (2006–2019)

Timeline

Discography

Studio albums

EPs

Live

References

External links

Musical groups from Gothenburg
Swedish power metal musical groups
Musical groups established in 1999
Century Media Records artists
1999 establishments in Sweden

Dream Evil


The Second Epistle to the Timothy is the fifty-fifth book in the Christian Bible, and the sixteenth in the New Testament.

This book is believed to a letter from the Apostle Paul to Timothy. It is thought to be the last letter Paul wrote before his death although some think is was written by one of Paul's followers some time after his death.

Content

In the letter, Paul tells Timothy not to have a "spirit of fear" and not to "be ashamed to talk openly about our Lord (Jesus)" (Chapter 1, verses 7 and 8). He also tells Timothy to come to visit him before winter, and to bring Mark with him (cf. Philippians Chapter 2, verse 22).  He thought that "the time of his death was at hand" (Chapter 4 ,verse 6), and he tells his "son Timothy" to work hard and be strong in the face of false teachings, and to be faithful in all the duties of his office of pastor (Chapter 4, verses 1 to 5), knowing that he would someday stand before the Judge of the living and the dead (God).

Paul thinks he will soon be killed and talks about that. In Chapter 4, verses 6 to 8 he writes "For I am now ready to be offered, and the time of my departure is at hand.  I have fought a good fight, I have finished my course(race), I have kept the faith: in the future there is laid up for me a crown of righteousness, which the Lord, the righteous judge, shall give me at that day: and not to me only, but unto all them also that love his appearing."

Other websites
 II Timothy (NIV)
 II Timothy (KJV)

Pauline epistles
New Testament books

Second Epistle to Timothy


In enzymology, a (R)-2-hydroxy-fatty-acid dehydrogenase () is an enzyme that catalyzes the chemical reaction

(R)-2-hydroxystearate + NAD  2-oxostearate + NADH + H

Thus, the two substrates of this enzyme are (R)-2-hydroxystearate and NAD, whereas its 3 products are 2-oxostearate, NADH, and H. This reaction is important in fatty acid metabolism.

This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-OH group of donor with NAD or NADP as acceptor. The systematic name of this enzyme class is (R)-2-hydroxystearate:NAD oxidoreductase. Other names in common use include D-2-hydroxy fatty acid dehydrogenase, and 2-hydroxy fatty acid oxidase.

References

EC 1.1.1
NADH-dependent enzymes
Enzymes of unknown structure

(R)-2-hydroxy-fatty-acid dehydrogenase


A lightning rod or lightning conductor is an iron rod that is used to make lightning strike it, rather than strike something else. It is part of a lightning protection system. Such a system is made of many such rods. These rods are usually placed at high points of buildings and structures. In addition, paths are made the electricity can take from the rooftop to the ground, it was made in the year 1749 later improved in 1752.

History
Lightning can damage structures made of most materials (masonry, wood, concrete and even steel). The huge currents involved can heat materials, and especially water to high temperatures. This will cause fire, loss of strength and explosions from super-heated steam and air.

Europe

The church tower was usually the highest structure or building in medieval European towns and villages. It was also the building very often hit by lightning. Early on, Christian churches tried to prevent the damage of lightning by prayers. Priests prayed,
 "temper the destruction of hail and cyclones and the force of tempests and lightning; check hostile thunders and great winds; and cast down the spirits of storms and the powers of the air."
Peter Ahlwardts ("Reasonable and Theological Considerations about Thunder and Lightning", 1745) said people who sought to protect themselves from lightning should go anywhere except in or around a church.

In Europe, the lightning rod was invented by a theologian and natural scientist, Václav Prokop Diviš, between 1750 and 1754. He is the inventor of the first grounded lightning rod, which he erected on 15 July 1754 in the garden of his home in Přímětice u Znojma. It consisted of 400 sharp metal spikes attached at the top of a 42 m tall supporting pylon. The structure was fastened by three metal chains, conductively attached to the iron grounding cones buried in the packed down soil. He described his 'weather machine' in the treatise 'Descriptio machinae meteorologicae'. The original idea was to continually sap the electricity out of the clouds and so actually prevent the lightning and the storms, only in case this failed, the machine should have also been able to directly attract the lighting and channel it to the ground. He proposed his machine to be used on church towers and ships. He was sending his observations regarding the machine operation to Jan Antonín Scrinci, the physics professor at the Charles University in Prague, who published them in 'Prager Postzeitungen', 'Brünner Intelligenz-Zettel' and in 'Stuttgartisches Journal'. The machine is also mentioned by Leonhard Euler in 'Lettres à une Princesse d' Allemagne'. In 1755 Diviš asked the Emperor Ferdinand I of Austria to let him build more machines on several places for the welfare of the people. The emperor let the mathematicians in Vienna judge the proposal, but they refused it. Abbé Marci, court mathematician and Diviš' friend commented: 'Blasphemant, quae ignorant' (condemning what they do not know). In 1756 the machine was damaged by wind and then rebuilt, and then on 10 March 1760, angry villagers of Přímětice tore down the structure, blaming Diviš for drought which struck the region that year. Later in the year, after the summer during which the thunderstorms did a lot of damage to the fields and vineyards, the people besought him to rebuild the machine, which he did in the precinct of Loucky monastery, and built another one on the top of the church tower in Přímětice.

United States
In the United States, the pointed lightning rod conductor, often incorrectly referred to as the "lightning attractor," was invented by Benjamin Franklin as part of his groundbreaking explorations of electricity. Franklin thought that, with an iron rod sharpened to a point at the end,

"The electrical fire would, I think, be drawn out of a cloud silently, before it could come near enough to strike [...]."

Franklin speculated about lightning rods for several years before his reported kite experiment. This experiment, in fact, took place because he was tired of waiting for Christ Church in Philadelphia to be completed so he could place a lightning rod on top of it. There was some resistance from churches who felt that it was defying divine will to install these rods. Franklin countered that there is no religious objection to roofs on buildings to resist precipitation, so lightning, which he proved to be simply a giant electrical spark, should be no different. As an act of philanthropy, Franklin decided against patenting the invention.

In the 19th century the lightning rod became a symbol of American ingenuity and a decorative motif. Lightning rods were often embellished with ornamental glass balls (now prized by collectors). The ornamental appeal of these glass balls has also been incorporated into weather vanes.

Balls of solid glass occasionally were used in a method thought to prevent lightning strikes to ships. It is worth noting here not because it worked, which it did not, but because it reveals a lot about pre-scientific thought. Glass objects do not conduct electricity well. They are seldom struck by lightning. Therefore, goes the theory, there must be something about glass that repels lightning. Hence the best method for preventing a lightning strike to a wooden ship was to bury a small solid glass ball in the tip of the highest mast. The random behavior of lightning ensured that the method gained a good bit of credence even after the development of the marine lightning rod soon after Franklin's initial work.

Nikola Tesla's  was an improvement in lightning protectors. The patent was granted due to a fault in Franklin's original theory of operation; the pointed lightning rod actually ionizes the air around itself. This makes the air conductive, which in turn raises the probability of a strike. Many years after receiving his patent, in 1919 Dr. Tesla wrote an article for The Electrical Experimenter entitled "Famous Scientific Illusions", in which he explains the logic of Franklin's pointed lightning rod and discloses his improved method and apparatus.

References

Electricity

Lightning rod


Hrœrekr Ringslinger or Ringscatterer (Old Norse: Hrærekr slöngvanbaugi, Old Danish: Rørik Slængeborræ or Rørik Slyngebond) was a legendary 7th-century king of Zealand or Denmark, who appears in Chronicon Lethrense, Annals of Lund, Gesta Danorum, Sögubrot, Njáls saga, Hversu Noregr byggðist, Skjöldunga saga, and Bjarkarímur. Connection with such historical figures such as Horik I, who ruled Denmark around 854 for a dozen or so years, or the founder of the Rurik dynasty is fraught with difficulty.

Beside the name, the Danish and the West Norse traditions have little more in common than his living a few generations after Hrólfr Kraki, his name and his title. In the Danish tradition, he is described as the grandfather of Prince Hamlet.

Name
The name Slængeborræ, in Chronicon lethrense and the Annals of Lund is a corruption of Slænganbøghe, which is the Old East Norse form of Old West Norse slöngvanbaugi meaning "ring slinger", i.e. a king who was generous with his gold. Saxo's version Slyngebond means "bracelet slinger" and the motivation Saxo gives is strikingly different (see below).

Danish tradition
In the Danish tradition Rørik is the son of an earthly Höðr, and notably the grandfather of Prince Hamlet through his mother Gertrude. Rørik is described as a powerful king of Denmark.

Chronicon lethrense and Annals of Lund
The Chronicon lethrense and the Annals of Lund make Rørik the son of an earthly Höðr who killed Balder, Odin's son in battle. Höðr was himself killed by Odin's son Both.

Rørik Slængeborræ was a victorious king who conquered Courland, Wendland and Sweden and made them pay tribute to him. He appointed Orwendel and Feng as the commanders of Jutland and gave his sister to Orwendel. The sister and Orwendel were the parents of Amblothe (Hamlet). Rørik was succeeded by Wighlek.

Gesta Danorum
The Gesta Danorum (book 3) by Saxo Grammaticus agrees with the Chronicon lethrense and the Annals of Lund by making Rørik Slyngebond the son of Höðr (Høther). When Odin's son Boe had killed Höðr, the Swedes, the Curonians and the Slavs rebelled against Denmark (Saxo patriotically ignores the fact that he had previously given Höðr as a prince of Sweden who ruled Denmark) and attacked Rørik.

When the Slavic and Danish forces met, a Slavic wizard suggested that instead of having a large battle and lose a great many lives, two men should meet in a duel. If the Slav won, the tribute would be cancelled, but if the Dane won, the tribute would be paid as in the old days. A Dane asked Rørik what the reward would be for the Danish champion if he won the fight. Rørik promised a chain of six laced bracelets. The Dane entered the duel but was defeated and died.

The next day, the winning Slavic champion was emboldened by his victory and asked if there was a second Dane who wanted to meet him in combat. A warrior named Ubbe who was both strong and skilled in seiðr asked Rørik what the prize would be if he killed the Slav. Once again Rørik promised the chain of bracelets. The Dane asked Rørik if he would leave the chain of bracelets to a third trustworthy man, so that he could not change his mind when the Danish champion had won. Rørik agreed, but the man who would take the chain was on another ship, and when Rørik threw the chain of bracelets across, he underestimated the distance and so the chain fell into the water, and was lost forever. This gave Rørik the cognomen Slyngebond (sling-bracelets). However, Ubbe decided to take the challenge anyway. In the duel both champions died, but the Slavs were impressed and agreed to continue paying the tribute.

Rørik appointed Horwendil and Feng as the rulers of Jutland. Horwendil spent a great deal of time pillaging and won so much fame that Rørik gave him his daughter Gerutha (Gertrude) who bore him the son Amleth (Hamlet).

When Rørik died, he was succeeded by Wiglek.

Skjôldunga saga

Here, Rørik is the son of Ingjald Frodason (Ingeld), and the half brother of king Halfdan in Lejre, the father of Hroðgar. Ingeld kills Healfdene, and takes his wife as his own. Rørik is the result of this union. The name Slöngvanbaugi is connected to an incident where he threw some rings into the ocean (the ring-slinger).

West Norse tradition
The Norwegian and Icelandic tradition only mentions Hrœrekr in relation to the Scanian chieftain Ivar Vidfamne who made himself the ruler of both Denmark and Sweden. There is no information on his parentage, nor any Hamlet. In these sources, Hrœrekr is only the king of Zealand, Skåne and Jutland being in the hands of other rulers.

Sögubrot
Sögubrot relates that when Ivar Vidfamne was the king of Sweden, he gave his daughter Auðr the Deep-Minded to Hrœrekr, even though she wanted to marry Hrœrekr's brother Helgi the Sharp. Hrœrekr and Auðr then had the son Harald Wartooth. Ivar told Hrærekr that Auðr was unfaithful with his brother Helgi. The ruse worked and Hrœrekr killed his brother, after which Ivar attacked and killed Hrœrekr too. However, Auðr arrived with the Zealand army and chased her father Ivar back to Sweden. The following year, Auðr went to Garðaríki with her son Harald and many powerful men and married its king Raðbarðr. This was the opportunity for Ivar to conquer Zealand.

Sögubrot adds a second Hrœrekr slöngvanbaugi who was the son of Harald Wartooth, and consequently named after his grandfather.

Njals saga
Njals saga only mentions Hrœrekr Slöngvanbaugi as an ancestor of a man named Valgarðr. It tells that he was the father of Harald Wartooth, and then it states that Harald's mother was Auðr, the daughter of Ivar Vidfamne, the son of Halfdan the Valiant. It does not mention whether Hrœrekr was married to Auðr, but assumes that the reader is familiar with their story.

Hyndluljóð
In the poem Hyndluljóð the goddess Freyja meets the völva Hyndla and they ride together towards Valhalla. Freyja rides on her boar Hildisvíni and Hyndla on a wolf. Their mission is to find out the pedigree of Óttarr so that he can touch his inheritance, and the lay consists mostly of Hyndla reciting a number of names from Óttarr's ancestry, among them Hrærekr's in stanza 28.

Hversu Noregr byggðist
Hversu Noregr byggðist, agrees with Sögubrot by giving Hrœrekr as the father of Harald Wartooth. It also adds that he had the son Randver, the father of the Swedish and Danish king Sigurd Hring. However, other sources disagree with Hversu (Sögubrot and the Lay of Hyndla says that Randver's father was Raðbarðr, whereas Hervarar saga says that it was Valdar).

Notes

External links
 Peter Tunstall's translation of the Chronicon lethrense at The Chronicle of the Kings of Lejre and Northvegr: The Saga of Hrolf Kraki: The Chronicle of the Kings of Lejre.
Book Three of Gesta Danorum at the Medieval and Classical Literature Library
Hyndluljóð Guðni Jónsson's edition with normalized spelling
Hyndluljoth Translation and commentary by Henry A. Bellows
Sacred Texts: Appendix A: Fl. Book 1.21,22: How Norway was inhabited a translation of Hversu Noregr byggðist. (The genealogies of the descendants of Nór and the Ættartolur are not translated here.)
Sögubrot in Old Norse

Mythological kings of Denmark
Scyldings

Hrœrekr Ringslinger


Night vision is being able to see in the dark. Some animals, like cats, have natural night vision - they can see in very low light without any help. Humans do not have good night vision. If there is not enough light to see well, a human may need a night vision device such as night vision goggles to help them see.

Night vision goggles come in two types:

Amplification - This increases the visible light, and makes it bright enough for our eyes to see.  It works well outside but cannot be used in a completely dark place, such as a cave.
 Infrared - Uses a different part of the light that we cannot see.  It sees heat energy.  Animals and vehicles produce heat and are easily seen in infrared, even when it is completely black.

Vision

Night vision


John J. Ghezzi (January 1, 1911 – May 9, 1983 Albany, Albany County, New York) was an American lawyer and politician.

Life
He was born in Albany, New York, on January 1, 1911 and was educated in the Albany Public School system. He graduated from Albany High school in 1928.
He attended Fordham University and Albany Law School, and graduated, with honors, from St. John's University School of Law in 1933. He worked for the Louis Yaguda law firm after passing the bar exam. He enlisted in the U.S. Army on March 13, 1942 and was assigned to the 109th Infantry Regiment of the 28th Infantry Division. He was honorably discharged as a First Sergeant in October 1945 after serving 22 months in the European Theater of Operations. He entered state government service in 1949, serving as an unemployment insurance referee and an attorney in the corporations division of the Department of State until he was appointed Director of the State Elections and Law Bureau in 1959. He had been Deputy Secretary of State in charge of the Division of Corporations since 1965 when he was appointed Secretary of State of New York by Governor Malcolm Wilson in 1974.

Sources
 Obit in NYT on May 11, 1983
 Military enlistment file, at National Archives

1911 births
1983 deaths
Secretaries of State of New York (state)
St. John's University School of Law alumni
20th-century American politicians

John J. Ghezzi


The starlings are a family of small to medium-sized birds, the Sturnidae. This family are passerine songbirds, whose best-known species is Sternus, the common starling.

Starlings occur naturally in the Old World, from  Europe, Asia and Africa. Species (usually the common starling) have been introduced to  North America, Hawaii and New Zealand. In these new areas they compete for habitat with native birds, and are considered as invasive species.

Starlings have strong feet, their flight is strong and direct, and they are very gregarious (social). Their preferred habitat is fairly open country. They are omnivores. They eat insects and fruit. Several species live around humans. Many species search for food by opening the bill after probing it into dense vegetation; this behavior is called 'open-bill probing'. Plumage is usually dark with a metallic sheen and white flecks (spots). Most species nest in holes, laying blue or white eggs.

Many Asian species, particularly the larger ones, are called mynas, and many African species are known as glossy starlings because of their iridescent plumage.

Starlings have varied and complex songs, and may copy sounds from their surroundings, including car alarms, and human speech. The birds can recognize particular individuals by their calls.

Flocks
North-East European starlings migrate, but in southern and western Europe the birds are resident. Starlings are generally a highly social family. Most species associate in flocks of varying sizes throughout the year. These flocks may include other species of starlings and sometimes species from other families. This social activity is obvious in their roosting behaviour. In the non-breeding season some roosts can number thousands of birds. Flocks in Britain used to number millions of birds, though numbers are now fewer than they used to be.

Sternus vulgaris is a highly gregarious species in autumn and winter. Flock size is variable: huge flocks are a spectacular sight and sound. These flocks often attract birds of prey such as sparrowhawks. Flocks form a tight sphere-like formation in flight, frequently expanding and contracting and changing shape, seemingly without any leader.

Very large roosts, sometimes up to 1.5 million birds, can form in city centers, woodlands, or reedbeds, causing problems with their droppings.
Huge flocks of more than a million starlings are observed just before sunset in spring in southwestern Jutland, Denmark. There they gather in March until they leave for their breeding ranges by mid-April. Their flocking creates complex shapes against the sky, a phenomenon known locally as "Black Sun". To witness this spectacle, the best place are the seaward marshlands of Tønder and Esbjerg .

Flocks of anything from five to fifty thousand starlings form in areas of the UK just before sundown during mid winter. These flocks are commonly called a murmeration, sometimes a Starling Moot.(meaning meeting or council)

Collective animal behaviour

North America

Although there are approximately 200 million starlings in North America, they are all descendants of 60 birds released in 1890 (and 40 more in 1891) in Central Park, New York, by Eugene Schieffelin. He was a member of the Acclimation Society of North America, which  tried to introduce to North America every bird species mentioned in the works of William Shakespeare.

As an introduced species, European starlings are not protected under the Migratory Bird Treaty Act. Starlings are considered a nuisance species in North America. The birds, which travel in enormous flocks, often pose dangers to air travel, disrupt cattle operations, chase off native birds, and roost on city blocks. They leave behind corrosive droppings and hundreds of millions of dollars of damage every year. In 2008, U.S. government agents poisoned, shot and trapped 1.7 million starlings, more than any other nuisance species.

The starling family includes a lot of birds which look different to the common starling. One large group is called the mynas, which genetic analysis shows is not a natural group.

References

Passeri

Starling


Pressurized watter reactors (PWRs) constitute the muckle feck o the world's nuclear pouer plants (notable exceptions being the Unitit Kinrick, Japan, an Canada) and are one of three types of light watter reactor (LWR), the other types being bylin watter reactors (BWRs) and supercritical watter reactors (SCWRs). In a PWR, the primary coolant (watter) is pumped under high pressure tae the reactor core where it is heated bi the energy released by the fission o atoms. The heated watter then flows to a steam generator where it transfers its thermal energy tae a secondary system where steam is generated an flows tae steam turbines which, in turn, spin an electric generator. In contrast tae a boiling watter reactor, pressure in the primary coolant loop prevents the watter from boiling within the reactor. All LWRs use ordinary watter as both coolant an neutron moderator.

PWRs were originally designed tae serve as nuclear marine propulsion for nuclear submarines and were used in the original design of the second commercial pouer plant at Shippingport Atomic Pouer Station, Pennsylvanie, Unitit States.

PWRs currently operating in the Unitit States are considered Generation II reactors. Roushie's VVER reactors are similar to U.S. PWRs. France operates many PWRs tae generate the bulk o its electricity.

Key tae diagram

    Reactor pressure vessel
    Fuel assembly
    Control rod (controls reactivity within the reactor)
    Control rod drive mechanism
    Pressurizer (for primary coolant loop)
    Steam generator (inverted U-tube teep)
    Feedwatter
    High-pressure turbine
    Low-pressure turbine
    Generator
    Exciter
    Condenser
    Cooling watter
    Feedwatter heater
    Feedwatter pump
    Cooling watter pump
    Reactor coolant pump
    Generated electricity
    Main steam line
    Containment

Nuclear pouer reactor teeps

Pressurized watter reactor


A topoisomerase is one of a group of enzymes that unwind and wind DNA in order to help the creation of DNA structures.

DNA is in a helix/spiral which helps make the structure of DNA strong and stable. However, when undergoing DNA replication, the spiral needs to be untwisted, and when spirals are being untwisted knots, and breaks can happen. When studying the structure of DNA, James D. Watson and Francis Crick knew that there was need for an enzyme to overcome this problem.

Topoisomerase binds to either side of the DNA strands and allows the DNA to be untangled or unwound.

Molecular biology
Enzymes

Topoisomerase


Benzoylureas are chemical derivatives of N-benzoyl--phenylurea (benzoylurea). They are best known for their use as insecticides. They act as insect growth regulators by inhibiting synthesis of chitin in the insect's body.

One of the more commonly used benzoylurea pesticides is diflubenzuron. Others include chlorfluazuron, flufenoxuron, hexaflumuron, and triflumuron. Lufenuron is the active compound in flea control medication for pet dogs and cats.

3-(Iodoacetamido)-benzoylurea (3-IAABU) is one of several benzoylurea compounds which have been investigated as potential anticancer agents.

Environmental toxicity

When applied in a dispersed way, for example through fumigation or spraying, these chemicals have an effect against a wide range of insect species, some of which may be beneficial to human activities, including crop-pollinators such as bees. In addition, as with many insecticides, application may result in the killing of natural predators or controls along with the pest, risking the possibility of a 'rebound effect' or pest resurgence, where the original target for the treatment returns with equal or even greater voracity.

Flufenoxuron was banned in the European Union in 2011 due to its high potential for bioaccumulation in the food chain and high risk to aquatic organisms. Flufenoxuron is marketed as having 'high persistence' in the environment and the product data-sheet states that it does not biodegrade easily.

References

Further reading
Lewis, W.H. and M.P.F. Elvin-Lewis. (2003). Medical Botany. Hoboken: Wiley. pg. 590

Insecticides
Ureas

Benzoylurea


Sardinie (, ) is the seicont-lairgest island in the Mediterranean Sea (efter Sicily an afore Cyprus). It is an autonomous region o Italy, an the nearest land masses are (clockwise frae north) the French island o Corsica, the Italian Peninsula, Sicily, Tunisie an the Spaingie Balearic Islands.

The name Sardinie is frae the pre-Roman noun sard, romanised as sardus (feminine sarda); that the name haed a releegious connotation is suggestit frae its uise an aa as the adjective for the auncient Sardinie meethological hero-god Sardus Pater "Sardinie Faither" (misunnerstuid bi mony modren Sardinies/Italians as being "Faither Sardus"), as well as being the stem o the adjective "sardonic". Sardinie wis cawed Ichnusa (the Laitinised form o the Greek Hyknousa), Sandalion, Sardinia an Sardo bi the auncient Greeks an the Romans.

Islands o Italy
Mediterranean islands
NUTS 2 statistical regions o the European Union
Wine regions o Italy
Autonomous regions o Italy

Sardinie


The Radcliffe Line became the international border between India and Pakistan (which also included what is now Bangladesh) during the partition of India. The line divided Bengal into Indian held West Bengal and East Bengal which became East Pakistan in 1956. The line was decided by the Border Commissions headed by , who was to divide equitably  of territory with 88 million people.
The line took effect on 17 August 1947 after the Partition of India. When the partition was implemented, there were some problems:
The Chittagong Hill Tracts had a moslty Buddhist population, but they were given to East Pakistan (now Bangladesh).
To counterbalance the relatively small share of Gurdaspur district awarded to Pakistan, Radcliffe attempted to instead transfer Ferozpur and Zira tehsils in Muslim-Majority Ferozpur District to Pakistan. This was opposed by the Maharaja of Bikaner because Harike headworks on the confluence of the Sutlej and the Beas rivers, from where a canal originated, was the only source of water for his desert state was in Ferozepore. It was only after he threatened Lord Louis Mountbatten, that he would accede his princely state to Pakistan if Firozpur was awarded to West Punjab province, that the award was changed at the last minute and all of Firozpur District was awarded to East Punjab in the Republic of India.
The Gurdaspur District was moslty Muslim, but was given to India.
Sometimes the line  divided villages, so one part of the village was in each country. At other instances, it went through houses, different rooms of the same house were in different countries.

Related pages
 Punjab (India)
 Bengal (India)

Borders of Pakistan
Borders of India
Geography of Bangladesh
Pakistan Movement
Partition of India

Radcliffe Line


Ella Enchanted is a Newbery Honor book. It was written by Gail Carson Levine. It was published in 1997. It is also the title of the American movie based on the novel, released April 9, 2004. The movie was directed by Tommy O'Haver and starred Anne Hathaway and Hugh Dancy. The story is a retelling of Cinderella featuring various mythical creatures including elves, ogres, dwarves and giants.

1997 books
American children's books
Newbery Honor books
Movies about giants

Ella Enchanted


Rigor Mortis, the first sign of post-mortem decomposition, literally translates to 'stiffness of death' in Latin. As the name suggest, rigor mortis is the process in which a body stiffens after death. During this process, all the muscles in the body contract, and they do not relax for approximately 36 hours.

Three to four hours after death, bodies begin to show signs of rigor mortis, and all muscles are fully contracted after 12 hours.
The use of muscles in everyday actions causes the filaments in our muscles to knit together. When we stop using the muscles, the Adenosine triphosphate (the energy within the cell - ATP) helps untangle the filaments. But when someone dies, their body no longer can create ATP, so the muscles are unable to untangle, so they remain contracted.
Rigor mortis ends when autolysis (the self-digestion of cells) takes place. Post mortem, the cell digests its own walls, and the muscles break down, meaning they no longer have the strength to remain rigid.

Death

Rigor mortis


The theory known as spontaneous generation held that complex, living organisms are generated by decaying organic substances. Mice might spontaneously appear in stored grain or maggots could spontaneously appear in meat.

According to Aristotle it was a readily observable truth that aphids arise from the dew which falls on plants, fleas from putrid matter, mice from dirty hay, crocodiles from  logs rotting at the bottom of bodies of water, and so forth. In the 17th century these things started to be questioned.
Sir Thomas Browne wrote a book called Pseudodoxia Epidemica. He subtitled it Enquiries into Very many Received Tenets, and Commonly Presumed Truths. He published it in 1646. He wrote it as an attack on false beliefs and "vulgar errors".

Scientists failed to accept the conclusions he reached. For example, Alexander Ross, a scientist who lived at the same time as Browne, wrote about it: "To question this (he meant: to question spontaneous generation) is to question reason, sense and experience.  If he doubts of this let him go to Egypt, and there he will find the fields swarming with mice, begot of the mud of Nylus, to the great calamity of the inhabitants."

In 1546 the physician Girolamo Fracastoro theorized that epidemic diseases were caused by tiny, invisible particles or "spores", which might not be living creatures, but this was not widely accepted. Next, Robert Hooke published the first drawings of a microorganism in 1665. He is also credited for naming the cell which he discovered while observing cork samples.

In 1676, Anthony van Leeuwenhoek discovered microorganisms that were probably protozoa and bacteria. This sparked new interest in the microscopic world.

The first step was taken by the Italian Francesco Redi. In 1668, Redi proved that no maggots appeared in meat when flies were prevented from laying eggs.  From the 17th century onwards it was gradually shown that, at least in the case of all the higher and readily visible organisms, the previous sentiment regarding spontaneous generation was false. The alternative seemed to be omne vivum ex ovo: that every living thing came from a pre-existing living thing (literally, everything from an egg).

In 1768 Lazzaro Spallanzani proved that microbes came from the air, and could be killed by boiling. Yet it was not until 1861 that Louis Pasteur performed a series of careful experiments. With these experiments, Pasteur proved that organisms such as bacteria and fungi do not appear in nutrient-rich media of their own accord in non-living material. This experiment supported cell theory.

References

Related page
Origin of life

Philosophy
Biology

Spontaneous generation


Aya dua harti ngeunaan watesan gerak Brown: hiji, dina fénoména fisik salaku gerak partikel dina fluida nu mangrupa gerak acak, sarta nu séjénna dina modél matematik nu dipaké pikeun ngajelaskeun hal éta.

Modél matematik bisa ogé digunakeun keur ngajelaskeun lobana fénoména séjén anu teu kasusun (ku matematik séjénna) ku gerak acak partikel. Nu biasa dipaké conto séjénna nyaéta turun unggahna pasar stok (Ing. stock market), sarta conto penting séjénna evolusi karakter fisik dina rekaman fosil.

Gerak Brown mangrupa prosés stokastik pangbasajanna dina domain kontinyu, and it is a limit of both simpler (see random walk) and more complicated stochastic processes. This universality is closely related to the universality of the normal distribution. In both cases, it is often mathematical convenience rather than actual accuracy as modéls that dictates their use. All three quoted examples of Brownian motion are cases of this: it has been argued that Lévy flights are a more accurate, if still imperfect, modél of stock-market fluctuations; the physical Brownian motion can be modélled more accurately by more general diffusion process; and the dust hasn't settled yet on what the best modél for the fossil
record is, even after correcting for non-Gaussian data.

Sajarah gerak Brown

Gerak Brown kapanggih ku ahli biologi Robert Brown taun 1827. The story goes that Brown was studying pollen particles floating in water under the
microscope, and he observed minute particles within vacuoles in the pollen grains executing the jittery motion that now béars his name. By doing the same with particles of dust, he was able to rule out that the motion was due to pollen being "alive", but it remained to explain the origin of the motion. Nu pangheulana méré téori ngeunaan gerak Brown taya lian ti Albert Einstein taun 1905.

At that time the atomic nature of matter was still a controversial idéa. Einstein observed that, if the kinetic theory of
fluids was right, then the molecules of water would move at random and so a small particle would receive a random
number of impacts of random strength and from random directions in any short period of time. This random bombardment by
the molecules of the fluid would cause a sufficiently small particle to move in exactly the way described by Brown.

Dadaran modél matematis

Sacara matematik, gerak Brown mangrupa prosés Wiener nu mana sebaran kondisional probailiti tina posisi partikel dina waktu t+dt, nu dina posisi waktu t nyaéta p, mangrupa sebaran normal mibanda mean p+μ dt sarta varian σ2 dt; paraméter μ mangrupa simpangan kecepatan, sarta paraméter σ2 mangrupa power noise. These properties cléarly establish that Brownian motion is Markovian (i.e. it satisfies the Markov property). Brownian motion is related to the random walk problem and it is generic in the sense that many different stochastic processes reduce to Brownian motion in suitable limits.

In fact, the Wiener process is the only time-homogeneous stochastic process with independent increments and which is continuous in probability. These are all réasonable approximations to the physical properties of Brownian motion.

The mathematical théory of Brownian motion has been applied in contexts ranging far beyond the movement of particles in fluids. For example, in the modérn théory of option pricing, asset classes are sometimes modéled as if they move according to a Brownian motion with drift.

It turns out that the Wiener process is not a physically réalistic modél of the motion of Brownian particles. More sophisticated formulations of the problem have led to the mathematical théory of diffusion processes. The accompanying equation of motion is called the Langevin equation or the Fokker-Planck equation depending on whether it is formulated in terms of random trajectories or probability densities.

Tempo ogé

osmosis, tangkal brown (Ing. brownian tree), ultramikroskop, Brownian ratchet

Tumbu kaluar
 Edward Nelson, Dynamical Theories of Brownian Motion (1967) PDF of this out of print book available on the author's webpage.

Prosés stokastik

Gerak Brown


The Zaragoza Birthplace State Historic Park is located  adjacent to Presidio La Bahía in Goliad State Park and Historic Site, Goliad County in the U.S. state of Texas.  An amphitheater and bronze statue of Ignacio Zaragoza are also on the grounds.

General Zaragoza
Ignacio Zaragoza was a hero of the Battle of Puebla, which is commemorated each year by Cinco de Mayo celebrations. On May 5, 1862, General Zaragoza and 600 of his forces repelled 6,500 French forces in the city of Puebla, and prevented a French invasion into Mexico.

The house
Zaragoza was born in Goliad on this site March 24, 1829. In September 1961, the county of Goliad donated  at Zaragoza's birth site, for a memorial in his honor. The Texas Parks and Wildlife Department reconstructed his birth home on the foundation. Architectural plans were drawn up for the Parks Department by Raiford Stripling of San Augustine. Stein Lumber Company of Fredericksburg completed construction December 1974.  The birthplace was opened to the public on the 114th anniversary of Cinco de Mayo, May 5, 1976. The site also includes an amphitheater.

A  bronze statue to commemorate Zaragoza was donated by the people of Puebla, Mexico and unveiled on September 13, 1980. It is located on the grounds of the birthplace in front of the amphitheater.

Facilities, hours, admission
Goliad State Park is open 7 days a week. Entrance fees apply. The Zaragoza house is located outside the park grounds about one mile south of the entrance to Goliad State Park
. Group tours need to be arranged in advance.

The Texas State Park Store gift shop is located on Goliad park grounds.

Goliad Park facilities also contain restrooms, a museum, and a playground.

See also
Museums in the Texas Gulf Coast
National Register of Historic Places listings in Goliad County, Texas

References

External links
Zaragoza Birthplace State Historic Site

History museums in Texas
Protected areas of Goliad County, Texas
Texas state historic sites
Protected areas established in 1976
Museums in Goliad County, Texas
Birthplaces of individual people
1976 establishments in Texas

Zaragoza Birthplace State Historic Site


In cell biology, focal adhesions (also cell–matrix adhesions or FAs) are large macromolecular assemblies through which mechanical force and regulatory signals are transmitted between the extracellular matrix (ECM) and an interacting cell. More precisely, focal adhesions are the sub-cellular structures that mediate the regulatory effects (i.e., signaling events) of a cell in response to ECM adhesion.

Focal adhesions serve as the mechanical linkages to the ECM, and as a biochemical signaling hub to concentrate and direct numerous signaling proteins at sites of integrin binding and clustering.

Structure and function
Focal adhesions are integrin-containing, multi-protein structures that form mechanical links between intracellular actin bundles and the extracellular substrate in many cell types. Focal adhesions are large, dynamic protein complexes through which the cytoskeleton of a cell connects to the ECM. They are limited to clearly defined ranges of the cell, at which the plasma membrane closes to within 15 nm of the ECM substrate. Focal adhesions are in a state of constant flux: proteins associate and disassociate with it continually as signals are transmitted to other parts of the cell, relating to anything from cell motility to cell cycle. Focal adhesions can contain over 100 different proteins, which suggests a considerable functional diversity. More than anchoring the cell, they function as signal carriers (sensors), which inform the cell about the condition of the ECM and thus affect their behavior. In sessile cells, focal adhesions are quite stable under normal conditions, while in moving cells their stability is diminished: this is because in motile cells, focal adhesions are being constantly assembled and disassembled as the cell establishes new contacts at the leading edge, and breaks old contacts at the trailing edge of the cell. One example of their important role is in the immune system, in which white blood cells migrate along the connective endothelium following cellular signals to damaged biological tissue.

Morphology

Connection between focal adhesions and proteins of the extracellular matrix generally involves integrins. Integrins bind to extra-cellular proteins via short amino acid sequences, such as the RGD motif (found in proteins such as fibronectin, laminin, or vitronectin), or the DGEA and GFOGER motifs found in collagen. Integrins are heterodimers which are formed from one beta and one alpha subunit. These subunits are present in different forms, their corresponding ligands classify these receptors into four groups: RGD receptors, laminin receptors, leukocyte-specific receptors and collagen receptors. Within the cell, the intracellular domain of integrin binds to the cytoskeleton via adapter proteins such as talin, α-actinin, filamin, vinculin and tensin. Many other intracellular signalling proteins, such as focal adhesion kinase, bind to and associate with this integrin-adapter protein–cytoskeleton complex, and this forms the basis of a focal adhesion.

Adhesion dynamics with migrating cells
The dynamic assembly and disassembly of focal adhesions plays a central role in cell migration. During cell migration, both the composition and the morphology of the focal adhesion change. Initially, small (0.25μm²) focal adhesions called focal complexes (FXs) are formed at the leading edge of the cell in lamellipodia: they consist of integrin, and some of the adapter proteins, such as talin, paxillin and tensin. Many of these focal complexes fail to mature and are disassembled as the lamellipodia withdraw. However, some focal complexes mature into larger and stable focal adhesions, and recruit many more proteins such as zyxin. Recruitment of components to the focal adhesion occurs in an ordered, sequential manner. Once in place, a focal adhesion remains stationary with respect to the extracellular matrix, and the cell uses this as an anchor on which it can push or pull itself over the ECM. As the cell progresses along its chosen path, a given focal adhesion moves closer and closer to the trailing edge of the cell. At the trailing edge of the cell the focal adhesion must be dissolved. The mechanism of this is poorly understood and is probably instigated by a variety of different methods depending on the circumstances of the cell. One possibility is that the calcium-dependent protease calpain is involved: it has been shown that the inhibition of calpain leads to the inhibition of focal adhesion-ECM separation. Focal adhesion components are amongst the known calpain substrates, and it is possible that calpain degrades these components to aid in focal adhesion disassembly

Actin retrograde flow
The assembly of nascent focal adhesions is highly dependent on the process of retrograde actin flow. This is the phenomenon in a migrating cell where actin filaments polymerize at the leading edge and flow back towards the cell body. This is the source of traction required for migration; the focal adhesion acts as a molecular clutch when it tethers to the ECM and impedes the retrograde movement of actin, thus generating the pulling (traction) force at the site of the adhesion that is necessary for the cell to move forward. This traction can be visualized with traction force microscopy. A common metaphor to explain actin retrograde flow is a large number of people being washed downriver, and as they do so, some of them hang on to rocks and branches along the bank to stop their downriver motion. Thus, a pulling force is generated onto the rock or branch that they are hanging on to. These forces are necessary for the successful assembly, growth, and maturation of focal adhesions.

Natural biomechanical sensor
Extracellular mechanical forces, which are exerted through focal adhesions, can activate Src kinase and stimulate the growth of the adhesions. This indicates that focal adhesions may function as mechanical sensors, and suggests that force generated from myosin fibers could contribute to maturing the focal complexes.
This gains further support from the fact that inhibition of myosin-generated forces leads to slow disassembly of focal adhesions, by changing the turnover kinetics of the focal adhesion proteins.

The relationship between forces on focal adhesions and their compositional maturation, however, remains unclear. For instance, preventing focal adhesion maturation by inhibiting myosin activity or stress fiber assembly does not prevent forces sustained by focal adhesions, nor does it prevent cells from migrating. Thus force propagation through focal adhesions may not be sensed directly by cells at all time and force scales.

Their role in mechanosensing is important for durotaxis.

See also

Actin
TES (protein)
Paxillin

References

External links
MBInfo - Focal Adhesion
MBInfo - Focal Adhesion Assembly
MBInfo - Regulation of Focal Adhesion Assembly
AdhesomeFAnetwork  Database with all known focal adhesion proteins and their biochemical interactions
 Intercellular Connections
 Zaidel-Bar Cell Adhesion Lab

Cell biology
Cell movement
Cell signaling
Actin-based structures

Focal adhesion


Northern Italy (Italia Settentrionale, Italia del Nord, Padania, Alta Italia, Norditalia or just Nord) is an area that is made up of two areas in Italy:

North-West (Nord-Ovest): Aosta Valley, Piedmont, Lombardy, Liguria;
North-East (Nord-Est): Friuli-Venezia Giulia, Veneto, Trentino-Alto Adige/Südtirol, Emilia-Romagna.
Northern Italy is more a business area compared to the south and is colder. People from the south sometimes emigrate to the north because of this.
This region has 26,835,082 inhabitants and an area of 46,301 mi² (119,921 km²). The largest city is Milan. It is generally seen as having a higher wealth than the southern regions of Italy. This is due to the 'North-South' Divide which is said to split the country in half in terms of means of development.

Geography of Italy

Northern Italy


Gannett Government Media was formerly the Army Times Publishing Company. It is a United States company which publishes newspapers, magazines, Web sites, and other publications about the U.S. and other militaries.  It was Founded in 1940 and was purchased by the Gannett Company in August 1997.

It publishes four weekly newspapers aimed at current and former U.S. military personnel, collectively called the Military Times Media Group: Army Times (founded 1940), Navy Times (founded 1951), Air Force Times (founded 1947), and Marine Corps Times.

Its Defense News Media Group publishes Defense News (founded 1986), Armed Forces Journal (founded in 1863), Training & Simulation Journal and C4ISR Journal. The company also publishes Federal Times.

According to a Huffington Post AOL News online news article from Boston, Massachusetts by Jim Finkle of Thomson Reuters, dated Wednesday, June 29, 2011:
"Hackers broke into a Gannett Co database containing personal information about subscribers to publications read by U.S. government officials, military leaders, and rank-and-file soldiers, the media company said on Tuesday."

Notes

Other websites

Publishing companies of the United States
Companies based in Virginia
1940 establishments in the United States

Gannett Government Media


This article is about the medieval bastide near Condom-en-Armagnac. Other meanings are at Valence

Valence-sur-Baïse is a city in the Gers department of the Midi-Pyrénees region in France. It is near Condom-en-Armagnac. It was founded in 1274 by Gerald V, Count of Armagnac, and the Cistercian Abbey of Flaran as a Bastide (a fortified city). In 1999, 1151 people lived there. There is an old cisercian abbey at the place. Today the abbey serves as a cultural center. There is also a public washing basin, and a port, where ships can land.

Bastides
Communes in Gers

Valence-sur-Baïse


The Ohio Players were a funk and R&B band from the United States. The group formed in 1959. They were best known for the songs "Fire", "Funky Worm" and "Love Rollercoaster". This group was most popular in the 1970s. They were from Dayton, Ohio.

The group's first big song was "Funky Worm". The song hit the Top 20 on the Billboard Hot 100. It also hit #1 on the Billboard R&B chart.

They had seven Top 40 songs between 1973 and 1976. The songs included "Fire" in 1975 and "Love Rollercoaster" in 1976.

References

American R&B bands
Musicians from Dayton, Ohio
1959 establishments in the United States
20th-century establishments in Ohio

Ohio Players


Bir Lahmar is a toun in soothren Tunisie locatit atween Medenine 15 mile north an 30 mile sooth o Medinine an Tataouine respectively. It is surroondit bi the muntains o Jebel Dahar in the wast an the coastal plain o the east Djeffara.

Attacht tae the Tataouine Govrenorate, it is a municipality o 8418 inhabitants.

As its name implies ("well red" in Arabic), the ceety grew aroond a water source, valuable component in an aurie traditionally covered bi desert caravans.

See an aa
Leet o ceeties in Tunisie

References

Populatit places in Tataouine Govrenorate
Communes o Tunisie

Bir Lahmar


Zalutumumab (proposed trade name HuMax-EGFR) is a fully human IgG1 monoclonal antibody (mAb) directed towards the epidermal growth factor receptor (EGFR).  It is a product developed by Genmab in Utrecht, the Netherlands. Specifically, zalutumumab is designed for the treatment of squamous cell carcinoma of the head and neck (SCCHN), a type of cancer.

Mechanism of action
Zalutumumab works through inhibition of the EGFR signal.  The EGFR is a receptor tyrosine kinase. Its structure includes an extracellular binding domain, a transmembrane lipophilic segment, and an intracellular tyrosine kinase domain.

Mechanism of EGFR
EGFR is over-expressed by many tumor cells. Upon binding by a ligand, such as the epidermal growth factor or TGF alpha, dimerization occurs, leading to autophosphorylation on the intracellular tyrosine residues.  Following phosphorylation, the Grb2-SOS signaling complex is stimulated.  This causes the activation of the G protein RAS through the exchange of guanosine diphosphate (GDP) for guanosine triphosphate (GTP).  The exchange of GDP for GTP induces a conformational change of RAS to allow it to bind to Raf-1.  Raf-1 is then activated through another multistep mechanism in which dephosphorylation of inhibitory sites by protein phosphatase 2A (PP2A), as well as the phosphorylation of activating sites by p21 activated kinase (PAK) occurs.  After this, Raf-1 activates MAPK/ERK kinase (MEK), which then goes on to activate extracellular-signal-regulated kinase (ERK).  ERK is then able to enter the cell nucleus and control gene expression by phosphorylating various transcription factors, such as Elk-1. It is from there that the specific gene transcription occurs to initiate the cell cycle. Through this mechanism, apoptosis is inhibited, angiogenesis, migration, adhesion, and invasion occur.  Each of these is a functional element to the progression and development of cancer, which is defined as an abnormal growth of cells with a tendency to proliferate in an uncontrolled way and, in some cases, to metastasize.

Mechanism of zalutumumab
In order to combat SCCHN, zalutumumab was designed to inhibit the EGFR signaling.  Specifically, it binds to the EGFR Domain III on the cell surface.  This locks the receptor in an inactive conformation, making the drug an inverse agonist. In doing this it is also acting as a competitive antagonist for the EGF ligand. In the inactive conformation, the distance between the intracellular tyrosine kinase residues is larger, which inhibits dimerization. Phosphorylation is consequently inhibited, so that no signal is released.  Without a signal, cell cycle characteristics to enhance tumor growth are inhibited and the cancer progression is suppressed.

This is not the only way in which zalutumumab works. It also is responsible for some antitumor affects through antibody-dependent cellular cytotoxicity (ADCC). The Fab, or fragment antigen binding region of the antibody, binds to the antigen on the EGFr expressing tumor cells. Through an immunological response, the body's natural killer (NK) cells, which are a type of lymphocyte, recognize and bind to the Fc portion on the antibody through an Fc receptor, CD16. The NK cell is then activated through the cross linking of the Fc receptors which sends a signal to induce apoptosis and cell death. The target tumor cell is then destroyed.

Developmental status
2009: Zalutumumab treatment was approved for Fast Track status by the U.S. Food and Drug Administration for patients suffering from SCCHN who have failed standard therapies and have no other options.  The drug has undergone pre-clinical and Phase I and II studies and is also in Phases I and II for SCCHN front-line with chemo-radiation and SCCHN with radiation.  Additionally, a Phase II is under way for SCCHN and Phase III studies are also being performed for SCCHN and SCCHN front-line with radio therapy.

2010:A phase III study (of zalutumumab as an addition to 'best supportive care' in patients after failed standard platinum-based chemotherapy) reported a non-significant improvement in overall survival, and a significant 61% improvement in Progression-free survival

2014:A study of zalutumumab as addition to chemoradiation for SCCHN showed no benefit, and 94% developed a skin rash (11% severe enough to discontinue).

2015:Genmab not proceeding with zalutumumab.

References

Monoclonal antibodies for tumors
Abandoned drugs

Zalutumumab


Philip of Naples and Sicily, "Duke of Calabria", Infante of Spain (13 June 1747 – 19 September 1777) was the eldest son and heir-apparent of Charles III of Spain, but was excluded from the succession to the thrones of Spain and Naples due to his imbecility. His younger brothers, Charles IV of Spain and Ferdinand I of the Two Sicilies replaced him in the succession. When his father became King of Spain in 1759, Philip remained in Naples where he lived until his death from smallpox at the age of 30.

Heir apparent
Born at the Royal Palace of Portici in the Kingdom of Naples, he was the sixth child and eldest son of Charles VII and V, then King of Naples and Sicily, and his wife Maria Amalia of Saxony. His birth was a joyful event since his parents previously had five princesses, three of whom had died in childhood. The Prince was baptized Filippo Antonio Gennaro Pasquale Francesco de Paula. His grandfather, King Philip V of Spain, in whose honor he was named, had died on 9 July 1746. The child's godparents were his paternal uncle and aunt, King Ferdinand VI of Spain and Barbara of Portugal. As the heir apparent to his father, he was given the title of Duke of Calabria; the traditional title for the heir apparent of the Kingdom of Naples. Although he was born plump and rosy, it was soon evident that there was something wrong with him. His wet nurses had to be changed several times and the child had epileptic fits. As he grew up, it was confirmed that he had disabilities, especially his peculiar face. According to one observer, the prince had "a great heaviness of head, which makes him gloomy and ill-humored".

In 1754, the ambassador of Sardinia reported that " the prince royal does not appear to enjoy good health"  adding that "there is something in his eyes that does not harmonize with the rest of his features. I have been assure[d] that although he is seven years old he does not speak, and that he can scarcely utter a word." However, his parents tried to conceal his deficiencies both from the public and from themselves making the child appear in court ceremonies as if there was nothing wrong with him. Until the age of seven Philip remained with his sisters and younger brothers under the care of a governess. In 1755, he was placed with his brother Charles under the tutorship of the Prince of San Nicandro.

Exclusion from the succession
The death of his half-uncle, King Ferdinand VI of Spain, on August 10, 1759, forced the parents to confront the status of their son. Since Charles III was to depart to Spain to take possession of the Spanish crown, he had to abdicate the thrones of Naples and Sicily in favour of a son. A committee of high officials, magistrates and six physicians examined the mental state of the Prince, who was twelve years old at the time, to determine his capacity to reign. The Prince was kept under close observation for two weeks after which the committee declared that his mental state made him incapable to govern and he was thus excluded from the succession to the thrones due to his mental disabilities. His younger brothers Charles and Ferdinand replaced him in the lines of succession. Philip remained in Naples out of sight from the Neapolitan courts at the palaces of Capodimonte and the newly constructed Palace of Caserta. His brother Ferdinand visited him and showed him affection treating him almost like a mascot.

"He is  rarely visible," wrote Samuel Sharp, "but the regency think proper to exhibit him a few times a year, namely, when the king removes from Naples to Portici, and from Portici to Naples. I took the opportunity, when the family came to town, of entertaining myself with the spectacle... The administration acts wisely in exposing him now and then to the eyes of the public, as the very sight of him is a full vindication of their conduct in regard to the sentence of idiotism and disinheritance passed on him some years ago. The court was in mourning, but he was as well dressed as a youth in mourning can be, and his hair as well combed and as well powdered. With all these advantages, however, the very first glance of him convinced me that he wants every one faculty of the mind. He has that wandering roll of the eye which is peculiar to idiots and new born infants, who, not having the endowment of thought and reflection, consequently cannot fix their attention to one object. There are some knavish quacks, and some silly doctors, who say the cure is not impossible, and that he may be restored to his senses... By what I can learn, he leads a happy kind of animal life. He eats and drinks with much pleasure, is subject to no gust of passion, and enjoys such infantile amusements as a child in arms may be supposed to enjoy "

Later life

According to William Hamilton who was the British Ambassador to the Kingdom of Naples, Infante Philip "was  treated with certain distinctions, having chamberlains placed about him in constant attendance, who watched him with unremitting attention; as otherwise he would have committed a thousand excesses. Care was particularly taken to keep him from having any connection with the other sex, for which he manifested the strongest propensity; but it became at last impossible to prevent him altogether from attempting to emancipate himself in this respect. He has many times eluded the vigilance of his keepers, and on seeing ladies pass through the portents of the place, would attack them with the same impetuosity as Pan or the Satyrs are described by Ovid, when pursuing the Nymphs; and with the same intentions. More than one lady of the Court has been critically rescued from his embraces. On particular days of the year, he was allowed to hold a sort of Court, when the Foreign ministers repaired to his apartments to pay their compliments to him. His greatest amusement consisted in having his hand held up by his attendants while gloves were put upon it, one larger than another to the number of fifteen or sixteen.

In September 1777, Infante Philip contracted smallpox. The King and Queen, fearing contagion, fled to Caserta.  Philip died at the Palace of Portici in Naples at the age of 30. He was buried at the Basilica of Santa Chiara in Naples.

Ancestry

Notes

References
Acton, Harold. The Bourbons of Naples (1734-1825). Prion books limited, London, 1989 (first published in 1957).
Rubio, Maria José. Reinas de España. La Esfera de los Libros, Madrid, 2009.

|-

House of Bourbon (Spain)
Heirs apparent who never acceded
Knights of the Golden Fleece of Spain
1747 births
1777 deaths
Neapolitan princes
Sicilian princes
Hereditary Princes of Naples
Spanish infantes
Dukes of Calabria
Deaths from smallpox
Burials at the Basilica of Santa Chiara
People from Portici
Royalty and nobility with epilepsy
Spanish royalty and nobility with disabilities
Sons of kings

Infante Philip, Duke of Calabria