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From the 980s, Gerbert of Aurillac (later Pope Sylvester II) used his position to spread knowledge of the numerals in Europe. Gerbert studied in Barcelona in his youth. He was known to have requested mathematical treatises concerning the astrolabe from Lupitus of Barcelona after he had returned to France. The reception of Arabic numerals in the West was gradual and lukewarm, as other numeral systems circulated in addition to the older Roman numbers. As a discipline, the first to adopt Arabic numerals as part of their own writings were astronomers and astrologists, evidenced from manuscripts surviving from mid-12th-century Bavaria. Reinher of Paderborn (1140–1190) used the numerals in his calendrical tables to calculate the dates of Easter more easily in his text "". Italy. Leonardo Fibonacci was a Pisan mathematician who had studied in the Pisan trading colony of Bugia, in what is now Algeria, and he endeavored to promote the numeral system in Europe with his 1202 book ": When my father, who had been appointed by his country as public notary in the customs at Bugia acting for the Pisan merchants going there, was in charge, he summoned me to him while I was still a child, and having an eye to usefulness and future convenience, desired me to stay there and receive instruction in the school of accounting. There, when I had been introduced to the art of the Indians' nine symbols through remarkable teaching, knowledge of the art very soon pleased me above all else and I came to understand it.
The "s analysis highlighting the advantages of positional notation was widely influential. Likewise, Fibonacci's use of the Béjaïa digits in his exposition ultimately led to their widespread adoption in Europe. Fibonacci's work coincided with the European commercial revolution of the 12th and 13th centuries centered in Italy. Positional notation facilitated complex calculations (such as currency conversion) to be completed more quickly than was possible with the Roman system. In addition, the system could handle larger numbers, did not require a separate reckoning tool, and allowed the user to check their work without repeating the entire procedure. Late medieval Italian merchants did not stop using Roman numerals or other reckoning tools: instead, Arabic numerals were adopted for use in addition to their preexisting methods. Europe. By the late 14th century, only a few texts using Arabic numerals appeared outside of Italy. This suggests that the use of Arabic numerals in commercial practice, and the significant advantage they conferred, remained a virtual Italian monopoly until the late 15th century. This may in part have been due to language barriers: although Fibonacci's "" was written in Latin, the Italian abacus traditions were predominantly written in Italian vernaculars that circulated in the private collections of abacus schools or individuals.
The European acceptance of the numerals was accelerated by the invention of the printing press, and they became widely known during the 15th century. Their use grew steadily in other centers of finance and trade such as Lyon. Early evidence of their use in Britain includes: an equal hour horary quadrant from 1396, in England, a 1445 inscription on the tower of Heathfield Church, Sussex; a 1448 inscription on a wooden lych-gate of Bray Church, Berkshire; and a 1487 inscription on the belfry door at Piddletrenthide church, Dorset; and in Scotland a 1470 inscription on the tomb of the first Earl of Huntly in Elgin Cathedral. In central Europe, the King of Hungary Ladislaus the Posthumous, started the use of Arabic numerals, which appear for the first time in a royal document of 1456. By the mid-16th century, they had been widely adopted in Europe, and by 1800 had almost completely replaced the use of counting boards and Roman numerals in accounting. Roman numerals were mostly relegated to niche uses such as years and numbers on clock faces.
Russia. Prior to the introduction of Arabic numerals, Cyrillic numerals, derived from the Cyrillic alphabet, were used by South and East Slavs. The system was used in Russia as late as the early 18th century, although it was formally replaced in official use by Peter the Great in 1699. Reasons for Peter's switch from the alphanumerical system are believed to go beyond a surface-level desire to imitate the West. Historian Peter Brown makes arguments for sociological, militaristic, and pedagogical reasons for the change. At a broad, societal level, Russian merchants, soldiers, and officials increasingly came into contact with counterparts from the West and became familiar with the communal use of Arabic numerals. Peter also covertly travelled throughout Northern Europe from 1697 to 1698 during his Grand Embassy and was likely informally exposed to Western mathematics during this time. The Cyrillic system was found to be inferior for calculating practical kinematic values, such as the trajectories and parabolic flight patterns of artillery. With its use, it was difficult to keep pace with Arabic numerals in the growing field of ballistics, whereas Western mathematicians such as John Napier had been publishing on the topic since 1614.
China. The Chinese Shang dynasty numerals from the 14th century BC predates the Indian Brahmi numerals by over 1000 years and shows substantial similarity to the Brahmi numerals. Similar to the modern Arabic numerals, the Shang dynasty numeral system was also decimal based and positional. While positional Chinese numeral systems such as the counting rod system and Suzhou numerals had been in use prior to the introduction of modern Arabic numerals, the externally-developed system was eventually introduced to medieval China by the Hui people. In the early 17th century, European-style Arabic numerals were introduced by Spanish and Portuguese Jesuits. Encoding. The ten Arabic numerals are encoded in virtually every character set designed for electric, radio, and digital communication, such as Morse code. They are encoded in ASCII (and therefore in Unicode encodings) at positions 0x30 to 0x39. Masking all but the four least-significant binary digits gives the value of the decimal digit, a design decision facilitating the digitization of text onto early computers. EBCDIC used a different offset, but also possessed the aforementioned masking property.
ABM ABM or Abm may refer to:
Apuleius Apuleius ( ; also called Lucius Apuleius Madaurensis; c. 124 – after 170) was a Numidian Latin-language prose writer, Platonist philosopher and rhetorician. He was born in the Roman province of Numidia, in the Berber city of Madauros, modern-day M'Daourouch, Algeria. He studied Platonism in Athens, travelled to Italy, Asia Minor, and Egypt, and was an initiate in several cults or mysteries. The most famous incident in his life was when he was accused of using magic to gain the attentions (and fortune) of a wealthy widow. He declaimed and then distributed his own defense before the proconsul and a court of magistrates convened in Sabratha, near Oea (modern Tripoli, Libya). This is known as the "Apologia". His most famous work is his bawdy picaresque novel the "Metamorphoses", otherwise known as "The Golden Ass". It is the only Latin novel that has survived in its entirety. It relates the adventures of its protagonist, Lucius, who experiments with magic and is accidentally turned into a donkey. Lucius goes through various adventures before he is turned back into a human being by the goddess Isis.
Life. Apuleius was born in Madauros, a "colonia" in Numidia on the North African coast bordering Gaetulia, and he described himself as "half-Numidian half-Gaetulian." Madaurus was the same "colonia" where Augustine of Hippo later received part of his early education, and, though located well away from the Romanized coast, is today the site of some pristine Roman ruins. As to his first name, no "praenomen" is given in any ancient source; late-medieval manuscripts began the tradition of calling him "Lucius" from the name of the hero of his novel. Details regarding his life come mostly from his defense speech ("Apology") and his work "Florida", which consists of snippets taken from some of his best speeches. His father was a municipal magistrate ("duumvir") who bequeathed at his death the sum of nearly two million sesterces to his two sons. Apuleius studied with a master at Carthage (where he later settled) and later at Athens, where he studied Platonist philosophy among other subjects. He subsequently went to Rome to study Latin rhetoric and, most likely, to speak in the law courts for a time before returning to his native North Africa. He also travelled extensively in Asia Minor and Egypt, studying philosophy and religion, burning up his inheritance while doing so.
Apuleius was an initiate in several Greco-Roman mysteries, including the Dionysian Mysteries. He was a priest of Asclepius and, according to Augustine, "sacerdos provinciae Africae" (i.e., priest of the province of Carthage). Not long after his return home he set out upon a new journey to Alexandria. On his way there he was taken ill at the town of Oea (modern-day Tripoli) and was hospitably received into the house of Sicinius Pontianus, with whom he had been friends when he had studied in Athens. The mother of Pontianus, Pudentilla, was a very rich widow. With her son's consent – indeed encouragement – Apuleius agreed to marry her. Meanwhile, Pontianus himself married the daughter of one Herennius Rufinus; he, indignant that Pudentilla's wealth should pass out of the family, instigated his son-in-law, together with a younger brother, Sicinius Pudens, a mere boy, and their paternal uncle, Sicinius Aemilianus, to join him in impeaching Apuleius upon the charge that he had gained the affections of Pudentilla by charms and magic spells. The case was heard at Sabratha, near Tripoli, c. 158 AD, before Claudius Maximus, proconsul of Africa. The accusation itself seems to have been ridiculous, and the spirited and triumphant defence spoken by Apuleius is still extant. This is known as the "Apologia (A Discourse on Magic)".
Apuleius accused an extravagant personal enemy of turning his house into a brothel and prostituting his wife. Of his subsequent career, we know little. Judging from the many works of which he was author, he must have devoted himself diligently to literature. He occasionally gave speeches in public to great reception; he had the charge of exhibiting gladiatorial shows and wild beast events in the province, and statues were erected in his honour by the senate of Carthage and of other senates. The date, place and circumstances of Apuleius' death are not known. There is no record of his activities after 170, a fact which has led some people to believe that he must have died about then (say in 171), although other scholars feel that he may still have been alive in 180 or even 190. Works. "The Golden Ass". "The Golden Ass" ("Asinus Aureus") or "Metamorphoses" is the only Latin novel that has survived in its entirety. It relates the adventures of one Lucius, who introduces himself as related to the famous philosophers Plutarch and Sextus of Chaeronea. Lucius experiments with magic and is accidentally turned into an ass. In this guise, he hears and sees many unusual things, until escaping from his predicament in a rather unexpected way. Within this frame story are found many digressions, the longest among them being the well-known tale of Cupid and Psyche. This story is a rare instance of a fairy tale preserved in an ancient literary text.
The "Metamorphoses" ends with the (once again human) hero, Lucius, eager to be initiated into the mystery cult of Isis; he abstains from forbidden foods, bathes, and purifies himself. He is introduced to the "Navigium Isidis". Then the secrets of the cult's books are explained to him, and further secrets are revealed before he goes through the process of initiation, which involves a trial by the elements on a journey to the underworld. Lucius is then asked to seek initiation into the cult of Osiris in Rome, and eventually is initiated into the "pastophoroi" – a group of priests that serves Isis and Osiris. "Apologia". () is the version of the defence presented in Sabratha, in 158–159, before the proconsul Claudius Maximus, by Apuleius accused of the crime of magic. Between the traditional exordium and peroratio, the argumentation is divided into three sections: The main interest of the is historical, as it offers substantial information about its author, magic and life in Africa in the second century. Other.
His other works are: Apuleius wrote many other works which have not survived. He wrote works of poetry and fiction, as well as technical treatises on politics, dendrology, agriculture, medicine, natural history, astronomy, music, and arithmetic, and he translated Plato's "Phaedo". Spurious. Extant works wrongly attributed to Apuleius include: Apuleian Sphere. The Apuleian Sphere described in "Petosiris to Nechepso", also known as "Columcille's Circle" or "Petosiris' Circle", is a magical prognosticating device for predicting the survival of a patient.
Alexander Selkirk Alexander Selkirk (167613 December 1721) was a Scottish privateer and Royal Navy officer who spent four years and four months as a castaway (1704–1709) after being marooned by his captain, initially at his request, on an uninhabited island in the South Pacific Ocean. Selkirk was an unruly youth and joined buccaneering voyages to the South Pacific during the War of the Spanish Succession. One such expedition was on "Cinque Ports", captained by Thomas Stradling, under the overall command of William Dampier. Stradling's ship stopped to resupply at the uninhabited Juan Fernández Islands, west of South America, and Selkirk judged correctly that the craft was unseaworthy and asked to be left there. Selkirk's suspicions were soon justified, as "Cinque Ports" foundered near Malpelo Island 400 km (250 mi) from the coast of what is now Colombia. By the time he was eventually rescued by the privateer Woodes Rogers, who was accompanied by Dampier, Selkirk had become adept at hunting and making use of the resources that he found on the island. His story of survival was widely publicized after his return, becoming one of the reputed sources of inspiration for the English writer Daniel Defoe's fictional character Robinson Crusoe.
Early life and privateering. Alexander Selkirk was the son of a shoemaker and tanner in Lower Largo, Fife, Scotland, born in 1676. In his youth, he displayed a quarrelsome and unruly disposition. He was summoned before the Kirk Session in August 1693 for his "indecent conduct in church", but he "did not appear, being gone to sea". He was back at Largo in 1701 when he again came to the attention of church authorities for assaulting his brothers. Early on, he was engaged in buccaneering. In 1703, he joined an expedition of English privateer and explorer William Dampier to the South Pacific Ocean, setting sail from Kinsale in Ireland on 11 September. They carried letters of marque from the Lord High Admiral authorizing their armed merchant ships to attack foreign enemies as the War of the Spanish Succession was then going on between England and Spain. Dampier was captain of "St George" and Selkirk served on "Cinque Ports", "St George"s companion ship, as sailing master under Captain Thomas Stradling. By this time, Selkirk must have had considerable experience at sea.
In February 1704, following a stormy passage around Cape Horn, the privateers fought a long battle with a well-armed French vessel, "St Joseph", only to have it escape to warn its Spanish allies of their arrival in the Pacific. A raid on the Panamanian gold mining town of Santa María failed when their landing party was ambushed. The easy capture of "Asunción", a heavily laden merchantman, revived the men's hopes of plunder, and Selkirk was put in charge of the prize ship. Dampier took off some much-needed provisions of wine, brandy, sugar, and flour, then abruptly set the ship free, arguing that the gain was not worth the effort. In May 1704, Stradling decided to abandon Dampier and strike out on his own. Castaway. In September 1704, after parting ways with Dampier, Captain Stradling brought "Cinque Ports" to an island known to the Spanish as Más a Tierra located in the uninhabited Juan Fernández archipelago off the coast of Chile for a mid-expedition restocking of fresh water and supplies. Selkirk had grave concerns about the seaworthiness of their vessel and wanted to make the necessary repairs before going any further. He declared that he would rather stay on Juan Fernández than continue in a dangerously leaky ship. Stradling took him up on the offer and landed Selkirk on the island with a musket, a hatchet, a knife, a cooking pot, a Bible, bedding and some clothes. Selkirk immediately regretted his rashness, but Stradling refused to let him back on board.
"Cinque Ports" later foundered off the coast of what is now Colombia. Stradling and "six or seven of his Men" survived the loss of their ship but were forced to surrender to the Spanish. They were taken to Lima where they endured a harsh imprisonment. Stradling attempted escape after stealing a canoe in Lima, but was recaptured and punished. The Spanish governor threatened to send all the survivors to the mines. The survivors ultimately returned to England after four years of imprisonment. Life on the island. At first, Selkirk remained along the shoreline of Más a Tierra. During this time, he ate spiny lobsters and scanned the ocean daily for rescue, suffering all the while from loneliness, misery, and remorse. Hordes of raucous sea lions, gathering on the beach for the mating season, eventually drove him to the island's interior. Once inland, his way of life took a turn for the better. More foods were available there: feral goats—introduced by earlier sailors—provided him with meat and milk, while wild turnips, the leaves of the indigenous cabbage tree and dried "Schinus" fruits (pink peppercorns) offered him variety and spice. Rats would attack him at night, but he was able to sleep soundly and in safety by domesticating and living near feral cats.
Selkirk proved resourceful in using materials that he found on the island: he forged a new knife out of barrel hoops left on the beach; built two huts out of pepper trees, one of which he used for cooking and the other for sleeping; and employed his musket to hunt goats and his knife to clean their carcasses. As his gunpowder dwindled, he had to chase prey on foot. During one such chase, he was badly injured when he tumbled from a cliff, lying helpless and unable to move for about a day. His prey had cushioned his fall, probably sparing him a broken back. Childhood lessons learned from his father, a tanner, now served him well. For example, when his clothes wore out, he made new ones from hair-covered goatskins using a nail for sewing. As his shoes became unusable, he did not need to replace them, since his toughened, calloused feet made protection unnecessary. He sang psalms and read from the Bible, finding it a comfort in his situation and a prop for his English. During his sojourn on the island, two vessels came to anchor. Unfortunately for Selkirk, both were Spanish. Being British and a privateer, he would have faced a grim fate if captured and therefore did his best to hide. Once, he was spotted and chased by a group of Spanish sailors from one of the ships. His pursuers urinated beneath the tree in which he was hiding but failed to notice him. The would-be captors then gave up and sailed away.
Rescue. Selkirk's long-awaited deliverance came on 2 February 1709 by way of "Duke", a privateering ship piloted by William Dampier, and its sailing companion "Duchess". Thomas Dover led the landing party that met Selkirk. After four years and four months without human company, Selkirk was almost incoherent with joy. The "Duke" captain and leader of the expedition was Woodes Rogers, who wryly referred to Selkirk as the governor of the island. The agile castaway caught two or three goats a day and helped restore the health of Rogers' men, who had developed scurvy. Captain Rogers was impressed by Selkirk's physical vigour, but also by the peace of mind that he had attained while living on the island, observing: "One may see that solitude and retirement from the world is not such an insufferable state of life as most men imagine, especially when people are fairly called or thrown into it unavoidably, as this man was." He made Selkirk "Duke"s second mate, later giving him command of one of their prize ships, "Increase", before it was ransomed by the Spanish.
Selkirk returned to privateering with a vengeance. At Guayaquil in present-day Ecuador, he led a boat crew up the Guayas River where several wealthy Spanish ladies had fled, and looted the gold and jewels they had hidden inside their clothing. His part in the hunt for treasure galleons along the coast of Mexico resulted in the capture of "Nuestra Señora de la Encarnación y Desengaño", renamed "Bachelor", on which he served as sailing master under Captain Dover to the Dutch East Indies. Selkirk completed the around-the-world voyage by the Cape of Good Hope as the sailing master of "Duke", arriving at the Downs off the English coast on 1 October 1711. He had been away for eight years. Later life and influence. Selkirk's experience as a castaway aroused a great deal of attention in Britain. His fellow crewman Edward Cooke mentioned Selkirk's ordeal in a book chronicling their privateering expedition, "A Voyage to the South Sea and Round the World" (1712). A more detailed recounting was published by the expedition's leader, Rogers, within months. The following year, prominent essayist Richard Steele wrote an article about him for "The Englishman" newspaper. Selkirk appeared set to enjoy a life of ease and celebrity, claiming his share of "Duke" plundered wealth—about £800 (equivalent to £ today). However, legal disputes made the amount of any payment uncertain.
After a few months in London, he began to seem more like his former self again. However, he still missed his secluded and solitary moments, remarking, "I am now worth eight hundred pounds, but shall never be as "happy" as when I was not worth a farthing." In September 1713, he was charged with assaulting a shipwright in Bristol and might have been kept in confinement for two years. He returned to Lower Largo, where he met Sophia Bruce, a young dairymaid. They eloped to London early and married on 4 March 1717. He was soon off to sea again, having enlisted in the Royal Navy. While on a visit to Plymouth in 1720, he married a widowed innkeeper named Frances Candis. He was serving as an officer on board , engaged in an anti-piracy patrol off the west coast of Africa. The ship arrived near the mouth of the River Gambia in March 1721 and lingered due to damage from bad weather. The locals took several crew hostage and ransomed them for "gold and food." As the ship sailed down the coast of West Africa, men went into the forests to cut wood and began to contract yellow fever from the swarms of mosquitoes, and perhaps typhoid. Four died in June and, by September, "so many men were dying a makeshift hospital was erected on shore" near Cape Coast Castle. Selkirk became sick in November with the same symptoms as his crewmates. He died on 13 December 1721 along with shipmate William King, and both were buried at sea; three more died the following day.
When Daniel Defoe published "The Life and Surprising Adventures of Robinson Crusoe" (1719), few readers could have missed the resemblance to Selkirk. An illustration on the first page of the novel shows "a rather melancholy-looking man standing on the shore of an island, gazing inland", in the words of modern explorer Tim Severin. He is dressed in the familiar hirsute goatskins, his feet and shins bare. Yet Crusoe's island is located not in the mid-latitudes of the South Pacific but away in the Caribbean, where the furry attire would hardly be comfortable in the tropical heat. This incongruity supports the popular belief that Selkirk was a model for the fictional character, though most literary scholars now accept that he was "just one of many survival narratives that Defoe knew about". In film. "Selkirk, the Real Robinson Crusoe" is a stop motion film by Walter Tournier based on Selkirk's life. It premièred simultaneously in Argentina, Chile, and Uruguay on 2 February 2012, distributed by The Walt Disney Company. It was the first full-length animated feature to be produced in Uruguay.
Commemoration. Selkirk has been memorialized in his Scottish birthplace. Lord Aberdeen delivered a speech on 11 December 1885, after which his wife, Lady Aberdeen, unveiled a bronze statue and plaque in memory of Selkirk outside a house on the site of his original home on the Main Street of Lower Largo. David Gillies of Cardy House, Lower Largo, a descendant of the Selkirks, donated the statue created by Thomas Stuart Burnett. The Scotsman is also remembered in his former island home. In 1869 the crew of placed a bronze tablet at a spot called Selkirk's Lookout on a mountain of Más a Tierra, Juan Fernández Islands, to mark his stay. On 1 January 1966 Chilean president Eduardo Frei Montalva renamed Más a Tierra Robinson Crusoe Island after Defoe's fictional character to attract tourists. The largest of the Juan Fernández Islands, known as Más Afuera, became Alejandro Selkirk Island, although Selkirk probably never saw that island since it is located to the west. Archaeological findings. An archaeological expedition to the Juan Fernández Islands in February 2005 found part of a nautical instrument that likely belonged to Selkirk. It was "a fragment of copper alloy identified as being from a pair of navigational dividers" dating from the early 18th (or late 17th) century. Selkirk is the only person known to have been on the island at that time who is likely to have had dividers and was even said by Rogers to have had such instruments in his possession. The artifact was discovered while excavating a site not far from Selkirk's Lookout where the famous castaway is believed to have lived. In 1825, during John Howell's research of Alexander Selkirk's biography, his "flip-can" was in the possession of his great-grand-nephew John Selkirk, and Alexander's musket was "in the possession of Major Lumsden of Lathallan."
Anti-ballistic missile An anti-ballistic missile (ABM) is a surface-to-air missile designed to destroy in-flight ballistic missiles. They achieve this explosively (chemical or nuclear), or via hit-to-kill kinetic vehicles, which may also have self-maneuvering. Tactical systems are widely deployed to counter short and intermediate-range ballistic missiles that carry conventional warheads. Strategic systems, deployed by the United States, Russia, and Israel, are capable of intercepting intercontinental ballistic missiles, typically used to carry strategic nuclear warheads. During the Cold War, the 1972 ABM Treaty limited the nuclear arms race; excessive ICBM production would have been favoured to overwhelm ABM systems. Of the modern strategic ABM systems, only Russia's are themselves armed with nuclear warheads. Current counter-ICBM systems. There are a limited number of systems worldwide that can intercept intercontinental ballistic missiles: American plans for Central European site. During 1993, a symposium was held by western European nations to discuss potential future ballistic missile defence programs. In the end, the council recommended deployment of early warning and surveillance systems as well as regionally controlled defence systems.
During spring 2006 reports about negotiations between the United States, Poland, and the Czech Republic were published. The plans propose the installation of a latest generation ABM system with a radar site in the Czech Republic and the launch site in Poland. The system was announced to be aimed against ICBMs from Iran and North Korea. This caused harsh comments by Russian President Vladimir Putin at the Organization for Security and Co-operation in Europe (OSCE) security conference during spring 2007 in Munich. Other European ministers commented that any change of strategic weapons should be negotiated on NATO level and not 'unilaterally' [sic, actually bilaterally] between the U.S. and other states (although most strategic arms reduction treaties were between the Soviet Union and U.S., not NATO). The German foreign minister Frank-Walter Steinmeier, a Social Democrat, expressed severe concerns about the way in which the U.S. had conveyed its plans to its European partners and criticised the U.S. administration for not having consulted Russia prior to announcing its endeavours to deploy a new missile defence system in Central Europe. According to a July 2007 survey, a majority of Poles were opposed to hosting a component of the system in Poland.
By 28 July 2016 Missile Defense Agency planning and agreements had clarified enough to give more details about the Aegis Ashore sites in Romania (2014) and Poland (2018). Current tactical systems. People's Republic of China. Historical Project 640. Project 640 had been the PRC's indigenous effort to develop ABM capability. The Academy of Anti-Ballistic Missile & Anti-Satellite was established from 1969 for the purpose of developing Project 640. The project was to involve at least three elements, including the necessary sensors and guidance/command system, the Fan Ji (FJ) missile interceptor, and the XianFeng missile-intercepting cannon. The FJ-1 had completed two successful flight tests during 1979, while the low-altitude interceptor FJ-2 completed some successful flight tests using scaled prototypes. A high altitude FJ-3 interceptor was also proposed. Despite the development of missiles, the programme was slowed down due to financial and political reasons. It was finally closed down during 1980 under a new leadership of Deng Xiaoping as it was seemingly deemed unnecessary after the 1972 Anti-Ballistic Missile Treaty between the Soviet Union and the United States and the closure of the US Safeguard ABM system.
Operational Chinese systems. In March 2006, China tested an interceptor system comparable to the U.S. Patriot missiles. China has acquired and is license-producing the S-300PMU-2/S-300PMU-1 series of terminal ABM-capable SAMs. The HQ-9 SAM system and HQ-15 may possess terminal ABM capabilities. PRC Navy's operating modern air-defense destroyers known as the Type 052C Destroyer and Type 051C Destroyer are armed with naval HQ-9 missiles. The HQ-19, roughly analogous to the THAAD, was first tested in 2003, and subsequently a few more times, including in November 2015. The HQ-29, a counterpart to the MIM-104F PAC-3, was first tested in 2011. China carried out a land-based anti-ballistic missile test on 11 January 2010. The test was exoatmospheric and the intercept performed in midcourse phase by a kinetic kill vehicle. The interceptor missile was a SC-19. The sources suggest the system was not operationally deployed as of 2010. On 27 January 2013, China conducted another anti-ballistic missile test. According to the Chinese Defense Ministry, the missile launch was defensive in character and was not aimed against any countries. On 4 February 2021, China reportedly conducted a mid-course intercept anti-ballistic missile test.
Europe. Aster. The Aster is a family of missiles jointly developed by France and Italy. The Aster 30 variants are capable of ballistic missile defense. An export customer, the United Kingdom also operates the Aster 30 Block 0. On 18 October 2010, France announced a successful tactical ABM test of the Aster 30 missile and on 1 December 2011 a successful interception of a Black Sparrow ballistic target missile. The s in French and Italian service, the Royal Navy's Type 45 destroyers, and the French and Italian FREMM-class frigates are all armed with PAAMS (or variants of it) integrating Aster 15 and Aster 30 missiles. France and Italy are developing a new variant, the Aster 30 Block II, which can destroy ballistic missiles up to a maximum range of . It will incorporate a kill vehicle warhead. HYDIS².
EU HYDEF. Competing against HYDIS², the EU HYDEF (European Hypersonic Defence Interceptor) also covers the concept phase to develop an endo-atmospheric interceptor and is related to TWISTER. Selected in July 2022, it is also partially funded by the EDF. It is coordinated by Spain's SENER Aeroespacial Sociedad Anonima, while Germany's Diehl Defence is serving as the overall technical lead. They are heading a consortium of partners and subcontractors from various EU countries. India. In November 2006, India successfully conducted the PADE (Prithvi Air Defence Exercise) in which an anti-ballistic missile, called the Prithvi Air Defence (PAD), an "exo-atmospheric" (outside the atmosphere) interceptor system, intercepted a Prithvi-II ballistic missile. The PAD missile has the secondary stage of the Prithvi missile and can reach altitude of . During the test, the target missile was intercepted at a altitude. On 6 December 2007, the Advanced Air Defence (AAD) missile system was tested successfully. This missile is an endo-atmospheric interceptor with an altitude of . First reported in 2009, the Defence Research and Development Organisation (DRDO) is developing a new Prithvi interceptor missile code-named PDV. The PDV is designed to take out the target missile at altitudes above . The first PDV was successfully test fired on 27 April 2014. On 15 May 2016, India successfully launched AAD renamed Ashwin from Abdul Kalam Island off the coast of Odisha.
As of 8 January 2020, the BMD programme has been completed and the Indian Air Force and the DRDO are awaiting government's final approval before the system is deployed to protect New Delhi and then Mumbai. After these two cities, it will be deployed in other major cities and regions. PAD and PDV are designed for mid-course interception, while AAD is for terminal phase interception. India had previously planned to acquire NASAMS-II but the Indian Air Force instead is now seeking a domestic alternative (potentially the land-based VL-SRSAM). Iran. Iran used Arman and S-300 missile systems for ballistic missile defense. Israel. Arrow 2. The Arrow project was begun after the U.S. and Israel agreed to co-fund it on 6 May 1986. The Arrow ABM system was designed and constructed in Israel with financial support by the United States by a multibillion-dollar development program called "Minhelet Homa" (Wall Administration) with the participation of companies like Israel Military Industries, Tadiran and Israel Aerospace Industries.
During 1998 the Israeli military conducted a successful test of their Arrow missile. Designed to intercept incoming missiles travelling at up to 2-mile/s (3 km/s), the Arrow is expected to perform much better than the Patriot did in the Gulf War. On 29 July 2004 Israel and the United States carried out a joint experiment in the US, in which the Arrow was launched against a real Scud missile. The experiment was a success, as the Arrow destroyed the Scud with a direct hit. During December 2005 the system was deployed successfully in a test against a replicated Shahab-3 missile. This feat was repeated on 11 February 2007. Arrow 3. The Arrow 3 system is capable of exo-atmosphere interception of ballistic missiles, including of ICBMs. It also acts as an anti-satellite weapon. Lieutenant General Patrick J. O'Reilly, Director of the US Missile Defense Agency, said: "The design of Arrow 3 promises to be an extremely capable system, more advanced than what we have ever attempted in the U.S. with our programs." On 10 December 2015 Arrow 3 scored its first intercept in a complex test designed to validate how the system can detect, identify, track and then discriminate real from decoy targets delivered into space by an improved Silver Sparrow target missile. According to officials, the milestone test paves the way toward low-rate initial production of the Arrow 3.
David’s sling. David's Sling (Hebrew: קלע דוד), also sometimes called Magic Wand (Hebrew: שרביט קסמים), is an Israel Defense Forces military system being jointly developed by the Israeli defense contractor Rafael Advanced Defense Systems and the American defense contractor Raytheon, designed to intercept tactical ballistic missiles, as well as medium- to long-range rockets and slower-flying cruise missiles, such as those possessed by Hezbollah, fired at ranges from 40 km to 300 km. It is designed with the aim of intercepting the newest generation of tactical ballistic missiles, such as Iskander. Japan. Since 1998, when North Korea launched a Taepodong-1 missile over northern Japan, the Japanese have been jointly developing a new surface-to-air interceptor known as the Patriot Advanced Capability 3 (PAC-3) with the US. Tests have been successful, and there are 11 locations that are planned for the PAC-3 to be installed. The approximate locations are near major air bases, like Kadena Air Base, and ammunition storage centers of the Japanese military. The exact location are not known to the public. A military spokesman said that tests had been done on two sites, one of them a business park in central Tokyo, and Ichigaya – a site not far from the Imperial Palace.
Along with the PAC-3, Japan has installed a US-developed ship-based anti-ballistic missile system, which was tested successfully on 18 December 2007. Japan has 4 destroyers of this type capable of carrying RIM-161 Standard Missile 3 and equipped with the Aegis Ballistic Missile Defense System. Japan is currently modifying another 4 destroyers so that they can take part of their defense force against ballistic missiles, bringing the total number to 8 ships. Soviet Union/Russian Federation. The Moscow ABM defense system was designed with the aim of being able to intercept the ICBM warheads aimed at Moscow and other important industrial regions, and is based on: United States. In several tests, the U.S. military have demonstrated the feasibility of destroying long and short range ballistic missiles. Combat effectiveness of newer systems against 1950s tactical ballistic missiles seems very high, as the MIM-104 Patriot (PAC-1 and PAC-2) had a 100% success rate in Operation Iraqi Freedom. The U.S. Navy Aegis Ballistic Missile Defense System (Aegis BMD) uses RIM-161 Standard Missile 3, which hit a target going faster than ICBM warheads. On 16 November 2020 an SM-3 Block IIA interceptor successfully destroyed an ICBM in mid-course, under Link-16 Command and Control, Battle Management, and Communications (C2BMC).
The U.S. Army Terminal High Altitude Area Defense (THAAD) system began production in 2008. Its stated range as a short to intermediate ballistic missile interceptor means that it is not designed to hit midcourse ICBMs, which can reach terminal phase speeds of mach 8 or greater. The THAAD interceptor has a reported maximum speed of mach 8, and THAAD has repeatedly proven it can intercept descending exoatmospheric missiles in a ballistic trajectory. The U.S. Army Ground-Based Midcourse Defense (GMD) system was developed by the Missile Defense Agency. It combines ground-based AN/FPS-132 Upgraded Early Warning Radar installations and mobile AN/TPY-2 X-band radars with 44 exoatmospheric interceptors stationed in underground silos around California and Alaska, to protect against low-count ICBM attacks from rogue states. Each Ground-Based Interceptor (GBI) rocket carries an Exoatmospheric Kill Vehicle (EKV) kinetic kill interceptor, with 97% probability of intercept when four interceptors are launched at the target.
Since 2004, the United States Army plans to replace Raytheon's Patriot missile (SAM) engagement control station (ECS), along with seven other forms of ABM defense command systems, with Integrated Air and Missile Defense Battle Command System (IBCS) designed to shoot down short, medium, and intermediate range ballistic missiles in their terminal phase by intercepting with a hit-to-kill approach. Northrop Grumman was selected as the prime contractor in 2010; the Army spent $2.7 billion on the program between 2009 and 2020. IBCS engagement stations will support identification and tracking of targets using sensor fusion from disparate data streams, and selection of appropriate kill vehicles from available launcher systems. In February 2022 THAAD radar and TFCC (THAAD Fire Control & Communication) demonstrated their interoperability with Patriot PAC-3 MSE missile launchers, engaging targets using both THAAD and Patriot interceptors. Republic of China. Procurement of MIM-104 Patriot and indigenous Tien-Kung anti-ballistic missile systems. With the tense situations with China, Taiwan developed the Sky Bow (or Tien-Kung), this surface-to-air missile can intercept and destroy enemy aircraft and ballistic missiles. These system was created in partnership with Raytheon Technologies, using Lockheed Martin ADAR-HP as inspiration to create the Chang Bai S-band radar system. The missiles have a range of 200 km and was designed to take on fast moving vehicles with low radar cross-section. The latest variant of this system is the Sky Bow III (TK-3).
South Korea. Since North Korea started developing its nuclear weapon program, South Korea has been under imminent danger. South Korea started its BDM program by acquiring 8 batteries of the MIM-104 Patriot (PAC-2) missiles from the United States. The PAC-2 was developed to destroy incoming aircraft and is now unreliable in defending a ballistic missile attack from North Korea, as they have developed further their nuclear program. As of 2018, South Korea decided to improve its defense system by upgrading to the PAC-3, which has a hit-to-kill capability against incoming missiles. The main reason that the South Korean anti-ballistic defense system is not very developed is because they have tried to developed their own, without help from other countries, since the beginning of the 1990s. The South Korean Defense Acquisition Program Administration (DAPA) has confirmed that it has test launched the L-SAM system in February 2022. This particular missile has been in development since 2019 and is South Korea's next anti-ballistic missile generation. It is expected to have a range of 150 km and be able to intercept targets between 40 km and 100 km of altitude, and it can also be used as an aircraft interceptor. The L-SAM system is expected to be complete and ready to use in 2024.
History. 1940s and 1950s. The idea of destroying rockets before they can hit their target dates from the first use of modern missiles in warfare, the German V-1 and V-2 program of World War II. British fighters destroyed some V-1 "buzz bombs" in flight, although concentrated barrages of heavy anti-aircraft artillery had greater success. Under the lend-lease program, 200 US 90 mm AA guns with SCR-584 radars and Western Electric/Bell Labs computers were sent to the UK. These demonstrated a 95% success rate against V-1s that flew into their range. The V-2, the first true ballistic missile, has no known record of being destroyed in the air. SCR-584's could be used to plot the trajectories of the missiles and provide some warning, but were more useful in backtracking their ballistic trajectory and determining the rough launch locations. The Allies launched Operation Crossbow to find and destroy V-2s before launch, but these operations were largely ineffective. In one instance a Spitfire happened upon a V-2 rising through the trees, and fired on it with no effect. This led to allied efforts to capture launching sites in Belgium and the Netherlands.
A wartime study by Bell Labs into the task of shooting down ballistic missiles in flight concluded it was not possible. In order to intercept a missile, one needs to be able to steer the attack onto the missile before it hits. A V-2's speed would require guns of effectively instantaneous reaction time, or some sort of weapon with ranges on the order of dozens of miles, neither of which appeared possible. This was, however, just before the emergence of high-speed computing systems. By the mid-1950s, things had changed considerably, and many forces worldwide were considering ABM systems. The American armed forces began experimenting with anti-missile missiles soon after World War II, as the extent of German research into rocketry became clear. Project Wizard began in 1946, with the aim of creating a missile capable of intercepting the V-2. But defences against Soviet long-range bombers took priority until 1957, when the Soviet Union demonstrated its advances in ICBM technology with the launch of Sputnik, the Earth's first artificial satellite. The US Army accelerated development of their LIM-49 Nike Zeus system in response. Zeus was criticized throughout its development program, especially from those within the US Air Force and nuclear weapons establishments who suggested it would be much simpler to build more nuclear warheads and guarantee mutually assured destruction. Zeus was eventually cancelled in 1963.
In 1958, the U.S. sought to explore whether airbursting nuclear weapons might be used to ward off ICBMs. It conducted several test explosions of low-yield nuclear weapons – 1.7kt boosted fission W25 warheads – launched from ships to very high altitudes over the southern Atlantic Ocean. Such an explosion releases a burst of X-rays in the Earth's atmosphere, causing secondary showers of charged particles over an area hundreds of miles across. These can become trapped in the Earth' magnetic field, creating an artificial radiation belt. It was believed that this might be strong enough to damage warheads traveling through the layer. This proved not to be the case, but Argus returned key data about a related effect, the nuclear electromagnetic pulse (NEMP). Canada. Other countries were also involved in early ABM research. A more advanced project was at CARDE in Canada, which researched the main problems of ABM systems. A key problem with any radar system is that the signal is in the form of a cone, which spreads with distance from the transmitter. For long-distance interceptions like ABM systems, the inherent inaccuracy of the radar makes an interception difficult. CARDE considered using a terminal guidance system to address the accuracy concerns, and developed several advanced infrared detectors for this role. They also studied a number of missile airframe designs, a new and much more powerful solid rocket fuel, and numerous systems for testing it all. After a series of drastic budget reductions during the late 1950s the research ended. One offshoot of the project was Gerald Bull's system for inexpensive high-speed testing, consisting of missile airframes shot from a sabot round, which would later be the basis of Project HARP. Another was the CRV7 and Black Brant rockets, which used the new solid rocket fuel.
Soviet Union. The Soviet military had requested funding for ABM research as early as 1953, but were only given the go-ahead to begin deployment of such a system on 17 August 1956. Their test system, known simply as System A, was based on the V-1000 missile, which was similar to the early US efforts. The first successful test interception was carried out on 24 November 1960, and the first with a live warhead on 4 March 1961. In this test, a dummy warhead was released by a R-12 ballistic missile launched from the Kapustin Yar, and intercepted by a V-1000 launched from Sary-Shagan. The dummy warhead was destroyed by the impact of 16,000 tungsten-carbide spherical impactors 140 seconds after launch, at an altitude of . The V-1000 missile system was nonetheless considered not reliable enough and abandoned in favour of nuclear-armed ABMs. Retired V-1000 was used to develop 1Ya2TA sounding rocket, capable of launching 520 kg scientific payload to an altitude of 400 km. A much larger missile, the Fakel 5V61 (known in the west as Galosh), was developed to carry the larger warhead and carry it much further from the launch site. Further development continued, and the A-35 anti-ballistic missile system, designed to protect Moscow, became operational in 1971. A-35 was designed for exoatmospheric interceptions, and would have been highly susceptible to a well-arranged attack using multiple warheads and radar black-out techniques.
A-35 was upgraded during the 1980s to a two-layer system, the A-135. The Gorgon (SH-11/ABM-4) long-range missile was designed to handle intercepts outside the atmosphere, and the Gazelle (SH-08/ABM-3) short-range missile endoatmospheric intercepts that eluded Gorgon. The A-135 system is considered to be technologically equivalent to the United States Safeguard system of 1975. American Nike-X and Sentinel. Nike Zeus failed to be a credible defense in an era of rapidly increasing ICBM counts due to its ability to attack only one target at a time. Additionally, significant concerns about its ability to successfully intercept warheads in the presence of high-altitude nuclear explosions, including its own, lead to the conclusion that the system would simply be too costly for the very low amount of protection it could provide. By the time it was cancelled in 1963, potential upgrades had been explored for some time. Among these were radars capable of scanning much greater volumes of space and able to track many warheads and launch several missiles at once. These, however, did not address the problems identified with radar blackouts caused by high-altitude explosions. To address this need, a new missile with extreme performance was designed to attack incoming warheads at much lower altitudes, as low as 20 km. The new project encompassing all of these upgrades was launched as Nike-X.
The main missile was LIM-49 Spartan—a Nike Zeus upgraded for longer range and a much larger 5 megaton warhead intended to destroy enemy's warheads with a burst of x-rays outside the atmosphere. A second shorter-range missile called Sprint with very high acceleration was added to handle warheads that evaded longer-ranged Spartan. Sprint was a very fast missile (some sources claimed it accelerated to 8,000 mph (13 000 km/h) within 4 seconds of flight—an average acceleration of "90 g") and had a smaller W66 enhanced radiation warhead in the 1–3 kiloton range for in-atmosphere interceptions. The experimental success of Nike X persuaded the Lyndon B. Johnson administration to propose a thin ABM defense, that could provide almost complete coverage of the United States. In a September 1967 speech, Defense Secretary Robert McNamara referred to it as "Sentinel". McNamara, a private ABM opponent because of cost and feasibility (see cost-exchange ratio), claimed that Sentinel would be directed not against the Soviet Union's missiles (since the USSR had more than enough missiles to overwhelm any American defense), but rather against the potential nuclear threat of the People's Republic of China.
In the meantime, a public debate over the merit of ABMs began. Difficulties that had already made an ABM system questionable for defending against an all-out attack. One problem was the Fractional Orbital Bombardment System (FOBS) that would give little warning to the defense. Another problem was high altitude EMP (whether from offensive or defensive nuclear warheads) which could degrade defensive radar systems. When this proved infeasible for economic reasons, a much smaller deployment using the same systems was proposed, namely Safeguard (described later). Defense against MIRVs. ABM systems were developed initially to counter single warheads launched from large intercontinental ballistic missiles (ICBMs). The economics seemed simple enough; since rocket costs increase rapidly with size, the price of the ICBM launching a large warhead should always be greater than the much smaller interceptor missile needed to destroy it. In an arms race the defense would always win. In addition to the blast effect, the detonation of nuclear devices against attacking intercontinental ballistic missiles produces a neutron kill effect from the strong radiation emitted, and this neutralizes the warhead, or warheads, of the attacking missile. Most A.B.M. devices depend on neutron kill for their effectiveness.
In practice, the price of the interceptor missile was considerable, due to its sophistication. The system had to be guided all the way to an interception, which demanded guidance and control systems that worked within and outside the atmosphere. Due to their relatively short ranges, an ABM missile would be needed to counter an ICBM wherever it might be aimed. That implies that dozens of interceptors are needed for every ICBM since warhead's targets couldn't be known in advance. This led to intense debates about the "cost-exchange ratio" between interceptors and warheads. Conditions changed dramatically in 1970 with the introduction of multiple independently targetable reentry vehicle (MIRV) warheads. Suddenly, each launcher was throwing not one warhead, but several. These would spread out in space, ensuring that a single interceptor would be needed for each warhead. This simply added to the need to have several interceptors for each warhead in order to provide geographical coverage. Now it was clear that an ABM system would always be many times more expensive than the ICBMs they defended against.
Anti-Ballistic Missile Treaty of 1972. Technical, economic and political problems described resulted in the ABM treaty of 1972, which restricted the deployment of strategic (not tactical) anti-ballistic missiles. By the ABM treaty and a 1974 revision, each country was allowed to deploy a mere 100 ABMs to protect a single, small area. The Soviets retained their Moscow defences. The U.S. designated their ICBM sites near Grand Forks Air Force Base, North Dakota, where Safeguard was already under advanced development. The radar systems and anti-ballistic missiles were approximately 90 miles north/northwest of Grand Forks AFB, near Concrete, North Dakota. The missiles were deactivated in 1975. The main radar site (PARCS) is still used as an early warning ICBM radar, facing relative north. It is located at Cavalier Air Force Station, North Dakota. Brief use of Safeguard in 1975/1976. The U.S. Safeguard system, which utilized the nuclear-tipped LIM-49A Spartan and Sprint missiles, in the short operational period of 1975/1976, was the second counter-ICBMs system in the world. Safeguard protected only the main fields of US ICBMs from attack, theoretically ensuring that an attack could be responded to with a US launch, enforcing the mutually assured destruction principle.
SDI experiments in the 1980s. The Reagan-era Strategic Defense Initiative (often referred to as "Star Wars"), along with research into various energy-beam weaponry, brought new interest in the area of ABM technologies. SDI was an extremely ambitious program to provide a total shield against a massive Soviet ICBM attack. The initial concept envisioned large sophisticated orbiting laser battle stations, space-based relay mirrors, and nuclear-pumped X-ray laser satellites. Later research indicated that some planned technologies such as X-ray lasers were not feasible with then-current technology. As research continued, SDI evolved through various concepts as designers struggled with the difficulty of such a large complex defense system. SDI remained a research program and was never deployed. Several post-SDI technologies are used by the present Missile Defense Agency (MDA). Lasers originally developed for the SDI plan are in use for astronomical observations. Used to ionize gas in the upper atmosphere, they provide telescope operators with a target to calibrate their instruments.
Tactical ABMs deployed in 1990s. The Israeli Arrow missile system was tested initially during 1990, before the first Gulf War. The Arrow was supported by the United States throughout the 1990s. The Patriot was the first deployed tactical ABM system, although it was not designed from the outset for that task and consequently had limitations. It was used during the 1991 Gulf War to attempt to intercept Iraqi Scud missiles. Post-war analyses show that the Patriot was much less effective than initially thought because of its radar and control system's inability to discriminate warheads from other objects when the Scud missiles broke up during reentry. Testing ABM technology continued during the 1990s with mixed success. After the Gulf War, improvements were made to several U.S. air defense systems. A new Patriot, PAC-3, was developed and tested—a complete redesign of the PAC-2 deployed during the war, including a totally new missile. The improved guidance, radar and missile performance improves the probability of kill over the earlier PAC-2. During Operation Iraqi Freedom, Patriot batteries engaged 100% of enemy TBMs within their engagement territory. Of these engagements, 8 of them were verified as kills by multiple independent sensors; the remaining was listed as a probable kill due to lack of independent verification. Patriot was involved in three friendly fire incidents: two incidents of Patriot shootings at coalition aircraft and one of U.S. aircraft shooting at a Patriot battery.
A new version of the Hawk missile was tested during the early to mid-1990s and by the end of 1998 the majority of US Marine Corps Hawk systems were modified to support basic theater anti-ballistic missile capabilities. The MIM-23 Hawk missile is not operational in U.S. service since 2002, but is used by many other countries. Soon after the Gulf War, the Aegis Combat System was expanded to include ABM capabilities. The Standard missile system was also enhanced and tested for ballistic missile interception. During the late 1990s, SM-2 block IVA missiles were tested in a theater ballistic missile defense function. Standard Missile 3 (SM-3) systems have also been tested for an ABM role. In 2008, an SM-3 missile launched from the , successfully intercepted a non-functioning satellite. Brilliant Pebbles concept. Approved for acquisition by the Pentagon during 1991 but never realized, Brilliant Pebbles was a proposed space-based anti-ballistic system that was meant to avoid some of the problems of the earlier SDI concepts. Rather than use sophisticated large laser battle stations and nuclear-pumped X-ray laser satellites, Brilliant Pebbles consisted of a thousand very small, intelligent orbiting satellites with kinetic warheads. The system relied on improvements of computer technology, avoided problems with overly centralized command and control and risky, expensive development of large, complicated space defense satellites.
It promised to be much less expensive to develop and have less technical development risk. The name Brilliant Pebbles comes from the small size of the satellite interceptors and great computational power enabling more autonomous targeting. Rather than rely exclusively on ground-based control, the many small interceptors would cooperatively communicate among themselves and target a large swarm of ICBM warheads in space or in the late boost phase. Development was discontinued later in favor of a limited ground-based defense. Transformation of SDI into MDA, development of NMD/GMD. While the Reagan era Strategic Defense Initiative was intended to shield against a massive Soviet attack, during the early 1990s, President George H. W. Bush called for a more limited version using rocket-launched interceptors based on the ground at a single site. Such system was developed since 1992, was expected to become operational in 2010 and capable of intercepting small number of incoming ICBMs. First called the National Missile Defense (NMD), since 2002 it was renamed Ground-Based Midcourse Defense (GMD). It was planned to protect all 50 states from a rogue missile attack. The Alaska site provides more protection against North Korean missiles or accidental launches from Russia or China, but is likely less effective against missiles launched from the Middle East. The Alaska interceptors may be augmented later by the naval Aegis Ballistic Missile Defense System or by ground-based missiles in other locations.
During 1998, Defense Secretary William Cohen proposed spending an additional $6.6 billion on intercontinental ballistic missile defense programs to build a system to protect against attacks from North Korea or accidental launches from Russia or China. In terms of organization, during 1993 SDI was reorganized as the Ballistic Missile Defense Organization. In 2002, it was renamed to Missile Defense Agency (MDA). 21st century. On 13 June 2002, the United States withdrew from the Anti-Ballistic Missile Treaty and recommenced developing missile defense systems that would have formerly been prohibited by the bilateral treaty. The action was stated as needed to defend against the possibility of a missile attack conducted by a rogue state. The next day, the Russian Federation dropped the START II agreement, intended to completely ban MIRVs.
On 15 December 2016, the US Army SMDC had a successful test of a U.S. Army Zombie Pathfinder rocket, to be used as a target for exercising various anti-ballistic missile scenarios. The rocket was launched as part of NASA's sounding rocket program, at White Sands Missile Range. In November 2020, the US successfully destroyed a dummy ICBM. The ICBM was launched from Kwajalein Atoll in the general direction of Hawaii, triggering a satellite warning to a Colorado Air Force base, which then contacted the . The ship launched a SM-3 Block IIA missile to destroy the US dummy, still outside the atmosphere.
Acre The acre ( ) is a unit of land area used in the British imperial and the United States customary systems. It is traditionally defined as the area of one chain by one furlong (66 by 660 feet), which is exactly equal to 10 square chains, of a square mile, 4,840 square yards, or 43,560 square feet, and approximately 4,047 m2, or about 40% of a hectare. Based upon the international yard and pound agreement of 1959, an acre may be declared as exactly 4,046.8564224 square metres. The acre is sometimes abbreviated ac but is usually spelled out as the word "acre". Traditionally, in the Middle Ages, an acre was conceived of as the area of land that could be ploughed by one man using a team of eight oxen in one day. The acre is still a statutory measure in the United States. Both the international acre and the US survey acre are in use, but they differ by only four parts per million (see below). The most common use of the acre is to measure tracts of land. The acre is used in many established and former Commonwealth of Nations countries by custom. In a few, it continues as a statute measure, although not since 2010 in the UK, and not for decades in Australia, New Zealand, and South Africa. In many places where it is not a statute measure, it is still lawful to "use for trade" if given as supplementary information and is not used for land registration.
Description. One acre equals (0.0015625) square mile, 4,840 square yards, 43,560 square feet, or about (see below). While all modern variants of the acre contain 4,840 square yards, there are alternative definitions of a yard, so the exact size of an acre depends upon the particular yard on which it is based. Originally, an acre was understood as a strip of land sized at forty perches (660 ft, or 1 furlong) long and four perches (66 ft) wide; this may have also been understood as an approximation of the amount of land a yoke of oxen could plough in one day (a furlong being "a furrow long"). A square enclosing one acre is approximately 69.57 yards, or 208 feet 9 inches (), on a side. As a unit of measure, an acre has no prescribed shape; any area of 43,560 square feet is an acre. US survey acres. In the international yard and pound agreement of 1959, the United States and five countries of the Commonwealth of Nations defined the international yard to be exactly 0.9144 metre. The US authorities decided that, while the refined definition would apply nationally in all other respects, the US survey foot (and thus the survey acre) would continue 'until such a time as it becomes desirable and expedient to readjust [it]'. By inference, an "international acre" may be calculated as exactly square metres but it does not have a basis in any international agreement.
Both the international acre and the US survey acre contain of a square mile or 4,840 square yards, but alternative definitions of a yard are used (see survey foot and survey yard), so the exact size of an acre depends upon the yard upon which it is based. The US survey acre is about 4,046.872 square metres; its exact value ( m2) is based on an inch defined by 1 metre = 39.37 inches exactly, as established by the Mendenhall Order of 1893. Surveyors in the United States use both international and survey feet, and consequently, both varieties of acre. Since the difference between the US survey acre and international acre (0.016 square metres, 160 square centimetres or 24.8 square inches), is only about a quarter of the size of an A4 sheet or US letter, it is usually not important which one is being discussed. Areas are seldom measured with sufficient accuracy for the different definitions to be detectable. In October 2019, the US National Geodetic Survey and the National Institute of Standards and Technology announced their joint intent to end the "temporary" continuance of the US survey foot, mile, and acre units (as permitted by their 1959 decision, above), with effect from the end of 2022.
Spanish acre. The Puerto Rican "cuerda" () is sometimes called the "Spanish acre" in the continental United States. Use. The acre is commonly used in many current and former Commonwealth countries by custom, and in a few it continues as a statute measure. These include Antigua and Barbuda, American Samoa, The Bahamas, Belize, the British Virgin Islands, Canada, the Cayman Islands, Dominica, the Falkland Islands, Grenada, Ghana, Guam, the Northern Mariana Islands, Jamaica, Montserrat, Samoa, Saint Lucia, St. Helena, St. Kitts and Nevis, St. Vincent and the Grenadines, Turks and Caicos, the United Kingdom, the United States and the US Virgin Islands. Republic of Ireland. In the Republic of Ireland, the hectare is legally used under European units of measurement directives; however, the acre (the same standard statute as used in the UK, not the old Irish acre, which was of a different size) is still widely used, especially in agriculture. Indian subcontinent. In India, residential plots are measured in square feet or square metre, while agricultural land is measured in acres. In Sri Lanka, the division of an acre into 160 perches or 4 roods is common.
In Pakistan, residential plots are measured in (20 = 1 = 605 sq yards) and open/agriculture land measurement is in acres (8 = 1 acre) and (25 acres = 1 = 200 ), and . United Kingdom. Its use as a primary unit for trade in the United Kingdom ceased to be permitted from 1 October 1995, due to the 1994 amendment of the Weights and Measures Act, where it was replaced by the hectare though its use as a supplementary unit continues to be permitted indefinitely. This was with the exemption of land registration, which records the sale and possession of land; in 2010 HM Land Registry ended its exemption. The measure is still used to communicate with the public and informally (non-contract) by the farming and property industries. Equivalence to other units of area. 1 international acre is equal to the following metric units: 1 United States survey acre is equal to: 1 acre (both variants) is equal to the following customary units: Perhaps the easiest way for US residents to envision an acre is as a rectangle measuring 88 yards by 55 yards ( of 880 yards by of 880 yards), about the size of a standard American football field. To be more exact, one acre is 90.75% of a 100-yd-long by 53.33-yd-wide American football field (without the end zone). The full field, including the end zones, covers about .
For residents of other countries, the acre might be envisioned as rather more than half of a football pitch. Historical origin. The word acre is derived from the Norman, attested for the first time in a text of Fécamp in 1006 to the meaning of «agrarian measure». Acre dates back to the old Scandinavian akr “cultivated field, ploughed land” which is perpetuated in Icelandic and the Faroese “field (wheat)”, Norwegian and Swedish , Danish “field”, cognate with German , Dutch , Latin , Sanskrit , and Greek (). In English, an obsolete variant spelling was "aker". According to the Act on the Composition of Yards and Perches, dating from around 1300, an acre is "40 perches [rods] in length and four in breadth", meaning 220 yards by 22 yards. As detailed in the diagram, an acre was roughly the amount of land tillable by a yoke of oxen in one day. Before the enactment of the metric system, many countries in Europe used their own official acres. In France, the traditional unit of area was the "arpent carré", a measure based on the Roman system of land measurement.
The was used only in Normandy (and neighbouring places outside its traditional borders), but its value varied greatly across Normandy, ranging from 3,632 to 9,725 square metres, with 8,172 square metres being the most frequent value. But inside the same of Normandy, for instance in pays de Caux, the farmers (still in the 20th century) made the difference between the (68 ares, 66 centiares) and the (56 to 65 ca). The Normandy was usually divided in 4 (roods) and 160 square , like the English acre. The Normandy was equal to 1.6 , the unit of area more commonly used in Northern France outside of Normandy. In Canada, the Paris used in Quebec before the metric system was adopted is sometimes called "French acre" in English, even though the Paris and the Normandy were two very different units of area in ancient France (the Paris became the unit of area of French Canada, whereas the Normandy was never used in French Canada). In Germany, the Netherlands, and Eastern Europe the traditional unit of area was . Like the acre, the "morgen" was a unit of ploughland, representing a strip that could be ploughed by one man and an ox or horse in a morning. There were many variants of the "morgen", differing between the different German territories, ranging from . It was also used in Old Prussia, in the Balkans, Norway, and Denmark, where it was equal to about .
Statutory values for the acre were enacted in England, and subsequently the United Kingdom, by acts of: Historically, the size of farms and landed estates in the United Kingdom was usually expressed in acres (or acres, roods, and perches), even if the number of acres was so large that it might conveniently have been expressed in square miles. For example, a certain landowner might have been said to own 32,000 acres of land, not 50 square miles of land. The acre is related to the square mile, with 640 acres making up one square mile. One mile is 5280 feet (1760 yards). In western Canada and the western United States, divisions of land area were typically based on the square mile, and fractions thereof. If the square mile is divided into quarters, each quarter has a side length of mile (880 yards) and is square mile in area, or 160 acres. These subunits are typically then again divided into quarters, with each side being mile long, and being of a square mile in area, or 40 acres. In the United States, farmland was typically divided as such, and the phrase "the back 40" refers to the 40-acre parcel to the back of the farm. Most of the Canadian Prairie Provinces and the US Midwest are on square-mile grids for surveying purposes.
Adenosine triphosphate Adenosine triphosphate (ATP) is a nucleoside triphosphate that provides energy to drive and support many processes in living cells, such as muscle contraction, nerve impulse propagation, and chemical synthesis. Found in all known forms of life, it is often referred to as the "molecular unit of currency" for intracellular energy transfer. When consumed in a metabolic process, ATP converts either to adenosine diphosphate (ADP) or to adenosine monophosphate (AMP). Other processes regenerate ATP. It is also a precursor to DNA and RNA, and is used as a coenzyme. An average adult human processes around 50 kilograms (about 100 moles) daily. From the perspective of biochemistry, ATP is classified as a nucleoside triphosphate, which indicates that it consists of three components: a nitrogenous base (adenine), the sugar ribose, and the triphosphate. Structure. ATP consists of an adenine attached by the #9-nitrogen atom to the 1′ carbon atom of a sugar (ribose), which in turn is attached at the 5' carbon atom of the sugar to a triphosphate group. In its many reactions related to metabolism, the adenine and sugar groups remain unchanged, but the triphosphate is converted to di- and monophosphate, giving respectively the derivatives ADP and AMP. The three phosphoryl groups are labeled as alpha (α), beta (β), and, for the terminal phosphate, gamma (γ).
In neutral solution, ionized ATP exists mostly as ATP4−, with a small proportion of ATP3−. Metal cation binding. Polyanionic and featuring a potentially chelating polyphosphate group, ATP binds metal cations with high affinity. The binding constant for is (). The binding of a divalent cation, almost always magnesium, strongly affects the interaction of ATP with various proteins. Due to the strength of the ATP-Mg2+ interaction, ATP exists in the cell mostly as a complex with bonded to the phosphate oxygen centers. A second magnesium ion is critical for ATP binding in the kinase domain. The presence of Mg2+ regulates kinase activity. It is interesting from an RNA world perspective that ATP can carry a Mg ion which catalyzes RNA polymerization. Chemical properties. Salts of ATP can be isolated as colorless solids. ATP is stable in aqueous solutions between pH 6.8 and 7.4 (in the absence of catalysts). At more extreme pH levels, it rapidly hydrolyses to ADP and phosphate. Living cells maintain the ratio of ATP to ADP at a point ten orders of magnitude from equilibrium, with ATP concentrations fivefold higher than the concentration of ADP. In the context of biochemical reactions, the P-O-P bonds are frequently referred to as "high-energy bonds".
Reactive aspects. The hydrolysis of ATP into ADP and inorganic phosphate releases of enthalpy. This may differ under physiological conditions if the reactant and products are not exactly in these ionization states. The values of the free energy released by cleaving either a phosphate (Pi) or a pyrophosphate (PPi) unit from ATP at standard state concentrations of 1 mol/L at pH 7 are: These abbreviated equations at a pH near 7 can be written more explicitly (R = adenosyl): At cytoplasmic conditions, where the ADP/ATP ratio is 10 orders of magnitude from equilibrium, the Δ"G" is around −57 kJ/mol. Along with pH, the free energy change of ATP hydrolysis is also associated with Mg2+ concentration, from ΔG°' = −35.7 kJ/mol at a Mg2+ concentration of zero, to ΔG°' = −31 kJ/mol at [Mg2+] = 5 mM. Higher concentrations of Mg2+ decrease free energy released in the reaction due to binding of Mg2+ ions to negatively charged oxygen atoms of ATP at pH 7. Production from AMP and ADP. Production, aerobic conditions. A typical intracellular concentration of ATP may be 1–10 μmol per gram of tissue in a variety of eukaryotes. The dephosphorylation of ATP and rephosphorylation of ADP and AMP occur repeatedly in the course of aerobic metabolism.
ATP can be produced by a number of distinct cellular processes; the three main pathways in eukaryotes are (1) glycolysis, (2) the citric acid cycle/oxidative phosphorylation, and (3) beta-oxidation. The overall process of oxidizing glucose to carbon dioxide, the combination of pathways 1 and 2, known as cellular respiration, produces about 30 equivalents of ATP from each molecule of glucose. ATP production by a non-photosynthetic aerobic eukaryote occurs mainly in the mitochondria, which comprise nearly 25% of the volume of a typical cell. Glycolysis. In glycolysis, glucose and glycerol are metabolized to pyruvate. Glycolysis generates two equivalents of ATP through substrate phosphorylation catalyzed by two enzymes, phosphoglycerate kinase (PGK) and pyruvate kinase. Two equivalents of nicotinamide adenine dinucleotide (NADH) are also produced, which can be oxidized via the electron transport chain and result in the generation of additional ATP by ATP synthase. The pyruvate generated as an end-product of glycolysis is a substrate for the Krebs Cycle.
Glycolysis is viewed as consisting of two phases with five steps each. In phase 1, "the preparatory phase", glucose is converted to 2 d-glyceraldehyde-3-phosphate (g3p). One ATP is invested in Step 1, and another ATP is invested in Step 3. Steps 1 and 3 of glycolysis are referred to as "Priming Steps". In Phase 2, two equivalents of g3p are converted to two pyruvates. In Step 7, two ATP are produced. Also, in Step 10, two further equivalents of ATP are produced. In Steps 7 and 10, ATP is generated from ADP. A net of two ATPs is formed in the glycolysis cycle. The glycolysis pathway is later associated with the Citric Acid Cycle which produces additional equivalents of ATP. Regulation. In glycolysis, hexokinase is directly inhibited by its product, glucose-6-phosphate, and pyruvate kinase is inhibited by ATP itself. The main control point for the glycolytic pathway is phosphofructokinase (PFK), which is allosterically inhibited by high concentrations of ATP and activated by high concentrations of AMP. The inhibition of PFK by ATP is unusual since ATP is also a substrate in the reaction catalyzed by PFK; the active form of the enzyme is a tetramer that exists in two conformations, only one of which binds the second substrate fructose-6-phosphate (F6P). The protein has two binding sites for ATP – the active site is accessible in either protein conformation, but ATP binding to the inhibitor site stabilizes the conformation that binds F6P poorly. A number of other small molecules can compensate for the ATP-induced shift in equilibrium conformation and reactivate PFK, including cyclic AMP, ammonium ions, inorganic phosphate, and fructose-1,6- and -2,6-biphosphate.
Citric acid cycle. In the mitochondrion, pyruvate is oxidized by the pyruvate dehydrogenase complex to the acetyl group, which is fully oxidized to carbon dioxide by the citric acid cycle (also known as the Krebs cycle). Every "turn" of the citric acid cycle produces two molecules of carbon dioxide, one equivalent of ATP guanosine triphosphate (GTP) through substrate-level phosphorylation catalyzed by succinyl-CoA synthetase, as succinyl-CoA is converted to succinate, three equivalents of NADH, and one equivalent of FADH2. NADH and FADH2 are recycled (to NAD+ and FAD, respectively) by oxidative phosphorylation, generating additional ATP. The oxidation of NADH results in the synthesis of 2–3 equivalents of ATP, and the oxidation of one FADH2 yields between 1–2 equivalents of ATP. The majority of cellular ATP is generated by this process. Although the citric acid cycle itself does not involve molecular oxygen, it is an obligately aerobic process because O2 is used to recycle the NADH and FADH2. In the absence of oxygen, the citric acid cycle ceases.
The generation of ATP by the mitochondrion from cytosolic NADH relies on the malate-aspartate shuttle (and to a lesser extent, the glycerol-phosphate shuttle) because the inner mitochondrial membrane is impermeable to NADH and NAD+. Instead of transferring the generated NADH, a malate dehydrogenase enzyme converts oxaloacetate to malate, which is translocated to the mitochondrial matrix. Another malate dehydrogenase-catalyzed reaction occurs in the opposite direction, producing oxaloacetate and NADH from the newly transported malate and the mitochondrion's interior store of NAD+. A transaminase converts the oxaloacetate to aspartate for transport back across the membrane and into the intermembrane space. In oxidative phosphorylation, the passage of electrons from NADH and FADH2 through the electron transport chain releases the energy to pump protons out of the mitochondrial matrix and into the intermembrane space. This pumping generates a proton motive force that is the net effect of a pH gradient and an electric potential gradient across the inner mitochondrial membrane. Flow of protons down this potential gradient – that is, from the intermembrane space to the matrix – yields ATP by ATP synthase. Three ATP are produced per turn.
Although oxygen consumption appears fundamental for the maintenance of the proton motive force, in the event of oxygen shortage (hypoxia), intracellular acidosis (mediated by enhanced glycolytic rates and ATP hydrolysis), contributes to mitochondrial membrane potential and directly drives ATP synthesis. Most of the ATP synthesized in the mitochondria will be used for cellular processes in the cytosol; thus it must be exported from its site of synthesis in the mitochondrial matrix. ATP outward movement is favored by the membrane's electrochemical potential because the cytosol has a relatively positive charge compared to the relatively negative matrix. For every ATP transported out, it costs 1 H+. Producing one ATP costs about 3 H+. Therefore, making and exporting one ATP requires 4H+. The inner membrane contains an antiporter, the ADP/ATP translocase, which is an integral membrane protein used to exchange newly synthesized ATP in the matrix for ADP in the intermembrane space. Regulation. The citric acid cycle is regulated mainly by the availability of key substrates, particularly the ratio of NAD+ to NADH and the concentrations of calcium, inorganic phosphate, ATP, ADP, and AMP. Citrate – the ion that gives its name to the cycle – is a feedback inhibitor of citrate synthase and also inhibits PFK, providing a direct link between the regulation of the citric acid cycle and glycolysis.
Beta oxidation. In the presence of air and various cofactors and enzymes, fatty acids are converted to acetyl-CoA. The pathway is called beta-oxidation. Each cycle of beta-oxidation shortens the fatty acid chain by two carbon atoms and produces one equivalent each of acetyl-CoA, NADH, and FADH2. The acetyl-CoA is metabolized by the citric acid cycle to generate ATP, while the NADH and FADH2 are used by oxidative phosphorylation to generate ATP. Dozens of ATP equivalents are generated by the beta-oxidation of a single long acyl chain. Regulation. In oxidative phosphorylation, the key control point is the reaction catalyzed by cytochrome c oxidase, which is regulated by the availability of its substrate – the reduced form of cytochrome c. The amount of reduced cytochrome c available is directly related to the amounts of other substrates: which directly implies this equation: Thus, a high ratio of [NADH] to [NAD+] or a high ratio of [ADP] [Pi] to [ATP] imply a high amount of reduced cytochrome c and a high level of cytochrome c oxidase activity. An additional level of regulation is introduced by the transport rates of ATP and NADH between the mitochondrial matrix and the cytoplasm.
Ketosis. Ketone bodies can be used as fuels, yielding 22 ATP and 2 GTP molecules per acetoacetate molecule when oxidized in the mitochondria. Ketone bodies are transported from the liver to other tissues, where acetoacetate and "beta"-hydroxybutyrate can be reconverted to acetyl-CoA to produce reducing equivalents (NADH and FADH2), via the citric acid cycle. Ketone bodies cannot be used as fuel by the liver, because the liver lacks the enzyme β-ketoacyl-CoA transferase, also called thiolase. Acetoacetate in low concentrations is taken up by the liver and undergoes detoxification through the methylglyoxal pathway which ends with lactate. Acetoacetate in high concentrations is absorbed by cells other than those in the liver and enters a different pathway via 1,2-propanediol. Though the pathway follows a different series of steps requiring ATP, 1,2-propanediol can be turned into pyruvate. Production, anaerobic conditions. Fermentation is the metabolism of organic compounds in the absence of air. It involves substrate-level phosphorylation in the absence of a respiratory electron transport chain. The equation for the reaction of glucose to form lactic acid is:
Anaerobic respiration is respiration in the absence of . Prokaryotes can utilize a variety of electron acceptors. These include nitrate, sulfate, and carbon dioxide. ATP replenishment by nucleoside diphosphate kinases. ATP can also be synthesized through several so-called "replenishment" reactions catalyzed by the enzyme families of nucleoside diphosphate kinases (NDKs), which use other nucleoside triphosphates as a high-energy phosphate donor, and the family. ATP production during photosynthesis. In plants, ATP is synthesized in the thylakoid membrane of the chloroplast. The process is called photophosphorylation. The "machinery" is similar to that in mitochondria except that light energy is used to pump protons across a membrane to produce a proton-motive force. ATP synthase then ensues exactly as in oxidative phosphorylation. Some of the ATP produced in the chloroplasts is consumed in the Calvin cycle, which produces triose sugars. ATP recycling. The total quantity of ATP in the human body is about 0.1 mol/L. The majority of ATP is recycled from ADP by the aforementioned processes. Thus, at any given time, the total amount of ATP + ADP remains fairly constant.
The energy used by human cells in an adult requires the hydrolysis of 100 to 150 mol/L of ATP daily, which means a human will typically use their body weight worth of ATP over the course of the day. Each equivalent of ATP is recycled 1000–1500 times during a single day (), at approximately 9×1020 molecules/s. Biochemical functions. Intracellular signaling. ATP is involved in signal transduction by serving as substrate for kinases, enzymes that transfer phosphate groups. Kinases are the most common ATP-binding proteins. They share a small number of common folds. Phosphorylation of a protein by a kinase can activate a cascade such as the mitogen-activated protein kinase cascade. ATP is also a substrate of adenylate cyclase, most commonly in G protein-coupled receptor signal transduction pathways and is transformed to second messenger, cyclic AMP, which is involved in triggering calcium signals by the release of calcium from intracellular stores. This form of signal transduction is particularly important in brain function, although it is involved in the regulation of a multitude of other cellular processes.
DNA and RNA synthesis. ATP is one of four monomers required in the synthesis of RNA. The process is promoted by RNA polymerases. A similar process occurs in the formation of DNA, except that ATP is first converted to the deoxyribonucleotide dATP. Like many condensation reactions in nature, DNA replication and DNA transcription also consume ATP. Amino acid activation in protein synthesis. Aminoacyl-tRNA synthetase enzymes consume ATP in the attachment tRNA to amino acids, forming aminoacyl-tRNA complexes. Aminoacyl transferase binds AMP-amino acid to tRNA. The coupling reaction proceeds in two steps: The amino acid is coupled to the penultimate nucleotide at the 3′-end of the tRNA (the A in the sequence CCA) via an ester bond (roll over in illustration). ATP binding cassette transporter. Transporting chemicals out of a cell against a gradient is often associated with ATP hydrolysis. Transport is mediated by ATP binding cassette transporters. The human genome encodes 48 ABC transporters, that are used for exporting drugs, lipids, and other compounds.
Extracellular signalling and neurotransmission. Cells secrete ATP to communicate with other cells in a process called purinergic signalling. ATP serves as a neurotransmitter in many parts of the nervous system, modulates ciliary beating, affects vascular oxygen supply etc. ATP is either secreted directly across the cell membrane through channel proteins or is pumped into vesicles which then fuse with the membrane. Cells detect ATP using the purinergic receptor proteins P2X and P2Y. ATP has been shown to be a critically important signalling molecule for microglia - neuron interactions in the adult brain, as well as during brain development. Furthermore, tissue-injury induced ATP-signalling is a major factor in rapid microglial phenotype changes. Muscle contraction. ATP fuels muscle contractions. Muscle contractions are regulated by signaling pathways, although different muscle types being regulated by specific pathways and stimuli based on their particular function. However, in all muscle types, contraction is performed by the proteins actin and myosin.
ATP is initially bound to myosin. When ATPase hydrolyzes the bound ATP into ADP and inorganic phosphate, myosin is positioned in a way that it can bind to actin. Myosin bound by ADP and Pi forms cross-bridges with actin and the subsequent release of ADP and Pi releases energy as the power stroke. The power stroke causes actin filament to slide past the myosin filament, shortening the muscle and causing a contraction. Another ATP molecule can then bind to myosin, releasing it from actin and allowing this process to repeat. Protein solubility. ATP has recently been proposed to act as a biological hydrotrope and has been shown to affect proteome-wide solubility. Abiogenic origins. Acetyl phosphate (AcP), a precursor to ATP, can readily be synthesized at modest yields from thioacetate in pH 7 and 20 °C and pH 8 and 50 °C, although acetyl phosphate is less stable in warmer temperatures and alkaline conditions than in cooler and acidic to neutral conditions. It is unable to promote polymerization of ribonucleotides and amino acids and was only capable of phosphorylation of organic compounds. It was shown that it can promote aggregation and stabilization of AMP in the presence of Na+, aggregation of nucleotides could promote polymerization above 75 °C in the absence of Na+. It is possible that polymerization promoted by AcP could occur at mineral surfaces. It was shown that ADP can only be phosphorylated to ATP by AcP and other nucleoside triphosphates were not phosphorylated by AcP. This might explain why all lifeforms use ATP to drive biochemical reactions.
ATP analogues. Biochemistry laboratories often use "in vitro" studies to explore ATP-dependent molecular processes. ATP analogs are also used in X-ray crystallography to determine a protein structure in complex with ATP, often together with other substrates. Enzyme inhibitors of ATP-dependent enzymes such as kinases are needed to examine the binding sites and transition states involved in ATP-dependent reactions. Most useful ATP analogs cannot be hydrolyzed as ATP would be; instead, they trap the enzyme in a structure closely related to the ATP-bound state. Adenosine 5′-(γ-thiotriphosphate) is an extremely common ATP analog in which one of the gamma-phosphate oxygens is replaced by a sulfur atom; this anion is hydrolyzed at a dramatically slower rate than ATP itself and functions as an inhibitor of ATP-dependent processes. In crystallographic studies, hydrolysis transition states are modeled by the bound vanadate ion. Caution is warranted in interpreting the results of experiments using ATP analogs, since some enzymes can hydrolyze them at appreciable rates at high concentration.
Medical use. ATP is used intravenously for some heart-related conditions. History. ATP was discovered in 1929 by and Jendrassik and, independently, by Cyrus Fiske and Yellapragada Subba Rao of Harvard Medical School, both teams competing against each other to find an assay for phosphorus. It was proposed to be the intermediary between energy-yielding and energy-requiring reactions in cells by Fritz Albert Lipmann in 1941. It was first synthesized in the laboratory by Alexander Todd in 1948, and he was awarded the Nobel Prize in Chemistry in 1957 partly for this work. The 1978 Nobel Prize in Chemistry was awarded to Peter Dennis Mitchell for the discovery of the chemiosmotic mechanism of ATP synthesis. The 1997 Nobel Prize in Chemistry was divided, one half jointly to Paul D. Boyer and John E. Walker "for their elucidation of the enzymatic mechanism underlying the synthesis of adenosine triphosphate (ATP)" and the other half to Jens C. Skou "for the first discovery of an ion-transporting enzyme, Na+, K+ -ATPase."
Ægir Ægir (anglicised as Aegir; Old Norse 'sea'), Hlér (Old Norse 'sea'), or Gymir (Old Norse less clearly 'sea, engulfer'), is a jötunn and a personification of the sea in Norse mythology. In the Old Norse record, Ægir hosts the gods in his halls and is associated with brewing ale. Ægir is attested as married to a goddess, Rán, who also personifies the sea, and together the two produced daughters who personify waves, the Nine Daughters of Ægir and Rán, and Ægir's son is Snær, personified snow. Ægir may also be the father of the beautiful jötunn Gerðr, wife of the god Freyr, or these may be two separate figures who share the same name (see below and Gymir (father of Gerðr)). One of Ægir's names, "Hlér", is the namesake of the island Læsø (Old Norse "Hlésey" 'Hlér's island') and perhaps also Lejre in Denmark. Scholars have long analyzed Ægir's role in the Old Norse corpus, and the concept of the figure has had some influence in modern popular culture. Names. The Old Norse name "Ægir" ('sea') may stem from a Proto-Germanic form "āgwi-jaz" ('that of the river/water'), itself a derivative of the stem "ahwō-" ('river'; cf. Gothic "" 'body of water, river', Old English "ēa" 'stream', Old High German "aha" 'river'). Richard Cleasby and Guðbrandur Vigfússon saw his name as deriving from an ancient Indo-European root. Linguist Guus Kroonen argues that the Germanic stem "ahwō-" is probably of Proto-Indo-European (PIE) origin, as it may be cognate with Latin "aqua" (via a common form "h₂ekʷ-eh₂-"), and ultimately descend from the PIE root "h₂ep"- ('water'; cf. Sanskrit "áp-" 'water', Tocharian "āp-" 'water, river'). Linguist Michiel de Vaan notes that the connection between Proto-Germanic "ahwō"- and Old Norse "Ægir" remains uncertain, and that *"ahwō-" and "aqua", if cognates, may also be loanwords from a non-Indo-European language.
The name "Ægir" is identical to a noun for 'sea' in skaldic poetry, itself a base word in many kennings. For instance, a ship is described as "Ægir's horse" and the waves as the "daughters of Ægir". Poetic kennings in both "Hversu Noregr byggðist" (How Norway Was Settled) and "Skáldskaparmál" (The Language of Poetry) treat Ægir and the sea-jötunn Hlér, who lives on the Hlésey ('Hlér island', modern Læsø), as the same figure. The meaning of the Old Norse name "Gymir" is unclear. Proposed translations include 'the earthly' (from Old Norse "gumi"), 'the wintry one' (from "gemla"), or 'the protector', the 'engulfer' (from "geyma"). (For more on this topic, see discussion below) Attestations. Ægir is attested in a variety of Old Norse sources. "Sonatorrek". Ægir and Rán receive mention in the poem "Sonatorrek" attributed to 10th century Icelandic skald Egill Skallagrímsson. In the poem, Egill laments the death of his son Böðvar, who drowned at sea during a storm. In one difficult stanza, the skald expresses the pain of losing his son by invoking the image of slaying the personified sea, personified as Ægir (Old Norse "ǫlsmið[r]" 'ale-smith') and Rán ("Ægis man" 'Ægir's wife'):
The skald later references Ægir by way of the kenning 'Hlér's fire' ("Hlés viti"), meaning gold. "Poetic Edda". In the "Poetic Edda", Ægir receives mention in the eddic poems "Grímnismál", "Hymiskviða", "Lokasenna", and in the prose section of "Helgakviða Hundingsbana I". In "Grímnismál", the disguised god Odin references Ægir's status as a renowned host among the gods: In "Hymiskviða", Ægir plays a major role. In the poem, the gods have become thirsty after a successful hunt, and are keen to celebrate with drink. They "shook the twigs and looked at the augury" and "found that at Ægir's was an ample choice of cauldrons". Odin goes to Ægir, who he finds sitting in good cheer, and tells him he shall "often prepare a feast for the Æsir". Referring to Ægir as a jötunn, the poem describes how, now annoyed, Ægir hatches a plan: He asks Thor to fetch a particular cauldron, and that with it he could brew ale for them all. The gods are unable to find a cauldron of a size big enough to meet Ægir's request until the god Týr recommends one he knows of far away, setting the stage for the events of the rest of the poem.
According to the prose introduction to "Lokasenna", "Ægir, who is also called Gymir", was hosting a feast "with the great cauldron which has just been told about", which many of the gods and elves attended. The prose introduction describes the feast as featuring gold that shimmers like fire light and ale that serves itself, and that "it was a great place of peace". In attendance also were Ægir's servers, Fimafeng and Eldir. The gods praise the excellence of their service and, hearing this, Loki murders Fimafeng, enraging the gods, who chase him out to the woods before returning to drink. In the poem that follows the prose introduction (and in accompanying prose), Loki returns to the hall and greets Eldir: He says that before Eldir steps forward, he should first tell him what the gods are discussing in the hall. Eldir says that they're discussing weaponry and war, and having nothing good to say about Loki. Loki says that he will enter Ægir's halls and have a look at the feast, and with him bring quarrel and strife. Eldir notifies Loki that if he enters and causes trouble, he can expect them to return it to him. Loki enters the hall and the gods see him and become silent.
In "Helgakviða Hundingsbana I", a great wave is referred to as "Ægir's terrible daughter". "Prose Edda". Ægir receives numerous mentions in the "Prose Edda" book "Skáldskaparmál", where he sits at a banquet and asks the skaldic god Bragi many questions, and Bragi responds with narratives about the gods. The section begins as follows: Beyond this section of "Skáldskaparmál", Ægir receives several other mentions in kennings. Section 25 provides examples for 'sea', including 'visitor of the gods', 'husband of Rán', 'father of Ægir's daughters', 'land of Rán and Ægir's daughters'. Kennings cited to skalds in this section include 'the storm-happy daughters of Ægir' meaning 'waves' (Svein) and a kenning in a fragment of a work by the 11th century Icelandic skald Hofgarða-Refr Gestsson, where Rán is referred to as 'Gymir's ... völva': The section's author comments that the stanza "[implies] that they are all the same, Ægir and Hler and Gymir. Chapter 33b of "Skáldskaparmál" discusses why skalds may refer to gold as "Ægir's fire". The section traces the kenning to a narrative surrounding Ægir, in which the jötunn employs "glowing gold" in the center of his hall to light it "like fire" (which the narrator compares to flaming swords in Valhalla). The section explains that "Ran is the name of Ægir's wife, and the names of their nine daughters are as was written above ... Then the Æsir discovered that Ran had a net in which she caught everyone that went to sea ... so this is the story of the origin of gold being called fire or light or brightness of Ægir, Ran or Ægir's daughters, and from such kennings the practice has now developed of calling gold fire of the sea and of all terms for it, since Ægir and Ran's names are also terms for the sea, and hence gold is now called fire of lakes or rivers and of all river-names."
In chapter 61 provides yet more kennings. Among them the author notes that "Ran, who, it is said, was Ægir's wife" and that "the daughters of Ægir and Ran are nine". In chapter 75, Ægir occurs in a list of jötnar. Saga corpus. In what appears to be a Norwegian genealogical tradition, Ægir is portrayed as one of the three elements among the sea, the fire and the wind. The beginning of the "Orkneyinga saga" ('Saga of the Orkney Islanders') and "Hversu Noregr byggdisk" ('How Norway Was Settled') tell that the jötunn king Fornjót had three sons: Hlér ('sea'), whom he called Ægir, a second named Logi ('fire'), and a third called Kári ('wind'). Scholarly reception and interpretation. Banquets. Carolyne Larrington says that Ægir's role in "Hymiskviða" "may reflect Scandinavian royal practices in which the king enforces his authority on his subordinates by visiting their homes and demanding to be feasted". According to Andy Orchard, Ægir's role in "Skáldskaparmál", where he attends a banquet rather than hosting it, could be a deliberate inversion of the traditional motif of Ægir as host.
Gymir. The name "Gymir" may indicate that Ægir was understood as the father of the beautiful jötunn Gerðr; they may also have been two different figures sharing the same name (see Gymir, father of Gerðr). Both the prose introduction to "Lokasenna" and "Skáldskaparmál" state that Ægir is also known as "Gymir", the father of the jötunn Gerðr. Rudolf Simek argues that, if understood to be two different entities, this may stem from an erroneous interpretation of kennings in which different jötunn-names are used interchangeably. Hlér, Læsø, Lejre, and Snow. As highlighted above in "Skáldskaparmál", the name of the island Læsø in Denmark references Hlér (Old Norse "Hléysey" 'Hlér's Island'). Simek speculates that Hlér may therefore have been seen as something of an ancestor of the island. Two sources list the personified snow, Snær (Old Norse 'snow'), as Hlér's son. Book nine of Saxo Grammaticus's 12th century history of Denmark "Gesta Danorum" contains mention of a figure by the name of "Lerus" (from Old Norse "Hlér") whose son is "Snio" (from Old Norse "Snær" 'Snow'). The Danish chronicle of Lejre, "Chronicon Lethrense" also connects the two, and the name "Lejre" may, like "Læsø", derive from the jötunn.
Jötunn. Scholars have often discussed Ægir's role as host to the gods and his description as a jötunn. Anthony Faulkes observes that Ægir is "often described by modern writers as god of the sea" yet that he is nowhere described as a god in the "Prose Edda" and appears in a list of jötnar in "Skáldskaparmál". According to John Lindow, since his wife Rán is listed among the Ásynjur (goddesses) in the same part of the "Prose Edda", and since he had a close and friendly relationship with the Æsir (gods), Ægir's description as a jötunn appears questionable. Andy Orchard argues on the contrary that Ægir's inclusion among the Æsir is probably a late development since his daughters are described as jötnar and some sources mention him as the descendant of the jötunn Fornjót. According to Rudolf Simek, while attested as a jötunn, Ægir "has characteristics" of a sea god. Modern influence. Ægir has been the subject of a variety of art pieces. These include Nils Blommér's painting "Näcken och Ägirs döttrar" (1850), Johan Peter Molin's (d. 1874) fountain relief "Ægir", and Emil Doepler's "Ægir" (1901). Ægir is referenced in a variety of others ways in modern popular culture. For example, Shoto Todoroki from the Japanese anime "Boku no hero academia" has a move titled "Great Glacial Aegir". He is also the namesake of a Norwegian corvette produced in 1967 ("Ægir"), a coastal defense ship in the Imperial German Navy, and of an exoplanet, Epsilon Eridani b.
Antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention of such infections. They may either kill or inhibit the growth of bacteria. A limited number of antibiotics also possess antiprotozoal activity. Antibiotics are not effective against viruses such as the ones which cause the common cold or influenza. Drugs which inhibit growth of viruses are termed antiviral drugs or antivirals. Antibiotics are also not effective against fungi. Drugs which inhibit growth of fungi are called antifungal drugs. Sometimes, the term "antibiotic"—literally "opposing life", from the Greek roots ἀντι "anti", "against" and βίος "bios", "life"—is broadly used to refer to any substance used against microbes, but in the usual medical usage, antibiotics (such as penicillin) are those produced naturally (by one microorganism fighting another), whereas non-antibiotic antibacterials (such as sulfonamides and antiseptics) are fully synthetic. However, both classes have the same effect of killing or preventing the growth of microorganisms, and both are included in antimicrobial chemotherapy. "Antibacterials" include bactericides, bacteriostatics, antibacterial soaps, and chemical disinfectants, whereas antibiotics are an important class of antibacterials used more specifically in medicine and sometimes in livestock feed.
Antibiotics have been used since ancient times. Many civilizations used topical application of moldy bread, with many references to its beneficial effects arising from ancient Egypt, Nubia, China, Serbia, Greece, and Rome. The first person to directly document the use of molds to treat infections was John Parkinson (1567–1650). Antibiotics revolutionized medicine in the 20th century. Synthetic antibiotic chemotherapy as a science and development of antibacterials began in Germany with Paul Ehrlich in the late 1880s. Alexander Fleming (1881–1955) discovered modern day penicillin in 1928, the widespread use of which proved significantly beneficial during wartime. The first sulfonamide and the first systemically active antibacterial drug, Prontosil, was developed by a research team led by Gerhard Domagk in 1932 or 1933 at the Bayer Laboratories of the IG Farben conglomerate in Germany. However, the effectiveness and easy access to antibiotics have also led to their overuse and some bacteria have evolved resistance to them. Antimicrobial resistance (AMR), a naturally occurring process, is driven largely by the misuse and overuse of antimicrobials. Yet, at the same time, many people around the world do not have access to essential antimicrobials. The World Health Organization has classified AMR as a widespread "serious threat [that] is no longer a prediction for the future, it is happening right now in every region of the world and has the potential to affect anyone, of any age, in any country". Each year, nearly 5 million deaths are associated with AMR globally. Global deaths attributable to AMR numbered 1.27 million in 2019.
Etymology. The term 'antibiosis', meaning "against life", was introduced by the French bacteriologist Jean Paul Vuillemin as a descriptive name of the phenomenon exhibited by these early antibacterial drugs. Antibiosis was first described in 1877 in bacteria when Louis Pasteur and Robert Koch observed that an airborne bacillus could inhibit the growth of "Bacillus anthracis". These drugs were later renamed antibiotics by Selman Waksman, an American microbiologist, in 1947. The term "antibiotic" was first used in 1942 by Selman Waksman and his collaborators in journal articles to describe any substance produced by a microorganism that is antagonistic to the growth of other microorganisms in high dilution. This definition excluded substances that kill bacteria but that are not produced by microorganisms (such as gastric juices and hydrogen peroxide). It also excluded synthetic antibacterial compounds such as the sulfonamides. In current usage, the term "antibiotic" is applied to any medication that kills bacteria or inhibits their growth, regardless of whether that medication is produced by a microorganism or not.
The term "antibiotic" derives from "anti" + βιωτικός ("biōtikos"), "fit for life, lively", which comes from βίωσις ("biōsis"), "way of life", and that from βίος ("bios"), "life". The term "antibacterial" derives from Greek ἀντί ("anti"), "against" + βακτήριον ("baktērion"), diminutive of βακτηρία ("baktēria"), "staff, cane", because the first bacteria to be discovered were rod-shaped. Usage. Medical uses. Antibiotics are used to treat or prevent bacterial infections, and sometimes protozoan infections. (Metronidazole is effective against a number of parasitic diseases). When an infection is suspected of being responsible for an illness but the responsible pathogen has not been identified, an empiric therapy is adopted. This involves the administration of a broad-spectrum antibiotic based on the signs and symptoms presented and is initiated pending laboratory results that can take several days. When the responsible pathogenic microorganism is already known or has been identified, definitive therapy can be started. This will usually involve the use of a narrow-spectrum antibiotic. The choice of antibiotic given will also be based on its cost. Identification is critically important as it can reduce the cost and toxicity of the antibiotic therapy and also reduce the possibility of the emergence of antimicrobial resistance. To avoid surgery, antibiotics may be given for non-complicated acute appendicitis.
Antibiotics may be given as a preventive measure and this is usually limited to at-risk populations such as those with a weakened immune system (particularly in HIV cases to prevent pneumonia), those taking immunosuppressive drugs, cancer patients, and those having surgery. Their use in surgical procedures is to help prevent infection of incisions. They have an important role in dental antibiotic prophylaxis where their use may prevent bacteremia and consequent infective endocarditis. Antibiotics are also used to prevent infection in cases of neutropenia particularly cancer-related. The use of antibiotics for secondary prevention of coronary heart disease is not supported by current scientific evidence, and may actually increase cardiovascular mortality, all-cause mortality and the occurrence of stroke. Routes of administration.
Global consumption. Antibiotic consumption varies widely between countries. The WHO report on surveillance of antibiotic consumption published in 2018 analysed 2015 data from 65 countries. As measured in defined daily doses per 1,000 inhabitants per day. Mongolia had the highest consumption with a rate of 64.4. Burundi had the lowest at 4.4. Amoxicillin and amoxicillin/clavulanic acid were the most frequently consumed. Side effects. Antibiotics are screened for any negative effects before their approval for clinical use, and are usually considered safe and well tolerated. However, some antibiotics have been associated with a wide extent of adverse side effects ranging from mild to very severe depending on the type of antibiotic used, the microbes targeted, and the individual patient. Side effects may reflect the pharmacological or toxicological properties of the antibiotic or may involve hypersensitivity or allergic reactions. Adverse effects range from fever and nausea to major allergic reactions, including photodermatitis and anaphylaxis.
Common side effects of oral antibiotics include diarrhea, resulting from disruption of the species composition in the intestinal flora, resulting, for example, in overgrowth of pathogenic bacteria, such as "Clostridioides difficile". Taking probiotics during the course of antibiotic treatment can help prevent antibiotic-associated diarrhea. Antibacterials can also affect the vaginal flora, and may lead to overgrowth of yeast species of the genus "Candida" in the vulvo-vaginal area. Additional side effects can result from interaction with other drugs, such as the possibility of tendon damage from the administration of a quinolone antibiotic with a systemic corticosteroid. Some antibiotics may also damage the mitochondrion, a bacteria-derived organelle found in eukaryotic, including human, cells. Mitochondrial damage cause oxidative stress in cells and has been suggested as a mechanism for side effects from fluoroquinolones. They are also known to affect chloroplasts. Interactions. Birth control pills. There are few well-controlled studies on whether antibiotic use increases the risk of oral contraceptive failure. The majority of studies indicate antibiotics do not interfere with birth control pills, such as clinical studies that suggest the failure rate of contraceptive pills caused by antibiotics is very low (about 1%). Situations that may increase the risk of oral contraceptive failure include non-compliance (missing taking the pill), vomiting, or diarrhea. Gastrointestinal disorders or interpatient variability in oral contraceptive absorption affecting ethinylestradiol serum levels in the blood. Women with menstrual irregularities may be at higher risk of failure and should be advised to use backup contraception during antibiotic treatment and for one week after its completion. If patient-specific risk factors for reduced oral contraceptive efficacy are suspected, backup contraception is recommended.
In cases where antibiotics have been suggested to affect the efficiency of birth control pills, such as for the broad-spectrum antibiotic rifampicin, these cases may be due to an increase in the activities of hepatic liver enzymes' causing increased breakdown of the pill's active ingredients. Effects on the intestinal flora, which might result in reduced absorption of estrogens in the colon, have also been suggested, but such suggestions have been inconclusive and controversial. Clinicians have recommended that extra contraceptive measures be applied during therapies using antibiotics that are suspected to interact with oral contraceptives. More studies on the possible interactions between antibiotics and birth control pills (oral contraceptives) are required as well as careful assessment of patient-specific risk factors for potential oral contractive pill failure prior to dismissing the need for backup contraception. Alcohol. Interactions between alcohol and certain antibiotics may occur and may cause side effects and decreased effectiveness of antibiotic therapy. While moderate alcohol consumption is unlikely to interfere with many common antibiotics, there are specific types of antibiotics with which alcohol consumption may cause serious side effects. Therefore, potential risks of side effects and effectiveness depend on the type of antibiotic administered.
Antibiotics such as metronidazole, tinidazole, cephamandole, latamoxef, cefoperazone, cefmenoxime, and furazolidone, cause a disulfiram-like chemical reaction with alcohol by inhibiting its breakdown by acetaldehyde dehydrogenase, which may result in vomiting, nausea, and shortness of breath. In addition, the efficacy of doxycycline and erythromycin succinate may be reduced by alcohol consumption. Other effects of alcohol on antibiotic activity include altered activity of the liver enzymes that break down the antibiotic compound. Pharmacodynamics. The successful outcome of antimicrobial therapy with antibacterial compounds depends on several factors. These include host defense mechanisms, the location of infection, and the pharmacokinetic and pharmacodynamic properties of the antibacterial. The bactericidal activity of antibacterials may depend on the bacterial growth phase, and it often requires ongoing metabolic activity and division of bacterial cells. These findings are based on laboratory studies, and in clinical settings have also been shown to eliminate bacterial infection. Since the activity of antibacterials depends frequently on its concentration, "in vitro" characterization of antibacterial activity commonly includes the determination of the minimum inhibitory concentration and minimum bactericidal concentration of an antibacterial.
To predict clinical outcome, the antimicrobial activity of an antibacterial is usually combined with its pharmacokinetic profile, and several pharmacological parameters are used as markers of drug efficacy. Combination therapy. In important infectious diseases, including tuberculosis, combination therapy (i.e., the concurrent application of two or more antibiotics) has been used to delay or prevent the emergence of resistance. In acute bacterial infections, antibiotics as part of combination therapy are prescribed for their synergistic effects to improve treatment outcome as the combined effect of both antibiotics is better than their individual effect. Fosfomycin has the highest number of synergistic combinations among antibiotics and is almost always used as a partner drug. Methicillin-resistant "Staphylococcus aureus" infections may be treated with a combination therapy of fusidic acid and rifampicin. Antibiotics used in combination may also be antagonistic and the combined effects of the two antibiotics may be less than if one of the antibiotics was given as a monotherapy. For example, chloramphenicol and tetracyclines are antagonists to penicillins. However, this can vary depending on the species of bacteria. In general, combinations of a bacteriostatic antibiotic and bactericidal antibiotic are antagonistic.
In addition to combining one antibiotic with another, antibiotics are sometimes co-administered with resistance-modifying agents. For example, β-lactam antibiotics may be used in combination with β-lactamase inhibitors, such as clavulanic acid or sulbactam, when a patient is infected with a β-lactamase-producing strain of bacteria. Classes. Antibiotics are commonly classified based on their mechanism of action, chemical structure, or spectrum of activity. Most target bacterial functions or growth processes. Those that target the bacterial cell wall (penicillins and cephalosporins) or the cell membrane (polymyxins), or interfere with essential bacterial enzymes (rifamycins, lipiarmycins, quinolones, and sulfonamides) have bactericidal activities, killing the bacteria. Protein synthesis inhibitors (macrolides, lincosamides, and tetracyclines) are usually bacteriostatic, inhibiting further growth (with the exception of bactericidal aminoglycosides). Further categorization is based on their target specificity. "Narrow-spectrum" antibiotics target specific types of bacteria, such as gram-negative or gram-positive, whereas broad-spectrum antibiotics affect a wide range of bacteria. Following a 40-year break in discovering classes of antibacterial compounds, four new classes of antibiotics were introduced to clinical use in the late 2000s and early 2010s: cyclic lipopeptides (such as daptomycin), glycylcyclines (such as tigecycline), oxazolidinones (such as linezolid), and lipiarmycins (such as fidaxomicin).
Production. With advances in medicinal chemistry, most modern antibacterials are semisynthetic modifications of various natural compounds. These include, for example, the beta-lactam antibiotics, which include the penicillins (produced by fungi in the genus "Penicillium"), the cephalosporins, and the carbapenems. Compounds that are still isolated from living organisms are the aminoglycosides, whereas other antibacterials—for example, the sulfonamides, the quinolones, and the oxazolidinones—are produced solely by chemical synthesis. Many antibacterial compounds are relatively small molecules with a molecular weight of less than 1000 daltons. Since the first pioneering efforts of Howard Florey and Chain in 1939, the importance of antibiotics, including antibacterials, to medicine has led to intense research into producing antibacterials at large scales. Following screening of antibacterials against a wide range of bacteria, production of the active compounds is carried out using fermentation, usually in strongly aerobic conditions.
Resistance. Antimicrobial resistance (AMR or AR) is a naturally occurring process. AMR is driven largely by the misuse and overuse of antimicrobials. Yet, at the same time, many people around the world do not have access to essential antimicrobials. The emergence of antibiotic-resistant bacteria is a common phenomenon mainly caused by the overuse/misuse. It represents a threat to health globally. Each year, nearly 5 million deaths are associated with AMR globally. Emergence of resistance often reflects evolutionary processes that take place during antibiotic therapy. The antibiotic treatment may select for bacterial strains with physiologically or genetically enhanced capacity to survive high doses of antibiotics. Under certain conditions, it may result in preferential growth of resistant bacteria, while growth of susceptible bacteria is inhibited by the drug. For example, antibacterial selection for strains having previously acquired antibacterial-resistance genes was demonstrated in 1943 by the Luria–Delbrück experiment. Antibiotics such as penicillin and erythromycin, which used to have a high efficacy against many bacterial species and strains, have become less effective, due to the increased resistance of many bacterial strains.
Resistance may take the form of biodegradation of pharmaceuticals, such as sulfamethazine-degrading soil bacteria introduced to sulfamethazine through medicated pig feces. The survival of bacteria often results from an inheritable resistance, but the growth of resistance to antibacterials also occurs through horizontal gene transfer. Horizontal transfer is more likely to happen in locations of frequent antibiotic use. Antibacterial resistance may impose a biological cost, thereby reducing fitness of resistant strains, which can limit the spread of antibacterial-resistant bacteria, for example, in the absence of antibacterial compounds. Additional mutations, however, may compensate for this fitness cost and can aid the survival of these bacteria. Paleontological data show that both antibiotics and antibiotic resistance are ancient compounds and mechanisms. Useful antibiotic targets are those for which mutations negatively impact bacterial reproduction or viability.
Antibacterial-resistant strains and species, sometimes referred to as "superbugs", now contribute to the emergence of diseases that were, for a while, well controlled. For example, emergent bacterial strains causing tuberculosis that are resistant to previously effective antibacterial treatments pose many therapeutic challenges. Every year, nearly half a million new cases of multidrug-resistant tuberculosis (MDR-TB) are estimated to occur worldwide. For example, NDM-1 is a newly identified enzyme conveying bacterial resistance to a broad range of beta-lactam antibacterials. The United Kingdom's Health Protection Agency has stated that "most isolates with NDM-1 enzyme are resistant to all standard intravenous antibiotics for treatment of severe infections." On 26 May 2016, an "E. coli" "superbug" was identified in the United States resistant to colistin, "the last line of defence" antibiotic. In recent years, even anaerobic bacteria, historically considered less concerning in terms of resistance, have demonstrated high rates of antibiotic resistance, particularly "Bacteroides", for which resistance rates to penicillin have been reported to exceed 90%.
Misuse. Per "The ICU Book", "The first rule of antibiotics is to try not to use them, and the second rule is try not to use too many of them." Inappropriate antibiotic treatment and overuse of antibiotics have contributed to the emergence of antibiotic-resistant bacteria. However, potential harm from antibiotics extends beyond selection of antimicrobial resistance and their overuse is associated with adverse effects for patients themselves, seen most clearly in critically ill patients in Intensive care units. Self-prescribing of antibiotics is an example of misuse. Many antibiotics are frequently prescribed to treat symptoms or diseases that do not respond to antibiotics or that are likely to resolve without treatment. Also, incorrect or suboptimal antibiotics are prescribed for certain bacterial infections. The overuse of antibiotics, like penicillin and erythromycin, has been associated with emerging antibiotic resistance since the 1950s. Widespread usage of antibiotics in hospitals has also been associated with increases in bacterial strains and species that no longer respond to treatment with the most common antibiotics.
Common forms of antibiotic misuse include excessive use of prophylactic antibiotics in travelers and failure of medical professionals to prescribe the correct dosage of antibiotics on the basis of the patient's weight and history of prior use. Other forms of misuse include failure to take the entire prescribed course of the antibiotic, incorrect dosage and administration, or failure to rest for sufficient recovery. Inappropriate antibiotic treatment, for example, is their prescription to treat viral infections such as the common cold. One study on respiratory tract infections found "physicians were more likely to prescribe antibiotics to patients who appeared to expect them". Multifactorial interventions aimed at both physicians and patients can reduce inappropriate prescription of antibiotics. The lack of rapid point of care diagnostic tests, particularly in resource-limited settings is considered one of the drivers of antibiotic misuse. Several organizations concerned with antimicrobial resistance are lobbying to eliminate the unnecessary use of antibiotics. The issues of misuse and overuse of antibiotics have been addressed by the formation of the US Interagency Task Force on Antimicrobial Resistance. This task force aims to actively address antimicrobial resistance, and is coordinated by the US Centers for Disease Control and Prevention, the Food and Drug Administration (FDA), and the National Institutes of Health, as well as other US agencies. A non-governmental organization campaign group is "Keep Antibiotics Working". In France, an "Antibiotics are not automatic" government campaign started in 2002 and led to a marked reduction of unnecessary antibiotic prescriptions, especially in children.

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