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4,270,646 | https://en.wikipedia.org/wiki/The%20Planets%20%281999%20TV%20series%29 | The Planets is a documentary miniseries produced by the BBC and A&E and released in 1999. The series was remastered in 2004. It documents the Solar System and its nature, formation, and discovery by humans during the Space Age. The series of eight episodes includes a substantial amount of archival footage from both the United States and Soviet space programs. It also depicts the Solar System through computer graphics. There were a total of eight episodes produced for the series. The series featured appearances from famous pioneering space scientists and explorers, and was narrated by Samuel West in the original 1999 edition, and Mark Halliley in the 2004 remastered edition.
Episodes
Commentators in episode 1 include Hal Levison, George Wetherill, and David Levy.
Commentators in episode 4 include Apollo 17 Lunar Module Pilot Harrison Schmidt, while episode 5 features Apollo 12 Commander Charles Conrad and solar physicist Eugene Parker (of whom the NASA Parker Solar Probe was named in tribute), episode 6 retired USAF Colonel and Project Excelsiot pilot Joe Kittinger, and episode 8 Apollo 17 Commander and last human to walk on the Moon Eugene Cernan.
Commentators in episode 5 include Douglas Gough. It also talks about Angelo Secchi who pioneered the field of astronomical spectroscopy.
Other notable commentators include James Van Allen, Sergei Khrushchev (son of Nikita Khrushchev and aerospace engineer), Alexei Leonov, Boris Chertok and Carolyn Porco.
DVD release
The DVD of the series was released on 24 January 2000.
Book
A hardcover book accompanying the series broadcast was released on 22 April 1999. The Planets. David McNab and James Younger. Yale University Press.
References
External links
1999 British television series debuts
1999 British television series endings
1990s British documentary television series
Documentary television series about astronomy
Science education television series
BBC television documentaries about science
British English-language television shows
Documentary films about outer space | The Planets (1999 TV series) | [
"Astronomy"
] | 370 | [
"Documentary television series about astronomy",
"Space art",
"Documentary films about outer space",
"Works about astronomy"
] |
4,270,750 | https://en.wikipedia.org/wiki/Embellishment | In sewing and crafts, an embellishment is anything that adds design interest to the piece.
Embellishments allow individuals to express their personal style and identity. Clothing can be a form of self-expression, and the choice of embellishments can communicate one's personality, taste, and cultural background.
Examples in sewing and craft
appliqué can be made by sewing machine of decorative techniques and or
embroidery, done either by machine or by hand
piping made from either self-fabric, contrast fabric, or a simply a cord.
trim (sewing)
lace, either pre-made or home-made
Fringe (trim)
beads
batik
Items that normally serve a function may also be used as embellishment. For example:
buttons can be placed anywhere on the piece
zippers can be unzipped and be used as piping, or simply stitched on
buckles can be placed anywhere on the piece
grommets can be placed anywhere even when there is no cord is looped through them
sequins can be placed anywhere
References
Handicrafts
Fashion design
Sewing | Embellishment | [
"Engineering"
] | 221 | [
"Design",
"Fashion design"
] |
4,271,629 | https://en.wikipedia.org/wiki/Ky%C5%8Diku%20mama | is a Japanese pejorative term which translates literally as "education mother". The kyōiku mama is a stereotyped figure in modern Japanese society, portrayed as a mother who relentlessly drives her child to study, to the detriment of the child's social and physical development, and emotional well-being.
The kyōiku mama is one of the best-known and least-liked pop-culture figures in contemporary Japan. The kyōiku mama is analogous to American stereotypes such as the stage mother who forces her child to achieve show-business success in Hollywood, the stereotypical Chinese tiger mother who takes an enormous amount of effort to direct much of her maternal influence towards developing their children's educational and intellectual achievement, and the stereotypical Jewish mother's drive for her children to succeed academically and professionally, resulting in a push for perfection and a continual dissatisfaction with anything less or the critical, self-sacrificing mother who coerces her child into medical school or law school.
The stereotype is that a kyōiku mama is feared by her children, blamed by the press for school phobias and youth suicides, and envied and resented by the mothers of children who study less and fare less well on exams.
Factors influencing development of kyōiku mama
In the early 1960s, part-time women's labor began at a few major corporations in Japan and was adopted by other companies within a decade. It became popular among married women in the 1970s and even more so by 1985.
Women's return to the workplace is often explained two-fold: by financial demands to complement the family budget, and by psychological demands to relate themselves to society.
Child-rearing women in the 1960s inspired the media to produce the idiom kyōiku mama, which referred to "the domestic counterpart of sararii-man" (salaryman). This encompassed a major responsibility to "rear children, especially the males, to successfully pass the competitive tests needed to enter high school and college". No such idiom emerged that deemed men "education papas"; it was "mamas" who became a social phenomenon.
The education system
The education system and larger political economy it serves influence why mothers become obsessed with children's education. Social prejudices influence media stereotypes of kyōiku mamas that blame women rather than political conditions. Getting a good, steady job in the future very much depends on getting into a good university, which depends on attaining high scores on the national university exams in a student's last year of high school. Ordinary people, including mothers, feel powerless to change this system.
As a result, there is a clear map pointing students to the right nursery school that leads to the right kindergarten, the best elementary school, junior high school, and high school, all of which may be associated with prestigious universities. To ensure these results, some parents have been known to commit unethical or illegal acts to promote their child's success.
In one case, a restaurant owner paid a $95,000 bribe in an attempt to get his child enrolled in Aoyama Gakuin, a prestigious kindergarten for children who are three or four years old. Because of the kindergarten's affiliation with an elite university, parents are willing to go to extreme lengths to get their children enrolled. Aoyama Gakuin has room for 40 new students a year. Every year, it receives more than 2000 hopeful applicants. The tests the potential students take are known to be extremely difficult.
The issue is compounded by the notion that most important job positions in business and government are held by graduates of the University of Tokyo. In addition, which university a student attends is believed to affect one's choices for a future spouse. Because a child's life appears to be determined by what schools he or she attends, many mothers take extraordinary measures to get children into good schools.
Changing family structures
The older generation of Japanese grew up in larger households than those normally found in Japan today. Back then, ikuji (, "child-raising") included a larger surrounding environment, made up of more relatives and extended family, and more children: siblings and cousins. Children who grew up in that time learned responsibilities through the care of younger siblings. These children relied on themselves in the outside world through much of their childhood lives. In those days, child-raising was more of a private matter, handled only by the child's surrounding family.
In the 1970s, men's wages decreased and women left home earlier to find jobs. These women "considered themselves free" after the child's junior high education. The previous generation did not feel this until after the child had finished high school.
In contemporary Japan, couples are having fewer children and teaching the children self-reliance. This involves consulting child-raising professionals. This new need in professional advice is commonly termed "child-raising neurosis" by professionals. Reliance on professionals has largely created a new generation of young mothers with low self-confidence in their child-raising abilities. Indeed, most Japanese mothers today grew up in smaller families with only one or two children. Their mothers provided them with everything they needed and gave them little to no responsibilities involving their siblings. Thus, that generation of children has grown up to become mothers who have no idea how to raise their children.
In addition, in contemporary Japan there are mothers who completely devote themselves to child-raising. Another subtype, described by Nishioka Rice, is the kosodate mama (), who adds psychosociological elements into child-raising. In addition to providing for her a good education, she develops an emotional and psychological relationship with her children. One way to do this is through "skinship"—being in constant close physical contact with her children. This could, for example, involve carrying her child on her back wherever she goes or bathing with her children every night. Through skinship, ittaikan () is achieved, a "one-ness and balanced, positively valenced dependency" between mother and child.
Societal views
In Japan, a mother who works is commonly seen as selfish in a society where child-raising is linked directly with the physical closeness between mother and child. This emphasis can be a cause of the development of a kyōiku mama who always worries about her children's education success. This produces children that society views as lacking self-reliance, antisocial, and selfish.
When compared to American mothers, Japanese mothers have a stronger belief in effort as opposed to innate ability. Japanese children see their efforts as necessary to fulfill a social obligation to family, peers, and community. Children are forced to focus on their effort, seeing it as the cause of success. According to society, if a child does not succeed, they were not trying hard enough. This is unrelated to the child's grades; children always need to put forth more effort. Mothers pressure children because they are held strongly accountable for their children's actions.
It is very hard to find daycare in some parts of Japan, and it is socially looked down upon if a mother sends her child to one. The mother is seen as insufficient, not having the skills to raise a child on her own, or selfish, giving her child over to a caretaker while she pursues her own separate goals.
The term kyōiku mama became used in other similar contexts. For example, the former Ministry of International Trade and Industry was dubbed kyōiku mama for its approach and initiatives in guiding industrial growth, in a manner similar to the definition of a nanny state.
Media
Housewives are surrounded by popular media that encourages their actions. Daytime television, magazines, products, and services for mothers are largely focused on improving the home and raising the children. Thus, the job of motherhood is taken very seriously by mothers in Japan. A common description of a mother's free time is “three meals and a nap.”
Class distinctions
Kyōiku mamas, preparatory preschools, and heavily academic curricula exist in Japan, yet they are relatively rare and concentrated in urban, wealthy areas. Kyōiku mamas are prominent in the middle classes. Middle-class women train the children, the next generation of the middle class. In a speech at the 1909 Mitsukoshi children's exhibition, First Higher School principal Nitobe Inazō asserted, "The education of a citizenry begins not with the infant but with the education of a country's mothers."
In the post-World War II era in Japan, the mother was the creator of a new child-centered world stamped with middle-class values. The mother was linked with the success of the child's education. A woman was expected to be a "good wife, wise mother" and became the single most important figure in raising the child to become a successful future adult. Mothers needed to put their efforts into raising and teaching their children. Through self-cultivation and rearing of the children, the woman was crucial to a family's ability to claim a place in the so-called middle stratum.
As education credentials became the recognized prerequisite to social advancement in the early 20th century, kyōiku mama actively looked to the education system, especially admission into middle school for boys and higher school for girls, to help improve the family's social position. The competition to pass the entrance examination to middle school and girls' higher school became intense, creating the social phenomenon known as shiken jigoku (): examination hell. While risshin shusse (), or rising in the world, was the clarion call of the mass of the middle class, there was no risshin shusse without a kyōiku mama. For the education mother, making the child into a superior student was a concern that began with the child's entrance into elementary school at age six and extended to all aspects of the child's education.
Working-class mothers are not as intensely active in their children's education as middle-class mothers. An ethnographic study by Shimizu Tokuda (1991) portrayed one middle school that faced persistent academic problems in a working-class neighborhood of Osaka. The study illustrated efforts by teachers to improve the student's academic performance: providing tests, promoting monthly teacher discussions, painting walls to enhance the study environment, and restricting hours spent in extracurricular activities. While students' enrollment in high school slightly improved, academic achievement level remained lower than the national average. This study revealed that students' academic problems were deeply related to their home environments. Most students had parents who were uneducated and not involved in their children's education.
American view
In contrast to Japan's mostly negative images of kyōiku mamas, American leaders who put forth the image of "superhuman Japan" to boost American education performance extolled Japan's education-minded mothers. Both of Ronald Reagan's education secretaries focused attention on Japanese mothers as mirrors to improve American families and schools. Reagan's first Secretary of Education, Terrel Bell (credited for the wording of A Nation at Risk) wrote an enthusiastic foreword to Guy Odom's Mothers, Leadership and Success—a book whose basic point was that only vigorous, aggressive and intelligent Super Moms exemplified by Japanese mothers could reinvigorate America. William J. Bennett, head of the Department of Education in Reagan's second term, praised Japan's "one parent on the scene" who "stays in touch with the teachers, supervises the homework, arranges extra instructional help if needed, and buttresses the child's motivation to do well in school and beyond".
Contemporary kyōiku mamas
Many Japanese mothers dedicate much time to get their children from one entrance exam to another. At the national university entrance exams, held in Tokyo, most mothers travel with their children to the examination hall. They arrive and stay at a nearby hotel, grilling their children on last-minute statistics and making sure that they are not late to the exam.
Some mothers are beginning their children's education at even younger ages. A 30-year-old mother in Japan says, "This is my first baby, and I didn't know how to play with her or help her develop". She sends her 6-month-old daughter to a pre-pre-school in Tokyo. A headmaster at another pre-pre-school claims that the school, for children one year or older, helps to nurture and develop the children's curiosity through "tangerine-peeling or collecting and coloring snow".
Mothers are essentially in heavy competition with other mothers who want their children to get into the elite universities. In some cases, to make it seem like her own child is not studying as much, mothers will let their child use the parents' bedroom to study while the mothers watch television in the living room. Other mothers who pass by the house will see the child's bedroom light off, assuming that the child has shirked his or her studies to watch television. The next morning, the mother will report what happened on the shows to her child, who will go to school and talk about it to his or her classmates, who will also assume that their friend is a slacker, lowering their expectations of their friend and for themselves. However, when examination time rolls around, the "slacker" will be admitted into an elite school while his or her friends will drop behind.
Kyōiku mamas often give their children a big first appearance in the neighborhood through a kōen debyū (), where the mothers "parade their offspring around the neighborhood parks for approval".
Mothers send their children to cram schools (juku), where children may stay until 10 or 11pm. Japan has over 35,000 cram schools for college examinations. In addition to cram schools, children are sent to calligraphy, keyboard, abacus, or kendo classes. As revealed by Marie Thorsten, moral panics about juku and education mamas occurred at the same time, in the 1970s. "As 'second schools', the juku, as consumer services, appealed to mothers’ anxieties about their children, shaping the image of the 'normal' mother as one who sends her children to juku and stays up to date with commercialized trends in examination preparation."
Effects on children
In the 1950s, full-time mothers devoted themselves to a smaller number of children. Parental stress resulted in the commonality of new childhood problems; these include bronchial asthma, stammering, poor appetite, proneness to bone fractures, and school phobia. Children were aware they were their mother's purpose in life. Mothers played the role of their children's school teachers while they were at home.
Sometimes, a child who grows up with a kyōiku mama turns into a tenuki okusan (, "hands-off housewife"). This stereotype describes women who typically have jobs and are not around the children as much, essentially becoming the female version of the stereotypical absent Japanese father, a "leisure-time parent" or "Sunday friend". These mothers are said to not do a lot of homemaking, commonly making large, freezable meals that are easy to reheat in case they are not home or too busy to do the cooking. They do not attempt to represent their families in the community through participation in their children's school PTA and other community functions.
Compared to modern American children, Japanese youths have less drug use, depression, violence, and teenage pregnancy, although these may be caused due to harsher laws and intrinsic social values in the Japanese culture.
Government regulations
The Ministry of Education, Culture, Sports, Science and Technology has admitted that the education system and parental pressure are taking their toll on children. Education reforms that the Ministry of Education has enacted beginning in the 1970s have challenged Japan's egalitarian school system. To decrease academic pressure among students from examination competition, the Ministry of Education cut school hours and increased non-academic activities such as recess and clubs in elementary and junior high schools.
In 2002, the central government reduced school hours again, decreased content, and introduced a new curriculum at all public elementary schools to encourage individual students' learning interests and motivation. The Japanese Ministry of Education published a white paper stating that children do not have opportunities such as "coming into contact with nature, feeling awe and respect for life, and experiencing the importance of hard work learning from difficulties".
Japanese education and related stress
Post-war Japan in the 1950s made it a "national mission to accelerate its education program. Children of this era had to distinguish themselves from peers at an early age if they hoped to get into a top university. Entrance exams for these children began in kindergarten.
By the mid-1970s, pressure to achieve in children created the need for specialty schools. Seventy percent of students continued their long school day at juku or "cram schools".
In the 1980s, a series of suicides linked to school pressures began. Elementary and middle school students took their lives after failing entrance exams.
During the 1990s, the economic collapse in Japan (after its global economic dominance in the previous decade) led to a loss of motivation by students. The once highly touted academic ratings of Japan in math and science fell behind those of American levels. The stress began to lead to classroom disruption.
In 2001, the National Education Research Institute found that 33 percent of teachers and principals polled said that they had witnessed a complete breakdown of class "over a continuous period" due to defiant children "engaging in arbitrary activity". In 2002, the Japanese Education Ministry — pressured by the need to reform — eliminated 30 percent of its core curriculum. This freed up time for students to learn in groups according to the students' chosen path.
The use of the term mukatsuku, meaning "irritating and troublesome", has been rising in use among students as a description of the feelings they experience of being fed up with teachers, parents, and life.
See also
Education in Japan
Helicopter parent
Hong Kong children
Tiger parenting, a similar parenting style in Mainland China and other parts of East Asia, South Asia and Southeast Asia
Soccer mom
References
1960s neologisms
Academic pressure in East Asian culture
Behavior modification
Education in Japan
Japanese family structure
Japanese values
Maternity in Japan
Pejorative terms for women
Social issues in Japan
Stereotypes of middle class women
Suicide in Japan | Kyōiku mama | [
"Biology"
] | 3,747 | [
"Behavior modification",
"Human behavior",
"Behavior",
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4,271,664 | https://en.wikipedia.org/wiki/List%20of%20atmospheric%20dispersion%20models | Atmospheric dispersion models are computer programs that use mathematical algorithms to simulate how pollutants in the ambient atmosphere disperse and, in some cases, how they react in the atmosphere.
US Environmental Protection Agency models
Many of the dispersion models developed by or accepted for use by the U.S. Environmental Protection Agency (U.S. EPA) are accepted for use in many other countries as well. Those EPA models are grouped below into four categories.
Preferred and recommended models
AERMOD – An atmospheric dispersion model based on atmospheric boundary layer turbulence structure and scaling concepts, including treatment of multiple ground-level and elevated point, area and volume sources. It handles flat or complex, rural or urban terrain and includes algorithms for building effects and plume penetration of inversions aloft. It uses Gaussian dispersion for stable atmospheric conditions (i.e., low turbulence) and non-Gaussian dispersion for unstable conditions (high turbulence). Algorithms for plume depletion by wet and dry deposition are also included in the model. This model was in development for approximately 14 years before being officially accepted by the U.S. EPA.
CALPUFF – A non-steady-state puff dispersion model that simulates the effects of time- and space-varying meteorological conditions on pollution transport, transformation, and removal. CALPUFF can be applied for long-range transport and for complex terrain.
BLP – A Gaussian plume dispersion model designed to handle unique modelling problems associated with industrial sources where plume rise and downwash effects from stationary line sources are important.
CALINE3 – A steady-state Gaussian dispersion model designed to determine pollution concentrations at receptor locations downwind of highways located in relatively uncomplicated terrain.
CAL3QHC and CAL3QHCR – CAL3QHC is a CALINE3 based model with queuing calculations and a traffic model to calculate delays and queues that occur at signalized intersections. CAL3QHCR is a more refined version based on CAL3QHC that requires local meteorological data.
CTDMPLUS – A complex terrain dispersion model (CTDM) plus algorithms for unstable situations (i.e., highly turbulent atmospheric conditions). It is a refined point source Gaussian air quality model for use in all stability conditions (i.e., all conditions of atmospheric turbulence) for complex terrain.
OCD – Offshore and coastal dispersion model (OCD) is a Gaussian model developed to determine the impact of offshore emissions from point, area or line sources on the air quality of coastal regions. It incorporates overwater plume transport and dispersion as well as changes that occur as the plume crosses the shoreline.
Alternative models
ADAM – Air force dispersion assessment model (ADAM) is a modified box and Gaussian dispersion model which incorporates thermodynamics, chemistry, heat transfer, aerosol loading, and dense gas effects.
ADMS 5 – Atmospheric Dispersion Modelling System (ADMS 5) is an advanced dispersion model developed in the United Kingdom for calculating concentrations of pollutants emitted both continuously from point, line, volume and area sources, or discretely from point sources.
AFTOX – A Gaussian dispersion model that handles continuous or puff, liquid or gas, elevated or surface releases from point or area sources.
DEGADIS – Dense gas dispersion (DEGADIS) is a model that simulates the dispersion at ground level of area source clouds of denser-than-air gases or aerosols released with zero momentum into the atmosphere over flat, level terrain.
HGSYSTEM – A collection of computer programs developed by Shell Research Ltd. and designed to predict the source-term and subsequent dispersion of accidental chemical releases with an emphasis on dense gas behavior.
HOTMAC and RAPTAD – HOTMAC is a model for weather forecasting used in conjunction with RAPTAD which is a puff model for pollutant transport and dispersion. These models are used for complex terrain, coastal regions, urban areas, and around buildings where other models fail.
HYROAD – The hybrid roadway model integrates three individual modules simulating the pollutant emissions from vehicular traffic and the dispersion of those emissions. The dispersion module is a puff model that determines concentrations of carbon monoxide (CO) or other gaseous pollutants and particulate matter (PM) from vehicle emissions at receptors within 500 meters of the roadway intersections.
ISC3 – A Gaussian model used to assess pollutant concentrations from a wide variety of sources associated with an industrial complex. This model accounts for: settling and dry deposition of particles; downwash; point, area, line, and volume sources; plume rise as a function of downwind distance; separation of point sources; and limited terrain adjustment. ISC3 operates in both long-term and short-term modes.
OBODM – A model for evaluating the air quality impacts of the open burning and detonation (OB/OD) of obsolete munitions and solid propellants. It uses dispersion and deposition algorithms taken from existing models for instantaneous and quasi-continuous sources to predict the transport and dispersion of pollutants released by the open burning and detonation operations.
PANACHE – Fluidyn-PANACHE is an Eulerian (and Lagrangian for particulate matter), 3-dimensional finite volume fluid mechanics model designed to simulate continuous and short-term pollutant dispersion in the atmosphere, in simple or complex terrain.
PLUVUEII – A model that estimates atmospheric visibility degradation and atmospheric discoloration caused by plumes resulting from the emissions of particles, nitrogen oxides, and sulfur oxides. The model predicts the transport, dispersion, chemical reactions, optical effects and surface deposition of such emissions from a single point or area source.
SCIPUFF – A puff dispersion model that uses a collection of Gaussian puffs to predict three-dimensional, time-dependent pollutant concentrations. In addition to the average concentration value, SCIPUFF predicts the statistical variance in the concentrations resulting from the random fluctuations of the wind.
SDM – Shoreline dispersion model (SDM) is a Gaussian dispersion model used to determine ground-level concentrations from tall stationary point source emissions near a shoreline.
SLAB – A model for denser-than-air gaseous plume releases that utilizes the one-dimensional equations of momentum, conservation of mass and energy, and the equation of state. SLAB handles point source ground-level releases, elevated jet releases, releases from volume sources and releases from the evaporation of volatile liquid spill pools.
Screening models
These are models that are often used before applying a refined air quality model to determine if refined modelling is needed.
AERSCREEN – The screening version of AERMOD. It produces estimates of concentrations, without the need for meteorological data, that are equal to or greater than the estimates produced by AERMOD with a full set of meteorological data. The U.S. EPA released version 11060 of AERSCREEN on 11 March 2010 with a subsequent update, version 11076, on 17 March 2010. The U.S. EPA published the "Clarification memorandum on AERSCREEN as the recommended screening model" on 11 April 2011.
CTSCREEN – The screening version of CTDMPLUS.
SCREEN3 – The screening version of ISC3.
TSCREEN – Toxics screening model (TSCREEN) is a Gaussian model for screening toxic air pollutant emissions and their subsequent dispersion from possible releases at superfund sites. It contains 3 modules: SCREEN3, PUFF, and RVD (Relief Valve Discharge).
VALLEY – A screening, complex terrain, Gaussian dispersion model for estimating 24-hour or annual concentrations resulting from up to 50 point and area emission sources.
COMPLEX1 – A multiple point source screening model with terrain adjustment that uses the plume impaction algorithm of the VALLEY model.
RTDM3.2 – Rough terrain diffusion model (RTDM3.2) is a Gaussian model for estimating ground-level concentrations of one or more co-located point sources in rough (or flat) terrain.
VISCREEN – A model that calculates the impact of specified emissions for specific transport and dispersion conditions.
Photochemical models
Photochemical air quality models have become widely utilized tools for assessing the effectiveness of control strategies adopted by regulatory agencies. These models are large-scale air quality models that simulate the changes of pollutant concentrations in the atmosphere by characterizing the chemical and physical processes in the atmosphere. These models are applied at multiple geographical scales ranging from local and regional to national and global.
Models-3/CMAQ – The latest version of the community multi-scale air quality (CMAQ) model has state-of-the-science capabilities for conducting urban to regional scale simulations of multiple air quality issues, including tropospheric ozone, fine particles, toxics, acid deposition, and visibility degradation.
CAMx – The comprehensive air quality model with extensions (CAMx) simulates air quality over many geographic scales. It handles a variety of inert and chemically active pollutants, including ozone, particulate matter, inorganic and organic PM2.5/PM10, and mercury and other toxics.
REMSAD – The regional modeling system for aerosols and deposition (REMSAD) calculates the concentrations of both inert and chemically reactive pollutants by simulating the atmospheric processes that affect pollutant concentrations over regional scales. It includes processes relevant to regional haze, particulate matter and other airborne pollutants, including soluble acidic components and mercury.
UAM-V – The urban airshed model was a pioneering effort in photochemical air quality modelling in the early 1970s and has been used widely for air quality studies focusing on ozone.
Other models developed in the United States
CHARM – A model capable of simulating dispersion of toxics and particles. It can calculate impacts of thermal radiation from fires, overpressures from mechanical failures and explosions, and nuclear radiation from radionuclide releases. CHARM is capable of handling effects of complex terrain and buildings. A Lagrangian puff screening version and Eulerian full-function version are available. More information is available here.
HYSPLIT – Hybrid Single Particle Lagrangian Integrated Trajectory Model. Developed at NOAA's Air Resources Laboratory. The HYSPLIT model is a complete system for computing simple air parcel trajectories to complex dispersion and deposition simulations. More information about this model can be found at
PUFF-PLUME – A Gaussian chemical/radionuclide dispersion model that includes wet and dry deposition, real-time input of meteorological observations and forecasts, dose estimates from inhalation and gamma shine, and puff or plume dispersion modes. It is the primary model for emergency response use for atmospheric releases of radioactive materials at the Savannah River Site of the United States Department of Energy. It was first developed by the Pacific Northwest National Laboratory (PNNL) in the 1970s.
Puff model – Puff is a volcanic ash tracking model developed at the University of Alaska Fairbanks. It requires NWP wind field data on a geographic grid covering the area over which ash may be dispersed. Representative ash particles are initiated at the volcano's location and then allowed to advect, diffuse, and settle within the atmosphere. The location of the particles at any time after the eruption can be viewed using the post-processing software included with the model. Output data is in netCDF format and can also be viewed with a variety of software. More information on the model is available here.
Models developed in the United Kingdom
ADMS-5 – See the description of this model in the alternative models section of the models accepted by the U.S. EPA.
ADMS-URBAN – A model for simulating dispersion on scales ranging from a street scale to citywide or county-wide scale, handling most relevant emission sources such as traffic, industrial, commercial, and domestic sources. It is also used for air quality management and assessments of current and future air quality vis-a-vis national and regional standards in Europe and elsewhere.
ADMS-Roads – A model for simulating dispersion of vehicular pollutant emissions from small road networks in combination with emissions from industrial plants. It handles multiple road sources as well as multiple point, line or area emission sources and the model operation is similar to the other ADMS models
ADMS-Screen – A screening model for rapid assessment of the air quality impact of a single industrial stack to determine if more detailed modelling is needed. It combines the dispersion modelling algorithms of the ADMS models with a user interface requiring minimal input data.
GASTAR – A model for simulating accidental releases of denser-than-air flammable and toxic gases. It handles instantaneous and continuous releases, releases from jet sources, releases from evaporation of volatile liquid pools, variable terrain slopes and ground roughness, obstacles such as fences and buildings, and time-varying releases.
NAME – Numerical atmospheric-dispersion modelling environment (NAME) is a local to global scale model developed by the UK's Met Office. It is used for: forecasting of air quality, air pollution dispersion, and acid rain; tracking radioactive emissions and volcanic ash discharges; analysis of accidental air pollutant releases and assisting in emergency response; and long-term environmental impact analysis. It is an integrated model that includes boundary layer dispersion modelling.
UDM – Urban dispersion model is a Gaussian puff based model for predicting the dispersion of atmospheric pollutants in the range of 10m to 25 km throughout the urban environment. It is developed by the Defense Science and Technology Laboratory for the UK Ministry of Defence. It handles instantaneous, continuous, and pool releases, and can model gases, particulates, and liquids. The model has a three regime structure: that of single building (area density < 5%), urban array (area density > 5%) and open. The model can be coupled with the US model SCIPUFF to replace the open regime and extend the model's prediction range.
Models developed in continental Europe
The European Topic Centre on Air and Climate Change, which is part of the European Environment Agency (EEA), maintains an online Model Documentation System (MDS) that includes descriptions and other information for almost all of the dispersion models developed by the countries of Europe. The MDS currently (July 2012) contains 142 models, mostly developed in Europe. Of those 142 models, some were subjectively selected for inclusion here. Anyone interested in seeing the complete MDS can access it here.
Some of the European models listed in the MDS are public domain and some are not. Many of them include a pre-processor module for the input of meteorological and other data, and many also include a post-processor module for graphing the output data and/or plotting the area impacted by the air pollutants on maps.
The country of origin is included for each of the European models listed below.
AEROPOL (Estonia) – The AERO-POLlution model developed at the Tartu Observatory in Estonia is a Gaussian plume model for simulating the dispersion of continuous, buoyant plumes from stationary point, line and area sources over flat terrain on a local to regional scale. It includes plume depletion by wet and/or dry deposition as well as the effects of buildings in the plume path.
Airviro Gauss (Sweden) – A gaussian dispersion model that handles point, road, area and grid sources developed by SMHI. Plumes follow trajectories from a wind model and each plume has a cutoff dependent on wind speed. The model also support irregular calculation grids.
Airviro Grid (Sweden) – A simplified eulerian model developed by SMHI. Can handle point, road, area and grid sources. Includes dry and wet deposition and sedimentation.
Airviro Heavy Gas (Sweden) – A model for heavy gas dispersion developed by SMHI.
Airviro receptor model (Sweden)- An inverse dispersion model developed by SMHI. Used to find emission sources.
ATSTEP (Germany) – Gaussian puff dispersion and deposition model used in the decision support system RODOS (real-time on-line decision support) for nuclear emergency management. RODOS is operational in Germany by the Federal Office for Radiation Protection (BfS) and test-operational in many other European countries. More information on RODOS is available here and on the ATSTEP model here.
AUSTAL2000 (Germany) – The official air dispersion model to be used in the permitting of industrial sources by the German Federal Environmental Agency. The model accommodates point, line, area and volume sources of buoyant plumes. It has capabilities for building effects, complex terrain, plume depletion by wet or dry deposition, and first order chemical reactions. It is based on the LASAT model developed by Ingenieurbüro Janicke Gesellschaft für Umweltphysik.
BUO-FMI (Finland) – This model was developed by the Finnish Meteorological Institute (FMI) specifically for estimating the atmospheric dispersion of neutral or buoyant plume gases and particles emitted from fires in warehouses and chemical stores. It is a hybrid of a local scale Gaussian plume model and another model type. Plume depletion by dry deposition is included but wet deposition is not included.
CAR-FMI (Finland) – This model was developed by the Finnish Meteorological Institute (FMI) for evaluating atmospheric dispersion and chemical transformation of vehicular emissions of inert (CO, NOx) and reactive (NO, NO2, O3) gases from a road network of line sources on a local scale. It is a Gaussian line source model which includes an analytical solution for the chemical cycle NO-O3-NO2.
CAR-International (The Netherlands) – Calculation of air pollution from road traffic (CAR-International) is an atmospheric dispersion model developed by the Netherlands Organisation for Applied Scientific Research. It is used for simulating the dispersion of vehicular emissions from roadway traffic.
DIPCOT (Greece) – Dispersion over complex terrain (DIPCOT) is a model developed in the National Centre of Scientific Research "DEMOKRITOS" of Greece that simulates dispersion of buoyant plumes from multiple point sources over complex terrain on a local to regional scale. It does not include wet deposition or chemical reactions.
DISPERSION21 (Sweden) – This model was developed by the Swedish Meteorological and Hydrological Institute (SMHI) for evaluating air pollutant emissions from existing or planned industrial or urban sources on a local scale. It is a Gaussian plume model for point, area, line and vehicular traffic sources. It includes plume penetration of inversions aloft, building effects, NOx chemistry and it can handle street canyons. It does not include wet or dry deposition, complex atmospheric chemistry, or the effects of complex terrain.
DISPLAY-2 (Greece) – A vapour cloud dispersion model for neutral or denser-than-air pollution plumes over irregular, obstructed terrain on a local scale. It accommodates jet releases as well as two-phase (i.e., liquid-vapor mixtures) releases. This model was also developed at the National Centre of Scientific Research "DEMOKRITOS" of Greece.
EK100W (Poland) – A Gaussian plume model used for air quality impact assessments of pollutants from industrial point sources as well as for urban air quality studies on a local scale. It includes wet and dry deposition. The effects of complex terrain are not included.
FARM (Italy) – The Flexible Air quality Regional Model (FARM) is a multi-grid Eulerian model for dispersion, transformation and deposition of airborne pollutants in gas and aerosol phases, including photo-oxidants, aerosols, heavy metals and other toxics. It is suited for case studies, air quality assessments, scenarios analyses and pollutants forecast.
FLEXPART (Austria/Germany/Norway) – An efficient and flexible Lagrangian particle transport and diffusion model for regional to global applications, with capability for forward and backward mode. Freely available. Developed at BOKU Vienna, Technical University of Munich, and NILU.
GRAL (Austria) – The GRAz Lagrangian model was initially developed at the Graz University of Technology and it is a dispersion model for buoyant plumes from multiple point, line, area and tunnel portal sources. It handles flat or complex terrain (mesoscale prognostic flow field model) including building effects (microscale prognostic flow field model) but it has no chemistry capabilities. The model is freely available: http://lampz.tugraz.at/~gral/
HAVAR (Czech Republic) – A Gaussian plume model integrated with a puff model and a hybrid plume-puff model, developed by the Czech Academy of Sciences, is intended for routine and/or accidental releases of radionuclides from single point sources within nuclear power plants. The model includes radioactive plume depletion by dry and wet deposition as well as by radioactive decay. For the decay of some nuclides, the creation of daughter products that then grow into the plume is taken into account.
IFDM (Belgium) – The immission frequency distribution model, developed at the Flemish Institute for Technological Research (VITO), is a Gaussian dispersion model used for point and area sources dispersing over flat terrain on a local scale. The model includes plume depletion by dry or wet deposition and has been updated to handle building effects and the O3-NOx-chemistry. It is not designed for complex terrain or other chemically reactive pollutants.
INPUFF-U (Romania) – This model was developed by the National Institute of Meteorology and Hydrology in Bucharest, Romania. It is a Gaussian puff model for calculating the dispersion of radionuclides from passive emission plumes on a local to urban scale. It can simulate accidental or continuous releases from stationary or mobile point sources. It includes wet and dry deposition. Building effects, buoyancy effects, chemical reactions and effects of complex terrain are not included.
LAPMOD (Italy) – The LAPMOD (LAgrangian Particle MODel) modeling system is developed by Enviroware and it is available for free. LAPMOD is a Lagrangian partile model fully coupled to the diagnostic meteorological model CALMET and can be used to simulate the dispersion of inert pollutants as well as odors and radioactive substances. It includes dry and wet deposition algorithms and advanced numerical schemes for plume rise (Janicke and Janicke, Webster and Thomson). It can simulate inert pollutants, odors and radioactive substances and it is part of ARIES, the official Italian modeling system for nuclear emergencies operated by ISPRA and by the regional environmental protection agency of Emilia-Romagna, Italy.
LOTOS-EUROS (The Netherlands) – the long term ozone simulation – European operational smog (LOTOS-EUROS) model was developed by the Netherlands Organisation for Applied Scientific Research (TNO) and Netherlands National Institute for Public Health and the Environment (RIVM) in The Netherlands. It is designed for modelling the dispersion of pollutants (such as: photo-oxidants, aerosols, heavy metals) over all of Europe. It includes simple reaction chemistry as well as wet and dry deposition.
MATCH (Sweden) – A multi-scale atmospheric transport and chemistry (MATCH). A three-dimensional, Eulerian model, suitable from urban to global scale.
MEMO (Greece) – A Eulerian non-hydrostatic prognostic mesoscale model for wind flow simulation. It was developed by the Aristotle University of Thessaloniki in collaboration with the Universität Karlsruhe. This model is designed for describing atmospheric transport phenomena in the local-to-regional scale, often referred to as mesoscale air pollution models.
MERCURE (France) – An atmospheric dispersion modeling CFD code developed by Electricite de France (EDF) and distributed by ARIA Technologies, a French company. The code is a version of the CFD software ESTET, developed by EDF's Laboratoire National d'Hydraulique.
MODIM (Slovak Republic) – A model for calculating the dispersion of continuous, neutral or buoyant plumes on a local to regional scale. It integrates a Gaussian plume model for single or multiple point and area sources with a numerical model for line sources, street networks and street canyons. It is intended for regulatory and planning purposes.
MSS (France) – Micro-swift-spray is a Lagrangian particle model used to predict the transport and dispersion of contaminants in urban environments. The SWIFT portion of this model predicts a mass-consistent wind field that considers terrain; no-penetration conditions for building boundaries; Rockle zones for recirculation, edge, and rooftop separation; and background and locally generated turbulence. The spray portion of the tool handles the dispersion of passive gases, dense gases, and particulates. Spray also accounts for plume buoyancy effects, wet and dry depositions, and calculates microscale pressure fields for integration with building models. The MSS development team is found at ARIA Technologies (France) and U.S. integration activities are led by Leidos. Validation testing of MSS has been done in conjunction with JEM and HPAC tool releases and the model is coupled with SCIPUFF/UDM to create a nested dispersion capability inside HPAC. For more information on MSS see http://www.aria.fr.
MUSE (Greece) – A photochemical atmospheric dispersion model developed by Professor Nicolas Moussiopoulos at the Aristotle University of Thessaloniki in Greece. It is intended for the study of photochemical smog formation in urban areas and assessment of control strategies on a local to regional scale. It can simulate dry deposition and transformation of pollutants can be treated using any suitable chemical reaction mechanism.
OML (Denmark) – A model for dispersion calculations of continuous neutral or buoyant plumes from single or multiple, stationary point and area sources. It has some simple methods for handling photochemistry (primarily for NO2) and for handling complex terrain. The model was developed by the National Environmental Research Institute of Denmark. It is now maintained by the Department of Environmental Science, Aarhus University. For further reference see as well: OML home page
ONM9440 (Austria) – A Gaussian dispersion model for continuous, buoyant plumes from stationary sources for use in flat terrain areas. It includes plume depletion by dry deposition of solid particulates.
OSPM (Denmark) – The operational street pollution model (OSPM) is a practical street pollution model, developed by the National Environmental Research Institute of Denmark. It is now maintained by the Department of Environmental Science, Aarhus University. For almost 20 years, OSPM has been routinely used in many countries for studying traffic pollution, performing analyses of field campaign measurements, studying efficiency of pollution abatement strategies, carrying out exposure assessments and as reference in comparisons to other models. OSPM is generally considered as state-of-the-art in applied street pollution modelling. For further reference see as well: OSPM home page
PANACHE (France) – fluidyn-PANACHE is a self-contained fully 3D fluid dynamics software package designed to simulate accidental or continuous industrial and urban pollutant dispersion into the atmosphere. It simulates release and toxic/flammables pollutants dispersion in various weather conditions in calculated 3D complex winds and turbulence fields. Gas, particles, droplets induced flow and transport/diffusion is simulated with Navier-Stokes equations for jet-like, dense, cold, cryogenic or hot, buoyant releases. The application covers the very short scale (tens of meters) and the local scale (ten kilometers) where the complex flow pattern as related to obstacles, variable land uses, topography is calculated explicitly.
PROKAS-V (Germany) – A Gaussian dispersion model for evaluating the atmospheric dispersion of air pollutants emitted from vehicular traffic on a road network of line sources on a local scale.
PLUME (Bulgaria) – A conventional Gaussian plume model used in many regulatory applications. The basis of the model is a single simple formula which assumes constant wind speed and reflection from the ground surface. The horizontal and vertical dispersion parameters are a function of downwind distance and stability. The model was developed for routine applications in air quality assessment, regulatory purposes and policy support.
POLGRAPH (Portugal) – This model was developed at the University of Aveiro, Portugal by Professor Carlos Borrego. It was designed for evaluating the impact of industrial pollutant releases and for air quality assessments. It is a Gaussian plume dispersion model for continuous, elevated point sources to be used on a local scale over flat or gently rolling terrain.
RADM (France) – The random-walk advection and dispersion model (RADM) was developed by ACRI-ST, an independent research and development organization in France. It can model gas plumes and particles (including pollutants with exponential decay or formation rates) from single or multiple stationary, mobile or area sources. Chemical reaction, radioactive decay, deposition, complex terrain, and inversion conditions are accommodated.
RIMPUFF (Denmark) – A local and regional scale real-time puff diffusion model developed by Risø National Laboratory for Sustainable Energy, Technical University of Denmark. Risø DTU. RIMPUFF is an operational emergency response model in use for assisting emergency management organisations dealing with chemical, nuclear, biological and radiological (CBRN) releases to the atmosphere. RIMPUFF is in operation in several European national emergency centres for preparedness and prediction of nuclear accidental releases (RODOS, EURANOS, ARGOS), chemical gas releases (ARGOS), and serves also as a decision support tool during active combatting of airborne transmission of various biological infections, including e.g. Foot-and Mouth Disease outbreaks. DEFRA Foot and Mouth Disease.
SAFE AIR II (Italy) – The simulation of air pollution from emissions II (SAFE AIR II) was developed at the Department of Physics, University of Genoa, Italy to simulate the dispersion of air pollutants above complex terrain at local and regional scales. It can handle point, line, area and volume sources and continuous plumes as well as puffs. It includes first-order chemical reactions and plume depletion by wet and dry deposition, but it does not include any photochemistry.
SEVEX (Belgium) – The Seveso expert model simulates the accidental release of toxic and/or flammable material over flat or complex terrain from multiple pipe and vessel sources or from evaporation of volatile liquid spill pools. The accidental releases may be continuous, transient or catastrophic. The integrated model can handle denser-than-air gases as well as neutral gases (i.e., neither denser than or lighter than air). It does not include handling of multi-component material, nor does it provide for chemical transformation of the releases. The model's name is derived from the major disaster caused by the accidental release of highly toxic gases that occurred in Seveso, Italy in 1976.
SNAP (Norway) – The Severe Nuclear Accident Programme (SNAP) model is a Lagrangian type atmospheric dispersion model specialized on modelling dispersion of radioactive debris.
SPRAY (Italy, France) – A Lagrangian particle dispersion model (LPDM) which simulates the transport, dispersion and deposition of pollutants emitted from sources of different kind over complex terrain and with the presence of obstacles. The model easily takes into account complex situations, such as the presence of breeze cycles, strong meteorological inhomogeneities and non-stationary, low wind calm conditions and recirculations. Simulations can cover area ranging from very local (less than one kilometer) to regional (hundreds of kilometres) scales. Plume rise of hot emission from stack is taken into account using a Briggs formulation. Algorithms for particle-oriented dry/wet deposition processes and for considering the gravitational settling are present. Dry deposition can be computed on ground and also on ceil/roof and on lateral faces of obstacles. Dispersion under generalized geometries like arches, tunnels and walkways can be performed. Dense gas dispersion is simulated using five conservation equations (mass, energy, vertical momentum and two horizontal momenta) based on Glandening et al. (1984) and Hurley and Manins (1995). Plume spread at the ground due to gravity is also simulated by a method (Anfossi et al., 2009), based on Eidsvik (1980).
STACKS (The Netherlands) – A Gaussian plume dispersion model for point and area buoyant plumes to be used over flat terrain on a local scale. It includes building effects, NO2 chemistry and plume depletion by deposition. It is used for environmental impact studies and evaluation of emission reduction strategies.
STOER.LAG (Germany) – A dispersion model designed to evaluate accidental releases of hazardous and/or flammable materials from point or area sources in industrial plants. It can handle neutral and denser-than-air gases or aerosols from ground-level or elevated sources. The model accommodates building and terrain effects, evaporation of volatile liquid spill pools, and combustion or explosion of flammable gas-air mixtures (including the impact of heat and pressure waves caused by a fire or explosion).
SYMOS'97 (Czech Republic) – A model developed by the Czech Hydrometeorological Institute for dispersion calculations of continuous neutral or buoyant plumes from single or multiple point, area or line sources. It can handle complex terrain and it can also be used to simulate the dispersion of cooling tower plumes.
TCAM is a multiphase three-dimensional eulerian grid model designed by ESMA group of University of Brescia, for modelling dispersion of pollutants (in particular photochemical and aerosol) at mesoscale.
UDM-FMI (Finland) – This model was developed by the Finnish Meteorological Institute (FMI) as an integrated Gaussian urban scale model intended for regulatory pollution control. It handles multiple point, line, area and volume sources and it includes chemical transformation (for NO2), wet and dry deposition (for SO2), and downwash phenomena (but no building effects).
VANADIS (Poland) – 3D unsteady state eulerian type model – Demo – 3d dispersion model – please read vanadis_eng.txt.
Models developed in Australia
AUSPLUME – A dispersion model that has been designated as the primary model accepted by the Environmental Protection Authority (EPA) of the Australian state of Victoria. (update:AUSPLUME V6 will no longer be the air pollution dispersion regulatory model in Victoria from 1 January 2014. From this date the air pollution dispersion regulatory model in Victoria will be AERMOD.)
pDsAUSMOD – Australian graphical user interface for AERMOD
pDsAUSMET – Australian meteorological data processor for AERMOD
LADM – An advanced model developed by Australia's Commonwealth Scientific and Industrial Research Organisation (CSIRO) for simulating the dispersion of buoyant pollution plumes and predicting the photochemical formation of smog over complex terrain on a local to regional scale. The model can also handle fumigated plumes (see the books listed below in the "Further reading" section for an explanation of fumigated plumes).
TAPM – An advanced dispersion model integrated with a pre-processor for providing meteorological data inputs. It can handle multiple pollutants, and point, line, area and volume sources on a local, city or regional scale. The model capabilities include building effects, plume depletion by deposition, and a photochemistry module. This model was also developed by Australia's Commonwealth Scientific and Industrial Research Organisation (CSIRO).
DISPMOD – A Gaussian atmospheric dispersion model for point sources located in coastal regions. It was designed specifically by the Western Australian Department of Environment to simulate the plume fumigation that occurs when an elevated onshore pollution plume intersects a growing thermal internal boundary layer (TIBL) contained within offshore air flow coming onshore.
AUSPUFF – A Gaussian puff model designed for regulatory use by CSIRO. It includes some simple algorithms for the chemical transformation of reactive air pollutants.
Models developed in Canada
MLCD – Modèle Lagrangien à courte distance is a Lagrangian particle dispersion model (LPDM) developed in collaboration by Environment Canada's Canadian Meteorological Centre (CMC) and by the Department of Earth and Atmospheric Sciences of University of Alberta. This atmospheric dispersion and deposition model is designed to estimate air concentrations and surface deposition of pollutants for very short range emergency problems (less than ~10 km from the source).
MLDPn – Modèle Lagrangien de dispersion de particules d'ordre n is a Lagrangian particle dispersion model (LPDM) developed by Environment Canada's Canadian Meteorological Centre (CMC). This atmospheric and aquatic transport and dispersion model is designed to estimate air and water concentrations and ground deposition of pollutants for various emergency response problems at different scales (local to global). It is used to forecast and track volcanic ash, radioactive material, forest fire smoke, chemical hazardous substances as well as oil slicks.
Trajectory – The trajectory model, developed by Environment Canada's Canadian Meteorological Centre (CMC), is a simple tool designed to calculate the trajectory of a few air parcels moving in the 3D wind field of the atmosphere. The model provides a quick estimate of the expected trajectory of an air parcel by the advection transport mechanism, originating from (forward trajectory) or arriving at (backward trajectory) a specified geographical location and a vertical level.
Models developed in India
HAMS-GPS – Software used for management of environment, health and safety (EHS). It can be used for training as well as research involving dispersion modeling, accident analysis, fires, explosions, risk assessments and other related subjects.
Air pollution dispersion models
ADMS 5
AERMOD
CALPUFF
DISPERSION21
PUFF-PLUME
MERCURE
NAME
OSPM
SAFE AIR
RIMPUFF
HAMS-GPS EIA modeling
Others
Air pollution dispersion terminology
Atmospheric dispersion modeling
Bibliography of atmospheric dispersion modeling
Roadway air dispersion modeling
Wind profile power law
References
Schenk R (1996) Entwicklung von IBS Verkehr, Fördervorhaben des Ministeriums für Umwelt und Landwirtschaft des Landes Sachsen-Anhalt, FKZ 76213//95, 1996
Schenk R (1980) Numerische Behandlung instationärer Transportprobleme, Habilitation an der TU Dresden, 1980
Further reading
For those who would like to learn more about atmospheric dispersion models, it is suggested that either one of the following books be read:
www.crcpress.com
External links
Air Quality Modeling – From the website of Stuff in the Air
The Model Documentation System (MDS) of the European Topic Centre on Air and Climate Change (part of the European Environment Agency)
USA EPA Preferred/Recommended Models Alternative Models Screening Models Photochemical Models
Wiki on Atmospheric Dispersion Modelling. Addresses the international community of atmospheric dispersion modellers – primarily researchers, but also users of models. Its purpose is to pool experiences gained by dispersion modellers during their work.
The ADMS models and the GASTAR model
The AUSPLUME model
The CHARM model
Fluidyn-PANACHE: 3D Computational Fluid Dynamcis(CFD) model for Dispersion Analysis
The HAMS-GPS software
The LADM, DISPMOD and AUSPUFF models
The LAPMOD model
The NAME model
The RIMPUFF model
The SPRAY model
The TAPM model
Validation of the Urban Dispersion Model (UDM)
Atmospheric dispersion modeling | List of atmospheric dispersion models | [
"Chemistry",
"Engineering",
"Environmental_science"
] | 8,417 | [
"Atmospheric dispersion modeling",
"Environmental modelling",
"Environmental engineering"
] |
4,271,868 | https://en.wikipedia.org/wiki/Rubidium-82%20chloride | Rubidium-82 chloride is a form of rubidium chloride containing a radioactive isotope of rubidium. It is marketed under the brand name Cardiogen-82 by Bracco Diagnostics for use in Myocardial perfusion imaging. It is rapidly taken up by heart muscle cells, and therefore can be used to identify regions of heart muscle that are receiving poor blood flow in a technique called PET perfusion imaging. The half-life of rubidium-82 is only 1.27 minutes; it is normally produced at the place of use by rubidium generators.
References
Further reading
(Note: only about 1/2 page on Rb-generator)
Cardiac imaging
Rubidium compounds
Chlorides
Metal halides
Alkali metal chlorides
Radiopharmaceuticals | Rubidium-82 chloride | [
"Chemistry"
] | 154 | [
"Pharmacology",
"Chlorides",
"Medicinal radiochemistry",
"Inorganic compounds",
"Medicinal chemistry stubs",
"Salts",
"Chemicals in medicine",
"Radiopharmaceuticals",
"Metal halides",
"Pharmacology stubs"
] |
4,271,984 | https://en.wikipedia.org/wiki/Latent%20tuberculosis | Latent tuberculosis (LTB), also called latent tuberculosis infection (LTBI) is when a person is infected with Mycobacterium tuberculosis, but does not have active tuberculosis (TB). Active tuberculosis can be contagious while latent tuberculosis is not, and it is therefore not possible to get TB from someone with latent tuberculosis. Various treatment regimens are in use for latent tuberculosis. They generally need to be taken for several months.
Epidemiology
The latent tuberculosis is worldwide, approximately one third of the world's population is latently infected with M. tuberculosis, with a new case occurring approximately every second.
The spread of tuberculosis is uneven throughout the world, with approximately 80% of the population in many Asian and African countries testing positive on tuberculin tests, while only 5–10% of the US population tests positive.
Transmission
Latent disease
TB Bacteria Are Spread Only from a Person with Active TB Disease ... In people who develop active TB of the lungs, also called pulmonary TB, the TB skin test will often be positive. In addition, they will show all the signs and symptoms of TB disease, and can pass the bacteria to others. So, if a person with TB of the lungs sneezes, coughs, talks, sings, or does anything that forces the bacteria into the air, other people nearby may breathe in TB bacteria. Statistics show that approximately one-third of people exposed to pulmonary TB become infected with the bacteria, but only one in ten of these infected people develops active TB disease during their lifetimes.However, exposure to tuberculosis is very unlikely to happen when one is exposed for a few minutes in a store or in a few minutes social contact. "It usually takes prolonged exposure to someone with active TB disease for someone to become infected.
After exposure, it usually takes 8 to 10 weeks before the TB test would show if someone had become infected."Depending on ventilation and other factors, these tiny droplets [from the person who has active tuberculosis] can remain suspended in the air for several hours. Should another person inhale them, he or she may become infected with TB. The probability of transmission will be related to the infectiousness of the person with TB, the environment where the exposure occurred, the duration of the exposure, and the susceptibility of the host.In fact, "it isn't easy to catch TB. You need consistent exposure to the contagious person for a long time. For that reason, you're more likely to catch TB from a relative than a stranger."
If a person had latent tuberculosis, they do not have active/contagious tuberculosis. Once exposed, people very often have latent tuberculosis. To convert to active tuberculosis, the bacteria must become active.
In some countries like Canada people have medical privacy or "confidentiality" and do not have to reveal their active tuberculosis case to family, friends, or co-workers; therefore, the person who gets latent tuberculosis may never know who had the active case of tuberculosis that caused the latent tuberculosis diagnosis for them. Only by required testing (required in some jobs) or developing symptoms of active tuberculosis and visiting a medical doctor who does testing will a person know they have been exposed. Because tuberculosis is not common in the United States, doctors may not suspect tuberculosis; therefore, they may not test. If a person has symptoms of tuberculosis, it is wise to be tested.
Persons with diabetes may have an 18% chance of converting to active tuberculosis. In fact, death from tuberculosis was greater in diabetic patients. Persons with HIV and latent tuberculosis have a 10% chance of developing active tuberculosis every year. "HIV infection is the greatest known risk factor for the progression of latent M. tuberculosis infection to active TB. In many African countries, 30–60% of all new TB cases occur in people with HIV, and TB is the leading cause of death globally for HIV-infected people."
Reactivation
Once a person has been diagnosed with Latent Tuberculosis (LTBI) and a medical doctor confirms no active tuberculosis, the person should remain alert to symptoms of active tuberculosis for the remainder of their life. Even after completing the full course of medication, there is no guarantee that the tuberculosis bacteria have all been killed. "When a person develops active TB (disease), the symptoms (cough, fever, night sweats, weight loss etc.) may be mild for many months. This can lead to delays in seeking care, and results in transmission of the bacteria to others."
Tuberculosis does not always settle in the lungs. If the outbreak of tuberculosis is in the brain, organs, kidneys, joints, or others areas, the patient may have active tuberculosis for an extended period of time before discovering that they are active. "A person with TB disease may feel perfectly healthy or may only have a cough from time to time." However, these symptoms do not guarantee tuberculosis, and they may not exist at all, yet the patient may still have active tuberculosis. A person with symptoms listed may have active tuberculosis, and the person should immediately see a physician so that tuberculosis is not spread. If a person with the above symptoms does not see a physician, ignoring the symptoms can result in lung damage, eye damage, organ damage and eventually death.
When tuberculosis settles in other organs (rather than lungs) or other parts of the body (such as the skeletal), symptoms may be different from when it settles in the lungs (such as the symptoms listed above). Thus, without the cough or flu-like symptoms, a person can unwittingly have active tuberculosis. Other symptoms include back pain, flank pain, PID symptoms, confusion, coma, difficulty swallowing, and many other symptoms that would be a part of other diseases. (Please see the reference for more information on symptoms.) Therefore, seeing a physician and asking for a tuberculosis test is absolutely necessary to rule out tuberculosis when a patient has symptoms without a diagnosis of disease.
Risk factors
Situations in which tuberculosis may become reactivated are:
if there is onset of a disease affecting the immune system (such as AIDS) or a disease whose treatment affects the immune system (such as chemotherapy in cancer or systemic steroids in asthma or Enbrel, Humira or Orencia in rheumatoid arthritis);
malnutrition (which may be the result of illness or injury affecting the digestive system, or of a prolonged period of not eating, or disturbance in food availability such as during famine or residence in a refugee or concentration camp);
degradation of the immune system due to aging;
certain systemic diseases such as diabetes,;
other conditions such as debilitating disease (especially haematological and some solid cancers), use of steroid medication long-term, end-stage renal disease, silicosis, gastrectomy, and jejuno-ileal bypass;
being elderly; and
young age.
Diagnosis
There are two classes of tests commonly used to identify patients with latent tuberculosis: tuberculin skin tests and IFN-γ (Interferon-gamma) tests.
The skin tests currently include the following two:
Mantoux test
Heaf test
IFN-γ tests include the following three:
T-SPOT.TB
QuantiFERON-TB Gold
QuantiFERON-TB Gold In-Tube
Tuberculin skin testing
The tuberculin skin test (TST) in its first iteration, the Mantoux Test, was developed in 1908. Tuberculin (also called purified protein derivative or PPD) is a standardised dead extract of cultured TB, injected into the skin to measure the person's immune response to the bacteria. So, if a person has been exposed to the bacteria previously, they should express an immune reaction to the injection, usually a mild swelling or redness around the site. There have been two primary methods of TST: the Mantoux test, and the Heaf test. The Heaf test was discontinued in 2005 because the manufacturer deemed its production to be financially unsustainable, though it was previously preferred in the UK because it was felt to require less training to administer and involved less inter-observer variation in its interpretation than the Mantoux test. The Mantoux test was the preferred test in the US, and is now the most widely used TST globally.
Mantoux test
See: Mantoux test
The Mantoux test is now standardised by the WHO. 0.1 ml of tuberculin (100 units/ml), which delivers a dose of 5 units is given by intradermal injection into the surface of the lower forearm (subcutaneous injection results in false negatives). A waterproof ink mark is drawn around the injection site so as to avoid difficulty finding it later if the level of reaction is small. The test is read 48 to 72 hours later. The area of induration (NOT of erythema) is measured transversely across the forearm (left to right, not up and down) and recorded to the nearest millimetre.
Heaf test
See:Heaf test
The Heaf test was first described in 1951. The test uses a Heaf gun with disposable single-use heads; each head has six needles arranged in a circle. There are standard heads and pediatric heads: the standard head is used on all patients aged 2 years and older; the pediatric head is for infants under the age of 2. For the standard head, the needles protrude 2 mm when the gun is actuated; for the pediatric heads, the needles protrude 1 mm. Skin is cleaned with alcohol, then tuberculin (100,000 units/ml) is evenly smeared on the skin (about 0.1 ml); the gun is then applied to the skin and fired. The excess solution is then wiped off and a waterproof ink mark is drawn around the injection site. The test is read 2 to 7 days later.
Grade 0: no reaction, or induration of 3 or less puncture points;
Grade 1: induration of four or more puncture points;
Grade 2: induration of the six puncture points coalesce to form a circle;
Grade 3: induration of 5 mm; or more
Grade 4: induration of 10 mm or more, or ulceration
The results of both tests are roughly equivalent as follows:
Heaf grade 0 & 1 ~ Mantoux less than 5 mm;
Heaf grade 2 ~ Mantoux 5–14 mm;
Heaf grade 3 & 4 ~ Mantoux 15 or greater
Tuberculin conversion
Tuberculin conversion is said to occur if a patient who has previously had a negative tuberculin skin test develops a positive tuberculin skin test at a later test. It indicates a change from negative to positive, and usually signifies a new infection.
Boosting
The phenomenon of boosting is one way of obtaining a false positive test result. Theoretically, a person's ability to develop a reaction to the TST may decrease over time – for example, a person is infected with latent TB as a child, and is administered a TST as an adult. Because there has been such a long time since the immune responses to TB has been necessary, that person might give a negative test result. If so, there is a fairly reasonable chance that the TST triggers a hypersensitivity in the person's immune system – in other words, the TST reminds the person's immune system about TB, and the body overreacts to what it perceives as a reinfection. In this case, when that subject is given the test again (as is standard procedure, see above) they may have a significantly greater reaction to the test, giving a very strong positive; this can be commonly misdiagnosed as Tuberculin Conversion. This can also be triggered by receiving the BCG vaccine, as opposed to a proper infection. Although boosting can occur in any age group, the likelihood of the reaction increases with age.
Boosting is only likely to be relevant if an individual is beginning to undergo periodic TSTs (health care workers, for example). In this case the standard procedure is called two-step testing. The individual is given their first test and in the event of a negative, given a second test in 1 to 3 weeks. This is done to combat boosting in situations where, had that person waited up to a year to get their next TST, they might still have a boosted reaction, and be misdiagnosed as a new infection.
Here there is a difference in US and UK guidelines; in the US testers are told to ignore the possibility of false positive due to the BCG vaccine, as the BCG is seen as having waning efficacy over time. Therefore, the CDC urges that individuals be treated based on risk stratification regardless of BCG vaccination history, and if an individual receives a negative and then a positive TST they will be assessed for full TB treatment beginning with X-ray to confirm TB is not active and proceeding from there. Conversely, the UK guidelines acknowledge the potential effect of the BCG vaccination, as it is mandatory and therefore a prevalent concern – though the UK shares the procedure of administering two tests, one week apart, and accepting the second one as the accurate result, they also assume that a second positive is indicative of an old infection (and therefore certainly LTBI) or the BCG itself. In the case of BCG vaccinations confusing the results, Interferon-γ (IFN-γ) tests may be used as they will not be affected by the BCG.
Interpretation
According to the U.S. guidelines, there are multiple size thresholds for declaring a positive result of latent tuberculosis from the Mantoux test: For testees from high-risk groups, such as those who are HIV positive, the cutoff is 5 mm of induration; for medium risk groups, 10 mm; for low-risk groups, 15 mm. The U.S. guidelines recommend that a history of previous BCG vaccination should be ignored. For details of tuberculin skin test interpretation, please refer to the CDC guidelines (reference given below).
The UK guidelines are formulated according to the Heaf test: In patients who have had BCG previously, latent TB is diagnosed if the Heaf test is grade 3 or 4 and have no signs or symptoms of active TB; if the Heaf test is grade 0 or 1, then the test is repeated. In patients who have not had BCG previously, latent TB is diagnosed if the Heaf test is grade 2, 3 or 4, and have no signs or symptoms of active TB. Repeat Heaf testing is not done in patients who have had BCG (because of the phenomenon of boosting). For details of tuberculin skin test interpretation, please refer to the BTS guidelines (references given below).
Given that the US recommendation is that prior BCG vaccination be ignored in the interpretation of tuberculin skin tests, false positives with the Mantoux test are possible as a result of: (1) having previously had a BCG (even many years ago), or (2) periodical testing with tuberculin skin tests. Having regular TSTs boosts the immunological response in those people who have previously had BCG, so these people will falsely appear to be tuberculin conversions. This may lead to treating more people than necessary, with the possible risk of those patients developing adverse drug reactions. However, as Bacille Calmette-Guérin vaccine is not 100% effective, and is less protective in adults than pediatric patients, not treating these patients could lead to a possible infection. The current US policy seems to reflect a desire to err on the side of safety.
The U.S. guidelines also allow for tuberculin skin testing in immunosuppressed patients (those with HIV, or who are on immunosuppressive drugs), whereas the UK guidelines recommend that tuberculin skin tests should not be used for such patients because it is unreliable.
Interferon-γ testing
The role of IFN-γ tests is undergoing constant review and various guidelines have been published with the option for revision as new data becomes available.CDC:MMWR Health Protection Agency:UK
There are currently two commercially available interferon-γ release assays (IGRAs): QuantiFERON-TB Gold and T-SPOT.TB. These tests are not affected by prior BCG vaccination, and look for the body's response to specific TB antigens not present in other forms of mycobacteria and BCG (ESAT-6). Whilst these tests are new they are now becoming available globally.
CDC:
HPA Interim Guidance:
Drug-resistant strains
It is usually assumed by most medical practitioners in the early stages of a diagnosis that a case of latent tuberculosis is the normal or regular strain of tuberculosis. It will therefore be most commonly treated with Isoniazid (the most used treatment for latent tuberculosis.) Only if the tuberculosis bacteria does not respond to the treatment will the medical practitioner begin to consider more virulent strains, requiring significantly longer and more thorough treatment regimens.
There are 4 types of tuberculosis recognized in the world today:
Tuberculosis (TB)
Multi-drug-resistant tuberculosis (MDR TB)
Extensively drug-resistant tuberculosis (XDR TB)
Totally drug-resistant tuberculosis (TDR TB)
Treatment
The treatment of latent tuberculosis infection (LTBI) is essential to controlling and eliminating TB by reducing the risk that TB infection will progress to disease. Latent tuberculosis will convert to active tuberculosis in 10% of cases (or more in cases of immune compromised patients). Taking medication for latent tuberculosis is recommended by many doctors.
In the U.S., the standard treatment is nine months of isoniazid, but this regimen is not widely used outside of the US.
Terminology
There is no agreement regarding terminology: the terms preventive therapy and chemoprophylaxis have been used for decades, and are preferred in the UK because it involves giving medication to people who have no disease and are currently well: the reason for giving medication is primarily to prevent people from becoming unwell. In the U.S., physicians talk about latent tuberculosis treatment because the medication does not actually prevent infection: the person is already infected and the medication is intended to prevent existing silent infection from becoming active disease. There are no convincing reasons to prefer one term over the other.
Specific situations
"Populations at increased risk of progressing to active infection once exposed:
Persons with recent TB infection [those infected within the previous two years]
Congenital or acquired immunosuppressed patients (in particular, HIV-positive patients)
Illicit intravenous drug users; alcohol and other chronic substance users
Children (particularly those younger than 4 years old)
Persons with comorbid conditions (ie, chronic kidney failure, diabetes, malignancy, hematologic cancers, body weight of at least 10% less than ideal, silicosis, gastrectomy, jejunoileal bypass, asthma, or other disorders requiring long-term use of corticosteroids or other immunosuppressants)."
Treatment regimens
It is essential that assessment to rule out active TB be carried out before treatment for LTBI is started. To give treatment for latent tuberculosis to someone with active tuberculosis is a serious error: the tuberculosis will not be adequately treated and there is a serious risk of developing drug-resistant strains of TB.
There are several treatment regimens currently in use:
9H — isoniazid for 9 months is the gold standard (93% effective, in patients with positive test results and fibrotic pulmonary lesions compatible with tuberculosis).
6H — Isoniazid for 6 months might be adopted by a local TB program based on cost-effectiveness and patient compliance. This is the regimen currently recommended in the UK for routine use. The U.S. guidance excludes this regimen from use in children or persons with radiographic evidence of prior tuberculosis (old fibrotic lesions) (69% effective).
6 to 9H2 — An intermittent twice-weekly regimen for the above two treatment regimens is an alternative if administered under Directly observed therapy (DOT).
4R — rifampicin for 4 months is an alternative for those who are unable to take isoniazid or who have had known exposure to isoniazid-resistant TB.
3HR — Isoniazid and rifampin may be given daily for three months.
2RZ — The two-month regimen of rifampin and pyrazinamide is no longer recommended for treatment of LTBI because of the greatly increased risk of drug-induced hepatitis and death.
3HP – three-month (12-dose) regimen of weekly rifapentine and isoniazid. The 3HP regimen has to be administered under DOT. A self-administered therapy (SAT) of 3HP is investigated in a large international study.
Evidence for treatment effectiveness
A 2000 Cochrane review containing 11 double-blinded, randomized control trials and 73,375 patients examined six and 12 month courses of isoniazid (INH) for treatment of latent tuberculosis. HIV positive and patients currently or previously treated for tuberculosis were excluded. The main result was a relative risk (RR) of 0.40 (95% confidence interval (CI) 0.31 to 0.52) for development of active tuberculosis over two years or longer for patients treated with INH, with no significant difference between treatment courses of six or 12 months (RR 0.44, 95% CI 0.27 to 0.73 for six months, and 0.38, 95% CI 0.28 to 0.50 for 12 months).
A Cochrane systematic review published in 2013 evaluated four different alternatives regimens to INH monotherapy for preventing active TB in HIV-negative people with latent tuberculosis infection. The evidence from this review found no difference between shorter regimens of Rifampicin or weekly, directly observed Rifapentine plus INH compare to INH monotherapy in preventing active TB in HIV-negative people at risk of developing it . However the review found that the shorter Rifampicin regimen for four months and weekly directly observed Rifapentine plus INH for three months "may have additional advantages of higher treatment completion and improved safety." However the overall quality of evidence was low to moderate (as per GRADE criteria) and none of the included trials were conducted in LMIC nations with high TB transmission and hence might not be applicable to nations with high TB transmission.
Treatment efficacy
There is no guaranteed "cure" for latent tuberculosis. "People infected with TB bacteria have a lifetime risk of falling ill with TB..." with those who have compromised immune systems, those with diabetes and those who use tobacco at greater risk.
A person who has taken the complete course of Isoniazid (or other full course prescription for tuberculosis) on a regular, timely schedule may have been cured. "Current standard therapy is isoniazid (INH) which reduce the risk of active TB by as much as 90 per cent (in patients with positive LTBI test results and fibrotic pulmonary lesions compatible with tuberculosis) if taken daily for 9 months." However, if a person has not completed the medication exactly as prescribed, the "cure" is less likely, and the "cure" rate is directly proportional to following the prescribed treatment specifically as recommended. Furthermore, "If you don't take the medicine correctly and you become sick with TB a second time, the TB may be harder to treat if it has become drug resistant." If a patient were to be cured in the strictest definition of the word, it would mean that every single bacterium in the system is removed or dead, and that person cannot get tuberculosis (unless re-infected). However, there is no test to assure that every single bacterium has been killed in a patient's system. As such, a person diagnosed with latent TB can safely assume that, even after treatment, they will carry the bacteria – likely for the rest of their lives. Furthermore, "It has been estimated that up to one-third of the world's population is infected with M. tuberculosis, and this population is an important reservoir for disease reactivation." This means that in areas where TB is endemic treatment may be even less certain to "cure" TB, as reinfection could trigger activation of latent TB already present even in cases where treatment was followed completely.
Controversy
There is controversy over whether people who test positive long after infection have a significant risk of developing the disease (without re-infection). Some researchers and public health officials have warned that this test-positive population is a "source of future TB cases" even in the US and other wealthy countries, and that this "ticking time bomb" should be a focus of attention and resources.
On the other hand, Marcel Behr, Paul Edelstein, and Lalita Ramakrishnan reviewed studies concerning the concept of latent tuberculosis in order to determine whether tuberculosis-infected persons have life-long infection capable of causing disease at any future time. These studies, both published in the British Medical Journal (BMJ) in 2018 and 2019, show that the incubation period of tuberculosis is short, usually within months after infection, and very rarely more than two years after infection. They also show that more than 90% of people infected with M. tuberculosis for more than two years never develop tuberculosis even if their immune system is severely suppressed. Immunologic tests for tuberculosis infection such as the tuberculin skin test and interferon gamma release assays (IGRA) only indicate past infection, with the majority of previously infected persons no longer capable of developing tuberculosis. Ramakrishnan told the New York Times that researchers "have spent hundreds of millions of dollars chasing after latency, but the whole idea that a quarter of the world is infected with TB is based on a fundamental misunderstanding."
Writing in The Atlantic, science journalist Katherine J. Wu explains:
The first BMJ article disputing widespread latency was accompanied by an editorial written by Dr. Soumya Swaminathan, Deputy Director-General of the World Health Organization, who endorsed the findings and called for more funding of TB research directed at the most heavily afflicted parts of the world, rather than disproportionate attention to a relatively minor problem that affects just the wealthy countries.
The World Health Organization no longer endorses the concept that all those with immunologic evidence of past TB infection are currently infected and so are at risk of developing TB some time in the future. In 2022, the WHO issued corrigenda to its 2021 Global TB Report to clarify estimates on the worldwide burden of infected people. These corrigenda deleted "About a quarter of the world's population is infected with M. tuberculosis" and replaced it with "About a quarter of the world's population has been infected with M. tuberculosis." The corrigenda also removed the prior estimate of the lifetime risk of TB of 5 to 10% among those with evidence of past TB infection, indicating that they no longer have confidence in earlier estimates that a substantial percentage of those with positive immunologic test results will develop the disease.
See also
Silent disease
References
Further reading
External links
Immunologic tests
tuberculosis
Tuberculosis | Latent tuberculosis | [
"Biology"
] | 5,649 | [
"Immunologic tests"
] |
4,272,334 | https://en.wikipedia.org/wiki/Blancmange%20curve | In mathematics, the blancmange curve is a self-affine fractal curve constructible by midpoint subdivision. It is also known as the Takagi curve, after Teiji Takagi who described it in 1901, or as the Takagi–Landsberg curve, a generalization of the curve named after Takagi and Georg Landsberg. The name blancmange comes from its resemblance to a Blancmange pudding. It is a special case of the more general de Rham curve.
Definition
The blancmange function is defined on the unit interval by
where is the triangle wave, defined by ,
that is, is the distance from x to the nearest integer.
The Takagi–Landsberg curve is a slight generalization, given by
for a parameter ; thus the blancmange curve is the case . The value is known as the Hurst parameter.
The function can be extended to all of the real line: applying the definition given above shows that the function repeats on each unit interval.
Functional equation definition
The periodic version of the Takagi curve can also be defined as the unique bounded solution to the functional equation
Indeed, the blancmange function is certainly bounded, and solves the functional equation, since
Conversely, if is a bounded solution of the functional equation, iterating the equality one has for any N
whence . Incidentally, the above functional equations possesses infinitely many continuous, non-bounded solutions, e.g.
Graphical construction
The blancmange curve can be visually built up out of triangle wave functions if the infinite sum is approximated by finite sums of the first few terms. In the illustrations below, progressively finer triangle functions (shown in red) are added to the curve at each stage.
Properties
Convergence and continuity
The infinite sum defining converges absolutely for all Since for all
if The Takagi curve of parameter is defined on the unit interval (or ) if . The Takagi function of parameter is continuous. The functions defined by the partial sums
are continuous and converge uniformly toward
for all x when This bound decreases as By the uniform limit theorem, is continuous if |w| < 1.
Subadditivity
Since the absolute value is a subadditive function so is the function , and its dilations ; since positive linear combinations and point-wise limits of subadditive functions are subadditive, the Takagi function is subadditive for any value of the parameter .
The special case of the parabola
For , one obtains the parabola: the construction of the parabola by midpoint subdivision was described by Archimedes.
Differentiability
For values of the parameter the Takagi function is differentiable in the classical sense at any which is not a dyadic rational. By derivation under the sign of series, for any non dyadic rational one finds
where is the sequence of binary digits in the base 2 expansion of :
Equivalently, the bits in the binary expansion can be understood as a sequence of square waves, the Haar wavelets, scaled to width This follows, since the derivative of the triangle wave is just the square wave:
and so
For the parameter the function is Lipschitz of constant In particular for the special value one finds, for any non dyadic rational , according with the mentioned
For the blancmange function it is of bounded variation on no non-empty open set; it is not even locally Lipschitz, but it is quasi-Lipschitz, indeed, it admits the function as a modulus of continuity .
Fourier series expansion
The Takagi–Landsberg function admits an absolutely convergent Fourier series expansion:
with and, for
where is the maximum power of that divides .
Indeed, the above triangle wave has an absolutely convergent Fourier series expansion
By absolute convergence, one can reorder the corresponding double series for :
putting yields the above Fourier series for
Self similarity
The recursive definition allows the monoid of self-symmetries of the curve to be given. This monoid is given by two generators, g and r, which act on the curve (restricted to the unit interval) as
and
A general element of the monoid then has the form for some integers This acts on the curve as a linear function: for some constants a, b and c. Because the action is linear, it can be described in terms of a vector space, with the vector space basis:
In this representation, the action of g and r are given by
and
That is, the action of a general element maps the blancmange curve on the unit interval [0,1] to a sub-interval for some integers m, n, p. The mapping is given exactly by where the values of a, b and c can be obtained directly by multiplying out the above matrices. That is:
Note that is immediate.
The monoid generated by g and r is sometimes called the dyadic monoid; it is a sub-monoid of the modular group. When discussing the modular group, the more common notation for g and r is T and S, but that notation conflicts with the symbols used here.
The above three-dimensional representation is just one of many representations it can have; it shows that the blancmange curve is one possible realization of the action. That is, there are representations for any dimension, not just 3; some of these give the de Rham curves.
Integrating the Blancmange curve
Given that the integral of from 0 to 1 is 1/2, the identity allows the integral over any interval to be computed by the following relation. The computation is recursive with computing time on the order of log of the accuracy required. Defining
one has that
The definite integral is given by:
A more general expression can be obtained by defining
which, combined with the series representation, gives
Note that
This integral is also self-similar on the unit interval, under an action of the dyadic monoid described in the section Self similarity. Here, the representation is 4-dimensional, having the basis . The action of g on the unit interval is the commuting diagram
From this, one can then immediately read off the generators of the four-dimensional representation:
and
Repeated integrals transform under a 5,6,... dimensional representation.
Relation to simplicial complexes
Let
Define the Kruskal–Katona function
The Kruskal–Katona theorem states that this is the minimum number of (t − 1)-simplexes that are faces of a set of N t-simplexes.
As t and N approach infinity,
(suitably normalized) approaches the blancmange curve.
See also
Cantor function (also known as the Devil's staircase)
Minkowski's question mark function
Weierstrass function
Dyadic transformation
References
Benoit Mandelbrot, "Fractal Landscapes without creases and with rivers", appearing in The Science of Fractal Images, ed. Heinz-Otto Peitgen, Dietmar Saupe; Springer-Verlag (1988) pp 243–260.
Linas Vepstas, Symmetries of Period-Doubling Maps, (2004)
Donald Knuth, The Art of Computer Programming, volume 4a. Combinatorial algorithms, part 1. . See pages 372–375.
Further reading
External links
Takagi Explorer
(Some properties of the Takagi function)
De Rham curves
Theory of continuous functions | Blancmange curve | [
"Mathematics"
] | 1,499 | [
"Theory of continuous functions",
"Topology"
] |
4,272,803 | https://en.wikipedia.org/wiki/Vertical%20handover | Vertical handover or vertical handoff refers to a network node changing the type of connectivity it uses to access a supporting infrastructure, usually to support node mobility. For example, a suitably equipped laptop might be able to use both high-speed wireless LAN and cellular technology for Internet access. Wireless LAN connections generally provide higher speeds, while cellular technologies generally provide more ubiquitous coverage. Thus the laptop user might want to use a wireless LAN connection whenever one is available and to revert to a cellular connection when the wireless LAN is unavailable. Vertical handovers refer to the automatic transition from one technology to another in order to maintain communication. This is different from a horizontal handover between different wireless access points that use the same technology.
Vertical handoffs between WLAN and UMTS (WCDMA) have attracted a great deal of attention in all the research areas of the 4G wireless network, due to the benefit of utilizing the higher bandwidth and lower cost of WLAN as well as better mobility support and larger coverage of UMTS. Vertical handovers among a range of wired and wireless access technologies including WiMAX can be achieved using Media independent handover which is standardized as IEEE 802.21.
Related issues
Dual mode card
To support vertical handover, a mobile terminal needs to have a dual mode card, for example one that can work under both WLAN and UMTS frequency bands and modulation schemes.
Interworking architecture
For the vertical handover between UMTS and WLAN, there are two main interworking architecture: tight coupling and loose coupling.
The tight coupling scheme, which 3GPP adopted, introduces two more elements: WAG (Wireless Access Gateway) and PDG (Packet Data Gateway). So the data transfers from WLAN AP to a Corresponding Node on the internet must go through the Core Network of UMTS.
Loose coupling is more used when the WLAN is not operated by cellular operator but any private user. So the data transmitted through WLAN will not go through Cellular Networks.
Handover metrics
In traditional handovers, such as a handover between cellular networks, the handover decision is based mainly on RSS (Received Signal Strength) in the border region of two cells, and may also be based on call drop rate, etc. for resource management reasons.
In vertical handover, the situation is more complex. Two different kinds of wireless networks normally have incomparable signal strength metrics, for example, WLAN compared to UMTS. In, WLAN and UMTS networks both cover an area at the same time.
The handover metrics in this situation should include RSS, user preference, network conditions, application types, cost etc.
Handover decision algorithm
Based on the handover metrics mentioned above, the decision about how and when to switch the interface to which network will be made.
Many papers have given reasonable flow charts based on the better service and lower cost, etc. while some others, using fuzzy logic, neuron network or MADM methods to solve the problem.
Mobility management
When a mobile station transfers a user's session from one network to another, the IP address will change. In order to allow the Corresponding Node that the MS is communicating with to find it correctly and allow the session to continue, Mobility Management is used.
The Mobility Management problem can be solved in different layers, such as the Application Layer, Transport Layer, IP Layer, etc. The most common method is to use SIP (Session Initiation Protocol) and Mobile IP.
Handoff procedure
The handover procedure specifies the control signalling used to perform the handover and is invoked by the handover decision algorithm.
See also
Load balancing (computing)
Media-independent handover
Multihoming
Access network discovery and selection function
Related standards
3GPP TS 23.234 “3GPP system to WLAN interworking; System description
3GPP TS 23.228 IP Multimedia Subsystem
3GPP TS 23.237 IP Multimedia Subsystem (IMS) Service Continuity; Stage 2
802.21 Media independent handover
IEEE 802.21
Mobile IP
Wireless networking
Mobile telecommunications standards | Vertical handover | [
"Technology",
"Engineering"
] | 823 | [
"Mobile telecommunications",
"Wireless networking",
"Computer networks engineering",
"Mobile telecommunications standards"
] |
4,273,088 | https://en.wikipedia.org/wiki/Go%20Text%20Protocol | The Go Text Protocol (GTP) is a protocol used by several Go engines and Go servers for playing the board game Go on the computer. GTP version 1 has been implemented in GNU Go 3.0.0 but the protocol lacks a proper specification. The currently used version is GTP 2 which exists as a draft specification and has not been finalized.
See also
Computer Go
Go software
Internet Go servers
External links
GTP implementation in Ruby
Go (game) software | Go Text Protocol | [
"Technology"
] | 95 | [
"Computing stubs",
"Computer network stubs"
] |
4,273,222 | https://en.wikipedia.org/wiki/Separation%20logic | In computer science, separation logic is an extension of Hoare logic, a way of reasoning about programs.
It was developed by John C. Reynolds, Peter O'Hearn, Samin Ishtiaq and Hongseok Yang, drawing upon early work by Rod Burstall. The assertion language of separation logic is a special case of the logic of bunched implications (BI). A CACM review article by O'Hearn charts developments in the subject to early 2019.
Overview
Separation logic facilitates reasoning about:
programs that manipulate pointer data structures—including information hiding in the presence of pointers;
"transfer of ownership" (avoidance of semantic frame axioms); and
virtual separation (modular reasoning) between concurrent modules.
Separation logic supports the developing field of research described by Peter O'Hearn and others as local reasoning, whereby specifications and proofs of a program component mention only the portion of memory used by the component, and not the entire global state of the system. Applications include automated program verification (where an algorithm checks the validity of another algorithm) and automated parallelization of software.
Assertions: operators and semantics
Separation logic assertions describe "states" consisting of a store and a heap, roughly corresponding to the state of local (or stack-allocated) variables and dynamically-allocated objects in common programming languages such as C and Java. A store is a function mapping variables to values. A heap is a partial function mapping memory addresses to values. Two heaps and are disjoint (denoted ) if their domains do not overlap (i.e., for every memory address , at least one of and is undefined).
The logic allows to prove judgements of the form , where is a store, is a heap, and is an assertion over the given store and heap. Separation logic assertions (denoted as , , ) contain the standard boolean connectives and, in addition, , , , and , where and are expressions.
The constant asserts that the heap is empty, i.e., when is undefined for all addresses.
The binary operator takes an address and a value and asserts that the heap is defined at exactly one location, mapping the given address to the given value. I.e., when (where denotes the value of expression evaluated in store ) and is otherwise undefined.
The binary operator (pronounced star or separating conjunction) asserts that the heap can be split into two disjoint parts where its two arguments hold, respectively. I.e., when there exist such that and and and .
The binary operator (pronounced magic wand or separating implication) asserts that extending the heap with a disjoint part that satisfies its first argument results in a heap that satisfies its second argument. I.e,. when for every heap such that , also holds.
The operators and share some properties with the classical conjunction and implication operators. They can be combined using an inference rule similar to modus ponens
and they form an adjunction, i.e., if and only if for ; more precisely, the adjoint operators are and .
Reasoning about programs: triples and proof rules
In separation logic, Hoare triples have a slightly different meaning than in Hoare logic. The triple asserts that if the program executes from an initial state satisfying the precondition then the program will not go wrong (e.g., have undefined behaviour), and if it terminates, then the final state will satisfy the postcondition . In essence, during its execution, may access only memory locations whose existence is asserted in the precondition or that have been allocated by itself.
In addition to the standard rules from Hoare logic, separation logic supports the following very important rule:
This is known as the frame rule (named after the frame problem) and enables local reasoning. It says that a program that executes safely in a small state (satisfying ), can also execute in any bigger state (satisfying ) and that its execution will not affect the additional part of the state (and so will remain true in the postcondition). The side condition enforces this by specifying that none of the variables modified by occur free in , i.e. none of them are in the 'free variable' set of .
Sharing
Separation logic leads to simple proofs of pointer manipulation for data structures that exhibit regular sharing patterns which can be described simply using separating conjunctions; examples include singly and doubly linked lists and varieties of trees. Graphs and DAGs and other data structures with more general sharing
are more difficult for both formal and informal proof. Separation logic has, nonetheless, been applied successfully to reasoning about
programs with general sharing.
In their POPL'01 paper, O'Hearn and Ishtiaq explained how the magic wand connective could be used to reason in the presence of sharing, at least in principle.
For example, in the triple
we obtain the weakest precondition for a statement that mutates the heap at location , and this works for any postcondition, not only one that is laid out neatly using the separating conjunction. This idea was taken much further by Yang, who used to provide localized reasoning about mutations in the classic Schorr-Waite graph marking algorithm. Finally, one of the most recent works in this direction is that of Hobor and Villard, who
employ not only but also a connective
which has variously been called overlapping conjunction or sepish, and which can be used to describe overlapping data structures: holds of a heap when
and hold for subheaps and whose union is , but which possibly have a nonempty portion in common. Abstractly, can be seen to be a version of the fusion connective of relevance logic.
Concurrent separation logic
A Concurrent Separation Logic (CSL),
a version of separation logic for concurrent programs, was originally proposed by Peter O'Hearn,
using a proof rule
which allows independent reasoning about threads that access separate storage. O'Hearn's proof rules adapted an early approach of Tony Hoare to reasoning about concurrency,
replacing the use of scoping constraints to ensure separation by reasoning in separation logic. In addition to extending Hoare's approach to apply in the presence of heap-allocated pointers, O'Hearn showed how reasoning in concurrent separation logic could track dynamic ownership transfer of heap portions between processes; examples in the paper include a pointer-transferring buffer, and a memory manager.
Commenting on the early classical work on interference freedom by Susan Owicki and David Gries, O'Hearn says that explicit checking for non-interference isn't necessary because his system rules out interference in an implicit way, by the nature of the way proofs are constructed.
A model for concurrent separation logic was first provided by Stephen Brookes in a companion paper to O'Hearn's. The soundness of the logic had been a difficult problem, and in fact a counterexample of John Reynolds had shown the unsoundness of an earlier, unpublished version of the logic; the issue raised by Reynolds's example is described briefly in O'Hearn's paper, and more thoroughly in Brookes's.
At first it appeared that CSL was well suited to what Dijkstra had called loosely connected processes, but perhaps not to fine-grained concurrent algorithms with significant interference. However, gradually it was realized that the basic approach of CSL was considerably more powerful than first envisaged, if one employed non-standard models of the logical connectives and even the Hoare triples.
An abstract version of separation logic was proposed that works for Hoare triples
where the preconditions and postconditions are formulae interpreted over an arbitrary partial commutative monoid instead of a particular heap model.
Later, by suitable choice of commutative monoid, it was surprisingly found that the proof rules of abstract versions of concurrent separation logic could be used to reason about interfering concurrent processes, for example by encoding the rely-guarantee technique which had been originally proposed to reason about interference; in this work the elements of the model were considered not resources, but rather "views" of the program state, and a non-standard interpretation of Hoare triples accompanies the non-standard reading of pre and postconditions.
Finally, CSL-style principles have been used to compose reasoning about program histories instead of program states, in order to provide modular techniques for reasoning about fine-grained concurrent algorithms.
Versions of CSL have been included in many interactive and semi-automatic (or "in-between") verification tools as described in the next section. A particularly significant verification effort is that of the μC/OS-II kernel mentioned there. But, although steps have been made, as of yet CSL-style reasoning has been included in comparatively few
tools in the automatic program analysis category (and none mentioned in the next section).
O'Hearn and Brookes are co-recipients of the 2016 Gödel Prize for their invention of Concurrent Separation Logic.
Verification and program analysis tools
Tools for reasoning about programs fall on a spectrum from fully automatic program analysis tools, which do not require any user input, to interactive tools where the human
is intimately involved in the proof process. Many such tools have been developed; the following list includes a few representatives in each category.
Automatic Program Analyses. These tools typically look for restricted classes of bugs (e.g., memory safety errors) or attempt to prove their absence, but fall short of proving full correctness.
A current example is Facebook Infer, a static analysis tool for Java, C, and Objective-C based on separation logic and bi-abduction. As of 2015 hundreds of bugs per month were being found by Infer and fixed by developers before being shipped to Facebook's mobile apps
Other examples include SpaceInvader (one of the first SL analyzers), Predator (which has won several verification competitions), MemCAD (which mixes shape and numerical properties) and SLAyer (from Microsoft Research, focussed on data structures found in device drivers)
Interactive Proof. Proofs have been done using embeddings of Separation Logic into interactive theorem provers such as the Coq proof assistant and HOL (proof assistant). In comparison to the program analysis work, these tools require more in the way of human effort but prove deeper properties, up to functional correctness.
A proof of the FSCQ file system where the specification includes behaviour under crashes as well as normal operation. This work won the best paper award at the 2015 Symposium on Operating System Principles.
Verification of a large fragment of the Rust type system and some of its standard libraries in the RustBelt project using the Iris framework for separation logic in The Coq proof assistant.
Verification of an OpenSSL implementation of a cryptographic authentication algorithm, utilizing verifiable C
Verification of key modules of a commercial OS kernel, the μC/OS-II kernel, the first commercial pre-emptive kernel to have been verified.
Other examples include the Ynot library for the Coq proof assistant; the Holfoot embedding of Smallfoot in HOL; Fine-grained Concurrent Separation Logic, and Bedrock (a Coq library for low-level programming).
In Between. Many tools require more user intervention than program analyses, in that they expect the user to input assertions such as pre/post specs for functions or loop invariants, but after this input is given they attempt to be fully or almost fully automatic; this mode of verification goes back to classic works in the 1970s such as J King's verifier, and the Stanford Pascal Verifier. This style of verifier has recently been called auto active verification, a term which intends to evoke the way of interacting with a verifier via an assert-check loop, analogous to the interaction between a programmer and a type-checker.
The very first Separation Logic verifier, Smallfoot, was in this in-between category. It required the user to input pre/post specs, loop invariants, and resource invariants for locks. It introduced a method of symbolic execution, as well as an automatic way to infer frame axioms. Smallfoot included Concurrent Separation Logic.
SmallfootRG is a verifier for a marriage of separation logic and the classic rely/guarantee method for concurrent programs.
Heap Hop implements a separation logic for message passing, following the ideas in Singularity (operating system).
VeriFast is an advanced current tool in the in-between category. It has demonstrated proofs ranging from object-oriented patterns to highly concurrent algorithms and to systems programs.
Viper is a state-of-the-art automated verification infrastructure for permission-based reasoning. It mainly consists of a programming language and two verification backends, one based on symbolic execution and another one on verification condition generation (VCG). Based on the Viper infrastructure, several frontends for various programming languages have emerged: Gobra for Go, Nagini for Python, Prusti for Rust, and VerCors for C, Java, OpenCL, and OpenMP. These frontends translate the frontend programming language into Viper to then use a Viper verification backend for proving the input program's correctness.
The Mezzo Programming Language and Asynchronous Liquid Separation Types include ideas related to CSL in the type system for a programming language. The idea to include separation in a type system has earlier examples in Alias Types and Syntactic Control of Interference.
The distinction between interactive and in-between verifiers is not a sharp one. For example,
Bedrock strives for a high degree of automation, in what it terms mostly-automatic verification, where
Verifast sometimes requires annotations that resemble the tactics (little programs) used in interactive verifiers.
Decidability and complexity
The satisfiability problem for a quantifier-free, multi-sorted fragment of separation logic parameterized over the sorts of locations and data can be shown to be PSPACE-complete. An algorithm for solving this fragment in DPLL(T)-based SMT solvers has been integrated into cvc5. Extending this result, satisfiability for an analog of the Bernays–Schönfinkel class for separation logic with uninterpreted memory locations can also be shown to be PSPACE-complete, whereas the problem is undecidable with interpreted memory locations (e.g., integers) or further quantifier alternations
References
2002 introductions
Program logic
Substructural logic
Logic in computer science | Separation logic | [
"Mathematics"
] | 2,996 | [
"Substructural logic",
"Mathematical logic",
"Logic in computer science",
"Proof theory"
] |
4,273,403 | https://en.wikipedia.org/wiki/Speech%20segmentation | Speech segmentation is the process of identifying the boundaries between words, syllables, or phonemes in spoken natural languages. The term applies both to the mental processes used by humans, and to artificial processes of natural language processing.
Speech segmentation is a subfield of general speech perception and an important subproblem of the technologically focused field of speech recognition, and cannot be adequately solved in isolation. As in most natural language processing problems, one must take into account context, grammar, and semantics, and even so the result is often a probabilistic division (statistically based on likelihood) rather than a categorical one. Though it seems that coarticulation—a phenomenon which may happen between adjacent words just as easily as within a single word—presents the main challenge in speech segmentation across languages, some other problems and strategies employed in solving those problems can be seen in the following sections.
This problem overlaps to some extent with the problem of text segmentation that occurs in some languages which are traditionally written without inter-word spaces, like Chinese and Japanese, compared to writing systems which indicate speech segmentation between words by a word divider, such as the space. However, even for those languages, text segmentation is often much easier than speech segmentation, because the written language usually has little interference between adjacent words, and often contains additional clues not present in speech (such as the use of Chinese characters for word stems in Japanese).
Lexical recognition
In natural languages, the meaning of a complex spoken sentence can be understood by decomposing it into smaller lexical segments (roughly, the words of the language), associating a meaning to each segment, and combining those meanings according to the grammar rules of the language.
Though lexical recognition is not thought to be used by infants in their first year, due to their highly limited vocabularies, it is one of the major processes involved in speech segmentation for adults. Three main models of lexical recognition exist in current research: first, whole-word access, which argues that words have a whole-word representation in the lexicon; second, decomposition, which argues that morphologically complex words are broken down into their morphemes (roots, stems, inflections, etc.) and then interpreted and; third, the view that whole-word and decomposition models are both used, but that the whole-word model provides some computational advantages and is therefore dominant in lexical recognition.
To give an example, in a whole-word model, the word "cats" might be stored and searched for by letter, first "c", then "ca", "cat", and finally "cats". The same word, in a decompositional model, would likely be stored under the root word "cat" and could be searched for after removing the "s" suffix. "Falling", similarly, would be stored as "fall" and suffixed with the "ing" inflection.
Though proponents of the decompositional model recognize that a morpheme-by-morpheme analysis may require significantly more computation, they argue that the unpacking of morphological information is necessary for other processes (such as syntactic structure) which may occur parallel to lexical searches.
As a whole, research into systems of human lexical recognition is limited due to little experimental evidence that fully discriminates between the three main models.
In any case, lexical recognition likely contributes significantly to speech segmentation through the contextual clues it provides, given that it is a heavily probabilistic system—based on the statistical likelihood of certain words or constituents occurring together. For example, one can imagine a situation where a person might say "I bought my dog at a shop" and the missing word's vowel is pronounced as in "net", "sweat", or "pet". While the probability of "netshop" is extremely low, since "netshop" isn't currently a compound or phrase in English, and "sweatshop" also seems contextually improbable, "pet shop" is a good fit because it is a common phrase and is also related to the word "dog".
Moreover, an utterance can have different meanings depending on how it is split into words. A popular example, often quoted in the field, is the phrase "How to wreck a nice beach", which sounds very similar to "How to recognize speech". As this example shows, proper lexical segmentation depends on context and semantics which draws on the whole of human knowledge and experience, and would thus require advanced pattern recognition and artificial intelligence technologies to be implemented on a computer.
Lexical recognition is of particular value in the field of computer speech recognition, since the ability to build and search a network of semantically connected ideas would greatly increase the effectiveness of speech-recognition software. Statistical models can be used to segment and align recorded speech to words or phones. Applications include automatic lip-synch timing for cartoon animation, follow-the-bouncing-ball video sub-titling, and linguistic research. Automatic segmentation and alignment software is commercially available.
Phonotactic cues
For most spoken languages, the boundaries between lexical units are difficult to identify; phonotactics are one answer to this issue. One might expect that the inter-word spaces used by many written languages like English or Spanish would correspond to pauses in their spoken version, but that is true only in very slow speech, when the speaker deliberately inserts those pauses. In normal speech, one typically finds many consecutive words being said with no pauses between them, and often the final sounds of one word blend smoothly or fuse with the initial sounds of the next word.
The notion that speech is produced like writing, as a sequence of distinct vowels and consonants, may be a relic of alphabetic heritage for some language communities. In fact, the way vowels are produced depends on the surrounding consonants just as consonants are affected by surrounding vowels; this is called coarticulation. For example, in the word "kit", the [k] is farther forward than when we say 'caught'. But also, the vowel in "kick" is phonetically different from the vowel in "kit", though we normally do not hear this. In addition, there are language-specific changes which occur in casual speech which makes it quite different from spelling. For example, in English, the phrase "hit you" could often be more appropriately spelled "hitcha".
From a decompositional perspective, in many cases, phonotactics play a part in letting speakers know where to draw word boundaries. In English, the word "strawberry" is perceived by speakers as consisting (phonetically) of two parts: "straw" and "berry". Other interpretations such as "stra" and "wberry" are inhibited by English phonotactics, which does not allow the cluster "wb" word-initially. Other such examples are "day/dream" and "mile/stone" which are unlikely to be interpreted as "da/ydream" or "mil/estone" due to the phonotactic probability or improbability of certain clusters. The sentence "Five women left", which could be phonetically transcribed as [faɪvwɪmɘnlɛft], is marked since neither /vw/ in /faɪvwɪmɘn/ nor /nl/ in /wɪmɘnlɛft/ are allowed as syllable onsets or codas in English phonotactics. These phonotactic cues often allow speakers to easily distinguish the boundaries in words.
Vowel harmony in languages like Finnish can also serve to provide phonotactic cues. While the system does not allow front vowels and back vowels to exist together within one morpheme, compounds allow two morphemes to maintain their own vowel harmony while coexisting in a word. Therefore, in compounds such as "selkä/ongelma" ('back problem') where vowel harmony is distinct between two constituents in a compound, the boundary will be wherever the switch in harmony takes place—between the "ä" and the "ö" in this case. Still, there are instances where phonotactics may not aid in segmentation. Words with unclear clusters or uncontrasted vowel harmony as in "opinto/uudistus" ('student reform') do not offer phonotactic clues as to how they are segmented.
From the perspective of the whole-word model, however, these words are thought be stored as full words, so the constituent parts would not necessarily be relevant to lexical recognition.
In infants and non-natives
Infants are one major focus of research in speech segmentation. Since infants have not yet acquired a lexicon capable of providing extensive contextual clues or probability-based word searches within their first year, as mentioned above, they must often rely primarily upon phonotactic and rhythmic cues (with prosody being the dominant cue), all of which are language-specific. Between 6 and 9 months, infants begin to lose the ability to discriminate between sounds not present in their native language and grow sensitive to the sound structure of their native language, with the word segmentation abilities appearing around 7.5 months.
Though much more research needs to be done on the exact processes that infants use to begin speech segmentation, current and past studies suggest that English-native infants approach stressed syllables as the beginning of words. At 7.5 months, infants appear to be able to segment bisyllabic words with strong-weak stress patterns, though weak-strong stress patterns are often misinterpreted, e.g. interpreting "guiTAR is" as "GUI TARis". It seems that infants also show some complexity in tracking frequency and probability of words, for instance, recognizing that although the syllables "the" and "dog" occur together frequently, "the" also commonly occurs with other syllables, which may lead to the analysis that "dog" is an individual word or concept instead of the interpretation "thedog".
Language learners are another set of individuals being researched within speech segmentation. In some ways, learning to segment speech may be more difficult for a second-language learner than for an infant, not only in the lack of familiarity with sound probabilities and restrictions but particularly in the overapplication of the native language's patterns. While some patterns may occur between languages, as in the syllabic segmentation of French and English, they may not work well with languages such as Japanese, which has a mora-based segmentation system. Further, phonotactic restrictions like the boundary-marking cluster /ld/ in German or Dutch are permitted (without necessarily marking boundaries) in English. Even the relationship between stress and vowel length, which may seem intuitive to speakers of English, may not exist in other languages, so second-language learners face an especially great challenge when learning a language and its segmentation cues.
See also
Ambiguity
Hyphenation
Mondegreen
Sentence boundary disambiguation
Speech perception
Speech processing
Speech recognition
References
External links
"Phonolyze" speech segmentation software
SPPAS – the automatic annotation and analysis of speech
Natural language processing | Speech segmentation | [
"Technology"
] | 2,294 | [
"Natural language processing",
"Natural language and computing"
] |
4,273,427 | https://en.wikipedia.org/wiki/Famciclovir | Famciclovir is a guanosine analogue antiviral drug used for the treatment of various herpesvirus infections, most commonly for herpes zoster (shingles). It is a prodrug form of penciclovir with improved oral bioavailability. Famciclovir is marketed under the trade name Famvir (Novartis).
Famciclovir was patented in 1983 and approved for medical use in 1994. In 2007, the United States Food and Drug Administration approved the first generic version of famciclovir. Generic tablets are manufactured by TEVA Pharmaceuticals and Mylan Pharmaceuticals.
Medical uses
Famciclovir is indicated for the treatment of herpes zoster (shingles), treatment of herpes simplex virus 2 (genital herpes), herpes labialis (cold sores) in immunocompetent patients and for the suppression of recurring episodes of herpes simplex virus 2. It is also indicated for treatment of recurrent episodes of herpes simplex in HIV patients.
Adverse effects
Side effects: mild to extreme stomach upset, headaches, mild fever.
Herpes
Early treatment
Several studies in humans and mice provide evidence that early treatment with famciclovir soon after the first infection with herpes can significantly lower the chance of future outbreaks. Use of famciclovir in this manner has been shown to reduce the amount of latent virus in the neural ganglia compared to no treatment or treatment with valaciclovir. A review of human subjects treated for five days with famciclovir 250 mg three times daily during their first herpes episode found that only 4.2 percent experienced a recurrence within six months after the first outbreak, a fivefold decrease compared to the 19 percent recurrence in acyclovir-treated patients. Neither drug affected latency if treatment was delayed for several months.
References
Anti-herpes virus drugs
Prodrugs
Drugs developed by Novartis
Drugs developed by Schering-Plough
Purines
Acetate esters | Famciclovir | [
"Chemistry"
] | 432 | [
"Chemicals in medicine",
"Prodrugs"
] |
14,758,293 | https://en.wikipedia.org/wiki/3C%20109 | 3C 109 is a Seyfert galaxy located in the constellation Taurus. It is also a broad-line radio galaxy, classified as one of the most active polarized galaxies apart from blazars with quasar-like properties. The black hole in 3C 109 is said to have an estimated mass of 9.3 x 108 .
See also
Lists of galaxies
References
External links
Simbad
www.jb.man.ac.uk/atlas/
Seyfert galaxies
Taurus (constellation)
109
2817533
11.18
Radio galaxies | 3C 109 | [
"Astronomy"
] | 116 | [
"Taurus (constellation)",
"Galaxy stubs",
"Astronomy stubs",
"Constellations"
] |
14,758,305 | https://en.wikipedia.org/wiki/Pole%20splitting | Pole splitting is a phenomenon exploited in some forms of frequency compensation used in an electronic amplifier. When a capacitor is introduced between the input and output sides of the amplifier with the intention of moving the pole lowest in frequency (usually an input pole) to lower frequencies, pole splitting causes the pole next in frequency (usually an output pole) to move to a higher frequency. This pole movement increases the stability of the amplifier and improves its step response at the cost of decreased speed.
Example of pole splitting
This example shows that introduction of the capacitor referred to as CC in the amplifier of Figure 1 has two results: first it causes the lowest frequency pole of the amplifier to move still lower in frequency and second, it causes the higher pole to move higher in frequency. The amplifier of Figure 1 has a low frequency pole due to the added input resistance Ri and capacitance Ci, with the time constant Ci ( RA || Ri ). This pole is moved down in frequency by the Miller effect. The amplifier is given a high frequency output pole by addition of the load resistance RL and capacitance CL, with the time constant CL ( Ro || RL ). The upward movement of the high-frequency pole occurs because the Miller-amplified compensation capacitor CC alters the frequency dependence of the output voltage divider.
The first objective, to show the lowest pole moves down in frequency, is established using the same approach as the Miller's theorem article. Following the procedure described in the article on Miller's theorem, the circuit of Figure 1 is transformed to that of Figure 2, which is electrically equivalent to Figure 1. Application of Kirchhoff's current law to the input side of Figure 2 determines the input voltage to the ideal op amp as a function of the applied signal voltage , namely,
which exhibits a roll-off with frequency beginning at f1 where
which introduces notation for the time constant of the lowest pole. This frequency is lower than the initial low frequency of the amplifier, which for CC = 0 F is .
Turning to the second objective, showing the higher pole moves still higher in frequency, it is necessary to look at the output side of the circuit, which contributes a second factor to the overall gain, and additional frequency dependence. The voltage is determined by the gain of the ideal op amp inside the amplifier as
Using this relation and applying Kirchhoff's current law to the output side of the circuit determines the load voltage as a function of the voltage at the input to the ideal op amp as:
This expression is combined with the gain factor found earlier for the input side of the circuit to obtain the overall gain as
This gain formula appears to show a simple two-pole response with two time constants. (It also exhibits a zero in the numerator but, assuming the amplifier gain Av is large, this zero is important only at frequencies too high to matter in this discussion, so the numerator can be approximated as unity.) However, although the amplifier does have a two-pole behavior, the two time-constants are more complicated than the above expression suggests because the Miller capacitance contains a buried frequency dependence that has no importance at low frequencies, but has considerable effect at high frequencies. That is, assuming the output R-C product, CL ( Ro || RL ), corresponds to a frequency well above the low frequency pole, the accurate form of the Miller capacitance must be used, rather than the Miller approximation. According to the article on Miller effect, the Miller capacitance is given by
(For a positive Miller capacitance, Av is negative.) Upon substitution of this result into the gain expression and collecting terms, the gain is rewritten as:
with Dω given by a quadratic in ω, namely:
Every quadratic has two factors, and this expression looks simpler if it is rewritten as
where and are combinations of the capacitances and resistances in the formula for Dω. They correspond to the time constants of the two poles of the amplifier. One or the other time constant is the longest; suppose is the longest time constant, corresponding to the lowest pole, and suppose >> . (Good step response requires >> . See Selection of CC below.)
At low frequencies near the lowest pole of this amplifier, ordinarily the linear term in ω is more important than the quadratic term, so the low frequency behavior of Dω is:
where now CM is redefined using the Miller approximation as
which is simply the previous Miller capacitance evaluated at low frequencies. On this basis is determined, provided >> . Because CM is large, the time constant is much larger than its original value of Ci ( RA || Ri ).
At high frequencies the quadratic term becomes important. Assuming the above result for is valid, the second time constant, the position of the high frequency pole, is found from the quadratic term in Dω as
Substituting in this expression the quadratic coefficient corresponding to the product along with the estimate for , an estimate for the position of the second pole is found:
and because CM is large, it seems is reduced in size from its original value CL ( Ro || RL ); that is, the higher pole has moved still higher in frequency because of CC.
In short, introduction of capacitor CC moved the low pole lower and the high pole higher, so the term pole splitting seems a good description.
Selection of CC
What value is a good choice for CC? For general purpose use, traditional design (often called dominant-pole or single-pole compensation) requires the amplifier gain to drop at 20 dB/decade from the corner frequency down to 0 dB gain, or even lower.
With this design the amplifier is stable and has near-optimal step response even as a unity gain voltage buffer. A more aggressive technique is two-pole compensation.
The way to position f2 to obtain the design is shown in Figure 3. At the lowest pole f1, the Bode gain plot breaks slope to fall at 20 dB/decade. The aim is to maintain the 20 dB/decade slope all the way down to zero dB, and taking the ratio of the desired drop in gain (in dB) of 20 log10 Av to the required change in frequency (on a log frequency scale) of ( log10 f2 − log10 f1 ) = log10 ( f2 / f1 ) the slope of the segment between f1 and f2 is:
Slope per decade of frequency
which is 20 dB/decade provided f2 = Av f1 . If f2 is not this large, the second break in the Bode plot that occurs at the second pole interrupts the plot before the gain drops to 0 dB with consequent lower stability and degraded step response.
Figure 3 shows that to obtain the correct gain dependence on frequency, the second pole is at least a factor Av higher in frequency than the first pole. The gain is reduced a bit by the voltage dividers at the input and output of the amplifier, so with corrections to Av for the voltage dividers at input and output the pole-ratio condition for good step response becomes:
Using the approximations for the time constants developed above,
or
which provides a quadratic equation to determine an appropriate value for CC. Figure 4 shows an example using this equation. At low values of gain this example amplifier satisfies the pole-ratio condition without compensation (that is, in Figure 4 the compensation capacitor CC is small at low gain), but as gain increases, a compensation capacitance rapidly becomes necessary (that is, in Figure 4 the compensation capacitor CC increases rapidly with gain) because the necessary pole ratio increases with gain. For still larger gain, the necessary CC drops with increasing gain because the Miller amplification of CC, which increases with gain (see the Miller equation ), allows a smaller value for CC.
To provide more safety margin for design uncertainties, often Av is increased to two or three times Av on the right side of this equation. See Sansen or Huijsing and article on step response.
Slew rate
The above is a small-signal analysis. However, when large signals are used, the need to charge and discharge the compensation capacitor adversely affects the amplifier slew rate; in particular, the response to an input ramp signal is limited by the need to charge CC.
See also
Frequency compensation
Miller effect
Common source
Bode plot
Step response
CMOS amplifier
References and notes
External links
Bode Plots in the Circuit Theory Wikibook
Bode Plots in the Control Systems Wikibook
Analog circuits
Electronic design | Pole splitting | [
"Engineering"
] | 1,758 | [
"Electronic design",
"Analog circuits",
"Electronic engineering",
"Design"
] |
14,758,324 | https://en.wikipedia.org/wiki/UGT1A6 | UDP-glucuronosyltransferase 1-6 is an enzyme that in humans is encoded by the UGT1A6 gene.
Function
UDP-glucuronosyltransferase 1-6 is a UDP-glucuronosyltransferase, an enzyme of the glucuronidation pathway that transforms small lipophilic molecules, such as steroids, bilirubin, hormones, and drugs, into water-soluble, excretable metabolites.
This gene is part of a complex locus that encodes several UDP-glucuronosyltransferases. The locus includes thirteen unique alternate first exons followed by four common exons. Four of the alternate first exons are considered pseudogenes. Each of the remaining nine 5' exons may be spliced to the four common exons, resulting in nine proteins with different N-termini and identical C-termini. Each first exon encodes the substrate binding site, and is regulated by its own promoter. The enzyme encoded by this gene is active on phenolic and planar compounds. Alternative splicing in the unique 5' end of this gene results in two transcript variants.
This enzyme is also responsible for the inactivation of popular analgesic drugs, such as aspirin and acetaminophen, by glucuronidation. The loss of a functional UGT1A6 gene in certain hypercarnivores, and particularly cats, renders the animals extremely sensitive to the adverse effects of these analgesics.
References
Further reading | UGT1A6 | [
"Chemistry"
] | 342 | [
"Biochemistry stubs",
"Protein stubs"
] |
14,758,354 | https://en.wikipedia.org/wiki/CDC2L2 | PITSLRE serine/threonine-protein kinase CDC2L2 is an enzyme that in humans is encoded by the CDC2L2 gene.
References
External links
Further reading | CDC2L2 | [
"Chemistry"
] | 40 | [
"Biochemistry stubs",
"Protein stubs"
] |
14,758,602 | https://en.wikipedia.org/wiki/Rabin%20fairness | Rabin fairness is a fairness model invented by Matthew Rabin. It goes beyond the standard assumptions in modeling behavior, rationality and self-interest, to incorporate fairness. Rabin's fairness model incorporates findings from the economics and psychology fields to provide an alternative utility model. Fairness is one type of social preference.
Including fairness in the standard utility model
Past utility models incorporated altruism or the fact that people may care not only about their own well-being, but also about the well-being of others. However, evidence indicates that pure altruism does not occur often, contrarily most altruistic behavior demonstrates three facts (as defined by Rabin) and these facts are proven by past events. Due to the existence of these three facts, Rabin created a utility function that incorporates fairness.:
People are willing to sacrifice their own material well-being to help those who are being kind.
The attempt to provide public goods without coercion departs from pure self-interest.
Experiments show that people cooperate to contribute toward a public good to a degree greater than would be implied by pure self-interest. Individually optimal contribution rates, as defined by the standard utility model, are close to 0 percent.
During an experiment, the willingness for an individual to contribute to a public good is highly contingent on the behavior of others.
People are willing to sacrifice their own material well-being to punish those who are being unkind.
Evidence provided by the ultimatum game, consisting of two people, a proposer and decider, splitting a fixed amount of money. The proposer offers a division of the money, then the decider decides if he or she refuses or accepts the proposal. If the decider says yes, they split the money according to the proposer's offer, but if the decider says no, neither person gets any money.
Standard utility model would find that any offer proposed to the decider should be accepted if it is greater than zero because utility should increase with any increase in income. Along the same lines, the standard utility model would predict that the proposer would offer the smallest amount of money possible to the decider in order to maximize his or her own utility
However, data shows that deciders are willing to punish any unfair offer and proposers tend to make fair offers.
Both motivations 1 and 2 have a greater effect on behavior as the material cost of sacrificing becomes smaller.
Rabin's fairness model
Rabin formalized fairness using a two-person, modified game theory matrix with two decisions (a two by two matrix), where i is the person whose utility is being measured. Furthermore, within the game theory matrix payoffs for each person are allocated. The following formula was created by Rabin to model utility to include fairness:
Where:
ai represents player i's strategy, bj represents player i's belief about what player j's strategy will be, and ci represents what player i's beliefs about player j's beliefs about player i's strategy.
Although this seems complicated, a is simply player i's strategy, b is player j's strategy given how he/she believes player i will act, and c is player i's decision given what strategy player j is believed to partake in.
In the game below, a, b, and c, will all take the form of either Grab or Share and then the payoffs would be determined and placed into Rabin's Fairness Model.
represents the payoffs player i receives
Player i's kindness to player j is given by:
, where is player j's highest payoff and is player j's lowest payoff among points that are Pareto efficient
is the worst possible payoff in the matrix for player j
Player i's belief about how kind player j is being to him is given by:
is player i's worst possible payoff
, where is player i's highest payoff and is player i's lowest payoff among points that are Pareto efficient
The two functions above can now specify player's preferences. Player i chooses ai to maximize the expected utility of
Fairness model implications
The fairness model implies that if player j is treating player i badly, if , then player i wishes to treat player j badly as well by choosing an action, ai, that is low or negative. However, if player j is treating player i kindly, , then player i will act kindly towards player j, as well (For more in depth examples see Rabin (1993)).
Welfare and fairness: an application
Rabin also used the fairness model as a utility function to determine social welfare. Rabin used a game theory "Grabbing Game" which posited that there are two people shopping, with two cans of soup left. The payoffs for each are given as follows, where player i's payoffs are on the left of each pair and player j's payoffs are on the right of each pair:
If both grab or both share, each player i and j get one can of soup. However, one grabs, and the other does not, then the person who grabbed gets both cans of soup. There is a Nash Equilibrium present of (grab, grab). Moreover, applying Rabin's fairness model (grab, grab) will always be a fairness equilibrium but for small values of x the cooperative choice (share, share) will Pareto dominate (grab, grab). The reasoning behind this is that if the two people both grab for and therefore fight over the cans, the angriness and bad tempers that arise are likely to outweigh the importance of receiving the cans. Therefore, while (Grab, Grab) and (Share, Share) are fairness equilibria when material payoffs are small, (Share, Share) will dominate (Grab, Grab) since people are affected by the kindness, which increases utility, or unkindness, which decreases utility, of others. This example could be generalized further to describe the allocation of public goods.
Public goods provision and fairness
Stouten (2006) further generalized the principle of fairness to be applied to the provision of public goods. He and his colleagues ran three experiments to find how participants reacted when one member of their group violated the equality rule, which states that all group members will coordinate to equally and fairly contribute to the efficient provision of public goods. Their findings demonstrated that the participants believed that the equality rule should be applied to others and therefore when one person violated this rule punishment was used against this person, in terms of negative reactions. Therefore, the equality rule applied in real-life situations should lead to the efficient provision of public goods if violations of the important coordination and fairness rules can be detected. However, often these violations cannot be detected which then leads to the free rider problem and an under-provision of public goods.
See also
Inequity aversion
Altruism
Social welfare
Risk aversion
Social preferences
References
Economics models
Interpersonal relationships | Rabin fairness | [
"Biology"
] | 1,415 | [
"Behavior",
"Interpersonal relationships",
"Human behavior"
] |
14,759,475 | https://en.wikipedia.org/wiki/MacMinute | MacMinute was the name of a web site that provided news and information focused on Apple Inc and the Macintosh Operating system. It was founded by Canadian businessman Stan Flack in 2001 to "keep you up-to-date on everything that is going on in the world of Macintosh as soon as it happens". On the opening day, May 9, 2001, the update to the Mac OS X to 10.0.3 was announced.
Prior to creating MacMinute Stan Flack founded the MacCentral news website which he sold to MacWorld on June 1, 1999. This website was eventually folded into the MacWorld brand name and the last vestiges of MacCentral disappeared with the incorporation of the MacCentral Forum into the MacWorld forums in December 2007.
MacMinute was noted for its up to the minute digest of current breaking news about everything connected to the Macintosh and Apple products but one of its more important functions was to serve as a forum for the Macintosh community. This MacMinute Reader Cafe is an eclectic mix of Macintosh users who provide and share expertise in all aspects of the Macintosh platform.
Mr. Flack died of natural causes, from complications to a pre-existing condition, in his home on Prince Edward Island, Canada on April 14, 2008.
On May 22, 2008, the Flack family announced the closing of the Macminute website and forums. Some forum members decide to move to MacCentral Cafe as it reminds them of the single forum Stan Flack started with at the MacCentral news website.
On June 5, 2008 it is announced on the Macminute news site that MacTech's Community News Scan and Macsimum News will act as caretakers to the archives of MacMinute News and Forums. They also announced they would continue to host the MacMinute Forums which are now up and running smoothly as of November 2008. Stan's Lounge is crowded with MacCentral and MacMinute faithful in honor of Stan Flack and all that he did for the Macintosh community.
Abbreviated MacMinute Chronology
June 1, 1999 MacWorld purchases MacCentral from Canadian businessman Stan Flack.
May 9, 2001 MacMinute News site is published on the internet by Stan Flack.
May 19, 2001 MacMinute opens MacMinute Reader Café.
April 19, 2002 A major influx (more than 30) of MacCentral forum members create user accounts in the MacMinute Reader Café.
August 4. 2004 MacMinute forum member mikeb_X dies.
September 2, 2004 A "Political Forum" is created within the MacMinute Reader Café.
May 14, 2005 Lesh creates the neologism "malacarpism".
December 16, 2007 With the imminent closing of MacCentral forum another influx of users to MacMinute Café occurs.
January 3, 2008 The MacCentral Forum becomes read only causing a few more MCF members to become Macminuters.
April 14, 2008 Stan Flack passes away.
May 22, 2008 The Flack family announces the closing of Macminute.
June 5, 2008 MacTech's Community News Scan and Macsimum News announces the hosting of MacMinute Forums as well as archiving of all past MacMinute News.
November 6, 2008 Neil Ticktin of MacTech announces that the old MacMinute software has been upgraded and the forum moves to new servers as well.
External links
MacMinute as served on MacTech servers
References
(1) "Opening Day at MacMinute", "MacMinute News", May 9, 2001. Retrieved on December 18, 2007
(2) Duncan, Geoff. "Mac Publishing Buys MacCentral", "TidBits", 1999-6-7. Retrieved on December 18, 2007
(3) Beraut, Laura. "(NPL) Mac Publishing Acquires MacCentral Online" "MacTech", June 1, 1999, Retrieved on December 18, 2007
Macintosh websites
Technology websites
Macintosh magazines
Defunct websites
Defunct magazines published in Canada
Canadian news websites
Internet forums
Internet properties established in 2001
Internet properties disestablished in 2008
Online magazines published in Canada | MacMinute | [
"Technology"
] | 845 | [
"Macintosh websites",
"Computing websites"
] |
14,759,577 | https://en.wikipedia.org/wiki/Partner%20Institute%20for%20Computational%20Biology | The CAS-MPG Partner Institute for Computational Biology (PICB) was jointly established by the Chinese Academy of Sciences (CAS) and the German Max Planck Society (MPG) in May 2005. It is located in Xu Hui district in Shanghai, P. R. China.
The institute focuses its research on the interface between theoretical and experimental molecular and cell biology. The procedures of the establishment of the institute as well as the recruitment of the directors follows the model of the Max-Planck-Society, while the institute itself is integral part of and administrated by the Shanghai Institutes for Biological Sciences (SIBS).
External links
Partner Institute for Computational Biology
Organizations based in Shanghai
Bioinformatics organizations | Partner Institute for Computational Biology | [
"Biology"
] | 143 | [
"Bioinformatics",
"Bioinformatics organizations"
] |
14,759,592 | https://en.wikipedia.org/wiki/Post%20road | A post road is a road designated for the transportation of postal mail. In past centuries, only major towns had a post house and the roads used by post riders or mail coaches to carry mail among them were particularly important ones or, due to the special attention given them, became so. In various centuries and countries, post road became more or less equivalent to main road, royal road, or highway. The 20th century spread of postal service blurred the distinction.
Asia
Great Post Road (), from Anyer to Panarukan, Indonesia, was a notable post road in Asia, built during the governancy of Herman Willem Daendels of Dutch East Indies from 1808 to 1811.
Europe
Notable post roads in Europe include:
Antwerp-Venice Post Road, similar to the Dutch Post Road.
Bremen-Hamburg Post Road, approved by the king of Sweden on July 5, 1665 to establish regular mail service. A second route was routed from Cuxhaven through the Land of Wursten to Lehe.
Dutch Post Road, () established in 1490, connected the Netherlands with coaching inns in Germany and Italy.
North America
The following are notable post roads in Canada and the U.S.
Canada
Chemin du Roy was built between Montreal (Repentigny) and Quebec City from 1731 to 1737, for mail and as a means of travel for the key settlements in New France/Lower Canada. It was later incorporated as Quebec Route 2 and is now part of Quebec Route 138.
Two notable post roads built in the late 1700s and early 1800s were Dundas Road (The Governor's Road) and Kingston Road (Lakeshore Road or York Road) to provide a route for mail and stagecoaches between key settlements in Upper Canada.
The latter route, which became The Provincial Highway in 1917 (Ontario Highway 2 c. 1923), and the former which became a Dundas Highway in 1920 (Ontario Highway 5 in 1925), were the beginning of the provincial highway system in Ontario.
United States
In what was to later become the United States, post roads developed as the primary method of communicating information across and between the colonies.
The Articles of Confederation authorized the national government to create post offices but not post roads. Adoption of the U.S. Constitution changed this, as Article I, Section Eight, known as the Postal Clause, specifically authorizes Congress the enumerated power "to establish post offices and post roads." This was generally interpreted liberally, to include all public highways. U.S. Supreme Court justice Joseph Story defended the broad interpretation that had become dominant in his influential Commentaries on the Constitution of the United States (1833).
Notable American post roads built for the purpose include:
Albany Post Road, which connects New York City to Albany, the capital of New York State
Boston Post Road, which traverses New England from New York City to Boston, Massachusetts
White Plains Post Road, the southernmost section of New York State Route 22, known as the White Plains Post Road in the 18th and 19th centuries, was a major highway connecting New York City to White Plains, Westchester's county seat.
References
External links
Justice Joseph Story, Commentaries on the Constitution of the United States, 3 vols, (Boston: 1833)
Legal history of the United States
Postal systems
Types of roads | Post road | [
"Technology"
] | 659 | [
"Transport systems",
"Postal systems"
] |
14,759,741 | https://en.wikipedia.org/wiki/CHRNA1 | Neuronal acetylcholine receptor subunit alpha-1, also known as nAChRα1, is a protein that in humans is encoded by the CHRNA1 gene. The protein encoded by this gene is a subunit of certain nicotinic acetylcholine receptors (nAchR).
The muscle acetylcholine receptor consists of 5 subunits of 4 different types: 2 alpha isoforms and 1 each of beta, gamma, and delta subunits.2 This gene encodes an alpha subunit that plays a role in acetylcholine binding/channel gating. Alternatively spliced transcript variants encoding different isoforms have been identified.
Interactions
Cholinergic receptor, nicotinic, alpha 1 has been shown to interact with CHRND.
See also
Nicotinic acetylcholine receptor
References
Further reading
External links
Ion channels
Nicotinic acetylcholine receptors | CHRNA1 | [
"Chemistry"
] | 188 | [
"Neurochemistry",
"Ion channels"
] |
14,759,782 | https://en.wikipedia.org/wiki/FOSL1 | Fos-related antigen 1 (FRA1) is a protein that in humans is encoded by the FOSL1 gene.
Function
The Fos gene family consists of 4 members: c-Fos, FOSB, FOSL1, and FOSL2. These genes encode leucine zipper proteins that can dimerize with proteins of the JUN family, thereby forming the transcription factor complex AP-1. As such, the FOS proteins have been implicated as regulators of cell proliferation, differentiation, and transformation.
Interactions
FOSL1 has been shown to interact with USF1 (human gene) and C-jun.
See also
AP-1 (transcription factor)
References
Further reading
External links
Transcription factors | FOSL1 | [
"Chemistry",
"Biology"
] | 149 | [
"Induced stem cells",
"Gene expression",
"Transcription factors",
"Signal transduction"
] |
14,759,805 | https://en.wikipedia.org/wiki/ARID1A | AT-rich interactive domain-containing protein 1A is a protein that in humans is encoded by the ARID1A gene.
Function
ARID1A is a member of the SWI/SNF family, whose members have helicase and ATPase activities and are thought to regulate transcription of certain genes by altering the chromatin structure around those genes. The encoded protein is part of the large ATP-dependent chromatin remodelling complex SWI/SNF, which is required for transcriptional activation of genes normally repressed by chromatin. It possesses at least two conserved domains that could be important for its function. First, it has an ARID domain, which is a DNA-binding domain that can specifically bind an AT-rich DNA sequence known to be recognized by a SWI/SNF complex at the beta-globin locus. Second, the C-terminus of the protein can stimulate glucocorticoid receptor-dependent transcriptional activation. The protein encoded by this gene confers specificity to the SWI/SNF complex and recruits the complex to its targets through either protein-DNA or protein-protein interactions. Two transcript variants encoding different isoforms have been found for this gene.
Clinical significance
Gene encoding for ARID1A is the most frequently mutated SWI/SNF subunit across cancers. This gene has been commonly found mutated in different cancers leading to loss of function, including gastric cancers, colon cancer, ovarian clear cell carcinoma, liver cancer, lymphoma and pancreatic cancer.
In breast cancer distant metastases acquire inactivation mutations in ARID1A not seen in the primary tumor, and reduced ARID1A expression confers resistance to different drugs such as trastuzumab and mTOR inhibitors. These findings provide a rationale for why tumors accumulate ARID1A mutations.
Research
Lack of this gene/protein seems to protect rats from some types of liver damage.
Interactions
ARID1A has been shown to interact with SMARCB1 and SMARCA4.
References
Further reading
External links
Transcription factors | ARID1A | [
"Chemistry",
"Biology"
] | 431 | [
"Induced stem cells",
"Gene expression",
"Transcription factors",
"Signal transduction"
] |
14,759,898 | https://en.wikipedia.org/wiki/YAP1 | YAP1 (yes-associated protein 1), also known as YAP or YAP65, is a protein that acts as a transcription coregulator that promotes transcription of genes involved in cellular proliferation and suppressing apoptotic genes. YAP1 is a component in the hippo signaling pathway which regulates organ size, regeneration, and tumorigenesis. YAP1 was first identified by virtue of its ability to associate with the SH3 domain of Yes and Src protein tyrosine kinases. YAP1 is a potent oncogene, which is amplified in various human cancers.
Structure
Cloning of the YAP1 gene facilitated the identification of a modular protein domain, known as the WW domain. Two splice isoforms of the YAP1 gene product were initially identified, named YAP1-1 and YAP1-2, which differed by the presence of an extra 38 amino acids that encoded the WW domain. Apart from the WW domain, the modular structure of YAP1 contains a proline-rich region at the very amino terminus, which is followed by a TID (TEAD transcription factor interacting domain). Next, following a single WW domain, which is present in the YAP1-1 isoform, and two WW domains, which are present in the YAP1-2 isoform, there is the SH3-BM (Src Homology 3 binding motif). Following the SH3-BM is a TAD (transactivation domain) and a PDZ domain-binding motif (PDZ-BM) (Figure 1).
Function
YAP1 is a transcriptional co-activator and its proliferative and oncogenic activity is driven by its association with the TEAD family of transcription factors, which up-regulate genes that promote cell growth and inhibit apoptosis. Several other functional partners of YAP1 were identified, including RUNX, SMADs, p73, ErbB4, TP53BP2, LATS1/2, PTPN14, AMOTs, and ZO1/2. YAP1 and its close paralog, TAZ (WWTR1), are the main effectors of the Hippo tumor suppressor pathway. When the pathway is activated, YAP1 and TAZ are phosphorylated on a serine residue and sequestered in the cytoplasm by 14-3-3 proteins. When the Hippo pathway is not activated, YAP1/TAZ enter the nucleus and regulate gene expression.
It is reported that several genes are regulated by YAP1, including Birc2, Birc5, connective tissue growth factor (CTGF), amphiregulin (AREG), Cyr61, Hoxa1 and Hoxc13.
YAP/TAZ have also been shown to act as stiffness sensors, regulating mechanotransduction independently of the Hippo signalling cascade.
As YAP and TAZ are transcriptional co-activators, they do not have DNA-binding domains. Instead, when inside the nucleus, they regulate gene expression through TEAD1-4 which are sequence-specific transcription factors that mediate the main transcriptional output of the Hippo pathway. The YAP/TAZ and TEAD interaction competitively inhibits and actively dissociates the TEAD/VGLL4 interaction which functions as a transcriptional repressor. Mouse models with YAP over-expression have been shown to exhibit up-regulation of the TEAD target gene expression which results in increased expansion of progenitor cells and tissue overgrowth.
Regulation
Biochemical
At the biochemical level, YAP is part of and regulated by the Hippo signaling pathway where a kinase cascade results in its “inactivation”, along with that of TAZ. In this signaling cascade, TAO kinases phosphorylate Ste20-like kinases, MST1/2, at their activation loops (Thr183 for MST1 and Thr180 for MST2). Active MST1/2 then phosphorylate SAV1 and MOB1A/B which are scaffold proteins that assist in the recruitment and phosphorylation of LATS1/2. LATS1/2 can also be phosphorylated by two groups of MAP4Ks. LATS1/2 then phosphorylate YAP and TAZ which causes them to bind with 14-3-3, resulting in cytoplasmic sequestration of YAP and TAZ. The result of the activation of this pathway is the restriction of YAP/TAZ from entering the cell nucleus.
Mechanotransductive
Additionally, YAP is regulated by mechanical cues such as extracellular matrix (ECM) rigidity, strain, shear stress, or adhesive area, processes that are reliant on cytoskeletal integrity. These mechanically induced localization phenomena are thought to be the result of nuclear flattening induced pore size change, mechanosensitive nuclear membrane ion channels, mechanical protein stability, or a variety of other factors. These mechanical factors have also been linked to certain cancer cells via nuclear softening and higher ECM stiffnesses. Under this framework, the nuclear softening phenotype of cancer cells would promote nuclear flattening in response to a force, causing YAP localization, which could explain its over-expression and promoted proliferation in oncogenic cells. Additionally, the higher ECM stiffness phenotype commonly seen in tumors due to enhanced integrin signaling could flatten the cell and nucleus, once again causing higher YAP nuclear localization. Likewise, the opposite effect of nuclear stiffening as a result of a variety of stimuli such as an over-expression of lamin A, has been shown to decrease nuclear YAP localization.
Clinical significance
Cancer
Dysregulation of YAP/TAZ-mediated transcriptional activity is implicated in the development of abnormal cell growth and hyperactivation of YAP and TAZ has been observed amongst many cancers. Hence YAP1 represents a potential target for the treatment of cancer.
While YAP has been identified as a proto-oncogene, it can also act as a tumor suppressor depending on cellular context.
As a drug target
The YAP1 oncogene serves as a target for the development of new cancer drugs. Small compounds have been identified that disrupt the YAP1-TEAD complex or block the binding function of WW domains. These small molecules represent lead compounds for the development of therapies for cancer patients, who harbor amplified or overexpressed YAP oncogene.
Neuroprotection
The Hippo/YAP signaling pathway may exert neuroprotective effects through mitigating blood-brain barrier disruption after cerebral ischemia/reperfusion injury.
Mutations
Heterozygous loss-of-function mutations in the YAP1 gene have been identified in two families with major eye malformations with or without extra-ocular features such as hearing loss, cleft lip, intellectual disability and renal disease.
External links
References
Genes on human chromosome 11
Transcription factors | YAP1 | [
"Chemistry",
"Biology"
] | 1,507 | [
"Induced stem cells",
"Gene expression",
"Transcription factors",
"Signal transduction"
] |
14,759,991 | https://en.wikipedia.org/wiki/Homeobox%20A1 | Homeobox protein Hox-A1 is a protein that in humans is encoded by the HOXA1 gene.
Gene
Two transcript variants encoding two different isoforms have been found for this gene, with only one of the isoforms containing the homeodomain region.
Function
In vertebrates, the genes encoding the class of transcription factors called homeobox genes are found in clusters named A, B, C, and D on four separate chromosomes. Expression of these proteins is spatially and temporally regulated during embryonic development. This gene is part of the A cluster on chromosome 7 and encodes a DNA-binding transcription factor which may regulate gene expression, morphogenesis, and cellular differentiation. The homeobox protein Hox-A1 may be involved in the placement of hindbrain segments in the proper location along the anterior-posterior axis during development.
Clinical significance
A common polymorphism in the HOXA1 gene is associated with a susceptibility to autism spectrum disorder, with individuals possessing these gene variant have an approximately doubled risk of developing the disorder. Studies on knockout mice have indicated that the gene can alter embryological development of the brain stem (specifically the facial and superior olivary nuclei), as well as induce several other physical changes such as in ear shape. Both of these sets of changes can also be seen in patients with autism.
Other HOXA1 mutations are associated with Bosley-Salih-Alorainy syndrome (BSAS) or the Athabaskan brainstem dysgenesis syndrome (ABDS).
Regulation
The HOXA1 gene is repressed by the microRNA miR-10a.
See also
Homeobox
References
Further reading
External links
Transcription factors | Homeobox A1 | [
"Chemistry",
"Biology"
] | 346 | [
"Induced stem cells",
"Gene expression",
"Transcription factors",
"Signal transduction"
] |
14,760,036 | https://en.wikipedia.org/wiki/KCNA4 | Potassium voltage-gated channel subfamily A member 4 also known as Kv1.4 is a protein that in humans is encoded by the KCNA4 gene. It contributes to the cardiac transient outward potassium current (Ito1), the main contributing current to the repolarizing phase 1 of the cardiac action potential.
Description
Potassium channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. Four sequence-related potassium channel genes - shaker, shaw, shab, and shal - have been identified in Drosophila, and each has been shown to have human homolog(s). This gene encodes a member of the potassium channel, voltage-gated, shaker-related subfamily. This member contains six membrane-spanning domains with a shaker-type repeat in the fourth segment. It belongs to the A-type potassium current class, the members of which may be important in the regulation of the fast repolarizing phase of action potentials in heart and thus may influence the duration of cardiac action potential. The coding region of this gene is intronless, and the gene is clustered with genes KCNA3 and KCNA10 on chromosome 1 in humans.
KCNA4 (Kv1.4) contains a tandem inactivation domain at the N terminus. It is composed of two subdomains. Inactivation domain 1 (ID1, residues 1-38) consists of a flexible N terminus anchored at a 5-turn helix, and is thought to work by occluding the ion pathway, as is the case with a classical ball domain. Inactivation domain 2 (ID2, residues 40-50) is a 2.5 turn helix with a high proportion of hydrophobic residues that probably serves to attach ID1 to the cytoplasmic face of the channel. In this way, it can promote rapid access of ID1 to the receptor site in the open channel. ID1 and ID2 function together to bring about fast inactivation of the Kv1.4 channel, which is important for the role of the channel in short-term plasticity.
Interactions
KCNA4 has been shown to interact with DLG4, KCNA2 and DLG1.
See also
Voltage-gated potassium channel
Voltage-gated potassium-channel Kv1.4 IRES
References
Further reading
External links
Protein families
Ion channels | KCNA4 | [
"Chemistry",
"Biology"
] | 531 | [
"Protein families",
"Neurochemistry",
"Ion channels",
"Protein classification"
] |
14,760,042 | https://en.wikipedia.org/wiki/KCNN4 | Potassium intermediate/small conductance calcium-activated channel, subfamily N, member 4, also known as KCNN4, is a human gene encoding the KCa3.1 protein.
Function
The KCa3.1 protein is part of a potentially heterotetrameric voltage-independent potassium channel that is activated by intracellular calcium. Activation is followed by membrane hyperpolarization, which promotes calcium influx. The encoded protein may be part of the predominant calcium-activated potassium channel in T-lymphocytes. This gene is similar to other KCNN family potassium channel genes, but it differs enough to possibly be considered as part of a new subfamily.
History
The channel activity was first described in 1958 by György Gárdos in human erythrocytes. The channel is also named Gardos channel because of its discoverer.
See also
SK channel
Voltage-gated potassium channel
Senicapoc
References
Further reading
Ion channels | KCNN4 | [
"Chemistry"
] | 192 | [
"Neurochemistry",
"Ion channels"
] |
14,760,084 | https://en.wikipedia.org/wiki/MEIS1 | Homeobox protein Meis1 is a protein that in humans is encoded by the MEIS1 gene.
Function
Homeobox genes, of which the most well-characterized category is represented by the HOX genes, play a crucial role in normal development. In addition, several homeoproteins are involved in neoplasia. This gene encodes a homeobox protein belonging to the TALE ('three amino acid loop extension') family of homeodomain-containing proteins.
Interactions
MEIS1 has been shown to interact with PBX1 and HOXA9.
References
Further reading
External links
Transcription factors | MEIS1 | [
"Chemistry",
"Biology"
] | 128 | [
"Induced stem cells",
"Gene expression",
"Transcription factors",
"Signal transduction"
] |
14,760,240 | https://en.wikipedia.org/wiki/PROP1 | Homeobox protein prophet of PIT-1 is a protein that in humans is encoded by the PROP1 gene.
PROP1 has both DNA-binding and transcriptional activation ability. Its expression leads to ontogenesis of pituitary gonadotropes, as well as somatotropes, lactotropes, and caudomedial thyrotropes. Inactivating mutations in PROP1 result in deficiencies of luteinizing hormone (LH; MIM 152780), follicle-stimulating hormone (FSH; MIM 136530), growth hormone (GH; MIM 139250), prolactin (PRL; MIM 176760), and thyroid-stimulating hormone (TSH; MIM 188540). See combined pituitary hormone deficiency (CPHD; MIM 262600).[supplied by OMIM]
References
Further reading
External links
GeneReviews/NCBI/NIH/UW entry on PROP1- Related Combined Pituitary Hormone Deficiency (CPHD)
Transcription factors | PROP1 | [
"Chemistry",
"Biology"
] | 224 | [
"Induced stem cells",
"Gene expression",
"Transcription factors",
"Signal transduction"
] |
14,760,404 | https://en.wikipedia.org/wiki/60S%20ribosomal%20protein%20L10 | 60S ribosomal protein L10 is a protein that in humans is encoded by the RPL10 gene.
Function
Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together, these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 60S subunit. The protein belongs to the L10E family of ribosomal proteins. It is located in the cytoplasm. In vitro, studies have shown that the chicken protein can bind to c-Jun and can repress c-Jun-mediated transcriptional activation, but these activities have not been demonstrated in vivo. This gene was initially identified as a candidate for a Wilms tumor suppressor gene, but later studies determined that this gene is not involved in the suppression of Wilms tumor. This gene has been referred to as 'laminin receptor homolog' because a chimeric transcript consisting of sequence from this gene and sequence from the laminin receptor gene was isolated; however, it is not believed that this gene encodes a laminin receptor. Transcript variants utilizing alternative polyA signals exist. The variant with the longest 3' UTR overlaps the deoxyribonuclease I-like 1 gene on the opposite strand. This gene is co-transcribed with the small nucleolar RNA gene U70, which is located in its fifth intron. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome.
Interactions
RPL10 has been shown to interact with YES1.
References
Further reading
Ribosomal proteins | 60S ribosomal protein L10 | [
"Chemistry"
] | 348 | [
"Biochemistry stubs",
"Protein stubs"
] |
14,760,409 | https://en.wikipedia.org/wiki/40S%20ribosomal%20protein%20S27a | 40S ribosomal protein S27a is a protein that in humans is encoded by the RPS27A gene.
Ubiquitin, a highly conserved protein that has a major role in targeting cellular proteins for degradation by the 26S proteosome, is synthesized as a precursor protein consisting of either polyubiquitin chains or a single ubiquitin fused to an unrelated protein. This gene encodes a fusion protein consisting of ubiquitin at the N terminus and ribosomal protein S27a at the C terminus. When expressed in yeast, the protein is post-translationally processed, generating free ubiquitin monomer and ribosomal protein S27a. Ribosomal protein S27a is a component of the 40S subunit of the ribosome and belongs to the S27AE family of ribosomal proteins. It contains C4-type zinc finger domains and is located in the cytoplasm. Pseudogenes derived from this gene are present in the genome. As with ribosomal protein S27a, ribosomal protein L40 is also synthesized as a fusion protein with ubiquitin; similarly, ribosomal protein S30 is synthesized as a fusion protein with the ubiquitin-like protein fubi.
References
Further reading
Ribosomal proteins | 40S ribosomal protein S27a | [
"Chemistry"
] | 264 | [
"Biochemistry stubs",
"Protein stubs"
] |
14,760,489 | https://en.wikipedia.org/wiki/ZEB1 | Zinc finger E-box-binding homeobox 1 is a protein that in humans is encoded by the ZEB1 gene.
ZEB1 (previously known as TCF8) encodes a zinc finger and homeodomain transcription factor that represses T-lymphocyte-specific IL2 gene expression by binding to a negative regulatory domain 100 nucleotides 5-prime of the IL2 transcription start site. ZEB1 and its mammalian paralog ZEB2 belongs to the Zeb family within the ZF (zinc finger) class of homeodomain transcription factors. ZEB1 protein has seven zinc fingers and one homeodomain. The structure of the homeodomain is shown on the right.
Clinical significance
Mutations of the gene are linked to posterior polymorphous corneal dystrophy 3. ZEB1 downregulates E-cadherin and induces epithelial to mesenchymal transition in breast and other carcinomas A recent study suggested its contributing role in lung cancer invasiveness and metastasis development. Overexpression of ZEB1 has been identified as a potential risk factor for recurrence and poor prognosis in several types of cancers.
References
Further reading
External links
Transcription factors | ZEB1 | [
"Chemistry",
"Biology"
] | 263 | [
"Induced stem cells",
"Gene expression",
"Transcription factors",
"Signal transduction"
] |
14,760,518 | https://en.wikipedia.org/wiki/Alpha-tubulin%203C | Tubulin alpha-3C/D chain is a protein that in humans is encoded by the TUBA3C gene.
Function
Microtubules of the eukaryotic cytoskeleton perform essential and diverse functions and are composed of a heterodimer of alpha and beta tubulin. The genes encoding these microtubule constituents are part of the tubulin superfamily, which is composed of six distinct families. Genes from the alpha, beta and gamma tubulin families are found in all eukaryotes. The alpha and beta tubulins represent the major components of microtubules, while gamma tubulin plays a critical role in the nucleation of microtubule assembly. There are multiple alpha and beta tubulin genes and they are highly conserved among and between species. This gene is an alpha tubulin gene that encodes a protein 99% to the mouse testis-specific Tuba3 and Tuba7 gene products. This gene is located in the 13q11 region, which is associated with the genetic diseases Clouston hidrotic ectodermal dysplasia and Kabuki syndrome. Alternative splicing has been observed for this gene and two variants have been identified.
Interactions
Alpha-tubulin 3C has been shown to interact with FYN and NMI.
References
External links
Further reading | Alpha-tubulin 3C | [
"Chemistry"
] | 268 | [
"Biochemistry stubs",
"Protein stubs"
] |
14,760,562 | https://en.wikipedia.org/wiki/Mucin%205B | Mucin-5B (MUC-5B) is a protein that in humans is encoded by the MUC5B gene
and by the Muc5b gene in the mouse. It is one of the five gel-forming mucins. MUC-5B can be found in whole saliva, normal lung mucus, and cervical mucus. In some diseases, such as COPD, chronic rhinosinusitis (CRS), and H. pylori-associated gastric disease, the gene has been found to be upregulated, and this may be related to the pathogenesis of these conditions.
Synthesis
All mucins are synthesized in secretory cells known as goblet cells or mucous cells, depending on the tissue location. Their creation, while still not completely understood, begins in the endoplasmic reticulum. From there, the Golgi apparatus builds the O-linked glycans found in mucins. Finally, they are packaged into secretory granules.
References
05B | Mucin 5B | [
"Chemistry"
] | 216 | [
"Biochemistry stubs",
"Protein stubs"
] |
14,760,584 | https://en.wikipedia.org/wiki/FluoroPOSS | FluoroPOSS (Fluorinated Polyhedral Oligomeric Silsesquioxanes) is a synthetic microfiber with very low surface energy, which makes it oil-repellent. Mixed with an ordinary polymer, it forms a material which can be applied to other materials such as metal, glass, plastic, plant fibers or leaves. The application process is called electrospinning.
FluoroPOSS has been developed at the Massachusetts Institute of Technology (MIT).
See also
Wetting
External links
MIT creates oil-repelling materials
Fluid mechanics
Plastics additives | FluoroPOSS | [
"Physics",
"Engineering"
] | 119 | [
"Materials stubs",
"Materials",
"Civil engineering",
"Fluid mechanics",
"Matter"
] |
14,760,591 | https://en.wikipedia.org/wiki/Computational%20humor | Computational humor is a branch of computational linguistics and artificial intelligence which uses computers in humor research. It is a relatively new area, with the first dedicated conference organized in 1996.
Joke generators
Pun generation
An approach to analysis of humor is classification of jokes. A further step is an attempt to generate jokes basing on the rules that underlie classification.
Simple prototypes for computer pun generation were reported in the early 1990s, based on a natural language generator program, VINCI. Graeme Ritchie and Kim Binsted in their 1994 research paper described a computer program, JAPE, designed to generate question-answer-type puns from a general, i.e., non-humorous, lexicon. (The program name is an acronym for "Joke Analysis and Production Engine".) Some examples produced by JAPE are:
Q: What is the difference between leaves and a car?
A: One you brush and rake, the other you rush and brake.
Q: What do you call a strange market?
A: A bizarre bazaar.
Since then the approach has been improved, and the latest report, dated 2007, describes the STANDUP joke generator, implemented in the Java programming language. The STANDUP generator was tested on children within the framework of analyzing its usability for language skills development for children with communication disabilities, e.g., because of cerebral palsy. (The project name is an acronym for "System To Augment Non-speakers' Dialog Using Puns" and an allusion to standup comedy.) Children responded to this "language playground" with enthusiasm, and showed marked improvement on certain types of language tests.
The two young people, who used the system over a ten-week period, regaled their peers, staff, family and neighbors with jokes such as: "What do you call a spicy missile? A hot shot!" Their joy and enthusiasm at entertaining others was inspirational.
Other
Stock and Strapparava described a program to generate funny acronyms.
Joke recognition
A statistical machine learning algorithm to detect whether a sentence contained a "That's what she said" double entendre was developed by Kiddon and Brun (2011). There is an open-source Python implementation of Kiddon & Brun's TWSS system.
A program to recognize knock-knock jokes was reported by Taylor and Mazlack. This kind of research is important in analysis of human–computer interaction.
An application of machine learning techniques for the distinguishing of joke texts from non-jokes was described by Mihalcea and Strapparava (2006).
Takizawa et al. (1996) reported on a heuristic program for detecting puns in the Japanese language.
Applications
A possible application for assistance in language acquisition is described in the section "Pun generation". Another envisioned use of joke generators is in cases of a steady supply of jokes where quantity is more important than quality. Another obvious, yet remote, direction is automated joke appreciation.
It is known that humans interact with computers in ways similar to interacting with other humans that may be described in terms of personality, politeness, flattery, and in-group favoritism. Therefore, the role of humor in human–computer interaction is being investigated. In particular, humor generation in user interface to ease communications with computers was suggested.
Craig McDonough implemented the Mnemonic Sentence Generator, which converts passwords into humorous sentences. Based on the incongruity theory of humor, it is suggested that the resulting meaningless but funny sentences are easier to remember. For example, the password AjQA3Jtv is converted into "Arafat joined Quayle's Ant, while TARAR Jeopardized thurmond's vase," an example chosen by combining politicians names with verbs and common nouns.
Related research
John Allen Paulos is known for his interest in mathematical foundations of humor. His book Mathematics and Humor: A Study of the Logic of Humor demonstrates structures common to humor and formal sciences (mathematics, linguistics) and develops a mathematical model of jokes based on catastrophe theory.
Conversational systems which have been designed to take part in Turing test competitions generally have the ability to learn humorous anecdotes and jokes. Because many people regard humor as something particular to humans, its appearance in conversation can be quite useful in convincing a human interrogator that a hidden entity, which could be a machine or a human, is in fact a human.
See also
Theory of humor
World's funniest joke#Other findings
Further reading
"Computational humor", by Binsted, K.; Nijholt, A.; Stock, O.; Strapparava, C.; Ritchie, G.; Manurung, R.; Pain, H.; Waller, A.; Oapos;Mara, D., IEEE Intelligent Systems Volume 21, Issue 2, 2006, pp. 59 – 69
O. Stock, C. Strapparava & A. Nijholt (eds.) "The April Fools' Day Workshop on Computational Humour." Proc. Twente Workshop on Language Technology 20 (TWLT20), ISSN 0929-0672, ITC-IRST, Trento, Italy, April 2002, 146 pp
References
Artificial intelligence
Computational linguistics
Humor research
Computational fields of study | Computational humor | [
"Technology"
] | 1,076 | [
"Natural language and computing",
"Computational fields of study",
"Computational linguistics",
"Computing and society"
] |
14,760,613 | https://en.wikipedia.org/wiki/CDC2L1 | PITSLRE serine/threonine-protein kinase CDC2L1 is an enzyme that in humans is encoded by the CDK11B gene.
This gene encodes a member of the p34Cdc2 protein kinase family. p34Cdc2 kinase family members are known to be essential for eukaryotic cell cycle control. This gene is in close proximity to CDC2L2, a nearly identical gene in the same chromosomal region. The gene loci including this gene, CDC2L2, as well as metalloprotease MMP21/22, consist of two identical, tandemly linked genomic regions which are thought to be a part of the larger region that has been duplicated. This gene and CDC2L2 were shown to be deleted or altered frequently in neuroblastoma with amplified MYCN genes. The protein kinase encoded by this gene could be cleaved by caspases and was demonstrated to play roles in cell apoptosis. Several alternatively spliced variants of this gene have been reported.
Interactions
CDC2L1 has been shown to interact with Cyclin D3.
References
Further reading
External links
EC 2.7.11 | CDC2L1 | [
"Chemistry"
] | 250 | [
"Biochemistry stubs",
"Protein stubs"
] |
14,760,623 | https://en.wikipedia.org/wiki/CHRNB4 | Neuronal acetylcholine receptor subunit beta-4 is a protein that in humans is encoded by the CHRNB4 gene.
Interactive pathway map
See also
Nicotinic acetylcholine receptor
References
Further reading
External links
Ion channels
Nicotinic acetylcholine receptors | CHRNB4 | [
"Chemistry"
] | 61 | [
"Neurochemistry",
"Ion channels"
] |
14,760,713 | https://en.wikipedia.org/wiki/USP9Y | Ubiquitin specific peptidase 9, Y-linked (fat facets-like, Drosophila), also known as USP9Y, is an enzyme which in humans is encoded by the USP9Y gene. It is required for sperm production. This enzyme is a member of the peptidase C19 family and is similar to ubiquitin-specific proteases, which cleave the ubiquitin moiety from ubiquitin-fused precursors and ubiquitinylated proteins.
Clinical significance
Mutations in this gene have been associated with Sertoli cell-only syndrome (SCO) and male infertility.
The USP9Y gene is found on the azoospermia factor (AZF) region on the Y chromosome. Men who have impaired or no sperm production often have a deletion in the AZF region, especially in the USP9Y gene, and it was thought that USP9Y was necessary for sperm production. However, a man and his father with a USP9Y deletion who could produce sperm were recently reported. The corresponding gene is present but inactive in chimpanzees and bonobos.
References
Further reading | USP9Y | [
"Chemistry"
] | 256 | [
"Biochemistry stubs",
"Protein stubs"
] |
14,760,937 | https://en.wikipedia.org/wiki/EEF1B2 | Elongation factor 1-beta is a protein that in humans is encoded by the EEF1B2 gene.
Function
This gene encodes a translation elongation factor. The protein is a guanine nucleotide exchange factor involved in the transfer of aminoacylated tRNAs to the ribosome. Alternative splicing results in three transcript variants which differ only in the 5' UTR.
Interactions
EEF1B2 has been shown to interact with EEF1G and HARS.
References
Further reading | EEF1B2 | [
"Chemistry"
] | 108 | [
"Biochemistry stubs",
"Protein stubs"
] |
14,760,983 | https://en.wikipedia.org/wiki/C-fos-induced%20growth%20factor | C-fos-induced growth factor (FIGF) (or vascular endothelial growth factor D, VEGF-D) is a vascular endothelial growth factor that in humans is encoded by the FIGF gene.
Function
The protein encoded by this gene is a member of the platelet-derived growth factor/vascular endothelial growth factor (PDGF/VEGF) family and is active in angiogenesis, lymphangiogenesis, and endothelial cell growth. This secreted protein undergoes a complex proteolytic maturation, generating multiple processed forms that bind and activate VEGFR-2 and VEGFR-3 receptors. The structure and function of this protein is similar to those of vascular endothelial growth factor C.
Tumor metastasis to lymph nodes
Lymph node metastasis is very often associated with several types of human malignancies. Cancer cells’ journey to lymph node takes place largely through lymphatic tunnel located in and around of primary tumor. VEGF-D's interactions with VEGFR-3 predominantly expressed in lymphatic vessels plays a key role in restructuring lymphatic channel and, hence, able to alter its functions related to fluid and cell transport along the conduits. VEGF-D has been established to be over-expressed in both tumor tissues and patients’ serum samples in several types of human cancer. In addition, VEGF-D expression has been implicated with increased incidence of regional lymph node metastasis. In experimental mice study, genetically modified tumor cell that was forced to produce VEGF-D protein have been established to boost up regional lymph nodes metastases.
References
External links
Further reading
Growth factors
Genes associated with cancer | C-fos-induced growth factor | [
"Chemistry"
] | 363 | [
"Growth factors",
"Signal transduction"
] |
14,761,030 | https://en.wikipedia.org/wiki/HMGB2 | High-mobility group protein B2 also known as high-mobility group protein 2 (HMG-2) is a protein that in humans is encoded by the HMGB2 gene.
Function
This gene encodes a member of the non-histone chromosomal high-mobility group protein family. The proteins of this family are chromatin-associated and ubiquitously distributed in the nucleus of higher eukaryotic cells. In vitro studies have demonstrated that this protein is able to efficiently bend DNA and form DNA circles. These studies suggest a role in facilitating cooperative interactions between cis-acting proteins by promoting DNA flexibility. This protein was also reported to be involved in the final ligation step in DNA end-joining processes of DNA double-strand breaks repair and V(D)J recombination.
References
Further reading
Loss of HMGB2 (High-mobility group protein box 2) during senescence blunts SASP (senescence-associated secretory phenotype) gene expression by allowing for spreading of repressive heterochromatin into SASP gene loci. This correlates with incorporation of SASP gene loci into SAHF (senescence-associated heterochromatin foci), which in turn represses SASP gene expression
External links
Transcription factors | HMGB2 | [
"Chemistry",
"Biology"
] | 265 | [
"Induced stem cells",
"Gene expression",
"Transcription factors",
"Signal transduction"
] |
14,761,048 | https://en.wikipedia.org/wiki/HOXD10 | Homeobox D10, also known as HOXD10, is a protein which in humans is encoded by the HOXD10 gene.
Function
This gene is a member of the Abd-B homeobox family and encodes a protein with a homeobox DNA-binding domain. It is included in a cluster of homeobox D genes located on chromosome 2. The encoded nuclear protein functions as a sequence-specific transcription factor that is expressed in the developing limb buds and is involved in differentiation and limb development.
Clinical significance
Mutations in this gene have been associated with Wilms' tumor and congenital vertical talus (also known as "rocker-bottom foot" deformity or congenital convex pes valgus) and/or a foot deformity resembling that seen in Charcot-Marie-Tooth disease.
Regulation
The HOXD10 gene is repressed by the microRNAs miR-10a and miR-10b.
See also
Homeobox
References
Further reading
External links
Transcription factors | HOXD10 | [
"Chemistry",
"Biology"
] | 205 | [
"Induced stem cells",
"Gene expression",
"Transcription factors",
"Signal transduction"
] |
14,761,062 | https://en.wikipedia.org/wiki/IRF4 | Interferon regulatory factor 4 (IRF4) also known as MUM1 is a protein that in humans is encoded by the IRF4 gene. IRF4 functions as a key regulatory transcription factor in the development of human immune cells. The expression of IRF4 is essential for the differentiation of T lymphocytes and B lymphocytes as well as certain myeloid cells. Dysregulation of the IRF4 gene can result in IRF4 functioning either as an oncogene or a tumor-suppressor, depending on the context of the modification.
The MUM1 symbol is also the current HGNC official symbol for melanoma associated antigen (mutated) 1 (HGNC:29641).
Immune cell development
IRF4 is a transcription factor belonging to the Interferon Regulatory Factor (IRF) family of transcription factors. In contrast to some other IRF family members, IRF4 expression is not initiated by interferons; rather, IRF4 expression is promoted by a variety of bioactive stimuli, including antigen receptor engagement, lipopolysaccharide (LPS), IL-4, and CD40. IRF4 can function either as an activating or an inhibitory transcription factor depending on its transcription cofactors. IRF4 frequently cooperates with the cofactors B-cell lymphoma 6 protein (BCL6) and nuclear factor of activated T-cells (NFATs). IRF4 expression is limited to cells of the immune system, in particular T cells, B cells, macrophages and dendritic cells.
T cell differentiation
IRF4 plays an important role in the regulation of T cell differentiation. In particular, IRF4 ensures the differentiation of CD4+ T helper cells into distinct subsets. IRF4 is essential for the development of Th2 cells and Th17 cells. IRF4 regulates this differentiation via apoptosis and cytokine production, which can change depending on the stage of T cell development. For example, IRF4 limits production of Th2-associated cytokines in naïve T cells while its upregulates the production of Th2 cytokines in effector and memory T cells. While not essential, IRF4 is also believed to play a role in CD8+ cytotoxic T cell differentiation through its regulation of factors directly involved in this process, including BLIMP-1, BATF, T-bet, and RORγt. IRF4 is necessary for effector function of T regulatory cells due to its role as a regulatory factor for BLIMP-1.
B cell differentiation
IRF4 is an essential regulatory component at various stages of B cell development. In early B cell development, IRF4 functions alongside IRF8 to induce the expression of the Ikaros and Aiolos transcription factors, which decrease expression of the pre-B-cell-receptor. IRF4 then regulates the secondary rearrangement of κ and λ chains, making IRF4 essential for the continued development of the BCR.
IRF4 also occupies an essential position in the adaptive immune response of mature B cells. When IRF4 is absent, mature B cells fail to form germinal centers (GCs) and proliferate excessively in both the spleen and lymph nodes. IRF4 expression commences GC formation through its upregulation of transcription factors BCL6 and POU2AF1, which promote germinal center formation. IRF4 expression decreases in B cells once the germinal center forms, since IRF4 expression is not necessary for sustained GC function; however, IRF4 expression increases significantly when B cells prepare to leave the germinal center to form plasma cells.
Long-lived plasma cells
Long-lived plasma cells are memory B cells that secrete high-affinity antibodies and help preserve immunological memory to specific antigens. IRF4 plays a significant role at multiple stages of long-lived plasma cell differentiation. The effects of IRF4 expression are heavily dependent on the quantity of IRF4 present. A limited presence of IRF4 activates BCL6, which is essential for the formation of germinal centers, from which plasma cells differentiate. In contrast, elevated expression of IRF4 represses BCL6 expression and upregulates BLIMP-1 and Zbtb20 expression. This response, dependent on a high dose of IRF4, helps initiate the differentiation of germinal center B cells into plasma cells.
IRF4 expression is necessary for isotype class switch recombination in germinal center B cells that will become plasma cells. B cells that lack IRF4 fail to undergo immunoglobulin class switching. Without IRF4, B cells fail to upregulate the AID enzyme, a component necessary for inducing mutations in immunoglobulin switch regions of B cell DNA during somatic hypermutation. In the absence of IRF4, B cells will not differentiate into Ig-secreting plasma cells.
IRF4 expression continues to be necessary for long-lived plasma cells once differentiation has occurred. In the absence of IRF4, long-lived plasma cells disappear, suggesting that IRF4 plays a role in regulating molecules essential for the continued survival of these cells.
Myeloid cell differentiation
Among myeloid cells, IRF4 expression has been identified in dendritic cells (DCs) and macrophages.
Dendritic cells (DCs)
The transcription factors IRF4 and IRF8 work in concert to achieve DC differentiation. IRF4 expression is responsible for inducing development of CD4+ DCs, while IRF8 expression is necessary for the development of CD8+ DCs. Expression of either IRF4 or IRF8 can result in CD4-/CD8- DCs. Differentiation of DC subtypes also depends on IRF4's interaction with the growth factor GM-CSF. IRF4 expression is necessary for ensuring that monocyte-derived dendritic cells (Mo-DCs) can cross-present antigen to CD8+ cells.
Macrophages
IRF4 and IRF8 are also significant transcription factors in the differentiation of common myeloid progenitors (CMPs) into macrophages. IRF4 is expressed at a lower level than IRF8 in these progenitor cells; however, IRF4 expression appears to be particularly important for the development of M2 macrophages. JMJD3, which regulates IRF4, has been identified as an important regulator of M2 macrophage polarization, suggesting that IRF4 may also take part in this regulatory process.
Clinical significance
In melanocytic cells the IRF4 gene may be regulated by MITF. IRF4 is a transcription factor that has been implicated in acute leukemia. This gene is strongly associated with pigmentation: sensitivity of skin to sun exposure, freckles, blue eyes, and brown hair color. A variant has been implicated in greying of hair.
The World Health Organization (2016) provisionally defined large B-cell lymphoma with IRF4 rearrangement as a rare indolent large B-cell lymphoma of children and adolescents. This indolent lymphoma mimics, and must be distinguished from, pediatric-type follicular lymphoma.
The hallmark of large B-cell lymphoma with IRF4 rearrangement is the overexpression of the IRF4 gene by the disease's malignant cells. This overexpression is forced by the acquisition in these cells of a translocation of IRF4 from its site on the short (i.e. p) arm of chromosome 6 at position 25.3 to a site near the IGH@ immunoglobulin heavy locus on the long (i.e. q) arm of chromosome 14 at position 32.33
Interactions
IRF4 has been shown to interact with:
Aiolos,
BATF3,
Blimp-1,
BCL6,
CD40,
GM-CSF,
IL-4,
Ikaros,
IRF8,
JMJD3,
MMP12,
NFATC2,
SPI1, and
STAT6.
See also
Interferon regulatory factors
References
Further reading
External links
Transcription factors | IRF4 | [
"Chemistry",
"Biology"
] | 1,753 | [
"Induced stem cells",
"Gene expression",
"Transcription factors",
"Signal transduction"
] |
14,761,097 | https://en.wikipedia.org/wiki/MXI1 | MAX-interacting protein 1 is a protein that in humans is encoded by the MXI1 gene.
Function
Expression of the c-myc gene, which produces an oncogenic transcription factor, is tightly regulated in normal cells but is frequently deregulated in human cancers. The protein encoded by this gene is a transcriptional repressor thought to negatively regulate MYC function, and is therefore a potential tumor suppressor. This protein inhibits the transcriptional activity of MYC by competing for MAX, another basic helix-loop-helix protein that binds to MYC and is required for its function. Defects in this gene are frequently found in patients with prostate tumors. Three alternatively spliced transcripts encoding different isoforms have been described. Additional alternatively spliced transcripts may exist but the products of these transcripts have not been verified experimentally.
Interactions
MXI1 has been shown to interact with SMC3 and MAX.
References
Further reading
External links
Transcription factors | MXI1 | [
"Chemistry",
"Biology"
] | 197 | [
"Induced stem cells",
"Gene expression",
"Transcription factors",
"Signal transduction"
] |
14,761,101 | https://en.wikipedia.org/wiki/NCOA6 | Nuclear receptor coactivator 6 is a protein that in humans is encoded by the NCOA6 gene.
Function
The protein encoded by this gene is a transcriptional coactivator that can interact with nuclear hormone receptors to enhance their transcriptional activator functions. The encoded protein has been shown to be involved in the hormone-dependent coactivation of several receptors, including prostanoid, retinoid, vitamin D3, thyroid hormone, and steroid receptors. The encoded protein may also act as a general coactivator since it has been shown to interact with some basal transcription factors, histone acetyltransferases, and methyltransferases.
Interactions
NCOA6 has been shown to interact with:
ASCL2 and
Activating transcription factor 2,
Androgen receptor,
CREB-binding protein,
DNA-PKcs,
E2F1,
EP300,
Estrogen receptor alpha,
Estrogen receptor beta,
HBXIP,
HIST2H3C,
HSF1,
Ku70,
Ku80,
Liver X receptor beta,
MLL3,
RBBP5,
Retinoblastoma protein,
Retinoic acid receptor alpha,
Retinoid X receptor alpha,
Src,
TGS1,
TUBA4A,
TUBB,
Thyroid hormone receptor alpha, and
Thyroid hormone receptor beta.
See also
Transcription coregulator
References
Further reading
External links
Gene expression
Transcription coregulators
Human proteins | NCOA6 | [
"Chemistry",
"Biology"
] | 298 | [
"Gene expression",
"Molecular genetics",
"Cellular processes",
"Molecular biology",
"Biochemistry"
] |
14,761,350 | https://en.wikipedia.org/wiki/60S%20ribosomal%20protein%20L7a | 60S ribosomal protein L7a is a protein that in humans is encoded by the RPL7A gene.
Cytoplasmic ribosomes, organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 60S subunit. The protein belongs to the L7AE family of ribosomal proteins. It can interact with a subclass of nuclear hormone receptors, including thyroid hormone receptor, and inhibit their ability to transactivate by preventing their binding to their DNA response elements. This gene is included in the surfeit gene cluster, a group of very tightly linked genes that do not share sequence similarity. It is co-transcribed with the U24, U36a, U36b, and U36c small nucleolar RNA genes, which are located in its second, fifth, fourth, and sixth introns, respectively. This gene rearranges with the trk proto-oncogene to form the chimeric oncogene trk-2h, which encodes an oncoprotein consisting of the N terminus of ribosomal protein L7a fused to the receptor tyrosine kinase domain of trk. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome.
References
Further reading
Ribosomal proteins | 60S ribosomal protein L7a | [
"Chemistry"
] | 304 | [
"Biochemistry stubs",
"Protein stubs"
] |
14,761,366 | https://en.wikipedia.org/wiki/40S%20ribosomal%20protein%20S3a | 40S ribosomal protein S3a is a protein that in humans is encoded by the RPS3A gene.
Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 40S subunit. The protein belongs to the S3AE family of ribosomal proteins. It is located in the cytoplasm. Disruption of the gene encoding rat ribosomal protein S3a, also named v-fos transformation effector protein, in v-fos-transformed rat cells results in reversion of the transformed phenotype. Transcript variants utilizing alternative transcription start sites have been described. This gene is co-transcribed with the U73A and U73B small nucleolar RNA genes, which are located in its fourth and third introns, respectively. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome.
Interactions
RPS3A has been shown to interact with DNA damage-inducible transcript 3.
References
Further reading
Ribosomal proteins | 40S ribosomal protein S3a | [
"Chemistry"
] | 255 | [
"Biochemistry stubs",
"Protein stubs"
] |
14,761,409 | https://en.wikipedia.org/wiki/UGT1A10 | UDP-glucuronosyltransferase 1-10 is an enzyme that in humans is encoded by the UGT1A10 gene.
This gene encodes a UDP-glucuronosyltransferase, an enzyme of the glucuronidation pathway that transforms small lipophilic molecules, such as steroids, bilirubin, hormones, and drugs, into water-soluble, excretable metabolites. This gene is part of a complex locus that encodes several UDP-glucuronosyltransferases. The locus includes thirteen unique alternate first exons followed by four common exons. Four of the alternate first exons are considered pseudogenes. Each of the remaining nine 5' exons may be spliced to the four common exons, resulting in nine proteins with different N-termini and identical C-termini. Each first exon encodes the substrate binding site, and is regulated by its own promoter. The enzyme encoded by this gene has glucuronidase activity on mycophenolic acid, coumarins, and quinolines.
Interactive pathway map
References
Further reading | UGT1A10 | [
"Chemistry"
] | 251 | [
"Biochemistry stubs",
"Protein stubs"
] |
14,761,477 | https://en.wikipedia.org/wiki/Cyclin-dependent%20kinase%208 | Cell division protein kinase 8 is an enzyme that in humans is encoded by the CDK8 gene.
Function
The protein encoded by this gene is a member of the cyclin-dependent protein kinase (CDK) family. CDK8 and cyclin C associate with the mediator complex and regulate transcription by several mechanisms. CDK8 binds to and/or phosphorylates several transcription factors, which can have an activating or inhibitory effect on transcription factor function. CDK8 phosphorylates the Notch intracellular domain, SREBP, and STAT1 S727. CDK8 also inhibits transcriptional activation by influencing turnover of subunits in the mediator complex tail module. In addition, CDK8 influences binding of RNA polymerase II to the mediator complex.
Clinical significance
CDK8 is a colorectal cancer oncogene: the CDK8 gene is amplified in human colorectal tumors, activating β-catenin-mediated transcription that drives colon tumorigenesis. However, CDK8 may not be oncogenic in all cell types, and indeed may act as a tumor suppressor in the notch and EGFR signaling pathways. Specifically, CDK8 promotes turnover of the notch intracellular domain, and inhibits EGFR signaling-driven cell fates in C. elegans. Thus, CDK8 may be an oncogene in cancers driven by Wnt/β-catenin signaling, but could instead be a tumor suppressor gene in cancers driven by notch or EGFR signaling. In addition, CDK8 promotes transcriptional activation mediated by the tumor suppressor protein p53, indicating that it may have an important role in tumor suppression Further research is needed to delineate the effects of CDK8 inhibition in different tissues, so for the time being, drugs targeting CDK8 for cancer treatment remain untested in humans.
An autosomal dominant syndrome has been described that is associated with mutations in the ATP binding pocket of the kinase domain. The clinical features include agenesis of the corpus callosum, mild to moderate intellectual disability, hypotonia, seizures, hearing or visual impairments, behavioral disorders, variable facial dysmorphism, congenital heart disease and ano-rectal malformations.
As a potential drug target
The natural product cortistatin A is a potent and selective inhibitor of CDK8 and CDK19. Inhibition of CDK8 and CDK19 with cortistatin A suppresses AML cell growth and has anticancer activity in animal models of AML by causing selective and disproportionate up regulation of super-enhancer-associated genes including the cell identity genes CEBPA and IRF8.
Interactions
Cyclin-dependent kinase 8 has been shown to interact with:
CCNC
CREB binding protein
CRSP3
MED1
MED12
MED14
MED16
MED17
MED21
MED24
MED26
MED6
Notch proteins
POLR2A
SMARCB1
STAT1
SREBP
References
Further reading
External links
Cell cycle
Proteins
EC 2.7.11 | Cyclin-dependent kinase 8 | [
"Chemistry",
"Biology"
] | 642 | [
"Biomolecules by chemical classification",
"Cellular processes",
"Molecular biology",
"Proteins",
"Cell cycle"
] |
14,761,571 | https://en.wikipedia.org/wiki/ZBTB17 | Zinc finger and BTB domain-containing protein 17 is a protein that in humans is encoded by the ZBTB17 gene.
Interactions
ZBTB17 has been shown to interact with TOPBP1, Host cell factor C1 and Myc.
References
Further reading
External links
Transcription factors | ZBTB17 | [
"Chemistry",
"Biology"
] | 59 | [
"Induced stem cells",
"Gene expression",
"Transcription factors",
"Signal transduction"
] |
14,761,583 | https://en.wikipedia.org/wiki/PRDM2 | PR domain zinc finger protein 2 is a protein that in humans is encoded by the PRDM2 gene.
Function
This tumor suppressor gene is a member of a nuclear histone/protein methyltransferase superfamily. It encodes a zinc finger protein that can bind to retinoblastoma protein, estrogen receptor, and the TPA-responsive element (MTE) of the heme-oxygenase-1 gene. Although the functions of this protein have not been fully characterized, it may (1) play a role in transcriptional regulation during neuronal differentiation and pathogenesis of retinoblastoma, (2) act as a transcriptional activator of the heme-oxygenase-1 gene, and (3) be a specific effector of estrogen action. Three transcript variants encoding different isoforms have been found for this gene.
Interactions
PRDM2 has been shown to interact with Estrogen receptor alpha and Retinoblastoma protein.
References
Further reading
External links
Transcription factors | PRDM2 | [
"Chemistry",
"Biology"
] | 208 | [
"Induced stem cells",
"Gene expression",
"Transcription factors",
"Signal transduction"
] |
14,761,587 | https://en.wikipedia.org/wiki/HIST2H2AA3 | Histone H2A type 2-A is a protein that in humans is encoded by the HIST2H2AA3 gene.
Function
Histones are basic nuclear proteins that are responsible for the nucleosome structure of the chromosomal fiber in eukaryotes. Two molecules of each of the four core histones (H2A, H2B, H3, and H4) form an octamer, around which approximately 146 bp of DNA is wrapped in repeating units, called nucleosomes. The linker histone, H1, interacts with linker DNA between nucleosomes and functions in the compaction of chromatin into higher order structures. This gene is intronless and encodes a member of the histone H2A family. Transcripts from this gene lack polyA tails but instead contain a palindromic termination element. This gene is found in a histone cluster on chromosome 1. This gene is one of four histone genes in the cluster that are duplicated; this record represents the centromeric copy.
References
Further reading | HIST2H2AA3 | [
"Chemistry"
] | 226 | [
"Biochemistry stubs",
"Protein stubs"
] |
14,761,594 | https://en.wikipedia.org/wiki/HIST1H2BG | Histone H2B type 1-C/E/F/G/I is a protein that in humans is encoded by the HIST1H2BG gene.
Histones are basic nuclear proteins that are responsible for the nucleosome structure of the chromosomal fiber in eukaryotes. Nucleosomes consist of approximately 146 bp of DNA wrapped around a histone octamer composed of pairs of each of the four core histones (H2A, H2B, H3, and H4). The chromatin fiber is further compacted through the interaction of a linker histone, H1, with the DNA between the nucleosomes to form higher order chromatin structures. This gene is intronless and encodes a member of the histone H2B family. Transcripts from this gene lack polyA tails; instead, they contain a palindromic termination element. This gene is found in the large histone gene cluster on chromosome 6p22-p21.3.
References
Further reading | HIST1H2BG | [
"Chemistry"
] | 220 | [
"Biochemistry stubs",
"Protein stubs"
] |
14,761,759 | https://en.wikipedia.org/wiki/CRX%20%28gene%29 | Cone-rod homeobox protein is a protein that in humans is encoded by the CRX gene.
Function
The protein encoded by this gene is a photoreceptor-specific transcription factor which plays a role in the differentiation of photoreceptor cells. This homeodomain protein is necessary for the maintenance of normal cone and rod function. Mutations in this gene are associated with photoreceptor degeneration, Leber's congenital amaurosis type III and the autosomal dominant cone-rod dystrophy 2. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some variants has not been determined.
Mammalian CRX encodes a 299 amino acid protein containing a DNA binding homeodomain (HD) near its N-terminus followed by glutamine rich (Gln), and basic amino acid regions, then a C-terminal transactivation domain (AD). While structural biochemistry has demonstrated that the CRX HD adopts a canonical homeodomain protein fold, the AD is predicted to be flexible and disordered. The structural attributes of the CRX AD have yet to be solved.
Evolution
CRX is a divergent duplicate of OTX produced during the 2 rounds of vertebrate whole genome duplication.
In the eutherian mammals, CRX has again duplicated by tandem gene duplication, with six ancestral duplicates, which are collectively referred to as ETCHbox genes.
References
Further reading
External links
GeneReviews/NCBI/NIH/UW entry on Retinitis Pigmentosa Overview
Transcription factors | CRX (gene) | [
"Chemistry",
"Biology"
] | 335 | [
"Induced stem cells",
"Gene expression",
"Transcription factors",
"Signal transduction"
] |
14,761,821 | https://en.wikipedia.org/wiki/EPH%20receptor%20A3 | EPH receptor A3 (ephrin type-A receptor 3) is a protein that in humans is encoded by the EPHA3 gene.
Function
This gene belongs to the ephrin receptor subfamily of the protein-tyrosine kinase family. EPH and EPH-related receptors have been implicated in mediating developmental events, particularly in the nervous system. Receptors in the EPH subfamily typically have a single kinase domain and an extracellular region containing a Cys-rich domain and 2 fibronectin type III repeats. The ephrin receptors are divided into 2 groups based on the similarity of their extracellular domain sequences and their affinities for binding ephrin-A and ephrin-B ligands. This gene encodes a protein that binds ephrin-A ligands. Two alternatively spliced transcript variants have been described for this gene.
Interactions
EPH receptor A3 has been shown to interact with EFNB2 and EFNA5.
References
Further reading
Tyrosine kinase receptors | EPH receptor A3 | [
"Chemistry"
] | 211 | [
"Tyrosine kinase receptors",
"Signal transduction"
] |
14,761,876 | https://en.wikipedia.org/wiki/HOXA5 | Homeobox protein Hox-A5 is a protein that in humans is encoded by the HOXA5 gene.
Function
In vertebrates, the genes encoding the class of transcription factors called homeobox genes are found in clusters named A, B, C, and D on four separate chromosomes. Expression of these proteins is spatially and temporally regulated during embryonic development. This gene is part of the A cluster on chromosome 7 and encodes a DNA-binding transcription factor which may regulate gene expression, morphogenesis, and differentiation. Methylation of this gene may result in the loss of its expression and, since the encoded protein upregulates the tumor suppressor p53, this protein may play an important role in tumorigenesis.
HoxA5 is controlled, at least in part, by DNA methylation. HoxA5 has been shown to upregulate the tumor suppressor p53 and AKT1 by downregulation of PTEN. Suppression of HoxA5 has been shown to attenuate hemangioma growth. HoxA5 has far-reaching effects on gene expression, causing ~300 genes to become upregulated upon its induction in breast cancer cell lines. HoxA5 protein transduction domain overexpression prevents inflammation shown by inhibition of TNFα-inducible monocyte binding to HUVECs.
Comparison of the HoxA5 promoter methylation profile across cell types from the least differentiated (human embryonic stem cells) to the most endothelial-like (human umbilical vein endothelial cells, or HUVECs) shows that the HoxA5 promoter is normally heavily methylated in non-differentiated cells and becomes demethylated as cells differentiate down the endothelial lineage. HoxA5 contains a C-Amp Response Elements (CRE) in its promoter. POL2 and CTCF binding are enriched at the CpG-dense HoxA5 promoter in HUVECs, demonstrating transcriptional activity.
Clinical significance
HoxA5 is suppressed in acute myeloid leukemia (AML), and the DNMT inhibitor decitabine (5Aza) is used to treat this disease. While HoxA5 is known to be hypermethylated in AML, it has not yet been shown whether decitabine directly targets these genes for demethylation. HOXA5 has also been nominated as an oncogene in glioblastoma.
See also
Homeobox
References
External links
Transcription factors | HOXA5 | [
"Chemistry",
"Biology"
] | 515 | [
"Induced stem cells",
"Gene expression",
"Transcription factors",
"Signal transduction"
] |
14,761,885 | https://en.wikipedia.org/wiki/Creusot%20steam%20hammer | The Creusot steam hammer is a giant steam hammer built in 1877 by Schneider and Co. in the French industrial town of Le Creusot. With the ability to deliver a blow of up to 100 tons, the Creusot hammer was the most powerful in the world until 1891, when the Bethlehem Iron Company of the United States purchased patent rights from Schneider and built a steam hammer of almost identical design but capable of delivering a 125-ton blow.
The Creusot hammer is no longer operational, and is a tourist attraction in the town of Le Creusot, where it was built. With few remaining rivals, the hammer today is once again the largest of its kind in the world.
The Creusot steam hammer was named a Historic Mechanical Engineering Landmark by the American Society of Mechanical Engineers in 1981.
Origins
In 1836, Joseph Eugène Schneider and his brother Adolphe Schneider purchased a derelict ironworks in Burgundy, near the town of Le Creusot, and founded Schneider Brothers & Co. (later renamed Schneider & Co.). Two years later the company produced the first steam locomotive to be built in France. Eugène Schneider along with the company's chief engineer, François Bourdon, developed the world's first true steam hammer at the Schneider works in 1841. Schneider and Co. went on to build 110 steam hammers of all sizes between 1843 and 1867, 26 of which were employed by the firm itself. As the jobs grew more demanding, the hammers grew correspondingly larger, and the Schneiders eventually saw a need for a hammer of colossal proportions.
The Creusot steam hammer was completed in 1877, and with its ability to deliver a blow of up to 100 tons, eclipsed the previous record set by the German firm Krupp, whose steam hammer "Fritz", with its 50-ton blow, had held the title as the world's most powerful steam hammer since 1861. In celebration of this technological achievement, a full-scale wooden replica of the Creusot hammer was built and displayed at the Paris Universal Exposition of 1878.
Description
The hammer is composed of four distinct parts — the foundation including the anvil, the legs, the steam cylinder and its valves and linkages, and finally, the active mass itself — the piston, piston rod, hammerhead and die.
The anvil weighed a massive 750 tons, and in order to support the weight and the hammer blows, the machine's foundations were built of solid masonry resting on bedrock 11 meters below the soil. A one-metre thick bed of oak timber topped the masonry foundation and provided the immediate floor for the giant anvil.
The four legs are hollow cast and rectangular in cross-section. They were originally bolted to plates embedded in the masonry. The legs are 10.25 meters high and connected to one another at the top in a rigid A-frame design by a 30-ton "table", that in its working life both guided the hammerhead and distributed the shock of its blows. One leg supports the operator's platform from which the machine was controlled.
The steam cylinder itself is 6 meters high and has an inside diameter of 1.9 meters. Steam pressure averaging 5 kg/cm2 or 71 psi drove the cylinder upwards through two balanced single-acting slide valves, after which the force of gravity would allow the hammer to fall and deliver a blow.
The piston had a maximum travel of 5 meters and the piston rod was 35 centimeters in diameter. The hammerhead or tup was interchangeable, with a number of differently shaped dies which may account for the hammer's reported variable force of between 75 and 100 tons. The actual energy delivered may have been in the order of 3.3 million foot-pounds (or 500,000 kilogram-metres).
Four separate furnaces provided steam power to four adjacent swan-necked cranes, which were used for manipulating the massive 120-ton iron and steel ingots delivered to the hammer for forging. Six Bessemer converters supplied the steel for the ingots, which were transported on a railway line built expressly for the purpose through the works.
For a comparison of scale, the world's largest modern hydraulic forging presses can apply force of about 80,000 tons.
Demonstrations
In its heyday, the hammer would sometimes give public demonstrations of its accuracy. It could be used to cork a bottle, crack a nut without damaging the contents, or tap a watch glass without breaking it. With such demonstrations, steam hammers for a time became symbols of industrial precision.
Redundancy
Steam hammers were eventually made redundant with the introduction of hydraulic and mechanical steel presses, which could apply force more evenly and create better quality product. The giant American hammer built by Bethlehem Iron which had superseded the Creusot hammer in 1891 was demolished by 1902, but the Creusot hammer itself had a much longer service life, in use for 54 years until its final retirement in 1930.
Tourist attraction
In 1969 the Creusot hammer was dismantled and reassembled in Le Creusot town square. Unfunctional, it serves as a tourist attraction and a reminder of a bygone era of technological achievement.
Footnotes
References
The Largest Hammer in the World — The New York Times, January 13, 1878.
Industrial Revolution
Steam hammers
Stationary steam engines
Steam engines
Landmarks in France
Historic Mechanical Engineering Landmarks
Schneider Electric | Creusot steam hammer | [
"Engineering"
] | 1,086 | [
"Steam hammers",
"Industrial machinery"
] |
14,761,887 | https://en.wikipedia.org/wiki/HOXA11 | Homeobox protein Hox-A11 is a protein that in humans is encoded by the HOXA11 gene.
Function
In vertebrates, the genes encoding the class of transcription factors called homeobox genes are found in clusters named A, B, C, and D on four separate chromosomes. Expression of these proteins is spatially and temporally regulated during embryonic development. This gene is part of the A cluster on chromosome 7 and encodes a DNA-binding transcription factor which may regulate gene expression, morphogenesis, and differentiation. This gene is involved in the regulation of uterine development and is required for female fertility. Mutations in this gene can cause radioulnar synostosis with amegakaryocytic thrombocytopenia.
See also
Homeobox
References
Further reading
External links
Transcription factors | HOXA11 | [
"Chemistry",
"Biology"
] | 169 | [
"Induced stem cells",
"Gene expression",
"Transcription factors",
"Signal transduction"
] |
14,761,897 | https://en.wikipedia.org/wiki/HES1 | Transcription factor HES1 (hairy and enhancer of split-1) is a protein that is encoded by the Hes1 gene, and is the mammalian homolog of the hairy gene in Drosophila. HES1 is one of the seven members of the Hes gene family (HES1-7). Hes genes code nuclear proteins that suppress transcription.
This protein belongs to the basic helix-loop-helix (bHLH) family of transcription factors. It is a transcriptional repressor of genes that require a bHLH protein for their transcription. The protein has a particular type of basic domain that contains a helix interrupting protein that binds to the N-box promoter region rather than the canonical enhancer box (E-box). As a member of the bHLH family, it is a transcriptional repressor that influences cell proliferation and differentiation in embryogenesis. HES1 regulates its own expression via a negative feedback loop, and oscillates with approximately 2-hour periodicity.
Structure
There are three conserved domains in Hes genes that impart transcriptional functions: the bHLH domain, the Orange domain, and the WRPW motif. Hes genes differ from other bHLH factors in that they have a proline residue in the middle of the basic DNA binding region. This proline has been proposed to give Hes proteins unique DNA binding capacity. While most bHLH factors bind to the E-box consensus sequence (CANNTG) that is present in the promoter region of target genes, Hes factors bind more preferentially to the Class C site or N box (CACNAG). The Orange domain serves to regulate the choice of bHLH heterodimer partners. The C-terminal WRPW domain inhibits transcription.
Interactions
Similarly to other HES proteins, Hes1 has been shown to interact with the co-repressors encoded by the Transducin-like E(spl) (TLE) genes and the Groucho-related gene (Grg), both homologs of the Drosophila groucho. Because Groucho in Drosophila inhibits transcription by recruiting histone deacetylase, it is likely that a Hes-Groucho complex actively blocks transcription by disabling chromatin. Hes proteins also heterodimerize with bHLH repressors such as Hey1 and Hey2, a process which also blocks transcription. Hes factors also heterodimerize with bHLH activators such as E47, also known as Tcfe2a, and Mash1, also known as Ascl1, both of which are the mammalian homologs to proneural genes in Drosophila. The E47-Hes and Mash1-Hes heterodimer complexes cannot bind DNA, and therefore repress transcription.
Hes1 also interacts with TLE2 and Sirtuin 1.
HES1 and stem cells
HES1 influences the maintenance of certain stem cells and progenitor cells. Specifically, HES1 influences the timing of differentiation by repressing bHLH activators, and determines binary cell fate. HES1 has been shown to play a large role in both the nervous, and digestive systems. HES1 has been shown to influence these two systems partially through the Notch signaling pathway.
Neural development
HES1 is expressed in both neuroepithelial cells and radial glial cells, both neural stem cells. Hes1 expression, along with that of Hes5, covers the majority of the developing embryo at embryonic day 10.5. After this point, expression of Hes1 is limited to the subventricular zone. In HES1 knockout (KO) mice, Mash1 is compensatorily upregulated, and neurogenesis is accelerated. Indeed, if the expression of Hes1, Hes3, and Hes5 genes is inhibited, the expression of proneural genes increases, and while neurogenesis is accelerated, neural stem cells become prematurely depleted. Contrariwise, if these HES genes are overexpressed, neurogenesis is inhibited. Thus HES1 genes are only involved in maintaining, not creating, neural stem cells.
Additionally, HES1 can guide neural stem cells down one of two paths of differentiation. HES1 can maintain neural stem cells expressing Pax6, but leads cells that are Pax6-negative to an astrocyte differentiation fate. Epigenetic modifications such as DNA methylation also influence HES1's ability to direct differentiation. Demethylation of HES1 target sites in the promoter region of astrocyte-specific genes hastens astrocyte differentiation. The oscillatory nature of Hes1 expression has a role in determining differentiation fate as well. HES1-high embryonic stem cells that received a differentiation signal often adopted a mesodermal fate, while HES1-low cells that received a differentiation signal differentiated into neuronal cells. These results were confirmed using quantitative PCR which showed that HES1-high cells showed high levels of Brachyury and Fgf5 expression (both of which are expressed highly in mesodermal cell types) with comparatively low levels genes expressed in neural cells such as Nestin. By contrast, HES1-low cells showed high levels of expression of genes involved in neural induction and low levels of expression of genes involved in mesodermal differentiation. Cycling HES1 levels also contribute to the maintenance of neural progenitor cells by regulating Neurogenin2 (Ngn2) and Dll1 oscillations. Hes1 levels fluctuate at different frequencies in different parts of the central nervous system: HES1 is continuously expressed at high levels in the boundaries, but vacillates in the compartments. This suggests that alternating HES1 levels may prompt differences in characteristics between anatomical elements of the central nervous system.
Interactions with the Notch pathway
HES1 also plays an important role in the Notch signaling pathway. In the absence of Notch signaling, RBPJ inhibits the expression of HES1. After Notch signals have been processed within the cell, however, the plasma membrane releases the intracellular domain of Notch, which moves to the nucleus where it associates with RBPJ. The binding causes a conformational change which leads co-repressors to disassociate and allows co-activators to bind. The new activating complex then prompts HES1 expression. Notch signaling activates HES1 expression. HES1 has been shown to target at least Notch ligands: Dll1, Jagged1 (Jag1), and Neurogenin-2., Dll1, as with other Notch ligands, has been shown to induce neural differentiation, and HES1 binding of Dll1 blocks neural differentiation and leads to the maintenance of the neural stem cells and neural progenitor cells. Notch signaling also occurs in the intestinal crypt cells. Hyperactivated Notch causes a reduction in the number of secretory cell types (i.e. goblet cells, enteroendocrine cells, and Paneth cells). Deletion of the Notch pathway by removing the Notch expression controller, Rbpsuh, causes the production of nearly only goblet cells.
Digestive system
HES1 has been shown to influence the differentiation decision of cells in the gastrointestinal tract. In pancreatic progenitor cells, HES1 expression inhibits the expression of Ptf1a, which controls exocrine cell differentiation, and Ngn3, which drives differentiation of endocrine cell types that will form the islets of Langerhans. The absence of Hes1 in the developing intestine of mice promotes the increase of Math1 (a protein required for the production of intestinal secretory cell types), which leads to an increase of goblet, enteroendocrine, and Paneth cells. When Hes1 is deleted in mouse and zebrafish, surplus goblet cells and enteroendocrine cells are made while few enterocytes are made., Liver progenitor cells differentiate into two different cell types: hepatocytes and biliary epithelial cells. When Hes1 expression is low, hepatocytes form normally, but bile ducts are completely absent. This phenotype resembles Alagille syndrome, a hallmark of which is mutations in Jagged1. Therefore, Hes-Notch interactions also play a role in digestive organ development.
References
Further reading
External links
Transcription factors | HES1 | [
"Chemistry",
"Biology"
] | 1,797 | [
"Induced stem cells",
"Gene expression",
"Transcription factors",
"Signal transduction"
] |
14,761,935 | https://en.wikipedia.org/wiki/KLF2 | Krüppel-like Factor 2 (KLF2), also known as lung Krüppel-like Factor (LKLF), is a protein that in humans is encoded by the KLF2 gene on chromosome 19. It is in the Krüppel-like factor family of zinc finger transcription factors, and it has been implicated in a variety of biochemical processes in the human body, including lung development, embryonic erythropoiesis, epithelial integrity, T-cell viability, and adipogenesis.
Discovery
Erythroid Krüppel-like Factor (EKLF or KLF1) was the first Krüppel-like Factor discovered. It is vital for embryonic erythropoiesis in promoting the switch from fetal hemoglobin (Hemoglobin F) to adult hemoglobin (Hemoglobin A) gene expression by binding to highly conserved CACCC domains. EKLF ablation in mouse embryos produces a lethal anemic phenotype, causing death by embryonic day 14, and natural mutations lead to β+ thalassemia in humans. However, expression of embryonic hemoglobin and fetal hemoglobin genes is normal in EKLF-deficient mice, and since all genes on the human β-globin locus exhibit the CACCC elements, researchers began searching for other Krüppel-like factors.
KLF2, initially called lung Krüppel-like Factor due to its high expression in the adult mouse lung, was first isolated in 1995 by using the zinc finger domain of EKLF as a hybridization probe. By transactivation assay in mouse fibroblasts, KLF2 was also noticed to bind to the β-globin gene promoter containing the CACCC sequence shown to be the binding site for EKLF, confirming KLF2 as a member of the Krüppel-like Factor family. Since then, many other KLF proteins have been discovered.
Structure
The main feature of the KLF family is the presence of three highly conserved Cysteine2/Histidine2 zinc fingers of either 21 or 23 amino acid residues in length, located at the C-terminus of the protein. These amino acid sequences each chelate a single zinc ion, coordinated between the two cysteine and two histidine residues. These zinc fingers are joined by a conserved seven-amino acid sequence; TGEKP(Y/F)X. The zinc fingers enable all KLF proteins to bind to CACCC gene promoters, so although they may complete varied functions (due to lack of homology away from the zinc fingers), they all recognize similar binding domains.
KLF2 also exhibits these structural features. The mRNA transcript is approximately 1.5 kilobases in length, and the 37.7 kDa protein contains 354 amino acids. KLF2 also shares some homology with EKLF at the N-terminus with a proline-rich region presumed to function as the transactivation domain.
Gene expression
KLF2 was first discovered, and is highly expressed in, the adult mouse lung, but it is also expressed temporally during embryogenesis in erythroid cells, endothelium, lymphoid cells, the spleen, and white adipose tissue. It is expressed as early as embryonic day 9.5 in the endothelium.
KLF2 has a particularly interesting expression profile in erythroid cells. It is minimally expressed in the primitive and fetal definitive erythroid cells, but is highly expressed in adult definitive erythroid cells, particularly in the proerythroblast and the polychromatic and orthochromatic normoblasts.
Mouse knockout
Homologous recombination of embryonic stem cells was used to generate KLF2-deficient mouse embryos. Both vasculogenesis and angiogenesis were normal in the embryos, but they died by embryonic day 14.5 from severe hemorrhaging. The vasculature displayed defective morphology, with thin tunica media and aneurysmal dilation that led to rupturing. Aortic vascular smooth muscle cells failed to organize into a normal tunica media, and pericytes were low in number. These KLF2-deficient mice thus demonstrated the important role of KLF2 in blood vessel stabilization during embryogenesis.
Due to embryonic lethality in KLF2-deficient embryos, it is difficult to examine the role of KLF2 in normal post-natal physiology, such as in lung development and function.
Function
Lung development
Lung buds removed from KLF2-deficient mouse embryos and cultured from normal tracheobronchial trees. In order to circumvent embryonic lethality usually observed in KLF2-deficient embryos, KLF2 homozygous null mouse embryonic stem cells were constructed and used to produce chimeric animals. These KLF2-deficient embryonic stem cells contribute significantly to development of skeletal muscle, spleen, heart, liver, kidney, stomach, brain, uterus, testis, and skin, but not to the development of the lung. These embryos had lungs arrested in the late canalicular stage of lung development, with undilated acinar tubules. In contrast, wild type embryos are born in the saccular stage of lung development with expanded alveoli. This suggests that KLF2 is an important transcription factor required in late gestation for lung development.
Embryonic erythropoiesis
KLF2 is now believed to play an important role in embryonic erythropoiesis, specifically in regulating embryonic and fetal β-like globin gene expression. In a murine KLF2-deficient embryo, expression of β-like globin genes normally expressed in primitive erythroid cells was significantly decreased, although adult β-globin gene expression was unaffected.
The role of KLF2 in human β-like globin gene expression was further elucidated by transfection of a murine KLF2-deficient embryo with the human β-globin locus. It was found that KLF2 was important for ε-globin (found in embryonic hemoglobin) and γ-globin (found in fetal hemoglobin) gene expression. However, as before, KLF2 plays no role in adult β-globin gene expression; this is regulated by EKLF.
However, KLF2 and EKLF have been found to interact in embryonic erythropoiesis. Deletion of both KLF2 and EKLF in mouse embryos results in fatal anemia earlier than in either single deletion at embryonic day 10.5. This indicates that KLF2 and EKLF interact in embryonic and fetal β-like globin gene expression. It has been shown using conditional knockout mice that both KLF2 and EKLF bind directly to β-like globin promoters. There is also evidence to suggest that KLF2 and EKLF synergistically bind to the Myc promoter, a transcription factor that is associated with gene expression of α-globin and β-globin in embryonic proerythroblasts.
Endothelial physiology
KLF2 expression is induced by fluid laminar flow shear stress, as is caused by blood flow in normal endothelium.
This activates mechanosensitive channels, which in turn activates two pathways; the MEK5/ERK5 pathway, which activates MEF2, a transcription factor that upregulates KLF2 gene expression; and PI3K inhibition, which increases the stability of KLF2 mRNA. Binding of cytokines such as TNFα and IL-1β to their receptors activates transcription factor p65, which also induces KLF2 expression. KLF2 then has four key functions in endothelium:
By inhibiting activation of p65 by transcription coactivator p300, VCAM1 and SELE expression is downregulated, genes that encode endothelial cell adhesion molecules, causing decreased lymphocyte and leukocyte activation and hence decreasing inflammation
It upregulates THBD (thrombomodulin) and NOS3 (endothelial nitric oxide synthase) expression, having an anti-thrombotic effect
Through the upregulation of NOS3, as well as NPPC (natriuretic precursor peptide C), KLF2 has a vasodilatory effect
KLF2 also inhibits VEGFR2 (VEGF receptor 2) expression, having an anti-angiogenic effect
Thus KLF2 has an important role in regulating normal endothelium physiology. It is hypothesized that myeloid-specific KLF2 plays a protective role in atherosclerosis. Gene expression changes in endothelial cells induced by KLF2 have been demonstrated to be atheroprotective.
T-cell differentiation
KLF2 has an important function in T-lymphocyte differentiation. T-cells are activated and more prone to apoptosis without KLF2, suggesting that KLF2 regulates T-cell quiescence and survival. KLF2-deficient thymocytes also do not express several receptors required for thymus emigration and differentiation into mature T-cells, such as sphingosine-1 phosphate receptor 1.
Adipogenesis
KLF2 is a negative regulator of adipocyte differentiation. KLF2 is expressed in preadipocytes, but not mature adipocytes, and it potently inhibits PPAR-γ (peroxisome proliferator-activated receptor-γ) expression by inhibiting promoter activity. This prevents differentiation of preadipocytes into adipocytes, and thus prevents adipogenesis.
See also
Krüppel-like factors
Erythroid Krüppel-like factor
Zinc finger transcription factors
References
External links
Transcription factors | KLF2 | [
"Chemistry",
"Biology"
] | 2,106 | [
"Induced stem cells",
"Gene expression",
"Transcription factors",
"Signal transduction"
] |
14,761,936 | https://en.wikipedia.org/wiki/RNPS1 | RNA-binding protein with serine-rich domain 1 is a protein that in humans is encoded by the RNPS1 gene.
Function
This gene encodes a protein that is part of a post-splicing multiprotein complex, the exon junction complex, involved in both mRNA nuclear export and mRNA surveillance. mRNA surveillance detects exported mRNAs with truncated open reading frames and initiates nonsense-mediated mRNA decay (NMD). When translation ends upstream from the last exon-exon junction, this triggers NMD to degrade mRNAs containing premature stop codons. This protein binds to the mRNA and remains bound after nuclear export, acting as a nucleocytoplasmic shuttling protein. This protein contains many serine residues. Two splice variants have been found for this gene; both variants encode the same protein.
Interactions
RNPS1 has been shown to interact with SART3 and Pinin.
References
Further reading
External links | RNPS1 | [
"Chemistry"
] | 196 | [
"Biochemistry stubs",
"Protein stubs"
] |
14,762,039 | https://en.wikipedia.org/wiki/KCNJ6 | G protein-activated inward rectifier potassium channel 2 is a protein that in humans is encoded by the KCNJ6 gene. Mutation in KCNJ6 gene has been proposed to be the cause of Keppen-Lubinsky Syndrome (KPLBS).
Function
Potassium channels are present in most mammalian cells, where they participate in a wide range of physiologic responses. The protein encoded by this gene is an integral membrane protein and inward-rectifier type potassium channel. The encoded protein, which has a greater tendency to allow potassium to flow into a cell rather than out of a cell, is controlled by G-proteins and may be involved in the regulation of insulin secretion by glucose. It associates with two other G-protein-activated potassium channels to form a heteromultimeric pore-forming complex.
Interactions
KCNJ6 has been shown to interact with KCNJ9 and DLG1.
See also
G protein-coupled inwardly-rectifying potassium channel
Inward-rectifier potassium ion channel
References
Further reading
External links
Ion channels | KCNJ6 | [
"Chemistry"
] | 226 | [
"Neurochemistry",
"Ion channels"
] |
14,762,060 | https://en.wikipedia.org/wiki/Lumican | Lumican, also known as LUM, is an extracellular matrix protein that, in humans, is encoded by the LUM gene on chromosome 12.
Structure
Lumican is a proteoglycan Class II member of the small leucine-rich proteoglycan (SLRP) family that includes decorin, biglycan, fibromodulin, keratocan, epiphycan, and osteoglycin.
Like the other SLRPs, lumican has a molecular weight of about 40 kilodaltons and has four major intramolecular domains:
a signal peptide of 16 amino acid residues;
a negatively-charged N-terminal domain containing sulfated tyrosine and disulfide bond(s);
ten tandem leucine-rich repeats allowing lumican to bind to other extracellular components such as collagen;
a carboxyl terminal domain of 50 amino acid residues containing two conserved cysteines 32 residues apart.
There are four N-linked sites within the leucine-rich repeat domain of the protein core that can be substituted with keratan sulfate. The core protein of lumican (like decorin and fibromodulin) is horseshoe shaped. This enables it bind to collagen molecules within a collagen fibril, thus helping keep adjacent fibrils apart.
Function
Lumican is a major keratan sulfate proteoglycan of the cornea but is ubiquitously distributed in most mesenchymal tissues throughout the body. Lumican is involved in collagen fibril organization and circumferential growth, corneal transparency, and epithelial cell migration and tissue repair. Corneal transparency is possible due to the exact alignment of collagen fibers by lumican (and keratocan) in the intrafibrillar space.
Clinical significance
Mice that have the lumican gene knocked out (Lum-/-) develop opacities of the cornea in both eyes and fragile skin. The lumican (LUM) gene was thought to be a candidate susceptibility gene for high myopia; however, a meta-analysis showed no association between LUM polymorphism and high myopia susceptibility in all genetic models studied.
Lum knockout mice also have abnormal collagen in their heart tissue, with fewer and thicker fibrils. Mice deficient in both lumican and fibromodulin develop severe tendinopathy (tendon pathology), revealing the importance of these SLRPs in the development of correctly sized and aligned collagen fibers in tendon. Along with other extracellular matrix components, lumican expression was increased in equine flexor tendons six weeks after an injury.
Lumican is present in the extracellular matrix of uteral tissues in fertile women. There is an increase of lumican during the proliferative to secretory phase of the endometrium. In menopausal endometrial tissue, the level of lumican expression decreases and is also low in pathological compared to normal endometrium.
Lumican is highly expressed in pleural effusions (lung fluid) of patients with adenocarcinoma. Its expression was low in cancer cells but high in the extracellular matrix surrounding the tumor. Lumican expression was not associated with tumor grade or stage. In about half the patients with pancreatic ductal adenocarcinoma tested, lumican in the extracellular matrix around the tumor was associated with a reduction in metastatic recurrence after surgery and with a three-fold longer survival than patients without stromal lumican. As lumican can directly bind to and inhibit matrix metalloproteinase-14 (MMP14), lumican may limit tumor progression by preventing extracellular matrix collagen proteolysis by this enzyme.
References
Further reading
Proteins | Lumican | [
"Chemistry"
] | 825 | [
"Biomolecules by chemical classification",
"Proteins",
"Molecular biology"
] |
14,762,075 | https://en.wikipedia.org/wiki/MEF2D | Myocyte-specific enhancer factor 2D is a protein that in humans is encoded by the MEF2D gene.
Interactions
MEF2D has been shown to interact with:
CABIN1,
EP300,
MAPK7,
Myocyte-specific enhancer factor 2A,
NFATC2
Sp1 transcription factor, and
YWHAQ.
See also
Mef2
References
Further reading
External links
Transcription factors | MEF2D | [
"Chemistry",
"Biology"
] | 87 | [
"Induced stem cells",
"Gene expression",
"Transcription factors",
"Signal transduction"
] |
14,762,315 | https://en.wikipedia.org/wiki/Green%20accounting | Green accounting is a type of accounting that attempts to factor environmental costs into the financial results of operations. It has been argued that gross domestic product ignores the environment and therefore policymakers need a revised model that incorporates green accounting. The major purpose of green accounting is to help businesses understand and manage the potential quid pro quo between traditional economics goals and environmental goals. It also increases the important information available for analyzing policy issues, especially when those vital pieces of information are often overlooked. Green accounting is said to only ensure weak sustainability, which should be considered as a step toward ultimately a strong sustainability.
It is a controversial practice however, since depletion may be already factored into accounting for the extraction industries and the accounting for externalities may be arbitrary. It is obvious therefore that a standard practice would need to be established in order for it to gain both credibility and use. Depletion is not the whole of environmental accounting however, with pollution being but one factor of business that is almost never accounted for specifically. Julian Lincoln Simon, a professor of business administration at the University of Maryland and a Senior Fellow at the Cato Institute, argued that use of natural resources results in greater wealth, as evidenced by the falling prices over time of virtually all nonrenewable resources.
Etymology
The term was first brought into common usage by economist and professor Peter Wood in the 1980s.
Practice
Environmental responsibility is a potent issue among businesses in this modern age. It has become necessary for corporation to formulate methods of promoting green causes for the present and the future. Green accounting helps promote a sustainable future for businesses as it brings green public procurement and green research and development into the big picture. Penalties for polluters and incentives (such as tax breaks, polluting permits, etc.) are also a crucial part of this type of accounting.
The System of National Accounts (SNA) defines Net Domestic Product (NDP) as:NDP = Net Exports + Final Consumption (C) + Net Investment (I)This is also a typical formula found in articles and texts about accounting.
Green Accounting, however, uses the System of Environmental Economic Accounting (SEEA), which focuses on the depletion of scarce natural resources and measures the costs of environmental degradation along with its prevention.
Thus, the NDP is newly defined as Green NDP, or also known as EDP. The green accounting formula is:EDP = Net Exports + C + NAp. ec + (NAnp.ec - NAnp.n)Where:
EDP = Environmental Domestic Product,
C = Final Consumption,
NApec = Net Accumulation of Produced Economic Assets,
NAnp.ec = Net Accumulation of Non-produced Economic Assets,
NAnp.n = Net Accumulation of Non-produced Natural Assets.
Challenges
Environmental protection and economic growth
The effect of environmental policies on the economy has always been a controversial topic. Many economists argue that sanctioned limits on pollution curtail economic growth. For instance, between 1973 and 1982, the United States imposed stricter regulations on pollution, which led to a 0.09% decrease per year in the national output growth. A study conducted in 1990 also analyzed the economic growth with during the time period between 1973 and 1980s. The result indicated that the government regulation reduced the annual GNP by 0.19% per year. Other researchers argue that those number is insignificant compared to protecting and sustaining the priceless environment.
Distributional impacts of environmental and natural resource policies
Not all industries pollute the same amount; chemical and paper manufacturing industries, for example, tend to pollute more than others. It is difficult to accurately measure the pollution level of each industry in order to categorize and to set up a fair set of policies. In particular, improved water quality might highly favor the higher income groups due to the fact that most improvements are done in the urban areas.
Links between trade and environmental and natural resource policies
During the time of globalization and the rapid expansion of the international market, the US policymakers have come to realize the importance of what is happening in other countries. Before making any decision and submitting the final draft to Congress, the policymakers were concerned about the effects of the North American Free Trade Agreement on the environment. National accounting systems that include environmental and natural resources could provide useful information during negotiations over the nations' commitments to restore or maintain natural capital.
Trade restrictions have not been used when a country's production and processing methods result in excessive discharges of pollutants (carbon, sulfur, nitrogen oxides, chlorofluorocarbons) across national boundaries. The difficulty comes in when determining the effects of trans-boundary pollutants on industry costs.
See also
References
External links
Green Budget.
Environmental economics | Green accounting | [
"Environmental_science"
] | 943 | [
"Environmental economics",
"Environmental social science"
] |
14,762,357 | https://en.wikipedia.org/wiki/ST13 | Hsc70-interacting protein also known as suppression of tumorigenicity 13 (ST13) is a protein that in humans is encoded by the ST13 gene.
Function
The protein encoded by this gene is an adaptor protein that mediates the association of the heat shock proteins HSP70 and HSP90. This protein has been shown to be involved in the assembly process of glucocorticoid receptor, which requires the assistance of multiple molecular chaperones. The expression of this gene is reported to be downregulated in colorectal carcinoma tissue suggesting that is a candidate tumor suppressor gene.
References
Further reading
Co-chaperones | ST13 | [
"Chemistry"
] | 137 | [
"Biochemistry stubs",
"Protein stubs"
] |
14,762,376 | https://en.wikipedia.org/wiki/TAF2 | Transcription initiation factor TFIID subunit 2 is a protein that in humans is encoded by the TAF2 gene.
Initiation of transcription by RNA polymerase II requires the activities of more than 70 polypeptides. The protein that coordinates these activities is transcription factor IID (TFIID), which binds to the core promoter to position the polymerase properly, serves as the scaffold for assembly of the remainder of the transcription complex, and acts as a channel for regulatory signals. TFIID is composed of the TATA binding protein (TBP) and a group of evolutionarily conserved proteins known as TBP-associated factors or TAFs. TAFs may participate in basal transcription, serve as coactivators, function in promoter recognition or modify general transcription factors (GTFs) to facilitate complex assembly and transcription initiation. This gene encodes one of the larger subunits of TFIID that is stably associated with the TFIID complex. It contributes to interactions at and downstream of the transcription initiation site, interactions that help determine transcription complex response to activators.
References
Further reading
External links
Transcription factors | TAF2 | [
"Chemistry",
"Biology"
] | 228 | [
"Induced stem cells",
"Gene expression",
"Transcription factors",
"Signal transduction"
] |
14,762,406 | https://en.wikipedia.org/wiki/TBX5%20%28gene%29 | T-box transcription factor TBX5, (T-box protein 5) is a protein that in humans is encoded by the TBX5 gene. Abnormalities in the TBX5 gene can result in altered limb development, Holt-Oram syndrome, Tetra-amelia syndrome, and cardiac and skeletal problems.
This gene is a member of a phylogenetically conserved family of genes that share a common DNA-binding domain, the T-box. T-box genes encode transcription factors involved in the regulation of developmental processes. This gene is closely linked to related family member T-box 3 (ulnar mammary syndrome) on human chromosome 12.
TBX5 is located on the long arm of chromosome 12. TBX5 produces a protein called T-box protein 5 that acts as a transcription factor. TBX5 is involved with forelimb and heart development. This gene impacts the early development of the forelimb by triggering fibroblast growth factor, FGF10.
Function
TBX5 is a transcription factor that codes for the protein called T-box 5. The transcription factors it encodes are necessary for development, especially in the pattern formation of upper limbs and cardiac growth. TBX5 is involved with the development of the four heart chambers, the electrical conducting system, and the septum separating the right and left sides of the heart. Along with playing roles in the development of the heart, septum, and electrical system of the heart, it also activates genes that are involved in the development of the upper limbs, the arms and hands.
This gene is also involved in the muscle connective tissue for muscle and tendon patterning. A study showed that deletion of TBX5 in forelimbs causes disruption in the muscle and tendon patterning without affecting the skeleton's development. T-box protein 5 expression is in the cells of the lateral plate mesoderm which form the forelimb bud and the cascade of limb initiation. In its absence, no forelimb bud forms.
The encoded protein plays a major role in limb development, specifically during limb bud initiation. For instance, in chickens Tbx5 specifies forelimb status. The activation of Tbx5 and other T-box proteins by Hox genes activates signaling cascades that involve the Wnt signaling pathway and FGF signals in limb buds. Ultimately, Tbx5 leads to the development of apical ectodermal ridge (AER) and zone of polarizing activity (ZPA) signaling centers in the developing limb bud, which specify the orientation growth of the developing limb. Together with Tbx4, Tbx5 plays a role in patterning the soft tissues (muscles and tendons) of the musculoskeletal system.
As a protein-coding gene, TBX5 encodes for the protein T-box Transcription Factor 5, which is a part of the T-box family of transcription factors. It also interacts with other genes, such as GATA4 and NKX2-5, and the BAF chromatin-remodeling complex to drive and repress gene expression during development.
Role in non-human animals
Mice that were genetically modified to not have the TBX5 gene did not survive gestation, due to the heart not developing past embryonic day E10.5. Mice that only had one working copy of TBX5 were born with morphological problems such as enlarged hearts, atrial and ventral septum defects, and limb malformations similar to those found in the Holt-Oram Syndrome.
Pigeons with feathered feet have Tbx5 active in the hind feet, which cause them to develop feathered hindlimbs with thicker bones, more similar to their frontlimb wings.
Role in human embyronic development
A gene "knockout" model for TBX5 by CRISPR/Cas9 genome editing has been created. This homozygous TBX5 knockout human embryonic stem cell line, called TBX5-KO maintained stem cell-like morphology, pluripotency markers, normal karyotype, and could differentiate into all three germ layers in vivo. This cell line can provide an in vitro platform for studying the pathogenic mechanisms and biological function of TBX5 in the heart development. By understanding what happens in development without this gene, further treatment options for fetuses with a TBX5 mutation might be possible to prevent the severe cardiac defects associated with Holt-Oram Syndrome.
Clinical significance
Mutations in this gene can result in Holt–Oram syndrome, a developmental disorder affecting the heart and upper limbs. Holt-Oram syndrome can cause a hole in the septum, bone abnormalities in the fingers, wrists, or arms, and a conduction disease leading to abnormal heart rates and arrhythmias. The most common cardiac issue associated with this condition is the malformation of the septum, which separates the left and right sides of the heart.
Tetra-amelia syndrome is a condition where forelimb malformation occurs because FGF-10 is not triggered due to Tbx5 mutations. This condition can lead to the absence of one or both forelimbs.
Skeletally, there may be abnormally bent fingers, sloping shoulders, and phocomelia. Cardiac defects include ventral and atrial septation and problems with the conduction system. Several transcript variants encoding different isoforms have been described for this gene.
Interactions
TBX5 (gene) has been shown to interact with:
GATA4 and
NKX2-5.
References
Further reading
External links
GeneReviews/NCBI/NIH/UW entry on Holt-Oram Syndrome
Transcription factors | TBX5 (gene) | [
"Chemistry",
"Biology"
] | 1,161 | [
"Induced stem cells",
"Gene expression",
"Transcription factors",
"Signal transduction"
] |
14,762,423 | https://en.wikipedia.org/wiki/ZNF148 | Zinc finger protein 148 is a protein that in humans is encoded by the ZNF148 gene.
Interactions
ZNF148 has been shown to interact with PTRF and P53.
See also
Zinc finger
References
Further reading
External links
Transcription factors | ZNF148 | [
"Chemistry",
"Biology"
] | 52 | [
"Protein stubs",
"Gene expression",
"Signal transduction",
"Biochemistry stubs",
"Induced stem cells",
"Transcription factors"
] |
14,762,468 | https://en.wikipedia.org/wiki/HIST1H4I | Histone H4 is a protein that, in humans, is encoded by the HIST1H4I gene.
Histones are basic nuclear proteins that are responsible for the nucleosome structure of the chromosomal fiber in eukaryotes. Two molecules of each of the four core histones (H2A, H2B, H3, and H4) form an octamer, around which approximately 146 bp of DNA is wrapped in repeating units, called nucleosomes. The linker histone, H1, interacts with linker DNA between nucleosomes and functions in the compaction of chromatin into higher order structures. This gene is intronless and encodes a member of the histone H4 family. Transcripts from this gene lack polyA tails but instead contain a palindromic termination element. This gene is found in the histone microcluster on chromosome 6p21.33.
References
Further reading | HIST1H4I | [
"Chemistry"
] | 202 | [
"Biochemistry stubs",
"Protein stubs"
] |
14,762,594 | https://en.wikipedia.org/wiki/CEBPE | CCAAT/enhancer binding protein (C/EBP), epsilon, also known as CEBPE and CRP1, is a type of ccaat-enhancer-binding protein. CEBPE is its human gene and is pro-apoptotic.
The protein encoded by this gene is a bZIP transcription factor which can bind as a homodimer to certain DNA regulatory regions. It can also form heterodimers with the related protein CEBP-δ. The encoded protein may be essential for terminal differentiation and functional maturation of committed granulocyte progenitor cells. Mutations in this gene have been associated with specific granule deficiency, a rare congenital disorder. Multiple variants of this gene have been described, but the full-length nature of only one has been determined.
References
Further reading
External links
Transcription factors | CEBPE | [
"Chemistry",
"Biology"
] | 177 | [
"Induced stem cells",
"Gene expression",
"Transcription factors",
"Signal transduction"
] |
14,762,774 | https://en.wikipedia.org/wiki/IRF9 | Interferon regulatory factor 9 is a protein that in humans is encoded by the IRF9 gene, previously known as ISGF3G.
Interactions
IRF9 has been shown to interact with STAT2 and STAT1.
References
Further reading
External links
Transcription factors | IRF9 | [
"Chemistry",
"Biology"
] | 54 | [
"Protein stubs",
"Gene expression",
"Signal transduction",
"Biochemistry stubs",
"Induced stem cells",
"Transcription factors"
] |
14,762,964 | https://en.wikipedia.org/wiki/IGKC | Immunoglobulin kappa constant, also known as IGKC, is a human gene that encodes the constant domain of kappa-type light chains for antibodies. It is found on chromosome 2, in humans, within the Immunoglobulin kappa locus, IGK@.
References
Further reading
Proteins | IGKC | [
"Chemistry"
] | 68 | [
"Biomolecules by chemical classification",
"Protein stubs",
"Biochemistry stubs",
"Molecular biology",
"Proteins"
] |
14,762,974 | https://en.wikipedia.org/wiki/IL1RAP | Interleukin-1 receptor accessory protein is a protein that in humans is encoded by the IL1RAP gene.
Interleukin 1 induces synthesis of acute phase and proinflammatory proteins during infection, tissue damage, or stress, by forming a complex at the cell membrane with an interleukin 1 receptor and an accessory protein. This gene encodes an interleukin 1 receptor accessory protein. Alternative splicing of this gene results in two transcript variants encoding two different isoforms, one membrane-bound and one soluble.
Interactions
IL1RAP has been shown to interact with TOLLIP and Interleukin 1 receptor, type I.
References
Further reading
External links
Proteins | IL1RAP | [
"Chemistry"
] | 146 | [
"Biomolecules by chemical classification",
"Proteins",
"Molecular biology"
] |
14,762,997 | https://en.wikipedia.org/wiki/IRF5 | Interferon regulatory factor 5 is a protein that in humans is encoded by the IRF5 gene. The IRF family is a group of transcription factors that are involved in signaling for virus responses in mammals along with regulation of certain cellular functions.
Function
IRF5 is a member of the interferon regulatory factor (IRF) family, a group of transcription factors with diverse roles, including virus-mediated activation of interferon, and modulation of cell growth, differentiation, apoptosis, and immune system activity. Members of the IRF family are characterized by a conserved N-terminal DNA-binding domain containing tryptophan (W) repeats. Alternative splice variants encoding different isoforms exist. The regulatory and repression regions of the IRF family are mainly located in the C-terminal of the IRF.
A 2020 study showed that an adaptor protein named TASL play an important regulatory role in IRF5 activation by being phosphorylated at the pLxIS motif, drawing a similar analogy to the IRF3 activation pathway through the adaptor proteins MAVS, STING and TRIF.
Clinical significance
IRF5 acts as a molecular switch that controls whether macrophages will promote or inhibit inflammation. Blocking the production of IRF5 in macrophages may help treat a wide range of autoimmune diseases, and that boosting IRF5 levels might help treat people whose immune systems are weak, compromised, or damaged. IRF5 seems to work "either by interacting with DNA directly, or by interacting with other proteins that themselves control which genes are switched on."
Signaling
The IRF family regulates the gene expression for the interferon (IFN) response to viral infections. IRF5 is a direct transducer to interferon signaling and is activated via phosphorylation. The IRF family can also initiate the JAK/STAT signaling pathway by binding to transmembrane receptors that activate JAK. IRFs, IFNs, and the JAK/STAT signaling pathway work together to fight viral infections in mammals through specific signals.
See also
Interferon regulatory factors
References
Further reading
External links
Transcription factors | IRF5 | [
"Chemistry",
"Biology"
] | 441 | [
"Induced stem cells",
"Gene expression",
"Transcription factors",
"Signal transduction"
] |
14,763,077 | https://en.wikipedia.org/wiki/Classical%20modal%20logic | In modal logic, a classical modal logic L is any modal logic containing (as axiom or theorem) the duality of the modal operators
that is also closed under the rule
Alternatively, one can give a dual definition of L by which L is classical if and only if it contains (as axiom or theorem)
and is closed under the rule
The weakest classical system is sometimes referred to as E and is non-normal. Both algebraic and neighborhood semantics characterize familiar classical modal systems that are weaker than the weakest normal modal logic K.
Every regular modal logic is classical, and every normal modal logic is regular and hence classical.
References
Chellas, Brian. Modal Logic: An Introduction. Cambridge University Press, 1980.
Modal logic | Classical modal logic | [
"Mathematics"
] | 159 | [
"Mathematical logic",
"Modal logic"
] |
14,763,146 | https://en.wikipedia.org/wiki/BACH1 | Transcription regulator protein BACH1 is a protein that in humans is encoded by the BACH1 gene.
Function
This gene encodes a transcription factor that belongs to the cap'n'collar type of basic region leucine zipper factor family (CNC-bZip). The encoded protein contains broad complex, tramtrack, bric-a-brac/poxvirus and zinc finger (BTB/POZ) domains, which is atypical of CNC-bZip family members. These BTB/POZ domains facilitate protein-protein interactions and formation of homo- and/or hetero-oligomers. The C-terminus of the protein is a leucine zipper of the bzip_maf family. When this protein forms a heterodimer with MafK, it functions as a repressor of Maf recognition element (MARE) and transcription is repressed. Multiple alternatively spliced transcript variants have been identified for this gene. Some exons of this gene overlap with some exons from the GRIK1-AS2 gene, which is transcribed in an opposite orientation to this gene but does not encode a protein.
See also
Small Maf (sMaf)
Bach1-sMaf heterodimer
References
Further reading
External links
Transcription factors | BACH1 | [
"Chemistry",
"Biology"
] | 268 | [
"Induced stem cells",
"Gene expression",
"Transcription factors",
"Signal transduction"
] |
14,763,164 | https://en.wikipedia.org/wiki/NFATC3 | Nuclear factor of activated T-cells, cytoplasmic 3 is a protein that in humans is encoded by the NFATC3 gene.
Function
The product of this gene is a member of the nuclear factors of activated T cells DNA-binding transcription complex. This complex consists of at least two components: a preexisting cytosolic component that translocates to the nucleus upon T cell receptor (TCR) stimulation and an inducible nuclear component. Other members of this family participate to form this complex also. The product of this gene plays a role in the regulation of gene expression in T cells and immature thymocytes. Four transcript variants encoding distinct isoforms have been identified for this gene.
See also
NFAT
References
Further reading
External links
Transcription factors
Human proteins | NFATC3 | [
"Chemistry",
"Biology"
] | 158 | [
"Induced stem cells",
"Gene expression",
"Transcription factors",
"Signal transduction"
] |
14,763,312 | https://en.wikipedia.org/wiki/RFX1 | MHC class II regulatory factor RFX1 is a protein that, in humans, is encoded by the RFX1 gene located on the short arm of chromosome 19.
Structure
The RFX1 gene is a member of the regulatory factor X (RFX) gene family, which encodes transcription factors that contain five conserved domains including a highly conserved, centrally located, winged helix DNA binding domain as well as a dimerization domain located in the C-terminal region of the sequence. Apart from the five conserved domains, the RFX proteins diverge significantly. The DNA binding and dimerization domains of the RFX family proteins show no similarities to the other domains with the same functions in other proteins.
Species distribution
The RFX protein family is conserved in S. pombe, S. cerevisiae, C. elegans, mice and humans. There are seven known RFX proteins in humans, five in mice, and one in C. elegans as well as one in each of the two species of yeast.
Function
The protein encoded by this gene is structurally related to regulatory factors X2, X3, X4, and X5. It is a transcriptional activator that can bind DNA as a monomer or as a heterodimer with RFX family members X2, X3, and X5, but not with X4. This protein binds to the Xboxes of MHC class II genes and is essential for their expression. Also, it can bind to an inverted repeat that is required for expression of hepatitis B virus genes. The RFX proteins were originally cloned and characterized due to their high affinity for a cis-acting promoter sequence, called the Xbox, found in all MHC class II genes.
Levels of mRNA encoding this protein as well as RFX2 and RFX3 are found to be consistently elevated in the testis and are variable in other tissues throughout the body.
RFX1 contains a C-terminal sequence with no apparent homology to other RFX proteins. This C-terminal tail contains an acidic region that is thought to aid in crossing the nuclear membrane. Two major functions are hypothesized to this exist for this domain: a contribution to the nuclear localization signal (NLS) as well as the contradictory down-regulation of DNA binding as well as nuclear association. These two functions were originally identified through sequence mutations and translational fusions with gfp (green fluorescent protein) and remain to be confirmed.
Interactions
RFX1 has been shown to interact with Abl gene.
References
Further reading
External links
Transcription factors | RFX1 | [
"Chemistry",
"Biology"
] | 524 | [
"Induced stem cells",
"Gene expression",
"Transcription factors",
"Signal transduction"
] |
14,763,333 | https://en.wikipedia.org/wiki/BRD2 | Bromodomain-containing protein 2 is a protein that in humans is encoded by the BRD2 gene. BRD2 is part of the Bromodomain and Extra-Terminal motif (BET) protein family that also contains BRD3, BRD4, and BRDT in mammals
Early descriptions demonstrated that BRD2 gene product is a mitogen-activated kinase which localizes to the nucleus. The gene maps to the major histocompatibility complex (MHC) class II region on chromosome 6p21.3 but sequence comparison suggests that the protein is not involved in the immune response. Homology to the Drosophila gene female sterile homeotic suggests that this human gene may be part of a signal transduction pathway involved in growth control.
Functions
BRD2 has been implicated in cancer.
BRD2 loss in mice causes obesity without diabetes for unknown reasons.
BRD2 may have functional overlap with close homolog BRD3.
BRD2 function is blocked by BET inhibitors.
Interactions
BRD2 has been shown to interact with E2F2, and many transcription factors including GATA1.
References
External links
Further reading | BRD2 | [
"Chemistry"
] | 235 | [
"Biochemistry stubs",
"Protein stubs"
] |
14,763,419 | https://en.wikipedia.org/wiki/DAZ3 | Deleted in azoospermia protein 3 is a protein that in humans is encoded by the DAZ3 gene.
This gene is a member of the DAZ gene family and is a candidate for the human Y-chromosomal azoospermia factor (AZF). Its expression is restricted to premeiotic germ cells, particularly in spermatogonia. It encodes an RNA-binding protein that is important for spermatogenesis. Four copies of this gene are found on chromosome Y within palindromic duplications; one pair of genes is part of the P2 palindrome and the second pair is part of the P1 palindrome. Each gene contains a 2.4 kb repeat including a 72-bp exon, called the DAZ repeat; the number of DAZ repeats is variable and there are several variations in the sequence of the DAZ repeat. Each copy of the gene also contains a 10.8 kb region that may be amplified; this region includes five exons that encode an RNA recognition motif (RRM) domain. This gene contains one copy of the 10.8 kb repeat.
References
Further reading | DAZ3 | [
"Chemistry"
] | 239 | [
"Biochemistry stubs",
"Protein stubs"
] |
14,763,498 | https://en.wikipedia.org/wiki/SMARCE1 | SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily E member 1 is a protein that in humans is encoded by the SMARCE1 gene.
Function
The protein encoded by this gene is part of the large ATP-dependent chromatin remodeling complex SWI/SNF, which is required for transcriptional activation of genes normally repressed by chromatin. The encoded protein, either alone or when in the SWI/SNF complex, can bind to 4-way junction DNA, which is thought to mimic the topology of DNA as it enters or exits the nucleosome. The protein contains a DNA-binding HMG domain, but disruption of this domain does not abolish the DNA-binding or nucleosome-displacement activities of the SWI/SNF complex. Unlike most of the SWI/SNF complex proteins, this protein has no yeast counterpart.
Interactions
SMARCE1 has been shown to interact with Estrogen receptor alpha, SMARCB1 and SMARCA4.
References
Further reading | SMARCE1 | [
"Chemistry"
] | 228 | [
"Biochemistry stubs",
"Protein stubs"
] |
14,763,517 | https://en.wikipedia.org/wiki/SOX4 | Transcription factor SOX-4 is a protein that in humans is encoded by the SOX4 gene.
Function
This intronless gene encodes a member of the SOX (SRY-related HMG-box) family of transcription factors involved in the regulation of embryonic development and in the determination of the cell fate. The encoded protein may act as a transcriptional regulator after forming a protein complex with other proteins, such as syndecan binding protein (syntenin). The protein may function in the apoptosis pathway leading to cell death as well as to tumorigenesis and may mediate downstream effects of parathyroid hormone (PTH) and PTH-related protein (PTHrP) in bone development. The solution structure has been resolved for the HMG-box of a similar mouse protein.
Sox4 is expressed in lymphocytes (B and T) and is required for B lymphocyte development.
Clinical significance
A genomic region close to the SOX4 gene has been associated with endometrial cancer development.
Interactions
SOX4 has been shown to interact with SDCBP.
See also
SOX gene family
References
Further reading
External links
Transcription factors | SOX4 | [
"Chemistry",
"Biology"
] | 240 | [
"Induced stem cells",
"Gene expression",
"Transcription factors",
"Signal transduction"
] |
14,763,666 | https://en.wikipedia.org/wiki/HIST2H4A | Histone H4 is a protein that in humans is encoded by the HIST2H4A gene.
Histones are basic nuclear proteins that are responsible for the nucleosome structure of the chromosomal fiber in eukaryotes. This structure consists of approximately 146 bp of DNA wrapped around a nucleosome, an octamer composed of pairs of each of the four core histones (H2A, H2B, H3, and H4). The chromatin fiber is further compacted through the interaction of a linker histone, H1, with the DNA between the nucleosomes to form higher order chromatin structures. This gene is intronless and encodes a member of the histone H4 family. Transcripts from this gene lack polyA tails; instead, they contain a palindromic termination element. This gene is found in a histone cluster on chromosome 1. This gene is one of four histone genes in the cluster that are duplicated; this record represents the centromeric copy.
References
Further reading | HIST2H4A | [
"Chemistry"
] | 223 | [
"Biochemistry stubs",
"Protein stubs"
] |
14,763,775 | https://en.wikipedia.org/wiki/CDKN2C | Cyclin-dependent kinase 4 inhibitor C is an enzyme that in humans is encoded by the CDKN2C gene.
Function
The protein encoded by this gene is a member of the INK4 family of cyclin-dependent kinase inhibitors. This protein has been shown to interact with CDK4 or CDK6, and prevent the activation of the CDK kinases, thus function as a cell growth regulator that controls cell cycle G1 progression. Ectopic expression of this gene was shown to suppress the growth of human cells in a manner that appears to correlate with the presence of a wild-type RB1 function. Studies in the knockout mice suggested the roles of this gene in regulating spermatogenesis, as well as in suppressing tumorigenesis. Two alternatively spliced transcript variants of this gene, which encode an identical protein, have been reported.
Interactions
CDKN2C has been shown to interact with Cyclin-dependent kinase 4 and Cyclin-dependent kinase 6.
References
Further reading
External links
Cell cycle regulators | CDKN2C | [
"Chemistry"
] | 216 | [
"Cell cycle regulators",
"Signal transduction"
] |
14,763,782 | https://en.wikipedia.org/wiki/CKMT1B | Creatine kinase, mitochondrial 1B also known as CKMT1B is one of two genes which encode the ubiquitous mitochondrial creatine kinase (ubiquitous mtCK or CKMT1).
Function
Mitochondrial creatine (MtCK) kinase is responsible for the transfer of high energy phosphate from mitochondria to the cytosolic carrier, creatine. It belongs to the creatine kinase isoenzyme family. It exists as two isoenzymes, sarcomeric MtCK (CKMT2) and ubiquitous MtCK, encoded by separate genes. Mitochondrial creatine kinase occurs in two different oligomeric forms: dimers and octamers, in contrast to the exclusively dimeric cytosolic creatine kinase isoenzymes. Ubiquitous mitochondrial creatine kinase has 80% homology with the coding exons of sarcomeric mitochondrial creatine kinase. Two genes located near each other on chromosome 15 (CKMT1A and CKMT1B (this gene)) have been identified which encode identical mitochondrial creatine kinase proteins.
Clinical significance
Many malignant cancers with poor prognosis have shown overexpression of ubiquitous mitochondrial creatine kinase; this may be related to high energy turnover and failure to eliminate cancer cells via apoptosis.
References
External links
Further reading | CKMT1B | [
"Chemistry"
] | 272 | [
"Biochemistry stubs",
"Protein stubs"
] |
14,764,119 | https://en.wikipedia.org/wiki/Khilwa | Khilwa, in Shariah law, is an offense consisting of being caught alone in private with a member of the opposite sex who is not an immediate family member (a state known as khalwat).
For example, in Malaysia in 2009, 197 students "were caught for khalwat" in the state of Kuala Terengganu within seven months. Muslims there who are unmarried, non-relatives of a person of the opposite sex can be apprehended by state religious police under the offence of khalwat (being in "close proximity" as The Star Online described it). Religious Department enforcement officers can conduct "checks, surveillance and raids to curtail khalwat cases," catch "students from secondary schools and higher learning institutes...for khalwat" and advise "youth organisations and student leaders on the bane of committing khalwat."
References
Interpersonal relationships
Sharia legal terminology | Khilwa | [
"Biology"
] | 190 | [
"Behavior",
"Interpersonal relationships",
"Human behavior"
] |
14,764,190 | https://en.wikipedia.org/wiki/EPHB6 | Ephrin type-B receptor 6 is a protein that in humans is encoded by the EPHB6 gene.
Ephrin receptors and their ligands, the ephrins, mediate numerous developmental processes, particularly in the nervous system. Based on their structures and sequence relationships, ephrins are divided into the ephrin-A (EFNA) class, which are anchored to the membrane by a glycosylphosphatidylinositol linkage, and the ephrin-B (EFNB) class, which are transmembrane proteins. The Eph family of receptors are divided into 2 groups based on the similarity of their extracellular domain sequences and their affinities for binding ephrin-A and ephrin-B ligands. Ephrin receptors make up the largest subgroup of the receptor tyrosine kinase (RTK) family. The ephrin receptor encoded by this gene lacks the kinase activity of most receptor tyrosine kinases and binds to ephrin-B ligands.
References
Further reading
Tyrosine kinase receptors | EPHB6 | [
"Chemistry"
] | 228 | [
"Tyrosine kinase receptors",
"Signal transduction"
] |
14,764,246 | https://en.wikipedia.org/wiki/HHEX | Hematopoietically-expressed homeobox protein HHEX is a protein that in humans is encoded by the HHEX gene and also known as Proline Rich Homeodomain protein PRH.
This gene encodes a member of the homeobox family of transcription factors, many of which are involved in developmental processes. Expression in specific hematopoietic lineages suggests that this protein may play a role in hematopoietic differentiation but the expression of this protein is not limited to hematopoietic cells.
Function
The HHEX transcription factor acts as a activator of transcription in some instances and a repressor of transcription others. It interacts with a number of other signaling molecules to play an important role in the development of multiple organs, such as the liver, thyroid and forebrain. HHEX serves to repress VEGFA, another protein which is important in endothelial cell development. SCL, a significant transcription factor for blood and endothelial cell differentiation, is shown to interact with HHEX to promote the correct development of the hematopoiesis process. HHEX appears to work together with another molecule, β-catenin, for the development of the anterior organizer. It also contributes to developmental remodeling and stabilization of endothelial cells in an unborn organism. The importance of this transcription factor is illustrated by the inability of HHEX knockout mice embryos to survive gestation. Without the expression of HHEX, these mice embryos die in utero between Day 13 and Day 16. HHEX knockout mice display a range of abnormalities including forebrain abnormalities in various levels of severity, as well as a number of other defects including heart, vasculature, liver, monocyte, and thyroid abnormalities. The HHEX protein is important in a variety of cancers and it can act as an tumour suppressor protein or as an oncoprotein depending on the cancer type.
Interactions
HHEX has been shown to interact with Promyelocytic leukemia protein.
References
Further reading
External links
Transcription factors | HHEX | [
"Chemistry",
"Biology"
] | 435 | [
"Induced stem cells",
"Gene expression",
"Transcription factors",
"Signal transduction"
] |
14,764,250 | https://en.wikipedia.org/wiki/HMGN1 | Non-histone chromosomal protein HMG-14 is a protein that in humans is encoded by the HMGN1 gene.
Function
Chromosomal protein HMG14 and its close analog HMG17 (MIM 163910) bind to the inner side of the nucleosomal DNA, potentially altering the interaction between the DNA and the histone octamer. The 2 proteins may be involved in the process that maintains transcribable genes in a unique chromatin conformation. Their ubiquitous distribution and relative abundance, as well as the high evolutionary conservation of the DNA-binding domain of the HMG14 family of proteins, suggest that they may be involved in an important cellular function.
Interactions
HMGN1 has been shown to interact with YWHAZ.
See also
HMGN2
High mobility group protein HMG14 and HMG17
References
Further reading | HMGN1 | [
"Chemistry"
] | 178 | [
"Biochemistry stubs",
"Protein stubs"
] |
14,764,284 | https://en.wikipedia.org/wiki/Regular%20modal%20logic | In modal logic, a regular modal logic is a modal logic containing (as axiom or theorem) the duality of the modal operators:
and closed under the rule
Every normal modal logic is regular, and every regular modal logic is classical.
References
Chellas, Brian. Modal Logic: An Introduction. Cambridge University Press, 1980.
Logic
Modal logic | Regular modal logic | [
"Mathematics"
] | 79 | [
"Mathematical logic",
"Modal logic"
] |
14,764,542 | https://en.wikipedia.org/wiki/PRDM1 | PR domain zinc finger protein 1, or B lymphocyte-induced maturation protein-1 (BLIMP-1), is a protein in humans encoded by the gene PRDM1 located on chromosome 6q21. BLIMP-1 is considered a 'master regulator' of hematopoietic stem cells, and plays a critical role in the development of plasma B cells, T cells, dendritic cells (DCs), macrophages, and osteoclasts. Pattern Recognition Receptors (PRRs) can activate BLIMP-1, both as a direct target and through downstream activation. BLIMP-1 is a transcription factor that triggers expression of many downstream signaling cascades. As a fine-tuned and contextual rheostat of the immune system, BLIMP-1 up- or down-regulates immune responses depending on the precise scenarios. BLIMP-1 is highly expressed in exhausted T-cells – clones of dysfunctional T-cells with diminished functions due to chronic immune response against cancer, viral infections, or organ transplant.
Function
As a potent repressor of beta-interferon (IFN-β), BLIMP-1 competes for interferon regulatory factors (IRF) binding sites in the IFN-β promoter due to its sequence similarity with IRF1 and IRF2. However, BLIMP-1 cools down and activates immune responses in a highly contextual manner. BLIMP-1 represses NFκB/TNF-R pathway repressor NLRP12, thus indirectly activating the immune response. BLIMP-1 expression is also upregulated by danger signals from double-stranded RNA (specific to virus), lipopolysaccharides (specific to gram-negative bacteria), unmethylated CpG DNA (abundant in bacterial genomes), and cancer inflammation via Toll-like receptor (TLR) 3, TLR-4, TLR-9, and STAT signaling, respectively.
The increased expression of the BLIMP-1 protein in B lymphocytes, T lymphocytes, NK cells and other immune system cells leads to an immune response through proliferation and differentiation of antibody secreting plasma cells. In a monocytic cell line, over-expression of BLIMP-1 can lead to differentiation into mature macrophages. BLIMP-1 also plays a role in osteoclastogenesis as well as in the modulation of dendritic cells. Other cells of the immune system such as human peripheral blood monocytes and granulocytes also express BLIMP-1.
As a transcriptional repressor, BLIMP-1 has a critical role in the foundation of the mouse germ cell lineage, as its disruption causes a block early in the process of primordial germ cell formation. BLIMP-1-deficient mutant embryos form a tight cluster of about 20 primordial germ cell-like cells, which fail to show the characteristic migration, proliferation and consistent repression of homeobox genes that normally accompany specification of primordial germ cells. BLIMP-1 is widely expressed in stem cells of developing embryos. The genetic lineage-tracing experiments indicate that the BLIMP-1-positive cells originating from the proximal posterior epiblast cells are indeed the lineage-restricted primordial germ cell precursors.
B cell development
BLIMP-1 is an important regulator of plasma cell differentiation. During B cell development, a B cell can either differentiate into a short-lived plasma cell or into a germinal center B cell after receiving proper activation and co-stimulation. BLIMP-1 acts as a master gene regulating the transcriptional network that regulates B cell terminal differentiation. Except for naïve and memory B cells, all antibody secreting cells express BLIMP-1 regardless of their location and differentiation history. BLIMP-1 directly initiates unfolded protein response (UPR) by activating Ire1, Xbp1, and Arf6, allowing the plasma B cells to produce vast amounts of antibody. BLIMP-1 expression is carefully controlled: the expression of BLIMP-1 is low or undetectable in primary B cells, and only upregulated in plasmablasts and plasma cells. BLIMP-1 is a direct transcriptional target of IRF-4, which is also necessary for B-cell differentiation. The premature expression of BLIMP-1 in primary B cells results in cell death, so only cells that are ready to initiate transcription driven by BLIMP-1 are able to survive and differentiate. However, without BLIMP-1, proliferating B cells are unable to differentiate to plasma cells, resulting in severe reduction in production of all isotypes of immunoglobulin.
T cell development
BLIMP-1 promotes naive T-cells to differentiate into T-helper (Th) 2 lineage, while repressing the differentiation into Th1, Th17, and follicular Th. BLIMP-1 is also required for differentiation of cytotoxic T-cell. Specifically, the expression of granzyme B (a source of cytotoxicity) in Tc depends on the presence of BLIMP-1 and interleukin-2 (IL-2) cytokine.
BLIMP-1 is a gatekeeper of T-cell activation and plays a key role in maintaining normal T cell homeostasis. BLIMP-1 deficiency leads to high numbers of activated T helper cells and severe autoimmune diseases in laboratory mice. BLIMP-1 is important in dampening autoimmunity, as well as antiviral and antitumor responses. BLIMP-1 regulates T cell activation through a negative feedback loop: T cell activation leads to IL-2 production, IL-2 leads to PRDM1 transcription, and BLIMP-1 feeds back to repress IL-2 gene transcription.
T cell exhaustion
Multiple studies have reported high expression of BLIMP-1 in exhausted T cells. T cell exhaustion is usually a result of chronic immune activations, commonly caused by viral infection (e.g. HIV), cancer, or organ transplant. High expression of BLIMP-1 in Tc and Th cells is associated with the transcription of receptors inhibiting immune responses, though it is unclear whether the relation between BLIMP-1 expression and T-cell exhaustion is causal or just associative.
BLIMP-1 helps the production of short-lived effector T cells and clonally exhausted T cells. It also helps with the migration of T cells out of the spleen and lymph nodes into peripheral tissues. However, BLIMP-1 does not promote the production of long-lived effector memory cells. BLIMP-1 allows the production of some longer lived effector memory cells but its absence allows for the generation of long term central memory cells, which are thought to have a higher potential of proliferation on secondary challenge.
DCs and macrophages development
BLIMP-1 has been shown in vitro as a cell lineage determinant in monocytes, inducing their differentiation into DCs and macrophages. It is speculated to have the similar effects in vivo. In addition, BLIMP-1 also suppressed myeloid cells from differentiating into granulocytes, which includes eosinophil, basophil, and neutrophils. The role of BLIMP-1 in DCs and macrophages development is a matter of interest because analysis have suggested that DCs, rather than B-cells, is the way in which individual with single nucleotide polymorphisms (SNP) near BLIMP-1 (specifically, rs548234 in Han Chinese, and rs6568431 in European) are predisposed to Systemic Lupus Erythematosus (SLE).
Osteoclast development
Osteoclasts are multinucleated cells that break down and resorb bone tissues. Together with osteoblasts, which form new bones, osteoclast helps maintain and repair bone in vertebrates. BLIMP-1 directly and indirectly represses anti-osteoclastogenesis genes such as Bcl6, IRF8, and MafB, helping monocytes differentiate into osteoclasts. In mice, insufficient expression of BLIMP-1 in osteoclast progenitors would lead to abnormal development of the skeleton.
Diseases related to BLIMP-1
SNPs near the PRDM1 gene have been identified in genome-wide association studies (GWAS) to be linked to lupus (SLE) and rheumatoid arthritis (RA). BLIMP-1 represses the expression of the proinflammatory cytokine Interleukin-6 (IL-6), and cathepsin S (CTSS), which promotes antigen processing and presentation. BLIMP-1 deficiency and IL-6 overexpression were linked to inflammatory bowel disease (IBD) and SLE.
Another GWAS has identified two genetic variations near the PRDM1 gene that predict an increased likelihood of developing a second cancer after radiation treatment for Hodgkin lymphoma.
References
Further reading
External links
Transcription factors | PRDM1 | [
"Chemistry",
"Biology"
] | 1,971 | [
"Induced stem cells",
"Gene expression",
"Transcription factors",
"Signal transduction"
] |
14,764,730 | https://en.wikipedia.org/wiki/PAX4 | Paired box gene 4, also known as PAX4, is a protein which in humans is encoded by the PAX4 gene.
Function
This gene is a member of the paired box (PAX) family of transcription factors. Members of this gene family typically contain a paired box domain, an octapeptide, and a paired-type homeodomain. These genes play critical roles during fetal development and cancer growth. The paired box gene 4 is involved in pancreatic islet development and mouse studies have demonstrated a role for this gene in differentiation of insulin-producing beta cells.
See also
Pax genes
Maturity onset diabetes of the young type 9
References
Further reading
External links
Transcription factors | PAX4 | [
"Chemistry",
"Biology"
] | 141 | [
"Induced stem cells",
"Gene expression",
"Transcription factors",
"Signal transduction"
] |
14,765,089 | https://en.wikipedia.org/wiki/TFCP2 | Alpha-globin transcription factor CP2 is a protein that in humans is encoded by the TFCP2 gene.
TFCP2 is also called Late SV40 factor (LSF) and it is induced by well-known oncogene AEG-1. LSF also acts as an oncogene in hepatocellular carcinoma. LSF enhances angiogenesis by transcriptionally up-regulating matrix metalloproteinase-9 (MMP9).
Along with its main oncogene function in hepatocellular carcinoma (HCC), it plays multifaceted role in chemoresistance, epithelial-mesenchymal transition (EMT), allergic response, inflammation and Alzheimer's disease. The small molecule FQI1 (factor quinolinone inhibitor 1) prevents LSF from binding with HCC DNA, which results in HCC cell death.
Interactions
TFCP2 has been shown to interact with APBB1 and RNF2.
References
Further reading
Transcription factors | TFCP2 | [
"Chemistry",
"Biology"
] | 220 | [
"Induced stem cells",
"Gene expression",
"Transcription factors",
"Signal transduction"
] |
14,765,455 | https://en.wikipedia.org/wiki/Green%20hosting | Green hosting or eco-friendly hosting is Internet hosting that involves strategies to reduce the environmental impact of their activities. These may include the increased use of renewable energy, planting trees, plants, and grass around and over data centers, and more day-to-day activities such as energy conservation and the use of energy-saving appliances.
Green hosting may also utilize green marketing to ease consumer concerns, and carbon offsetting, the purchasing of green certificates to offset carbon emissions. A deceitful web hosting service may participate in greenwashing where the eco-friendly marketing term does not reflect reality.
Take up
Adoption of green hosting was initially very slow in the early 2000s, largely because the hosting companies who were providing these services initially were doing at premium price. There was also limited awareness regarding green hosting among customers and how it helped the environment. Today, though, the market has changed dramatically, with many hosting companies offering green services at no additional cost. Consumer awareness has also increased. A recent study of 543 US adults found that more than 60 percent of people are more inclined to purchase from an online shop if the website explicitly claims to use green energy. Seventy-eight percent of consumers say that the environmental practices of online shops are important to them and over 70 percent believe that using a green hosting provider is a valid and acceptable way for a website to put across its green image.
World Internet usage statistics show that internet usage is still rapidly growing in the U.S. and growing from 400 to 1000% a year worldwide. In fact, in 2005, Jonathan Koomey reported that the total electric bill to operate those servers and related infrastructure equipment was $2.7 billion in the United States and $7.2 billion worldwide. a web server, on average, produces more than 630 kg of CO2 and consumes 1,000 kWh of energy annually. A green host, on the other hand, theoretically has zero . In 2008, it was estimated that if energy consumption due to web hosting keeps rising at the then-current rate by 2020, then the industry would be polluting the planet more than the airline industry.
The percentage of electricity consumption varies between organizations, but the United States Department of Energy estimates that 10 percent of the United States federal government's electricity use goes to data centers.
Green hosting strategies
A green organization does not necessarily have to have access to green power from wind, water, or solar energy, they can also purchase green certificates to offset the use and cost of conventional energy. Hosting sites that contain Green-e certification labels are organizations that voluntarily adhere to strict environmental guidelines. Other recognized certificates that regularly used in the web hosting industry include The Gold Standard, Green Power Partnership, VCS (Verified Carbon Standard), and Climate Action Reserve.
See also
Green computing
Internet hosting
Web hosting service
Clustered web hosting
References
Web hosting
Computers and the environment | Green hosting | [
"Technology"
] | 575 | [
"Computers and the environment",
"Computing and society",
"Computers"
] |
14,765,571 | https://en.wikipedia.org/wiki/Variable%20value%20stamp | A variable value stamp is a gummed or self-adhesive postage stamp of a common design, issued by a machine similar to an automatic teller machine (ATM), with a value of the user's choice printed at the time the stamp is dispensed. The value may be variable or from a fixed selection of postal rates. The stamps and machines are typically for use in retail or post office environments. As only the postal value varies from stamp to stamp, these stamps have been described as key type stamps. They are also closely related to meter stamps from postage meters.
As the concept has developed, a variety of different names have been used, including Automatenmarken (Germany), Computer vended postage stamp, ATM stamps (US), Autopost stamps (US), Frama labels (Europe) or machine labels (Stanley Gibbons catalogues).
History
There have been many experiments with similar systems over the years but none has been truly successful until the evolution of modern sophisticated computer printing technology. The development of the postage meter, which performs a similar function in businesses and organisations has also been instrumental in developing the technology.
The first patent for a machine to produce variable postage was taken out by Carl Bushe in 1884. In 1900 Christian Kahrs' machine was tested in Oslo. Similar machines were soon tried in Australia, New Zealand and the United States.
Frama labels
The Frama company of Switzerland produced a special type of patterned paper suitable for dispensing by machine and electronic printing that could be used to create an unlimited number of different stamp designs. The British Post Office used the paper experimentally in vending machines in 1984–85 but the experiment was not regarded as a success. Frama labels were also introduced in Switzerland in 1976. Frama labels were distinctive for the whole design being printed in one operation onto the special paper, including the value, rather than just the value being printed onto a pre-printed stamp.
ATM stamps and Autopost
The U.S. Postal Service experimented with similar stamps in 1989–90. Those experiments also were not considered a success. The U.S. Postal Service owns a patent for an ATM dispensable self-adhesive postage stamp construction.
Collecting
ATEEME, the Variable Value Stamps Study and Collecting Group, specializes in collecting these items.
InfoBrief: ATM. Ein Kulleraugen-Informationsdienst (Schellerten), (since October 1984)
See also
Horizon label
Post & Go stamps
References
Further reading
Tast, Hans-Jürgen; Abenteuer schreiben - Briefe, Reisen, Automaten (Schellerten 2008)
InfoBrief: ATM. Ein Kulleraugen-Informationsdienst (Schellerten), (since October 1984)
External links
ATEEME website
Postal systems
Philatelic terminology | Variable value stamp | [
"Technology"
] | 579 | [
"Transport systems",
"Postal systems"
] |
14,765,577 | https://en.wikipedia.org/wiki/TRIM24 | Tripartite motif-containing 24 (TRIM24) also known as transcriptional intermediary factor 1α (TIF1α) is a protein that, in humans, is encoded by the TRIM24 gene.
Function
The protein encoded by this gene mediates transcriptional control by interaction with the activation function 2 (AF2) region of several nuclear receptors, including the estrogen, retinoic acid, and vitamin D3 receptors. The protein localizes to nuclear bodies and is thought to associate with chromatin and heterochromatin-associated factors. The protein is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains – a RING, a B-box type 1 and a B-box type 2 – and a coiled-coil region. Two alternatively spliced transcript variants encoding different isoforms have been described for this gene.
Interactions
TRIM24 has been shown to interact with Mineralocorticoid receptor, TRIM33, Estrogen receptor alpha and Retinoid X receptor alpha.
See also
Transcription coregulator
References
Further reading
External links
Gene expression
Transcription coregulators | TRIM24 | [
"Chemistry",
"Biology"
] | 233 | [
"Gene expression",
"Molecular genetics",
"Cellular processes",
"Molecular biology",
"Biochemistry"
] |
14,765,980 | https://en.wikipedia.org/wiki/Hatley%E2%80%93Pirbhai%20modeling | Hatley–Pirbhai modeling is a system modeling technique based on the input–process–output model (IPO model), which extends the IPO model by adding user interface processing and maintenance and self-testing processing.
Overview
The five components—inputs, outputs, user interface, maintenance, and processing—are added to a system model template to allow for modeling of the system which allows for proper assignment to the processing regions. This modeling technique allows for creation of a hierarchy of detail of which the top level of this hierarchy should consist of a context diagram. The context diagram serves the purpose of "establish[ing] the information boundary between the system being implemented and the environment in which the system is to operate." Further refinement of the context diagram requires analysis of the system designated by the shaded rectangle through the development of a system functional flow block diagram. The flows within the model represent material, energy, data, or information.
References
Systems engineering
Software analysis patterns | Hatley–Pirbhai modeling | [
"Engineering"
] | 198 | [
"Software engineering",
"Systems engineering",
"Software engineering stubs"
] |
14,766,130 | https://en.wikipedia.org/wiki/EEF1G | Elongation factor 1-gamma is a protein that in humans is encoded by the EEF1G gene.
Function
This gene encodes a subunit of the elongation factor-1 complex, which is responsible for the enzymatic delivery of aminoacyl tRNAs to the ribosome. This subunit contains an N-terminal glutathione transferase domain, which may be involved in regulating the assembly of multisubunit complexes containing this elongation factor and aminoacyl-tRNA synthetases.
Interactions
EEF1G has been shown to interact with:
EEF1B2,
EEF1D,
HARS,
LZTS1,
LARS, and
RECQL5.
References
Further reading | EEF1G | [
"Chemistry"
] | 153 | [
"Biochemistry stubs",
"Protein stubs"
] |
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