prompt_front: Answer the question based on the given passages. Only give me the answer and do not output any other words.

Question: Henry Roth and Lewis Mumford are both this nationality?

The following are given passages.
Context 1: Passage 1:
Regional Planning Association of America
The Regional Planning Association of America ("RPAA"), formed by Clarence Stein was an urban reform association developed in 1923   The association was a diverse group of people all with their own talents and skills   The goal of this group was to “connect a diverse group of friends in a critical examination of the city, in the collaborative development and dissemination of ideas, in political action and in city building projects”   Throughout the ten-year span in which the association lasted, five leading members contributed to this goal   Clarence Stein, Benton MacKaye, Lewis Mumford, Charles Harris Whitaker, Alexander Bing, and Henry Wright were the essential backbone of the RPAA  Originally an idea of Clarence Stein’s, through a series of introductions and acquaintances in Washington DC in 1918, the Regional Planning Association began to form 

Founders
Clarence Stein
Clarence Stein attended the Ethical Culture Society’s Workingman’s School, which influenced his interest in the city life and social responsibility through its teaching  Stein was closely influenced by the founder of Ethical Culture, Felix Adler, and teacher, John Lovejoy Elliott, in involvement with movements and committees, such as the Hudson Guild Settlement House and the Progressive Reform movement in New York City at the turn-of-the-century   Therefore, Stein’s enrollment at Workingman’s School proved to be of strong influence on his later interests and achievements   The very principle of the Ethical Culture Society being “that an individual’s growth toward excellence comes from furthering the unlike excellence of others”, exemplifies the basis of Stein’s life achievements through the RPAA 
Stein first met future fellow RPAA members, Henry Wright and Alexander Bing, in Washington (in 1918) through a friend, Charles Whitaker (editor of the JAIA)   In 1920, Stein became the Associate Editor for Community Planning with the Journal of the American Institute of Architects and soon later discovered the idea to create the RPAA including his friends at the JAIA office, including Lewis Mumford, as well as many others  The group included members in various fields of study from architects to union leaders, city officials to writers, and engineers to sociologists  And so, on April 18, 1923, the first official meeting of the Regional Planning Association of America was held   The association began with only a total of eight people present at its first official meeting but it soon grew 

Benton MacKaye
The first major project of the RPAA was that of fellow RPAA member, Benton MacKaye; the Appalachian Trail, a trail which we would refer to today as a greenway, of which he wrote an article in the JAIA two years earlier (“An Appalachian Trail – A Project in Regional Planning”)   The trail was planned to connect a footpath from Maine to Georgia in an attempt to “lead civilization to the wilderness”   The project was not directly implemented by the RPAA, however, their part was successful in introducing their idea to others and helping the various groups of Mountain Clubs come together to create the final project   The majority of the trail was completed by the mid-1930s   From this project came another main goal of the RPAA which was to create “the preservation of large areas of the natural environment, including parts of the wilderness, as a green matrix for shaping a “regional city” and for serving its various-sized, spatially well defined, specialized communities” 

Lewis Mumford
The success in publicizing this project as well as others was in large part due to Lewis Mumford   Mumford was the RPAA’s leading journalist and spokesperson   Having published his first book in 1922, The Story of Utopia, and well on his way with another, Mumford was extremely useful to the association  He worked on not only books and articles related to the RPAA but also wrote/edited policy documents   Mumford also contributed to the group by sharing his interest of Patrick Geddes’ ideas on regional development and planning   Mumford contributed concepts of “a dispersed yet concentrated urban culture integrated with nature” which were integrated along with MacKaye’s concepts into the RPAA’s later projects 

Sunnyside and Radburn
The leading community building experiments conceptualized and implemented by the RPAA were Sunnyside Gardens, Queens and Radburn, New Jersey   Sunnyside started as a small-scale housing development experiment in Queens, New York   The goal was “to produce good homes at as low a price as possible, to make the company’s investment safe, and to use the work of building and selling houses as a laboratory to work out better house and block plans and better methods of building”   Radburn, New Jersey, would be the new and improved built community utilizing the analysis from the Sunnyside community experiment 

through not only his own real estate company and wealth but through his outstanding real estate and business skills   Bing, president of the RPAA, found the funds through outside contributions and personal contribution (more so than any other member) to support the projects of the association   For the Sunnyside community project Bing founded the City Housing Corporation through which he would establish the funding and opportunity to complete the project 

Henry Wright
Henry Wright, known as the analyst due to his never-ending questioning and analysis on projects, worked alongside Stein in site designs and development on such projects as Sunnyside, New York   Studied architecture at the University of Pennsylvania along with work as a landscape architect and site planner, Wright shared many interests with Stein   Close work in 1923 on the Sunnyside Homes development with Stein led to a trip to England in 1924 to study the designs of Unwin and Parker as well as that of Ebeneezer Howard   Though close at the beginning of the association’s organization, Wright went on to establish “The Housing Study Guild” along with several RPAA members which Stein viewed to work more independently than directly with the RPAA’s projects   This slight dispute would be the beginning point of the division and end of the Regional Planning Association of America   In 1933, many members began to move away and/or join various other movements or committees which quickly led to the association's end 

Legacy
The Regional Planning Association of America, led by Clarence Stein, Benton MacKaye, Lewis Mumford, Alexander Bing, Henry Wright, as well as many others started simply as a group of people with similar interests wanting to make a difference in the American towns and cities  Through the collaboration of these five, Clarence Stein – the organizer and manager, Benton MacKaye – the conservationist, Lewis Mumford – the writer, Alexander Bing – the developer-builder, and Henry Wright – the analyst, as well as the many other members, the RPAA conceptualized, experimented, and changed our view of American towns, cities, architecture, and planning in America 
Passage 2:
Lewis Mumford House
The Lewis Mumford House is located on Leedsville Road (Dutchess County Route 2) in the Town of Amenia, New York, United States  It is a white Federal style building dating to the 1830s 
Social philosopher, historian and cultural critic Lewis Mumford and his wife bought the house in the late 1920s, originally using it as a summer house  By the mid-1930s, they decided to make it their permanent residence for a few years  That period extended to more than half a century, the rest of Mumford's life  His experience of living in a rural area informed some of Mumford's thinking about cities and how they should be shaped  In 1999, a few years after his death, the property was  listed on the National Register of Historic Places 

Buildings and grounds
The property listed on the Register consists of two adjoining parcels: a 1 9-acre (7,700 m2) lot with the house and carriage house and a larger 11 7-acre (4 7 ha) open field stretching back to Webutuck Creek  Both are located on the west side of Leedsville Road, a street of large semi-wooded residential lots, most formerly part of larger farms, in the eastern section of Amenia  There is a similar 19th-century farmhouse just across the street  The Mumford property is a half-mile (1 km) south of state highway NY 343 and a similar distance west of the Connecticut state line  The house, carriage house and landscaping on the property are all considered contributing resources to the listing 

House
The main house's east (front) section is a three-bay two-story frame structure on a stone foundation sided in clapboard  It is topped with a side-gabled roof shingled in asphalt, pierced by two brick chimneys at either end  A perpendicular rear wing, similarly sided, is one and a half stories in height, with side entrances and a single-story sunroom added to the rear A single-bay porch with arched pediment and two round columns shelters the main entrance at the northern end of the front facade  All windows have solid wooden shutters  Semicircular windows at the attic level on either side elevation have been boarded in Federal-style crown moldings, pilasters and fielded side panels surround the main entrance  It opens to a small main hall that gives onto a living room with exposed ceiling beams  A study, kitchen and pantry, bathroom and the sunroom complete the first floor  The flooring is wide pine boards  The brick kitchen fireplace has a large mantel and bake oven Two staircases lead up to the second floor  The front one has been opened up to provide more light to the upstairs  The kitchen stair is narrow and steep  The basement has a dirt floor and the original, unfinished stone walls 

Carriage house and landscaping
To the rear of the house, at the end of the driveway, is the former carriage house, modified for use as an automotive garage  It is a single-story post and beam wood pegged structure sided in clapboard with an asphalt-shingled roof  It has a low loft inside, a northern addition to accommodate a car, and three windows on the south side Stone paths lead from the driveway south to the house  They are complemented in the landscaping by mature plantings including ornamental shrubs around the house and curvilinear flower beds in the rear yard  Intersecting paths lead through the woods to the open field in the rear 

History
There is some uncertainty about the age of the house  In his 1982 autobiography Sketches of Life, Mumford gives its construction date as 1837  Research done by New York's State Historic Preservation Office in preparation for the Register nomination found that it might be as much as a decade older Mumford, a mostly self-taught New York City native, and his wife Sophia had lived in Greenwich Village and Sunnyside Gardens in Queens following their 1921 marriage  After the success of Sticks and Stones, his 1924 history of American architecture, critic Joel Elias Spingarn invited him up to his Amenia estate, Troutbeck  The Mumfords spent the summer of 1926 there, and returned in the following years By 1929 they had decided to purchase a property of their own for their summers, and found the house just down the road from Troutbeck  For $2,500 ($43,000 in contemporary dollars), they bought the house and what Mumford later called its "weedy acre"  After seven more summers, the family decided to settle there year-round in 1936, and began adding additional acreage and upgrading the house with electricity and heating to make it livable in wintertime It was a considerable adjustment for the Mumfords, both of whom had up to that point been city dwellers  "There," wrote one scholar three decades later, "the rural life that previously he had only glimpsed became real to him " He took up gardening in earnest, and the Mumfords began landscaping the property, eventually adding paths that opened up vistas across the Webutuck valley to Oblong Mountain on the west  They bought a used 1932 Chevrolet, their first car  Mumford left it to his wife to drive after he nearly crashed it into the maple trees in front of the house on one attempt to learn, and swore never to get behind the wheel again The Mumfords primarily socialized with the Spingarns up the road  They nevertheless appreciated their neighbors' help in lending them tools and garden equipment and watching the house when they were away from it; one large family nearby was extremely helpful with the Mumford children  The experience reinforced Mumford's belief that livable city neighborhoods needed to have "something of the village" in them They told their friends in New York that they initially meant to stay in Amenia for only a few years  But Lewis gradually found the quiet rural environment a good place to write, and it was in the downstairs study that he turned out many of his later major works on the role of cities in civilization and the roots of industrialization  In the early 1940s, after his son Geddes was killed in action during World War II, Mumford recalled his son's childhood in and around the house in Green Memories "We gradually fell in love with our shabby house as a young man might fall in love with a homely girl whose voice and smile were irresistible", Mumford later recalled  "In no sense was this the house of dreams  But over our lifetime it has slowly turned into something better, the house of our realities     [T]his dear house has enfolded and remodeled our family character—exposing our limitations as well as our virtues "Over the rest of their lives, the Mumfords sometimes took residence elsewhere for Lewis's teaching or research positions, up to a year at a time  They always returned to what they called the "Great Good Place"  Mumford's biographer Donald Miller wrote:

In the act of living in this house and making it over it became like a person to them; and like a good friend they grew more fond of it with closer and deeper acquaintance  Every patch garden and lawn, every vista and view, carried the imprint of some of the best hours of their lives 
They made some changes to it, siding the first story in shingles and removing the south chimney  Inside they put bookcases on almost every wall In the 1980s, when Lewis could no longer write due to his advanced age, he retreated to the house  He died there in his bed in 1990, at the age of 94  Sophia followed him seven years later After her death, the house was sold to a local carpenter who decided to restore it to its original appearance and resell it  He removed all the bookcases and the nine layers of linoleum the Mumfords had added to the kitchen floor every time one wore out  Later renovations restored the original siding and chimney In 1999, after being listed on the National Register, the house was again put up for sale with a list price of $375,000  The restorations made it more difficult to sell despite the historic provenance, since it still lacked many amenities sought by contemporary buyers of country houses  It eventually did, and is now an occupied residence again 

See also
National Register of Historic Places listings in Dutchess County, New York
Passage 3:
The City in History
The City in History: Its Origins, Its Transformations, and Its Prospects is a 1961 National Book Award winner by American historian Lewis Mumford 
It was first published by Harcourt, Brace & World (New York) 

Synopsis
Mumford argues for a world not in which technology rules, but rather in which it achieves a balance with nature  His ideal vision is what can be described as an "organic city," where culture is not usurped by technological innovation but rather thrives with it  Mumford contrasts these cities with those constructed around wars, tyrants, poverty, etc  However, the book is not an attack on the city, but rather an evaluation of its growth, how it came to be, and where it is heading, as evidenced by the final chapter "Retrospect and Prospect "
Mumford notes apologetically in his preface that his "method demands personal experience and observation," and that therefore he has "confined [him]self as far as possible to cities and regions [he is] acquainted with at first hand "

Style
Mumford's florid writing style is also "organic" compared to the cold, mechanical style of many history texts   Stylistically, his works are full of metaphors and similes, as well as quotations from famous novelists, giving his prose shades of poetry   He refers to such texts as Great Expectations and Hard Times, sometimes using citations to illustrate to the reader what life was like during the industrial era and the city in which Dickens lived 
Articles have been written on Mumford's use of metaphors and how his works can often be read as "fiction," in the sense that they have narrative flow   That is evident in this book, in which, instead of a human protagonist on which the story centers, we have the city and its growth in a quasi-bildungsroman fashion 

Editions
Hardcover, MJF Books (August 1997) ISBN 978-1-56731-211-9
Paperback, Harvest Books (October 1968) ISBN 978-0-15-618035-1
Passage 4:
Megalopolis
A megalopolis () or a supercity, also called a megaregion, is a group of metropolitan areas which are perceived as a continuous urban area through common systems of transport, economy, resources, ecology, and so on  They are integrated enough that coordinating policy is valuable, although the constituent metropolises keep their individual identities  The megalopolis concept has become highly influential as it introduced a new, larger scale thinking about urban patterns and growth 

Etymology and earlier definitions
The term has specific geographic definitions dating from 1832, when its meaning was "a metropolis," that is, "a very large, heavily populated urban complex" 
In the late 1950s and early 1960s, Jean Gottmann, a professor of political science at the University of Paris and member of the Institute for Advanced Study at Princeton, directed "A Study of Megalopolis" for The Twentieth Century Fund, wherein he described a megalopolis as a "world of ideas"  Gottmann, in his extensive studies, applied the term megalopolis to an analysis of the urbanized northeastern seaboard of the U S , in particular from Boston, Massachusetts to Washington, D C 

Modern definitions
A megalopolis may also be called a megaregion  "Megalopolis" and other similar terms have been used by different scholars and countries to describe similar spatial forms 
A megalopolis, following the work of Gottmann, refers to two or more roughly adjacent metropolitan areas that, through a commonality of systems—e g , of transport, economy, resources, and ecologies—experience a blurring of the boundaries between the population centers, such that while some degree of separation may remain, their perception as a continuous urban area is of value, e g , "to coordinate policy at this expanded scale"  Simply put, a megalopolis (or a megaregion) is a clustered network of big cities  Gottmann defined its population as 25 million, while Doxiadis defined a small megalopolis a similar cluster with a population of about 10 million  America 2050, a program of the Regional Plan Association (RPA), lists 11 megaregions in the United States and Canada 
Megaregions of the United States were explored in a July 2005 report by Robert E  Lang and Dawn Dhavale of the Metropolitan Institute at Virginia Tech  A later 2007 article by Lang and Nelson uses 20 "megapolitan" areas grouped into 10 megaregions  The concept is based on the original "Megalopolis model" Modern interlinked ground transportation corridors, such as rail and highway, often aid in the development of megalopolises  Using these commuter passageways to travel throughout the megalopolis is informally called megaloping, a term coined by Davide Gadren and Stefan Berteau In Brazil, the term megarregião has a legal meaning, different from the English word megaregion: mesoregions of Brazil (mesorregião) and microregions of Brazil (microrregião) 
In China, the official term corresponding to the meaning of "megalopolis" is '城市群' (chéngshì qún), which, in Chinese, was originally coined by Yao Shimou and literally means "city cluster"  A "city cluster" is defined as "[a]n area in which cities are relatively densely distributed in a certain region"  In an older standard, the term was mistranslated as "agglomeration"  In 2019, National Development and Reform Commission (NDRC)  published guidelines and made a distinction from a similar concept "metropolitan area" (都市圈), which is of a smaller scale than a city cluster  In the latest standard terminologies of both economics and urban planning, 城市群 is translated as "city cluster", replacing "agglomeration" 

List of megalopolises
In popular culture
Metropolis
Metropolis is a 1927 German expressionist science-fiction drama film directed by Fritz Lang  Written by Thea von Harbou in collaboration with Lang, it stars Gustav Fröhlich, Alfred Abel, Rudolf Klein-Rogge and Brigitte Helm  Erich Pommer produced it in the Babelsberg Studios for Universum Film A G  (Ufa)  The silent film is regarded as a pioneering science-fiction movie, being among the first feature-length movies of that genre  Filming took place over 17 months in 1925–26 at a cost of over five million Reichsmarks 

Judge Dredd
In the Judge Dredd (1977) comic book series and its spinoff series, Mega-City One is a huge fictional megalopolis-size city-state covering much of what is now the Eastern United States and some of Canada  The exact geography of the city depends on which writer and artist has done which story, but from its first appearance it has been associated with New York City's urban sprawl; originally it was presented as a future New York, which was retconned as the centre of a "Mega-City One" in the very next story  The Architects' Journal placed it at No  1 in their list of "comic book cities" 

Blade Runner
Blade Runner is a 1982 neo-noir science fiction film directed by Ridley Scott, written by Hampton Fancher and David Peoples, and starring Harrison Ford, Rutger Hauer, Sean Young, and Edward James Olmos  It is a loose adaptation of Philip K  Dick's novel Do Androids Dream of Electric Sheep? (1968)  The film is set in a dystopian future Los Angeles of 2019, in which synthetic humans known as replicants are bio-engineered by the powerful Tyrell Corporation to work on off-world colonies  When a fugitive group of replicants led by Roy Batty (Hauer) escapes back to Earth, burnt-out cop Rick Deckard (Ford) reluctantly agrees to hunt them down 

Sprawl trilogy
In William Gibson's Sprawl trilogy, "the Sprawl" is a colloquial name for the "Boston-Atlanta Metropolitan Axis" (BAMA), an urban sprawl environment on a massive scale, and a fictional extension of the real Northeast megalopolis   The Sprawl is a visualization of a future where virtually the entire East Coast of the United States, from Boston to Atlanta, has melded into a single mass of urban sprawl  It has been enclosed in several geodesic domes and merged into one megacity  The city has become a separate world with its own climate, no real night/day cycle, and an artificial sky that is always grey 

Further reading
Hagler, Yoav (November 2009)  "Defining U S  Megaregions" (PDF)  America 2050  Retrieved February 19, 2022 – via RPA org  This work, while dated, is from Associate Planner Yoav Hagler of America 2050, and while not used as a source in this article, is one of the most focused articles available on the American aspects of the title subject  It includes history, methodology, and statistical and other criteria sections, and identifies the U S  megaregions as of its publication date America 2050 Staff (February 19, 2022)  "Megaregions"  America 2050  Archived from the original (homepage) on May 16, 2017  Retrieved February 19, 2022 – via RPA org  Starting point for access to articles from the America 2050 effort, while it was active  Note, an earlier cited article by Matt Taylor, on urban transit issues, appears among the works linked at this home page 

See also
Passage 5:
Critical Mass (book)
Critical Mass: How One Thing Leads to Another, a non-fiction book by English chemist and physicist Philip Ball originally published in 2004, discusses the concept of a "physics of society"  Ball discusses thinkers such as Thomas Hobbes, Lewis Mumford, Emyr Hughes, and Gottfried Achenwall who have attempted to apply (or argue against the use of) physics, chemistry, or mathematics in the study of mass social phenomena  He also discusses how the concept relates to recent research, including his own 

Physics of society
The outlines of Ball's Critical Mass, the most popular of his many noted books, beginning in various circa 2001 lectures, talks, and articles focused on what he calls a 'physics of society', similar to the social physics in the Auguste Comte sense, a subject Ball approaches using statistical mechanics viewing people as atoms or molecules that show characteristic behaviours in bulk  The following is an excerpt of his 2003 talk on the physical modeling of society:
"There seem to be 'laws' [of] social systems that have at least something of the character of natural physical laws, in that they do not yield easily to planned and arbitrary interventions  Over the past several decades, social, economic and political scientists have begun a dialogue with physical and biological scientists to try to discover whether there is truly a 'physics of society', and if so, what its laws and principles are  In particular, they have begun to regard complex modes of human activity as collections of many interacting 'agents' - somewhat analogous to a fluid of interacting atoms or molecules, but within which there is scope for decision-making, learning and adaptation "In his 2004 book, Ball summarizes this to the effect that "to develop a physics of society, we must take a bold step that some might regard as a leap of faith and others as preposterous idealization: particles become people " Nearly as soon as he gives this definition, however, Ball falls back on the two biggest hurdles to this perspective: that of the theories of being alive and of free will, both of which seem to contradict the physics viewpoint 

Other topics
Other topics discussed in the book include the business cycle, random walks, phase transitions, bifurcation theory, traffic flow, Zipf's law, Small world phenomenon, catastrophe theory, the Prisoner's dilemma  The overall theme is one of applying modern mathematical models to social and economic phenomena 

Awards
Critical Mass was the winner of the 2005 Aventis Prize for Science Books and the 2005 Royal Society Winton Prize for Science Books 

See also
Critical mass (sociodynamics)
Psychohistory
Historical materialism
Network economics
Passage 6:
Technics and Civilization
Technics and Civilization is a 1934 book by American philosopher and historian of technology Lewis Mumford   The book presents the history of technology and its role in shaping and being shaped by civilizations   According to Mumford, modern technology has its roots in the Middle Ages rather than in the Industrial Revolution  It is the moral, economic, and political choices we make, not the machines we use, Mumford argues, that have produced a capitalist industrialized machine-oriented economy, whose imperfect fruits serve the majority so imperfectly 

Background
Apart from its significance as a monumental work of scholarship in several disciplines, Mumford explicitly positioned the book as a call-to-action for the human race to consider its options in the face of the threats to its survival posed by possible ecological catastrophe or industrialised warfare  Technics and Civilization is the first book in Mumford's four-volume Renewal of Life series, followed by The Culture of Cities (1938), The Condition of Man (1944), and The Conduct of Life (1951) 

Synopsis
Mumford divides the development of technology into three overlapping phases: eotechnic (Greek, eos meaning "dawn"), paleotechnic and neotechnic The first phase  of technically civilized life (AD 1000 to 1800) begins with the clock, to Mumford the most important basis for the development of capitalism because time thereby becomes fungible (thus transferable)   The clock is the most important prototype for all other machines   He contrasts the development and use of glass, wood, wind and water with the inhumanly horrific work that goes into mining and smelting metal   The use of all of these materials, and the development of science during the eotechnic phase, is based on the abstraction from life of the elements that could be measured   He approves those people, cities and cultures who strove for a harmonious balance between the senses and the freedom from labor provided by science 

The second phase, the paleotechnic (roughly 1700 to 1900), is "an upthrust into barbarism, aided by the very forces and interests which originally had been directed toward the conquest of the environment and the perfection of human nature "  Inventions of the paleotechnic are made by men trying to solve specific problems rather than hunting for general scientific principles; in fact, scientific learning is devalued by men of business   The invention of coal-fired steam powered factories and the installation of capital-intensive machinery leads to a necessarily gigantic round-the-clock scale of production supported by unskilled machine tenders  Labour becomes a commodity, rather than an inalienable set of skills, the labourer who tended machines, lived in slums, and was paid starvation wages, became physically stunted and socially and spiritually stultified   Mumford notes that the death rate of urban slums compares unfavorably to the agricultural worker of the same time period, and furthermore that life in the nineteenth century compares unfavorably to cleanliness and standards of living available to workers in thirteenth century cities   He also identifies iron as the primary building material of the paleotechnic, and skyscrapers, bridges and steamships as première accomplishments of the age   War and mass sport he saw as social releases from mechanized life, and the hysteric duties of wartime production (or even the hysteria of a baseball team's victory) is a natural outgrowth of the tensions and structures of such paleotechnic life 
In describing the neotechnic age (from about 1900 to Mumford's present, 1930), he focuses on the invention of electricity, freeing the factory production line from the restrictions of coal through the addition of small electric motors to individual machines, and freeing the laborer to create small but competitive factories   Mumford presciently notes that a small producer can deliver what is needed when it is needed more efficiently than paleotechnic assembly lines  The neotechnic phase he saw was dominated by men of science, rather than mechanically apt machinists  Rather than pursuing accomplishments on the scale of the trains, it is concerned with the invisible, the rare, the atomic level of change and innovation   Compact and lightweight aluminum is the metal of the neotechnic,  and communication and information—even inflated amounts—he claimed was the coin 


== Notes ==
Passage 7:
Jack Hillmer
Jack Hillmer (1918–2007) was an American architect based in San Francisco, California   An exponent of what Lewis Mumford called the "Bay Region style," Hillmer is known for his meticulously hand-crafted modernist homes built from redwood   Jack Hillmer's most notable projects include the Ludekens house on Belvedere island, the Munger house in Napa, and the Cagliostro house in Berkeley   Architectural writer Alan Hess called Jack Hillmer "one of the most original architects produced by California "

Early life
Hillmer was born and raised in Texas   As a 15-year-old boy, he travelled to Chicago with his mother, a cousin and a friend to visit the 1933 World's Fair   It was there, in the California exhibit, that he encountered the redwood boards that would become a key feature of his later architectural practice:  four-foot by twenty-foot planks displayed under spotlights to highlight one of that state's key products   Several years later Hillmer received a scholarship to the University of Texas, where he enrolled in architecture   After college, Hillmer joined the air force, and was stationed in San Diego   Hillmer used his time-off during the war to explore the new modernist buildings that were being built in southern California, including renting a room in the Pueblo Rivera Apartments by R  M  Schindler, and living for a time at the La Jolla Art Center by Irving Gill   Toward the end of the war, Hillmer visited Frank Lloyd Wright at Taliesen West in Scottsdale, Arizona   Hillmer was invited by Wright to join his Taliesen Fellowship, but Hillmer declined despite his appreciation for Wright's work Hillmer first visited the San Francisco Bay Area in 1945, when he flew up the coast to Hamilton Air Force Base to deliver a new bomber on which he had worked as a draftsman   Hillmer was transferred to Travis Air Force Base in Solano County, California toward the end of the war   After he was discharged, Hillmer decided to remain in the Bay Area, where he opened an architectural office with his friend Warren Callister at 425 Bush Street in San Francisco 

Career
Hillmer and Callister's first commission was the Haines and Betty Hall house in 1947, a house with an abstract geometry built from redwood boards that were reclaimed from a dismantled barn on the property   The house would later be published in Life magazine Shortly after the Hall house was published, Callister and Hillmer dissolved their partnership and set up individual practices   Hillmer's first commission on his own came in 1948 from Fred Ludekens, a successful graphic artist who had purchased a lot on Belvedere Island with views across the Bay to San Francisco   Arguably Hillmer's most successful design, the Ludekens house featured rough redwood walls and airplane wing-like ceilings that soared above the walls of the building, seemingly supported only by glass   Shortly after its completion in 1951, the Ludekens House would be featured in Architectural Forum In the early 1950s, Hillmer was invited to teach as a lecturer at the University of California, Berkeley by the dean of the architecture school, William Wurster, and again in the 1960s by Charles Moore   Several significant commissions followed over the next three decades, including the Milton Munger house in Napa (1950), the Owen Stebbins house in Kent Woodlands (1960), the John and Patti Wright house in Inverness (1962), and the Dominic Cagliostro house in Berkeley (1977) 

Style
Jack Hillmer's style is most closely identified with the Second Bay Tradition period of architecture in the California Bay Area   Hillmer's work is characterized by "bold exterior fascias and interior cornice lines [that] turn the structure into its own ornament   He hones unnecessary details to a minimum; window frames are typically absent; the glass is often embedded directly into the wood structure   This approach is thoroughly Modern   Beauty is drawn from the inherent structure itself rather than from applied carving "Architect Pierluigi Serraino described Hillmer's architecture as "assertive, but it's always benevolent   It's always very delicate in the way it fits onto the site   It's not architecture that wants to scream, but it has its own monumentality "In Hillmer's own words:  "My approach to architecture was as an art   The approach of most other architects is as a business   I never really thought about how much money I was getting "
Passage 8:
Henry Roth
Henry Roth (February 8, 1906 – October 13, 1995) was an American novelist and short story writer who found success later in life after his 1934 novel Call It Sleep was reissued in paperback in 1964 

Biography
Roth was born in Tysmenitz near Stanislawow, Galicia, Austro-Hungary (now known as Tysmenytsia, near Ivano-Frankivsk, Galicia, Ukraine)  Although his parents never agreed on the exact date of his arrival in the United States, it is most likely that he and his mother landed at Ellis Island and began his life in New York in 1908  The family briefly lived in Brooklyn, and then on the Lower East Side, in the slums where his classic novel Call It Sleep is set  In 1914, they moved to Harlem  Roth lived there until 1927, when, as a senior at City College of New York, he moved in with Eda Lou Walton, a poet and New York University instructor who lived on Morton Street in Greenwich Village 
With Walton's support, he began Call It Sleep in about 1930, completed the novel in the spring of 1934, and it was published in December 1934, to mostly good reviews  Yet the New York Herald Tribune's book critic Lewis Gannett foresaw that the book would not prove popular with its bleak depiction of New York's Lower East Side, but wrote readers would "remember it and talk about it and watch excitedly" for Roth's next book  Call It Sleep sold slowly and poorly, and after it was out-of-print, critics writing in magazines such as Commentary and Partisan Review kept praising it, and asking for it to be reprinted  After being republished in hardback in 1960 and paperback in 1964, with more than 1,000,000 copies sold, and many weeks on the New York Times bestseller list, the novel was hailed as an overlooked Depression-era masterpiece and classic novel of immigration  Today, it is widely regarded as a masterpiece of Jewish American literature 
After the book's 1934 publication, Roth began a second novel that was contracted with editor Maxwell Perkins, of Scribner's  But Roth's growing ideological frustration and personal confusion contributed to a profound writer's block, which lasted until 1979, when he began the earliest drafts of Mercy of a Rude Stream (although material written much earlier than 1979 was also incorporated into this later work)  In 1938, during an unproductive sojourn at the artists' colony Yaddo in Saratoga Springs, New York, Roth met Muriel Parker, a pianist and composer; much of this period is depicted in Roth's final work, An American Type  Roth severed his relationship with Walton, moved out of her apartment, and married Parker in 1939, to the disapproval of her family  With the onset of World War II, he became a tool-and-gauge maker  The couple moved first to Boston with their two young sons, Jeremy and Hugh, and then, in 1946, to Maine  There, Roth worked as a woodsman, a schoolteacher, a psychiatric attendant in the state mental hospital, a waterfowl farmer, and a Latin and math tutor 
Arthur Hertzberg credited editor Harold U  Ribalow with "rediscovering" Roth  Ribelow found him on a farm in Maine, persuaded him to permit a new edition of the novel, and wrote an introduction to the new edition, which was published by Pageant Books in 1960   Many years later, after Ribalow had died and Roth was awarded the Ribalow Prize, he wrote to Ribalow's son, Meir Z  Ribalow, "Thanks for the encomia  Things like that keep me alive, I'm sure: what little is left me capable of feeling swells with pride like the staves of an old barrel when filled  Harold, to whom I owe so much, would have been happy to witness the occasion "In fact, Roth did not initially welcome the success of the 1964 reprint of Call It Sleep, valuing his privacy instead  But his writing block slowly began to break  In 1968, after Muriel's retirement from the Maine state school system, the couple moved to a trailer home in Albuquerque, New Mexico, closer to where Roth had stayed as writer-in-residence at the D  H  Lawrence ranch outside of Taos  Muriel began composing music again, while Roth collaborated with his friend and Italian translator Mario Materassi to put out a collection of essays called Shifting Landscape, published by the Jewish Publication Society in 1987  After Muriel's death, in 1990, Roth moved into a ramshackle former funeral parlor and occupied himself with revising the final volumes of his monumental work, Mercy of a Rude Stream  It has been alleged that the incestuous relationships between the protagonist, a sister, and a cousin in Mercy of a Rude Stream are autobiographical  Roth's sister, however, has denied that such events occurred 
Roth failed to garner the acclaim some say he deserves, perhaps because after the publication of Call It Sleep he failed to produce another novel for 60 years  He attributed his massive writer's block to personal problems, such as depression, and to political conflicts, including his disillusionment with Communism  At other times, he cited his early break with Judaism and his obsessive sexual preoccupations as probable causes  Roth died in Albuquerque, New Mexico, in 1995 
The character E  I  Lonoff in Philip Roth's Zuckerman novels (The Ghost Writer and Exit Ghost in this case), is a composite of Roth, Bernard Malamud and fictional elements 

Works and writing
Call It Sleep
Published in 1934, Call It Sleep centers on the turbulent experiences of a young boy, David Schearl, growing up in the Jewish immigrant slum of New York's Lower East Side in the early 20th century 

Mercy of a Rude Stream
Mercy of a Rude Stream is a monumental epic published in four volumes  It follows protagonist Ira Stigman from his family's arrival in Jewish-Irish Harlem in 1914 to the night before Thanksgiving in 1927, when Ira decides to leave the family tenement and move in with Edith Welles   According to critic David Mehegan, Roth's Mercy represents a "landmark of the American literary century" The first volume, A Star Shines over Mt  Morris Park was published in 1994 by St  Martin's Press and the second volume, called A Diving Rock on the Hudson, appeared from St  Martin's in 1995   In A Diving Rock on the Hudson, "Roth writes graphically about the sexual relationship between the protagonist, Ira Stigman, and Stigman's sister, Minnie, as teen-agers  Roth also describes an incestuous relationship between Stigman and his cousin, Stella " Roth's sister "chastise[d] Roth for writing about the 'revelation'" and "threaten[ed] to sue him and St  Martin's Press     Roth and his sister entered into a contract in which he agreed to pay his sister $10,000 in exchange for immunity from legal action  The contract     also stipulated that future volumes of Roth's novel would no longer portray Minnie Stigman 'as having any further sexual relationship with her brother, Ira Stigman '"From Bondage, which appeared in hardcover in 1996, was the first volume of the four Mercy books to appear posthumously  Requiem for Harlem, the fourth and final volume, appeared in 1998   Roth was able to revise both the third and fourth volumes in 1994 and 1995 with the help of his assistant, Felicia Steele, shortly before his death 
Before his death, Roth commented numerous times that Mercy of a Rude Stream comprised six volumes   In fact, Roth did write six separate books  He called the first four "Batch One," and the last two, "Batch Two "  Roth's editor at St  Martin's, Robert Weil, along with Felicia Steele, Larry Fox, and Roth's agent, Roslyn Targ, found the epic would be best served in four volumes, as the four books of "Batch One" contained a stylistic and thematic unity inconsistent with the remaining two books 
Explaining the difference between Mercy of a Rude Stream and Call It Sleep, critic Mario Materassi, Roth's longtime friend, argues that "Call It Sleep can be read as a vehicle through which, soon after breaking away from his family and his tradition, young Roth used some of the fragments of his childhood to shore up the ruins of what he already felt was a disconnected self   Forty-five years later, Roth embarked on another attempt to bring some retrospective order to his life's confusion:  Mercy of a Rude Stream, which he has long called a 'continuum,' can be read as a final, monumental effort on the part of the elderly author to come to terms with the pattern of rupture and discontinuity that has marked his life" Fran Lebowitz, writer and public intellectual, in her Netflix special "Pretend It's a City" speaks about how you can still appreciate the art of an individual separate from his actions 

An American Type
Roth's final novel, An American Type, emerged from "Batch 2," which Roth wrote during the late 1980s and early 1990s  With his assistant's help, Roth produced 1,900 typed pages of scenes beginning where Mercy left off and continuing through 1990   The manuscript of "Batch 2" remained untouched for over a decade until Weil sent it to The New Yorker, which published two excerpts from "Batch 2" in the summer of 2006 under the titles "God the Novelist" and "Freight " At The New Yorker the book came into the hands of Willing Davidson, then a young assistant in the magazine's fiction department  At the suggestion of Weil and Roth's literary executor, Lawrence Fox, Davidson edited "Batch 2" into An American Type, which was published by W W  Norton in 2010 Both a love story and a lamentation, the novel opens in 1938, and reintroduces us to Ira Stigman of the Mercy cycle, a thirty-two-year-old "slum-born Yiddle" eager to assimilate but traumatized by his impoverished immigrant past  Restless with his lover and literary mentor, English professor Edith Welles, Ira journeys to Yaddo, where he meets M (who only appeared in the old man's reveries in the Mercy series), a blond, aristocratic pianist whose "calm, Anglo-Saxon radiance" engages him 
The ensuing romantic crisis, as well as the conflict between his ghetto Jewish roots and the bourgeois comforts of Manhattan, forces Ira to abandon his paramour's Greenwich Village apartment and set out with an illiterate, boorish Communist on a quest for the promise of the American West  But feeling like a total failure in LA, Ira begins an epic journey home, thumbing rides from truckers and riding the rails with hobos through the Dust Bowl  Ira only knows that he must return to M, the woman he truly loves 
Sixty-five pages of excerpts from Batch Two consisting of short journal entries appeared in the journal, Fiction, Number 57, in 2011  The majority of these pages are about Roth's move to Maine, afraid that his associations with the Communist Party would haunt him at his factory job in Massachusetts  Purchasing a small farm, and surrounded by Yankee neighbors, Roth questions his identity as a Jew and struggles to wrest a living out of a Maine countryside where the soil is so hard that he has to dynamite in order to lay pipe deep enough to avoid the winter freezes  The extreme cold that he and his family endured, his work logging, bargaining over antiques and livestock with neighbors, and the world of backwoods and village America form the principal and unlikely drama of these pages  There is also return to the tense, incestuous world of the Roth family in Henry's childhood in the last of these extracts 

Themes
Henry Roth's writing centers on immigrant experience, particularly a Jewish-American experience in Depression-era America  He has also been hailed as a chronicler of New York City life 
Roth's work reveals an obsession with cultural depravity: the internal dislocation of the intellectual and of society at large that features so prominently in the work of the greatest Modernist writers  Indeed, Roth often fixates on human depravity in a multitude of forms  Sexually abhorrent acts such as incest, infidelity, and predation, for instance, inform much of his work, as does a more general climate of violence or abuse, often inflicted on others and masochistically turned inwards 
Throughout his life, Roth simultaneously embraced and rejected the notion of a forgiving God, and this ambivalence is also registered in his writing  Mario Materassi suggests, in "Shifting Urbanscape: Roth's 'Private' New York," that Roth "has never been interested in any story other than the anguished one of a man who, throughout his life, has contradicted each of his previously held positions and beliefs "While Roth's works are generally tragic, and often relentlessly so, his later work holds out for the possibility of redemption, or of mercy in a rude stream  This notion is especially evident in An American Type where the love between Ira and M becomes a means of transcendence 

Awards and honors
Roth received two honorary doctorates, one from the University of New Mexico and one from the Hebrew Union College–Jewish Institute of Religion  He won the 1987 International Nonino Prize in Italy  Posthumously, he was honored in 1995 with the Hadassah Harold Ribalow Lifetime Achievement Award and by the Museum of the City of New York with Manhattan Borough President Ruth Messinger having named February 29, 1996, as "Henry Roth Day" in New York City  From Bondage was cited by the National Book Critics Circle as being a finalist for its Fiction Prize in 1997, and it was in that same year that Henry Roth won the first Isaac Bashevis Singer Prize in Literature for From Bondage, an award put out by The Forward Foundation  In 2005, ten years after Roth's death, the first full biography of his life, the prize-winning Redemption: The Life of Henry Roth, by literary scholar Steven G  Kellman, was published, followed in 2006 by Henry Roth's centenary, which was marked by a literary tribute at the New York Public Library, sponsored by CCNY and organized by Lawrence I  Fox, Roth's literary executor 

Bibliography
Call It Sleep (1934)
"Where My Sympathy Lies," The New Masses, vol  22, no  10 (March 2, 1937), pg  9 —extols and justifies the Moscow Trials 
Nature's First Green (1979)
Shifting Landscape: A Composite, 1925–1987 (1987)
Mercy of a Rude Stream Vol  1: A Star Shines Over Mt  Morris Park (1994)
Mercy of a Rude Stream Vol  2: A Diving Rock on the Hudson (1995)
Mercy of a Rude Stream Vol  3: From Bondage (1996)
Mercy of a Rude Stream Vol  4: Requiem for Harlem (1998)
An American Type (2010)
Passage 9:
Lewis Mumford
Lewis Mumford (19 October 1895 – 26 January 1990) was an American historian, sociologist, philosopher of technology, and literary critic  Particularly noted for his study of cities and urban architecture, he had a broad career as a writer  He made signal contributions to social philosophy, American literary and cultural history, and the history of technology He was influenced by the work of Scottish theorist Sir Patrick Geddes and worked closely with his associate the British sociologist Victor Branford  
Mumford was also a contemporary and friend of Frank Lloyd Wright, Clarence Stein, Frederic Osborn, Edmund N  Bacon, and Vannevar Bush 

Life
Early life and education
Mumford was born in Flushing, Queens, New York, and graduated from Stuyvesant High School in 1912  He studied at the City College of New York and The New School for Social Research, but became ill with tuberculosis and never finished his degree  In 1918 he joined the navy to serve in World War I and was assigned as a radio electrician  He was discharged in 1919 and became associate editor of The Dial, an influential modernist literary journal  He later worked for The New Yorker where he wrote architectural criticism and commentary on urban issues 

First book
Mumford's earliest books in the field of literary criticism have had a lasting influence on contemporary American literary criticism  In The Golden Day (1926), he argued for a mid-19th-century American literary canon comprising Herman Melville, Ralph Waldo Emerson, Henry David Thoreau, Nathaniel Hawthorne and Walt Whitman, all of whom he argued reflected an antebellum American culture of the period that would be destroyed by the late-19th-century social changes wrought by the American Civil War and industrialization of the United States  Herman Melville (1929), which combined an account of Melville's life with an interpretive discussion of his work, was an important part of the Melville revival 

Correspondence
Mumford was a close friend of the psychologist Henry Murray, with whom he corresponded extensively from 1928 until the 1960s on topics including Herman Melville, psychology, American values and culture, and the nature of the self 

Urban planning
In his early writings on life in an urban area, Mumford was optimistic about human abilities and wrote, that the human race would use electricity and mass communication to build a better world for all humankind  
Mumford would later take a more pessimistic stance on the sweeping technological improvements brought by the second industrial revolution  His early architectural criticism also helped to bring wider public recognition to the work of Henry Hobson Richardson, Louis Sullivan and Frank Lloyd Wright 

Honours
Mumford was elected to the American Philosophical Society in 1941 and the American Academy of Arts and Sciences in 1947  In 1963, Mumford received the Frank Jewett Mather Award for art criticism from the College Art Association  Mumford received the Presidential Medal of Freedom in 1964  In 1975 Mumford was made an honorary Knight Commander of the Order of the British Empire (KBE)  In 1976, he was awarded the Prix mondial Cino Del Duca  In 1986, he was awarded the National Medal of Arts 

Further publications
He served as the architectural critic for The New Yorker magazine for over 30 years  His 1961 book, The City in History, received the National Book Award 

Retirement
Lewis Mumford died at the age of 94 at his home in Amenia, New York, on January 26, 1990  Nine years later the house was listed on the National Register of Historic Places  His wife Sophia died in 1997, at age 97 

Ideas
In his book The Condition of Man, published in 1944, Mumford characterized his orientation toward the study of humanity as "organic humanism "  The term is an important one because it sets limits on human possibilities, limits that are aligned with the nature of the human body  Mumford never forgot the importance of air quality, of food availability, of the quality of water, or the comfort of spaces, because all these elements had to be respected if people were to thrive  Technology and progress could never become a runaway train in his reasoning, so long as organic humanism was there to act as a brake  Indeed, Mumford considered the human brain from this perspective, characterizing it as hyperactive, a good thing in that it allowed humanity to conquer many of nature's threats, but potentially a bad thing if it were not occupied in ways that stimulated it meaningfully  Mumford's respect for human "nature", that is to say, the natural characteristics of being human, provided him with a platform from which to assess technologies, and technics in general  Thus his criticism and counsel with respect to the city and with respect to the implementation of technology was fundamentally organized around the organic humanism to which he ascribed  It was from the perspective of organic humanism that Mumford eventually launched a critical assessment of Marshall McLuhan, who argued that the technology, not the natural environment, would ultimately shape the nature of humankind, a possibility that Mumford recognized, but only as a nightmare scenario 
Mumford believed that what defined humanity, what set human beings apart from other animals, was not primarily our use of tools (technology) but our use of language (symbols)  He was convinced that the sharing of information and ideas amongst participants of primitive societies was completely natural to early humanity, and had obviously been the foundation of society as it became more sophisticated and complex   He had hopes for a continuation of this process of information "pooling" in the world as humanity moved into the future Mumford's choice of the word "technics" throughout his work was deliberate  For Mumford, technology is one part of technics  Using the broader definition of the Greek tekhne, which means not only technology but also art, skill, and dexterity, technics refers to the interplay of social milieu and technological innovation—the "wishes, habits, ideas, goals" as well as "industrial processes" of a society  As Mumford writes at the beginning of Technics and Civilization, "other civilizations reached a high degree of technical proficiency without, apparently, being profoundly influenced by the methods and aims of technics "

Megatechnics
In The Myth of the Machine Vol II: The Pentagon of Power (Chapter 12) (1970), Mumford criticizes the modern trend of technology, which emphasizes constant, unrestricted expansion, production, and replacement  He contends that these goals work against technical perfection, durability, social efficiency, and overall human satisfaction  Modern technology, which he called "megatechnics," fails to produce lasting, quality products by using devices such as consumer credit, installment buying, non-functioning and defective designs, planned obsolescence, and frequent superficial "fashion" changes  "Without constant enticement by advertising," he writes, "production would slow down and level off to normal replacement demand  Otherwise many products could reach a plateau of efficient design which would call for only minimal changes from year to year "
He uses his own refrigerator as an example, reporting that it "has been in service for nineteen years, with only a single minor repair: an admirable job  Both automatic refrigerators for daily use and deepfreeze preservation are inventions of permanent value      [O]ne can hardly doubt that if biotechnic criteria were heeded, rather than those of market analysts and fashion experts, an equally good product might come forth from Detroit, with an equally long prospect of continued use "

Biotechnics
Mumford was deeply concerned with the relationship between technics and bioviability   The latter term, not used by Mumford, characterizes an area's capability to support life up through its levels of complexity   Before the advent of technology, most areas of the planet were bioviable at some level or other; however, where certain forms of technology advance rapidly, bioviability decreases dramatically   Slag heaps, poisoned waters, parking lots, and concrete cities, for example, are extremely limited in terms of their bioviability  Non-bioviable regions are common in cinema in the form of dystopias (e g , Blade Runner)  Mumford did not believe it was necessary for bioviability to collapse as technics advanced, however, because he held it was possible to create technologies that functioned in an ecologically responsible manner, and he called that sort of technology biotechnics  Mumford believed that biotechnic consciousness (and possibly even community) was emerging as a later stage in the evolution of Darwinian thinking about the nature of human life  He believed this was the sort of technics needed to shake off the suicidal drive of "megatechnics " While Mumford recognized an ecological consciousness that traces back to the earliest communities, he regarded emerging biotechnics as a product of neo-Darwinian consciousness, as a post-industrial form of thinking, one that refuses to look away from the mutually-influencing relationship between the state of the living organism and the state of its environment  In Mumford's mind, the society organized around biotechnics would restrain its technology for the sake of that integral relationship 
In Mumford's understanding, the various technologies that arose in the megatechnic context have brought unintended and harmful side effects along with the obvious benefits they have bequeathed to us  He points out, for example, that the development of money (as a technology) created, as a side effect, a context for irrational accumulation of excess because it eliminated the burdensome aspects of object-wealth by making wealth abstract  In those eras when wealth was not abstract, plenitude had functioned as the organizing principle around its acquisition (i e , wealth, measured in grains, lands, animals, to the point that one is satisfied, but not saddled with it)  Money, which allows wealth to be conceived as pure quantity instead of quality, is an example of megatechnics, one which can spiral out of control  If Mumford is right in this conceptualization, historians and economists should be able to trace a relationship between the still-increasing abstraction of wealth and radical transformations with respect to wealth's distribution and role  And, indeed, it does appear that, alongside its many benefits, the movement toward electronic money has stimulated forms of economic stress and exploitation not yet fully understood and not yet come to their conclusion  A technology for distributing resources that was less given to abstract hoarding would be more suitable to a biotechnic conception of living 
Thus Mumford argued that the biotechnic society would not hold to the megatechnic delusion that technology must expand unceasingly, magnifying its own power and would shatter that delusion in order to create and preserve "livability " Rather than the megatechnic pursuit of power, the biotechnic society would pursue what Mumford calls "plenitude"; that is, a homeostatic relationship between resources and needs  This notion of plenitude becomes clearer if we suggest that the biotechnic society would relate to its technology in the manner an animal relates to available food–under circumstances of natural satisfaction, the pursuit of technological advance would not simply continue "for its own sake "
Alongside the limiting effect of satisfaction amidst plenitude, the pursuit of technological advance would also be limited by its potentially negative effects upon the organism  Thus, in a biotechnic society, the quality of air, the quality of food, the quality of water, these would all be significant concerns that could limit any technological ambitions threatening to them  The anticipated negative value of noise, radiation, smog, noxious chemicals, and other technical by-products would significantly constrain the introduction of new technical innovation  In Mumford's words, a biotechnic society would direct itself toward "qualitative richness, amplitude, spaciousness, and freedom from quantitative pressures and crowding  Self-regulation, self-correction, and self-propulsion are as much an integral property of organisms as nutrition, reproduction, growth, and repair " The biotechnic society would pursue balance, wholeness, and completeness; and this is what those individuals in pursuit of biotechnics would do as well 
Mumford's critique of the city and his vision of cities that are organized around the nature of human bodies, so essential to all Mumford's work on city life and urban design, is rooted in an incipient notion of biotechnics: "livability," a notion which Mumford got from his mentor, Patrick Geddes 
Mumford used the term biotechnics in the later sections of The Pentagon of Power, written in 1970  The term sits well alongside his early characterization of "organic humanism," in that biotechnics represent the concrete form of technique that appeals to an organic humanist  When Mumford described biotechnics, automotive and industrial pollution had become dominant technological concerns, along with the fear of nuclear annihilation  Mumford recognized, however, that technology had even earlier produced a plethora of hazards, and that it would do so into the future  For Mumford, human hazards are rooted in a power-oriented technology that does not adequately respect and accommodate the essential nature of humanity  Mumford is stating implicitly, as others would later state explicitly, that contemporary human life understood in its ecological sense is out of balance because the technical parts of its ecology (guns, bombs, cars, drugs) have spiraled out of control, driven by forces peculiar to them rather than constrained by the needs of the species that created them  He believed that biotechnics was the emerging answer and the only hope that could be set out against the problem of megatechnics   It was an answer, he believed, that was already beginning to assert itself in his time 
It is true that Mumford's writing privileges the term "biotechnics" more than the "biotechnic society " The reason is clear in the last sentence of The Pentagon of Power where he writes, "for those of us who have thrown off the myth of the machine, the next move is ours: for the gates of the technocratic prison will open automatically, despite their rusty ancient hinges, as soon as we choose to walk out " Mumford believed that the biotechnic society was a desideratum—one that should guide his contemporaries as they walked out the doors of their megatechnic confines (he also calls them "coffins")  Thus he ends his narrative, as he well understood, at the beginning of another one: the possible revolution that gives rise to a biotechnic society, a quiet revolution, for Mumford, one that would arise from the biotechnic consciousness and actions of individuals  Mumford was an avid reader of Alfred North Whitehead's philosophy of the organism 

Polytechnics versus monotechnics
A key idea, introduced in Technics and Civilization (1934) was that technology was twofold:

Polytechnic, which enlists many different modes of technology, providing a complex framework to solve human problems 
Monotechnic, which is technology only for its own sake, which oppresses humanity as it moves along its own trajectory Mumford commonly criticized modern America's transportation networks as being "monotechnic" in their reliance on cars  Automobiles become obstacles for other modes of transportation, such as walking, bicycle and public transit, because the roads they use consume so much space and are such a danger to people  Mumford explains that the thousands of maimed and dead each year as a result of automobile accidents are a ritual sacrifice the American society makes because of its extreme reliance on highway transport 

Three epochs of civilization
Also discussed at length in Technics and Civilization is Mumford's division of human civilization into three distinct epochs (following concepts originated by Patrick Geddes):

Eotechnic (the middle ages)
Paleotechnic (the time of the industrial revolution) and
Neotechnic (later, present-day)

Megamachines
Mumford also refers to large hierarchical organizations as megamachines—a machine using humans as its components  These organizations characterize Mumford's stage theory of civilization  The most recent megamachine manifests itself, according to Mumford, in modern technocratic nuclear powers—Mumford used the examples of the Soviet and United States power complexes represented by the Kremlin and the Pentagon, respectively  The builders of the pyramids, the Roman Empire and the armies of the World Wars are prior examples 
He explains that meticulous attention to accounting and standardization, and elevation of military leaders to divine status, are spontaneous features of megamachines throughout history  He cites such examples as the repetitive nature of Egyptian paintings which feature enlarged pharaohs and public display of enlarged portraits of Communist leaders such as Mao Zedong and Joseph Stalin  He also cites the overwhelming prevalence of quantitative accounting records among surviving historical fragments, from ancient Egypt to Nazi Germany 
Necessary to the construction of these megamachines is an enormous bureaucracy of humans which act as "servo-units", working without ethical involvement  According to Mumford, technological improvements such as the assembly line, or instant, global, wireless, communication and remote control, can easily weaken the perennial psychological barriers to certain types of questionable actions  An example which he uses is that of Adolf Eichmann, the Nazi official who organized logistics in support of the Holocaust  Mumford collectively refers to people willing to carry out placidly the extreme goals of these megamachines as "Eichmanns" 

The clock as herald of the Industrial Revolution
One of the better-known studies of Mumford is of the way the mechanical clock was developed by monks in the Middle Ages and subsequently adopted by the rest of society  He viewed this device as the key invention of the whole Industrial Revolution, contrary to the common view of the steam engine holding the prime position, writing: "The clock, not the steam-engine, is the key-machine of the modern industrial age      The clock     is a piece of power-machinery whose 'product' is seconds and minutes     "

Urban civilization
The City in History won the 1962 U S  National Book Award for Nonfiction  In this influential book Mumford explored the development of urban civilizations  Harshly critical of urban sprawl, Mumford argues that the structure of modern cities is partially responsible for many social problems seen in western society  While pessimistic in tone, Mumford argues that urban planning should emphasize an 'organic' relationship between people and their living spaces 
Mumford uses the example of the medieval city as the basis for the "ideal city," and claims that the modern city is too close to the Roman city (the sprawling megalopolis) which ended in collapse; if the modern city carries on in the same vein, Mumford argues, then it will meet the same fate as the Roman city 
Mumford wrote critically of urban culture believing the city is "a product of earth     a fact of nature     man's method of expression " Further, Mumford recognized the crises facing urban culture, distrustful of the growing finance industry, political structures, fearful that a local community culture was not being fostered by these institutions  Mumford feared "metropolitan finance," urbanization, politics, and alienation  Mumford wrote: "The physical design of cities and their economic functions are secondary to their relationship to the natural environment and to the spiritual values of human community "

Suburbs
Suburbia did not escape Mumford's criticism either:

In the suburb one might live and die without marring the image of an innocent world, except when some shadow of evil fell over a column in the newspaper  Thus the suburb served as an asylum for the preservation of illusion  Here domesticity could prosper, oblivious of the pervasive regimentation beyond  This was not merely a child-centered environment; it was based on a childish view of the world, in which reality was sacrificed to the pleasure principle 

Religion and spirituality
Mumford is also among the first urban planning scholars who paid serious attention to religion in the planning field  In one of his least well-known books, Faith for Living (1940, p  216), Mumford argues that:

The segregation of the spiritual life from the practical life is a curse that falls impartially upon both sides of our existence 

Influence
Mumford's interest in the history of technology and his explanation of  "polytechnics", along with his general philosophical bent, has been an important influence on a number of more recent thinkers concerned that technology serve human beings as broadly and well as possible  Some of these authors—such as Jacques Ellul, Witold Rybczynski, Richard Gregg, Amory Lovins, J  Baldwin, E  F  Schumacher, Herbert Marcuse, Erich Fromm, Murray Bookchin, Thomas Merton, Marshall McLuhan, Colin Ward and Kevin Carson—have been intellectuals and persons directly involved with technological development and decisions about the use of technology 
Mumford also had an influence on the American environmental movement, with thinkers like Barry Commoner and Bookchin being influenced by his ideas on cities, ecology and technology  Ramachandra Guha noted his work contains "some of the earliest and finest thinking on bioregionalism, anti-nuclearism, biodiversity, alternate energy paths, ecological urban planning and appropriate technology "Mumford's influence is also evident in the work of some artists including Berenice Abbott's photographs of New York City in the late 1930s Mumford was an inspiration for Ellsworth Toohey, the antagonist in Ayn Rand's novel The Fountainhead (1943) 

Works
Context 2: Passage 1:
Power factor
In electrical engineering, the power factor of an AC power system is defined as the ratio of the real power absorbed by the load to the apparent power flowing in the circuit   Real power is the average of the instantaneous product of voltage and current and represents the capacity of the electricity for performing work  Apparent power is the product of RMS current and voltage  Due to energy stored in the load and returned to the source, or due to a non-linear load that distorts the wave shape of the current drawn from the source, the apparent power may be greater than the real power, so more current flows in the circuit than would be required to transfer real power alone  A power factor magnitude of less than one indicates the voltage and current are not in phase, reducing the average product of the two  A negative power factor occurs when the device (which is normally the load) generates real power, which then flows back towards the source 
In an electric power system, a load with a low power factor draws more current than a load with a high power factor for the same amount of useful power transferred  The higher currents increase the energy lost in the distribution system and require larger wires and other equipment  Because of the costs of larger equipment and wasted energy, electrical utilities will usually charge a higher cost to industrial or commercial customers where there is a low power factor 
Power-factor correction increases the power factor of a load, improving efficiency for the distribution system to which it is attached  Linear loads with a low power factor (such as induction motors) can be corrected with a passive network of capacitors or inductors  Non-linear loads, such as rectifiers, distort the current drawn from the system  In such cases, active or passive power factor correction may be used to counteract the distortion and raise the power factor  The devices for correction of the power factor may be at a central substation, spread out over a distribution system, or built into power-consuming equipment 

General case
The general expression for power factor is given by

  
    
      
        
          
            power factor
          
        
        =
        P
        
          /
        
        
          P
          
            a
          
        
      
    
    {\displaystyle {\mbox{power factor}}=P/P_{a}}
  

  
    
      
        
          P
          
            a
          
        
        =
        
          I
          
            r
            m
            s
          
        
        
          V
          
            r
            m
            s
          
        
      
    
    {\displaystyle P_{a}=I_{rms}V_{rms}}
  where 
  
    
      
        P
      
    
    {\displaystyle P}
   is the real power measured by an ideal wattmeter, 
  
    
      
        
          I
          
            r
            m
            s
          
        
      
    
    {\displaystyle I_{rms}}
   is the rms current measured by an ideal ammeter, and 
  
    
      
        
          V
          
            r
            m
            s
          
        
      
    
    {\displaystyle V_{rms}}
   is the rms voltage measured by an ideal voltmeter   Apparent power, 
  
    
      
        
          P
          
            a
          
        
      
    
    {\displaystyle P_{a}}
  , is the product of the rms current and the rms voltage 
If the load is sourcing power back toward the generator, then 
  
    
      
        P
      
    
    {\displaystyle P}
   and 
  
    
      
        
          
            power factor
          
        
      
    
    {\displaystyle {\mbox{power factor}}}
   will be negative 

Periodic waveforms
If the waveforms are periodic with the same period which is much shorter than the averaging time of the physical meters, then the power factor can be computed by the following

  
    
      
        
          
            power factor
          
        
        =
        P
        
          /
        
        
          P
          
            a
          
        
      
    
    {\displaystyle {\mbox{power factor}}=P/P_{a}}
  

  
    
      
        
          P
          
            a
          
        
        =
        
          I
          
            r
            m
            s
          
        
        
          V
          
            r
            m
            s
          
        
      
    
    {\displaystyle P_{a}=I_{rms}V_{rms}}
  

  
    
      
        P
        =
        
          
            1
            T
          
        
        
          ∫
          
            
              t
              ′
            
          
          
            
              t
              ′
            
            +
            T
          
        
        i
        (
        t
        )
        v
        (
        t
        )
        d
        t
      
    
    {\displaystyle P={\frac {1}{T}}\int _{t'}^{t'+T}i(t)v(t)dt}
  

  
    
      
        
          I
          
            r
            m
            s
          
          
            2
          
        
        =
        
          
            1
            T
          
        
        
          ∫
          
            
              t
              ′
            
          
          
            
              t
              ′
            
            +
            T
          
        
        
          
            i
            (
            t
            )
          
          
            2
          
        
        d
        t
      
    
    {\displaystyle I_{rms}^{2}={\frac {1}{T}}\int _{t'}^{t'+T}{i(t)}^{2}dt}
  

  
    
      
        
          V
          
            r
            m
            s
          
          
            2
          
        
        =
        
          
            1
            T
          
        
        
          ∫
          
            
              t
              ′
            
          
          
            
              t
              ′
            
            +
            T
          
        
        
          
            v
            (
            t
            )
          
          
            2
          
        
        d
        t
      
    
    {\displaystyle V_{rms}^{2}={\frac {1}{T}}\int _{t'}^{t'+T}{v(t)}^{2}dt}
  where 
  
    
      
        i
        (
        t
        )
      
    
    {\displaystyle i(t)}
   is the instantaneous current, 
  
    
      
        v
        (
        t
        )
      
    
    {\displaystyle v(t)}
   is the instantaneous voltage, 
  
    
      
        
          t
          ′
        
      
    
    {\displaystyle t'}
   is an arbitrary starting time, and 
  
    
      
        T
      
    
    {\displaystyle T}
   is the period of the waveforms 

Nonperiodic waveforms
If the waveforms are not periodic and the physical meters have the same averaging time, then the equations for the periodic case can be used with the exception that 
  
    
      
        T
      
    
    {\displaystyle T}
   is the averaging time of the meters instead of the waveform period 

Linear time-invariant circuits
Linear time-invariant circuits (referred to simply as linear circuits for the rest of this article), for example, circuits consisting of combinations of resistors, inductors and capacitors have a sinusoidal response to the sinusoidal line voltage  A linear load does not change the shape of the input waveform but may change the relative timing (phase) between voltage and current, due to its inductance or capacitance 
In a purely resistive AC circuit, voltage and current waveforms are in step (or in phase), changing polarity at the same instant in each cycle  All the power entering the load is consumed (or dissipated) 
Where reactive loads are present, such as with capacitors or inductors, energy storage in the loads results in a phase difference between the current and voltage waveforms  During each cycle of the AC voltage, extra energy, in addition to any energy consumed in the load, is temporarily stored in the load in electric or magnetic fields then returned to the power grid a fraction of the period later 
Electrical circuits containing predominantly resistive loads (incandescent lamps, heating elements) have a power factor of almost 1, but circuits containing inductive or capacitive loads (electric motors, solenoid valves, transformers, fluorescent lamp ballasts, and others) can have a power factor well below 1 
In the electric power grid, reactive loads cause a continuous ebb and flow of nonproductive power   A circuit with a low power factor will use a greater amount of current to transfer a given quantity of real power than a circuit with a high power factor thus causing increased losses due to resistive heating in power lines, and requiring the use of higher-rated conductors and transformers 

Definition and calculation
AC power has two components:

Real power or active power (
  
    
      
        P
      
    
    {\displaystyle P}
  ) (sometimes called average power), expressed in watts (W)
Reactive power (
  
    
      
        Q
      
    
    {\displaystyle Q}
  ), usually expressed in reactive volt-amperes (var)Together, they form the complex power (
  
    
      
        S
      
    
    {\displaystyle S}
  ) expressed as volt-amperes (VA)  The magnitude of the complex power is the apparent power (
  
    
      
        
          |
        
        S
        
          |
        
      
    
    {\displaystyle |S|}
  ), also expressed in volt-amperes (VA) 
The VA and var are non-SI units mathematically identical to the watt, but are used in engineering practice instead of the watt to state what quantity is being expressed  The SI explicitly disallows using units for this purpose or as the only source of information about a physical quantity as used The power factor is defined as the ratio of real power to apparent power  As power is transferred along a transmission line, it does not consist purely of real power that can do work once transferred to the load, but rather consists of a combination of real and reactive power, called apparent power  The power factor describes the amount of real power transmitted along a transmission line relative to the total apparent power flowing in the line The power factor can also be computed as the cosine of the angle θ by which the current waveform lags or leads the voltage waveform, 

Power triangle
One can relate the various components of AC power by using the power triangle in vector space  Real power extends horizontally in the real axis and reactive power extends in the direction of the imaginary axis  Complex power (and its magnitude, apparent power) represents a combination of both real and reactive power, and therefore can be calculated by using the vector sum of these two components  We can conclude that the mathematical relationship between these components is:

  
    
      
        
          
            
              
                S
              
              
                
                =
                P
                +
                j
                Q
              
            
            
              
                
                  |
                
                S
                
                  |
                
              
              
                
                =
                
                  
                    
                      P
                      
                        2
                      
                    
                    +
                    
                      Q
                      
                        2
                      
                    
                  
                
              
            
            
              
                
                  pf
                
              
              
                
                =
                cos
                ⁡
                
                  θ
                
                =
                
                  
                    P
                    
                      
                        |
                      
                      S
                      
                        |
                      
                    
                  
                
                =
                cos
                ⁡
                
                  
                    (
                    
                      arctan
                      ⁡
                      
                        
                          (
                          
                            
                              Q
                              P
                            
                          
                          )
                        
                      
                    
                    )
                  
                
              
            
            
              
                Q
              
              
                
                =
                P
                
                tan
                ⁡
                (
                arccos
                ⁡
                (
                
                  pf
                
                )
                )
              
            
          
        
      
    
    {\displaystyle {\begin{aligned}S&=P+jQ\\|S|&={\sqrt {P^{2}+Q^{2}}}\\{\text{pf}}&=\cos {\theta }={\frac {P}{|S|}}=\cos {\left(\arctan {\left({\frac {Q}{P}}\right)}\right)}\\Q&=P\,\tan(\arccos({\text{pf}}))\end{aligned}}}
  As the angle θ increases with fixed total apparent power, current and voltage are further out of phase with each other  Real power decreases, and reactive power increases 

Lagging, leading and unity power factors
Power factor is described as leading if the current waveform is advanced in phase with respect to voltage, or lagging when the current waveform is behind the voltage waveform  A lagging power factor signifies that the load is inductive, as the load will consume reactive power  The reactive component 
  
    
      
        Q
      
    
    {\displaystyle Q}
   is positive as reactive power travels through the circuit and is consumed by the inductive load  A leading power factor signifies that the load is capacitive, as the load supplies reactive power, and therefore the reactive component 
  
    
      
        Q
      
    
    {\displaystyle Q}
   is negative as reactive power is being supplied to the circuit 

If θ is the phase angle between the current and voltage, then the power factor is equal to the cosine of the angle, 
  
    
      
        cos
        ⁡
        θ
      
    
    {\displaystyle \cos \theta }
  :

  
    
      
        
          |
        
        P
        
          |
        
        =
        
          |
        
        S
        
          |
        
        cos
        ⁡
        θ
      
    
    {\displaystyle |P|=|S|\cos \theta }
  Since the units are consistent, the power factor is by definition a dimensionless number between -1 and 1  When power factor is equal to 0, the energy flow is entirely reactive and stored energy in the load returns to the source on each cycle  When the power factor is 1, referred to as unity power factor, all the energy supplied by the source is consumed by the load  Power factors are usually stated as leading or lagging to show the sign of the phase angle  Capacitive loads are leading (current leads voltage), and inductive loads are lagging (current lags voltage) 
If a purely resistive load is connected to a power supply, current and voltage will change polarity in step, the power factor will be 1, and the electrical energy flows in a single direction across the network in each cycle  Inductive loads such as induction motors (any type of wound coil) consume reactive power with the current waveform lagging the voltage  Capacitive loads such as capacitor banks or buried cables generate reactive power with the current phase leading the voltage  Both types of loads will absorb energy during part of the AC cycle, which is stored in the device's magnetic or electric field, only to return this energy back to the source during the rest of the cycle 
For example, to get 1 kW of real power, if the power factor is unity, 1 kVA of apparent power needs to be transferred (1 kW ÷ 1 = 1 kVA)  At low values of power factor, more apparent power needs to be transferred to get the same real power  To get 1 kW of real power at 0 2 power factor, 5 kVA of apparent power needs to be transferred (1 kW ÷ 0 2 = 5 kVA)  This apparent power must be produced and transmitted to the load and is subject to losses in the production and transmission processes 
Electrical loads consuming alternating current power consume both real power and reactive power  The vector sum of real and reactive power is the complex power, and its magnitude is the apparent power  The presence of reactive power causes the real power to be less than the apparent power, and so, the electric load has a power factor of less than 1 
A negative power factor (0 to −1) can result from returning active power to the source, such as in the case of a building fitted with solar panels when surplus power is fed back into the supply 

Power factor correction of linear loads
A high power factor is generally desirable in a power delivery system to reduce losses and improve voltage regulation at the load  Compensating elements near an electrical load will reduce the apparent power demand on the supply system  Power factor correction may be applied by an electric power transmission utility to improve the stability and efficiency of the network  Individual electrical customers who are charged by their utility for low power factor may install correction equipment to increase their power factor so as to reduce costs 
Power factor correction brings the power factor of an AC power circuit closer to 1 by supplying or absorbing reactive power, adding capacitors or inductors that act to cancel the inductive or capacitive effects of the load, respectively  In the case of offsetting the inductive effect of motor loads, capacitors can be locally connected  These capacitors help to generate reactive power to meet the demand of the inductive loads  This will keep that reactive power from having to flow all the way from the utility generator to the load  In the electricity industry, inductors are said to consume reactive power and capacitors are said to supply it, even though reactive power is just energy moving back and forth on each AC cycle 
The reactive elements in power factor correction devices can create voltage fluctuations and harmonic noise when switched on or off  They will supply or sink reactive power regardless of whether there is a corresponding load operating nearby, increasing the system's no-load losses  In the worst case, reactive elements can interact with the system and with each other to create resonant conditions, resulting in system instability and severe overvoltage fluctuations  As such, reactive elements cannot simply be applied without engineering analysis 

An automatic power factor correction unit consists of a number of capacitors that are switched by means of contactors  These contactors are controlled by a regulator that measures power factor in an electrical network  Depending on the load and power factor of the network, the power factor controller will switch the necessary blocks of capacitors in steps to make sure the power factor stays above a selected value 
In place of a set of switched capacitors, an unloaded synchronous motor can supply reactive power  The reactive power drawn by the synchronous motor is a function of its field excitation  It is referred to as a synchronous condenser  It is started and connected to the electrical network  It operates at a leading power factor and puts vars onto the network as required to support a system's voltage or to maintain the system power factor at a specified level 
The synchronous condenser's installation and operation are identical to those of large electric motors  Its principal advantage is the ease with which the amount of correction can be adjusted; it behaves like a variable capacitor  Unlike with capacitors, the amount of reactive power supplied is proportional to voltage, not the square of voltage; this improves voltage stability on large networks   Synchronous condensers are often used in connection with high-voltage direct-current transmission projects or in large industrial plants such as steel mills 
For power factor correction of high-voltage power systems or large, fluctuating industrial loads, power electronic devices such as the static VAR compensator or STATCOM are increasingly used  These systems are able to compensate sudden changes of power factor much more rapidly than contactor-switched capacitor banks and, being solid-state, require less maintenance than synchronous condensers 

Non-linear loads
Examples of non-linear loads on a power system are rectifiers (such as used in a power supply), and arc discharge devices such as fluorescent lamps, electric welding machines, or arc furnaces  Because current in these systems is interrupted by a switching action, the current contains frequency components that are multiples of the power system frequency  Distortion power factor is a measure of how much the harmonic distortion of a load current decreases the average power transferred to the load 

Non-sinusoidal components
In linear circuits having only sinusoidal currents and voltages of one frequency, the power factor arises only from the difference in phase between the current and voltage  This is displacement power factor Non-linear loads change the shape of the current waveform from a sine wave to some other form  Non-linear loads create harmonic currents in addition to the original (fundamental frequency) AC current  This is of importance in practical power systems that contain non-linear loads such as rectifiers, some forms of electric lighting, electric arc furnaces, welding equipment, switched-mode power supplies, variable speed drives and other devices  Filters consisting of linear capacitors and inductors can prevent harmonic currents from entering the supplying system 
To measure the real power or reactive power, a wattmeter designed to work properly with non-sinusoidal currents must be used 

Distortion power factor
The distortion power factor is the distortion component associated with the harmonic voltages and currents present in the system 

  
    
      
        
          
            
              
                
                  
                    distortion power factor
                  
                
              
              
                
                =
                
                  
                    
                      I
                      
                        1
                      
                    
                    
                      I
                      
                        r
                        m
                        s
                      
                    
                  
                
              
            
            
              
              
                
                =
                
                  
                    
                      I
                      
                        1
                      
                    
                    
                      
                        I
                        
                          1
                        
                        
                          2
                        
                      
                      +
                      
                        I
                        
                          2
                        
                        
                          2
                        
                      
                      +
                      
                        I
                        
                          3
                        
                        
                          2
                        
                      
                      +
                      
                        I
                        
                          4
                        
                        
                          2
                        
                      
                      +
                      ⋯
                    
                  
                
              
            
            
              
              
                
                =
                
                  
                    1
                    
                      1
                      +
                      
                        
                          
                            
                              I
                              
                                2
                              
                              
                                2
                              
                            
                            +
                            
                              I
                              
                                3
                              
                              
                                2
                              
                            
                            +
                            
                              I
                              
                                4
                              
                              
                                2
                              
                            
                            +
                            ⋯
                          
                          
                            I
                            
                              1
                            
                            
                              2
                            
                          
                        
                      
                    
                  
                
              
            
            
              
              
                
                =
                
                  
                    1
                    
                      1
                      +
                      T
                      H
                      
                        D
                        
                          i
                        
                        
                          2
                        
                      
                    
                  
                
              
            
          
        
      
    
    {\displaystyle {\begin{aligned}{\mbox{distortion power factor}}&={\frac {I_{1}}{I_{rms}}}\\&={\frac {I_{1}}{\sqrt {I_{1}^{2}+I_{2}^{2}+I_{3}^{2}+I_{4}^{2}+\cdots }}}\\&={\frac {1}{\sqrt {1+{\frac {I_{2}^{2}+I_{3}^{2}+I_{4}^{2}+\cdots }{I_{1}^{2}}}}}}\\&={\frac {1}{\sqrt {1+THD_{i}^{2}}}}\\\end{aligned}}}
  
  
    
      
        
          
            
              THD
            
          
          
            i
          
        
      
    
    {\displaystyle {\mbox{THD}}_{i}}
   is the total harmonic distortion of the load current  

  
    
      
        T
        H
        
          D
          
            i
          
        
        =
        
          
            
              
                
                  ∑
                  
                    h
                    =
                    2
                  
                  
                    ∞
                  
                
                
                  I
                  
                    h
                  
                  
                    2
                  
                
              
            
            
              I
              
                1
              
            
          
        
        =
        
          
            
              
                I
                
                  2
                
                
                  2
                
              
              +
              
                I
                
                  3
                
                
                  2
                
              
              +
              
                I
                
                  4
                
                
                  2
                
              
              +
              ⋯
            
            
              I
              
                1
              
            
          
        
      
    
    {\displaystyle THD_{i}={\frac {\sqrt {\displaystyle \sum _{h=2}^{\infty }I_{h}^{2}}}{I_{1}}}={\frac {\sqrt {I_{2}^{2}+I_{3}^{2}+I_{4}^{2}+\cdots }}{I_{1}}}}
  
  
    
      
        
          I
          
            1
          
        
      
    
    {\displaystyle I_{1}}
   is the fundamental component of the current and 
  
    
      
        
          I
          
            
              rms
            
          
        
      
    
    {\displaystyle I_{\mbox{rms}}}
   is the total current – both are root mean square-values (distortion power factor can also be used to describe individual order harmonics, using the corresponding current in place of total current)  This definition with respect to total harmonic distortion assumes that the voltage stays undistorted (sinusoidal, without harmonics)  This simplification is often a good approximation for stiff voltage sources (not being affected by changes in load downstream in the distribution network)  Total harmonic distortion of typical generators from current distortion in the network is on the order of 1–2%, which can have larger scale implications but can be ignored in common practice The result when multiplied with the displacement power factor (DPF) is the overall, true power factor or just power factor (PF):

  
    
      
        
          
            PF
          
        
        =
        
          
            
              cos
              ⁡
              
                φ
              
            
            
              1
              +
              T
              H
              
                D
                
                  i
                
                
                  2
                
              
            
          
        
      
    
    {\displaystyle {\mbox{PF}}={\frac {\cos {\varphi }}{\sqrt {1+THD_{i}^{2}}}}}

Distortion in three-phase networks
In practice, the local effects of distortion current on devices in a three-phase distribution network rely on the magnitude of certain order harmonics rather than the total harmonic distortion 
For example, the triplen, or zero-sequence, harmonics (3rd, 9th, 15th, etc ) have the property of being in-phase when compared line-to-line  In a delta-wye transformer, these harmonics can result in circulating currents in the delta windings and result in greater resistive heating  In a wye-configuration of a transformer, triplen harmonics will not create these currents, but they will result in a non-zero current in the neutral wire  This could overload the neutral wire in some cases
and create error in kilowatt-hour metering systems and billing revenue   The presence of current harmonics in a transformer also result in larger eddy currents in the magnetic core of the transformer  Eddy current losses generally increase as the square of the frequency, lowering the transformer's efficiency, dissipating additional heat, and reducing its service life Negative-sequence harmonics (5th, 11th, 17th, etc ) combine 120 degrees out of phase, similarly to the fundamental harmonic but in a reversed sequence   In generators and motors, these currents produce magnetic fields which oppose the rotation of the shaft and sometimes result in damaging mechanical vibrations 

Switched-mode power supplies
A particularly important class of non-linear loads is the millions of personal computers that typically incorporate switched-mode power supplies (SMPS) with rated output power ranging from a few watts to more than 1 kW  Historically, these very-low-cost power supplies incorporated a simple full-wave rectifier that conducted only when the mains instantaneous voltage exceeded the voltage on the input capacitors   This leads to very high ratios of peak-to-average input current, which also lead to a low distortion power factor and potentially serious phase and neutral loading concerns 
A typical switched-mode power supply first converts the AC mains to a DC bus by means of a bridge rectifier  The output voltage is then derived from this DC bus  The problem with this is that the rectifier is a non-linear device, so the input current is highly non-linear  That means that the input current has energy at harmonics of the frequency of the voltage  This presents a problem for power companies, because they cannot compensate for the harmonic current by adding simple capacitors or inductors, as they could for the reactive power drawn by a linear load  Many jurisdictions are beginning to require power factor correction for all power supplies above a certain power level 
Regulatory agencies such as the EU have set harmonic limits as a method of improving power factor  Declining component cost has hastened implementation of two different methods  To comply with current EU standard EN61000-3-2, all switched-mode power supplies with output power more than 75 W must at least include passive power factor correction  80 Plus power supply certification requires a power factor of 0 9 or more 

Power factor correction (PFC) in non-linear loads
Passive PFC
The simplest way to control the harmonic current is to use a filter that passes current only at line frequency (50 or 60 Hz)  The filter consists of capacitors or inductors and makes a non-linear device look more like a linear load  An example of passive PFC is a valley-fill circuit 
A disadvantage of passive PFC is that it requires larger inductors or capacitors than an equivalent power active PFC circuit  Also, in practice, passive PFC is often less effective at improving the power factor 

Active PFC
Active PFC is the use of power electronics to change the waveform of current drawn by a load to improve the power factor   Some types of the active PFC are buck, boost, buck-boost and synchronous condenser   Active power factor correction can be single-stage or multi-stage 
In the case of a switched-mode power supply, a boost converter is inserted between the bridge rectifier and the main input capacitors  The boost converter attempts to maintain a constant voltage at its output while drawing a current that is always in phase with and at the same frequency as the line voltage  Another switched-mode converter inside the power supply produces the desired output voltage from the DC bus  This approach requires additional semiconductor switches and control electronics but permits cheaper and smaller passive components  It is frequently used in practice 
For a three-phase SMPS, the Vienna rectifier configuration may be used to substantially improve the power factor 
SMPSs with passive PFC can achieve power factor of about 0 7–0 75, SMPSs with active PFC, up to 0 99 power factor, while a SMPS without any power factor correction have a power factor of only about 0 55–0 65 Due to their very wide input voltage range, many power supplies with active PFC can automatically adjust to operate on AC power from about 100 V (Japan) to 240 V (Europe)  That feature is particularly welcome in power supplies for laptops 

Dynamic PFC
Dynamic power factor correction (DPFC), sometimes referred to as real-time power factor correction, is used for electrical stabilization in cases of rapid load changes (e g  at large manufacturing sites)  DPFC is useful when standard power factor correction would cause over or under correction   DPFC uses semiconductor switches, typically thyristors, to quickly connect and disconnect capacitors or inductors to improve power factor 

Importance in distribution systems
Power factors below 1 0 require a utility to generate more than the minimum volt-amperes necessary to supply the real power (watts)  This increases generation and transmission costs  For example, if the load power factor were as low as 0 7, the apparent power would be 1 4 times the real power used by the load  Line current in the circuit would also be 1 4 times the current required at 1 0 power factor, so the losses in the circuit would be doubled (since they are proportional to the square of the current)  Alternatively, all components of the system such as generators, conductors, transformers, and switchgear would be increased in size (and cost) to carry the extra current  When the power factor is close to unity, for the same kVA rating of the transformer more load current can be supplied Utilities typically charge additional costs to commercial customers who have a power factor below some limit, which is typically 0 9 to 0 95   Engineers are often interested in the power factor of a load as one of the factors that affect the efficiency of power transmission 
With the rising cost of energy and concerns over the efficient delivery of power, active PFC has become more common in consumer electronics  Current Energy Star guidelines for computers call for a power factor of ≥ 0 9 at 100% of rated output in the PC's power supply  According to a white paper authored by Intel and the U S  Environmental Protection Agency, PCs with internal power supplies will require the use of active power factor correction to meet the ENERGY STAR 5 0 Program Requirements for Computers In Europe, EN 61000-3-2 requires power factor correction be incorporated into consumer products 
Small customers, such as households, are not usually charged for reactive power and so power factor metering equipment for such customers will not be installed 

Measurement techniques
The power factor in a single-phase circuit (or balanced three-phase circuit) can be measured with the wattmeter-ammeter-voltmeter method, where the power in watts is divided by the product of measured voltage and current  The power factor of a balanced polyphase circuit is the same as that of any phase  The power factor of an unbalanced polyphase circuit is not uniquely defined 
A direct reading power factor meter can be made with a moving coil meter of the electrodynamic type, carrying two perpendicular coils on the moving part of the instrument  The field of the instrument is energized by the circuit current flow  The two moving coils, A and B, are connected in parallel with the circuit load   One coil, A, will be connected through a resistor and the second coil, B, through an inductor, so that the current in coil B is delayed with respect to current in A  At unity power factor, the current in A is in phase with the circuit current, and coil A provides maximum torque, driving the instrument pointer toward the 1 0 mark on the scale  At zero power factor, the current in coil B is in phase with circuit current, and coil B provides torque to drive the pointer towards 0  At intermediate values of power factor, the torques provided by the two coils add and the pointer takes up intermediate positions Another electromechanical instrument is the polarized-vane type  In this instrument a stationary field coil produces a rotating magnetic field, just like a polyphase motor  The field coils are connected either directly to polyphase voltage sources or to a phase-shifting reactor if a single-phase application   A second stationary field coil, perpendicular to the voltage coils, carries a current proportional to current in one phase of the circuit  The moving system of the instrument consists of two vanes that are magnetized by the current coil  In operation, the moving vanes take up a physical angle equivalent to the electrical angle between the voltage source and the current source  This type of instrument can be made to register for currents in both directions, giving a four-quadrant display of power factor or phase angle



ground_truth: American

prompt_front: Answer the question based on the given passages. Only give me the answer and do not output any other words.

Question: What was the nationality and profession of the person responsible for the concept of a dimensionless number in physics and engineering?

The following are given passages.
Context 2: 
Digital instruments exist that directly measure the time lag between voltage and current waveforms  Low-cost instruments of this type measure the peak of the waveforms  More sophisticated versions measure the peak of the fundamental harmonic only, thus giving a more accurate reading for phase angle on distorted waveforms  Calculating power factor from voltage and current phases is only accurate if both waveforms are sinusoidal Power Quality Analyzers, often referred to as Power Analyzers, make a digital recording of the voltage and current waveform (typically either one phase or three phase) and accurately calculate true power (watts), apparent power (VA) power factor, AC voltage, AC current, DC voltage, DC current, frequency, IEC61000-3-2/3-12 Harmonic measurement, IEC61000-3-3/3-11 flicker measurement, individual phase voltages in delta applications where there is no neutral line, total harmonic distortion, phase and amplitude of individual voltage or current harmonics, etc 

Mnemonics
English-language power engineering students are advised to remember:
ELI the ICE man or ELI on ICE – the voltage E, leads the current I, in an inductor L  The current I leads the voltage E in a capacitor C 
Another common mnemonic is CIVIL – in a capacitor (C) the current (I) leads voltage (V), voltage (V) leads current (I) in an inductor (L) 
Passage 2:
Womersley number
The Womersley number (
  
    
      
        α
      
    
    {\displaystyle \alpha }
   or 
  
    
      
        
          Wo
        
      
    
    {\displaystyle {\text{Wo}}}
  ) is a dimensionless number in biofluid mechanics and biofluid dynamics  It is a dimensionless expression of the pulsatile flow frequency in relation to viscous effects  It is named after John R  Womersley (1907–1958) for his work with blood flow in arteries  The Womersley number is important in keeping dynamic similarity when scaling an experiment  An example of this is scaling up the vascular system for experimental study  The Womersley number is also important in determining the thickness of the boundary layer to see if entrance effects can be ignored 
The square root of this number is also referred to as Stokes number, 
  
    
      
        
          Stk
        
        =
        
          
            Wo
          
        
      
    
    {\displaystyle {\text{Stk}}={\sqrt {\text{Wo}}}}
  , due to the pioneering work done by Sir George Stokes on the Stokes second problem 

Derivation
The Womersley number, usually denoted 
  
    
      
        α
      
    
    {\displaystyle \alpha }
  , is defined by the relation

where 
  
    
      
        L
      
    
    {\displaystyle L}
   is an appropriate length scale (for example the radius of a pipe), 
  
    
      
        ω
      
    
    {\displaystyle \omega }
   is the angular frequency of the oscillations, and 
  
    
      
        ν
      
    
    {\displaystyle \nu }
  , 
  
    
      
        ρ
      
    
    {\displaystyle \rho }
  , 
  
    
      
        μ
      
    
    {\displaystyle \mu }
   are the kinematic viscosity, density, and dynamic viscosity of the fluid, respectively  The Womersley number is normally written in the powerless form

In the cardiovascular system, the pulsation frequency, density, and dynamic viscosity are constant, however the Characteristic length, which in the case of blood flow is the vessel diameter, changes by three orders of magnitudes (OoM) between the aorta and fine capillaries  The Womersley number thus changes due to the variations in vessel size across the vasculature system  The Womersley number of human blood flow can be estimated as follows:

  
    
      
        α
        =
        L
        
          
            (
            
              
                
                  ω
                  ρ
                
                μ
              
            
            )
          
          
            
              1
              2
            
          
        
        
         
      
    
    {\displaystyle \alpha =L\left({\frac {\omega \rho }{\mu }}\right)^{\frac {1}{2}}\, }
  
Below is a list of estimated Womersley numbers in different human blood vessels:

It can also be written in terms of the dimensionless Reynolds number (Re) and Strouhal number (St):

The Womersley number arises in the solution of the linearized Navier–Stokes equations for oscillatory flow (presumed to be laminar and incompressible) in a tube   It expresses the ratio of the transient or oscillatory inertia force to the shear force  When 
  
    
      
        α
      
    
    {\displaystyle \alpha }
   is small (1 or less), it means the frequency of pulsations is sufficiently low that a parabolic velocity profile has time to develop during each cycle, and the flow will be very nearly in phase with the pressure gradient, and will be given to a good approximation by Poiseuille's law, using the instantaneous pressure gradient   When 
  
    
      
        α
      
    
    {\displaystyle \alpha }
   is large (10 or more), it means the frequency of pulsations is sufficiently large that the velocity profile is relatively flat or plug-like, and the mean flow lags the pressure gradient by about 90 degrees  Along with the Reynolds number, the Womersley number governs dynamic similarity The boundary layer thickness 
  
    
      
        δ
      
    
    {\displaystyle \delta }
   that is associated with the transient acceleration is inversely related to the Womersley number  This can be seen by recognizing the Womersley number as the square root of the Stokes number 
where 
  
    
      
        L
      
    
    {\displaystyle L}
   is a characteristic length 

Biofluid mechanics
In a flow distribution network that progresses from a large tube to many small tubes (e g  a blood vessel network), the frequency, density, and dynamic viscosity are (usually) the same throughout the network, but the tube radii change  Therefore, the Womersley number is large in large vessels and small in small vessels  As the vessel diameter decreases with each division the Womersley number soon becomes quite small  The Womersley numbers tend to 1 at the level of the terminal arteries  In the arterioles, capillaries, and venules the Womersley numbers are less than one  In these regions the inertia force becomes less important and the flow is determined by the balance of viscous stresses and the pressure gradient  This is called microcirculation Some typical values for the Womersley number in the cardiovascular system for a canine at a heart rate of 2 Hz are:
Ascending aorta – 13 2
Descending aorta – 11 5
Abdominal aorta – 8
Femoral artery – 3 5
Carotid artery – 4 4
Arterioles – 0 04
Capillaries – 0 005
Venules – 0 035
Inferior vena cava – 8 8
Main pulmonary artery – 15It has been argued that universal biological scaling laws (power-law relationships that describe variation of quantities such as metabolic rate, lifespan, length, etc , with body mass) are a consequence of the need for energy minimization, the fractal nature of vascular networks, and the crossover from high to low Womersley number flow as one progresses from large to small vessels 
Passage 3:
Weissenberg number
The Weissenberg number (Wi) is a dimensionless number used in the study of viscoelastic flows  It is named after Karl Weissenberg  The dimensionless number compares the elastic forces to the viscous forces  It can be variously defined, but it is usually given by the relation of stress relaxation time of the fluid and a specific process time  For instance, in simple steady shear, the Weissenberg number, often abbreviated as Wi or We, is defined as the shear rate 
  
    
      
        
          
            
              γ
              ˙
            
          
        
      
    
    {\displaystyle {\dot {\gamma }}}
   times the relaxation time 
  
    
      
        λ
      
    
    {\displaystyle \lambda }
    Using the Maxwell model and the Oldroyd-B model, the elastic forces can be written as the first Normal force (N1) 

  
    
      
        
          Wi
        
        =
        
          
            
              
                elastic forces
              
              
                viscous forces
              
            
          
        
        =
        
          
            
              
                τ
                
                  x
                  x
                
              
              −
              
                τ
                
                  y
                  y
                
              
            
            
              τ
              
                x
                y
              
            
          
        
        =
        
          
            
              2
              λ
              μ
              
                
                  
                    
                      γ
                      ˙
                    
                  
                
                
                  2
                
              
            
            
              μ
              
                
                  
                    γ
                    ˙
                  
                
              
            
          
        
        =
        2
        
          
            
              γ
              ˙
            
          
        
        λ
         
        
      
    
    {\displaystyle {\text{Wi}}={\dfrac {\mbox{elastic forces}}{\mbox{viscous forces}}}={\frac {\tau _{xx}-\tau _{yy}}{\tau _{xy}}}={\frac {2\lambda \mu {\dot {\gamma }}^{2}}{\mu {\dot {\gamma }}}}=2{\dot {\gamma }}\lambda  \,}
  Since this number is obtained from scaling the evolution of the stress, it contains choices for the shear or elongation rate, and the length-scale  Therefore the exact definition of all non dimensional numbers should be given as well as the number itself 
While Wi is similar to the Deborah number and is often confused with it in technical literature, they have different physical interpretations  The Weissenberg number indicates the degree of anisotropy or orientation generated by the deformation, and is appropriate to describe flows with a constant stretch history, such as simple shear  In contrast, the Deborah number should be used to describe flows with a non-constant stretch history, and physically represents the rate at which elastic energy is stored or released 
Passage 4:
Ericksen number
In the study of liquid crystals, the Ericksen number (Er) is a dimensionless number used to describe the deformation of the director field under flow  It is defined as the ratio of the viscous to elastic forces  In the limit of low Ericksen number the elastic forces will exceed the viscous forces and so the director field will not be strongly affected by the flow field  The Ericksen number is named after American mathematics professor Jerald Ericksen of the University of Minnesota   The number is defined:

  
    
      
        
          
            E
            r
          
        
        =
        
          
            
              μ
              v
              L
            
            K
          
        
      
    
    {\displaystyle {\mathit {Er}}={\frac {\mu vL}{K}}}
  where

  
    
      
        μ
      
    
    {\displaystyle \mu }
   is the fluid's dynamic viscosity,

  
    
      
        v
      
    
    {\displaystyle v}
   is a characteristic scale for the fluid's velocity,

  
    
      
        L
      
    
    {\displaystyle L}
   is a characteristic scale length for the fluid flow,

  
    
      
        K
      
    
    {\displaystyle K}
   is an elasticity force, for example the elasticity modulus times an area 
Passage 5:
Qualified Person for Pharmacovigilance
In the European Union, the Qualified Person Responsible For Pharmacovigilance (QPPV) is an individual, usually an employee of a pharmaceutical company, who is personally responsible for the safety of the human pharmaceutical products marketed by that company in the EU  This function was established in 2004 by article 23 of regulation (EC) No 726/2004  The article establishes that the holder of a marketing authorization for a drug for human use must have a QPPV  When a company submits an application for permission to bring a medicinal product onto the market, the company submits a description of its system for monitoring the safety of the product in actual use (a pharmacovigilance system) and proof that the services of a QPPV are in place "The holder of an authorisation for a medicinal product for human use granted in accordance with the provisions of this Regulation shall have permanently and continuously at his disposal an appropriately qualified person responsible for pharmacovigilance "

Responsibilities
Per Article 23, the QPPV is responsible for:

Establishing and maintaining a pharmacovigilance system
Preparing pharmacovigilance reports as defined by regulations
Answering requests from Health Authorities
Providing Health Authorities with any other information relevant to product safetyThe Good Pharmacovigilance Practices (GVP) provide further guidance regarding these responsibilities of the QPPV (Module I, Section I C 1 3: Role of the qualified person responsible for pharmacovigilance in the EU  Per GVP, the QPPV is responsible for the establishment and maintenance of the marketing authorisation holder's pharmacovigilance system and therefore shall have sufficient authority to influence the performance of the quality system and the pharmacovigilance activities and to promote, maintain and improve compliance with the legal requirements  The QPPV is specifically responsible for:

Establishing and maintaining/managing the pharmaceutical company's pharmacovigilance system
Having an overview of the safety profiles and any emerging safety concerns for the company's drugs
Acting as a single contact point for the Health Authorities on a 24-hour basis

Criteria for QPPV role
The QPPV must reside in the EU, and should be permanently and continuously at the disposal of the MAH  Each company (i e  Applicant/Marketing Authorisation Holder or group of Marketing Authorisation Holders using a common pharmacovigilance system) should appoint one QPPV responsible for overall pharmacovigilance for all medicinal products for which the company holds marketing authorisations within the EU 
Detailed information on the role and responsibilities of the QPPV, and guidance for a Marketing Authorisation Holder on how to adequately support the QPPV are specified in Guideline on good pharmacovigilance practices (GVP; Module I – Pharmacovigilance systems and their quality systems) "   At a minimum the QPPV should be appropriately qualified, with documented experience in all aspects of pharmacovigilance in order to fulfil the responsibilities and tasks of the post  If the QPPV is not medically qualified, access to a medically qualified person should be available 
In addition, there are national regulations in some EU member states that also require a nominated individual in that country who has specific legal obligations as a QPPV at a national level 

See also
Pharmacovigilance
European Medicines Agency
Passage 6:
Joseph Fourier
Jean-Baptiste Joseph Fourier (; French: [fuʁje]; 21 March 1768 – 16 May 1830) was a French mathematician and physicist born in Auxerre and best known for initiating the investigation of Fourier series, which eventually developed into Fourier analysis and harmonic analysis, and their applications to problems of heat transfer and vibrations  The Fourier transform and Fourier's law of conduction are also named in his honour  Fourier is also generally credited with the discovery of the greenhouse effect 

Biography
Fourier was born in Auxerre (now in the Yonne département of France), the son of a tailor  He was orphaned at the age of nine  Fourier was recommended to the Bishop of Auxerre and, through this introduction, he was educated by the Benedictine Order of the Convent of St  Mark  The commissions in the scientific corps of the army were reserved for those of good birth, and being thus ineligible, he accepted a military lectureship on mathematics  He took a prominent part in his own district in promoting the French Revolution, serving on the local Revolutionary Committee  He was imprisoned briefly during the Terror but, in 1795, was appointed to the École Normale and subsequently succeeded Joseph-Louis Lagrange at the École Polytechnique 
Fourier accompanied Napoleon Bonaparte on his Egyptian expedition in 1798, as scientific adviser, and was appointed secretary of the Institut d'Égypte  Cut off from France by the British fleet, he organized the workshops on which the French army had to rely for their munitions of war  He also contributed several mathematical papers to the Egyptian Institute (also called the Cairo Institute) which Napoleon founded at Cairo, with a view of weakening British influence in the East  After the British victories and the capitulation of the French under General Menou in 1801, Fourier returned to France 

In 1801, Napoleon appointed Fourier Prefect (Governor) of the Department of Isère in Grenoble, where he oversaw road construction and other projects  However, Fourier had previously returned home from the Napoleon expedition to Egypt to resume his academic post as professor at École Polytechnique when Napoleon decided otherwise in his remark

    the Prefect of the Department of Isère having recently died, I would like to express my confidence in citizen Fourier by appointing him to this place 
Hence being faithful to Napoleon, he took the office of Prefect  It was while at Grenoble that he began to experiment on the propagation of heat  He presented his paper On the Propagation of Heat in Solid Bodies to the Paris Institute on 21 December 1807  He also contributed to the monumental Description de l'Égypte In 1822, Fourier succeeded Jean Baptiste Joseph Delambre as Permanent Secretary of the French Academy of Sciences  In 1830, he was elected a foreign member of the Royal Swedish Academy of Sciences 
Fourier never married In 1830, his diminished health began to take its toll:

Fourier had already experienced, in Egypt and Grenoble, some attacks of aneurysm of the heart  At Paris, it was impossible to be mistaken with respect to the primary cause of the frequent suffocations which he experienced  A fall, however, which he sustained on the 4th of May 1830, while descending a flight of stairs, aggravated the malady to an extent beyond what could have been ever feared 
Shortly after this event, he died in his bed on 16 May 1830 
Fourier was buried in the Père Lachaise Cemetery in Paris, a tomb decorated with an Egyptian motif to reflect his position as secretary of the Cairo Institute, and his collation of Description de l'Égypte  His name is one of the 72 names inscribed on the Eiffel Tower 
A bronze statue was erected in Auxerre in 1849, but it was melted down for armaments during World War II  Joseph Fourier University in Grenoble was named after him 

The Analytic Theory of Heat
In 1822, Fourier published his work on heat flow in Théorie analytique de la chaleur (The Analytical Theory of Heat),  in which he based his reasoning on Newton's law of cooling, namely, that the flow of heat between two adjacent molecules is proportional to the extremely small difference of their temperatures  This book was translated, with editorial 'corrections', into English 56 years later by Freeman (1878)  The book was also edited, with many editorial corrections, by Darboux and republished in French in 1888 There were three important contributions in this work, one purely mathematical, two essentially physical  In mathematics, Fourier claimed that any function of a variable, whether continuous or discontinuous, can be expanded in a series of sines of multiples of the variable  Though this result is not correct without additional conditions, Fourier's observation that some discontinuous functions are the sum of infinite series was a breakthrough  The question of determining when a Fourier series converges has been fundamental for centuries  Joseph-Louis Lagrange had given particular cases of this (false) theorem, and had implied that the method was general, but he had not pursued the subject  Peter Gustav Lejeune Dirichlet  was the first to give a satisfactory demonstration of it with some restrictive conditions  This work provides the foundation for what is today known as the Fourier transform 
One important physical contribution in the book was the concept of dimensional homogeneity in equations; i e  an equation can be formally correct only if the dimensions match on either side of the equality; Fourier made important contributions to dimensional analysis  The other physical contribution was Fourier's proposal of his partial differential equation for conductive diffusion of heat  This equation is now taught to every student of mathematical physics 

Real roots of polynomials
Fourier left an unfinished work on determining and locating real roots of polynomials, which was edited by Claude-Louis Navier and published in 1831  This work contains much original matter—in particular, Fourier's theorem on polynomial real roots, published in 1820  Fourier's theorem on real roots of polynomials states that a polynomial with real coefficients has a real root between any two consecutive zeros of its derivative  François Budan, in 1807 and 1811, had published independently his theorem (also known by the name of Fourier), which is very close to Fourier's theorem (each theorem is a corollary of the other)  Fourier's proof is the one that was usually given, during 19th century, in textbooks on the theory of equations  A complete solution of the problem was given in 1829 by Jacques Charles François Sturm 

Discovery of the greenhouse effect
In the 1820s, Fourier calculated that an object the size of the Earth, and at its distance from the Sun, should be considerably colder than the planet actually is if warmed by only  the effects of incoming solar radiation  He examined various possible sources of the additional observed heat in articles published in 1824 and 1827  However, in the end, because of the large 33-degree difference between his calculations and observations, Fourier mistakenly believed that there is a significant contribution of radiation from interstellar space  Still, Fourier's consideration of the possibility that the Earth's atmosphere might act as an insulator of some kind is widely recognized as the first proposal of what is now known as the greenhouse effect, although Fourier never called it that In his articles, Fourier referred to an experiment by de Saussure, who lined a vase with blackened cork  Into the cork, he inserted several panes of transparent glass, separated by intervals of air  Midday sunlight was allowed to enter at the top of the vase through the glass panes  The temperature became more elevated in the more interior compartments of this device  Fourier concluded that gases in the atmosphere could form a stable barrier like the glass panes  This conclusion may have contributed to the later use of the metaphor of the "greenhouse effect" to refer to the processes that determine atmospheric temperatures  Fourier noted that the actual mechanisms that determine the temperatures of the atmosphere included convection, which was not present in de Saussure's experimental device 

Works
See also
Fourier analysis
Fourier–Deligne transform
Heat equation
Least-squares spectral analysis
List of things named after Joseph Fourier
Passage 7:
Morton number
In fluid dynamics, the Morton number (Mo) is a dimensionless number used together with the Eötvös number or Bond number to characterize the shape of bubbles or drops moving in a surrounding fluid or continuous phase, c 
It is named after Rose Morton, who described it with W  L  Haberman in 1953 

Definition
The Morton number is defined as

  
    
      
        
          M
          o
        
        =
        
          
            
              g
              
                μ
                
                  c
                
                
                  4
                
              
              
              Δ
              ρ
            
            
              
                ρ
                
                  c
                
                
                  2
                
              
              
                σ
                
                  3
                
              
            
          
        
        ,
      
    
    {\displaystyle \mathrm {Mo} ={\frac {g\mu _{c}^{4}\,\Delta \rho }{\rho _{c}^{2}\sigma ^{3}}},}
  where g is the acceleration of gravity, 
  
    
      
        
          μ
          
            c
          
        
      
    
    {\displaystyle \mu _{c}}
   is the viscosity of the surrounding fluid, 
  
    
      
        
          ρ
          
            c
          
        
      
    
    {\displaystyle \rho _{c}}
   the density of the surrounding fluid, 
  
    
      
        Δ
        ρ
      
    
    {\displaystyle \Delta \rho }
   the difference in density of the phases, and 
  
    
      
        σ
      
    
    {\displaystyle \sigma }
   is the surface tension coefficient   For the case of a bubble with a negligible inner density the Morton number can be simplified to 

  
    
      
        
          M
          o
        
        =
        
          
            
              g
              
                μ
                
                  c
                
                
                  4
                
              
            
            
              
                ρ
                
                  c
                
              
              
                σ
                
                  3
                
              
            
          
        
         
      
    
    {\displaystyle \mathrm {Mo} ={\frac {g\mu _{c}^{4}}{\rho _{c}\sigma ^{3}}} }

Relation to other parameters
The Morton number can also be expressed by using a combination of the Weber number, Froude number and Reynolds number,

  
    
      
        
          M
          o
        
        =
        
          
            
              
                W
                e
              
              
                3
              
            
            
              
                
                  F
                  r
                
                
                  2
                
              
              
              
                
                  R
                  e
                
                
                  4
                
              
            
          
        
         
      
    
    {\displaystyle \mathrm {Mo} ={\frac {\mathrm {We} ^{3}}{\mathrm {Fr} ^{2}\,\mathrm {Re} ^{4}}} }
  The Froude number in the above expression is defined as

  
    
      
        
          F
          
            r
            
              2
            
          
        
        =
        
          
            
              V
              
                2
              
            
            
              g
              d
            
          
        
      
    
    {\displaystyle \mathrm {Fr^{2}} ={\frac {V^{2}}{gd}}}
  where V is a reference velocity and d is the equivalent diameter of the drop or bubble 
Passage 8:
Kapitza number
The Kapitza number (Ka) is a dimensionless number named after the prominent Russian physicist Pyotr Kapitsa (Peter Kapitza)  He provided the first extensive study of the ways in which a thin film of liquid flows down inclined surfaces  Expressed as the ratio of surface tension forces to inertial forces, the Kapitza number acts as an indicator of the hydrodynamic wave regime in falling liquid films  Liquid film behavior represents a subset of the more general class of free boundary problems  and is important in a wide range of engineering and technological applications such as evaporators, heat exchangers, absorbers, microreactors, small-scale electronics/microprocessor cooling schemes, air conditioning and gas turbine blade cooling 
After World War II Kapitza was removed from all his positions, including director of his Institute for Physical Problems, for refusing to work on nuclear weapons  He was at his country house and devised experiments to work on there, including his experiments on falling films of liquid Unlike most dimensionless numbers used in the study of fluid mechanics, the Kapitza number represents a material property, as it is formed by combining powers of the surface tension, density, gravitational acceleration and kinematic viscosity 

  
    
      
        K
        a
        =
        
          
            σ
            
              ρ
              (
              g
              sin
              ⁡
              β
              
                )
                
                  1
                  
                    /
                  
                  3
                
              
              
                ν
                
                  4
                  
                    /
                  
                  3
                
              
            
          
        
      
    
    {\displaystyle Ka={\frac {\sigma }{\rho (g\sin \beta )^{1/3}\nu ^{4/3}}}}
  where σ is the surface tension (SI units: N/m), g is gravitational acceleration (m/s2), ρ is density (kg/m3), β is inclination angle (rad), and ν is kinematic viscosity (m2/s) 

Notes
Passage 9:
Fourier number
In the study of heat conduction, the Fourier number,  is the ratio of time, t, to a characteristic time scale for heat diffusion, td  This dimensionless group is named in honor of J B J  Fourier, who formulated the modern understanding of heat conduction  The time scale for diffusion characterizes the time needed for heat to diffuse over a distance, L  For a medium with thermal diffusivity, α, this time scale is td = L2/α, so that the Fourier number is t/td = αt/L2  The Fourier number is often denoted as Fo or FoL The Fourier number can also be used in the study of mass diffusion, if the thermal diffusivity is replaced by a mass diffusivity 
The Fourier number is used in analysis of time dependent transport phenomena, generally in conjunction with the Biot number if convection is present  The Fourier number arises naturally in nondimensionalization of the heat equation 

Definition
The general definition of the Fourier number, Fo, is:
For heat diffusion with a characteristic length scale L in a medium of thermal diffusivity, α,  the diffusion time scale is td =L2/α, so that

where:

α is the thermal diffusivity (m2/s)
t is the time (s)
L is the characteristic length through which conduction occurs (m)

Interpretation of the Fourier number
Consider transient heat conduction in  a slab of thickness L that is initially at a uniform temperature, T0  One side of the slab is heated to higher temperature, Th at time t = 0   The other side is adiabatic  The time needed for the other side of the object to show significant temperature change is the diffusion time, td   
When Fo ≪ 1, not enough time has passed for the other side to change temperature  In this case, significant temperature change only occurs close to the heated side, and most of the slab remains at T0 
When Fo ≅ 1, significant temperature change occurs all the way through the thickness L  None of the slab remains at temperature T0 
When Fo ≫ 1, enough time has passed for the slab to approach steady state  The entire slab approaches temperature Th 

Derivation and usage
The Fourier number can be derived by nondimenionalizing the time-dependent diffusion equation   As an example, consider a rod of length L that is being heated from an initial temperature, T0, by the imposition at time t = 0 of a higher temperature at x = L, TL (with x along the axis of the rod)  The heat equation in one spatial dimension, x, can be applied 

where T is the temperature for 0 < x < L and t > 0  The differential equation can be scaled into a dimensionless form  A dimensionless temperature may be defined as Θ = (T - TL)/(T0 - TL), and the equation may be divided through by α/L2:

The resulting dimensionless time variable is the Fourier number, FoL = αt/L2  The characteristic time scale for diffusion, td =L2/α, comes directly from this scaling of the heat equation  
The Fourier number is frequently used as the nondimensional time in studying transient heat conduction in solids    A second parameter, the Biot number arises in nondimensionalization when convective boundary conditions are applied to the heat equation  Together, the Fourier number and the Biot number determine the temperature response of a solid subjected to convective heating or cooling 

Application to mass transfer
An analogous Fourier number can be derived by nondimensionalization of Fick's second law of diffusion  The result is a mass transfer Fourier number, Fom defined as:
where:

Fom is the mass transfer Fourier number
D is the mass diffusivity (m2/s)
t is the time (s)
L is the length scale of interest (m)The mass transfer Fourier number can be applied to the study of certain time-dependent mass diffusion problems 

See also
Biot number
Convection
Heat conduction
Heat equation
Molecular diffusion
Context 3: Passage 1:
Short interspersed nuclear elements (SINEs)
Short interspersed nuclear elements (SINEs) are non-autonomous, non-coding transposable elements (TEs) that are about 100 to 700 base pairs in length  They are a class of retrotransposons, DNA elements that amplify themselves throughout eukaryotic genomes, often through RNA intermediates  SINEs compose about 13% of the mammalian genome The internal regions of SINEs originate from tRNA and remain highly conserved, suggesting positive pressure to preserve structure and function of SINEs   While SINEs are present in many species of vertebrates and invertebrates, SINEs are often lineage specific, making them useful markers of divergent evolution between species  Copy number variation and mutations in the SINE sequence make it possible to construct phylogenies based on differences in SINEs between species  SINEs are also implicated in certain types of genetic disease in humans and other eukaryotes 
In essence, short interspersed nuclear elements are genetic parasites which have evolved very early in the history of eukaryotes to utilize protein machinery within the organism as well as to co-opt the machinery from similarly parasitic genomic elements  The simplicity of these elements make them remarkably successful at persisting and amplifying (through retrotransposition)  within the genomes of eukaryotes  These "parasites" which have become ubiquitous in genomes can be very deleterious to organisms as discussed below  However, eukaryotes have been able to integrate short-interspersed nuclear elements into different signaling, metabolic and regulatory pathways and SINEs have become a great source of genetic variability  They seem to play a particularly important role in the regulation of gene expression and the creation of RNA genes  This regulation extends to chromatin re-organization and the regulation of genomic architecture  The different lineages, mutations, and activities among eukaryotes make short-interspersed nuclear elements a useful tool in phylogenetic analysis 

Classification and structure
SINEs are classified as non-LTR retrotransposons because they do not contain long terminal repeats (LTRs)  There are three types of SINEs common to vertebrates and invertebrates: CORE-SINEs, V-SINEs, and AmnSINEs  SINEs have 50-500 base pair internal regions which contain a tRNA-derived segment with A and B boxes that serve as an internal promoter for RNA polymerase III 

Internal structure
SINEs are characterized by their different modules, which are essentially a sectioning of their sequence  SINEs can, but do not necessarily have to possess a head, a body, and a tail  The head, is at the 5' end of short-interspersed nuclear elements and is an evolutionarily derived from an RNA synthesized by RNA Polymerase III such as ribosomal RNAs and tRNAs; the 5' head is indicative of which endogenous element that SINE was derived from and was able to parasitically utilize its transcriptional machinery  For example, the 5' of the Alu sine is derived from 7SL RNA, a sequence transcribed by RNA Polymerase III which codes for the RNA element of SRP, an abundant ribonucleoprotein  The body of SINEs possess an unknown origin but often share much homology with a corresponding LINE which thus allows SINEs to parasitically co-opt endonucleases coded by LINEs (which recognize certain sequence motifs)  Lastly, the 3′ tail of SINEs is composed of short simple repeats of varying lengths; these simple repeats are sites where two (or more) short-interspersed nuclear elements can combine to form a dimeric SINE  Short-interspersed nuclear elements which only possess a head and tail are called simple SINEs whereas short-interspersed nuclear elements which also possess a body or are a combination of two or more SINEs are complex SINEs 

Transcription
Short-interspersed nuclear elements are transcribed by RNA polymerase III which is known to transcribe ribosomal RNA and tRNA, two types of RNA vital to ribosomal assembly and mRNA translation  SINEs, like tRNAs and many small-nuclear RNAs possess an internal promoter and thus are transcribed differently than most protein-coding genes   In other words, short-interspersed nuclear elements have their key promoter elements within the transcribed region itself  Though transcribed by RNA polymerase III, SINEs and other genes possessing internal promoters, recruit different transcriptional machinery and factors than genes possessing upstream promoters 

Effects on gene expression
Changes in chromosome structure influence gene expression primarily by affecting the accessibility of genes to transcriptional machinery  The chromosome has a very complex and hierarchical system of organizing the genome  This system of organization, which includes histones, methyl groups, acetyl groups, and a variety of proteins and RNAs allows different domains within a chromosome to be accessible to polymerases, transcription factors, and other associated proteins to different degrees   Furthermore, the shape and density of certain areas of a chromosome can affect the shape and density of neighboring (or even distant regions) on the chromosome through interaction facilitated by different proteins and elements  Non-coding RNAs  such as short-interspersed nuclear elements, which have been known to associate with and contribute to chromatin structure, can thus play huge role in regulating gene expression   Short-interspersed-nuclear-elements similarly can be involved in gene regulation by modifying genomic architecture 
In fact Usmanova et al  2008 suggested that short-interspersed nuclear elements can serve as direct signals in chromatin rearrangement and structure   The paper examined the global distribution of SINEs in mouse and human chromosomes and determined that this distribution was very similar to genomic distributions of genes and CpG motifs  The distribution of SINEs to genes was significantly more similar than that of other non-coding genetic elements and even differed significantly from the distribution of long-interspersed nuclear elements  This suggested that the SINE distribution was not a mere accident caused by LINE-mediated retrotransposition but rather that SINEs possessed a role in gene-regulation  Furthermore, SINEs frequently contain motifs for YY1 polycomb proteins  YY1 is a zinc-finger protein that acts as a transcriptional repressor for a wide-variety of genes essential for development and signaling   Polycomb protein YY1 is believed to mediate the activity of histone deacetylases and histone acetyltransferases to facilitate chromatin re-organization; this is often to facilitate the formation of heterochromatin (gene-silencing state)  Thus, the analysis suggests that short-interspersed nuclear elements can function as a ‘signal-booster' in the polycomb-dependent silencing of gene-sets through chromatin re-organization   In essence, it is the cumulative effect of many types of interactions that leads to the difference between euchromatin, which is not tightly packed and generally more accessible to transcriptional machinery, and heterochromatin, which is tightly packed and generally not accessible to transcriptional machinery; SINEs seem to play an evolutionary role in this process 
In addition to directly affecting chromatin structure, there are a number of ways in which SINEs can potentially regulate gene expression  For example, long non-coding RNA can directly interact with transcriptional repressors and activators, attenuating or modifying their function   This type of regulation can occur in different ways: the RNA transcript can directly bind to the transcription factor as a co-regulator; also, the RNA can regulate and modify the ability of co-regulators to associate with the transcription factor   For example, Evf-2, a certain long non-coding RNA, has been known to function as a co-activator for certain homeobox transcription factors which are critical to nervous system development and organization  Furthermore, RNA transcripts can interfere with the functionality of the transcriptional complex by interacting or associating with RNA polymerases during the transcription or loading processes  Moreover, non-coding RNAs like SINEs can bind or interact directly with the DNA duplex coding the gene and thus prevent its transcription Also, many non-coding RNAs are distributed near protein-coding genes, often in the reverse direction  This is especially true for short-interspersed nuclear elements as seen in Usmanova et al  These non-coding RNAs, which lie adjacent to or overlap gene-sets provide a mechanism by which transcription factors and machinery can be recruited to increase or repress the transcription of local genes  The particular example of SINEs potentially recruiting the YY1 polycomb transcriptional repressor is discussed above   Alternatively, it also provides a mechanism by which local gene expression can be curtailed and regulated because the transcriptional complexes can hinder or prevent nearby genes from being transcribed  There is research to suggest that this phenomenon is particularly seen in the gene-regulation of pluripotent cells In conclusion, non-coding RNAs such as SINEs are capable of affecting gene expression on a multitude of different levels and in different ways  Short-interspersed nuclear elements are believed to be deeply integrated into a complex regulatory network capable of fine-tuning gene expression across the eukaryotic genome 

Propagation and regulation
The RNA coded by the short-interspersed nuclear element does not code for any protein product but is nonetheless reverse-transcribed and inserted back into an alternate region in the genome  For this reason, short interspersed nuclear elements are believed to have co-evolved with long interspersed nuclear element (LINEs), as LINEs do in fact encode protein products which enable them to be reverse- transcribed and integrated back into the genome   SINEs are  believed to have co-opted the proteins coded by LINEs which are contained in 2 reading frames  Open reading frame 1 (ORF 1)  encodes a protein which binds to RNA and acts as a chaperone to facilitate and maintain the LINE protein-RNA complex structure  Open reading frame 2 (ORF 2) codes a protein which possesses both endonuclease and reverse transcriptase activities  This enables the LINE mRNA to be reverse-transcribed into DNA and integrated into the genome based on the sequence-motifs recognized by the protein's endonuclease domain 
LINE-1 (L1) is transcribed and retrotransposed most frequently in the germ-line and during early development; as a result SINEs move around the genome most during these periods  SINE transcription is down-regulated by transcription factors in somatic cells after early development, though stress can cause up-regulation of normally silent SINEs  SINEs can be transferred between individuals or species via horizontal transfer through a viral vector SINEs are known to share sequence homology with LINES which gives a basis by which the LINE machinery can reverse transcribe and integrate SINE transcripts  Alternately, some SINEs are believed to use a much more complex system of integrating back into the genome; this system involves the use random double-stranded DNA breaks (rather than the endonuclease coded by related long-interspersed nuclear elements creating an insertion-site)  These DNA breaks are utilized to prime reverse transcriptase, ultimately integrating the SINE transcript back into the genome  SINEs nonetheless depend on enzymes coded by other DNA elements and are thus known as non-autonomous retrotransposons as they depend on the machinery of LINEs, which are known as autonomous retrotransposons <The theory that short-interspersed nuclear elements have evolved to utilize the retrotransposon machinery of long-interspersed nuclear elements is supported by studies which examine the presence and distribution of LINEs and SINEs in taxa of different species  For example, LINEs and SINEs in rodents and primates show very strong homology at the insertion-site motif  Such evidence is a basis for the proposed mechanism in which integration of the SINE transcript can be co-opted with LINE-coded protein products  This is specifically demonstrated by a detailed analysis of over 20 rodent species profiled LINEs and SINEs, mainly L1s and B1s respectively; these are families of LINEs and SINEs found at high frequencies in rodents along with other mammals  The study sought to provide phylogenetic clarity within the context of LINE and SINE activity 
The study arrived at a candidate taxa believed to be the first instance of L1 LINE extinction; it expectedly discovered that there was no evidence to suggest that B1 SINE activity occurred in species which did not have L1 LINE activity  Also, the study suggested that B1 short-interspersed nuclear element silencing in fact occurred before L1 long-interspersed nuclear element extinction; this is due to the fact that B1 SINEs are silenced in the genus most-closely related to the genus which does not contain active L1 LINEs (though the genus with B1 SINE silencing still contains active L1 LINEs)   Another genus was also found which similarly contained active L1 long-interspersed nuclear elements but did not contain B1 short-interspersed nuclear elements; the opposite scenario, in which active B1 SINEs were present in a genus which did not possess active L1 LINEs was not found  This result was expected and strongly supports the theory that SINEs have evolved to co-opt the RNA-binding proteins, endonucleases, and reverse-transcriptases coded by LINEs  In taxa which do not actively transcribe and translate long-interspersed nuclear elements protein-products, SINEs do not have the theoretical foundation by which to retrotranspose within the genome  The results obtained in Rinehart et al  are thus very supportive of the current model of SINE retrotransposition 

Effects of SINE transposition
Insertion of a SINE upstream of a coding region may result in exon shuffling or changes to the regulatory region of the gene  Insertion of a SINE into the coding sequence of a gene can have deleterious effects and unregulated transposition can cause genetic disease  The transposition and recombination of SINEs and other active nuclear elements is thought to be one of the major contributions of genetic diversity between lineages during speciation 

Common SINEs
Short-interspersed nuclear elements are believed to have parasitic origins in eukaryotic genomes  These SINEs have mutated and replicated themselves a large number of times on an evolutionary time-scale and thus form many different lineages  Their early evolutionary origin has caused them to be ubiquitous in many eukaryotic lineages 
Alu elements, short-interspersed nuclear element of about 300 nucleotides, are the most common SINE in humans, with >1,000,000 copies throughout the genome, which is over 10 percent of the total genome; this is not uncommon among other species  Alu element copy number differences can be used to distinguish between and construct phylogenies of primate species  Canines differ primarily in their abundance of SINEC_Cf repeats throughout the genome, rather than other gene or allele level mutations  These dog-specific SINEs may code for a splice acceptor site, altering the sequences that appear as exons or introns in each species Apart from mammals, SINEs can reach high copy numbers in a range of species, including nonbony vertebrates (elephant shark) and some fish species (coelacanths)  In plants, SINEs are often restricted to closely related species and have emerged, decayed, and vanished frequently during evolution  Nevertheless, some SINE families such as the Au-SINEs and the Angio-SINEs are unusually widespread across many often unrelated plant species 

Diseases
There are >50 human diseases associated with SINEs  When inserted near or within the exon, SINEs can cause improper splicing, become coding regions, or change the reading frame, often leading to disease phenotypes in humans and other animals  Insertion of Alu elements in the human genome is associated with breast cancer, colon cancer, leukemia, hemophilia, Dent's disease, cystic fibrosis, neurofibromatosis, and many others 

microRNAs
The role of short-interspersed nuclear elements in gene regulation within cells has been supported by multiple studies  One such study examined the correlation between a certain family of SINEs with microRNAs (in zebrafish)  The specific family of SINEs being examined was the Anamnia V-SINEs; this family of short interspersed nuclear elements is often found in the untranslated region of the 3' end of many genes and is present in vertebrate genomes   The study involved a computational analysis in which the genomic distribution and activity of the Anamnia V-SINEs in Danio rerio zebrafish was examined; furthermore, these V-SINEs potential to generate novel microRNA loci was analyzed   It was found that genes which were predicted to possess V-SINEs were targeted by microRNAs with significantly higher hybridization E-values (relative to other areas in the genome)   The genes that had high hybridization E-values were genes particularly involved in metabolic and signaling pathways  Almost all miRNAs identified to have a strong ability to hybridize to putative V-SINE sequence motifs in genes have been identified (in mammals) to have regulatory roles  These results which establish a correlation between short-interspersed nuclear elements and different regulatory microRNAs strongly suggest that V-SINEs have a significant role in attenuating responses to different signals and stimuli related to metabolism, proliferation and differentiation  Many other studies must be undertaken to establish the validity and extent of short-interspersed nuclear element retrotransposons' role in regulatory gene-expression networks  In conclusion, though not much is known about the role and mechanism by which SINEs generate miRNA gene loci  it is generally understood that SINEs have played a significant evolutionary role in the creation of "RNA-genes", this is also touched upon above in SINEs and pseudogenes 
With such evidence suggesting that short-interspersed nuclear elements have been evolutionary sources for microRNA loci generation it is important to further discuss the potential relationships between the two as well as the mechanism by which the microRNA regulates RNA degradation and more broadly, gene expression   A microRNA is a non-coding RNA generally 22 nucleotides in length  This non-protein coding oligonucleotide is itself coded by longer nuclear DNA sequence usually transcribed by RNA polymerase II which is also responsible for the transcription of most mRNAs and snRNAs in eukaryotes   However, some research suggests that some microRNAs that possess upstream short-interspersed nuclear elements are transcribed by RNA polymerase III which is widely implicated in ribosomal RNA and tRNA, two transcripts vital to mRNA translation   This provides an alternate mechanism by which short-interspersed nuclear elements could be interacting with or mediating gene-regulatory networks involving microRNAs 
The regions coding miRNA can be independent RNA-genes often being anti-sense to neighboring protein-coding genes, or can be found within the introns of protein-coding genes  The co-localization of microRNA and protein-coding genes provides a mechanistic foundation by which microRNA regulates gene-expression  Furthermore, Scarpato et al   reveals (as discussed above) that genes predicted to possess short-interspersed nuclear elements (SINEs) through sequence analysis were targeted and hybridized by microRNAs significantly greater than other genes  This provides an evolutionarily path by which the parasitic SINEs were co-opted and utilized to form RNA-genes (such as microRNAs) which have evolved to play a role in complex gene-regulatory networks 
The microRNAs are transcribed as part of longer RNA strands of generally about 80 nucleotides which through complementary base-pairing are able to form hairpin loop structures These structures are recognized and processed in the nucleus by the nuclear protein DiGeorge Syndrome Critical Region 8 (DGCR8) which recruits and associates with the Drosha protein   This complex is responsible for cleaving some of the hair-pin structures from the pre-microRNA which is transported to the cytoplasm  The pre-miRNA is processed by the protein DICER into a double stranded 22 nucleotide   Thereafter, one of the strands is incorporated into a multi-protein RNA-induced silencing complex (RISC)  Among these proteins are proteins from the Argonaute family which are critical to the complex's ability to interact with and repress the translation of the target mRNA Understanding the different ways in which microRNA regulates gene-expression, including mRNA-translation and degradation is key to understanding the potential evolutionary role of SINEs in gene-regulation and in the generation of microRNA loci  This, in addition to SINEs' direct role in regulatory networks (as discussed in SINEs as long non-coding RNAs) is crucial to beginning to understand the relationship between SINEs and certain diseases  Multiple studies have suggested that increased SINE activity is correlated with certain gene-expression profiles and post-transcription regulation of certain genes   In fact, Peterson et al  2013 demonstrated that high SINE RNA expression correlates with post-transcriptional downregulation of BRCA1, a tumor suppressor implicated in multiple forms of cancer, namely breast cancer  Furthermore, studies have established a strong correlation between transcriptional mobilization of SINEs and certain cancers and conditions such as hypoxia; this can be due to the genomic instability caused by SINE activity as well as more direct-downstream effects   SINEs have also been implicated in countless other diseases  In essence, short-interspersed nuclear elements have become deeply integrated in countless regulatory, metabolic and signaling pathways and thus play an inevitable role in causing disease  Much is still to be known about these genomic parasites but it is clear they play a significant role within eukaryotic organisms 

SINEs and pseudogenes
The activity of SINEs however has genetic vestiges which do not seem to play a significant role, positive or negative, and manifest themselves in the genome as pseudogenes   SINEs however should not be mistaken as RNA pseudogenes  In general, pseudogenes are generated when processed mRNAs of protein-coding genes are reverse-transcribed and incorporated back into the genome (RNA pseudogenes are reverse transcribed RNA genes)  Pseudogenes are generally functionless as they descend from processed RNAs independent of their evolutionary-context which includes introns and different regulatory elements which enable transcription and processing  These pseudogenes, though non-functional may in some cases still possess promoters, CpG islands, and other features which enable transcription; they thus can still be transcribed and may possess a role in the regulation of gene expression (like SINEs and other non-coding elements)   Pseudogenes thus differ from SINEs in that they are derived from transcribed- functional RNA whereas SINEs are DNA elements which retrotranspose by co-opting RNA genes transcriptional machinery  However, there are studies which suggest  that retro-transposable elements such as short-interspersed nuclear elements are not only capable of copying themselves in alternate regions in the genome but are also able to do so for random genes too   Thus SINEs can be playing a vital role in the generation of pseudogenes, which themselves are known to be involved in regulatory networks  This is perhaps another means by which SINEs have been able to influence and contribute to gene-regulation 
Passage 2:
Exonuclease VII
The enzyme exodeoxyribonuclease VII (EC 3 1 11 6, Escherichia coli exonuclease VII, E  coli exonuclease VII, endodeoxyribonuclease VII, exodeoxyribonuclease VII) is a bacterial exonuclease enzyme  It is composed of two nonidentical subunits; one large subunit and 4 small ones  that catalyses exonucleolytic cleavage in either 5′- to 3′- or 3′- to 5′-direction to yield nucleoside 5′-phosphates  The large subunit also contains an N-terminal OB-fold domain that binds to nucleic acids 
Passage 3:
Ribosomal protein
A ribosomal protein (r-protein or rProtein) is any of the proteins that, in conjunction with rRNA, make up the ribosomal subunits involved in the cellular process of translation  E  coli, other bacteria and Archaea have a 30S small subunit and a 50S large subunit, whereas humans and yeasts have a 40S small subunit and a 60S large subunit  Equivalent subunits are frequently numbered differently between bacteria, Archaea, yeasts and humans A large part of the knowledge about these organic molecules has come from the study of E  coli ribosomes  All ribosomal proteins have been isolated and many specific antibodies have been produced  These, together with electronic microscopy and the use of certain reactives, have allowed for the determination of the topography of the proteins in the ribosome   More recently, a near-complete (near)atomic picture of the ribosomal proteins is emerging from the latest high-resolution cryo-EM data (including PDB: 5AFI​) 

Conservation
Ribosomal proteins are among the most highly conserved proteins across all life forms  Among the 40 proteins found in various small ribosomal subunits (RPSs), 15 subunits are universally conserved across prokaryotes and eukaryotes  However, 7 subunits are only found in bacteria (bS21, bS6, bS16, bS18, bS20, bS21, and bTHX), while 17 subunits are only found in archaea and eukaryotes  Typically 22 proteins are found in bacterial small subunits and 32 in yeast, human and most likely most other eukaryotic species  Twenty-seven (out of 32) proteins of the eukaryotic small ribosomal subunit proteins are also present in archaea (no ribosomal protein is exclusively found in archaea), confirming that they are more closely related to eukaryotes than to bacteria Among the large ribosomal subunit (RPLs), 18 proteins are universal, i e  found in both bacteria, eukaryotes, and archaea  14 proteins are only found in bacteria, while 27 proteins are only found in archaea and eukaryotes  Again, archaea have no proteins unique to them 

Essentiality
Despite their high conservation over billions of years of evolution, the absence of several ribosomal proteins in certain species shows that ribosomal subunits have been added and lost over the course of evolution  This is also reflected by the fact that several ribosomal proteins do not appear to be essential when deleted  For instance, in E  coli nine ribosomal proteins (uL15, bL21, uL24, bL27, uL29, uL30, bL34, uS9, and uS17) are nonessential for survival when deleted  Taken together with previous results, 22 of the 54 E  coli ribosomal protein genes can be individually deleted from the genome  Similarly, 16 ribosomal proteins (uL1, bL9, uL15, uL22, uL23, bL28, uL29, bL32, bL33 1, bL33 2, bL34, bL35, bL36, bS6, bS20, and bS21) were successfully deleted in Bacillus subtilis  In conjunction with previous reports, 22 ribosomal proteins have been shown to be nonessential in B  subtilis, at least for cell proliferation 

Assembly
In E  coli
The ribosome of E  coli has about 22 proteins in the small subunit (labelled S1 to S22) and 33 proteins in the large subunit (somewhat counter-intuitively called L1 to L36)  All of them are different with three exceptions: one protein is found in both subunits (S20 and L26), L7 and L12 are acetylated and methylated forms of the same protein, and L8 is a complex of L7/L12 and L10  In addition, L31 is known to exist in two forms, the full length at 7 9 kilodaltons (kDa) and fragmented at 7 0 kDa  This is why the number of proteins in a ribosome is of 56  Except for S1 (with a molecular weight of 61 2 kDa), the other proteins range in weight between 4 4 and 29 7 kDa Recent de novo proteomics experiments where the authors characterized in vivo ribosome-assembly intermediates and associated assembly factors from wild-type Escherichia coli cells using a general quantitative mass spectrometry (qMS) approach have confirmed the presence of all the known small and large subunit components and have identified a total of 21 known and potentially new ribosome-assembly-factors that co-localise with various ribosomal particles 

Disposition in the small ribosomal subunit
In the small (30S) subunit of E  coli ribosomes, the proteins denoted uS4, uS7, uS8, uS15, uS17, bS20 bind independently to 16S rRNA  After assembly of these primary binding proteins, uS5, bS6, uS9, uS12, uS13, bS16, bS18, and uS19 bind to the growing ribosome  These proteins also potentiate the addition of uS2, uS3, uS10, uS11, uS14, and bS21  Protein binding to helical junctions is important for initiating the correct tertiary fold of RNA and to organize the overall structure  Nearly all the proteins contain one or more globular domains  Moreover, nearly all contain long extensions that can contact the RNA in far-reaching regions  Additional stabilization results from the proteins' basic residues, as these neutralize the charge repulsion of the RNA backbone  Protein–protein interactions also exist to hold structure together by electrostatic and hydrogen bonding interactions  Theoretical investigations pointed to correlated effects of protein-binding onto binding affinities during the assembly processIn one study, the net charges (at pH 7 4) of the ribosomal proteins comprising the highly conserved S10-spc cluster were found to have an inverse relationship with the halophilicity/halotolerance levels in bacteria and archaea  In non-halophilic bacteria, the S10-spc proteins are generally basic, contrasting with the overall acidic whole proteomes of the extremely halophiles  The universal uL2 lying in the oldest part of the ribosome, is always positively charged irrespective of the strain/organism it belongs to 

In eukaryotes
Ribosomes in eukaryotes contain 79–80 proteins and four ribosomal RNA (rRNA) molecules 
General or specialized chaperones solubilize the ribosomal proteins and facilitate their import into the nucleus  Assembly of the eukaryotic ribosome appears to be driven by the ribosomal proteins in vivo when assembly is also aided by chaperones   Most ribosomal proteins assemble with rRNA co-transcriptionally, becoming associated more stably as assembly proceeds, and the active sites of both subunits are constructed last 

Table of ribosomal proteins
In the past, different nomenclatures were used for the same ribosomal protein in different organisms  Not only were the names not consistent across domains; the names also differed between organisms within a domain, such as humans and S  cervisiae, both eukaryotes  This was due to researchers assigning names before the sequences were known, causing trouble for later research  The following tables use the unified nomenclature by Ban et al , 2014  The same nomenclature is used by UniProt's "family" curation In general, cellular ribosomal proteins are to be called simply using the cross domain name, e g  "uL14" for what is currently called L23 in humans  A suffix is used for the organellar versions, so that "uL14m" refers to the human mitochondrial uL14 (MRPL14)  Organelle-specific proteins use their own cross-domain prefixes, for example "mS33" for MRPS33: Table S3,S4  and "cL37" for PSRP5 : Table S2,S3  (See the two proceeding citations, also partially by Ban N, for the organelle nomenclatures )

See also
Alpha operon ribosome binding site
Ribosomal protein L20 leader
Mitochondrial ribosome, for a list of its protein subunits
Passage 4:
Nuclear cap-binding protein complex
Nuclear cap-binding protein complex is a RNA-binding protein which binds to the 5' cap of pre-mRNA  The cap and nuclear cap-binding protein have many functions in mRNA biogenesis including splicing, 3'-end formation by stabilizing the interaction of the 3'-end processing machinery, nuclear export and protection of the transcripts from nuclease degradation  When RNA is exported to the cytoplasm the nuclear cap-binding protein complex is replaced by cytoplasmic cap binding complex  The nuclear cap-binding complex is a functional heterodimer and composed of Cbc1/Cbc2 in yeast and CBC20/CBC80 in multicellular eukaryotes  Human nuclear cap-binding protein complex shows the large subunit, CBC80 consists of 757 amino acid residues  Its secondary structure contains approximately sixty percent of helical and one percent of beta sheet in the strand  The small subunit, CBC20 has 98 amino acid residues  Its secondary structure contains approximately twenty percent of helical and twenty-four percent of beta sheet in the strand  Human nuclear cap-binding protein complex plays important role in the maturation of pre-mRNA and in uracil-rich small nuclear RNA 
Passage 5:
Ribozyme
Ribozymes (ribonucleic acid enzymes) are RNA molecules that have the ability to catalyze specific biochemical reactions, including RNA splicing in gene expression, similar to the action of protein enzymes  The 1982 discovery of ribozymes demonstrated that RNA can be both genetic material (like DNA) and a biological catalyst (like protein enzymes), and contributed to the RNA world hypothesis, which suggests that RNA may have been important in the evolution of prebiotic self-replicating systems The most common activities of natural or in vitro evolved ribozymes are the cleavage (or ligation) of RNA and DNA and peptide bond formation  For example, the smallest ribozyme known (GUGGC-3') can aminoacylate a GCCU-3' sequence in the presence of PheAMP  Within the ribosome, ribozymes function as part of the large subunit ribosomal RNA to link amino acids during protein synthesis  They also participate in a variety of RNA processing reactions, including RNA splicing, viral replication, and transfer RNA biosynthesis  Examples of ribozymes include the hammerhead ribozyme, the VS ribozyme, leadzyme, and the hairpin ribozyme 
Researchers who are investigating the origins of life through the RNA world hypothesis have been working on discovering a ribozyme with the capacity to self-replicate, which would require it to have the ability to catalytically synthesize polymers of RNA  This should be able to happen in prebiotically plausible conditions with high rates of copying accuracy to prevent degradation of information but also allowing for the occurrence of occasional errors during the copying process to allow for Darwinian evolution to proceed Attempts have been made to develop ribozymes as therapeutic agents, as enzymes which target defined RNA sequences for cleavage, as biosensors, and for applications in functional genomics and gene discovery 

Discovery
Before the discovery of ribozymes, enzymes—which are defined as catalytic proteins—were the only known biological catalysts  In 1967, Carl Woese, Francis Crick, and Leslie Orgel were the first to suggest that RNA could act as a catalyst  This idea was based upon the discovery that RNA can form complex secondary structures  These ribozymes were found in the intron of an RNA transcript, which removed itself from the transcript, as well as in the RNA component of the RNase P complex, which is involved in the maturation of pre-tRNAs  In 1989, Thomas R  Cech and Sidney Altman shared the Nobel Prize in chemistry for their "discovery of catalytic properties of RNA"  The term ribozyme was first introduced by Kelly Kruger et al  in a paper published in Cell in 1982 It had been a firmly established belief in biology that catalysis was reserved for proteins  However, the idea of RNA catalysis is motivated in part by the old question regarding the origin of life: Which comes first, enzymes that do the work of the cell or nucleic acids that carry the information required to produce the enzymes? The concept of "ribonucleic acids as catalysts" circumvents this problem  RNA, in essence, can be both the chicken and the egg In the 1980s, Thomas Cech, at the University of Colorado Boulder, was studying the excision of introns in a ribosomal RNA gene in Tetrahymena thermophila  While trying to purify the enzyme responsible for the splicing reaction, he found that the intron could be spliced out in the absence of any added cell extract  As much as they tried, Cech and his colleagues could not identify any protein associated with the splicing reaction  After much work, Cech proposed that the intron sequence portion of the RNA could break and reform phosphodiester bonds  At about the same time, Sidney Altman, a professor at Yale University, was studying the way tRNA molecules are processed in the cell when he and his colleagues isolated an enzyme called RNase-P, which is responsible for conversion of a precursor tRNA into the active tRNA  Much to their surprise, they found that RNase-P contained RNA in addition to protein and that RNA was an essential component of the active enzyme  This was such a foreign idea that they had difficulty publishing their findings  The following year, Altman demonstrated that RNA can act as a catalyst by showing that the RNase-P RNA subunit could catalyze the cleavage of precursor tRNA into active tRNA in the absence of any protein component 
Since Cech's and Altman's discovery, other investigators have discovered other examples of self-cleaving RNA or catalytic RNA molecules  Many ribozymes have either a hairpin – or hammerhead – shaped active center and a unique secondary structure that allows them to cleave other RNA molecules at specific sequences  It is now possible to make ribozymes that will specifically cleave any RNA molecule  These RNA catalysts may have pharmaceutical applications  For example, a ribozyme has been designed to cleave the RNA of HIV  If such a ribozyme were made by a cell, all incoming virus particles would have their RNA genome cleaved by the ribozyme, which would prevent infection 

Structure and mechanism
Despite having only four choices for each monomer unit (nucleotides), compared to 20 amino acid side chains found in proteins, ribozymes have diverse structures and mechanisms



ground_truth: French mathematician and physicist

prompt_front: Answer the question based on the given passages. Only give me the answer and do not output any other words.

Question: The large subunit and small subunit that use two types of RNA are major components that make up what?

The following are given passages.
Context 3:  In many cases they are able to mimic the mechanism used by their protein counterparts  For example, in self cleaving ribozyme RNAs, an in-line SN2 reaction is carried out using the 2’ hydroxyl group as a nucleophile attacking the bridging phosphate and causing 5’ oxygen of the N+1 base to act as a leaving group  In comparison, RNase A, a protein that catalyzes the same reaction, uses a coordinating histidine and lysine to act as a base to attack the phosphate backbone Like many protein enzymes, metal binding is also critical to the function of many ribozymes  Often these interactions use both the phosphate backbone and the base of the nucleotide, causing drastic conformational changes  There are two mechanism classes for the cleavage of a phosphodiester backbone in the presence of metal  In the first mechanism, the internal 2’- OH group attacks the phosphorus center in a SN2 mechanism  Metal ions promote this reaction by first coordinating the phosphate oxygen and later stabling the oxyanion  The second mechanism also follows a SN2 displacement, but the nucleophile comes from water or exogenous hydroxyl groups rather than RNA itself  The smallest ribozyme is UUU, which can promote the cleavage between G and A of the GAAA tetranucleotide via the first mechanism in the presence of Mn2+  The reason why this trinucleotide (rather than the complementary tetramer) catalyzes this reaction may be because the UUU-AAA pairing is the weakest and most flexible trinucleotide among the 64 conformations, which provides the binding site for Mn2+ Phosphoryl transfer can also be catalyzed without metal ions  For example, pancreatic ribonuclease A and hepatitis delta virus (HDV) ribozymes can catalyze the cleavage of RNA backbone through acid-base catalysis without metal ions  Hairpin ribozyme can also catalyze the self-cleavage of RNA without metal ions, but the mechanism for this is still unclear Ribozyme can also catalyze the formation of peptide bond between adjacent amino acids by lowering the activation entropy 

Activities
Although ribozymes are quite rare in most cells, their roles are sometimes essential to life  For example, the functional part of the ribosome, the biological machine that translates RNA into proteins, is fundamentally a ribozyme, composed of RNA tertiary structural motifs that are often coordinated to metal ions such as Mg2+ as cofactors  In a model system, there is no requirement for divalent cations in a five-nucleotide RNA catalyzing trans-phenylalanation of a four-nucleotide substrate with 3 base pairs complementary with the catalyst, where the catalyst/substrate were devised by truncation of the C3 ribozyme The best-studied ribozymes are probably those that cut themselves or other RNAs, as in the original discovery by Cech and Altman  However, ribozymes can be designed to catalyze a range of reactions, many of which may occur in life but have not been discovered in cells RNA may catalyze folding of the pathological protein conformation of a prion in a manner similar to that of a chaperonin 

Ribozymes and the origin of life
RNA can also act as a hereditary molecule, which encouraged Walter Gilbert to propose that in the distant past, the cell used RNA as both the genetic material and the structural and catalytic molecule rather than dividing these functions between DNA and protein as they are today; this hypothesis is known as the "RNA world hypothesis" of the origin of life  Since nucleotides and RNA (and thus ribozymes) can arise by inorganic chemicals, they are candidates for the first enzymes, and in fact, the first "replicators" (i e , information-containing macro-molecules that replicate themselves)  An example of a self-replicating ribozyme that ligates two substrates to generate an exact copy of itself was described in 2002 
The discovery of the catalytic activity of RNA solved the "chicken and egg" paradox of the origin of life, solving the problem of origin of peptide and nucleic acid central dogma  According to this scenario, at the origin of life, all enzymatic activity and genetic information encoding was done by one molecule: RNA 
Ribozymes have been produced in the laboratory that are capable of catalyzing the synthesis of other RNA molecules from activated monomers under very specific conditions, these molecules being known as RNA polymerase ribozymes  The first RNA polymerase ribozyme was reported in 1996, and was capable of synthesizing RNA polymers up to 6 nucleotides in length  Mutagenesis and selection has been performed on an RNA ligase ribozyme from a large pool of random RNA sequences, resulting in isolation of the improved "Round-18" polymerase ribozyme in 2001 which could catalyze RNA polymers now up to 14 nucleotides in length  Upon application of further selection on the Round-18 ribozyme, the B6 61 ribozyme was generated and was able to add up to 20 nucleotides to a primer template in 24 hours, until it decomposes by cleavage of its phosphodiester bonds The rate at which ribozymes can polymerize an RNA sequence multiples substantially when it takes place within a micelle The next ribozyme discovered was the "tC19Z" ribozyme, which can add up to 95 nucleotides with a fidelity of 0 0083 mutations/nucleotide  Next, the "tC9Y" ribozyme was discovered by researchers and was further able to synthesize RNA strands up to 206 nucleotides long in the eutectic phase conditions at below-zero temperature, conditions previously shown to promote ribozyme polymerase activity The RNA polymerase ribozyme (RPR) called tC9-4M was able to polymerize RNA chains longer than itself (i e  longer than 177 nt) in magnesium ion concentrations close to physiological levels, whereas earlier RPRs required prebiotically implausible concentrations of up to 200 mM  The only factor required for it to achieve this was the presence of a very simple amino acid polymer called lysine decapeptide The most complex RPR synthesized by that point was called 24-3, which was newly capable of polymerizing the sequences of a substantial variety of nucleotide sequences and navigating through complex secondary structures of RNA substrates inaccessible to previous ribozymes  In fact, this experiment was the first to use a ribozyme to synthesize a tRNA molecule  Starting with the 24-3 ribozyme, Tjhung et al  applied another fourteen rounds of selection to obtain an RNA polymerase ribozyme by in vitro evolution termed '38-6' that has an unprecedented level of activity in copying complex RNA molecules  However, this ribozyme is unable to copy itself and its RNA products have a high mutation rate  In a subsequent study, the researchers began with the 38-6 ribozyme and applied another 14 rounds of selection to generate the '52-2' ribozyme, which compared to 38-6, was again many times more active and could begin generating detectable and functional levels of the class I ligase, although it was still limited in its fidelity and functionality in comparison to copying of the same template by proteins such as the T7 RNA polymerase An RPR called t5(+1) adds triplet nucleotides at a time instead of just one nucleotide at a time  This heterodimeric RPR can navigate secondary structures inaccessible to 24-3, including hairpins  In the initial pool of RNA variants derived only from a previously synthesized RPR known as the Z RPR, two sequences separately emerged and evolved to be mutualistically dependent on each other  The Type 1 RNA evolved to be catalytically inactive, but complexing with the Type 5 RNA boosted its polymerization ability and enabled intermolecular interactions with the RNA template substrate obviating the need to tether the template directly to the RNA sequence of the RPR, which was a limitation of earlier studies  Not only did t5(+1) not need tethering to the template, but a primer was not needed either as t5(+1) had the ability to polymerize a template in both 3' → 5' and 5' 3 → 3' directions A highly evolved RNA polymerase ribozyme was able to function as a reverse transcriptase, that is, it can synthesize a DNA copy using an RNA template  Such an activity is considered to have been crucial for the transition from RNA to DNA genomes during the early history of life on earth  Reverse transcription capability could have arisen as a secondary function of an early RNA-dependent RNA polymerase ribozyme 
An RNA sequence that folds into a ribozyme is capable of invading duplexed RNA, rearranging into an open holopolymerase complex, and then searching for a specific RNA promoter sequence, and upon recognition rearrange again into a processive form that polymerizes a complementary strand of the sequence  This ribozyme is capable of extending duplexed RNA by up to 107 nucleotides, and does so without needing to tether the sequence being polymerized 

Artificial ribozymes
Since the discovery of ribozymes that exist in living organisms, there has been interest in the study of new synthetic ribozymes made in the laboratory  For example, artificially produced self-cleaving RNAs with good enzymatic activity have been produced  Tang and Breaker isolated self-cleaving RNAs by in vitro selection of RNAs originating from random-sequence RNAs  Some of the synthetic ribozymes that were produced had novel structures, while some were similar to the naturally occurring hammerhead ribozyme 
In 2015, researchers at Northwestern University and the University of Illinois Chicago engineered a tethered ribosome that works nearly as well as the authentic cellular component that produces all the proteins and enzymes within the cell  Called Ribosome-T, or Ribo-T, the artificial ribosome was created by Michael Jewett and Alexander Mankin  The techniques used to create artificial ribozymes involve directed evolution  This approach takes advantage of RNA's dual nature as both a catalyst and an informational polymer, making it easy for an investigator to produce vast populations of RNA catalysts using polymerase enzymes  The ribozymes are mutated by reverse transcribing them with reverse transcriptase into various cDNA and amplified with error-prone PCR  The selection parameters in these experiments often differ  One approach for selecting a ligase ribozyme involves using biotin tags, which are covalently linked to the substrate  If a molecule possesses the desired ligase activity, a streptavidin matrix can be used to recover the active molecules 
Lincoln and Joyce used in vitro evolution to develop ribozyme ligases capable of self-replication in about an hour, via the joining of pre-synthesized highly complementary oligonucleotides Although not true catalysts, the creation of artificial self-cleaving riboswitches, termed aptazymes, has also been an active area of research  Riboswitches are regulatory RNA motifs that change their structure in response to a small molecule ligand to regulate translation  While there are many known natural riboswitches that bind a wide array of metabolites and other small organic molecules, only one ribozyme based on a riboswitch has been described: glmS  Early work in characterizing self-cleaving riboswitches was focused on using theophylline as the ligand  In these studies, an RNA hairpin is formed which blocks the ribosome binding site, thus inhibiting translation  In the presence of the ligand, in these cases theophylline, the regulatory RNA region is cleaved off, allowing the ribosome to bind and translate the target gene  Much of this RNA engineering work was based on rational design and previously determined RNA structures rather than directed evolution as in the above examples  More recent work has broadened the ligands used in ribozyme riboswitches to include thymine pyrophosphate  Fluorescence-activated cell sorting has also been used to engineering aptazymes 

Applications
Ribozymes have been proposed and developed for the treatment of disease through gene therapy  One major challenge of using RNA-based enzymes as a therapeutic is the short half-life of the catalytic RNA molecules in the body  To combat this, the 2’ position on the ribose is modified to improve RNA stability  One area of ribozyme gene therapy has been the inhibition of RNA-based viruses 
A type of synthetic ribozyme directed against HIV RNA called gene shears has been developed and has entered clinical testing for HIV infection Similarly, ribozymes have been designed to target the hepatitis C virus RNA, SARS coronavirus (SARS-CoV), Adenovirus and influenza A and B virus RNA  The ribozyme is able to cleave the conserved regions of the virus's genome, which has been shown to reduce the virus in mammalian cell culture  Despite these efforts by researchers, these projects have remained in the preclinical stage 

Known ribozymes
Well-validated naturally occurring ribozyme classes:

See also
Notes and references
Further reading
External links
Tom Cech's Short Talk: "Discovering Ribozymes"
Passage 6:
Ribosome
Ribosomes () are macromolecular machines, found within all  cells, that perform biological protein synthesis (mRNA translation)  Ribosomes link amino acids together in the order specified by the codons of messenger RNA (mRNA) molecules to form polypeptide chains  Ribosomes consist of two major components: the small and large ribosomal subunits  Each subunit consists of one or more ribosomal RNA (rRNA) molecules and many ribosomal proteins (RPs or r-proteins)  The ribosomes and associated molecules are also known as the translational apparatus 

Overview
The sequence of DNA that encodes the sequence of the amino acids in a protein is transcribed into a messenger RNA chain  Ribosomes bind to messenger RNAs and use their sequences for determining the correct sequence of amino acids to generate a given protein  Amino acids are selected and carried to the ribosome by transfer RNA (tRNA) molecules, which enter the ribosome and bind to the messenger RNA chain via an anti-codon stem loop  For each coding triplet (codon) in the messenger RNA, there is a unique transfer RNA that must have the exact anti-codon match, and carries the correct amino acid for incorporating into a growing polypeptide chain  Once the protein is produced, it can then fold to produce a functional three-dimensional structure 
A ribosome is made from complexes of RNAs and proteins and is therefore a ribonucleoprotein complex  Each ribosome is composed of small (30S) and large (50S) components, called subunits, which are bound to each other:

(30S) has mainly a decoding function and is also bound to the mRNA
(50S) has mainly a catalytic function and is also bound to the aminoacylated tRNAs The synthesis of proteins from their building blocks takes place in four phases: initiation, elongation, termination, and recycling  The start codon in all mRNA molecules has the sequence AUG  The stop codon is one of UAA, UAG, or UGA; since there are no tRNA molecules that recognize these codons, the ribosome recognizes that translation is complete  When a ribosome finishes reading an mRNA molecule, the two subunits separate and are usually broken up but can be re-used  Ribosomes are ribozymes, because the catalytic peptidyl transferase activity that links amino acids together is performed by the ribosomal RNA Ribosomes are often associated with the intracellular membranes that make up the rough endoplasmic reticulum 
Ribosomes from bacteria, archaea and eukaryotes in the three-domain system resemble each other to a remarkable degree, evidence of a common origin  They differ in their size, sequence, structure, and the ratio of protein to RNA  The differences in structure allow some antibiotics to kill bacteria by inhibiting their ribosomes, while leaving human ribosomes unaffected  In all species, more than one ribosome may move along a single mRNA chain at one time (as a polysome), each "reading" a specific sequence and producing a corresponding protein molecule 
The mitochondrial ribosomes of eukaryotic cells functionally resemble many features of those in bacteria, reflecting the likely evolutionary origin of mitochondria 

Discovery
Ribosomes were first observed in the mid-1950s by Romanian-American cell biologist George Emil Palade, using an electron microscope, as dense particles or granules   They were initially called  Palade granules due to their granular structure   The term "ribosome" was proposed in 1958:

During the course of the symposium a semantic difficulty became apparent  To some of the participants, "microsomes" mean the ribonucleoprotein particles of the microsome fraction contaminated by other protein and lipid material; to others, the microsomes consist of protein and lipid contaminated by particles  The phrase "microsomal particles" does not seem adequate, and "ribonucleoprotein particles of the microsome fraction" is much too awkward  During the meeting, the word "ribosome" was suggested, which has a very satisfactory name and a pleasant sound  The present confusion would be eliminated if "ribosome" were adopted to designate ribonucleoprotein particles in sizes ranging from 35 to 100S 
Albert Claude, Christian de Duve, and George Emil Palade were jointly awarded the Nobel Prize in Physiology or Medicine, in 1974, for the discovery of the ribosome  The Nobel Prize in Chemistry 2009 was awarded to Venkatraman Ramakrishnan, Thomas A  Steitz and Ada E  Yonath for determining the detailed structure and mechanism of the ribosome 

Structure
The ribosome is a complex cellular machine  It is largely made up of specialized RNA known as ribosomal RNA (rRNA) as well as dozens of distinct proteins (the exact number varies slightly between species)  The ribosomal proteins and rRNAs are arranged into two distinct ribosomal pieces of different sizes, known generally as the large and small subunit of the ribosome  Ribosomes consist of two subunits that fit together (Figure 2) and work as one to translate the mRNA into a polypeptide chain during protein synthesis (Figure 1)  Because they are formed from two subunits of non-equal size, they are slightly longer in the axis than in diameter 

Prokaryotic ribosomes
Prokaryotic ribosomes are around 20 nm (200 Å) in diameter and are composed of 65% rRNA and 35% ribosomal proteins  Eukaryotic ribosomes are between 25 and 30 nm (250–300 Å) in diameter with an rRNA-to-protein ratio that is close to 1  Crystallographic work has shown that there are no ribosomal proteins close to the reaction site for polypeptide synthesis  This suggests that the protein components of ribosomes do not directly participate in peptide bond formation catalysis, but rather that these proteins act as a scaffold that may enhance the ability of rRNA to synthesize protein (See: Ribozyme) 

The ribosomal subunits of prokaryotes and eukaryotes are quite similar The unit of measurement used to describe the ribosomal subunits and the rRNA fragments is the Svedberg unit, a measure of the rate of sedimentation in centrifugation rather than size  This accounts for why fragment names do not add up: for example, bacterial 70S ribosomes are made of 50S and 30S subunits 
Prokaryotes have 70S ribosomes, each consisting of a small (30S) and a large (50S) subunit  E  coli, for example, has a 16S RNA subunit (consisting of 1540 nucleotides) that is bound to 21 proteins  The large subunit is composed of a 5S RNA subunit (120 nucleotides), a 23S RNA subunit (2900 nucleotides) and 31 proteins 
Affinity label for the tRNA binding sites on the E  coli ribosome allowed the identification of A and P site proteins most likely associated with the peptidyltransferase activity; labelled proteins are L27, L14, L15, L16, L2; at least L27 is located at the donor site, as shown by E  Collatz and A P  Czernilofsky  Additional research has demonstrated that the S1 and S21 proteins, in association with the 3′-end of 16S ribosomal RNA, are involved in the initiation of translation 

Archaeal ribosomes
Archaeal ribosomes share the same general dimensions of bacteria ones, being a 70S ribosome made up from a 50S large subunit, a 30S small subunit, and containing three rRNA chains  However, on the sequence level, they are much closer to eukaryotic ones than to bacterial ones  Every extra ribosomal protein archaea have compared to bacteria has a eukaryotic counterpart, while no such relation applies between archaea and bacteria 

Eukaryotic ribosomes
Eukaryotes have 80S ribosomes located in their cytosol, each consisting of a small (40S) and large (60S) subunit  Their 40S subunit has an 18S RNA (1900 nucleotides) and 33 proteins  The large subunit is composed of a 5S RNA (120 nucleotides), 28S RNA (4700 nucleotides), a 5 8S RNA (160 nucleotides) subunits and 49 proteins 
During 1977, Czernilofsky published research that used affinity labeling to identify tRNA-binding sites on rat liver ribosomes  Several proteins, including L32/33, L36, L21, L23, L28/29 and L13 were implicated as being at or near the peptidyl transferase center 

Plastoribosomes and mitoribosomes
In eukaryotes, ribosomes are present in mitochondria (sometimes called mitoribosomes) and in plastids such as chloroplasts (also called plastoribosomes)  They also consist of large and small subunits bound together with proteins into one 70S particle  These ribosomes are similar to those of bacteria and these organelles are thought to have originated as symbiotic bacteria  Of the two, chloroplastic ribosomes are closer to bacterial ones than mitochondrial ones are  Many pieces of ribosomal RNA in the mitochondria are shortened, and in the case of 5S rRNA, replaced by other structures in animals and fungi  In particular, Leishmania tarentolae has a minimalized set of mitochondrial rRNA  In contrast, plant mitoribosomes have both extended rRNA and additional proteins as compared to bacteria, in particular, many pentatricopetide repeat proteins The cryptomonad and chlorarachniophyte algae may contain a nucleomorph that resembles a vestigial eukaryotic nucleus  Eukaryotic 80S ribosomes may be present in the compartment containing the nucleomorph 

Making use of the differences
The differences between the bacterial and eukaryotic ribosomes are exploited by pharmaceutical chemists to create antibiotics that can destroy a bacterial infection without harming the cells of the infected person  Due to the differences in their structures, the bacterial 70S ribosomes are vulnerable to these antibiotics while the eukaryotic 80S ribosomes are not  Even though mitochondria possess ribosomes similar to the bacterial ones, mitochondria are not affected by these antibiotics because they are surrounded by a double membrane that does not easily admit these antibiotics into the organelle  A noteworthy counterexample, however, includes the antineoplastic antibiotic chloramphenicol, which successfully inhibits bacterial 50S and eukaryotic mitochondrial 50S ribosomes  Ribosomes in chloroplasts, however, are different: Antibiotic resistance in chloroplast ribosomal proteins is a trait that has to be introduced as a marker, with genetic engineering 

Common properties
The various ribosomes share a core structure, which is quite similar despite the large differences in size  Much of the RNA is highly organized into various tertiary structural motifs, for example pseudoknots that exhibit coaxial stacking  The extra RNA in the larger ribosomes is in several long continuous insertions, such that they form loops out of the core structure without disrupting or changing it  All of the catalytic activity of the ribosome is carried out by the RNA; the proteins reside on the surface and seem to stabilize the structure 

High-resolution structure
The general molecular structure of the ribosome has been known since the early 1970s  In the early 2000s, the structure has been achieved at high resolutions, of the order of a few ångströms 
The first papers giving the structure of the ribosome at atomic resolution were published almost simultaneously in late 2000  The 50S (large prokaryotic) subunit was determined from the archaeon Haloarcula marismortui and the bacterium Deinococcus radiodurans, and the structure of the 30S subunit was determined from Thermus thermophilus  These structural studies were awarded the Nobel Prize in Chemistry in 2009  In May 2001 these coordinates were used to reconstruct the entire T  thermophilus 70S particle at 5 5 Å resolution Two papers were published in November 2005 with structures of the Escherichia coli 70S ribosome  The structures of a vacant ribosome were determined at 3 5 Å resolution using X-ray crystallography  Then, two weeks later, a structure based on cryo-electron microscopy was published, which depicts the ribosome at 11–15 Å resolution in the act of passing a newly synthesized protein strand into the protein-conducting channel 
The first atomic structures of the ribosome complexed with tRNA and mRNA molecules were solved by using X-ray crystallography by two groups independently, at 2 8 Å and at 3 7 Å  These structures allow one to see the details of interactions of the Thermus thermophilus ribosome with mRNA and with tRNAs bound at classical ribosomal sites  Interactions of the ribosome with long mRNAs containing Shine-Dalgarno sequences were visualized soon after that at 4 5–5 5 Å resolution In 2011, the first complete atomic structure of the eukaryotic 80S ribosome from the yeast Saccharomyces cerevisiae   was obtained by crystallography  The model reveals the architecture of eukaryote-specific elements and their interaction with the universally conserved core  At the same time, the complete model of a eukaryotic 40S ribosomal structure in Tetrahymena thermophila was published and described the structure of the 40S subunit, as well as much about the 40S subunit's interaction with eIF1 during translation initiation  Similarly, the eukaryotic 60S subunit structure was also determined from Tetrahymena thermophila in complex with eIF6 

Function
Ribosomes are minute particles consisting of RNA and associated proteins that function to synthesize proteins  Proteins are needed for many cellular functions such as repairing damage or directing chemical processes  Ribosomes can be found floating within the cytoplasm or attached to the endoplasmic reticulum  Their main function is to convert genetic code into an amino acid sequence and to build protein polymers from amino acid monomers 
Ribosomes act as catalysts in two extremely important biological processes called peptidyl transfer and peptidyl hydrolysis  The "PT center is responsible for producing protein bonds during protein elongation" In summary, ribosomes have two main functions: Decoding the message, and the formation of peptide bonds  These two functions reside in the ribosomal subunits  Each subunit is made of one or more rRNAs and many r-proteins  The small subunit (30S in bacteria and archaea, 40S in eukaryotes) has the decoding function, whereas the large subunit (50S in bacteria and archaea, 60S in eukaryotes) catalyzes the formation of peptide bonds, referred to as the peptidyl-transferase activity  The bacterial (and archaeal) small subunit contains the 16S rRNA and 21 r-proteins (Escherichia coli), whereas the eukaryotic small subunit contains the 18S rRNA and 32 r-proteins (Saccharomyces cerevisiae; although the numbers vary between species)  The bacterial large subunit contains the 5S and 23S rRNAs and 34 r-proteins (E  coli), with the eukaryotic large subunit containing the 5S, 5 8S, and 25S / 28S rRNAs and 46 r-proteins (S  cerevisiae; again, the exact numbers vary between species) 

Translation
Ribosomes are the workplaces of protein biosynthesis, the process of translating mRNA into protein  The mRNA comprises a series of codons which are decoded by the ribosome so as to make the protein  Using the mRNA as a template, the ribosome traverses each codon (3 nucleotides) of the mRNA, pairing it with the appropriate amino acid provided by an aminoacyl-tRNA  Aminoacyl-tRNA contains a complementary anticodon on one end and the appropriate amino acid on the other  For fast and accurate recognition of the appropriate tRNA, the ribosome utilizes large conformational changes (conformational proofreading)  The small ribosomal subunit, typically bound to an aminoacyl-tRNA containing the first amino acid methionine, binds to an AUG codon on the mRNA and recruits the large ribosomal subunit  The ribosome contains three RNA binding sites, designated A, P, and E  The A-site binds an aminoacyl-tRNA or termination release factors; the P-site binds a peptidyl-tRNA (a tRNA bound to the poly-peptide chain); and the E-site (exit) binds a free tRNA  Protein synthesis begins at a start codon AUG near the 5' end of the mRNA  mRNA binds to the P site of the ribosome first  The ribosome recognizes the start codon by using the Shine-Dalgarno sequence of the mRNA in prokaryotes and Kozak box in eukaryotes 
Although catalysis of the peptide bond involves the C2 hydroxyl of RNA's P-site adenosine in a proton shuttle mechanism, other steps in protein synthesis (such as translocation) are caused by changes in protein conformations  Since their catalytic core is made of RNA, ribosomes are classified as "ribozymes," and it is thought that they might be remnants of the RNA world 
In Figure 5, both ribosomal subunits (small and large) assemble at the start codon (towards the 5' end of the mRNA)  The ribosome uses tRNA that matches the current codon (triplet) on the mRNA to append an amino acid to the polypeptide chain  This is done for each triplet on the mRNA, while the ribosome moves towards the 3' end of the mRNA  Usually in bacterial cells, several ribosomes are working parallel on a single mRNA, forming what is called a polyribosome or polysome 

Cotranslational folding
The ribosome is known to actively participate in the protein folding  The structures obtained in this way are usually identical to the ones obtained during protein chemical refolding; however, the pathways leading to the final product may be different  In some cases, the ribosome is crucial in obtaining the functional protein form  For example, one of the possible mechanisms of folding of the deeply knotted proteins relies on the ribosome pushing the chain through the attached loop 

Addition of translation-independent amino acids
Presence of a ribosome quality control protein Rqc2 is associated with mRNA-independent protein elongation  This elongation is a result of ribosomal addition (via tRNAs brought by Rqc2) of CAT tails: ribosomes extend the C-terminus of a stalled protein with random, translation-independent sequences of alanines and threonines 

Ribosome locations
Ribosomes are classified as being either "free" or "membrane-bound" 

Free and membrane-bound ribosomes differ only in their spatial distribution; they are identical in structure  Whether the ribosome exists in a free or membrane-bound state depends on the presence of an ER-targeting signal sequence on the protein being synthesized, so an individual ribosome might be membrane-bound when it is making one protein, but free in the cytosol when it makes another protein 
Ribosomes are sometimes referred to as organelles, but the use of the term organelle is often restricted to describing sub-cellular components that include a phospholipid membrane, which ribosomes, being entirely particulate, do not  For this reason, ribosomes may sometimes be described as "non-membranous organelles" 

Free ribosomes
Free ribosomes can move about anywhere in the cytosol, but are excluded from the cell nucleus and other organelles  Proteins that are formed from free ribosomes are released into the cytosol and used within the cell  Since the cytosol contains high concentrations of glutathione and is, therefore, a reducing environment, proteins containing disulfide bonds, which are formed from oxidized cysteine residues, cannot be produced within it 

Membrane-bound ribosomes
When a ribosome begins to synthesize proteins that are needed in some organelles, the ribosome making this protein can become "membrane-bound"  In eukaryotic cells this happens in a region of the endoplasmic reticulum (ER) called the "rough ER"  The newly produced polypeptide chains are inserted directly into the ER by the ribosome undertaking vectorial synthesis and are then transported to their destinations, through the secretory pathway  Bound ribosomes usually produce proteins that are used within the plasma membrane or are expelled from the cell via exocytosis 

Biogenesis
In bacterial cells, ribosomes are synthesized in the cytoplasm through the transcription of multiple ribosome gene operons  In eukaryotes, the process takes place both in the cell cytoplasm and in the nucleolus, which is a region within the cell nucleus  The assembly process involves the coordinated function of over 200 proteins in the synthesis and processing of the four rRNAs, as well as assembly of those rRNAs with the ribosomal proteins 

Origin
The ribosome may have first originated as a protoribosome, possibly containing a peptidyl transferase centre (PTC), in an RNA world, appearing as a self-replicating complex that only later evolved the ability to synthesize proteins when amino acids began to appear  Studies suggest that ancient ribosomes constructed solely of rRNA could have developed the ability to synthesize peptide bonds  In addition, evidence strongly points to ancient ribosomes as self-replicating complexes, where the rRNA in the ribosomes had informational, structural, and catalytic purposes because it could have coded for tRNAs and proteins needed for ribosomal self-replication  Hypothetical cellular organisms with self-replicating RNA but without DNA are called ribocytes (or ribocells) As amino acids gradually appeared in the RNA world under prebiotic conditions, their interactions with catalytic RNA would increase both the range and efficiency of function of catalytic RNA molecules  Thus, the driving force for the evolution of the ribosome from an ancient self-replicating machine into its current form as a translational machine may have been the selective pressure to incorporate proteins into the ribosome's self-replicating mechanisms, so as to increase its capacity for self-replication 

Heterogeneous ribosomes
Ribosomes are compositionally heterogeneous between species and even within the same cell, as evidenced by the existence of cytoplasmic and mitochondria ribosomes within the same eukaryotic cells  Certain researchers have suggested that heterogeneity in the composition of ribosomal proteins in mammals is important for gene regulation, i e , the specialized ribosome hypothesis  However, this hypothesis is controversial and the topic of ongoing research Heterogeneity in ribosome composition was first proposed to be involved in translational control of protein synthesis by Vince Mauro and Gerald Edelman  They proposed the ribosome filter hypothesis to explain the regulatory functions of ribosomes  Evidence has suggested that specialized ribosomes specific to different cell populations may affect how genes are translated  Some ribosomal proteins exchange from the assembled complex with cytosolic copies suggesting that the structure of the in vivo ribosome can be modified without synthesizing an entire new ribosome 
Certain ribosomal proteins are absolutely critical for cellular life while others are not  In budding yeast, 14/78 ribosomal proteins are non-essential for growth, while in humans this depends on the cell of study  Other forms of heterogeneity include post-translational modifications to ribosomal proteins such as acetylation, methylation, and phosphorylation  Arabidopsis, Viral internal ribosome entry sites (IRESs) may mediate translations by compositionally distinct ribosomes  For example, 40S ribosomal units without eS25 in yeast and mammalian cells are unable to recruit the CrPV IGR IRES Heterogeneity of ribosomal RNA modifications plays a significant role in structural maintenance and/or function and most mRNA modifications are found in highly conserved regions  The most common rRNA modifications are pseudouridylation and 2’-O methylation of ribose 

See also



ground_truth: Ribosomes