text:
Black 47

Black 47 was an American Celtic rock band from New York City, formed in 1989 by Larry Kirwan and Chris Byrne, and derives its name from a traditional term for the summer of 1847, the worst year of the Great Famine in Ireland.

Beginnings
Kirwan originally arrived in New York City from Wexford aged 19, and played in a succession of bands before teaming with Byrne, a Brooklyn policeman, in 1989. The combination of Kirwan's electric guitar and Byrne's use of traditional Irish instruments initially received a poor reception, but a year later, with the addition of new members Geoff Blythe (founding member of Dexy's Midnight Runners), Fred Parcells and Thomas Hamlin, they were playing regularly at Paddy Reilly's bar on Manhattan's East Side. The band began to play three to five nights a week, and garnered praise for both the socio-political lyrics and "off-the-wall" live shows, quickly drawing a fan base from both the political left and right. Kirwan stated in an interview that the band was "formed to be political", with the socialist lyrics attracting one half of the political spectrum, and the songs of the day-to-day life in America attracting traditionally right-leaning "cops, firemen and construction workers."

Breakout
The band got their first big break when their debut release, Home of the Brave, launched as a cassette at a St. Patrick's day gig at Reilly's in 1990, was heard by Frank Murray, manager of The Pogues, who signed them to his newly launched label. They went on to open for The Pogues at Brixton Academy in December of the same year, and following the collapse of Murray's label the band released an eponymous independent album in 1991, which brought them to the attention of EMI. They went into the studio with Ric Ocasek of The Cars, where they re-recorded parts of their self-titled album for the 1992 release of Fire of Freedom, which was described as "the most fun you can squeeze out of a five-inch disc." and drew comparisons with Kevin Rowland and Bruce Springsteen. Black 47 gained access to a significantly wider audience when "Funky Céilí (Bridie's Song)", a track from Fire of Freedom gained extended air-play on music channel MTV, becoming the band's breakout single. The song was praised for the use of a traditional jig, riotous conclusion and as "a knockout example of how Irish music can rock." A second song from the album, "Black 47", caused a stir amongst older fans of Irish music who had maintained close emotional ties to their ancestors who lived during the famine, traditionally a subject rarely addressed in song. The band followed up with Home of the Brave in 1994 with Jerry Harrison serving as producer, and a move from EMI to Mercury Records in 1996 followed with the release of Green Suede Shoes.

Throughout the late 1990s the band continued to perform around 150 nights a year both on tour and at Reilly's, but was plagued by a series of tragedies behind the scenes, and their political stance on affairs in Northern Ireland resulted in UK record companies being unwilling to support or promote the band, restricting a potentially lucrative market. At the 1996 St. Patrick's Day gig a very inebriated 22-year-old off-duty police officer, Christopher Gargan, used his department issued 9mm pistol to shoot himself in the head and the single bullet also injured Sharon Callahan-Wormworth and June Anderson, tour manager Nico Wormworth's wife and Kirwan's wife, respectively. In 1997 one of the band's sound engineers, Johnny Byrne (immortalised in the band's single "Johnny Byrne's Jig"), died from injuries suffered after falling from his apartment window in New York City not long after recording an album of children's songs with Kirwan. The late 1990s also saw band member Thomas Hamlin's apartment burn down, Kevin Jenkins retire after a car crash whilst on tour and John Murphy, a close friend of the band, die after falling into a coma after a motorcycle accident. These events are reflected upon in "Those Saints", a song on the Trouble in the Land album, released in 2000. 2000 also saw the release of the band's first compilation album to mark their tenth anniversary, Ten Bloody Years, and the departure of Byrne who amicably left the band to concentrate on his solo project, Seanchai and the Unity Squad.

Post Byrne
Black 47 went on an unofficial recording hiatus, although they maintained their live performances, influenced as much by the events of 9/11 as the departure of Byrne. The release of New York Town in 2004 reflected the city before and after the attacks, where a number of Black 47 fans, such as FDNY chaplain Mychal Judge, honoured in the song "Mychal", were casualties. Post-9/11 Black 47 had started to play regularly at Connolly's Pub in midtown Manhattan, playing shows Kirwan described as intense in order to allow fans who had lost loved ones an outlet for their emotions, and this was channelled into making the album. New York Town was a critical success, drawing parallels to Joyce's Dubliners due to it being a series of short, unrelated stories centered around New York City, and Kirwan was praised for painting a picture of the everyday life of New Yorkers, although the appearance of guest singers such as David Johansen of the New York Dolls and Christine Ohlman was noted for highlighting the weakness in Kirwan's own voice.

Following the release of Elvis Murphys Green Suede Shoes, a companion to Kirwan's memoir, Green Suede Shoes - An Irish-American Odyssey in 2005, the band released a second greatest hits album, Bittersweet Sixteen in 2006 to celebrate sixteen years. Elvis Murphy was generally well received, as despite the lyrics at times having literary 'problems' it was considered challenging yet enjoyable and for making "real emotional sense" and touching both the heart and soul. Bittersweet Sixteen was praised for being both a great introduction to the band and a treasure for seasoned fans, containing rare tracks such as the original version of "Funky Céilí".

Prior to the invasion of Iraq in 2003, the band became outspoken critics of the potential war, speaking out regularly at gigs. When the invasion was announced they were playing live, and due to the political mix the band attracted some fans begun to scuffle and walk out in response to the left-leaning lyrics of the anti-war songs. They released a collection of such songs in 2008 on an album simply titled Iraq. Inspiration for the lyrics came from Kirwan's communication with fans serving on the front line, as a significant demographic of the fanbase is young men who enlist to fund their futures. Kirwan called the album a response to the war being forgotten about, as stories moved away from the front pages, drawing similarities in the way violence in Northern Ireland became 'acceptable'.

The band returned to drawing from a wider ranger of subjects with their 2010 album Bankers and Gangsters. It was noted that this album, unsurprisingly, was less political than its predecessor, and was also criticised for returning to the safe haven and not bringing anything new to the band's discography. However the album was generally well received, with praise going to the high standard of Kirwan's storytelling ability so far into the band's lifetime as well as the "rollicking spirit" of the bands. Kirwan relates his noted ability and passion in biographical songs such as "Bobby Sands MP" to his time spent as a playwright, likening his performance singing them to method acting. The album has also been considered one of the band's best, referencing the "sharp social commentary and genre-bending sounds."

Disbanding
On September 18, 2013 Black 47 issued this statement: "In early November 2014, exactly 25 years after our first gig, Black 47 will disband. There are no fights, differences over musical policy, or general skulduggery, we remain as good friends as when we first played together. We just have a simple wish to finish up at the top our game after 25 years of relentless touring and, as always, on our own terms. The last gig we played at the South Buffalo Irish Festival was as good as any we've ever performed. Our goal now is to play another full year plus and dedicate all of those gigs to you who've supported us through thick and thin. Rather than just running out the clock we will be recording "Last Call," an album of new songs in November and as usual will be working out the material onstage. We would like to say goodbye to you all personally and will make every effort to come play in your city, town, college, pub, club, [and] performing arts center. Black 47 has always been more than a band, we've spoken out for the nationalist population in the North of Ireland, against the war but for the troops in Iraq, for our gay brothers & sisters, immigrants, legal and undocumented, as well as for the voiceless of 1845-47; but in the end it all comes down to the music, the songs, and the desire to give audiences the time of their lives and send them home smiling and, perhaps, with a question on their lips. We look forward to seeing you all at the upcoming gigs. Thanks for the support and the memories - lets make many more over the next year."

Politics
A 1993 Time magazine article on Irish rock in America said it was "the proletariat passion of Black 47's songs that make the group stand out."

Irish Republicanism
In an early interview Kirwan spoke of the British "attempt at racial cleansing" and exploitation in Ireland, and many of the band's songs directly relate to Irish republicanism, such as "James Connolly", "Bobby Sands MP" and "Vinegar Hill". The presence of this content has at times brought criticism on the band from listeners who are politically neutral to the situation, as well as restricting their promotion in the UK. Speaking of the period that inspired the band name, Kirwan said, "I'm not one of those people who believe the British did [the famine] on purpose... But what they did do was they allowed millions of people to starve and leave the land because they didn't want to change the particular economic system they had at the time."

They have been described as 'the musical wing of the IRA’.

Iraq War
On top of the Iraq album, Kirwan noted that the war was one which "the working class is fighting". He also stated that politicians wasted an opportunity (after 9/11) to change the world for the better, placing most blame on the shoulders of then-president Bush Kirwan argued that had there been a Churchill-esque leader then America would have taken the opportunity to rid themselves of dependence on foreign oil, and change the way America communicated with the rest of the world. He also criticised Bush for using the memory of the victims of 9/11 to justify war as the biggest tragedy that came out of the event.

Concert recording
Kirwan actively encourages the videotaping, recording and photography of Black 47's live shows, citing that no two shows are the same and its good to have a record of it. The band's official website has also encouraged US soldiers posted in the Middle East to pass around bootlegged copies of albums.

Criticism
Black 47 band has been criticized as most members only have a tenuous link to Ireland. Ed Power of The Guardian noting their minuscule connection with Ireland as being ‘sweet feck all to do with Oscar Wilde, Christy Ring or Samuel Beckett.’

They have been described as 'the musical wing of the IRA’, which was a paramilitary organisation in Northern Ireland and was designated a terrorist organisation in the United Kingdom and an illegal organisation in the Republic of Ireland. The IRA have been held responsible for the killing of 1,705 people during The Troubles, including many civilians.

Influence
They have been recognised as "the premier Irish-American rock group" who created an environment where bands such as Dropkick Murphys and Flogging Molly have been able to flourish.

Band members

 * Geoffrey Blythe: tenor saxophone, soprano saxophone, clarinet
 * Joseph "Bearclaw" Burcaw : bass, vocals
 * Thomas Hamlin : drums, percussion
 * Larry Kirwan : lead vocals, guitar
 * Joseph Mulvanerty : uilleann pipes, flute, bodhrán
 * Fred Parcells : trombone, tin whistle

 * Past members
 * Chris Byrne : uilleann pipes, tin whistle, bodhrán and vocals (1989–2000)
 * David Conrad : bass (1991–1993)
 * Erik Boyd : bass (1993-1994)
 * Kevin Jenkins : bass (1994–1995)
 * Andrew Goodsight: bass (1995–2006)

title: Black 47


text:
Firedamp

Firedamp is any flammable gas found in coal mines, typically coalbed methane. It is particularly found in areas where the coal is bituminous. The gas accumulates in pockets in the coal and adjacent strata and when they are penetrated the release can trigger explosions. Historically, if such a pocket was highly pressurized, it was termed a "bag of foulness".

Name
Damp is the collective name given to all gases (other than air) found in coal mines in Great Britain and North America.

As well as firedamp, other damps include blackdamp (nonbreathable mixture of carbon dioxide, water vapour and other gases); whitedamp (carbon monoxide and other gases produced by combustion); poisonous, explosive stinkdamp (hydrogen sulfide), with its characteristic rotten-egg odour; and the insidiously lethal afterdamp (carbon monoxide and other gases) which are produced following explosions of firedamp or coal dust.

Etymology
Often hyphenated as fire-damp, this term for a flammable type of underground mine gas in first part derives via the Old English fyr, and from the proto-Germanic fūr for "fire" (the origin of the same word in Dutch and German, with similar original spellings in Old Saxon, Frisian, and Norse, as well as Middle Dutch and Old High German). In the second part, the meaning of "damp" (most commonly understood to imply humidity) presents evidence of having been separated from that newer, irrelevant meaning at least by the first decade of the 18th century, where the original relevant meaning of "vapor" also derives from a Proto-Germanic origin, dampaz, which gave rise to its immediate English predecessor, the Middle Low German damp (with no record of an Old English intermediary). As with the derivation of the first, the proto-Germanic dampaz gave rise to many other cognates, including the Old High German damph, the Old Norse dampi, and the modern German Dampf, the last of which still translates as "vapor".

Contribution to mine deaths
Firedamp is explosive at concentrations between 4% and 16%, with most explosions occurring at around 10%. It caused many deaths in coal mines before the invention of the Geordie lamp and Davy lamp. Even after the safety lamps were brought into common use, firedamp explosions could still be caused by sparks produced when coal contaminated with pyrites was struck with metal tools. The presence of coal dust in the air increased the risk of explosion with firedamp and could cause explosions even in the absence of firedamp. The Tyneside coal mines in England had the deadly combination of bituminous coal contaminated with pyrites and there was a great number of deaths in accidents caused by firedamp explosions, including 102 dead at Wallsend in 1835.

The problem of firedamp in mines had been brought to the attention of the Royal Society by 1677 and in 1733 James Lowther reported that as a shaft was being sunk for a new pit at Saltom near Whitehaven there had been a major release when a layer of black stone had been broken through into a coal seam. Ignited with a candle, it had given a steady flame "about half a Yard in Diameter, and near two Yards high". The flame being extinguished and a wider penetration through the black stone made, reigniting of the gas gave a bigger flame, a yard in diameter and about three yards high, which was extinguished only with difficulty. The blower was panelled off from the shaft and piped to the surface, where more than two and a half years later it continued as fast as ever, filling a large bladder in a few seconds. The society members elected Sir James Fellow but were unable to come up with any solution nor improve on the assertion (eventually found to be incorrect) of Carlisle Spedding, the author of the paper, that "this sort of Vapour, or damp Air, will not take Fire except by Flame; Sparks do not affect it, and for that Reason it is frequent to use Flint and Steel in Places affected with this sort of Damp, which will give a glimmering Light, that is a great Help to the Workmen in difficult Cases."

A great step forward in countering the problem of firedamp came when safety lamps, intended to provide illumination whilst being incapable of igniting firedamp, were proposed by both George Stephenson and Humphry Davy in response to accidents such as the Felling mine disaster near Newcastle upon Tyne, which killed 92 people on 25 May 1812. Davy experimented with brass gauze, determining the maximum size of the gaps and the optimum wire thickness to prevent a flame passing through the gauze. If a naked flame was thus enclosed totally by such a gauze, then methane could pass into the lamp and burn safely above the flame. Stephenson's lamp (the "Geordie lamp") worked on a different principle: the flame was enclosed by glass; air access to the flame was through tubes sufficiently narrow that the flame could not burn-back in incoming firedamp and the exiting gases were too low in oxygen to allow the enclosed flame to reach the surrounding atmosphere. Both principles were combined in later versions of safety lamps.

Even after the widespread introduction of the safety lamp, explosions continued because the early lamps were fragile and easily damaged. For example the iron gauze on a Davy lamp needed to lose only one wire to become unsafe. The light was also very poor (compared with a naked flame) and there were continuous attempts to improve the basic design. The height of the cone of burning methane in a flame safety lamp can be used to estimate the concentration of the gas in the local atmosphere. It was not until the 1890s that safe and reliable electric lamps became available in collieries.

The Firedamp whistle was developed by Fritz Haber in 1913, as a prophylactic indicator of firedamp, but calibration in a working colliery ultimately proved impractical.

license: Creative Commons - Attribution Share-Alike - https://creativecommons.org/licenses/by-sa/4.0/

title: Firedamp


text:
Robert Barton

Robert Childers Barton (14 March 1881 – 10 August 1975) was an Anglo-Irish politician, Irish nationalist and farmer who participated in the negotiations leading up to the signature of the Anglo-Irish Treaty. His father was Charles William Barton and his mother was Agnes Alexandra Frances Childers. His wife was Rachel Warren of Boston, daughter of Fiske Warren. His double first cousin and close friend was Erskine Childers.

Early life
He was born in County Wicklow into a wealthy Irish Protestant land-owning family; namely of Glendalough House. Educated in England at Rugby and Oxford, he became an officer in the Royal Dublin Fusiliers on the outbreak of World War I. He was stationed in Dublin during the 1916 Easter Rising and came into contact with many of its imprisoned leaders in the aftermath while on duty at Richmond Barracks. He resigned his commission in protest at the heavy-handed British government suppression of the revolt. He then joined the Irish Republican Brotherhood.

Family
Charles William Barton (father) was born on 13 July 1836. He married Agnes Alexandra Frances Childers, daughter of Rev. Canon Charles Childers, on 26 October 1876. He died on 3 October 1890 at age 54. Robert's two younger brothers, Erskine and Thomas, died in the British Army during World War I.

Politics
At the 1918 general election to the British House of Commons Barton was elected as the Sinn Féin member for Wicklow West. In common with all Sinn Féin members, he boycotted the Westminster parliament and sat instead in Dáil Éireann (the First Dáil). Arrested in February 1919 for sedition, he escaped from Mountjoy Prison on St. Patrick's Day (leaving a note to the governor explaining that, owing to the discomfort of his cell, the occupant felt compelled to leave, and requesting the governor to keep his luggage until he sent for it). He was appointed as Director of Agriculture in the Dáil Ministry in April 1919. He was recaptured in January 1920 and sentenced to three years' imprisonment, but was released under the general amnesty of July 1921.

In May of that year, prior to his release, he was elected as a Sinn Féin member for Kildare–Wicklow in the 1921 Irish election to the House of Commons of Southern Ireland. Once again all Sinn Féin members boycotted this parliament, sitting as the Second Dáil. In August 1921, he was appointed to cabinet as Secretary for Economic Affairs.

Barton was one of the Irish plenipotentiaries to travel to London for the Anglo-Irish Treaty negotiations. His cousin was a secretary to the delegation. Barton reluctantly signed the Treaty on 6 December 1921, defending it "as the lesser of two outrages forced upon me and between which I had to choose".

Although he had signed the Treaty and voted for it in the Dáil, he stood for election in June 1922 for Anti-Treaty Sinn Féin, the only TD who had voted for the Treaty to do so, and won a seat in the Third Dáil. In common with other Anti-Treaty TDs, he did not take his seat. In October 1922 he was appointed Minister for Economic Affairs in de Valera's "Emergency Government", a shadow government in opposition to the Provisional Government and later to the Executive Council of the Irish Free State. Barton's memoir of this period was completed in 1954, and can be seen on the Bureau of Military History website. He was arrested and interned for most of the war at the Curragh Camp.

He was defeated at the 1923 general election, and retired from politics for the law, practicing as a barrister. He later became a judge. He was chairman of the Agricultural Credit Corporation from 1934 to 1954. Barton died at home in County Wicklow on 10 August 1975, at the age of 94, the last surviving signatory of the Anglo-Irish Treaty. Éamon de Valera died only nineteen days later, on 29 August 1975.

Interview
In 1969, RTÉ Television interviewed Barton, alongside Ernest Blythe and James Ryan about the 1918 general election.

Glendalough House
Glendalough House, run by Barton for over 70 years right up until his death, is still considered one of Ireland's most notable properties, alongside nearby Powerscourt Estate. The house was the center of numerous political meetings and gatherings from 1910 to 1922. It's also been featured as a location in many large Hollywood films including Excalibur, Saving Private Ryan and Braveheart.

Barton’s grandfather Thomas Johnston Barton, who acquired Glendalough House in 1838, was a younger son of Hugh Barton, owner of the Langoa Barton and Léoville Barton vineyards in France and co-founder of the Bordeaux wine house of Barton & Guestier. The vineyards are now owned by Lilian Barton, a descendant of Hugh Barton’s eldest son, and she and her husband Michel Sartorius added Château Mauvesin Barton to these domaines in 2011.

title: Robert Barton


text:
DnaA

DnaA is a protein that activates initiation of DNA replication in bacteria. Based on the Replicon Model, a positively active initiator molecule contacts with a particular spot on a circular chromosome called the replicator to start DNA replication. It is a replication initiation factor which promotes the unwinding of DNA at oriC. The DnaA proteins found in all bacteria engage with the DnaA boxes to start chromosomal replication. The onset of the initiation phase of DNA replication is determined by the concentration of DnaA. DnaA accumulates during growth and then triggers the initiation of replication. Replication begins with active DnaA binding to 9-mer (9-bp) repeats upstream of oriC. Binding of DnaA leads to strand separation at the 13-mer repeats. This binding causes the DNA to loop in preparation for melting open by the helicase DnaB.

Function
DnaA consists mainly in two different forms, the active ATP-form and the inactive ADP. The level of active DnaA within a cell is low immediately after a cell has divided. Although the active form of DnaA requires ATP, the formation of the oriC/DnaA complex and subsequent DNA unwinding does not require ATP hydrolysis.

The oriC site in E. coli has three AT rich 13 base pair regions (DUEs) followed by four 9 bp regions with the sequence TTAT(C or A)CA(C or A)A. Around 10 DnaA molecules bind to the 9 bp regions, which wrap around the proteins causing the DNA at the AT-rich region to unwind. There are 8 DnaA binding sites within oriC, to which DnaA binds with differential affinity. When DNA replication is about to commence, DnaA occupies all of the high and low affinity binding sites. The denatured AT-rich region allows for the recruitment of DnaB (helicase), which complexes with DnaC (helicase loader). DnaC helps the helicase to bind to and to properly accommodate the ssDNA at the 13 bp region; this is accomplished by ATP hydrolysis, after which DnaC is released. Single-strand binding proteins (SSBs) stabilize the single DNA strands in order to maintain the replication bubble. DnaB is a 5'→3' helicase, so it travels on the lagging strand. It associates with DnaG (a primase) to form the only primer for the leading strand and to add RNA primers on the lagging strand. The interaction between DnaG and DnaB is necessary to control the longitude of Okazaki fragments on the lagging strand. DNA polymerase III is then able to start DNA replication.

DnaA is made up of four domains: the first is the N-terminal that associates with regulatory proteins, the second is a helical linker region, the third domain is a AAA+ region that binds to ATP, and the fourth domain is the C-terminal DNA binding region. DnaA contains two conserved regions: the first is located in the central part of the protein and corresponds to the ATP-binding domain, the second is located in the C-terminal half and is involved in DNA-binding.

DnaA mutants
The first strains to have the dnaA gene mutated were the temperature-sensitive K-12 strains CRT46 and CRT83, with the corresponding strain numbers beingdnaA46 and dnaA83. In contrary to dnaA mutants, the PC2 strain has a mutation in the dnaC gene, which codes for the loading factor for the DNA helicase dnaB.

Synthesis
DnaA has the ability to bind its own promoter. When DnaA binds to its own promoter it blocks RNA polymerase from binding the promoter and inhibits initiation of transcription. In this way, DnaA is able to regulate its own expression. This process is called autoregulation.

Regulation
Each cell division cycle triggers a new round of chromosome replication by DnaA, the initiator protein. It is crucial to regulate DnaA-ATP monomer interactions with oriC during helicase loading and unwinding of origin DNA for precise timing. DnaA recognition sites in Escherichia coli are arranged in OriC to facilitate staged pre-replication complex assembling, with DnaA interacting with low affinity sites at it oligomerizes to fill the gaps between high affinity sites as it oligomerizes. There may be numerous gap-filling strategies to link OriC functions to bacterial lifestyles in nature, which may account for the wide variability of OriC DnaA recognition site patterns. The two forms of DnaA, the active ATP- and ADP-form are regulated. The ATP-form is converted to the ADP-form through either Regulatory inactivation of DnaA (RIDA), which in turn consists of the Hda protein and the β sliding clamp (DnaN) and datA-dependent DnaA-ATP hydrolysis. The ADP-form is converted to the ATP-form by DnaA-reactivating sequences 1 and 2 (DARS1 and DARS2).

DnaA protein structure
There are four disciplines within the DnaA protein. An initial comparison of Escherichia coli and Bacillus subtilis proteins led to the discovery of a sphere structure, which revealed a relatively conserved N-terminus and a largely conserved large C-terminus separated by a region that was mostly variable. As an example, the Enterobacterial proteins have nearly identical N- and C-terminal sequences, however they are characterized by numerous amino acid adjustments, elisions, and insertions in the variable regions. There is an AAA+ family ATPase motif and an independent DNA binding sphere in the C-terminal region. It was determined by NMR that Escherichia coli sphere IV had a crystal-clear structure when complexed with a DnaA- box. As a result, it was confirmed that the DNA list is intermediated by a combination of a helix-turn-helix motif and an introductory circle. When bound to ATP, but not to ADP, DnaA forms a super-helical structure with four monomers per turn. The structure of sphere I has been determined from three additional bacterial species and Escherichia coli by NMR.

Autoregulation of DnaA protein synthesis
The research on dnaA(Ts) mutants provided the first proof that the dnaA gene is autoregulated. DnaA protein is still produced at non-permissive temperatures where it is inactive, but in some mutants it can be made active again by returning to a temperature that is conducive to development. This reversible initiation capacity—which was larger than anticipated given the mass gain of the culture—could be seen in the absence of protein synthesis at the permissive temperature and suggested that the DnaA protein synthesis was derepressed at the high growth temperature. These results prompted a thorough investigation of the dnaA46 mutant under permissive, intermediate, and non-permissive development conditions. The study's findings revealed that as growth temperature increased, the DnaA46 protein's activity decreased, leading to progressively decreasing DNA and origin concentrations at intermediate temperatures. An increase in initiation capacity was seen concurrently with a decrease in DnaA protein activity. Hansen and Rasmussen (1977) argued that the DnaA protein had a positive effect in replication initiation aing transcripts entering the dnaA gene were found as a result of sequencing the dnaA promoter region and the dnaA gene. The DnaA promoter region has nine GATC sites within 225 base pairs, and a sequence that is similar to nd a negative role in its own synthesis based on these observations. Two promoters providrepetitions (DnaA-boxes) in the oriC region was found between the two promoters. According to several studies, the DnaA protein negatively regulates both promoters. In these research, it was discovered that the dnaA transcription was upregulated by 4- to 5-fold at non-permissive temperatures in dnaATs mutants and repressed by the same amount when DnaA protein was overproduced. The autoregulation of the dnaA gene requires the DnaA-box. The sequence of the dnaA2p promoter region has some intriguing characteristics that can be seen more clearly. This promoter contains two GATC sites, one in the 10 sequence and the other in the 35 sequence, and both in vivo and in vitro, methylation increases transcription from this promoter by a factor of two. In addition, DnaA protein binds to regions upstream of the dnaA2p promoter with a high affinity.

title: DnaA


text:
Talk:KPPP

Historical
For the VfD vote to keep this article, see

title: Talk:KPPP


text:
Eyeglass prescription

An eyeglass prescription is an order written by an eyewear prescriber, such as an optometrist, that specifies the value of all parameters the prescriber has deemed necessary to construct and/or dispense corrective lenses appropriate for a patient. If an eye examination indicates that corrective lenses are appropriate, the prescriber generally provides the patient with an eyewear prescription at the conclusion of the exam.

The parameters specified on spectacle prescriptions vary, but typically include the patient's name, power of the lenses, any prism to be included, the pupillary distance, expiration date, and the prescriber's signature. The prescription is typically determined during a refraction, using a phoropter and asking the patient which of two lenses is better, or by an automated refractor, or through the technique of retinoscopy. A dispensing optician will take a prescription written by an optometrist and order and/or assemble the frames and lenses to then be dispensed to the patient.

Sphere component
Every corrective lens prescription includes a spherical correction in diopters. Convergent powers are positive (e.g., +4.00 D) and condense light to correct for farsightedness/long-sightedness (hyperopia) or allow the patient to read more comfortably (see presbyopia and binocular vision disorders). Divergent powers are negative (e.g., −3.75 D) and spread out light to correct for nearsightedness/short-sightedness (myopia). If neither convergence nor divergence is required in the prescription, "plano" is used to denote a refractive power of zero.

The term "sphere" comes from the geometry of lenses. Lenses derive their power from curved surfaces. A spherical lens has the same curvature in every direction perpendicular to the optical axis. Spherical lenses are adequate correction when a person has no astigmatism. To correct for astigmatism, the "cylinder" and "axis" components specify how a particular lens is different from a lens composed of purely spherical surfaces.

Cylinder component
Patients with astigmatism need a cylindrical lens, or more generally a toric lens to see clearly. The geometry of a toric lens focuses light differently in different meridians. A meridian, in this case, is a plane that is incident with the optical axis. For example, a toric lens, when rotated correctly, could focus an object to the image of a horizontal line at one focal distance while focusing a vertical line to a separate focal distance.

The power of a toric lens can be specified by describing how the cylinder (the meridian that is most different from the spherical power) differs from the spherical power. Power evenly transitions between the two powers as you move from the meridian with the most convergence to the meridian with the least convergence. For regular toric lenses, these powers are perpendicular to each other and their location relative to vertical and horizontal are specified by the axis component.

There are two different conventions for indicating the amount of cylinder: "plus cylinder notation" and "minus cylinder notation". In the former, the cylinder power is a number of diopters more convergent than the sphere power. That means the spherical power describes the most divergent meridian and the cylindrical component describes the most convergent. In the minus cylinder notation, the cylinder power is a number of diopters more divergent than the sphere component. In this convention, the sphere power describes the most convergent meridian and the cylinder component describes the most divergent. Europe typically follows the plus cylinder convention while in the United States the minus cylinder notation is used by optometrists and the plus cylinder notation is used by ophthalmologists. Minus cylinder notation is also more common in Asia, although either style may be encountered there. There is no difference in these forms of notation and it is easy to convert between them: For example, a lens with a vertical power of −3.75 and a horizontal power of −2.25 could be specified as either −2.25 −1.50 × 180 or −3.75 +1.50 × 090.
 * Add the sphere and cylinder numbers together to produce the converted sphere
 * Invert the sign of cylinder value
 * Add 90° to axis value, and if the new axis value exceeds 180°, subtract 180° from the result

Axis component
The axis defines the location of the sphere and cylinder powers. The name "axis" comes from the concept of generating a cylinder by rotating a line around an axis. The curve of that cylinder is 90° from that axis of rotation. When dealing with toric lenses, the axis defines the orientation of the steepest and flattest curvatures relative to horizontal and vertical. The "3 o'clock" position is defined as zero, and the 90th meridian is a vertical line. A horizontal line passes through both zero and the 180th meridians. By convention, a horizontal axis is recorded as 180.

In a regular toric lens, the flattest and steepest curvatures are separated by 90°. As a result, the axis of the cylinder is also the meridian with the same power as the recorded sphere power. The cylinder power, as defined above is the power that is most different from the sphere power. Because they are defined relative to each other, it is important to know if the lens is being described in minus cylinder notation, where the sphere power is the most convergent / least divergent power. When using plus cylinder notation, the opposite is true.

If the lens is spherical (there is no cylinder component) then there is no need for an axis. A prescription like this is written with D.S. (diopters sphere) after the sphere power (e.g., −3.00 D.S.). This verifies that the prescription is truly spherical rather than the cylinder power being omitted in error.

Summary

 * correction power is measured in diopters
 * by convention, an axis of 90° is vertical, 0° or 180° are horizontal
 * if the cylinder power is positive, the lens is most convergent 90° from the axis
 * if the cylinder power is negative, the lens is most divergent 90° from the axis
 * if the cylinder power is zero, the lens is spherical and has the same power in every meridian

Sample prescription
A prescription of −1.00 +0.25 × 180 describes a lens that has a horizontal power of −1.00 D and a vertical power of −0.75 D. Only ophthalmologists write prescriptions in + cylinder. An optometrist would write a prescription in - (minus) cylinder. All spectacle and contact lenses would be made in minus cylinder. Therefore, the above prescription would be written as −0.75 −0.25 × 90.

Abbreviations and terms

Similar to medical prescriptions, eyeglass prescriptions are written on paper pads or included in a patient's electronic health record, and contain a number of different abbreviations and terms:
 * DV is an abbreviation for distance vision. This specifies the part of the prescription designed primarily to improve far vision. In a bifocal lens, this generally indicates what is to be placed in the top segment.
 * NV is an abbreviation for near vision. This may represent a single-vision lens prescription to improve near work, or the reading portion of a bifocal lens.
 * OD is an abbreviation for oculus dexter, Latin for right eye from the patient's point of view. Oculus means eye.
 * OS is an abbreviation for oculus sinister, Latin for left eye from the patient's point of view.
 * OU is an abbreviation for oculi uterque, Latin for both eyes.
 * N.B.: In some countries, such as the United Kingdom, RE (right eye), LE (left eye), and BE (both eyes) are used. Sometimes, just right and left are used.
 * SPH, CYL, and AXIS are values for describing the power of the lens using plus cylinder or minus cylinder notation.
 * ADD is an abbreviation for Near Addition. This is the additional refractive power to be combined, or added, to the distance power to achieve the ideal near power.
 * Prism and Base Prism refers to a displacement of the image through the lens, often used to treat strabismus and other binocular vision disorders. The prism value is measured in prism diopters, and Base refers to the direction of displacement.
 * PL is an abbreviation for plano or plain, meaning no prescription
 * PD or IPD Pupillary Distance or Interpupillary Distance, respectively. It is the distance between pupil centers.
 * BVD Back vertex distance is the distance between the back of the spectacle lens and the front of the cornea (the front surface of the eye). This is significant in higher prescriptions (usually beyond ±4.00D) as slight changes in the vertex distance for in this range can cause a power to be delivered to the eye other than what was prescribed.

title: Eyeglass prescription


text:
Index of Michigan-related articles

The following is an alphabetical list of articles related to the U.S. state of Michigan.

0–9

 * .mi.us – Internet second-level domain for the state of Michigan
 * 2020 coronavirus pandemic in Michigan

A

 * Adjacent states and province:
 * Ontario
 * Illinois
 * Indiana
 * Minnesota
 * Ohio
 * Wisconsin
 * Administrative divisions of Michigan
 * Agriculture in Michigan
 * Alger, Smith and Co.
 * Alpena News
 * Ambassador Bridge
 * Amusement parks in Michigan
 * Ann Arbor Railroad
 * Aquademics
 * Aquaria in Michigan
 * commons:Category:Aquaria in Michigan
 * Arboreta in Michigan
 * commons:Category:Arboreta in Michigan
 * Archaeological sites in Michigan
 * commons:Category:Archaeological sites in Michigan
 * Area codes in Michigan
 * Art museums and galleries in Michigan
 * commons:Category:Art museums and galleries in Michigan
 * Astronomical observatories in Michigan
 * commons:Category:Astronomical observatories in Michigan

B

 * Bath School disaster
 * Binder Park Zoo
 * Blue Water Bridge
 * Big Chief Sugar
 * Botanical gardens in Michigan
 * commons:Category:Botanical gardens in Michigan
 * Buildings and structures in Michigan
 * commons:Category:Buildings and structures in Michigan

C

 * Cabinet counties
 * Capital of the State of Michigan
 * Capitol of the State of Michigan
 * commons:Category:Michigan State Capitol
 * Casinos in Michigan
 * Cass Lake (Michigan)
 * Central Michigan
 * Chicago and West Michigan Railway
 * Christmas, Michigan
 * Chrysler Corporation
 * Cincinnati, Saginaw and Mackinaw Railroad
 * Climate of Michigan
 * Climate change in Michigan
 * Clinton-Kalamazoo Canal
 * Communications in Michigan
 * commons:Category:Communications in Michigan
 * Constitution of Michigan
 * Convention centers in Michigan
 * commons:Category:Convention centers in Michigan
 * Copper Country
 * Copper mining in Michigan
 * Counties of the state of Michigan
 * commons:Category:Counties in Michigan
 * Category:Michigan culture
 * commons:Category:Michigan culture

D

 * Demographics of Michigan
 * Detroit, Michigan, territorial capital 1805-1812 and 1813–1837, state capital 1837-1847
 * Detroit and Mackinac Railway
 * Detroit Free Press
 * Detroit Ignition
 * Detroit Lions
 * Detroit Pistons
 * Detroit Red Wings
 * Detroit River
 * Detroit Shock
 * Detroit Sunday Journal
 * Detroit Tigers
 * Detroit Zoo
 * DeYoung Family Zoo
 * Dow Chemical Company
 * Dow Corning

E

 * Eastern white pine
 * Economy of Michigan
 * Category:Economy of Michigan
 * commons:Category:Economy of Michigan
 * Education in Michigan
 * Category:Education in Michigan
 * commons:Category:Education in Michigan
 * Elections in the state of Michigan
 * Category:Michigan elections
 * commons:Category:Michigan elections
 * Emerald ash borer
 * Environment of Michigan
 * commons:Category:Environment of Michigan

F

 * List of festivals in Michigan
 * commons:Category:Festivals in Michigan
 * Flag of the State of Michigan
 * Flint/Tri-Cities
 * List of Michigan flowers
 * Ford Motor Company
 * Forts in Michigan
 * Category:Forts in Michigan
 * commons:Category:Forts in Michigan
 * Marshall Fredericks
 * Frederick Carl Frieseke

G

 * Garlyn Zoo
 * General Motors Corporation
 * Geography of Michigan
 * Category:Geography of Michigan
 * commons:Category:Geography of Michigan
 * Geology of Michigan
 * commons:Category:Geology of Michigan
 * Gerald Ford
 * Ghost towns in Michigan
 * Category:Ghost towns in Michigan
 * commons:Category:Ghost towns in Michigan
 * Golf clubs and courses in Michigan
 * Government of the state of Michigan website
 * Category:Government of Michigan
 * commons:Category:Government of Michigan
 * Governor of the State of Michigan
 * List of governors of Michigan
 * Grand River Avenue
 * Great Lakes
 * Great Lakes Central Railroad
 * Great Lakes region
 * Great Lakes Waterway
 * Great Seal of the State of Michigan

H

 * Hartwick Pines State Park
 * Heritage railroads in Michigan
 * commons:Category:Heritage railroads in Michigan
 * Hiawatha National Forest
 * Highway system of Michigan
 * Hiking trails in Michigan
 * commons:Category:Hiking trails in Michigan
 * History of Michigan
 * Historical outline of Michigan
 * Category:History of Michigan
 * commons:Category:History of Michigan
 * Huron National Forest
 * Huron-Manistee National Forests
 * Houghton, Michigan

I

 * Images of Michigan
 * commons:Category:Michigan
 * Category:Images of Metro Detroit
 * Interlochen State Park
 * Islands of Michigan
 * Isle Royale National Park

J

 * John Ball Park

K

 * Kmart
 * Keweenaw Peninsula
 * Keweenaw Waterway

L

 * Lakes in Michigan
 * Lake Erie
 * Lake Huron
 * Lake Michigan
 * Lake Saint Clair
 * Lake Superior
 * Category:Lakes of Michigan
 * commons:Category:Lakes of Michigan
 * Landmarks in Michigan
 * commons:Category:Landmarks in Michigan
 * Lansing, Michigan, state capital since 1847
 * Lansing Lugnuts
 * Law schools in Michigan
 * Lighthouses of Michigan
 * Lighthouses in the United States
 * Lists related to the state of Michigan:
 * List of airports in Michigan
 * List of automobile manufacturers of Michigan
 * List of ballot measures in Michigan
 * List of butterflies in Michigan
 * List of cities, villages, and townships in Michigan
 * List of Civil War regiments from Michigan
 * List of colleges and universities in Michigan
 * List of companies based in Michigan
 * List of counties of Michigan
 * List of county-designated highways in Michigan
 * List of covered bridges in Michigan
 * List of dams and reservoirs in Michigan
 * List of ghost towns in Michigan
 * List of governors of Michigan
 * List of governors of Michigan Territory
 * List of high schools in Michigan
 * List of individuals executed in Michigan
 * List of Interstate Highways in Michigan
 * List of islands of Michigan
 * List of lakes in Michigan
 * List of law enforcement agencies in Michigan
 * List of lighthouses in Michigan
 * List of mayors of Detroit, Michigan
 * List of mayors of Grand Rapids, Michigan
 * List of mayors of Lansing, Michigan
 * List of mayors of Saginaw, Michigan
 * List of mines in Michigan
 * List of municipalities in Michigan (by population)
 * List of museums in Michigan
 * List of National Historic Landmarks in Michigan
 * List of newspapers in Michigan
 * List of Olympic medalists from Michigan
 * List of people from Michigan
 * List of people from Saginaw, Michigan
 * List of power stations in Michigan
 * List of protected areas in Michigan
 * List of Pure Michigan Byways
 * List of radio stations in Michigan
 * List of railroads in Michigan
 * List of Registered Historic Places in Michigan
 * List of rivers in Michigan
 * List of school districts in Michigan
 * List of shopping malls in Michigan
 * List of sister cities in Michigan
 * List of state forests in Michigan
 * List of state parks in Michigan
 * List of state prisons in Michigan
 * List of symbols of the State of Michigan
 * List of state trunklines in Michigan
 * List of tallest buildings in Michigan
 * List of telephone area codes in Michigan
 * List of television stations in Michigan
 * List of threatened fauna of Michigan
 * List of townships in Michigan
 * List of United States congressional delegations from Michigan
 * List of United States congressional districts in Michigan
 * List of United States representatives from Michigan
 * List of United States senators from Michigan
 * List of U.S. Highways in Michigan
 * List of weather records of Michigan
 * Lower Peninsula of Michigan
 * Lumberman's Monument

M

 * Mackinac Bridge
 * Manistee National Forest
 * Maps of Michigan
 * commons:Category:Maps of Michigan
 * Jacques Marquette
 * Marquette, Michigan
 * Merit Network
 * Metro Detroit
 * MI – United States Postal Service postal code for the State of Michigan
 * MiCorps
 * Mid-Michigan
 * Midwest
 * Michiana
 * Michigan
 * Category:Michigan
 * commons:Category:Michigan
 * commons:Category:Maps of Michigan
 * Michigan AuSable Valley Railroad
 * Michigan Basin
 * Michigan Court of Appeals
 * Michigan Democratic Party
 * Michigander
 * Michigan Intercollegiate Athletic Association
 * Michigan Islands Wilderness Area
 * Michigan Islands National Wildlife Refuge
 * Michigan left
 * Michigan maps
 * Michigan Mountain Biking Association
 * Michigan Public Transit Association
 * Michigan Religious Freedom Restoration Act
 * Michigan Republican Party
 * Michigan Schools and Government Credit Union
 * Michigan State Capitol
 * Michigan State Police
 * Michigan State University
 * Michigan Sugar Company
 * Michigan Supreme Court
 * Michigan Technological University
 * Michigan Territory
 * Michigan wine
 * The Mining Journal
 * Monuments and memorials in Michigan
 * commons:Category:Monuments and memorials in Michigan
 * Mountains of Michigan
 * commons:Category:Mountains of Michigan
 * Museums in Michigan
 * Category:Museums in Michigan
 * commons:Category:Museums in Michigan
 * Music of Michigan
 * commons:Category:Music of Michigan
 * Category:Musical groups from Michigan
 * Category:Musicians from Michigan

N

 * National Forests of Michigan
 * commons:Category:National Forests of Michigan
 * Natural gas pipelines in Michigan
 * Natural history of Michigan
 * commons:Category:Natural history of Michigan
 * Nature centers in Michigan
 * commons:Category:Nature centers in Michigan
 * Nestlé
 * Newspapers published in Michigan
 * Non-profit organizations based in Michigan
 * Nordhouse Dunes Wilderness
 * Northern Michigan
 * Northern Michigan Football League
 * Northland Center (Michigan)
 * Northville, Michigan
 * Northwest Territory
 * Northern Michigan University
 * Novi, Michigan

O

 * Ottawa National Forest
 * Outdoor sculptures in Michigan
 * commons:Category:Outdoor sculptures in Michigan

P

 * The Palace of Auburn Hills
 * People from Michigan
 * Category:People from Michigan
 * commons:Category:People from Michigan
 * Category:People by populated place in Michigan
 * Category:People from Michigan by county
 * Category:People from Michigan by occupation
 * Pere Marquette Railway
 * Petoskey stone
 * Pewabic Pottery
 * Pictured Rocks National Lakeshore
 * Pioneer Sugar
 * Pioneer Surgical Technology
 * Orlando Poe
 * Politics of Michigan
 * commons:Category:Politics of Michigan
 * Potter Park Zoological Gardens
 * Protected areas of Michigan
 * Category:Protected areas of Michigan
 * commons:Category:Protected areas of Michigan
 * Pure Michigan
 * Pure Michigan Byway

R

 * Railroad museums in Michigan
 * commons:Category:Railroad museums in Michigan
 * Regions of Michigan
 * Religion in Michigan
 * Category:Religion in Michigan
 * commons:Category:Religion in Michigan
 * Repopulation of wolves in Midwestern United States
 * Rockwell Medical

S

 * St. Clair River
 * St. Mary's River
 * Henry Schoolcraft
 * Saginaw Trail
 * Scouting in Michigan
 * Seamanite
 * Settlements in Michigan
 * Cities in Michigan
 * Villages in Michigan
 * Townships in Michigan
 * Census Designated Places in Michigan
 * Other unincorporated communities in Michigan
 * List of ghost towns in Michigan
 * Ski areas and resorts in Michigan
 * commons:Category:Ski areas and resorts in Michigan
 * Sleeping Bear Dunes National Lakeshore
 * Solar power in Michigan
 * Southern Michigan
 * Southwest Michigan Devil Rays
 * Sports in Michigan
 * commons:Category:Sports in Michigan
 * Sports venues in Michigan
 * commons:Category:Sports venues in Michigan
 * State of Michigan website
 * Government of the State of Michigan
 * Category:Government of Michigan
 * commons:Category:Government of Michigan
 * Stratton, Mary Chase Perry
 * Structures in Michigan
 * commons:Category:Buildings and structures in Michigan
 * Symbols of the State of Michigan
 * Michigan state bird: American robin (Turdus migratorius)
 * Michigan state coat-of-arms: Coat-of-Arms of the State of Michigan
 * Michigan state fish: brook trout (Salvelinus fontinalis)
 * Michigan state flag: Flag of the State of Michigan
 * Michigan state flower: apple blossom (Malus domestica)
 * Michigan state fossil: mastodon (Mammut americanum)
 * Michigan state game animal: white-tailed deer (Odocoileus virginianus)
 * Michigan state gem: Isle Royale greenstone (chlorastrolite)
 * Michigan state mammal: wolverine (Gulo gulo luscus) (unofficial)
 * Michigan state motto: Si quaeris peninsulam amoenam circumspice (Latin for "If you seek a pleasant peninsula, look about you") (unofficial)
 * Michigan state nicknames: Wolverine State and Great Lakes State (unofficial)
 * Michigan state reptile: western painted turtle (Chrysemys picta bellii)
 * Michigan state seal: Great Seal of the State of Michigan
 * Michigan state soil: Kalkaska sand
 * Michigan state song: "My Michigan" website
 * Michigan state stone: Petoskey stone
 * Michigan state tree: eastern white pine (Pinus strobus)
 * Michigan state wildflower: dwarf lake iris (Iris lacustris)
 * United States quarter dollar - Michigan 20042004 MI Proof.png

T

 * Telecommunications in Michigan
 * commons:Category:Communications in Michigan
 * Telephone area codes in Michigan
 * Television stations
 * The Thumb
 * Theatres in Michigan
 * commons:Category:Theatres in Michigan
 * Tiger Stadium
 * Toledo Strip
 * Toledo War
 * Tourism in Michigan website
 * commons:Category:Tourism in Michigan
 * Transportation in Michigan
 * Category:Transportation in Michigan
 * commons:Category:Transport in Michigan
 * Traverse City Record-Eagle

U

 * United States of America
 * States of the United States of America
 * United States census statistical areas of Michigan
 * United States congressional delegations from Michigan
 * United States congressional districts in Michigan
 * United States Court of Appeals for the Sixth Circuit
 * United States District Court for the Eastern District of Michigan
 * United States District Court for the Western District of Michigan
 * United States representatives from Michigan
 * United States senators from Michigan
 * University of Michigan
 * Upper Midwest
 * Upper Peninsula of Michigan
 * US-MI – ISO 3166-2:US region code for the State of Michigan

W

 * Water in Michigan
 * Water parks in Michigan
 * Waterfalls of Michigan
 * commons:Category:Waterfalls of Michigan
 * West Michigan Whitecaps
 * Western Michigan
 * Wikimedia
 * Wikimedia Commons:Category:Michigan
 * commons:Category:Maps of Michigan
 * Wikinews:Category:Michigan
 * Wikinews:Portal:Michigan
 * Wikipedia Category:Michigan
 * Wikipedia Portal:Michigan
 * WikiProject Michigan
 * Category:WikiProject Michigan articles
 * WikiProject Michigan/Members
 * Wind power in Michigan
 * Wisconsin v. Michigan

Y

 * Yooper

Z

 * Zoos in Michigan
 * commons:Category:Zoos in Michigan

title: Index of Michigan-related articles


text:
Cooperativity

Cooperativity is a phenomenon displayed by systems involving identical or near-identical elements, which act dependently of each other, relative to a hypothetical standard non-interacting system in which the individual elements are acting independently. One manifestation of this is enzymes or receptors that have multiple binding sites where the affinity of the binding sites for a ligand is apparently increased, positive cooperativity, or decreased, negative cooperativity, upon the binding of a ligand to a binding site. For example, when an oxygen atom binds to one of hemoglobin's four binding sites, the affinity to oxygen of the three remaining available binding sites increases; i.e. oxygen is more likely to bind to a hemoglobin bound to one oxygen than to an unbound hemoglobin. This is referred to as cooperative binding.

We also see cooperativity in large chain molecules made of many identical (or nearly identical) subunits (such as DNA, proteins, and phospholipids), when such molecules undergo phase transitions such as melting, unfolding or unwinding. This is referred to as subunit cooperativity. However, the definition of cooperativity based on apparent increase or decrease in affinity to successive ligand binding steps is problematic, as the concept of "energy" must always be defined relative to a standard state. When we say that the affinity is increased upon binding of one ligand, it is empirically unclear what we mean since a non-cooperative binding curve is required to rigorously define binding energy and hence also affinity. A much more general and useful definition of positive cooperativity is: A process involving multiple identical incremental steps, in which intermediate states are statistically underrepresented relative to a hypothetical standard system (null hypothesis) where the steps occur independently of each other.

Likewise, a definition of negative cooperativity would be a process involving multiple identical incremental steps, in which the intermediate states are overrepresented relative to a hypothetical standard state in which individual steps occur independently. These latter definitions for positive and negative cooperativity easily encompass all processes which we call "cooperative", including conformational transitions in large molecules (such as proteins) and even psychological phenomena of large numbers of people (which can act independently of each other, or in a co-operative fashion).

Cooperative binding
When a substrate binds to one enzymatic subunit, the rest of the subunits are stimulated and become active. Ligands can either have positive cooperativity, negative cooperativity, or non-cooperativity.

An example of positive cooperativity is the binding of oxygen to hemoglobin. One oxygen molecule can bind to the ferrous iron of a heme molecule in each of the four chains of a hemoglobin molecule. Deoxy-hemoglobin has a relatively low affinity for oxygen, but when one molecule binds to a single heme, the oxygen affinity increases, allowing the second molecule to bind more easily, and the third and fourth even more easily. The oxygen affinity of 3-oxy-hemoglobin is ~300 times greater than that of deoxy-hemoglobin. This behavior leads the affinity curve of hemoglobin to be sigmoidal, rather than hyperbolic as with the monomeric myoglobin. By the same process, the ability for hemoglobin to lose oxygen increases as fewer oxygen molecules are bound. ''See also Oxygen-hemoglobin dissociation curve.

Negative cooperativity means that the opposite will be true; as ligands bind to the protein, the protein's affinity for the ligand will decrease, i.e. it becomes less likely for the ligand to bind to the protein. An example of this occurring is the relationship between glyceraldehyde-3-phosphate and the enzyme glyceraldehyde-3-phosphate dehydrogenase.

Homotropic cooperativity refers to the fact that the molecule causing the cooperativity is the one that will be affected by it. Heterotropic cooperativity is where a third party substance causes the change in affinity. Homotropic or heterotropic cooperativity could be of both positives as well as negative types depend upon whether it support or oppose further binding of the ligand molecules to the enzymes.

Subunit cooperativity
Cooperativity is not only a phenomenon of ligand binding, but also applies anytime energetic interactions make it easier or more difficult for something to happen involving multiple units as opposed to with single units. (That is, easier or more difficult compared with what is expected when only accounting for the addition of multiple units). For example, unwinding of DNA involves cooperativity: Portions of DNA must unwind in order for DNA to carry out replication, transcription and recombination. Positive cooperativity among adjacent DNA nucleotides makes it easier to unwind a whole group of adjacent nucleotides than it is to unwind the same number of nucleotides spread out along the DNA chain. The cooperative unit size is the number of adjacent bases that tend to unwind as a single unit due to the effects of positive cooperativity. This phenomenon applies to other types of chain molecules as well, such as the folding and unfolding of proteins and in the "melting" of phospholipid chains that make up the membranes of cells. Subunit cooperativity is measured on the relative scale known as Hill's Constant.

Hill equation
A simple and widely used model for molecular interactions is the Hill equation, which provides a way to quantify cooperative binding by describing the fraction of saturated ligand binding sites as a function of the ligand concentration.

Hill coefficient
The Hill coefficient is a measure of ultrasensitivity (i.e. how steep is the response curve).

From an operational point of view the Hill coefficient can be estimated as:

where and  are the input values needed to produce the 10% and 90% of the maximal response, respectively.

Response coefficient
Global sensitivity measures such as the Hill coefficient do not characterise the local behaviours of the s-shaped curves. Instead, these features are well captured by the response coefficient measure defined as:

 * $$ R(x) = \frac{x}{y}\frac{dy}{dx} $$

In systems biology, such responses are referred to as elasticities.

Link between Hill coefficient and response coefficient
Altszyler et al. (2017) have shown that these ultrasensitivity measures can be linked by the following equation:

where $$\langle X \rangle_{a,b}$$ denoted the mean value of the variable x over the range [a,b].

Ultrasensitivity in function composition
Consider two coupled ultrasensitive modules, disregarding effects of sequestration of molecular components between layers. In this case, the expression for the system's dose-response curve, $F$, results from the mathematical composition of the functions, $$f_i$$, which describe the input/output relationship of isolated modules $$i=1,2$$:

 * $$ F(I_1)=f_2\big(f_1(I_1)\big) $$

Brown et al. (1997) have shown that the local ultrasensitivity of the different layers combines multiplicatively:

 * $$ R(x)=R_{2}(f_{1}(x) ) . R_{1}(x) $$.

In connection with this result, Ferrell et al. (1997) showed, for Hill-type modules, that the overall cascade global ultrasensitivity had to be less than or equal to the product of the global ultrasensitivity estimations of each cascade's layer,

 * $$ n \leq n_{1} . n_{2} $$,

where $$n_1$$ and $$n_2$$ are the Hill coefficient of modules 1 and 2 respectively.

Altszyler et al. (2017) have shown that the cascade's global ultrasensitivity can be analytically calculated:

 * $$ n = 2 \overbrace{\langle R_2 \rangle_{X10_2,X90_2}}^{\nu_2} \overbrace{\langle R_1 \rangle_{X10_1,X90_1}}^{\nu_1} = 2 \,\nu_2 \, \nu_1$$

where $$X10_i$$ and $$X90_i$$ delimited the Hill input's working range of the composite system, i.e. the input values for the i-layer so that the last layer (corresponding to $$i=2$$ in this case) reached the 10% and 90% of it maximal output level. It followed this equation that the system's Hill coefficient $n$ could be written as the product of two factors, $$\nu_1$$ and $$\nu_2$$, which characterized local average sensitivities over the relevant input region for each layer: $$[X10_i,X90_i ]$$, with $$i=1,2$$ in this case.

For the more general case of a cascade of $N$ modules, the Hill coefficient can be expressed as:

 * $$ n =\nu_{N} \, \nu_{N-1}...\nu_{1} $$,

Supramultiplicativity
Several authors have reported the existence of supramultiplicative behavior in signaling cascades (i.e. the ultrasensitivity of the combination of layers is higher than the product of individual ultrasensitivities), but in many cases the ultimate origin of supramultiplicativity remained elusive. Altszyler et al. (2017) framework naturally suggested a general scenario where supramultiplicative behavior could take place. This could occur when, for a given module, the corresponding Hill's input working range was located in an input region with local ultrasensitivities higher than the global ultrasensitivity of the respective dose-response curve.

title: Cooperativity


text:
Filter binding assay

In biochemistry or chemistry, filter binding assay is a simple way to quickly study many samples. One of the ways to learn about an interaction between two molecules is to determine the binding constant, which is a number that describes the ratio of unbound and bound molecules. This information reveals the affinity between the two molecules and allows prediction of the amount bound given any set of initial conditions.

In order to measure a binding constant, one must find a way to measure the amount of complex formed over a range of starting concentrations. This can be achieved by "labeling" one of the species with a fluorescent, or in this case, a radioactive tag. The DNA is "labeled" by the addition of radioactive phosphate derived from adenosine triphosphate.

Description
A filter binding assay measures affinities between two molecules (often protein and DNA) using a filter. The filter is constructed of nitrocellulose paper, which is negatively charged. Since most proteins have a net positive charge, nitrocellulose paper is ideal for immobilizing proteins. DNA is negatively charged due to the phosphate backbone and will not "stick" to the nitrocellulose on its own, however, any DNA that has been bound by protein will stick. The exact amount of DNA "stuck" to the nitrocellulose is quantified by measuring the amount of radioactivity on the filter using a scintillation counter.

Protein and DNA are mixed in a series of microfuge tubes in which the amount of DNA is kept constant, but the amount of protein is incrementally increased. These samples are allowed to equilibrate. After equilibration, an equal volume from each tube is squirted onto small, round, nitrocellulose filters which are arranged on a vacuum plate (a flat surface that has a vacuum applied from below to suck fluid downward). All of the protein will stick, but only the protein that has bound DNA will register in the scintillation counter.

Now, you will have a number that describes the amount of DNA bound for each concentration of protein used, this information can be plotted on a binding curve to determine the binding constant.

This assay is no longer used widely, but it is rapid and simple, and can give a lot of information. It would be used for relatively detailed analysis of a particular protein-DNA interaction, for example.

Measure the equilibrium constant:

 * Incubate labeled DNA with protein.
 * Allow enough time to allow the system to reach equilibrium.
 * Filter the mixture through a filter disk made of nitrocellulose. Proteins bind to nitrocellulose, but DNA does not.
 * Any DNA that is retained on the filter is there because it is interacting with the protein.
 * Dry the filters and count.

Measure the off-rate:

 * Take the filter with DNA-protein complex bound on it
 * Wash the filter with buffer
 * Quantify the amount of DNA remained on filter after it has been washed for a certain amount of time.

Another way of measuring off-rate:

 * Radioactive labeled DNA and protein were pre-incubated together in high concentrations
 * At time 0, the mixture was diluted
 * Aliquotes were assayed at various times using nitrocellulose filters

title: Filter binding assay


text:
Daybreak Star Cultural Center

The Daybreak Star Indian Cultural Center is a Native American cultural center in Seattle, Washington, described by its parent organization United Indians of All Tribes as "an urban base for Native Americans in the Seattle area." Located on 20 acres (81,000 m²) in Seattle's Discovery Park in the Magnolia neighborhood, the center developed from activism by Bernie Whitebear and other Native Americans, who staged a generally successful self-styled "invasion" and occupation of the land in 1970. Most of the former Fort Lawton military base had been declared surplus by the U.S. Department of Defense. "The claim [Whitebear and others made] to Fort Lawton was based on rights under 1865 U.S.-Indian treaties promising reversion of surplus military lands to their original owners."

The existing building, a work of modern architecture incorporating many elements of traditional Northwest Native architecture, was designed by Arai Jackson Architects and Planners and completed in 1977. In 2004, plans were approved to supplement it with a complex of three additional related buildings, to be known as the People's Lodge. This was Whitebear's final dream project before he died of cancer in 2000. But in 2006, after agreements had been reached between the tribes, the city and nearby residents on a reduced size for the new project, the Center decided to postpone construction indefinitely for lack of funds.

Daybreak Star, a major nucleus of Native American cultural activity in its region, functions as a conference center, a location for pow wows, the location for a Head Start school program, and an art gallery. The center's permanent art collection includes a variety of large art works by and about Native Americans, notably Blue Jay, a 30-foot (9 m) wide, 12 foot (3.7 m) high sculpture by Lawney Reyes, Whitebear's brother. It was commissioned by and hung prominently for more than 30 years at the Bank of California building in downtown Seattle. (After the Bank of California merged with Union Bank in 1996 to form Union Bank of California, the work was donated to the Daybreak Star Center.) Also included in that donation was a major oil painting by Guy Anderson, based on a traditional Northwest Native representation of a whale.

Bernie Whitebear is memorialized by the Bernie Whitebear Memorial Ethnobotanical Garden next to the Center building.

History
In 1970, the U.S. federal government was in the process of reviewing military needs and planned to declare as surplus much of the grounds of Fort Lawton, located on Puget Sound in the northwestern section of the Magnolia neighborhood. The state's two U.S. Senators, Henry M. "Scoop" Jackson and Warren G. Magnuson amended the U.S. Land and Water Conservation Act of 1965, reducing the previous 50-100 percent cost of acquiring surplus federal government property to 0-50 percent, so that such property might be acquired by bodies other than real estate developers. The property would initially be transferred to the city but was not constrained in use. In that period of Indian activism, many of Seattle's urban Indians were concerned to gain a land base within the city. (As of the early 21st century, about 25,000 Indians from a variety of tribes live in the Seattle area.)

A group arose, initially identifying as Kinatechitapi, Blackfoot for "All Indians"; the name referred to the Indians of All Tribes (IAT), a group of mostly student activists then occupying Alcatraz Island in San Francisco Bay. Joe DeLaCruz, leader of the Quinault, conducted outreach to every tribe in Washington State to try to gain their support for gaining land in Seattle.

Kinatechitapi's first efforts to open discussions about the property with the City of Seattle, in advance of surplus land being transferred to the city, failed. The City, under mayor Wes Uhlman, said it would not open discussions until it had acquired the land, and referred the group to the Bureau of Indian Affairs (BIA). As Whitebear later wrote, "This action displayed their ignorance of both the BIA's restricted service policy, which excluded urban Indians, and also the disregard and disfavor urban Indians held for the BIA." The City said that the Indian Center in a former church near Stewart Street downtown was an adequate facility for Seattle's Indians. The members of the Magnolia Community Club, a group with significant political clout, were opposed to an Indian presence on the Fort Lawton land.

Kinatechitapi members split between a faction that called for direct action and one that preferred to wait until the city acquired the land, in order to conduct negotiations. Prominent among those who preferred to wait was Pearl Warren, founder of the American Indian Women's Service League, who was concerned that a militant attitude would result in the city's reducing its provision of services to urban Indians. Members agreed that those who wished to take more extreme action would not use the name Kinatechitapi. Warren lost the next election for presidency of the Service League to Joyce Reyes, who was aligned with those promoting direct action. All significant Seattle Indian organizations agreed on taking action.

Direct action
The more militant faction, led by Bernie Whitebear, soon adopted the name "American Indian Fort Lawton Occupation Forces". The faction included Bob Satiacum, initially a rival to Whitebear for the top leadership role. A group vote settled on Whitebear as leader. Some of the Indians of All Tribes traveled to Seattle from Alcatraz for the action, including Richard Oakes, leader of that action; other activists came from Canada. Grace Thorpe, daughter of athlete Jim Thorpe, also arrived to give support. Local activists Ella Aquino and Ramona Bennett helped plan the occupation. The group planned to invade the base from two directions, with one group scaling the bluffs from Elliott Bay while another scaled the fence near the Lawton Wood community on the north side of the base. The group committed to nonviolence in this action.

American Indian soldiers and others were protesting at Fort Lewis, near Tacoma, linking native rights to opposition to the Vietnam War. At the behest of the Fort Lewis coalition, actress Jane Fonda came to Seattle at the time of the invasion of Fort Lawton. According to Whitebear, her presence "'captured the imagination of the world press. American Indians were attacking active military forts along with one of the nation's leading opponents of United States involvement in the Vietnam War.' Her presence transformed 'an effort to secure a land base for urban Indians' into 'a bizarre, ready-for-prime-time, movie scenario, complete with soldiers, modern-day Indians, and anti-war activists. Without really appreciating it at the time, the Indian movement had achieved through Jane Fonda's presence, a long-sought credibility which would not have been possible otherwise.'"

On the evening of March 7, 1970, at a pow-wow held at the Filipino Community Hall in south Seattle, invasion plans were announced. The following day, March 8, 1970, about 100 "Native Americans and sympathizers" confronted military police in riot gear at the fort, while about 500 supporters staged a legal protest outside the gates. Some of the invaders reached the base chapel, where a Sunday service was in progress, but in general, skirmish lines were quickly formed and the military police contained the invasion. Some of the invaders failed to maintain non-violence, especially when confronted by what Whitebear characterized as "overly aggressive handling by the MPs". MPs (Military Police), aided by regular Army troops and Seattle Police, initially placed the invaders in the fort stockade, then ejected them from the fort. The Indian activists established a tipi encampment outside the fort. Mayor Uhlman and Senator Jackson held a press conference about the Fort Lawton property, promising a city park at the site above Puget Sound. They did not refer to the Indian action.

United Indians of All Tribes Foundation
Organizing as the United Indians of All Tribes Foundation (UIATF) with Whitebear as executive director, the Indians used tactics ranging from politicking to occupation of land to celebrity appearances to gain more support. For three months, activists engaged in what Whitebear later described as "Invasion, arrests, jailings, letters of expulsion from military property, physical escort off the fort, re-invasion." The Army cordoned off the fort with concertina wire, brought in two companies of troops from Fort Lewis to prevent incursions, and dug foxholes.

By this time more than 40 non-Indian organizations in King County supported the Indians' efforts. Gary and Beverly Beaver, Randy Lewis, Grace Thorpe, Douglas Remington, and Bernie Whitebear testified before a congressional committee chaired by Morris Udall, and received support from US congressman Brock Adams from Seattle. Whitebear forged a relationship with Tom McLaughlin, deputy regional director of the United States Department of Health, Education, and Welfare and through him with Buck Kelley, the regional director and top political appointee for HEW in the region. UIATF, which had previously avoided dealing with the BIA, now went through the National Congress of American Indians to approach the BIA and request a freeze on plans to transfer land at Fort Lawton until the issue between UIATF and the City was resolved. BIA commissioner Louis Bruce imposed such a freeze for a time, but eventually backed off at the behest of his boss, the Department of the Interior.

When the federal government officially put the surplus land up for offers, UIATF filed to acquire a portion of the fort directly from the federal government. Thanks to Whitebear's maneuvering, UIATF's application to acquire part of the land was technically filed prior to the City's application for the whole parcel. The federal General Services Administration, which handled the surplus process, ultimately insisted that the City and UIATF come up with a joint plan for the property. In November 1971, the parties agreed that the city would grant UIATF with a 99-year lease on 20 acres (81,000 m²) in what would become Seattle's Discovery Park, with options for renewal without renegotiation. In addition, the City granted $600,000 to the American Indian Women's Service League for a social services center.

Whitebear was soon elected as CEO of the UIATF, and undertook fundraising (including a one million dollar grant from the state), and supervision of design and construction. Whitebear's brother Lawney Reyes joined with architects of Arai Jackson to design the facility, which used traditional Native American elements in a modern building. It opened in 1977.

In the same era when Daybreak Star was being constructed, Whitebear was appointed to the Seattle Arts Commission. The UIATF was granted an $80,000 arts grant for the center. The Center has wireless Internet access ("UIATF-A").

title: Daybreak Star Cultural Center


text:
Spermatogenesis

Spermatogenesis is the process by which haploid spermatozoa develop from germ cells in the seminiferous tubules of the testicle. This process starts with the mitotic division of the stem cells located close to the basement membrane of the tubules. These cells are called spermatogonial stem cells. The mitotic division of these produces two types of cells. Type A cells replenish the stem cells, and type B cells differentiate into primary spermatocytes. The primary spermatocyte divides meiotically (Meiosis I) into two secondary spermatocytes; each secondary spermatocyte divides into two equal haploid spermatids by Meiosis II. The spermatids are transformed into spermatozoa (sperm) by the process of spermiogenesis. These develop into mature spermatozoa, also known as sperm cells. Thus, the primary spermatocyte gives rise to two cells, the secondary spermatocytes, and the two secondary spermatocytes by their subdivision produce four spermatozoa and four haploid cells.

Spermatozoa are the mature male gametes in many sexually reproducing organisms. Thus, spermatogenesis is the male version of gametogenesis, of which the female equivalent is oogenesis. In mammals it occurs in the seminiferous tubules of the male testes in a stepwise fashion. Spermatogenesis is highly dependent upon optimal conditions for the process to occur correctly, and is essential for sexual reproduction. DNA methylation and histone modification have been implicated in the regulation of this process. It starts during puberty and usually continues uninterrupted until death, although a slight decrease can be discerned in the quantity of produced sperm with increase in age (see Male infertility).

Spermatogenesis starts in the bottom part of seminiferous tubes and, progressively, cells go deeper into tubes and moving along it until mature spermatozoa reaches the lumen, where mature spermatozoa are deposited. The division happens asynchronically; if the tube is cut transversally one could observe different maturation states. A group of cells with different maturation states that are being generated at the same time is called a spermatogenic wave.

Purpose
Spermatogenesis produces mature male gametes, commonly called sperm but more specifically known as spermatozoa, which are able to fertilize the counterpart female gamete, the oocyte, during conception to produce a single-celled individual known as a zygote. This is the cornerstone of sexual reproduction and involves the two gametes both contributing half the normal set of chromosomes (haploid) to result in a chromosomally normal (diploid) zygote.

To preserve the number of chromosomes in the offspring – which differs between species – one of each gamete must have half the usual number of chromosomes present in other body cells. Otherwise, the offspring will have twice the normal number of chromosomes, and serious abnormalities may result. In humans, chromosomal abnormalities arising from incorrect spermatogenesis results in congenital defects and abnormal birth defects (Down syndrome, Klinefelter syndrome) and in most cases, spontaneous abortion of the developing foetus.

Location in humans
Spermatogenesis takes place within several structures of the male reproductive system. The initial stages occur within the testes and progress to the epididymis where the developing gametes mature and are stored until ejaculation. The seminiferous tubules of the testes are the starting point for the process, where spermatogonial stem cells adjacent to the inner tubule wall divide in a centripetal direction—beginning at the walls and proceeding into the innermost part, or lumen—to produce immature sperm. Maturation occurs in the epididymis. The location [Testes/Scrotum] is specifically important as the process of spermatogenesis requires a lower temperature to produce viable sperm, specifically 1°-8 °C lower than normal body temperature of 37 °C (98.6 °F). Clinically, small fluctuations in temperature such as from an athletic support strap, causes no impairment in sperm viability or count.

Duration
For humans, the entire process of spermatogenesis is variously estimated as taking 74 days (according to tritium-labelled biopsies) and approximately 120 days (according to DNA clock measurements). Including the transport on ductal system, it takes 3 months. Testes produce 200 to 300 million spermatozoa daily. However, only about half or 100 million of these become viable sperm.

Stages
The entire process of spermatogenesis can be broken up into several distinct stages, each corresponding to a particular type of cell in humans. In the following table, ploidy, copy number and chromosome/chromatid counts are for one cell, generally prior to DNA synthesis and division (in G1 if applicable). The primary spermatocyte is arrested after DNA synthesis and prior to division.

Spermatocytogenesis
Spermatocytogenesis is the male form of gametocytogenesis and results in the formation of spermatocytes possessing half the normal complement of genetic material. In spermatocytogenesis, a diploid spermatogonium, which resides in the basal compartment of the seminiferous tubules, divides mitotically, producing two diploid intermediate cells called primary spermatocytes. Each primary spermatocyte then moves into the adluminal compartment of the seminiferous tubules and duplicates its DNA and subsequently undergoes meiosis I to produce two haploid secondary spermatocytes, which will later divide once more into haploid spermatids. This division implicates sources of genetic variation, such as random inclusion of either parental chromosomes, and chromosomal crossover that increases the genetic variability of the gamete. The DNA damage response (DDR) machinery plays an important role in spermatogenesis. The protein FMRP binds to meiotic chromosomes and regulates the dynamics of the DDR machinery during spermatogenesis. FMRP appears to be necessary for the repair of DNA damage.

Each cell division from a spermatogonium to a spermatid is incomplete; the cells remain connected to one another by bridges of cytoplasm to allow synchronous development. Not all spermatogonia divide to produce spermatocytes; otherwise, the supply of spermatogonia would run out. Instead, spermatogonial stem cells divide mitotically to produce copies of themselves, ensuring a constant supply of spermatogonia to fuel spermatogenesis.

Spermatidogenesis
Spermatidogenesis is the creation of spermatids from secondary spermatocytes. Secondary spermatocytes produced earlier rapidly enter meiosis II and divide to produce haploid spermatids. The brevity of this stage means that secondary spermatocytes are rarely seen in histological studies.

Spermiogenesis
During spermiogenesis, the spermatids begin to form a tail by growing microtubules on one of the centrioles, which turns into basal body. These microtubules form an axoneme. Later the centriole is modified in the process of centrosome reduction. The anterior part of the tail (called midpiece) thickens because mitochondria are arranged around the axoneme to ensure energy supply. Spermatid DNA also undergoes packaging, becoming highly condensed. The DNA is packaged firstly with specific nuclear basic proteins, which are subsequently replaced with protamines during spermatid elongation. The resultant tightly packed chromatin is transcriptionally inactive. The Golgi apparatus surrounds the now condensed nucleus, becoming the acrosome.

Maturation then takes place under the influence of testosterone, which removes the remaining unnecessary cytoplasm and organelles. The excess cytoplasm, known as residual bodies, is phagocytosed by surrounding Sertoli cells in the testes. The resulting spermatozoa are now mature but lack motility. The mature spermatozoa are released from the protective Sertoli cells into the lumen of the seminiferous tubule in a process called spermiation.

The non-motile spermatozoa are transported to the epididymis in testicular fluid secreted by the Sertoli cells with the aid of peristaltic contraction. While in the epididymis the spermatozoa gain motility and become capable of fertilization. However, transport of the mature spermatozoa through the remainder of the male reproductive system is achieved via muscle contraction rather than the spermatozoon's recently acquired motility.

Role of Sertoli cells

At all stages of differentiation, the spermatogenic cells are in close contact with Sertoli cells which are thought to provide structural and metabolic support to the developing sperm cells. A single Sertoli cell extends from the basement membrane to the lumen of the seminiferous tubule, although the cytoplasmic processes are difficult to distinguish at the light microscopic level.

Sertoli cells serve a number of functions during spermatogenesis, they support the developing gametes in the following ways:
 * Maintain the environment necessary for development and maturation, via the blood-testis barrier
 * Secrete substances initiating meiosis
 * Secrete supporting testicular fluid
 * Secrete androgen-binding protein (ABP), which concentrates testosterone in close proximity to the developing gametes
 * Testosterone is needed in very high quantities for maintenance of the reproductive tract, and ABP allows a much higher level of fertility
 * Secrete hormones affecting pituitary gland control of spermatogenesis, particularly the polypeptide hormone, inhibin
 * Phagocytose residual cytoplasm left over from spermiogenesis
 * Secretion of anti-Müllerian hormone causes deterioration of the Müllerian duct
 * Protect spermatids from the immune system of the male, via the blood-testis barrier
 * Contribute to the spermatogonial stem cell niche

The intercellular adhesion molecules ICAM-1 and soluble ICAM-1 have antagonistic effects on the tight junctions forming the blood-testis barrier. ICAM-2 molecules regulate spermatid adhesion on the apical side of the barrier (towards the lumen).

Influencing factors
The process of spermatogenesis is highly sensitive to fluctuations in the environment, particularly hormones and temperature. Testosterone is required in large local concentrations to maintain the process, which is achieved via the binding of testosterone by androgen binding protein present in the seminiferous tubules. Testosterone is produced by interstitial cells, also known as Leydig cells, which reside adjacent to the seminiferous tubules.

Seminiferous epithelium is sensitive to elevated temperature in humans and some other species, and will be adversely affected by temperatures as high as normal body temperature. In addition, spermatogonia do not achieve maturity at body temperature in most of mammals, as β-polimerase and spermatogenic recombinase need a specific optimal temperature. Consequently, the testes are located outside the body in a sac of skin called the scrotum. The optimal temperature is maintained at 2 °C (man) (8 °C mouse) below body temperature. This is achieved by regulation of blood flow and positioning towards and away from the heat of the body by the cremasteric muscle and the dartos smooth muscle in the scrotum.

One important mechanism is a thermal exchange between testicular arterial and venous blood streams. Specialized anatomic arrangements consist of two zones of coiling along the internal spermatic artery. This anatomic arrangement prolongs the time of contact and the thermal exchange between the testicular arterial and venous blood streams and may, in part, explain the temperature gradient between aortic and testicular arterial blood reported in dogs and rams. Moreover, reduction in pulse pressure, occurring in the proximal one third of the coiled length of the internal spermatic artery. Moreover, the activity of spermatogenic recombinase decreases, and this is supposed to be an important factor of testicles degeneration.

Dietary deficiencies (such as vitamins B, E and A), anabolic steroids, metals (cadmium and lead), x-ray exposure, dioxin, alcohol, and infectious diseases will also adversely affect the rate of spermatogenesis. In addition, the male germ line is susceptible to DNA damage caused by oxidative stress, and this damage likely has a significant impact on fertilization and pregnancy. According to the study by Omid Mehrpour et al exposure to pesticides also affects spermatogenesis.

Hormonal control
Hormonal control of spermatogenesis varies among species. In humans the mechanism is not completely understood; however it is known that initiation of spermatogenesis occurs at puberty due to the interaction of the hypothalamus, pituitary gland and Leydig cells. If the pituitary gland is removed, spermatogenesis can still be initiated by follicle stimulating hormone (FSH) and testosterone. In contrast to FSH, luteinizing hormone (LH) appears to have little role in spermatogenesis outside of inducing gonadal testosterone production.

FSH stimulates both the production of androgen binding protein (ABP) by Sertoli cells, and the formation of the blood-testis barrier. ABP is essential to concentrating testosterone in levels high enough to initiate and maintain spermatogenesis. Intratesticular testosterone levels are 20–100 or 50–200 times higher than the concentration found in blood, although there is variation over a 5- to 10-fold range amongst healthy men. Testosterone production does not remain constant throughout the day, but follows a circadian rhythm. The maximum peak of testosterone occurs at 8 a.m., which explains why men frequently suffer from morning erections. In younger men, testosterone peaks are higher. FSH may initiate the sequestering of testosterone in the testes, but once developed only testosterone is required to maintain spermatogenesis. However, increasing the levels of FSH will increase the production of spermatozoa by preventing the apoptosis of type A spermatogonia. The hormone inhibin acts to decrease the levels of FSH. Studies from rodent models suggest that gonadotropins (both LH and FSH) support the process of spermatogenesis by suppressing the proapoptotic signals and therefore promote spermatogenic cell survival.

The Sertoli cells themselves mediate parts of spermatogenesis through hormone production. They are capable of producing the hormones estradiol and inhibin. The Leydig cells are also capable of producing estradiol in addition to their main product testosterone. Estrogen has been found to be essential for spermatogenesis in animals. However, a man with estrogen insensitivity syndrome (a defective ERα) was found produce sperm with a normal sperm count, albeit abnormally low sperm viability; whether he was sterile or not is unclear. Levels of estrogen that are too high can be detrimental to spermatogenesis due to suppression of gonadotropin secretion and by extension intratesticular testosterone production. The connection between spermatogenesis and prolactin levels appears to be moderate, with optimal prolactin levels reflecting efficient sperm production.

Disorders
Disorders of spermatogenesis may cause oligospermia, which is semen with a low concentration of sperm and is a common finding in male infertility.

title: Spermatogenesis


text:
List of national parks of Slovakia

There are nine national parks in Slovakia:

title: List of national parks of Slovakia