title: Brainfuck

text: The language consists of eight commands, listed below. A brainfuck program is a sequence of these commands, possibly interspersed with other characters (which are ignored). The commands are executed sequentially, with some exceptions: an instruction pointer begins at the first command, and each command it points to is executed, after which it normally moves forward to the next command. The program terminates when the instruction pointer moves past the last command.


title: Brainfuck

text: The brainfuck language uses a simple machine model consisting of the program and instruction pointer, as well as a one-dimensional array of at least 30,000 byte cells initialized to zero; a movable data pointer (initialized to point to the leftmost byte of the array); and two streams of bytes for input and output (most often connected to a keyboard and a monitor respectively, and using the ASCII character encoding).


title: Brainfuck

text: codice_5 and codice_6 match as parentheses usually do: each codice_5 matches exactly one codice_6 and vice versa, the codice_5 comes first, and there can be no unmatched codice_5 or codice_6 between the two.


title: Brainfuck

text: Brainfuck programs can be translated into C using the following substitutions, assuming codice_18 is of type codice_19 and has been initialized to point to an array of zeroed bytes:


title: Brainfuck

text: As the name suggests, Brainfuck programs tend to be difficult to comprehend. This is partly because any mildly complex task requires a long sequence of commands and partly because the program's text gives no direct indications of the program's state. These, as well as Brainfuck's inefficiency and its limited input/output capabilities, are some of the reasons it is not used for serious programming. Nonetheless, like any Turing complete language, Brainfuck is theoretically capable of computing any computable function or simulating any other computational model, if given access to an unlimited amount of memory. A variety of Brainfuck programs have been written. Although Brainfuck programs, especially complicated ones, are difficult to write, it is quite trivial to write an interpreter for Brainfuck in a more typical language such as C due to its simplicity. There even exist Brainfuck interpreters written in the Brainfuck language itself.


title: Brainfuck

text: Brainfuck is an example of a so-called Turing tarpit: It can be used to write "any" program, but it is not practical to do so, because Brainfuck provides so little abstraction that the programs get very long or complicated.


title: Brainfuck

text: As a first, simple example, the following code snippet will add the current cell's value to the next cell: Each time the loop is executed, the current cell is decremented, the data pointer moves to the right, that next cell is incremented, and the data pointer moves left again. This sequence is repeated until the starting cell is 0.


title: Brainfuck

text: For "readability", this code has been spread across many lines, and blanks and comments have been added. Brainfuck ignores all characters except the eight commands codice_20 so no special syntax for comments is needed (as long as the comments do not contain the command characters). The code could just as well have been written as:


title: Brainfuck

text: This program enciphers its input with the ROT13 cipher. To do this, it must map characters A-M (ASCII 65–77) to N-Z (78-90), and vice versa. Also it must map a-m (97-109) to n-z (110-122) and vice versa. It must map all other characters to themselves; it reads characters one at a time and outputs their enciphered equivalents until it reads an EOF (here assumed to be represented as either -1 or "no change"), at which point the program terminates.


title: Brainfuck

text: The basic approach used is as follows. Calling the input character "x", divide "x"-1 by 32, keeping quotient and remainder. Unless the quotient is 2 or 3, just output "x", having kept a copy of it during the division. If the quotient is 2 or 3, divide the remainder (("x"-1) modulo 32) by 13; if the quotient here is 0, output "x"+13; if 1, output "x"-13; if 2, output "x".


title: Brainfuck

text: Regarding the division algorithm, when dividing "y" by "z" to get a quotient "q" and remainder "r", there is an outer loop which sets "q" and "r" first to the quotient and remainder of 1/"z", then to those of 2/"z", and so on; after it has executed "y" times, this outer loop terminates, leaving "q" and "r" set to the quotient and remainder of "y"/"z". (The dividend "y" is used as a diminishing counter that controls how many times this loop is executed.) Within the loop, there is code to increment "r" and decrement "y", which is usually sufficient; however, every "z"th time through the outer loop, it is necessary to zero "r" and increment "q". This is done with a diminishing counter set to the divisor "z"; each time through the outer loop, this counter is decremented, and when it reaches zero, it is refilled by moving the value from "r" back into it.


title: Brainfuck

text: Partly because Urban Müller did not write a thorough language specification, the many subsequent brainfuck interpreters and compilers have implemented slightly different dialects of brainfuck.


title: Brainfuck

text: In the classic distribution, the cells are of 8-bit size (cells are bytes), and this is still the most common size. However, to read non-textual data, a brainfuck program may need to distinguish an end-of-file condition from any possible byte value; thus 16-bit cells have also been used. Some implementations have used 32-bit cells, 64-bit cells, or bignum cells with theoretically unlimited range, but programs that use this extra range are likely to be slow, since storing the value formula_1 into a cell requires formula_2 time as a cell's value may only be changed by incrementing and decrementing.


title: Brainfuck

text: In all these variants, the codice_21 and codice_22 commands still read and write data in bytes. In most of them, the cells wrap around, i.e. incrementing a cell which holds its maximal value (with the codice_1 command) will bring it to its minimal value and vice versa. The exceptions are implementations which are distant from the underlying hardware, implementations that use bignums, and implementations that try to enforce portability.


title: Brainfuck

text: It is usually easy to write brainfuck programs that do not ever cause integer wraparound or overflow, and therefore don't depend on cell size. Generally this means avoiding increment of +255 (unsigned 8-bit wraparound), or avoiding overstepping the boundaries of [-128, +127] (signed 8-bit wraparound) (since there are no comparison operators, a program cannot distinguish between a signed and unsigned two's complement fixed-bit-size cell and negativeness of numbers is a matter of interpretation). For more details on integer wraparound, see the Integer overflow article.


title: Brainfuck

text: In the classic distribution, the array has 30,000 cells, and the pointer begins at the leftmost cell. Even more cells are needed to store things like the millionth Fibonacci number, and the easiest way to make the language Turing complete is to make the array unlimited on the right.


title: Brainfuck

text: A few implementations extend the array to the left as well; this is an uncommon feature, and therefore portable brainfuck programs do not depend on it.


title: Brainfuck

text: When the pointer moves outside the bounds of the array, some implementations will give an error message, some will try to extend the array dynamically, some will not notice and will produce undefined behavior, and a few will move the pointer to the opposite end of the array. Some tradeoffs are involved: expanding the array dynamically to the right is the most user-friendly approach and is good for memory-hungry programs, but it carries a speed penalty. If a fixed-size array is used it is helpful to make it very large, or better yet let the user set the size. Giving an error message for bounds violations is very useful for debugging but even that carries a speed penalty unless it can be handled by the operating system's memory protections.


title: Brainfuck

text: Different operating systems (and sometimes different programming environments) use subtly different versions of ASCII. The most important difference is in the code used for the end of a line of text. MS-DOS and Microsoft Windows use a CRLF, i.e. a 13 followed by a 10, in most contexts. UNIX and its descendants (including Linux and macOS) and Amigas use just 10, and older Macs use just 13. It would be difficult if brainfuck programs had to be rewritten for different operating systems. However, a unified standard was easy to create. Urban Müller's compiler and his example programs use 10, on both input and output; so do a large majority of existing brainfuck programs; and 10 is also more convenient to use than CRLF. Thus, brainfuck implementations should make sure that brainfuck programs that assume newline = 10 will run properly; many do so, but some do not.


title: Brainfuck

text: This assumption is also consistent with most of the world's sample code for C and other languages, in that they use "\n", or 10, for their newlines. On systems that use CRLF line endings, the C standard library transparently remaps "\n" to "\r\n" on output and "\r\n" to "\n" on input for streams not opened in binary mode.


title: Brainfuck

text: The behavior of the codice_21 command when an end-of-file condition has been encountered varies. Some implementations set the cell at the pointer to 0, some set it to the C constant EOF (in practice this is usually -1), some leave the cell's value unchanged. There is no real consensus; arguments for the three behaviors are as follows.


title: Brainfuck

text: Setting the cell to 0 avoids the use of negative numbers, and makes it marginally more concise to write a loop that reads characters until EOF occurs. This is a language extension devised by Panu Kalliokoski.


title: Brainfuck

text: Setting the cell to -1 allows EOF to be distinguished from any byte value (if the cells are larger than bytes), which is necessary for reading non-textual data; also, it is the behavior of the C translation of codice_21 given in Müller's readme file. However, it is not obvious that those C translations are to be taken as normative.


title: Brainfuck

text: Leaving the cell's value unchanged is the behavior of Urban Müller's brainfuck compiler. This behavior can easily coexist with either of the others; for instance, a program that assumes EOF = 0 can set the cell to 0 before each codice_21 command, and will then work correctly on implementations that do either EOF = 0 or EOF = "no change". It is so easy to accommodate the "no change" behavior that any brainfuck programmer interested in portability should do so.


title: Brainfuck

text: Although it is trivial to make a naive brainfuck interpreter, writing an optimizing compiler or interpreter becomes more of a challenge and amusement much like writing programs in brainfuck itself is: to produce reasonably fast results, the compiler needs to piece together the fragmentary instructions forced by the language. Possible optimizations range from simple run-length peephole optimizations on repeated commands and common loop patterns like , to more complicated ones like dead code elimination and constant folding.


title: Brainfuck

text: In addition to optimization, other types of unusual brainfuck interpreters have also been written. Several brainfuck compilers have been made smaller than 200 bytes – one is only 100 bytes in x86 machine code.


title: Brainfuck

text: Many people have created brainfuck equivalents (languages with commands that directly map to brainfuck) or brainfuck derivatives (languages that extend its behavior or alter its semantics).


title: C

text: C, or c, is the third letter in the Latin alphabet, used in the modern English alphabet, the alphabets of other western European languages and others worldwide. Its name in English is "cee" (pronounced ), plural "cees".


title: C

text: "C" comes from the same letter as "G". The Semites named it gimel. The sign is possibly adapted from an Egyptian hieroglyph for a staff sling, which may have been the meaning of the name "gimel". Another possibility is that it depicted a camel, the Semitic name for which was "gamal". Barry B. Powell, a specialist in the history of writing, states "It is hard to imagine how gimel = "camel" can be derived from the picture of a camel (it may show his hump, or his head and neck!)".


title: C

text: In the Etruscan language, plosive consonants had no contrastive voicing, so the Greek 'Γ' (Gamma) was adopted into the Etruscan alphabet to represent . Already in the Western Greek alphabet, Gamma first took a '' form in Early Etruscan, then '' in Classical Etruscan. In Latin it eventually took the " form in Classical Latin. In the earliest Latin inscriptions, the letters " were used to represent the sounds and (which were not differentiated in writing). Of these, " was used to represent or before a rounded vowel, " before ", and " elsewhere. During the 3rd century BC, a modified character was introduced for , and " itself was retained for . The use of " (and its variant ") replaced most usages of " and ". Hence, in the classical period and after, " was treated as the equivalent of Greek gamma, and " as the equivalent of kappa; this shows in the romanization of Greek words, as in 'ΚΑΔΜΟΣ', 'ΚΥΡΟΣ', and 'ΦΩΚΙΣ' came into Latin as ", " and ", respectively.


title: C

text: Other alphabets have letters homoglyphic to 'c' but not analogous in use and derivation, like the Cyrillic letter Es (С, с) which derives from the lunate sigma, named due to its resemblance to the crescent moon.


title: C

text: When the Roman alphabet was introduced into Britain, represented only , and this value of the letter has been retained in loanwords to all the insular Celtic languages: in Welsh, Irish, Gaelic, represents only . The Old English Latin-based writing system was learned from the Celts, apparently of Ireland; hence in Old English also originally represented ; the Modern English words "kin, break, broken, thick", and "seek" all come from Old English words written with : , and . However, during the course of the Old English period, before front vowels ( and ) were palatalized, having changed by the tenth century to , though was still used, as in . On the continent, meanwhile, a similar phonetic change before the same two vowels had also been going on almost all modern romance languages (for example, in Italian).


title: C

text: In Vulgar Latin, became palatalized to in Italy and Dalmatia; in France and the Iberian peninsula, it became . Yet for these new sounds was still used before the letters and . The letter thus represented two distinct values. Subsequently, the Latin phoneme (spelled ) de-labialized to meaning that the various Romance languages had before front vowels. In addition, Norman used the letter so that the sound could be represented by either or , the latter of which could represent either or depending on whether it preceded a front vowel letter or not. The convention of using both and was applied to the writing of English after the Norman Conquest, causing a considerable re-spelling of the Old English words. Thus while Old English , remained unchanged, , were now (without any change of sound) spelled , and ; even ('knight') was subsequently changed to and ('thick') changed to or . The Old English was also at length displaced by the French so that the Old English ('queen') and ('quick') became Middle English and , respectively. The sound , to which Old English palatalized had advanced, also occurred in French, chiefly from Latin before . In French it was represented by the digraph , as in "champ" (from Latin ) and this spelling was introduced into English: the Hatton Gospels, written , have in Matt. i-iii, , for the of the Old English version whence they were copied. In these cases, the Old English gave way to , and ; on the other hand, in its new value of appeared largely in French words like and , and was also substituted for in a few Old English words, as , in early Middle English . By the end of the thirteenth century both in France and England, this sound de-affricated to ; and from that time has represented before front vowels either for etymological reasons, as in "lance, cent", or to avoid the ambiguity due to the "etymological" use of for , as in "ace, mice, once, pence, defence".


title: C

text: Thus, to show etymology, English spelling has "advise", "devise" (instead of "*advize", "*devize"), while "advice, device, dice, ice, mice, twice", etc., do not reflect etymology; example has extended this to "hence, pence, defence", etc., where there is no etymological reason for using . Former generations also wrote "sence" for "sense". Hence, today the Romance languages and English have a common feature inherited from Vulgar Latin spelling conventions where takes on either a "hard" or "soft" value depending on the following letter.


title: C

text: In English orthography, generally represents the "soft" value of before the letters (including the Latin-derived digraphs and , or the corresponding ligatures and ), , and , and a "hard" value of before any other letters or at the end of a word. However, there are a number of exceptions in English: "soccer" and "Celt" are words that have where would be expected.


title: C

text: The "soft" may represent the sound in the digraph when this precedes a vowel, as in the words 'delicious' and 'appreciate', and also in the word "ocean" and its derivatives.


title: C

text: The digraph most commonly represents , but can also represent (mainly in words of Greek origin) or (mainly in words of French origin). For some dialects of English, it may also represent in words like "loch", while other speakers pronounce the final sound as . The trigraph always represents .


title: C

text: C is the twelfth most frequently used letter in the English language (after E, T, A, O, I, N, S, H, R, D, and L), with a frequency of about 2.8% in words.


title: C

text: In the Romance languages French, Spanish, Italian, Romanian and Portuguese, generally has a "hard" value of and a "soft" value whose pronunciation varies by language. In French, Portuguese, Catalan and Spanish from Latin America and some places in Spain, the soft value is as it is in English. In the Spanish spoken in most of Spain, the soft is a voiceless dental fricative . In Italian and Romanian, the soft is .


title: C

text: Germanic languages usually use c for Romance loans or digraphs, such as and , but the rules vary across languages. Dutch uses the most, for all Romance loans and the digraph , but unlike English, does not use for native Germanic words like "komen", "come". German uses in the digraphs and , and the trigraph , but only by itself in unassimilated loanwords and place names. Danish keeps soft in Romance words but changes hard to . Swedish has the same rules for soft and hard as Danish, and also uses in the digraph and the very common word "och", "and". Norwegian, Afrikaans, and Icelandic are the most restrictive, replacing all cases of with or , and reserving for unassimilated loanwords and names.


title: C

text: All Balto-Slavic languages that use the Latin alphabet, as well as Albanian, Hungarian, Pashto, several Sami languages, Esperanto, Ido, Interlingua, and Americanist phonetic notation (and those aboriginal languages of North America whose practical orthography derives from it) use to represent , the voiceless alveolar or voiceless dental sibilant affricate. In Hanyu Pinyin, the standard romanization of Mandarin Chinese, the letter represents an aspirated version of this sound, .


title: C

text: Among non-European languages that have adopted the Latin alphabet, represents a variety of sounds. Yup'ik, Indonesian, Malay, and a number of African languages such as Hausa, Fula, and Manding share the soft Italian value of . In Azeri, Crimean Tatar, Kurmanji Kurdish, and Turkish stands for the voiced counterpart of this sound, the voiced postalveolar affricate . In Yabem and similar languages, such as Bukawa, stands for a glottal stop . Xhosa and Zulu use this letter to represent the click . In some other African languages, such as Berber languages, is used for . In Fijian, stands for a voiced dental fricative , while in Somali it has the value of .


title: C

text: The letter is also used as a transliteration of Cyrillic in the Latin forms of Serbian, Macedonian, and sometimes Ukrainian, along with the digraph .


title: C

text: As a phonetic symbol, lowercase is the International Phonetic Alphabet (IPA) and X-SAMPA symbol for the voiceless palatal plosive, and capital is the X-SAMPA symbol for the voiceless palatal fricative.


title: C

text: There are several common digraphs with , the most common being , which in some languages (such as German) is far more common than alone. takes various values in other languages.


title: C

text: As in English, , with the value , is often used after short vowels in other Germanic languages such as German and Swedish (other Germanic languages, such as Dutch and Norwegian, use instead). The digraph is found in Polish and in Hungarian, representing and respectively. The digraph represents in Old English, Italian, and a few languages related to Italian (where this only happens before front vowels, while otherwise it represents ). The trigraph represents in German.


title: C

text: In Unicode, C is also encoded in various font styles for mathematical purposes; see Mathematical Alphanumeric Symbols.


title: C

text: In the hexadecimal (base 16) numbering system, C is a number that corresponds to the number 12 in decimal (base 10) counting.


title: 99942 Apophis

text: 99942 Apophis is a near-Earth asteroid and potentially hazardous asteroid with a diameter of that caused a brief period of concern in December 2004 when initial observations indicated a probability up to 2.7% that it would hit Earth on April 13, 2029. Additional observations provided improved predictions that eliminated the possibility of an impact on Earth in 2029. Until 2006, a small probability nevertheless remained that, during its 2029 close encounter with Earth, Apophis would pass through a gravitational keyhole of no more than about in diameter, which would have set up a future impact exactly seven years later on April 13, 2036. This possibility kept it at Level 1 on the Torino impact hazard scale until August 2006, when the probability that Apophis would pass through the keyhole was determined to be very small and Apophis' rating on the Torino scale was lowered to zero. By 2008, the keyhole had been determined to be less than 1 km wide. During the short time when it had been of greatest concern, Apophis set the record for highest rating ever on the Torino scale, reaching level 4 on December 27, 2004.


title: 99942 Apophis

text: The diameter of Apophis is estimated to be approximately . Preliminary observations by Goldstone radar in January 2013 effectively ruled out the possibility of an Earth impact by Apophis in 2036. By May 6, 2013 (April 15, 2013, observation arc), the possibility of an impact on April 13, 2036 had been eliminated altogether. Apophis will make two modestly close approaches to Earth in 2036, but even the planet Venus will come closer to Earth in 2036. On April 12, 2068, the nominal trajectory has Apophis from Earth. Entering March 2021, six asteroids each had a more notable cumulative Palermo Technical Impact Hazard Scale than Apophis, and none of those has a Torino level above 0. On average, an asteroid the size of Apophis (370 metres) is expected to impact Earth once in about 80,000 years. Observations in 2020 by the Subaru telescope confirmed David Vokrouhlický's 2015 Yarkovsky effect predictions. The Goldstone radar observed Apophis March 3–11, 2021, helping to refine the orbit again, and on March 25, 2021, the Jet Propulsion Laboratory announced that Apophis has no chance of impacting Earth in the next 100 years. The uncertainty in the 2029 approach distance has been reduced from hundreds of kilometers to now just a couple of kilometers, greatly enhancing predictions of future approaches. Apophis was removed altogether from the Sentry Risk Table the next day.


title: 99942 Apophis

text: Apophis was discovered on June 19, 2004, by Roy A. Tucker, David J. Tholen, and Fabrizio Bernardi at the Kitt Peak National Observatory. On December 21, 2004, Apophis passed from Earth. Precovery observations from March 15, 2004, were identified on December 27, and an improved orbit solution was computed. Radar astrometry in January 2005 further refined its orbit solution. The discovery was notable in that it was at a very low solar elongation (56°) and at very long range (1.1 AU). See diagram below:


title: 99942 Apophis

text: When first discovered, the object received the provisional designation , and early news and scientific articles naturally referred to it by that name. Once its orbit was sufficiently well calculated, it received the permanent number 99942 (on June 24, 2005). Receiving a permanent number made it eligible for naming by its discoverers, and they chose the name "Apophis" on July 19, 2005. Apophis is the Greek name of Apep, an enemy of the Ancient Egyptian sun-god Ra. He is the Uncreator, an evil serpent that dwells in the eternal darkness of the Duat and tries to swallow Ra during his nightly passage. Apep is held at bay by Set, the Ancient Egyptian god of storms and the desert.


title: 99942 Apophis

text: Tholen and Tucker, two of the co-discoverers of the asteroid, are reportedly fans of the television series "Stargate SG-1". One of the show's persistent villains is an alien named Apophis. He is one of the principal threats to the existence of civilization on Earth through the first few seasons, thus likely why the asteroid was named after him. In the fictional world of the show, the alien's backstory was that he had lived on Earth during ancient times and had posed as a god, thereby giving rise to the myth of the Egyptian god of the same name.


title: 99942 Apophis

text: The mythological creature Apophis is pronounced with the accent on the first syllable (/ˈæpəfɪs/). In contrast, the asteroid's name is generally accented on the second syllable (/əˈpɒfɪs/) as the name was pronounced in the TV series.


title: 99942 Apophis

text: Based upon the observed brightness, Apophis's diameter was initially estimated at ; a more refined estimate based on spectroscopic observations at NASA's Infrared Telescope Facility in Hawaii by Binzel, Rivkin, Bus, and Tokunaga (2005) is . NASA's impact risk page lists the diameter at and lists a mass of 4 kg based on an assumed density of 2.6 g/cm. The mass estimate is more approximate than the diameter estimate, but should be accurate to within a factor of three. Apophis's surface composition probably matches that of LL chondrites.


title: 99942 Apophis

text: Based on Goldstone and Arecibo radar images taken in 2012–2013, Brozović et al. have estimated that Apophis is an elongated object 450 × 170 metres in size, and that it is bilobed (possibly a contact binary) with a relatively bright surface albedo of . Its rotation axis has an obliquity of −59° against the ecliptic, which means that Apophis is a retrograde rotator.


title: 99942 Apophis

text: During the 2029 approach, Apophis's brightness will peak at magnitude 3.1, easily visible to the naked eye if one knows where to look, with a maximum angular speed of 42° per hour. The maximum apparent angular diameter will be ~2 arcseconds. This is roughly equivalent to the angular diameter of Neptune from earth. Therefore, the asteroid will be barely resolved by ground-based telescopes not equipped with adaptive optics but very well resolved by those that are. Due to the closeness of the approach, it is likely that tidal forces will alter Apophis's rotation axis. A partial resurfacing of the asteroid is possible, which might change its spectral class from a weathered Sq- to an unweathered Q-type.


title: 99942 Apophis

text: Apophis has a low inclination orbit (3.3°) that varies from just outside the orbit of Venus (0.746 AU) to just outside the orbit of Earth (1.099 AU). After the 2029 Earth approach the orbit will vary from just inside of Earth's to just inside of Mars.


title: 99942 Apophis

text: The closest known approach of Apophis occurs at April 13, 2029 21:46 UT, when Apophis will pass Earth closer than geosynchronous communication satellites, but will come no closer than above Earth's surface. Using the June 2021 orbit solution which includes the Yarkovsky effect, the 3-sigma uncertainty region in the 2029 approach distance is about ±3.4 km. The distance, a hair's breadth in astronomical terms, is five times the radius of the Earth, ten times closer than the Moon, and closer than more than 500 geostationary satellites currently orbiting the earth. It will be the closest asteroid of its size in recorded history. On that date, it will become as bright as magnitude 3.1 (visible to the naked eye from rural as well as darker suburban areas, visible with binoculars from most locations). The close approach will be visible from Europe, Africa, and western Asia. During the approach, Earth will perturb Apophis from an Aten-class orbit with a semi-major axis of 0.92 AU to an Apollo-class orbit with a semi-major axis of 1.1 AU. Perihelion will lift from 0.746 AU to 0.894 AU and aphelion will lift from 1.099 AU to 1.31 AU.


title: 99942 Apophis

text: In 2036 Apophis will approach the Earth at a third the distance of the Sun in both March and December. Using the 2021 orbit solution, the Earth approach on March 27, 2036, will be no closer than , but more likely about . The planet Venus will be closer to Earth at on May 30, 2036.


title: 99942 Apophis

text: Around April 19–20, 2051, Apophis will pass about from Earth and it will be the first time since 2029 that Apophis has passed within 10 million km of Earth.


title: 99942 Apophis

text: In the 2060s Apophis will approach Earth in September 2066, and then from February 2067 to December 2071 Apophis will remain further from Earth than the Sun is. On April 12, 2068, JPL Horizons calculates that Apophis will be about from Earth, making the asteroid much further than the Sun.


title: 99942 Apophis

text: By 2116 the JPL Small-Body Database and NEODyS close approach data start to become divergent. In April 2116 Apophis is expected to pass about from Earth, but could pass as close as or could pass as far as .


title: 99942 Apophis

text: Six months after discovery, and shortly after a close approach to Earth on December 21, 2004, the improved orbital estimates led to the prediction of a very close approach on April 13, 2029, by both NASA's automatic Sentry system and NEODyS, a similar automatic program run by the University of Pisa and the University of Valladolid. Subsequent observations decreased the uncertainty in Apophis's trajectory. The probability of an impact event in 2029 temporarily climbed, peaking at 2.7% (1 in 37) on December 27, 2004, when the uncertainty region had shrunk to 83,000 km. This probability, combined with its size, caused Apophis to be assessed at level 4 on the Torino scale and 1.10 on the Palermo Technical Impact Hazard Scale, scales scientists use to represent how dangerous a given asteroid is to Earth. These are the highest values for which any object has been rated on either scale. The chance that there would be an impact in 2029 was eliminated by late December 27, 2004, as a result of a precovery image that extended the observation arc back to March 2004. The danger of a 2036 passage was lowered to level 0 on the Torino scale in August 2006. With a cumulative Palermo Scale rating of −3.22, the risk of impact from Apophis is less than one thousandth the background hazard level.


title: 99942 Apophis

text: In July 2005, former Apollo astronaut Rusty Schweickart, as chairman of the B612 Foundation, formally asked NASA to investigate the possibility that the asteroid's post-2029 orbit could be in orbital resonance with Earth, which would increase the probability of future impacts. Schweickart also asked NASA to investigate whether a transponder should be placed on the asteroid to enable more accurate tracking of how its orbit is affected by the Yarkovsky effect. On January 31, 2011, astronomers took the first new images of Apophis in more than 3 years.


title: 99942 Apophis

text: The close approach in 2029 will substantially alter the object's orbit, prompting Jon Giorgini of JPL to say in 2011: "If we get radar ranging in 2013 [the next good opportunity], we should be able to predict the location of out to at least 2070." Apophis passed within of Earth in 2013, allowing astronomers to refine the trajectory for future close passes. Just after the closest approach on January 9, 2013, the asteroid peaked at an apparent magnitude of about 15.6. The Goldstone radar observed Apophis during that approach from January 3 through January 17. The Arecibo Observatory observed Apophis once it entered Arecibo's declination window after February 13, 2013. The 2013 observations basically ruled out any chance of a 2036 impact.


title: 99942 Apophis

text: A NASA assessment as of February 21, 2013, that did not use the January and February 2013 radar measurements gave an impact probability of 2.3 in a million for 2068. As of May 6, 2013, using observations through April 15, 2013, the odds of an impact on April 12, 2068, as calculated by the JPL Sentry risk table had increased slightly to 3.9 in a million (1 in 256,000).


title: 99942 Apophis

text: As of January 2019, Apophis had not been observed since 2015, mostly because its orbit has kept it very near the Sun from the perspective of Earth. It was not further than 60 degrees from the Sun between April 2014 and December 2019. With the early 2015 observations, the April 12, 2068, impact probability was 6.7 in a million (1 in 150,000), and the asteroid had a cumulative 9 in a million (1 in 110,000) chance of impacting Earth before 2106.


title: 99942 Apophis

text: No observations of Apophis were made between January 2015 and February 2019, and then observations started occurring regularly in January 2020. In March 2020, astronomers David Tholen and Davide Farnocchia measured the acceleration of Apophis due to the Yarkovsky effect for the first time, significantly improving the prediction of its orbit past the 2029 flyby. Tholen and Farnocchia found that the Yarkovsky effect caused Apophis to drift by about 170 meters per year. In late 2020, Apophis approached the Earth again. It passed from Earth on March 6, 2021, brightening to +15 mag at the time. Radar observations of Apophis were planned at Goldstone in March 2021. The asteroid has been observed by NEOWISE (between December 2020 and April 2021) and by NEOSSat (in January 2021). Apophis was the target of an observing campaign by IAWN, resulting in the collection of light curves, spectra, and astrometry. The observations were used to practice and coordinate the response to an actual impact threat.


title: 99942 Apophis

text: On February 21, 2021, Apophis was removed from the Sentry Risk Table, as an impact in the next 100 years was finally ruled out.


title: 99942 Apophis

text: Several occultations of bright stars (apparent magnitude 8-11) by Apophis occurred in March and April 2021. A total of five separate occultations were observed successfully, marking the first time that an asteroid as small as Apophis was observed using the occultation method (beating the previous record set in 2019 by asteroid 3200 Phaeton by more than a factor of ten). The first event, on March 7, was successfully observed from the United States by multiple observers. The next potential occultation, which occurred on March 11, was predicted to be visible from central Europe. This event was missed, mainly due to bad weather (two negative observations were recorded from Greece). On March 22, another occultation was observed only by a single observer from the United States, amateur astronomer Roger Venable. Due to larger-than-expected residuals in the March 7 data, the majority of observers had been deployed outside of the actual path for the March 22 occultation. This single detection then allowed the prediction of several more events that would have been unobservable otherwise, including an occultation on April 4, which was observed from New Mexico, again by Venable, alongside others. Two more occultations, observable on April 10 and April 11 from Japan and New Mexico, respectively, were seen by several observers each.


title: 99942 Apophis

text: On March 9, 2021, using radar observations from Goldstone taken on March 3–8 and three positive detections of the stellar occultation on March 7, 2021, Apophis became the asteroid with the most precisely measured Yarkovsky effect of all asteroids, at a signal-to-noise ratio (SNR) of 186.4, surpassing 101955 Bennu (SNR=181.6).


title: 99942 Apophis

text: The Sentry Risk Table estimates that Apophis would impact Earth with kinetic energy equivalent to 1,200 megatons of TNT.


title: 99942 Apophis

text: In comparison, the Chicxulub impact which caused the mass extinction event responsible for wiping out the dinosaurs has been estimated to have released about as much energy as 100,000,000 megatons (100 teratons). The exact effects of any impact would vary based on the asteroid's composition, and the location and angle of impact. Any impact would be extremely detrimental to an area of thousands of square kilometres, but would be unlikely to have long-lasting global effects, such as the initiation of an impact winter. Assuming Apophis is a stony asteroid with a density of 3,000 kg/m, if it were to impact into sedimentary rock, Apophis would create a impact crater.


title: 99942 Apophis

text: In 2008, the B612 Foundation made estimates of Apophis's path if a 2036 Earth impact were to occur, as part of an effort to develop viable deflection strategies. The result was a narrow corridor a few kilometres wide, called the "path of risk", extending across southern Russia, across the north Pacific (relatively close to the coastlines of California and Mexico), then right between Nicaragua and Costa Rica, crossing northern Colombia and Venezuela, ending in the Atlantic, just before reaching Africa. Using the computer simulation tool NEOSim, it was estimated that the hypothetical impact of Apophis in countries such as Colombia and Venezuela, which were in the path of risk, could have more than 10 million casualties. A deep-water impact in the Atlantic or Pacific oceans would produce an incoherent short-range tsunami with a potential destructive radius (inundation height of >2 m) of roughly for most of North America, Brazil and Africa, for Japan and for some areas in Hawaii.


title: 99942 Apophis

text: The "OSIRIS-REx" spacecraft is expected to return a sample of Bennu to Earth in 2023. After ejecting the sample canister, the spacecraft can use its remaining fuel to target another body during an extended mission. Apophis is the only asteroid which the spacecraft could reach for a long-duration rendezvous, rather than a brief flyby. In April 2022, the extension was approved, and "OSIRIS-REx" will perform a rendezvous with Apophis in April 2029, a few days after the close approach to Earth. It will study the asteroid for 18 months and perform a maneuver similar to the one it made during sample collection at Bennu, by approaching the surface and firing its thrusters. This will expose the asteroid's subsurface and allow mission scientists to learn more about the asteroid's material properties. For its Apophis mission after the sample return, "OSIRIS-REx" will be renamed "OSIRIS-APEX" (short for OSIRIS-Apophis Explorer).


title: 99942 Apophis

text: In 2007, The Planetary Society, a California-based space advocacy group, organized a $50,000 competition to design an uncrewed space probe that would 'shadow' Apophis for almost a year, taking measurements that would "determine whether it will impact Earth, thus helping governments decide whether to mount a deflection mission to alter its orbit". The society received 37 entries from 20 countries on 6 continents.


title: 99942 Apophis

text: The commercial competition was won by a design called 'Foresight' created by SpaceWorks Enterprises, Inc. SpaceWorks proposed a simple orbiter with only two instruments and a radio beacon at a cost of ~US$140 million, launched aboard a Minotaur IV between 2012 and 2014, to arrive at Apophis five to ten months later. It would then rendezvous with, observe, and track the asteroid. Foresight would orbit the asteroid to gather data with a multi-spectral imager for one month. It would then leave orbit and fly in formation with Apophis around the Sun at a range of . The spacecraft would use laser ranging to the asteroid and radio tracking from Earth for ten months to accurately determine the asteroid's orbit and how it might change.


title: 99942 Apophis

text: Pharos, the winning student entry, would be an orbiter with four science instruments (a multi-spectral imager, near-infrared spectrometer, laser rangefinder, and magnetometer) that would rendezvous with and track Apophis. Earth-based tracking of the spacecraft would then allow precise tracking of the asteroid. The Pharos spacecraft would also carry four instrumented probes that it would launch individually over the course of two weeks. Accelerometers and temperature sensors on the probes would measure the seismic effects of successive probe impacts, a creative way to explore the interior structure and dynamics of the asteroid.


title: 99942 Apophis

text: Second place, for $10,000, went to a European team led by Deimos Space S.L. of Madrid, Spain, in cooperation with EADS Astrium, Friedrichshafen, Germany; University of Stuttgart, Germany; and University of Pisa, Italy. Juan L. Cano was principal investigator.


title: 99942 Apophis

text: Another European team took home $5,000 for third place. Their team lead was EADS Astrium Ltd, United Kingdom, in conjunction with EADS Astrium SAS, France; IASF-Roma, INAF, Rome, Italy; Open University, UK; Rheinisches Institut für Umweltforschung, Germany; Royal Observatory of Belgium; and Telespazio, Italy. The principal investigator was Paolo D'Arrigo.


title: 99942 Apophis

text: Two teams tied for second place in the Student Category: Monash University, Clayton Campus, Australia, with Dilani Kahawala as principal investigator; and University of Michigan, with Jeremy Hollander as principal investigator. Each second-place team won $2,000. A team from Hong Kong Polytechnic University and Hong Kong University of Science and Technology, under the leadership of Peter Weiss, received an honorable mention and $1,000 for the most innovative student proposal.


title: 99942 Apophis

text: Apophis is one of two asteroids that were considered by the European Space Agency as the target of its Don Quijote mission concept to study the effects of impacting an asteroid.


title: 99942 Apophis

text: China had planned an encounter with Apophis in 2022, several years prior to the close approach in 2029. This mission, now known as "ZhengHe", would have included exploration and close study of three asteroids including an extended encounter with Apophis for close observation, and land on the asteroid 1996 FG3 to conduct in situ sampling analysis on the surface. The launch date is now scheduled for 2024, with a different set of targets.


title: 99942 Apophis

text: Studies by NASA, ESA, and various research groups in addition to the Planetary Society contest teams, have described a number of proposals for deflecting Apophis or similar objects, including gravitational tractor, kinetic impact, and nuclear bomb methods.


title: 99942 Apophis

text: On December 30, 2009, Anatoly Perminov, the director of the Russian Federal Space Agency, said in an interview that Roscosmos will also study designs for a possible deflection mission to Apophis.


title: 99942 Apophis

text: On August 16, 2011, researchers at China's Tsinghua University proposed launching a mission to knock Apophis onto a safer course using an impactor spacecraft in a retrograde orbit, steered and powered by a solar sail. Instead of moving the asteroid on its potential resonant return to Earth, Shengping Gong and his team believe the secret is shifting the asteroid away from entering the gravitational keyhole in the first place.


title: 99942 Apophis

text: On February 15, 2016, Sabit Saitgarayev, of the Makeyev Rocket Design Bureau, announced intentions to use Russian ICBMs to target relatively small near-Earth objects. Although the report stated that likely targets would be between the 20 to 50 metres in size, it was also stated that 99942 Apophis would be an object subject to tests by the program.


title: 99942 Apophis

text: In October 2022, a method of mapping the insides of a potentially problematic asteroid, such as 99942 Apophis, in order to determine the best area for impact was proposed.


title: 99942 Apophis

text: In Id Software's video game "Rage", the backstory involves the asteroid colliding with Earth on August 23, 2029. The asteroid almost wipes out the human race and ushers in a post-apocalyptic age.


title: Antibody

text: An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the pathogen, called an antigen. Each tip of the "Y" of an antibody contains a paratope (analogous to a lock) that is specific for one particular epitope (analogous to a key) on an antigen, allowing these two structures to bind together with precision. Using this binding mechanism, an antibody can "tag" a microbe or an infected cell for attack by other parts of the immune system, or can neutralize it directly (for example, by blocking a part of a virus that is essential for its invasion).


title: Antibody

text: To allow the immune system to recognize millions of different antigens, the antigen-binding sites at both tips of the antibody come in an equally wide variety.


title: Antibody

text: In contrast, the remainder of the antibody is relatively constant. It only occurs in a few variants, which define the antibody's "class" or "isotype": IgA, IgD, IgE, IgG, and IgM.


title: Antibody

text: The constant region at the trunk of the antibody includes sites involved in interactions with other components of the immune system. The class hence determines the function triggered by an antibody after binding to an antigen, in addition to some structural features.


title: Antibody

text: Antibodies from different classes also differ in where they are released in the body and at what stage of an immune response.


title: Antibody

text: Together with B and T cells, antibodies comprise the most important part of the adaptive immune system.


title: Antibody

text: They occur in two forms: one that is attached to a B cell, and the other, a soluble form, that is unattached and found in extracellular fluids such as blood plasma.


title: Antibody

text: Initially, all antibodies are of the first form, attached to the surface of a B cell – these are then referred to as B-cell receptors (BCR).


title: Antibody

text: After an antigen binds to a BCR, the B cell activates to proliferate and differentiate into either plasma cells, which secrete soluble antibodies with the same paratope, or memory B cells, which survive in the body to enable long-lasting immunity to the antigen.


title: Antibody

text: Because these fluids were traditionally known as humors, antibody-mediated immunity is sometimes known as, or considered a part of, humoral immunity.


title: Antibody

text: The terms antibody and immunoglobulin are often used interchangeably, though the term 'antibody' is sometimes reserved for the secreted, soluble form, i.e. excluding B-cell receptors.


title: Antibody

text: In humans and most mammals, an antibody unit consists of four polypeptide chains; two identical "heavy chains" and two identical "light chains" connected by disulfide bonds.


title: Antibody

text: Light chains consist of one variable domain V and one constant domain C, while heavy chains contain one variable domain V and three to four constant domains C1, C2, ...


title: Antibody

text: Structurally an antibody is also partitioned into two antigen-binding fragments (Fab), containing one V, V, C, and C1 domain each, as well as the crystallisable fragment (Fc), forming the trunk of the Y shape.


title: Antibody

text: In between them is a hinge region of the heavy chains, whose flexibility allows antibodies to bind to pairs of epitopes at various distances, to form complexes (dimers, trimers, etc.), and to bind effector molecules more easily.


title: Antibody

text: In an electrophoresis test of blood proteins, antibodies mostly migrate to the last, gamma globulin fraction.


title: Antibody

text: Conversely, most gamma-globulins are antibodies, which is why the two terms were historically used as synonyms, as were the symbols Ig and γ.


title: Antibody

text: This variant terminology fell out of use due to the correspondence being inexact and due to confusion with γ (gamma) heavy chains which characterize the IgG class of antibodies.


title: Antibody

text: The variable domains can also be referred to as the F region. It is the subregion of Fab that binds to an antigen.


title: Antibody

text: More specifically, each variable domain contains three "hypervariable regions" – the amino acids seen there vary the most from antibody to antibody.


title: Antibody

text: When the protein folds, these regions give rise to three loops of β-strands, localized near one another on the surface of the antibody.


title: Antibody

text: These loops are referred to as the complementarity-determining regions (CDRs), since their shape complements that of an antigen.


title: Antibody

text: Three CDRs from each of the heavy and light chains together form an antibody-binding site whose shape can be anything from a pocket to which a smaller antigen binds, to a larger surface, to a protrusion that sticks out into a groove in an antigen.


title: Antibody

text: The existence of two identical antibody-binding sites allows antibody molecules to bind strongly to multivalent antigen (repeating sites such as polysaccharides in bacterial cell walls, or other sites at some distance apart), as well as to form antibody complexes and larger antigen-antibody complexes. The resulting cross-linking plays a role in activating other parts of the immune system.


title: Antibody

text: and Nikoloudis et al. However, describing an antibody's binding site using only one single static structure limits the understanding and characterization of the antibody's function and properties. To improve antibody structure prediction and to take the strongly correlated CDR loop and interface movements into account, antibody paratopes should be described as interconverting states in solution with varying probabilities.


title: Antibody

text: In the framework of the immune network theory, CDRs are also called idiotypes. According to immune network theory, the adaptive immune system is regulated by interactions between idiotypes.


title: Antibody

text: The Fc region (the trunk of the Y shape) is composed of constant domains from the heavy chains. Its role is in modulating immune cell activity: it is where effector molecules bind to, triggering various effects after the antibody Fab region binds to an antigen.


title: Antibody

text: Effector cells (such as macrophages or natural killer cells) bind via their Fc receptors (FcR) to the Fc region of an antibody, while the complement system is activated by binding the C1q protein complex. IgG or IgM can bind to C1q, but IgA cannot, therefore IgA does not activate the classical complement pathway.


title: Antibody

text: Another role of the Fc region is to selectively distribute different antibody classes across the body. In particular, the neonatal Fc receptor (FcRn) binds to the Fc region of IgG antibodies to transport it across the placenta, from the mother to the fetus.


title: Antibody

text: Antibodies are glycoproteins, that is, they have carbohydrates (glycans) added to conserved amino acid residues.


title: Antibody

text: These conserved glycosylation sites occur in the Fc region and influence interactions with effector molecules.


title: Antibody

text: Each immunoglobulin domain has a similar structure, characteristic of all the members of the immunoglobulin superfamily:


title: Antibody

text: it is composed of between 7 (for constant domains) and 9 (for variable domains) β-strands, forming two beta sheets in a Greek key motif.


title: Antibody

text: However, some antibody classes also form dimers with two Ig units (as with IgA), tetramers with four Ig units (like teleost fish IgM), or pentamers with five Ig units (like shark IgW or mammalian IgM, which occasionally forms hexamers as well, with six units).


title: Antibody

text: Antibodies also form complexes by binding to antigen: this is called an antigen-antibody complex or "immune complex".


title: Antibody

text: Small antigens can cross-link two antibodies, also leading to the formation of antibody dimers, trimers, tetramers, etc.


title: Antibody

text: An extreme example is the clumping, or agglutination, of red blood cells with antibodies in the Coombs test to determine blood groups: the large clumps become insoluble, leading to visually apparent precipitation.


title: Antibody

text: The membrane-bound form of an antibody may be called a "surface immunoglobulin" (sIg) or a "membrane immunoglobulin" (mIg). It is part of the "B cell receptor" (BCR), which allows a B cell to detect when a specific antigen is present in the body and triggers B cell activation. The BCR is composed of surface-bound IgD or IgM antibodies and associated Ig-α and Ig-β heterodimers, which are capable of signal transduction. A typical human B cell will have 50,000 to 100,000 antibodies bound to its surface. Upon antigen binding, they cluster in large patches, which can exceed 1 micrometer in diameter, on lipid rafts that isolate the BCRs from most other cell signaling receptors.


title: Antibody

text: These patches may improve the efficiency of the cellular immune response. In humans, the cell surface is bare around the B cell receptors for several hundred nanometers, which further isolates the BCRs from competing influences.


title: Antibody

text: Antibodies can come in different varieties known as "isotypes" or "classes". In placental mammals there are five antibody classes known as IgA, IgD, IgE, IgG, and IgM, which are further subdivided into subclasses such as IgA1, IgA2.


title: Antibody

text: The prefix "Ig" stands for "immunoglobulin", while the suffix denotes the type of heavy chain the antibody contains: the heavy chain types α (alpha), γ (gamma), δ (delta), ε (epsilon), μ (mu) give rise to IgA, IgG, IgD, IgE, IgM, respectively.


title: Antibody

text: The distinctive features of each class are determined by the part of the heavy chain within the hinge and Fc region.


title: Antibody

text: The classes differ in their biological properties, functional locations and ability to deal with different antigens, as depicted in the table.


title: Antibody

text: For example, IgE antibodies are responsible for an allergic response consisting of histamine release from mast cells, often a sole contributor to asthma (though other pathways exist as do exist symptoms very similar to yet not technically asthma). The antibody's variable region binds to allergic antigen, for example house dust mite particles, while its Fc region (in the ε heavy chains) binds to Fc receptor ε on a mast cell, triggering its degranulation: the release of molecules stored in its granules.


title: Antibody

text: The antibody isotype of a B cell changes during cell development and activation. Immature B cells, which have never been exposed to an antigen, express only the IgM isotype in a cell surface bound form. The B lymphocyte, in this ready-to-respond form, is known as a "naive B lymphocyte." The naive B lymphocyte expresses both surface IgM and IgD. The co-expression of both of these immunoglobulin isotypes renders the B cell ready to respond to antigen. B cell activation follows engagement of the cell-bound antibody molecule with an antigen, causing the cell to divide and differentiate into an antibody-producing cell called a plasma cell. In this activated form, the B cell starts to produce antibody in a secreted form rather than a membrane-bound form. Some daughter cells of the activated B cells undergo isotype switching, a mechanism that causes the production of antibodies to change from IgM or IgD to the other antibody isotypes, IgE, IgA, or IgG, that have defined roles in the immune system.


title: Antibody

text: In mammals there are two types of immunoglobulin light chain, which are called lambda (λ) and kappa (κ). However, there is no known functional difference between them, and both can occur with any of the five major types of heavy chains. Each antibody contains two identical light chains: both κ or both λ. Proportions of κ and λ types vary by species and can be used to detect abnormal proliferation of B cell clones. Other types of light chains, such as the iota (ι) chain, are found in other vertebrates like sharks (Chondrichthyes) and bony fishes (Teleostei).


title: Antibody

text: Jawed fish appear to be the most primitive animals that are able to make antibodies similar to those of mammals, although many features of their adaptive immunity appeared somewhat earlier.


title: Antibody

text: Cartilaginous fish (such as sharks) produce heavy-chain-only antibodies (i.e., lacking light chains) which moreover feature longer chain pentamers (with five constant units per molecule). Camelids (such as camels, llamas, alpacas) are also notable for producing heavy-chain-only antibodies.


title: Antibody

text: The antibody's paratope interacts with the antigen's epitope. An antigen usually contains different epitopes along its surface arranged discontinuously, and dominant epitopes on a given antigen are called determinants.


title: Antibody

text: Antibody and antigen interact by spatial complementarity (lock and key). The molecular forces involved in the Fab-epitope interaction are weak and non-specific – for example electrostatic forces, hydrogen bonds, hydrophobic interactions, and van der Waals forces. This means binding between antibody and antigen is reversible, and the antibody's affinity towards an antigen is relative rather than absolute. Relatively weak binding also means it is possible for an antibody to cross-react with different antigens of different relative affinities.


title: Antibody

text: More indirectly, an antibody can signal immune cells to present antibody fragments to T cells, or downregulate other immune cells to avoid autoimmunity.


title: Antibody

text: Activated B cells differentiate into either antibody-producing cells called plasma cells that secrete soluble antibody or memory cells that survive in the body for years afterward in order to allow the immune system to remember an antigen and respond faster upon future exposures.


title: Antibody

text: At the prenatal and neonatal stages of life, the presence of antibodies is provided by passive immunization from the mother. Early endogenous antibody production varies for different kinds of antibodies, and usually appear within the first years of life. Since antibodies exist freely in the bloodstream, they are said to be part of the humoral immune system. Circulating antibodies are produced by clonal B cells that specifically respond to only one antigen (an example is a virus capsid protein fragment). Antibodies contribute to immunity in three ways: They prevent pathogens from entering or damaging cells by binding to them; they stimulate removal of pathogens by macrophages and other cells by coating the pathogen; and they trigger destruction of pathogens by stimulating other immune responses such as the complement pathway. Antibodies will also trigger vasoactive amine degranulation to contribute to immunity against certain types of antigens (helminths, allergens).


title: Antibody

text: Antibodies that bind to surface antigens (for example, on bacteria) will attract the first component of the complement cascade with their Fc region and initiate activation of the "classical" complement system. This results in the killing of bacteria in two ways. First, the binding of the antibody and complement molecules marks the microbe for ingestion by phagocytes in a process called opsonization; these phagocytes are attracted by certain complement molecules generated in the complement cascade. Second, some complement system components form a membrane attack complex to assist antibodies to kill the bacterium directly (bacteriolysis).


title: Antibody

text: To combat pathogens that replicate outside cells, antibodies bind to pathogens to link them together, causing them to agglutinate. Since an antibody has at least two paratopes, it can bind more than one antigen by binding identical epitopes carried on the surfaces of these antigens. By coating the pathogen, antibodies stimulate effector functions against the pathogen in cells that recognize their Fc region.


title: Antibody

text: Those cells that recognize coated pathogens have Fc receptors, which, as the name suggests, interact with the Fc region of IgA, IgG, and IgE antibodies. The engagement of a particular antibody with the Fc receptor on a particular cell triggers an effector function of that cell; phagocytes will phagocytose, mast cells and neutrophils will degranulate, natural killer cells will release cytokines and cytotoxic molecules; that will ultimately result in destruction of the invading microbe. The activation of natural killer cells by antibodies initiates a cytotoxic mechanism known as antibody-dependent cell-mediated cytotoxicity (ADCC) – this process may explain the efficacy of monoclonal antibodies used in biological therapies against cancer. The Fc receptors are isotype-specific, which gives greater flexibility to the immune system, invoking only the appropriate immune mechanisms for distinct pathogens.


title: Antibody

text: Humans and higher primates also produce "natural antibodies" that are present in serum before viral infection. Natural antibodies have been defined as antibodies that are produced without any previous infection, vaccination, other foreign antigen exposure or passive immunization. These antibodies can activate the classical complement pathway leading to lysis of enveloped virus particles long before the adaptive immune response is activated. Many natural antibodies are directed against the disaccharide galactose α(1,3)-galactose (α-Gal), which is found as a terminal sugar on glycosylated cell surface proteins, and generated in response to production of this sugar by bacteria contained in the human gut. Rejection of xenotransplantated organs is thought to be, in part, the result of natural antibodies circulating in the serum of the recipient binding to α-Gal antigens expressed on the donor tissue.


title: Antibody

text: Virtually all microbes can trigger an antibody response. Successful recognition and eradication of many different types of microbes requires diversity among antibodies; their amino acid composition varies allowing them to interact with many different antigens. It has been estimated that humans generate about 10 billion different antibodies, each capable of binding a distinct epitope of an antigen. Although a huge repertoire of different antibodies is generated in a single individual, the number of genes available to make these proteins is limited by the size of the human genome. Several complex genetic mechanisms have evolved that allow vertebrate B cells to generate a diverse pool of antibodies from a relatively small number of antibody genes.


title: Antibody

text: The chromosomal region that encodes an antibody is large and contains several distinct gene loci for each domain of the antibody—the chromosome region containing heavy chain genes (IGH@) is found on chromosome 14, and the loci containing lambda and kappa light chain genes (IGL@ and IGK@) are found on chromosomes 22 and 2 in humans. One of these domains is called the variable domain, which is present in each heavy and light chain of every antibody, but can differ in different antibodies generated from distinct B cells. Differences between the variable domains are located on three loops known as hypervariable regions (HV-1, HV-2 and HV-3) or complementarity-determining regions (CDR1, CDR2 and CDR3). CDRs are supported within the variable domains by conserved framework regions. The heavy chain locus contains about 65 different variable domain genes that all differ in their CDRs. Combining these genes with an array of genes for other domains of the antibody generates a large cavalry of antibodies with a high degree of variability. This combination is called V(D)J recombination discussed below.


title: Antibody

text: Somatic recombination of immunoglobulins, also known as "V(D)J recombination", involves the generation of a unique immunoglobulin variable region. The variable region of each immunoglobulin heavy or light chain is encoded in several pieces—known as gene segments (subgenes). These segments are called variable (V), diversity (D) and joining (J) segments. V, D and J segments are found in Ig heavy chains, but only V and J segments are found in Ig light chains. Multiple copies of the V, D and J gene segments exist, and are tandemly arranged in the genomes of mammals. In the bone marrow, each developing B cell will assemble an immunoglobulin variable region by randomly selecting and combining one V, one D and one J gene segment (or one V and one J segment in the light chain). As there are multiple copies of each type of gene segment, and different combinations of gene segments can be used to generate each immunoglobulin variable region, this process generates a huge number of antibodies, each with different paratopes, and thus different antigen specificities. The rearrangement of several subgenes (i.e. V2 family) for lambda light chain immunoglobulin is coupled with the activation of microRNA miR-650, which further influences biology of B-cells.


title: Antibody

text: RAG proteins play an important role with V(D)J recombination in cutting DNA at a particular region. Without the presence of these proteins, V(D)J recombination would not occur.


title: Antibody

text: After a B cell produces a functional immunoglobulin gene during V(D)J recombination, it cannot express any other variable region (a process known as allelic exclusion) thus each B cell can produce antibodies containing only one kind of variable chain.


title: Antibody

text: Following activation with antigen, B cells begin to proliferate rapidly. In these rapidly dividing cells, the genes encoding the variable domains of the heavy and light chains undergo a high rate of point mutation, by a process called "somatic hypermutation" (SHM). SHM results in approximately one nucleotide change per variable gene, per cell division. As a consequence, any daughter B cells will acquire slight amino acid differences in the variable domains of their antibody chains.


title: Antibody

text: This serves to increase the diversity of the antibody pool and impacts the antibody's antigen-binding affinity. Some point mutations will result in the production of antibodies that have a weaker interaction (low affinity) with their antigen than the original antibody, and some mutations will generate antibodies with a stronger interaction (high affinity). B cells that express high affinity antibodies on their surface will receive a strong survival signal during interactions with other cells, whereas those with low affinity antibodies will not, and will die by apoptosis. Thus, B cells expressing antibodies with a higher affinity for the antigen will outcompete those with weaker affinities for function and survival allowing the average affinity of antibodies to increase over time. The process of generating antibodies with increased binding affinities is called "affinity maturation". Affinity maturation occurs in mature B cells after V(D)J recombination, and is dependent on help from helper T cells.


title: Antibody

text: Isotype or class switching is a biological process occurring after activation of the B cell, which allows the cell to produce different classes of antibody (IgA, IgE, or IgG). The different classes of antibody, and thus effector functions, are defined by the constant (C) regions of the immunoglobulin heavy chain. Initially, naive B cells express only cell-surface IgM and IgD with identical antigen binding regions. Each isotype is adapted for a distinct function; therefore, after activation, an antibody with an IgG, IgA, or IgE effector function might be required to effectively eliminate an antigen. Class switching allows different daughter cells from the same activated B cell to produce antibodies of different isotypes. Only the constant region of the antibody heavy chain changes during class switching; the variable regions, and therefore antigen specificity, remain unchanged. Thus the progeny of a single B cell can produce antibodies, all specific for the same antigen, but with the ability to produce the effector function appropriate for each antigenic challenge. Class switching is triggered by cytokines; the isotype generated depends on which cytokines are present in the B cell environment.


title: Antibody

text: Class switching occurs in the heavy chain gene locus by a mechanism called class switch recombination (CSR). This mechanism relies on conserved nucleotide motifs, called "switch (S) regions", found in DNA upstream of each constant region gene (except in the δ-chain). The DNA strand is broken by the activity of a series of enzymes at two selected S-regions. The variable domain exon is rejoined through a process called non-homologous end joining (NHEJ) to the desired constant region (γ, α or ε). This process results in an immunoglobulin gene that encodes an antibody of a different isotype.


title: Antibody

text: An antibody can be called "monospecific" if it has specificity for the same antigen or epitope, or bispecific if they have affinity for two different antigens or two different epitopes on the same antigen. A group of antibodies can be called "polyvalent" (or "unspecific") if they have affinity for various antigens or microorganisms. Intravenous immunoglobulin, if not otherwise noted, consists of a variety of different IgG (polyclonal IgG). In contrast, monoclonal antibodies are identical antibodies produced by a single B cell.


title: Antibody

text: Heterodimeric antibodies, which are also asymmetrical antibodies, allow for greater flexibility and new formats for attaching a variety of drugs to the antibody arms. One of the general formats for a heterodimeric antibody is the "knobs-into-holes" format. This format is specific to the heavy chain part of the constant region in antibodies. The "knobs" part is engineered by replacing a small amino acid with a larger one. It fits into the "hole", which is engineered by replacing a large amino acid with a smaller one. What connects the "knobs" to the "holes" are the disulfide bonds between each chain. The "knobs-into-holes" shape facilitates antibody dependent cell mediated cytotoxicity. Single chain variable fragments (scFv) are connected to the variable domain of the heavy and light chain via a short linker peptide. The linker is rich in glycine, which gives it more flexibility, and serine/threonine, which gives it specificity. Two different scFv fragments can be connected together, via a hinge region, to the constant domain of the heavy chain or the constant domain of the light chain. This gives the antibody bispecificity, allowing for the binding specificities of two different antigens. The "knobs-into-holes" format enhances heterodimer formation but doesn't suppress homodimer formation.


title: Antibody

text: To further improve the function of heterodimeric antibodies, many scientists are looking towards artificial constructs. Artificial antibodies are largely diverse protein motifs that use the functional strategy of the antibody molecule, but aren't limited by the loop and framework structural constraints of the natural antibody. Being able to control the combinational design of the sequence and three-dimensional space could transcend the natural design and allow for the attachment of different combinations of drugs to the arms.


title: Antibody

text: Heterodimeric antibodies have a greater range in shapes they can take and the drugs that are attached to the arms don't have to be the same on each arm, allowing for different combinations of drugs to be used in cancer treatment. Pharmaceuticals are able to produce highly functional bispecific, and even multispecific, antibodies. The degree to which they can function is impressive given that such a change of shape from the natural form should lead to decreased functionality.


title: Antibody

text: The first use of the term "antibody" occurred in a text by Paul Ehrlich. The term "Antikörper" (the German word for "antibody") appears in the conclusion of his article "Experimental Studies on Immunity", published in October 1891, which states that, "if two substances give rise to two different "Antikörper", then they themselves must be different". However, the term was not accepted immediately and several other terms for antibody were proposed; these included "Immunkörper", "Amboceptor", "Zwischenkörper", "substance sensibilisatrice", "copula", "Desmon", "philocytase", "fixateur", and "Immunisin". The word "antibody" has formal analogy to the word "antitoxin" and a similar concept to "Immunkörper" ("immune body" in English). As such, the original construction of the word contains a logical flaw; the antitoxin is something directed against a toxin, while the antibody is a body directed against something.


title: Antibody

text: The study of antibodies began in 1890 when Emil von Behring and Kitasato Shibasaburō described antibody activity against diphtheria and tetanus toxins. Von Behring and Kitasato put forward the theory of humoral immunity, proposing that a mediator in serum could react with a foreign antigen. His idea prompted Paul Ehrlich to propose the side-chain theory for antibody and antigen interaction in 1897, when he hypothesized that receptors (described as "side-chains") on the surface of cells could bind specifically to toxins – in a "lock-and-key" interaction – and that this binding reaction is the trigger for the production of antibodies. Other researchers believed that antibodies existed freely in the blood and, in 1904, Almroth Wright suggested that soluble antibodies coated bacteria to label them for phagocytosis and killing; a process that he named opsoninization.


title: Antibody

text: In the 1920s, Michael Heidelberger and Oswald Avery observed that antigens could be precipitated by antibodies and went on to show that antibodies are made of protein. The biochemical properties of antigen-antibody-binding interactions were examined in more detail in the late 1930s by John Marrack. The next major advance was in the 1940s, when Linus Pauling confirmed the lock-and-key theory proposed by Ehrlich by showing that the interactions between antibodies and antigens depend more on their shape than their chemical composition. In 1948, Astrid Fagraeus discovered that B cells, in the form of plasma cells, were responsible for generating antibodies.


title: Antibody

text: Further work concentrated on characterizing the structures of the antibody proteins. A major advance in these structural studies was the discovery in the early 1960s by Gerald Edelman and Joseph Gally of the antibody light chain, and their realization that this protein is the same as the Bence-Jones protein described in 1845 by Henry Bence Jones. Edelman went on to discover that antibodies are composed of disulfide bond-linked heavy and light chains. Around the same time, antibody-binding (Fab) and antibody tail (Fc) regions of IgG were characterized by Rodney Porter. Together, these scientists deduced the structure and complete amino acid sequence of IgG, a feat for which they were jointly awarded the 1972 Nobel Prize in Physiology or Medicine. The Fv fragment was prepared and characterized by David Givol. While most of these early studies focused on IgM and IgG, other immunoglobulin isotypes were identified in the 1960s: Thomas Tomasi discovered secretory antibody (IgA); David S. Rowe and John L. Fahey discovered IgD; and Kimishige Ishizaka and Teruko Ishizaka discovered IgE and showed it was a class of antibodies involved in allergic reactions. In a landmark series of experiments beginning in 1976, Susumu Tonegawa showed that genetic material can rearrange itself to form the vast array of available antibodies.


title: Antibody

text: Detection of particular antibodies is a very common form of medical diagnostics, and applications such as serology depend on these methods. For example, in biochemical assays for disease diagnosis, a titer of antibodies directed against Epstein-Barr virus or Lyme disease is estimated from the blood. If those antibodies are not present, either the person is not infected or the infection occurred a "very" long time ago, and the B cells generating these specific antibodies have naturally decayed.


title: Antibody

text: In clinical immunology, levels of individual classes of immunoglobulins are measured by nephelometry (or turbidimetry) to characterize the antibody profile of patient. Elevations in different classes of immunoglobulins are sometimes useful in determining the cause of liver damage in patients for whom the diagnosis is unclear. For example, elevated IgA indicates alcoholic cirrhosis, elevated IgM indicates viral hepatitis and primary biliary cirrhosis, while IgG is elevated in viral hepatitis, autoimmune hepatitis and cirrhosis.


title: Antibody

text: Autoimmune disorders can often be traced to antibodies that bind the body's own epitopes; many can be detected through blood tests. Antibodies directed against red blood cell surface antigens in immune mediated hemolytic anemia are detected with the Coombs test. The Coombs test is also used for antibody screening in blood transfusion preparation and also for antibody screening in antenatal women.


title: Antibody

text: Practically, several immunodiagnostic methods based on detection of complex antigen-antibody are used to diagnose infectious diseases, for example ELISA, immunofluorescence, Western blot, immunodiffusion, immunoelectrophoresis, and magnetic immunoassay. Antibodies raised against human chorionic gonadotropin are used in over the counter pregnancy tests.


title: Antibody

text: New dioxaborolane chemistry enables radioactive fluoride (F) labeling of antibodies, which allows for positron emission tomography (PET) imaging of cancer.


title: Antibody

text: Targeted monoclonal antibody therapy is employed to treat diseases such as rheumatoid arthritis, multiple sclerosis, psoriasis, and many forms of cancer including non-Hodgkin's lymphoma, colorectal cancer, head and neck cancer and breast cancer.


title: Antibody

text: Some immune deficiencies, such as X-linked agammaglobulinemia and hypogammaglobulinemia, result in partial or complete lack of antibodies. These diseases are often treated by inducing a short-term form of immunity called passive immunity. Passive immunity is achieved through the transfer of ready-made antibodies in the form of human or animal serum, pooled immunoglobulin or monoclonal antibodies, into the affected individual.


title: Antibody

text: Rh factor, also known as Rh D antigen, is an antigen found on red blood cells; individuals that are Rh-positive (Rh+) have this antigen on their red blood cells and individuals that are Rh-negative (Rh–) do not. During normal childbirth, delivery trauma or complications during pregnancy, blood from a fetus can enter the mother's system. In the case of an Rh-incompatible mother and child, consequential blood mixing may sensitize an Rh- mother to the Rh antigen on the blood cells of the Rh+ child, putting the remainder of the pregnancy, and any subsequent pregnancies, at risk for hemolytic disease of the newborn.


title: Antibody

text: Rho(D) immune globulin antibodies are specific for human RhD antigen. Anti-RhD antibodies are administered as part of a prenatal treatment regimen to prevent sensitization that may occur when a Rh-negative mother has a Rh-positive fetus. Treatment of a mother with Anti-RhD antibodies prior to and immediately after trauma and delivery destroys Rh antigen in the mother's system from the fetus. It is important to note that this occurs before the antigen can stimulate maternal B cells to "remember" Rh antigen by generating memory B cells. Therefore, her humoral immune system will not make anti-Rh antibodies, and will not attack the Rh antigens of the current or subsequent babies. Rho(D) Immune Globulin treatment prevents sensitization that can lead to Rh disease, but does not prevent or treat the underlying disease itself.


title: Antibody

text: Specific antibodies are produced by injecting an antigen into a mammal, such as a mouse, rat, rabbit, goat, sheep, or horse for large quantities of antibody. Blood isolated from these animals contains "polyclonal antibodies"—multiple antibodies that bind to the same antigen—in the serum, which can now be called antiserum. Antigens are also injected into chickens for generation of polyclonal antibodies in egg yolk. To obtain antibody that is specific for a single epitope of an antigen, antibody-secreting lymphocytes are isolated from the animal and immortalized by fusing them with a cancer cell line. The fused cells are called hybridomas, and will continually grow and secrete antibody in culture. Single hybridoma cells are isolated by dilution cloning to generate cell clones that all produce the same antibody; these antibodies are called "monoclonal antibodies". Polyclonal and monoclonal antibodies are often purified using Protein A/G or antigen-affinity chromatography.


title: Antibody

text: In research, purified antibodies are used in many applications. Antibodies for research applications can be found directly from antibody suppliers, or through use of a specialist search engine. Research antibodies are most commonly used to identify and locate intracellular and extracellular proteins. Antibodies are used in flow cytometry to differentiate cell types by the proteins they express; different types of cells express different combinations of cluster of differentiation molecules on their surface, and produce different intracellular and secretable proteins. They are also used in immunoprecipitation to separate proteins and anything bound to them (co-immunoprecipitation) from other molecules in a cell lysate, in Western blot analyses to identify proteins separated by electrophoresis, and in immunohistochemistry or immunofluorescence to examine protein expression in tissue sections or to locate proteins within cells with the assistance of a microscope. Proteins can also be detected and quantified with antibodies, using ELISA and ELISpot techniques.


title: Antibody

text: Antibodies used in research are some of the most powerful, yet most problematic reagents with a tremendous number of factors that must be controlled in any experiment including cross reactivity, or the antibody recognizing multiple epitopes and affinity, which can vary widely depending on experimental conditions such as pH, solvent, state of tissue etc. Multiple attempts have been made to improve both the way that researchers validate antibodies and ways in which they report on antibodies. Researchers using antibodies in their work need to record them correctly in order to allow their research to be reproducible (and therefore tested, and qualified by other researchers). Less than half of research antibodies referenced in academic papers can be easily identified. Papers published in F1000 in 2014 and 2015 provide researchers with a guide for reporting research antibody use. The RRID paper, is co-published in 4 journals that implemented the RRIDs Standard for research resource citation, which draws data from the antibodyregistry.org as the source of antibody identifiers (see also group at Force11).


title: Antibody

text: Antibody regions can be used to further biomedical research by acting as a guide for drugs to reach their target. Several application involve using bacterial plasmids to tag plasmids with the Fc region of the antibody such as pFUSE-Fc plasmid.


title: Antibody

text: Traditionally, most antibodies are produced by hybridoma cell lines through immortalization of antibody-producing cells by chemically-induced fusion with myeloma cells. In some cases, additional fusions with other lines have created "triomas" and "quadromas". The manufacturing process should be appropriately described and validated. Validation studies should at least include:


title: Antibody

text: The importance of antibodies in health care and the biotechnology industry demands knowledge of their structures at high resolution. This information is used for protein engineering, modifying the antigen binding affinity, and identifying an epitope, of a given antibody. X-ray crystallography is one commonly used method for determining antibody structures. However, crystallizing an antibody is often laborious and time-consuming. Computational approaches provide a cheaper and faster alternative to crystallography, but their results are more equivocal, since they do not produce empirical structures. Online web servers such as "Web Antibody Modeling" (WAM) and "Prediction of Immunoglobulin Structure" (PIGS) enables computational modeling of antibody variable regions. Rosetta Antibody is a novel antibody F region structure prediction server, which incorporates sophisticated techniques to minimize CDR loops and optimize the relative orientation of the light and heavy chains, as well as homology models that predict successful docking of antibodies with their unique antigen. However, describing an antibody's binding site using only one single static structure limits the understanding and characterization of the antibody's function and properties. To improve antibody structure prediction and to take the strongly correlated CDR loop and interface movements into account, antibody paratopes should be described as interconverting states in solution with varying probabilities.


title: Antibody

text: The ability to describe the antibody through binding affinity to the antigen is supplemented by information on antibody structure and amino acid sequences for the purpose of patent claims. Several methods have been presented for computational design of antibodies based on the structural bioinformatics studies of antibody CDRs.


title: Antibody

text: There are a variety of methods used to sequence an antibody including Edman degradation, cDNA, etc.; albeit one of the most common modern uses for peptide/protein identification is liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). High volume antibody sequencing methods require computational approaches for the data analysis, including de novo sequencing directly from tandem mass spectra and database search methods that use existing protein sequence databases. Many versions of shotgun protein sequencing are able to increase the coverage by utilizing CID/HCD/ETD fragmentation methods and other techniques, and they have achieved substantial progress in attempt to fully sequence proteins, especially antibodies. Other methods have assumed the existence of similar proteins, a known genome sequence, or combined top-down and bottom up approaches. Current technologies have the ability to assemble protein sequences with high accuracy by integrating de novo sequencing peptides, intensity, and positional confidence scores from database and homology searches.


title: Antibody

text: Antibody mimetics are organic compounds, like antibodies, that can specifically bind antigens. They consist of artificial peptides or proteins, or aptamer-based nucleic acid molecules with a molar mass of about 3 to 20 kDa. Antibody fragments, such as Fab and nanobodies are not considered as antibody mimetics. Common advantages over antibodies are better solubility, tissue penetration, stability towards heat and enzymes, and comparatively low production costs. Antibody mimetics have being developed and commercialized as research, diagnostic and therapeutic agents.


title: Antibody

text: BAU (binding antibody unit, often as BAU/mL) is a measurement unit defined by the WHO for the comparison of assays detecting the same class of immunoglobulins with the same specificity.


title: Jodi Balfour

text: Jodi Balfour (born October 29, 1986) is a South African film and television actress, known for her role as Gladys Witham in the Canadian television drama series "Bomb Girls" and Ellen Waverly Wilson in the Apple TV+ space drama series "For All Mankind".


title: Jodi Balfour

text: Balfour grew up in Cape Town, South Africa. She was the co-host of the South African youth television series "Bling" in the early 2000s. She later studied drama at the University of Cape Town and competed in the Miss South Africa 2008 pageant.


title: Jodi Balfour

text: Since her graduation in 2009, she has worked as an actor primarily in British and Canadian film and television productions.


title: Jodi Balfour

text: She was cast as Gladys Witham in the Canadian television drama series "Bomb Girls" in 2013. She won a Canadian Screen Award for Best Lead Actress in a Television Film or Miniseries at the 3rd Canadian Screen Awards in 2015 for her performance in the series' follow-up television film "Bomb Girls: Facing the Enemy".


title: Jodi Balfour

text: Balfour is based in Vancouver, British Columbia, where in addition to her acting she is co-owner of a coffeehouse in the city's Gastown neighbourhood.


title: Jodi Balfour

text: On 30 June 2021, she announced on Instagram that she identifies as queer, stating that she found it freeing to "finally embrace and explore [her] queerness." On 24 October 2021, Balfour announced on Instagram that she and Abbi Jacobson had been romantically involved for a year. As of August 2022, Balfour and Jacobson are engaged.


title: Uniformed services of the United States

text: The United States has eight federal uniformed services that commission officers as defined by Title 10 and subsequently structured and organized by Titles 10, 14, 32, 33 and 42 of the U.S. Code.


title: Uniformed services of the United States

text: Each of the uniformed services is administratively headed by a federal executive department and its corresponding civilian Cabinet leader.


title: Uniformed services of the United States

text: The order of precedence within the Department of Defense is set by DoD Directive 1005.8 and is not dependent on the date of creation by the U.S. Congress.


title: Uniformed services of the United States

text: Prior to 1967, the Coast Guard was a part of the Department of the Treasury. In 1967, it became a part of the Department of Transportation. In 2002, it was placed under the Department of Homeland Security. During times of war, it may be transferred to the Department of the Navy, under the Department of Defense.


title: Uniformed services of the United States

text: The NOAA Corps was created as the United States Coast and Geodetic Survey Corps, a component of the United States Coast and Geodetic Survey, on 22 May 1917. It was removed from the Coast and Geodetic Survey and became a component of the Environmental Science Services Administration (ESSA) as the Environmental Science Services Administration Corps (ESSA Corps) upon the establishment of ESSA on 13 July 1965. The ESSA Corps became the NOAA Corps as a component of NOAA when ESSA was abolished and NOAA simultaneously was created on 3 October 1970. Under all three names, the corps has been an element of the Department of Commerce throughout its existence.


title: Uniformed services of the United States

text: The six uniformed services that make up the armed forces of the United States are defined in the previous clause, :


title: Uniformed services of the United States

text: All eight uniformed services are subject to the provisions of 10 USC 1408, the Uniformed Services Former Spouses' Protection Act.


title: Uniformed services of the United States

text: Six of the uniformed services make up the armed forces as defined by Title 10, five of which are within the Department of Defense. The Coast Guard is part of the Department of Homeland Security and has both military and law enforcement duties. Title 14 states that the Coast Guard is part of the armed forces at all times, making it the only branch of the military outside the Department of Defense. During a declared state of war, however, the President of the United States or U.S. Congress may direct that the Coast Guard operate as part of the Department of the Navy. The Public Health Service Commissioned Corps, along with the NOAA Commissioned Corps, operate under military rules with the exception of the applicability of the Uniform Code of Military Justice, to which they are subject only when militarized by executive order or while detailed to any component of the armed forces.


title: Uniformed services of the United States

text: Reserve components of the United States Armed Forces are all members of the military who serve in a reserve capacity. The National Guard is an additional reserve military component of the Army and Air Force, respectively, and is composed of National Guard units, which operate under Title 32 and under state authority as the Army National Guard and Air National Guard. The militia that later became the National Guard was first formed in the Colony of Virginia in 1607 and is the oldest uniformed military force founded in the New World. The National Guard can also be mobilized by the president to operate under federal authority through Title 10. When acting under federal direction, the National Guard is managed by the National Guard Bureau, which is a joint Army and Air Force activity under the Department of Defense, with a 4-star general from the Army or Air Force appointed as its top leader. However, in federal service, command and control of National Guard organizations will fall under the designated geographic or functional combatant commander. The National Guard of the United States serves as a reserve component for both the Army and the Air Force, and can be called up for federal active duty in times of war or national emergencies.


title: Uniformed services of the United States

text: Commissioned officers of the NOAA Corps and PHSCC wear uniforms that are derived from U.S. Navy and Coast Guard uniforms, except that the commissioning devices, buttons, and insignia reflect their specific service. Uniformed officers of the NOAA Corps and PHSCC are paid on the same scale as members of the armed services, with respective rank and time-in-grade. Additionally, PHSCC officers are covered by the Uniformed Services Employment and Re-employment Rights Act and the Servicemembers Civil Relief Act (formerly the Soldiers and Sailors Civil Relief Act). The NOAA Corps and PHSCC consist of commissioned officers only and have no warrant officer ranks or enlisted ranks.


title: Uniformed services of the United States

text: Commissioned officers of the NOAA Corps and PHSCC may be militarized by the president. Because they are commissioned officers, they can be classified as prisoners of war under the Geneva Conventions if captured by a belligerent entity. The PHSCC traces its origins to a system of marine hospitals created by An Act for the relief of sick and disabled seamen, passed by Congress in 1798; it adopted a military model of organization in 1871. The Coast and Geodetic Survey (USC&GS), a predecessor to NOAA, originally began commissioning its officers so that if captured while engaged in battlefield surveying, they would be protected under the law of armed conflict and could not be tried or executed as spies. The USC&GS Commissioned Officer Corps became the Environmental Science Services Administration Corps (ESSA Corps), upon the creation of the Environmental Science Services Administration on 13 July 1965, then became the NOAA Corps upon the creation of NOAA on 3 October 1970.


title: Stormy Daniels

text: Stephanie Gregory Clifford (born March 17, 1979), known professionally as Stormy Daniels, is an American pornographic film actress and director, and former stripper. She has won numerous industry awards, and is a member of the NightMoves, AVN and XRCO Halls of Fame. In 2009, a recruitment effort led her to consider challenging incumbent David Vitter for the 2010 Senate election in her native Louisiana.


title: Stormy Daniels

text: In 2018, Daniels became involved in a legal dispute with U.S. president Donald Trump and his attorney Michael Cohen. Trump and his surrogates paid $130,000 hush money to silence Daniels about an affair she says she had with Trump in 2006. Trump's spokespeople have denied the affair and accused Daniels of lying.


title: Stormy Daniels

text: Daniels' parents, Sheila and Bill Gregory, divorced about three or four years after she was born. She was then raised by her mother.


title: Stormy Daniels

text: She graduated from Scotlandville Magnet High School in Baton Rouge in 1997 and considered becoming a journalist.


title: Stormy Daniels

text: Daniels said she "came from an average, lower-income household… there [were] days without electricity", and she has described herself as coming from a "really bad neighborhood." During high school, Daniels had a job answering phones at a riding stable.


title: Stormy Daniels

text: Daniels's first experience as a stripper occurred when she was 17 and visiting a friend at a strip club; she was convinced to perform a "guest set". She began stripping for money at the Gold Club in Baton Rouge and became a featured entertainer with Continental Theatrical Agency in September 2000. She chose her stage name Stormy Daniels to reflect her love of American rock band Mötley Crüe, whose bassist, Nikki Sixx, named his daughter Storm.


title: Stormy Daniels

text: In 2004, Daniels won the Best New Starlet Award from "Adult Video News", which was a surprise to Daniels, who had made a $500 bet with another actress that Jesse Jane would win. She has directed for Wicked since 2004.