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Leon Francis Phillips (14 July 1935 – 24 September 2023) was a New Zealand physical chemist who specialised in the gas-liquid interface and atmospheric chemistry .
Born in Thames on 14 July 1935, Phillips was educated at Westport Technical College and Christchurch Boys' High School . [ 1 ] He studied at Canterbury University College , from where he graduated with an MSc with first-class honours in 1958. [ 2 ] After a PhD at the University of Cambridge and post-doctoral research at McGill University , he returned to lecture at Canterbury, rising to the rank of professor in 1966. [ 3 ]
In 1968, Phillips was elected a Fellow of the Royal Society of New Zealand , [ 4 ] and in 1979 he won the society's Hector Medal . [ 5 ]
In 1959, Phillips married Pamela Anne Johnstone, and the couple went on to have two children. [ 1 ] He died in Christchurch on 24 September 2023, at the age of 88. [ 6 ] [ 7 ]
This biographical article about a New Zealand academic is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Leon_Phillips_(chemist) |
The Leonard Medal honors outstanding contributions to the science of meteoritics and closely allied fields. It is awarded by the Meteoritical Society . It was established in 1962 to honor the first President of the Society, Frederick C. Leonard . [ 1 ] | https://en.wikipedia.org/wiki/Leonard_Medal |
The Leonhard Euler Gold Medal (Золотая медаль имени Леонарда Эйлера) is a medal named after the Swiss, German, and Russian mathematician Leonhard Euler , awarded by the Отделением математических наук (Branch of Mathematical Sciences of the Russian Academy of Sciences ) for outstanding results in mathematics and physics. The medal was awarded once in 1957 to two scientists and since 1991 has been awarded every five years. [ 1 ] | https://en.wikipedia.org/wiki/Leonhard_Euler_Gold_Medal |
Leonidas Zervas ( Greek : Λεωνίδας Ζέρβας , pronounced [leoˈniðas ˈzervas] ; 21 May 1902 – 10 July 1980) was a Greek organic chemist who made seminal contributions in peptide chemical synthesis . [ 1 ] [ 2 ] [ 3 ] [ 4 ] Together with his mentor Max Bergmann they laid the foundations for the field in 1932 with their major discovery, the Bergmann-Zervas carboxybenzoxy oligopeptide synthesis which remained unsurpassed in utility for the next two decades. [ 1 ] [ 2 ] The carboxybenzyl protecting group he discovered is often abbreviated Z in his honour. [ 1 ]
Throughout his life Zervas also served in many important posts, including President of the Academy of Athens or briefly Minister of Industry of Greece. [ 2 ] [ 4 ] He received numerous awards and honours during his life and posthumously, such as Foreign Member of the USSR Academy of Sciences or the first Max Bergmann golden medal. [ 1 ] [ 2 ] [ 3 ] [ 5 ]
Zervas was born in 1902 in the rural town of Megalopolis in Arcadia , southern Greece. [ 3 ] He was the first of 7 children of lawyer and parliamentarian Theodoros Zervas with Vasiliki Zerva (née Gyftaki). [ 2 ] [ 3 ] After finishing secondary education at the local Gymnasion of Kalamata in 1918, he went to study Chemistry at the University of Athens . [ 1 ] [ 2 ] Before finishing his studies there, he moved to Berlin in 1921 where he graduated with a degree in chemistry from the University of Berlin in 1924. [ 1 ] [ 2 ] [ 4 ]
Under the supervision of Max Bergmann , he finished his doctoral thesis on the reactions of amino acids with aldehydes and was awarded his Dr. rer. nat. from the University of Berlin in 1926. [ 4 ] He proceeded to work with Bergmann in the Kaiser Wilhelm Institute for Leather Research in Dresden , of which Bergmann was the founder and director. [ 1 ] From 1926 to 1929 Zervas was a research associate and eventually rose to head of the organic chemistry division and vice-director of the institute (1929–1934). [ 1 ] [ 2 ] It was at this period that the two men developed the Bergmann-Zervas oligopeptide synthesis which brought them international fame within academic circles. [ 1 ] [ 3 ]
Zervas, by that point a close personal friend of Bergmann, decided to follow the latter to the US in 1934 after Bergmann emigrated from Nazi Germany in 1933 under pressure due to his Jewish origin. [ 1 ] [ 3 ] In New York, Zervas spent 3 years as lecturer and researcher at the Rockefeller Institute for Medical Research . [ 1 ] [ 4 ]
In 1930, he married Hildegard Lange, and they remained together until his death. [ 2 ] [ 3 ]
After his Berlin, Dresden and New York years, Zervas decided to return to Greece in 1937. [ 3 ] He was immediately appointed full Professor of Organic Chemistry and Biochemistry at the Aristotle University of Thessaloniki in recognition of his distinguished international work. [ 2 ] [ 3 ] He stayed in this position until 1939, when he was invited to the Professorship of Organic Chemistry at the University of Athens and also appointed director of the Laboratory of Organic Chemistry of the same institution. [ 2 ] He continued conducting research, despite the severe limitations he often faced from the lack of equipment and funding. [ 2 ] Concurrent to research, Zervas taught organic chemistry, oversaw the laboratory and guided many generations of young chemists as doctoral advisor for the 29 years he held the post at the University of Athens. [ 1 ] [ 2 ]
During the Axis occupation of Greece Zervas played an active part in the Greek Resistance as a member of EDES ; he was imprisoned twice, first by the Italian and then by the German occupying forces, and his laboratory was destroyed. [ 2 ] [ 3 ] Following the liberation of Greece, Zervas managed to secure a small part of the American postwar aid for repairs in the University of Athens and the Athens Polytechnic , and thus rebuilt his laboratory in 1948 – 1951. [ 2 ]
In the following years, guided by a sense of personal and professional duty, Zervas voluntarily took on a variety of responsibilities within the Greek state. [ 2 ] At his own insistence, he never got paid for these posts and kept receiving only his professorial salary. [ 2 ] [ 3 ] Some notable positions he held in chronological order until 1968 include: [ 4 ]
The democratic ideals of Zervas made him a target of the military junta established in 1967, which removed him from his position in the University of Athens in 1968 after almost three decades of dedicated research and teaching. [ 2 ] [ 3 ] In response, the Academy of Athens of which Zervas had been a member since 1956 elected him as its president in 1970. [ 3 ] After his term as President of the Academy, Zervas retired in 1971.
With the restoration of democracy in 1974, Zervas was able to contribute once more to research and educational policy. [ 3 ] As previously, refusing to take a salary for these positions, he served a second time as the President of the Greek Atomic Energy Commission (1974–1975) and then as the President of the National Hellenic Research Foundation (1975–1979). [ 2 ] [ 3 ] [ 4 ]
Zervas had suffered from periodic issues with respiratory health throughout his adult life, but in his final years the situation deteriorated. [ 2 ] The extended use of phosgene in his research has been implicated as the cause of this chronic pulmonary disease. [ 3 ] He showed perseverance and a pleasant attitude despite his health issues, continuing to attend meetings of the Academy of Athens until the very end of his life. [ 3 ] This came in the summer of 1980 after an acute pulmonary episode, which lasted three weeks before he died at the age of 78. [ 2 ]
The enduring contributions of Zervas were made together with Bergmann and involved the first successful synthesis of substantial length oligopeptides . [ 1 ] They achieved this using the carboxybenzyl amine protecting group for the masking of the N -terminus of the growing oligopeptide chain to which amino acid residues are added in a serial manner. [ 1 ] [ 6 ] The carboxybenzyl group discovered by Zervas is introduced by reaction with benzyl chloroformate , originally in aqueous sodium carbonate solution at 0 °C: [ 6 ]
The protecting group is abbreviated Cbz or, in honour of Zervas, simply Z . [ 1 ] The typical route for deprotection involves hydrogenolysis under mild conditions e.g. with hydrogen gas and a catalyst such as palladium on charcoal . [ 6 ]
The discovery of the Bergmann-Zervas synthesis has been characterised as "epoch-making" [ 1 ] as it allowed the advent of controlled synthetic peptide chemistry, completing the work started in the early 20th century by Bergmann's mentor Emil Fischer . Previously impossible to synthesise oligopeptides with a highly specific sequence and reactive side chains were consequently produced in the 1930s by Bergmann and Zervas. [ 1 ] [ 2 ] The ability of Z-protection to prevent racemization of activated derivatives of the protected amino acids and the importance thereof were also noted by the two chemists. [ 1 ] [ 6 ]
Indeed, their method became the standard in the field for the following two decades until further developments in the early 1950s with the introduction of mixed anhydrides ( e.g. the Boc group ). [ 1 ]
Zervas continued his research on peptide synthesis in New York and later in Greece. [ 2 ] The first topic of his research once in Greece was the synthesis of N - or O - phosphorylated amino acids, in which he demonstrated the utility of dibenzyl chlorophosphonate. [ 1 ] He continued his efforts on the development of new methods within peptide chemistry, including the introduction of the o -nitrophenylsulfenyl (NPS) amino protecting group and peptide synthesis using N -tritylamino acids. [ 1 ]
One of the major issues which occupied his interests was the chemical synthesis of insulin after its characterisation by Frederick Sanger (1951). [ 1 ] The insulin peptide hormone features two protein chains cross-linked by disulfide bridges from cysteine thiols. For this reason, Zervas undertook a systematic study on asymmetric cysteine-containing peptides. [ 1 ] [ 2 ] In his attempts he introduced new mercaptan protecting groups ( e.g. trityl , benzhydryl or benzoyl ), which finally made it possible to produce disulfide bridges in a controlled manner. [ 1 ] This was a triumph for peptide chemistry in the lab, but could not be possibly scaled to industrial procedures. Building on this work, the first complete synthesis of insulin was simultaneously achieved in 1963 in RWTH Aachen University by Helmut Zahn and in the University of Pittsburgh by Panayotis Katsoyannis , a student of Zervas. [ 1 ] Further work on asymmetrical cysteine polypeptides was also done in Athens by Iphigenia Photaki , another student of his. [ 1 ] [ 3 ]
Overall, the research work of Zervas spans across six decades (1925–1979) and amounts to 96 publications in international chemistry journals. [ 2 ]
The scientific work of Leonidas Zervas had a global resonance and his contribution was recognised by multiple awards throughout his life. [ 1 ] [ 2 ] [ 3 ] [ 4 ] In 1960 he received an honorary doctorate from the University of Basel on the occasion of the university's 500th anniversary, upon recommendation of Hans Erlenmeyer and Nobel laureate Tadeusz Reichstein . [ 1 ] [ 3 ] In 1969 he was bestowed honorary membership of the American Society of Biological Chemists. [ 1 ] [ 2 ] In 1976 he was conferred the Order of Scientific Merit [ ro ] (1st class) by the Socialist Republic of Romania . [ 2 ] In the same year Zervas was made Foreign Member of the USSR Academy of Sciences , an indication of the great respect for his work in the Eastern Bloc , too. [ 2 ] [ 3 ] The Max-Bergmann-Kreis company of German peptide chemists planned to present Zervas with the first Max Bergmann golden medal for peptide chemistry in 1980, but his sudden death necessitated a posthumous award ceremony. [ 3 ]
In honour of Zervas, a commemorative bust has been unveiled in his birthtown Megalopolis in 1991 [ 5 ] and the main conference hall of the National Hellenic Research Foundation is called the "Leonidas Zervas amphitheatre". [ 7 ]
The European Peptide Society has established the Leonidas Zervas Award "in commemoration of his outstanding contributions to peptide science", awarded biennially since 1988. [ 8 ] The award is given to the "scientist who has made the most outstanding contributions to the chemistry, biochemistry and/or biology of peptides in the five years preceding the date of selection". [ 8 ] | https://en.wikipedia.org/wiki/Leonidas_Zervas |
Leopold Ružička ForMemRS ( Croatian pronunciation: [rǔʒitʃka] ; [ 3 ] born Lavoslav Stjepan Ružička ; 13 September 1887 – 26 September 1976) [ 5 ] was a Croatian-Swiss scientist and joint winner of the 1939 Nobel Prize in Chemistry "for his work on polymethylenes and higher terpenes " [ 6 ] [ 7 ] "including the first chemical synthesis of male sex hormones ." [ 8 ] He worked most of his life in Switzerland, and received eight doctorates honoris causa in science, medicine, and law; seven prizes and medals; and twenty-four honorary memberships in chemical, biochemical, and other scientific societies.
Ružička was born in Vukovar (until 1918 in the Austria-Hungary , today in Croatia ). His family of craftsmen and farmers was mostly of Croat origin, [ 9 ] with a Czech great-grandparent, Ružička , and a great-grandmother and a great-grandfather from Austria . [ 6 ] He lost his father, Stjepan, at the age of four, and his mother, Amalija Sever, took him and his younger brother Stjepan, to live in Osijek . [ 5 ]
Ružička attended the classics program secondary school in Osijek. He changed his original idea of becoming a priest and switched to studying technical disciplines. [ 10 ] Chemistry was his choice, probably because he hoped to get a position at the newly opened sugar refinery built in Osijek. [ 5 ]
Owing to the excessive hardship of everyday and political life, he left and chose the High Technical School in Karlsruhe in Germany. He was a good student in areas he liked and that he thought would be necessary and beneficial in the future, which was organic chemistry . That is why his physical chemistry professor, Fritz Haber ( Nobel laureate in 1918), opposed his summa cum laude degree . However, in the course of his studies, Ružička set up excellent cooperation with Hermann Staudinger (a Nobel laureate in 1953). Studying within Staudinger's department, he obtained his doctoral degree in 1910, then moved to Zürich as Staudinger's assistant.
Ružička's first works originated in the field of chemistry of natural compounds. [ 11 ] He remained in this field of research all his life. He investigated the ingredients of the Dalmatian insect powder Pyrethrum (from the herb Tanacetum cinerariifolium ), a highly esteemed insecticide found in pyrethrins , which were the focus of his work with Staudinger. Ružička later said of this time: "Toward the end of five and a half years of mainly synthetic work on the pyrethrins I had come to the firm conclusion that we were barking up the wrong tree." In this way, he came into contact with the chemistry of Terpineol , a fragrant oil of vegetable origin, interesting to the perfume industry . He and Staudinger split company when he started cooperation with the Chuit & Naef Company (later known as Firmenich ) in Geneva . [ 10 ] [ 5 ]
In 1916–1917, he received the support of the oldest perfume manufacturer in the world Haarman & Reimer , of Holzminden , Germany. He became a Swiss citizen in 1917, [ 5 ] and published his Habilitation in 1918. [ 10 ] Fornasir and he isolated linalool in 1919. [ 10 ]
With expertise in the terpene field, he became senior lecturer in 1918, and in 1923, honorary professor at the ETH (Eidgenössische Technische Hochschule) as well as the University of Zurich . Here, with a group of his doctoral students, he proved the structure of the compounds muscone and civetone , macrocyclic ketone scents derived from the musk deer ( Moschus moschiferus ) and the civet cat ( Viverra civetta ). [ 12 ] These were the first natural products shown to have rings with more than six atoms, and at the time that Ružička inferred that civetone as having a 17-member ring. [ 13 ] Synthetic techniques at the time were only known for rings of up to eight members. [ 14 ] Muscone had been isolated in 1904 [ 15 ] but was not identified as 3-methylcyclopentadecanone [ 16 ] until Ružička suspected a macrocycle , having characterised civetone. He also developed a method for synthesising macrocycles, now known as the Ružička large ring synthesis , [ 17 ] which he demonstrated by preparing civetone in 1927. [ 14 ] [ 18 ]
In 1921, the Geneva perfume manufacturers Chuit & Naef asked him to collaborate. [ 5 ] Working here, Ružička achieved financial independence, but not as big as he had planned, so he left Zürich to start working for the Basel -based CIBA . [ citation needed ] In 1927, he took over the organic chemistry chair at Utrecht University in the Netherlands. In the Netherlands, he remained for three years and then returned to Switzerland , which was superior in its chemical industry. A synergistic upheaval in both the administration and chemistry departments coincided to make his good fortune. [ 5 ]
Ružička was the first to synthesize musk at an industrial scale. Firmenech named this product Exaltone . Other Swiss manufacturers and DuPont were in competition with them. [ 19 ]
In 1934, Ružička synthesized the male hormone androsterone and also proved "its constitutional and configurational relation to the sterols ." This was followed in 1935 by the partial synthesis of the much more active male hormone testosterone . Both discoveries led to the pre-eminence of the Swiss industry in the steroid hormone field. [ 5 ] At ETH Zurich he became a professor of organic chemistry and started the most brilliant period of his professional career. He widened the area of his research, adding to it the chemistry of higher terpenes and steroids . After the successful synthesis in 1935 of sex hormones ( androsterone and testosterone ), [ 20 ] his laboratory became the world centre of organic chemistry. [ 21 ] He was awarded in 1936 an honorary degree from Harvard University . [ 20 ]
In 1939 he won the Nobel Prize in Chemistry with Adolf Butenandt . [ 6 ] Over the period 1934–1939 he published 70 papers in the field of medicinally important steroid sex hormones, and filed several dozen patents besides. [ 5 ]
In 1940, following the award, he was invited by the Croatian Chemical Association , where he delivered a lecture to an over-packed hall of dignitaries. The topic of the lecture was From the Dalmatian Insect Powder to Sex Hormones . In 1940 he became a foreign member of the Royal Netherlands Academy of Arts and Sciences , [ 4 ] in 1942 he was elected a foreign member of the Royal Society , [ 5 ] and in 1944 he became an international member of the US National Academy of Sciences . [ 22 ] During World War II , some of his excellent collaborators were lost, but Ružička restructured his laboratory with new, younger and promising people; among them was young scientist and future Nobel laureate Vladimir Prelog . With new people and ideas new research areas were opened.
In 1946, Ružička and Lardon "established that the fragrance of ambergris is based on the triterpene (named) ambrein ". [ 23 ] [ 5 ] [ 8 ]
Following 1950, Ružička returned to chemistry, which had entered a new era of research. Now he turned to the field of biochemistry , the problems of evolution and the genesis of life, particularly to the biogenesis of terpenes. In 1953, he published his hypothesis, the Biogenetic Isoprene Rule (that the carbon skeleton of terpenes is composed variously of regularly or irregularly linked isoprene units), which was the peak of his scientific career. [ 24 ] In 1952, Oskar Jeger and he supervised a team which isolated lanosterol and established the link between terpenes and steroids. [ 25 ] Ružička retired in 1957, turning over the running of the laboratory to Prelog. [ 26 ]
Ružička was the recipient of eight honorary doctorates and the 1938 Marcel Benoist Prize . [ 5 ] He was listed as an author on 583 scientific papers. [ 5 ] In 1965, he became an honorary member of the Polish Chemical Society , [ 27 ] and he was an honorary member of the American Academy of Arts and Sciences . [ 20 ] After the war he acquired a taste for Dutch masterpieces, which he later lodged in the Kunsthaus Zürich as the Ružička collection. [ 5 ] He militated against nuclear weapons . [ 28 ]
In 1970, Ružička delivered to the Nobel Laureate Conferences in Lindau a lecture entitled "Nobel Prizes and the chemistry of life". [ 5 ]
In later years, he served as a consultant to Sandoz A. G. of Basel. [ 5 ]
Ružička dedicated significant efforts to the problems of education. He insisted on a better organization of academic education and scientific work in the new Yugoslavia , and established the Swiss-Yugoslav Society . Ružička became an honorary academician at the then Yugoslav Academy of Sciences and Arts in Zagreb .
In 1974 he was awarded the Order of the Yugoslav Flag with Golden Wreath. [ 5 ]
At ETH Zurich , the Ružička Award was established in 1957 on the occasion of his retirement, for young chemists working in Switzerland. [ 10 ]
In his native Vukovar , a museum was opened in his honour in 1977. [ 5 ]
Ružička's archives are kept at ETH Zurich. [ 28 ]
The Ružička reaction is named after him. [ 29 ]
Ružička married twice: to Anna Hausmann in 1912, and in 1951 to Gertrud Acklin. [ 6 ] From 1929, he lived at Freudenbergstrasse 101 until the last years of his life. [ 5 ] He died in Mammern , Switzerland , a village on Lake Constance at the age of 89. [ 20 ] | https://en.wikipedia.org/wiki/Leopold_Ružička |
Leopold Blaschka (27 May 1822 – 3 July 1895) and his son Rudolf Blaschka (17 June 1857 – 1 May 1939) were glass artists from Dresden , Germany . They were known for their production of biological and botanical models, including glass sea creatures and Harvard University 's Glass Flowers .
The Blaschka family's roots trace to Josephthal in Erzgebirge , Bohemia , a region known for processing glass, metals , and gems. [ 1 ] Members of the Blaschka family worked in Venice , Bohemia , and Germany. [ 2 ] [ 3 ] [ 4 ] Leopold referred to this history in an 1889 letter to Mary Lee Ware :
Many people think that we have some secret apparatus by which we can squeeze glass suddenly into these forms, but it is not so. We have the touch. [ 5 ] My son Rudolf has more than I have because he is my son and the touch increases in every generation. The only way to become a glass modeler of skill, I have often said to people, is to get a good great-grandfather who loved glass; then he is to have a son with like tastes; he is to be your grandfather. He in turn will have a son who must, as your father, be passionately fond of glass. You, as his son, can then try your hand, and it is your own fault if you do not succeed. But, if you do not have such ancestors, it is not your fault. [ 6 ] [ 7 ]
Leopold was born in Český Dub , Bohemia , one of the three sons of Joseph Blaschke. Leopold himself would later Latinize the family name to Blaschka. [ 4 ] [ 8 ] He and his son were native to the Bohemian Czech-German borderland.
Leopold was apprenticed to a goldsmith and gem cutter in Turnov , a town in the Liberec Region of today's Czech Republic. [ 8 ] He then joined the family business which produced glass ornaments and glass eyes . [ 2 ] Leopold developed a technique which he termed "glass-spinning" which permitted the construction of highly precise and detailed works in glass. He soon began to focus the business on manufacturing glass eyes. [ 1 ]
In 1846, Leopold married Caroline Zimmermann, and within four years their son Josef Augustin Blaschka was born. [ 8 ] Caroline and Josef both died of cholera in 1850. A year later, Leopold's father died. Leopold "sought consolation in the natural world, sketching the plants in the countryside around his home." [ 9 ] [ 8 ]
In 1853, Leopold travelled to the United States. While on route, the ship was delayed at sea for two weeks due to a lack of trade winds . [ 10 ] During this time, Leopold studied and sketched local marine invertebrates , the glass-like transparency of their bodies intriguing him. [ 1 ] He wrote:
It is a beautiful night in May. Hopefully, we look out over the darkness of the sea, which is as smooth as a mirror; there emerges all around in various places a flash like bundle of light beams, as if it is surrounded by thousands of sparks, that form true bundles of fire and of other bright lighting spots, and the seemingly mirrored stars. There emerges close before us a small spot in a sharp greenish light, which becomes ever larger and larger and finally becomes a bright shining sunlike figure. [ 10 ]
On his return to Český Dub , Leopold focused on producing glass eyes, costume ornaments, lab equipment, and other goods and specialty items whose production was expected of master lampworkers . [ 11 ] He married his second wife, Caroline Riegel, in 1854. [ 8 ]
In his free time, he created glass models of plants. These would eventually become the basis of the Ware Collection of Blaschka Glass Models of Plants , also known as the Glass Flowers , which were collected many years later. During this period, Blaschka did not make any money producing the models. [ 11 ] Eventually, however, the models attracted the attention of Prince Camille de Rohan , who arranged to meet with Leopold at Sychrov Castle in 1857. [ 8 ] Prince Camille, an enthusiast of natural sciences, commissioned Leopold to craft 100 glass orchids for his private collection. [ 2 ] In 1862, "the prince exhibited about 100 models of orchids and other exotic plants, which he displayed on two artificial tree trunks in his palace in Prague." [ 10 ] [ 8 ] This royal commission brought Blaschka's craft to the attention of Professor Ludwig Reichenbach , [ 12 ] then director of the Natural History Museum in Dresden.
Professor Reichenbach admired the botanical models and convinced Leopold to try creating glass models of marine invertebrates. In the nineteenth century, the dominant method of displaying preserved marine invertebrates was wet-preservation , which involved taking a live specimen and placing it in a sealed jar, usually filled with alcohol. [ 13 ] This killed the specimen and frequently decomposed the specimens beyond recognition.
Initially, the designs for these were based on drawings in books, but Leopold was soon able to use his earlier drawings to produce models of other species. [ 1 ] His reputation spread quickly. Demand for the models pushed Leopold to further the training of his son and apprentice, Rudolf Blaschka. [ 2 ] A year after the success of the glass sea anemones, the family moved to Dresden to give young Rudolf better educational opportunities. [ 1 ]
In 1886, Edouard Van Beneden , founder of the Institute of Zoology, ordered 77 Blaschka models in order to illustrate zoology lessons. Some of these models are still on display at Treasure in the Aquarium-Museum in Liège . [ 14 ] [ 15 ]
By 1880, Rudolf was assisting his father in producing the glass models, including the production of 131 Glass sea creature models for the Boston Society of Natural History Museum (now the Museum of Science ). These models, along with the ones purchased by Harvard's Museum of Comparative Zoology , were seen by Professor George Lincoln Goodale , who was in the process of establishing and building the Harvard Botanical Museum 's collection. In 1886, Goodale, traveled to Dresden to meet with the Blaschkas and request a series of glass botanical models for Harvard. Some reports claim that Goodale saw a few glass orchids in the room where they met, surviving from the work two decades earlier. [ 6 ] Although initially reluctant, Leopold eventually agreed to send test-models to the U.S. Despite being badly damaged by U.S. Customs , Goodale appreciated their craftsmanship and showed them widely. [ 16 ]
Goodale was convinced that Blaschka's glass art was a worthy investment for Harvard, which was a global centre for the study of botany . At that time, botanical specimens were almost entirely showcased as dried, pressed and labeled specimens called "specimina exsiccata" (dried specimens), but this presented a number of problems. Pressed plant specimens were two-dimensional and tended to lose their color and form, making them difficult to use as accurate teaching tools. [ 17 ] [ 18 ] Dried specimens were also quite heavy and bulky, making their transport and storage expensive. Having already seen the intact Blaschka models at Harvard, Professor Goodale decided to commission the glass flowers. [ 18 ]
To cover the expensive enterprise, Goodale approached former student Mary Lee Ware and her mother, Elizabeth C. Ware, already funders of Harvard's botany department. [ 20 ] Mary convinced her mother to underwrite the consignment of the glass models, and in 1887, the Blaschkas contracted half of their time to producing the models for Harvard with the remaining time dedicated to making marine invertebrate models. [ 6 ] [ 21 ] However, in 1890, the Blaschkas insisted that it was impossible for them to craft the botanical models for half the year and do the sea creatures during the other half, declaring that they “must give up either one or the other." [ 22 ] To resolve this, the Blaschkas signed an exclusive ten-year contract with Harvard to make glass flowers for 8,800 marks per year. [ 21 ] New arrangements were also made to send the models directly to Harvard, where museum staff - possibly including Elizabeth Hodges Clark [ 23 ] - could open them safely under the observation of Customs staff. [ 6 ]
Their models showcased a range of plant specimens. In total, up to 164 taxonomic families and a diversity of plant part morphologies , including flowers, leaves, fruits, and roots, were created. Some were shown during pollination by insects; others were diseased in various ways. [ 1 ] Goodale noted that the activity of the Blaschkas was "greatly increased by their exclusive devotion to a single line of work." [ 22 ] Writing for the Annual reports of the President and Treasurer of Harvard College 1890-1891 :
It has been only within a comparatively short time that I have discovered the cause of the great reluctance of the elder Blaschka to the undertaking at the outset. It appears upon inquiry that he had constructed a few models of plants before beginning the preparation of the animal models to which he owes his wide celebrity; but these models of plants were, he thought, not appreciated by the persons for whom he had made them. The first set of models passed through various vicissitudes, and finally found a home in the Natural History Museum in Liège , where they were at last destroyed by fire. The artist did not have courage to undertake the experiment again, when he was succeeding so well with his animal models. He regards it as a pleasant turn in his fortunes which permits him to devote all of his time to the subject of his earliest studies. [ 22 ]
Claims arose that Leopold and his son were using secret methods to make their glass models. These claims were refuted by Leopold himself. Blaschka stated "One cannot hurry glass. It will take its own time. If we try to hasten it beyond its limits, it resists and no longer obeys us. We have to humor it." [ 24 ]
The Blaschkas used a mixture of clear and colored glass, sometimes supported with wire, to produce their models. [ 21 ] Many pieces were painted by Rudolf. [ 6 ] In order to represent plants which were not native to the Dresden area, father and son studied foreign plant collections at Pillnitz Palace [ 21 ] and the Dresden Botanical Garden. They also grew some from seeds sent from the United States. [ 21 ] In 1892, Rudolf was sent on a trip to the Caribbean and the U.S. to study additional plants, making extensive drawings and notes. [ 6 ] At this point, the number of glass models sent annually to Harvard was approximately 120. [ 22 ]
Leopold died in 1895 while Rudolf was on a second trip to the U.S. [ 6 ] Rudolf continued to work alone, but production slowed. By the early twentieth century, he found that he was unable to buy high quality glass and began making his own. [ 21 ] This was confirmed by Mary Lee Ware during her 1908 visit to Rudolf. In a letter she later wrote to the second director of the Botanical Museum, Professor Oakes Ames , she observed how "one change in the character of [Rudolf's] work and, consequently in the time necessary to accomplish results since I was last here, is very noteworthy. At that time […] he bought most of his glass and was just beginning to make some, and his finishes were in paint. Now he himself makes a large part of the glass and all the enamels, which he uses powders to use as paint." [ 6 ] [ 25 ] In addition to funding and visiting the project, Mary took an active role in its progress, going so far as to personally unpack each model and make arrangements for Rudolph's fieldwork in the U.S. and Jamaica . [ 26 ] [ 27 ]
Ames was less passionate about the Glass Flowers than his predecessor had been. However, he soon requested what he referred to as "Economic Botany", asking Rudolf to make glass models of olives and grapes. This eventually evolved into a series of glass fruit models in both rotting and edible condition. [ 28 ] Ames continued to exchange letters with Mary Lee Ware discussing the project and commented on the quality and speed of production declining with Rudolf's age, expressing concern whether Blaschka could continue to produce models of satisfactory quality. [ 28 ]
Rudolf continued making models for Harvard until 1938. By then 80 years old, he announced his retirement. [ 29 ] Neither he nor his father Leopold had taken on an apprentice and Rudolf left no successor, as he and his wife Frieda had no children. [ 1 ]
In total, Leopold and Rudolf made approximately 4,400 models for Harvard, 780 of which showed species at life-size. As of 2016, fewer than 75 per cent of the models are on regular display at the Harvard Museum of Natural History in the Ware Collection. Older exhibitions contained up to 3,000 models, but this number was reduced during renovations of the museum's collections . [ 21 ] Unlike the glass sea creatures which were "a profitable global mail-order business", the Glass Flowers were commissioned solely for Harvard. [ 17 ]
Over the course of their collective lives, Leopold and Rudolf crafted as many as ten thousand glass marine invertebrate models and 4,400 botanical models, the most famous being Harvard's Glass Flowers . [ 30 ] [ 31 ]
The Blaschka studio survived the bombing of Dresden in World War II and, in 1993, the Corning Museum of Glass and Harvard Museum of Natural History jointly purchased the remaining Blaschka studio materials from Frieda Blaschka's niece, Gertrud Pones. [ 32 ]
The Pisa Charterhouse , which houses the Museum of Natural History of the University of Pisa , has a collection of 51 Blaschka glass marine invertebrates. [ 33 ]
Leopold and Rudolf and their spouses are buried together in the Hosterwitz cemetery in Dresden . | https://en.wikipedia.org/wiki/Leopold_and_Rudolf_Blaschka |
The Leopold matrix is a qualitative environmental impact assessment method developed in 1971 by Luna Leopold and collaborators for the USGS . [ 1 ] It is used to identify and assign numerical weightings to potential environmental impacts of proposed projects on the environment . [ 1 ] It came as a response to the National Environmental Policy Act of 1969 which was criticized for lacking adequate guidance for government agencies on how to properly predict potential environmental impacts and consequently prepare impact reports . [ 1 ]
The system consists of a grid of 100 rows representing the possible project activities on the horizontal axis and 88 columns representing environmental factors on the vertical axis, for a total of 8800 possible interactions. [ 1 ] In practice, only a select few (25-50) of these interactions are likely to be of sufficient importance to be thoroughly considered. [ 1 ] Where an impact is expected, the appropriate cell of the matrix is split diagonally from the top right corner to the bottom left corner in order for the magnitude and importance of each interaction to be recorded. [ 2 ] The magnitude (from -10 to +10) is inserted on the top-left diagonal and the importance (from 1 to 10) is inserted on the bottom-right diagonal. [ 1 ] Measurements of magnitude and importance tend to be related, but do not necessarily directly correlate. Magnitude can be measured more tangibly in terms of how much area is affected by the development or how severely, however, the importance is a more subjective measurement. While a proposed development may have a large impact in terms of magnitude, the effects it causes may not actually significantly affect the environment as a whole. The example given by author Luna Leopold is of a stream that significantly alters the erosion patterns in a specific area, which may be scored highly in terms of magnitude but may not be necessarily significant, provided the stream in question is swift-moving and transports large amounts of sediment regardless. [ 1 ] In this case, an impact of significant magnitude may not actually be important to the environment in question.
As outlined by the original authors, the matrix provides a structured framework for practitioners of environmental impact assessment to systematically rank potential significant environmental cause-and-effect relationships. [ 1 ] A structured approach avoids the downsides of less organized ad hoc approaches to impact prediction in which impacts can be either underestimated or completely overlooked. [ 3 ] Additionally, the grid format allows for a visual display of results that can be easily understood by policymakers and the public. [ 4 ] [ 5 ] The matrix is also capable of expanding and contracting based on the scope and environmental context of any given undertaking, rendering it functional for both large and small-scale projects. [ 2 ] Finally, it is beneficial to practitioners that the tool can be applied at various temporal stages of the environmental impact assessment process. [ 6 ]
One of the fundamental downfalls of the method is the lack of criteria or standard methods for assigning magnitude and significance values which may lead to subjective judgements. [ 7 ] [ 8 ] [ 9 ] In the same vein, the method has also been identified as lacking the ability to facilitate any degree of public involvement, primarily due to the subjective value judgements of the user. [ 10 ] Another potential pitfall is the sheer size of the matrix with a total of 17 600 items of information potentially being analyzed. [ 11 ] [ 12 ] The size of the matrix has also been criticized as being too detailed for some projects while simultaneously being too imprecise for others. [ 13 ] In terms of direct content, the chance of double-counting certain impacts is also present. [ 14 ] [ 15 ] The matrix has further been identified as being highly biased toward biophysical impacts making the social impacts of a given project difficult to assess. [ 6 ] [ 16 ] Of the impacts that are covered, the matrix is seldom capable of taking into consideration secondary or cumulative impacts which are often significant considerations in environmental impact assessment. [ 17 ] [ 18 ] [ 19 ] Another area that the method can be deficient in is having a mechanism capable of distinguishing between long-term impacts and short-term impacts. [ 20 ] [ 21 ] [ 22 ] Due to the presentation of completed matrices, the method has also been identified as treating interactions as though they are certain to occur, with no consideration of probability. [ 17 ] | https://en.wikipedia.org/wiki/Leopold_matrix |
Lepidiota stigma , also known as sugarcane white grub, [ 2 ] is a species of insect native to Southeast Asia. The species is known to attack sugarcane fields in the region. [ 3 ]
This Melolonthinae article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Lepidiota_stigma |
Lepidium peruvianum
Lepidium meyenii , known as maca or Peruvian ginseng , is an edible herbaceous biennial plant of the family Brassicaceae that is native to South America in the high Andes mountains of Peru and Bolivia . It was rediscovered for commercial purposes at the Meseta de Bombón plateau close to Lake Junin in the late 1980s. [ 1 ] It is grown for its fleshy hypocotyl that is fused with a taproot , which is typically dried but may also be freshly cooked as a root vegetable . As a cash crop, it is primarily exported as a powder that may be raw or processed further as a gelatinized starch or as an extract . If dried, it may be processed into a flour for baking or as a dietary supplement .
Its Spanish and Quechua names include maca-maca , maino , ayak chichira , and ayak willku .
Antonio Vázquez de Espinosa described the plant following his visit to Peru circa 1598, and Bernabé Cobo described this plant in the early 17th century. [ 2 ] Gerhard Walpers named the species Lepidium meyenii in 1843. In the 1990s, Gloria Chacon further distinguished a different species. She considered the widely cultivated natural maca of today to be a newer domesticated species, L. peruvianum . [ 3 ]
However, most botanists doubt this distinction and continue to call the cultivated maca L. meyenii . The Latin name recognized by the USDA similarly continues to be Lepidium meyenii . [ 4 ] It has been debated whether it is botanically correct to consider meyenii and peruvianum to be distinct from one another. [ 1 ] A 2015 multi-center study found differences in taxonomy, visual appearance, phytochemical profiles and DNA sequences when comparing L. meyenii and L. peruvianum , suggesting that they are different and that their names should not be considered synonyms. [ 5 ]
The growth habit, size, and proportions of maca are roughly similar to those of radishes and turnips , to which it is related, but it also resembles a parsnip . The green, fragrant tops are short and lie along the ground. [ 6 ] The thin, frilly leaves sprout in a rosette at the soil surface, not growing more than 12–20 cm (4.7–7.9 in) in height. The leaves show a dimorphism according to the reproductive stage. They are more prominent in the vegetative phase and continuously renew from the center as the outer leaves die. The off-white, self-fertile flowers are borne on a central raceme , and are followed by 4–5 mm (0.16–0.20 in) siliculate fruits, each containing two small 2.0–2.5 mm (0.079–0.098 in) reddish-gray ovoid seeds . Seeds are the maca's only means of reproduction. Maca reproduces mainly through self-pollination: it is an autogamous species. The genome consists of 64 chromosomes. Maca is a short-day plant from experiments with different day lengths. [ 1 ] Some sources consider the maca an annual plant, as in favorable years, it can complete a lifecycle within a year. [ 6 ]
Maca is the only member of the genus Lepidium with a fleshy hypocotyl , which is fused with the taproot to form a rough inverted pear-shaped body. Traditionally, native growers have acknowledged four varieties of maca based on their root color: cream-yellow, half-purple, purple, and black; varying levels of anthocyanin are primarily responsible for the color differences. [ 2 ] Maca hypocotyls may be gold or cream, red, purple, blue, black, or green. Each is considered a "genetically unique variety," as the seeds of the parent plants grow to have roots of the same color. Specific phenotypes (in maca, 'phenotype' pertains mainly to root color) have been propagated exclusively to increase commercial interest. [ 7 ] Cream-colored roots are the most widely grown and are favored in Peru for their enhanced sweetness and size. Black maca is both sweet and slightly bitter.
The natural environment of the maca is at 11–12ºS latitude and at an elevation of 3,800–4,400 m (12,500–14,400 ft) above sea level. [ 7 ] At this elevation, temperatures of the growing season vary from −2 to 13 °C (28 to 55 °F) in monthly mean minimum or maximum, respectively. Temperatures can decline, however, as low as −10 °C (14 °F) and frosts are common. Of the cultivated plants, maca is one of the most frost tolerant. [ 8 ] Strong winds and sunlight are also characteristics of the native habitat of the maca. Maca today is still mainly cultivated in Peru , in the high Andes of Bolivia, and to a small extent also in Brazil . [ 6 ] Maca can be cultivated beyond its natural elevation range, over 4,400 m (14,400 ft) above sea level. [ 9 ]
Maca (Peruvian ginseng) seedlings usually emerge about one month after sowing, with the onset of the rainy season in October. In the vegetative phase, from May to June, the lower part of the hypocotyl, as well as the upper part of the tap root, grows in size. After 260 to 280 days, it is formed into the harvestable hypocotyl. If the root is left in the soil, it is dormant for two to three months in the time of the cold, dry season until August. Then, it will form a generative shoot on which the seeds ripen five months later. One plant can form up to 1000 tiny seeds, 1600 of which weigh about one gram. Thus, only relatively few plants are needed for propagation. The cultivated plants are selected for preferred size and color, then placed 50–100 mm deep in pits with alternate layers of grass and soil to protect them from drying out. They are fertilized heavily, as maca is an exhaustive crop of soil. [ 2 ] The cultivation cycle is strictly linked to seasonality. [ 1 ] [ 6 ]
Traditionally, land preparation was done by hand. Nowadays, tractor plowing is also used. As maca grows on sites where no other crops can be cultivated, it is often found after long fallows of sheep grazing pastures. [ 1 ] Maca croplands, thus, traditionally are only fertilized with sheep and alpaca manure; however, fertilizer application could prevent soils from depleting in nutrients [ citation needed ] .
Weeding or pesticide application usually is not necessary. The climate is not suitable for most weeds or pests. Nearly all maca cultivation in Peru is carried out organically; maca is seldom attacked. Maca is sometimes interplanted with potatoes, as it is known to maca farmers that the plant naturally repels most root crop pests. [ citation needed ]
The harvest is done manually, with the leaves left in the field as livestock feed or organic fertilizer .
The yield for a cultivated hectare may reach an estimated 15 tons in fresh hypocotyls, resulting in around 5 tons of dried material. [ 6 ] According to the Ministry of Agriculture of Peru , however, average maca yields for 2005 were only 7 t/ha, with a great variation between different sites. [ 1 ] Although maca has been cultivated outside the Andes, it is unclear whether it develops the same active constituents or potency outside of its natural habitat. Hypocotyls grown from Peruvian seeds form with difficulty at low elevations, in greenhouses, or warm climates.
The average composition, on a dry matter basis, is 60–75% carbohydrates (primarily as polysaccharides ), [ 10 ] 10–14% protein , 8.5% dietary fiber , and 2.2% fats . [ 11 ]
Maca contains glucotropaeolin , m -methoxyglucotropaeolin, benzyl glucosinolates , polyphenols , (1 R ,3 S )-1-methyl-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid (MTCA), and p -methoxybenzyl isothiocyanate . [ 7 ] [ 12 ] Alkamides are also present in maca. [ 13 ] Maca contains several N-benzylamides referred to as macamides that are structurally related to anandamide . [ 14 ]
No pharmacokinetic data have been published for maca. [ 12 ] The presence of (1 R ,3 S )-1-methyl-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid (MTCA) in the extracts of maca indicate a potential safety issue as a monoamine oxidase inhibitor (re. which see β-carboline ) and possibility as a mutagen . [ 12 ] Due to these potential mutagenic properties of MTCA, the Agency for Sanitary Security in France warned consumers about the possible health risks of powdered maca root, a declaration disputed on the assumption that MTCA would be deactivated by boiling to process maca roots. [ 12 ] MTCA-like compounds are associated with craving behaviour. [ 12 ]
Due to its purported effect on fertility , maca grew in agricultural, commercial, and research interest from the 1990s to 2014. [ 1 ] [ 15 ] Market studies showed low acceptance of the particular maca taste by consumers when first exposed to it, creating a barrier for popularity of this food as a culinary vegetable. The economic interest existed more in the perceived but unproven health effects of the root's constituents supplied as an extract in a dietary supplement. [ 1 ] [ 15 ]
By 2014, agricultural and market interest in maca grew in China, but with challenges from Peruvian institutions who accused Chinese companies of illegally exporting maca and of biopiracy , as several Chinese patents had been filed to improve maca's propagation and genetic diversity. [ 16 ]
Maca is mainly grown for the consumption of its roots. The majority of harvested maca is dried. In this form, the hypocotyls can be stored for several years. [ 1 ] [ 17 ] In Peru, maca is prepared and consumed in various ways, although traditionally, it is always cooked. The freshly harvested hypocotyl may be roasted in a pit (called huatia ) and is considered a delicacy. Fresh roots usually are available only in the vicinity of the growers. The root can also be mashed and boiled to produce a sweet, thick liquid, then dried and mixed with milk to form a porridge, mazamorra . [ 8 ] The cooked roots are also used with other vegetables in empanadas , jams, or soups. The root may be ground to produce flour for bread, cakes, or pancakes. If fermented, a weak beer called chicha de maca may be produced. In 2010, a U.S.-based brewery called Andean Brewing Company became the first company to produce and commercialize beer made from maca under the brand KUKA Beer. [ 18 ] From the black morphotype, a liquor is produced. Also, the leaves are edible or may serve as animal fodder. They can be prepared raw in salads or cooked much like L. sativum and L. campestre , which are closely related genetically. [ citation needed ]
The prominent product for export is maca flour , a baking flour ground from the hard, dried roots. It is called harina de maca . Maca flour (powder) is a relatively inexpensive bulk commodity, like wheat flour or potato flour. The supplement industry uses both dry roots and maca flour for different types of processing and concentrated extracts. Another common form is maca, processed by gelatinization . This extrusion process separates and removes the tough fiber from the roots using gentle heat and pressure, as raw maca is difficult to digest due to its thick fibers.
Archaeological evidence exists for varying degrees of cultivation of maca in the Lake Junin region from around 1700 BC to 1200 AD. [ 19 ] Maca has been harvested and used by humans in the puna grasslands of the Andean Mountains for centuries. Contrary to frequent claims that maca cultivation was common in what is today Peru, until the late 1980s, maca has been cultivated only in a limited area around Lake Junin in central Peru. Historically, maca was often traded for lowland tropical food staples, such as maize , rice , manioc (tapioca roots), quinoa , and papaya . It also was used as a form of payment for Spanish imperial taxes. [ 6 ] [ 20 ]
Maca is said to have medicinal properties, but scientific research remains inconclusive. [ 21 ] [ 22 ] [ 23 ] A 2016 systematic review found evidence suggesting that it improves semen quality in healthy and infertile men. [ 24 ] A 2011 systematic review found the evidence for the effectiveness of maca as a treatment for menopausal symptoms in women inconclusive. [ 25 ] | https://en.wikipedia.org/wiki/Lepidium_meyenii |
A leptocephalus (meaning "slim head" [ 1 ] ) is the flat and transparent larva of eels and other members of the superorder Elopomorpha . This is one of the most diverse groups of teleosts , containing 801 species in 4 orders, 24 families, and 156 genera. This group is thought to have arisen in the Cretaceous period over 140 million years ago. [ 2 ]
Fishes with a leptocephalus larval stage include the most familiar eels such as the conger , moray eel , and garden eel as well as members of the family Anguillidae , plus more than 10 other families of lesser-known types of marine eels. These are all true eels of the order Anguilliformes . Leptocephali of eight species of eels from the South Atlantic Ocean were described by Meyer-Rochow [ 3 ]
The fishes of the other four traditional orders of elopomorph fishes that have this type of larvae are more diverse in their body forms and include the tarpon , bonefish , spiny eel , pelican eel and deep sea species like Cyema atrum [ 3 ] and Notacanthidae species, the latter with giant Leptocephalus-like larvae. [ 4 ]
Leptocephali (singular leptocephalus) all have laterally compressed bodies [ 5 ] that contain transparent jelly-like substances on the inside of the body and a thin layer of muscle with visible myomeres on the outside. Their body organs are small and they have only a simple tube for a gut. This combination of features results in them being very transparent when they are alive. Leptocephali have dorsal and anal fins confluent with caudal fins , but lack pelvic fins .
They also lack red blood cells until they begin to metamorphose into the juvenile glass eel stage when they start to look like eels. Leptocephali are also characterized by their fang-like teeth that are present until metamorphosis, when they are lost. [ 6 ]
Leptocephali differ from most fish larvae because they grow to much larger sizes [ 5 ] and have long larval periods of about three months to more than a year. Another distinguishing feature of these organisms is their mucinous pouch. [ 2 ] They move with typical anguilliform swimming motions and can swim forwards and backwards. [ 5 ] Their food source was difficult to determine because zooplankton , which are the typical food of fish larvae, were never seen in their guts. [ 7 ]
Leptocephali appear to feed on tiny particles floating freely in the ocean, which are often referred to as marine snow . Leptocephali larvae live primarily in the upper 100 metres (330 ft) of the ocean at night, [ 5 ] and often a little deeper during the day. Leptocephali are present worldwide in the oceans from southern temperate to tropical latitudes, where adult eels and their close relatives live. American eels, European eels, conger eels, and some oceanic species spawn and are found in the Sargasso Sea . [ 8 ]
Leptocephalus brevirostris was declared as a biological species in 1856, but was later found to be the larva of Anguilla anguilla , which was declared by Linnaeus in 1758 and thus has priority. [ 9 ]
The eggs of eels in the order Anguilliformes are quite large compared to those of many other fishes. They are about 1–4 millimetres (1,000–4,000 μm; 39–157 thou) in diameter. Once the larvae are newly hatched, the yolk extends posteriorly. Some larvae hatch with features of the head more developed than others. The preleptocephalus stage is the period immediately after the larvae hatch. During this stage, the larvae do not yet feed externally. These larvae typically have poorly developed eyes and few or no teeth. [ 5 ]
The leptocephalus stage of the larvae begins after the nutrients from the yolk have been absorbed and the eyes and teeth are formed. At this point, the larvae usually have long forward-facing pointy teeth. As the larvae grow larger, the teeth will be replaced by shorter teeth and will increase in number. The maximum size larvae reach varies from about 5–10 centimetres (2–4 in) but can be as large as 30 centimetres (12 in) or more depending on the species. After the leptocephali have reached their maximum size, they enter their glass eel stage. Their laterally compressed bodies tend to become more rounded in this stage. The head also thickens, the olfactory organ enlarges, and their teeth are lost. [ 5 ]
Leptocephali differ from other fish larvae in their development. In other teleosts (those without leptocephali), the egg hatches and then the larvae get nutrients from a yolk sac . Following this, external feeding begins once the yolk sac has depleted. The larvae begin to increase in size and develop into a juvenile fish once external feeding begins. In those fish with a leptocephalus stage; however, after hatching and obtaining nutrients from the yolk, the larvae do not begin external feeding. This is peculiar because the larvae still continue to grow in size. From this information, it is concluded that one of the biggest and most basic differences in the developmental cycles of teleosts without leptocephali and teleosts with leptocephali is the food source that the larvae use. [ 10 ]
Leptocephali are poorly understood, partly because they are very fragile and eat particulate material instead of zooplankton, and their good swimming ability lets them avoid most standard-sized plankton nets used by marine biologists. A video recording of a naturally swimming leptocephalus filmed at night off the island of Hawaii shows an example of their swimming behavior. [ 11 ]
Two facts are known regarding the visual system of the leptocephali. The first is that they have a rod-dominated visual system. [ 12 ] The second is that the Synaphobranchidae (a specific family of leptocephali) have telescopic eyes, meaning a tubular eye with a sphere-shaped lens on the top occurs. [ 5 ]
Some progress has been made to grow the leptocephali of the Japanese eel in the laboratory. The goal of that effort is to produce glass eels through artificial spawning and larval rearing, to be used for aquaculture to produce unagi for food. Unagi is a popular food in Japan and East Asia. [ 13 ] Due to the strange nature of the leptocephali, this has not been easy. Trying to artificially recreate marine snow has proven difficult for scientists. [ 14 ]
Leptocephali are rarely used as food, except in some parts of Japan. The leptocephali of the common Japanese conger, Conger myriaster , are called noresore · のれそれ in Kōchi Prefecture , Japan , and are often served uncooked to the table, and are eaten after dipping in tosazu mixed vinegar . It is a spring seasonal specialty. [ 15 ] | https://en.wikipedia.org/wiki/Leptocephalus |
In physical cosmology , leptogenesis is the generic term for hypothetical physical processes that produced an asymmetry between leptons and antileptons in the very early universe , resulting in the present-day dominance of leptons over antileptons. In the currently accepted Standard Model , lepton number is nearly conserved at temperatures below the TeV scale, but tunneling processes can change this number; at higher temperature it may change through interactions with sphalerons , particle-like entities. [ 1 ] In both cases, the process involved is related to the weak nuclear force , and is an example of chiral anomaly .
Such processes could have hypothetically created leptons in the early universe. In these processes baryon number is also non-conserved, and thus baryons should have been created along with leptons. Such non-conservation of baryon number is indeed assumed to have happened in the early universe, and is known as baryogenesis . However, in some theoretical models, it is suggested that leptogenesis also occurred prior to baryogenesis; thus the term leptogenesis is often used to imply the non-conservation of leptons without corresponding non-conservation of baryons. In the Standard Model, the difference between the lepton number and the baryon number is precisely conserved, so that leptogenesis without baryogenesis is impossible. Thus such leptogenesis implies extensions to the Standard Model. [ 1 ]
The lepton and baryon asymmetries affect the much better understood Big Bang nucleosynthesis at later times, during which light atomic nuclei began to form. Successful synthesis of the light elements requires that there be an imbalance in the number of baryons and antibaryons to one part in a billion when the universe is a few minutes old. [ 2 ] An asymmetry in the number of leptons and antileptons is not mandatory for Big Bang nucleosynthesis. However, charge conservation suggests that any asymmetry in the charged leptons and antileptons ( electrons , muons and tau particles ) should be of the same order of magnitude as the baryon asymmetry. [ 3 ] Observations of the primordial helium-4 abundance place an upper limit on any lepton asymmetry residing in the neutrino sector, which is not very stringent. [ 2 ]
Leptogenesis theories employ sub-disciplines of physics such as quantum field theory , and statistical physics , to describe such possible mechanisms. Baryogenesis, the generation of a baryon–antibaryon asymmetry, and leptogenesis can be connected by processes that convert baryon number and lepton number into each other. The (non-perturbative) quantum Adler–Bell–Jackiw anomaly can result in sphalerons , which can convert leptons into baryons and vice versa . [ 4 ] Thus, the Standard Model is in principle able to provide a mechanism to create baryons and leptons.
A simple modification of the Standard Model that is instead able to realize the program of Sakharov is the one suggested by M. Fukugita and T. Yanagida . [ 5 ] The Standard Model is extended by adding right-handed neutrinos , permitting implementation of the see-saw mechanism and providing the neutrinos with mass. At the same time, the extended model is able to spontaneously generate leptons from the decays of right-handed neutrinos. Finally, the sphalerons are able to convert the spontaneously generated lepton asymmetry into the observed baryonic asymmetry. Due to its popularity, this entire process is sometimes referred to simply as leptogenesis. [ 6 ] | https://en.wikipedia.org/wiki/Leptogenesis |
In particle physics , lepton number (historically also called lepton charge ) [ 1 ] is a conserved quantum number representing the difference between the number of leptons and the number of antileptons in an elementary particle reaction. [ 2 ] Lepton number is an additive quantum number , so its sum is preserved in interactions (as opposed to multiplicative quantum numbers such as parity, where the product is preserved instead). The lepton number L {\displaystyle L} is defined by L = n ℓ − n ℓ ¯ , {\displaystyle L=n_{\ell }-n_{\overline {\ell }},} where
Lepton number was introduced in 1953 to explain the absence of reactions such as
in the Cowan–Reines neutrino experiment , which instead observed
This process, inverse beta decay , conserves lepton number, as the incoming antineutrino has lepton number −1, while the outgoing positron (antielectron) also has lepton number −1.
In addition to lepton number, lepton family numbers are defined as [ 4 ]
Prominent examples of lepton flavor conservation are the muon decays
and
In these decay reactions, the creation of an electron is accompanied by the creation of an electron antineutrino , and the creation of a positron is accompanied by the creation of an electron neutrino. Likewise, a decaying negative muon results in the creation of a muon neutrino , while a decaying positive muon results in the creation of a muon antineutrino . [ 5 ]
Finally, the weak decay of a lepton into a lower-mass lepton always results in the production of a neutrino - antineutrino pair:
One neutrino carries through the lepton number of the decaying heavy lepton, (a tauon in this example, whose faint residue is a tau neutrino ) and an antineutrino that cancels the lepton number of the newly created, lighter lepton that replaced the original. (In this example, a muon antineutrino with L μ = − 1 {\displaystyle L_{\mathrm {\mu } }=-1} that cancels the muon's L μ = + 1 {\displaystyle L_{\mathrm {\mu } }=+1} .
Lepton flavor is only approximately conserved, and is notably not conserved in neutrino oscillation . [ 6 ] However, both the total lepton number and lepton flavor are still conserved in the Standard Model.
Numerous searches for physics beyond the Standard Model incorporate searches for lepton number or lepton flavor violation, such as the hypothetical decay [ 7 ]
Experiments such as MEGA and SINDRUM have searched for lepton number violation in muon decays to electrons; MEG set the current branching limit of order 10 −13 and plans to lower to limit to 10 −14 after 2016. [ 8 ] Some theories beyond the Standard Model, such as supersymmetry , predict branching ratios of order 10 −12 to 10 −14 . [ 7 ] The Mu2e experiment, in construction as of 2017, has a planned sensitivity of order 10 −17 . [ 9 ]
Because the lepton number conservation law in fact is violated by chiral anomalies , there are problems applying this symmetry universally over all energy scales. However, the quantum number B − L is commonly conserved in Grand Unified Theory models.
If neutrinos turn out to be Majorana fermions , neither individual lepton numbers, nor the total lepton number L ≡ L e + L μ + L τ , {\displaystyle L\equiv L_{\mathrm {e} }+L_{\mathrm {\mu } }+L_{\mathrm {\tau } },} nor
would be conserved, e.g. in neutrinoless double beta decay , where two neutrinos colliding head-on might actually annihilate, similar to the (never observed) collision of a neutrino and antineutrino.
Some authors prefer to use lepton numbers that match the signs of the charges of the leptons involved, following the convention in use for the sign of weak isospin and the sign of strangeness quantum number ( for quarks ), both of which conventionally have the otherwise arbitrary sign of the quantum number match the sign of the particles' electric charges.
When following the electric-charge-sign convention, the lepton number (shown with an over-bar here, to reduce confusion) of an electron , muon , tauon , and any neutrino counts as L ¯ = − 1 ; {\displaystyle {\bar {L}}=-1;} the lepton number of the positron , antimuon , antitauon , and any antineutrino counts as L ¯ = + 1. {\displaystyle {\bar {L}}=+1.} When this reversed-sign convention is observed, the baryon number is left unchanged, but the difference B − L is replaced with a sum: B + L , whose number value remains unchanged, since
and | https://en.wikipedia.org/wiki/Lepton_number |
Leptosin is an aurone glycoside derived from kusrunt 's leaves. [ 1 ]
This biochemistry article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Leptosin |
The leptotene stage , also known as leptonema, is the first of five substages of prophase I during meiosis , the specialized cell division that reduces the chromosome number by half to produce haploid gametes in sexually reproducing organisms.
The term "leptonema" derives from Greek words meaning "thin threads". [ 1 ] : 27 A cell destined to become a gamete enters the leptotene stage after its chromosomes are duplicated during interphase.
During the leptotene stage, the duplicated chromosomes - each consisting of two sister chromatids - condense from diffuse chromatin into long, thin strands that are more visible within the nucleoplasm (nucleus contents). The chromosomes become visible as thin threadlike structures known as leptonema under a light microscope. [ 1 ] : 27 [ 2 ] : 353
Each chromosome consists of two identical sister chromatids held together by cohesin proteins along the entire length, connected at the centromere region. As the chromosomes condense, the nuclear envelope starts to fragment, and the nucleolus disperses as the cell prepares for division.
During this stage, the chromosomes attach themselves by their ends (telomeres) to the inner membrane of the nuclear envelope. At the transition to the zygotene stage, the telomeres usually aggregate at a sector of the nuclear envelope, thereby forming a "meiotic bouquet" arrangement. [ 3 ]
A key event is the initiation of synapsis between homologous chromosomes, which carry the same genetic information but may have different allelic variations. The homologous chromosomes begin pairing and association along their lengths, facilitated by lateral (axial) elements of the synaptonemal complex protein structure that forms between the homologs. [ 4 ]
The synaptonemal complex consists of two lateral elements associated with each homolog, and a central region where they are held together. As synapsis begins, the chromosomes adopt a more extended configuration to expose the DNA for pairing.
The leptotene stage also sees the initiation of genetic recombination between homologs. This involves programmed DNA double-strand breaks and their repair to generate crossovers between non-sister chromatids of homologous pairs.
Proteins like SPO11 generate the breaks, while strand exchange proteins like RAD51 and DMC1 facilitate repair and exchange of genetic material. Recombination continues through zygotene as synapsis completes, generating new genetic diversity. [ 5 ]
Studies in male mouse meiosis have shown that after DNA damaging treatments like gamma irradiation, two types of repair responses occur depending on the meiotic stage: [ 5 ]
Leptotene is followed by the zygotene stage, where synapsis between homologous chromosomes progresses further and the chromosomes continue condensing. [ 6 ]
Synizesis (biology) | https://en.wikipedia.org/wiki/Leptotene_stage |
The Leray projection , named after Jean Leray , is a linear operator used in the theory of partial differential equations , specifically in the fields of fluid dynamics . Informally, it can be seen as the projection on the divergence-free vector fields. It is used in particular to eliminate both the pressure term and the divergence-free term in the Stokes equations and Navier–Stokes equations .
Source: [ 1 ]
For vector fields u {\displaystyle \mathbf {u} } (in any dimension n ≥ 2 {\displaystyle n\geq 2} ), the Leray projection P {\displaystyle \mathbb {P} } is defined by
This definition must be understood in the sense of pseudo-differential operators : its matrix valued Fourier multiplier m ( ξ ) {\displaystyle m(\xi )} is given by
Here, δ {\displaystyle \delta } is the Kronecker delta . Formally, it means that for all u ∈ S ( R n ) n {\displaystyle \mathbf {u} \in {\mathcal {S}}(\mathbb {R} ^{n})^{n}} , one has
where S ( R n ) {\displaystyle {\mathcal {S}}(\mathbb {R} ^{n})} is the Schwartz space . We use here the Einstein notation for the summation.
Source: [ 2 ]
One can show that a given vector field u {\displaystyle \mathbf {u} } can be decomposed as
Different than the usual Helmholtz decomposition , the
Helmholtz–Leray decomposition of u {\displaystyle \mathbf {u} } is unique (up to an
additive constant for q {\displaystyle q} ). Then we can define P ( u ) {\displaystyle \mathbb {P} (\mathbf {u} )} as
The Leray projector is defined similarly on function spaces other than the Schwartz space, and on different domains with different boundary conditions. The four properties listed below will continue to hold in those cases.
The Leray projection has the following properties:
The incompressible Navier–Stokes equations are the partial differential equations given by
where u {\displaystyle \mathbf {u} } is the velocity of the fluid, p {\displaystyle p} the pressure, ν > 0 {\displaystyle \nu >0} the viscosity and f {\displaystyle \mathbf {f} } the external volumetric force.
By applying the Leray projection to the first equation, we may rewrite the Navier-Stokes equations as an abstract differential equation on an infinite dimensional phase space , such as C 0 ( 0 , T ; L 2 ( Ω ) ) {\displaystyle C^{0}\left(0,T;L^{2}(\Omega )\right)} , the space of continuous functions from [ 0 , T ] {\displaystyle [0,T]} to L 2 ( Ω ) {\displaystyle L^{2}(\Omega )} where T > 0 {\displaystyle T>0} and L 2 ( Ω ) {\displaystyle L^{2}(\Omega )} is the space of square-integrable functions on the physical domain Ω {\displaystyle \Omega } : [ 3 ]
where we have defined the Stokes operator A {\displaystyle A} and the bilinear form B {\displaystyle B} by [ 2 ]
The pressure and the divergence free condition are "projected away". In general, we assume for simplicity that f {\displaystyle \mathbf {f} } is divergence free, so that P ( f ) = f {\displaystyle {\mathbb {P} }({\mathbf {f} })={\mathbf {f} }} ; this can always be done, by adding the term f − P ( f ) {\displaystyle \mathbf {f} -\mathbb {P} (\mathbf {f} )} to the pressure. | https://en.wikipedia.org/wiki/Leray_projection |
In mathematics , the Leray–Schauder degree is an extension of the degree of a base point preserving continuous map between spheres ( S n , ∗ ) → ( S n , ∗ ) {\displaystyle (S^{n},*)\to (S^{n},*)} or equivalently to boundary-sphere-preserving continuous maps between balls ( B n , S n − 1 ) → ( B n , S n − 1 ) {\displaystyle (B^{n},S^{n-1})\to (B^{n},S^{n-1})} to boundary-sphere-preserving maps between balls in a Banach space f : ( B ( V ) , S ( V ) ) → ( B ( V ) , S ( V ) ) {\displaystyle f:(B(V),S(V))\to (B(V),S(V))} , assuming that the map is of the form f = i d − C {\displaystyle f=id-C} where i d {\displaystyle id} is the identity map and C {\displaystyle C} is some compact map (i.e. mapping bounded sets to sets whose closure is compact ). [ 1 ]
The degree was invented by Jean Leray and Juliusz Schauder to prove existence results for partial differential equations. [ 2 ] [ 3 ]
This topology-related article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Leray–Schauder_degree |
The Lerche–Newberger , or Newberger , sum rule , discovered by B. S. Newberger in 1982, [ 1 ] [ 2 ] [ 3 ] finds the sum of certain infinite series involving Bessel functions J α of the first kind .
It states that if μ is any non-integer complex number , γ ∈ ( 0 , 1 ] {\displaystyle \scriptstyle \gamma \in (0,1]} , and Re ( α + β ) > −1, then
Newberger's formula generalizes a formula of this type proven by Lerche in 1966; Newberger discovered it independently. Lerche's formula has γ =1; both extend a standard rule for the summation of Bessel functions, and are useful in plasma physics. [ 4 ] [ 5 ] [ 6 ] [ 7 ]
This mathematical analysis –related article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Lerche–Newberger_sum_rule |
The Lerner symmetry theorem is a result used in international trade theory, which states that an ad valorem import tariff (a percentage of value or an amount per unit) will have the same effects as an export tax. The theorem is based on the observation that the effect on relative prices is the same regardless of which policy (ad valorem tariffs or export taxes) is applied.
The theorem was developed by economist Abba P. Lerner in 1936. [ 1 ] [ 2 ]
This economics -related article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Lerner_symmetry_theorem |
Leroy "Lee" Edward Hood (born October 10, 1938) is an American biologist who has served on the faculties at the California Institute of Technology (Caltech) and the University of Washington . [ 2 ] Hood has developed ground-breaking scientific instruments which made possible major advances in the biological sciences and the medical sciences. These include the first gas phase protein sequencer (1982), for determining the sequence of amino acids in a given protein; [ 3 ] [ 4 ] a DNA synthesizer (1983), to synthesize short sections of DNA; [ 3 ] [ 5 ] a peptide synthesizer (1984), to combine amino acids into longer peptides and short proteins; [ 4 ] [ 6 ] the first automated DNA sequencer (1986), to identify the order of nucleotides in DNA; [ 2 ] [ 7 ] [ 8 ] ink-jet oligonucleotide technology for synthesizing DNA [ 9 ] [ 10 ] and nanostring technology for analyzing single molecules of DNA and RNA. [ 11 ] [ 12 ]
The protein sequencer, DNA synthesizer, peptide synthesizer, and DNA sequencer were commercialized through Applied Biosystems, Inc. [ 13 ] and the ink-jet technology was commercialized through Agilent Technologies . [ 9 ] [ 10 ] The automated DNA sequencer was an enabling technology for the Human Genome Project . [ 7 ] The peptide synthesizer was used in the synthesis of the HIV protease by Stephen Kent and others, and the development of a protease inhibitor for AIDS treatment. [ 6 ] [ 14 ] [ 15 ]
Hood established the first cross-disciplinary biology department, the Department of Molecular Biotechnology (MBT), at the University of Washington in 1992, [ 16 ] [ 8 ] and co-founded the Institute for Systems Biology in 2000. [ 11 ] Hood is credited with introducing the term " systems biology ", [ 17 ] and advocates for "P4 medicine", medicine that is "predictive, personalized , preventive, and participatory." [ 18 ] [ 19 ] Scientific American counted him among the 10 most influential people in the field of biotechnology in 2015. [ 20 ]
Hood was elected a member of the National Academy of Engineering in 2007 for the invention and commercialization of key instruments, notably the automated DNA sequencer, that have enabled the biotechnology revolution.
Hood was born on October 10, 1938, in Missoula, Montana , to Thomas Edward Hood and Myrtle Evylan Wadsworth. [ 21 ] and grew up in Shelby . [ 22 ] His father was an electrical engineer , and his mother had a degree in home economics . Hood was one of four children, including a sister and two brothers, including a brother with Down syndrome . One of his grandfathers was a rancher and ran a summer geology camp for university students, which Hood attended as a high school student. Hood excelled in math and science, being one of forty students nationally to win a Westinghouse Science Talent Search . [ 1 ] In addition, Hood played several high school sports and debate, the latter of which he would credit for his success in science communication later in his career. [ 23 ]
Hood received his undergraduate education from the California Institute of Technology (Caltech), where his professors included notables such as Richard Feynman [ 17 ] and Linus Pauling . [ 13 ] [ 1 ] Hood received an MD from Johns Hopkins School of Medicine in 1964 and a PhD from Caltech in 1968, [ 24 ] where he worked with William J. Dreyer on antibody diversity. [ 16 ] Dreyer is credited with giving Hood two important pieces of advice: “If you want to practice biology, do it on the leading edge, and if you want to be on the leading edge, invent new tools for deciphering biological information.” [ 25 ]
In 1967, Hood joined the National Institutes of Health (NIH), to work in the immunology branch of the National Cancer Institute as a senior investigator. [ 26 ]
In 1970, he returned to Caltech as an assistant professor . [ 16 ] He was promoted to associate professor in 1973, full professor in 1975, and was named Bowles Professor of Biology in 1977. He served as chairman of the Division of Biology from 1980-1989 and director of Caltech's Special Cancer Center in 1981. [ 21 ]
Hood has been a leader and a proponent of cross-disciplinary research in chemistry and biology. [ 16 ] In 1989 he stepped down as chairman of the Division of Biology to create and become director of a newly funded NSF Science and Technology Center at Caltech. [ 27 ] The NSF Center for the Development of an Integrated Protein and Nucleic Acid Biotechnology became one of the founding research centers of the Beckman Institute at Caltech in 1989. [ 28 ] [ 29 ] By this time, Hood's laboratory included more than 100 researchers, a much larger group than was usual at Caltech. A relatively small school, Caltech was not well-suited to the creation of the type of large interdisciplinary research organization that Hood sought. [ 30 ]
In October 1991, Hood announced that he would move to the University of Washington at Seattle, to found and direct the first cross-disciplinary biology department, the Department of Molecular Biotechnology (MBT) at the University of Washington Medical School. [ 16 ] [ 8 ] The new department was financed by a US $12-million gift from Bill Gates , who shared Hood's interest in combining biological research and computer technology and applying them to medical research. [ 31 ] [ 32 ] Roger Perlmutter , who had worked in Hood's lab at Caltech before moving to UW as chair of the immunology department, played a key role organizing his recruitment to UW. [ 23 ] Hood and other scientists from Caltech's NSF center moved to the University of Washington during 1992-1994, where they received renewed support from the NSF as the Center for Molecular Biotechnology. [ 27 ] [ 33 ] (Later, in 2001, the department of molecular biotechnology and the genetics department at UW reorganized to form the department of genome sciences. [ 34 ] )
In 2000 Hood resigned his position at the University of Washington to become co-founder and president of the non-profit Institute for Systems Biology (ISB), [ 35 ] possibly the first independent systems biology organization. [ 36 ] His co-founders were protein chemist Ruedi Aebersold and immunologist Alan Aderem . [ 37 ] Hood is still an affiliate professor at the University of Washington in Computer Science, [ 38 ] Bioengineering [ 39 ] and Immunology. [ 40 ] In April 2017, the ISB announced that Hood will be succeeded as president of ISB as of January 2018 by James Heath , while continuing to lead his research group at ISB and serving on ISB's board of directors. [ 37 ]
Hood believes that a combination of big data and systems biology has the potential to revolutionize healthcare and create a proactive medical approach focused on maximizing the wellness of the individual. He coined the term "P4 medicine" in 2003. [ 41 ] [ 42 ] In 2010 ISB partnered with the Ohio State University Wexner Medical Center in Columbus, Ohio , to establish the nonprofit P4 Medicine Institute (P4MI). Its goal was stated as being "to lead the transformation of healthcare from a reactive system to one that predicts and prevents disease, tailors diagnosis and therapy to the individual consumer and engages patients in the active pursuit of a quantified understanding of wellness; i.e. one that is predictive, preventive, personalized and participatory (P4)." [ 43 ] In 2012, P4 Medical Institute established an agreement with its first community health partner, PeaceHealth . PeaceHealth is a not-for-profit Catholic health care system, operating in a variety of communities in Alaska, Washington and Oregon. [ 44 ] [ 45 ] In 2016, ISB affiliated with Providence Health & Services , [ 46 ] and Hood became the senior vice president of Providence St. Joseph Health and its chief science officer. [ 37 ]
Hood has published more than 700 peer-reviewed papers, received 36 patents, and co-authored textbooks in biochemistry, immunology, molecular biology, and genetics. In addition, he co-authored, with Daniel J. Kevles, The Code of Codes , a popular book on the sequencing of the human genome. [ 47 ]
He has been instrumental in founding 15 biotechnology companies, [ 11 ] including Amgen , Applied Biosystems, Systemix, Darwin, Rosetta Inpharmatics, Integrated Diagnostics, and Accelerator Corporation. [ 48 ] In 2015, he co-founded a startup called Arivale offering a subscription-based 'scientific wellness' service [ 49 ] which shut down in 2019. [ 50 ] While praising the quality of its offering, industry commentators attributed Arivale's closure to a failure to capture sufficient Customer lifetime value to create a profit from providing the service, suggesting that insufficient numbers of customers stuck with the data-driven, personalized dietary and lifestyle coaching it provided for long enough at a price point which would make the business model work. [ 51 ]
At Caltech, Hood and his colleagues created the technological foundation for the study of genomics and proteomics by developing five groundbreaking instruments - the protein sequencer (1982), the DNA synthesizer (1983), the peptide synthesizer (1984),the automated DNA sequencer (1986) and later the ink-jet DNA synthesizer. [ 3 ] [ 52 ] [ 2 ] [ 7 ] [ 8 ] Hood's instruments incorporated concepts of high throughput data accumulation through automation and parallelization. When applied to the study of protein and DNA chemistries, these ideas were essential to the rapid deciphering of biological information. [ 52 ] [ 53 ] [ 54 ]
Hood had a strong interest in commercial development, actively filing patents and seeking private funding. [ 55 ] Applied Biosystems, Inc. (initially named GeneCo.) was formed in 1981 in Foster City, California, to commercialize instruments developed by Hood, Hunkapiller, Caruthers, and others. The company was supported by venture capitalist William K. Bowes , who hired Sam H. Eletr and André Marion as president and vice-president of the new company. The company shipped the first gas phase protein sequencer, Model 4790A, in August 1982. The 380 DNA synthesizer was commercialized in 1983, the 430A peptide synthesizer in 1984, and the 370A DNA sequencing system in 1986. [ 56 ] [ 5 ]
These new instruments had a major impact on the emerging fields of proteomics and genomics. [ 3 ] [ 57 ] The gas-liquid phase protein sequencer was developed with Michael W. Hunkapiller, then a
research fellow at Caltech. [ 24 ] [ 58 ] The instrument makes use of the chemical process known as the Edman degradation , devised by Pehr Edman . [ 58 ] Edman and Begg's 1967 design involves placing a protein or peptide sample into a spinning cup in a temperature controlled chamber. Reagents are added to cleave the protein one amino acid at the time, followed by solvents to allow extraction of reagents and byproducts. A series of analysis cycles is performed to identify a sequence, one cycle for each amino acid, and the cycle times were lengthy. [ 59 ] Hood and Hunkapiller made a number of modifications, further automating steps in the analysis and improving effectiveness and shortening cycle time. By applying reagents in the gas phase instead of the liquid phase, the retention of the sample during the analysis and the sensitivity of the instrument were increased. [ 58 ] Polybrene was used as a substrate coating to better anchor proteins and peptides, [ 60 ] and the purification of reagents was improved. HPLC analysis techniques were used to reduce analysis times and extend the technique's applicable range. [ 58 ] The amount of protein required for an analysis decreased, from 10-100 nanomoles for Edman and Begg's protein sequencer, to the low picomole range, a revolutionary increase in the sensitivity of the technology. [ 58 ] [ 61 ] [ 16 ] [ 62 ] The new sequencer offered significant advantages in speed and sample size compared to commercial sequencers of the time, the most popular of which were built by Beckman Instruments . [ 55 ] Commercialized as the Model 470A protein sequencer, it allowed scientists to determine partial amino acid sequences of proteins that had not previously been accessible, characterizing new proteins and better understanding their activity, function, and effects in therapeutics. These discoveries had significant ramifications in biology, medicine, and pharmacology. [ 63 ] [ 5 ] [ 64 ]
The first automated DNA synthesizer resulted from a collaboration with Marvin H. Caruthers of the University of Colorado Boulder , and was based on Caruthers' work elucidating the chemistry of phosphoramidite oligonucleotide synthesis . [ 65 ] [ 66 ] [ 67 ] Caltech staff scientist Suzanna J. Horvath worked with Hood and Hunkapiller to learn Caruthers' techniques in order to design a prototype that automated the repetitive steps involved in Caruthers' method for DNA synthesis. [ 68 ] [ 69 ] The resulting prototype was capable of forming short pieces of DNA called oligonucleotides, which could be used in DNA mapping and gene identification. [ 68 ] [ 5 ] The first commercial phosphoramidite DNA synthesizer was developed from this prototype by Applied Biosystems, [ 67 ] who installed the first Model 380A in Caruthers' lab at the University of Colorado in December 1982, before beginning official commercial shipment of the new instrument. [ 65 ] Revolutionizing the field of molecular biology, the DNA synthesizer enabled biologists to synthesize DNA fragments for cloning and other genetic manipulations. Molecular biologists were able to produce DNA probes and primers for use in DNA sequencing and mapping, gene cloning, and gene synthesis. The DNA synthesizer played a critical role in the identification of many important genes and in the development of the polymerase chain reaction (PCR), the critical technique used to amplify segments of DNA a million-fold. [ 5 ] [ 6 ]
The first commercial automated peptide synthesizer, sometimes referred to as a protein synthesizer, was developed by Hood and Stephen B. H. Kent , a senior research associate at Caltech from 1983 to 1989. [ 70 ] [ 69 ] The automated, programmable peptide synthesizer had previously been invented and developed by Bruce Merrifield and colleagues at Rockefeller University, and Merrifield received the Novel Prize for this invention [ 71 ] The peptide synthesizer assembles long peptides and short proteins from amino acid subunits, [ 6 ] in quantities sufficient for subsequent analysis of their structure and function. The commercially available instrument from Applied Biosystems led to a number of significant results, including the synthesis of HIV-1 protease in a collaboration between Kent and Merck and the analysis of its crystalline structure. Based on this research, Merck developed an important antiprotease drug for the treatment of AIDS . Kent carried out a number of important synthesis and structure-function studies in Hood's lab at Caltech. [ 69 ]
Among the notable of the inventions from Hood's lab was the automated DNA sequencer. It made possible high-speed sequencing of the structure of DNA, including the human genome. It automated many of the tasks that researchers had previously done by hand. [ 30 ] [ 72 ] [ 73 ] Researchers Jane Z. Sanders and Lloyd M. Smith developed a way to color code the basic nucleotide units of DNA with fluorescent tags, green for adenine (A), yellow-green for guanine (G), orange for cytosine (C) and red for thymine (T). [ 74 ] Four differently colored fluorophores , each one specific to a reaction with one of the bases, are covalently attached to the oligonucleotide primer for the enzymatic DNA sequence analysis. [ 75 ] During the analysis, fragments are passed downwards through a gel tube, the smallest and lightest fragments passing through the gel tube first. A laser light passed through a filter wheel causes the bases to fluoresce. The resulting fluorescent colors are detected by a photomultiplier and recorded by a computer. The first DNA fragment to be sequenced was a common cloning vector , M13 . [ 74 ] [ 76 ] [ 75 ]
The DNA sequencer was a critical technology for the Human Genome Project . [ 7 ] [ 75 ] Hood was involved with the Human Genome Project from its first meeting, held at the University of California, Santa Cruz , in 1985. Hood became an enthusiastic advocate for The Human Genome Project and its potential. [ 1 ] [ 52 ] [ 77 ] [ 53 ] Hood directed the Human Genome Center’s sequencing of portions of human chromosomes 14 and 15 . [ 78 ] [ 79 ] [ 80 ] [ 81 ] [ 82 ]
At the University of Washington in the 1990s, Hood, Alan Blanchard, and others developed ink-jet DNA synthesis technology for creating DNA microarrays . [ 83 ] [ 84 ] By 2004, their ink-jet DNA synthesizer supported high-throughput identification and quantification of nucleic acids through the creation of one of the first DNA array chips, with expression levels numbering tens of thousands of genes. [ 9 ] [ 85 ] Array analysis has become a standard technique for molecular biologists who wish to monitor gene expression. [ 85 ] DNA ink-jet printer technology has had a significant impact on genomics, biology, and medicine. [ 86 ] [ 87 ] [ 88 ]
Hood also made generative discoveries in the field of molecular immunology . His studies of the amino acid sequences of immunoglobulins (also known as antibodies) helped to fuel the 1970s’ debate regarding the generation of immune diversity and supported the hypothesis advanced by William J. Dreyer that immunoglobulin (antibody) chains are encoded by two separate genes (a constant and a variable gene). He (and others) conducted pioneering studies on the structure and diversity of the antibody genes. This research led to verification of the "two genes, one polypeptide" hypothesis and insights into the mechanisms responsible for the diversification of the immunoglobulin variable genes. [ 16 ] [ 89 ] [ 90 ] [ 91 ] [ 54 ] Hood shared the Lasker Award in 1987 for these studies. [ 92 ]
Additionally, Hood was among the first to study, at the gene level, the MHC (major histocompatibility complex) gene family [ 93 ] [ 94 ] and the T-cell receptor gene families [ 95 ] as well as being among first to demonstrate that alternative RNA splicing was a fundamental mechanism for generating alternative forms of antibodies. He showed that RNA splicing is the mechanism for generating the membrane bound and the secreted forms of antibodies. [ 96 ] [ 97 ]
In neurobiology, Hood and his colleagues were the first to clone and study the myelin basic protein (MBP) gene. The MBP is a central component in the sheath that wraps and protects neurons. [ 98 ] [ 99 ] Hood demonstrated that the condition called "shiverer mouse" arose from a defect in the MBP gene. Hood's research group corrected the neurological defect in mice (the shiverer defect) by transferring a normal MBP gene into the fertilized egg of the shiverer mouse. These discoveries led to extensive studies of MBP and its biology. [ 100 ]
Beginning in the 1990s, Hood focused more on cross-disciplinary biology and systems biology. He established in 1992 the first cross-disciplinary biology department, the Molecular Biotechnology Department at the University of Washington . [ 31 ] [ 32 ] In 2000, he co-founded the Institute for Systems Biology (ISB) in Seattle, Washington to develop strategies and technologies for systems approaches to biology and medicine. [ 11 ] [ 35 ] [ 36 ] He co-led the Hood-Price research lab at ISB with Nathan Price until Price left to join Center for Human Healthspan at the Buck Institute for Research on Aging.
Hood pioneered the systems biology concept of considering human biology as a "network of networks." [ 101 ] [ 102 ] In this model, understanding how systems function requires knowledge of: (1) the components of each network (including genetic, molecular, cellular, organ networks), (2) how these networks inter- and intra-connect, (3) how the networks change over time and undergo perturbations, and (4) how function is achieved within these networks. [ 103 ] At the ISB under Hood's direction, genomic, transcriptomic, metabolomic and proteomic technologies are used to understand the "network of networks" and are focused on diverse biological systems [ 104 ] (e.g. yeast, mice and humans). [ 105 ]
Hood applies the notion of systems biology to the study of medicine, [ 106 ] [ 107 ] specifically to cancer [ 108 ] and neurodegenerative disease . [ 109 ] His research article on a systems approach to prion diseases in 2009 was one of the first to thoroughly explore the use of systems biology to interrogate the dynamic network changes in disease models. These studies are the first to explain the dynamics of diseased-perturbed networks and have expanded to include frontal temporal dementia and Huntington's disease . [ 110 ] [ 111 ] Hood is also studying glioblastoma in mice and humans from the systems viewpoint. [ 112 ]
Hood advocates several practices in the burgeoning field of systems medicine , including:
(1) The use of family genome sequencing, integrating genetics and genomics, to identify genetic variants associated with health and disease [ 113 ] (2) The use of targeted proteomics and biomarkers as a window into health and disease. [ 114 ] [ 115 ] He has pioneered the discovery of biomarker panels for lung cancer [ 116 ] and posttraumatic stress syndrome . [ 117 ] (3) The use of systems biology to stratify disease into its different subtypes allowing for more effective treatment. [ 118 ] [ 54 ] (4) The use of systems strategies to identify new types of drug targets to facilitate and accelerate the drug discovery process. [ 108 ]
Since 2002 Hood has progressively expanded his vision of the future of medicine: first focusing on predictive and preventive (2P) Medicine; then predictive, preventive and personalized (3P) Medicine; and finally predictive, preventive, personalized and participatory, also known as P4 Medicine. [ 119 ] Hood states that P4 Medicine is the convergence of systems medicine, big data and patient (consumer) driven healthcare and social networks. [ 118 ]
Hood envisions that by the mid-2020s each individual will be surrounded by a virtual cloud of billions of data points and will have the computational tools to analyze this data and produce simple approaches to optimize wellness and minimize disease for each individual. [ 42 ] [ 53 ] [ 54 ] According to this view, the patient's demand for better healthcare will be the real driving force for the acceptance of P4 Medicine by the medical community. This driving force is exemplified by the movement known as the quantified self , which uses digital devices to monitor self-parameters such as weight, activity, sleep, diet, etc. His view is that P4 Medicine will transform the practice of medicine over the next decade, moving it from a largely reactive, disease-care approach to a proactive P4 approach that is predictive, preventive, personalized and participatory. [ 118 ]
In 2010, Hood co-founded the P4 Medicine institute (P4Mi), for the development of Predictive, Preventive, Personalized and Participatory (P4) Medicine. [ 43 ] In 2021 Hood founded Phenome Health, a non profit focused on implementing his vision. He argues that P4 Medicine will improve healthcare, decrease its cost and promote innovation. [ 120 ]
Leroy Hood is a member of the National Academy of Sciences (NAS, 1982), [ 121 ] the National Academy of Engineering (2007), [ 122 ] the National Academy of Medicine (formerly the Institute of Medicine, 2003), [ 123 ] and the National Academy of Inventors (2012). [ 124 ] He is one of only 15 scientists ever elected to all three national academies. [ 125 ] He is also
a member of the American Academy of Arts and Sciences (1982), [ 126 ] a member of the American Philosophical Society (2000), [ 127 ] a fellow of the American Society for Microbiology , [ 128 ] and a charter fellow of the National Academy of Inventors (2012). [ 129 ] [ 130 ] He has received 17 honorary degrees [ 11 ] from institutions including Johns Hopkins [ 131 ] and Yale University . [ 132 ]
In 1987 Hood shared the Albert Lasker Award for Basic Medical Research with Philip Leder and Susumu Tonegawa for studies of the mechanism of immune diversity. [ 92 ] He subsequently was awarded the Dickson Prize in 1988. [ 133 ] In 1987, Hood also received the Golden Plate Award of the American Academy of Achievement . [ 134 ]
He won the 2002 Kyoto Prize for Advanced Technology for developing automated technologies for analyzing proteins and genes; [ 2 ] the 2003 Lemelson-MIT Prize for Innovation and Invention for inventing "four instruments that have unlocked much of the mystery of human biology" by helping decode the genome ; [ 135 ] the 2004 Biotechnology Heritage Award ; [ 136 ] [ 137 ] the 2004 Association for Molecular Pathology Award for Excellence in Molecular Diagnostics [ 138 ] the 2006 Heinz Award in Technology, the Economy and Employment, [ 139 ] for breakthroughs in biomedical science on the genetic level;
inclusion in the 2007 Inventors Hall of Fame for the automated DNA sequencer; [ 140 ] the 2008 Pittcon Heritage Award for helping to transform the biotechnology industry; [ 141 ] [ 142 ] and
the 2010 Kistler Prize for contributions to genetics that have increased knowledge of the human genome and its relationship to society. [ 18 ] Leroy Hood won the 2011 Fritz J. and Dolores H. Russ Prize "for automating DNA sequencing that revolutionized biomedicine and forensic science"; [ 143 ] the 2011 National Medal of Science , presented at a White House ceremony by President Obama in early 2013; [ 144 ] the IEEE Medal for Innovations in Healthcare Technology in 2014, [ 9 ] and
the 2016 Ellis Island Medal of Honor . [ 125 ] In 2017 he received the NAS Award for Chemistry in Service to Society . [ 8 ] In 2019 Hood was awarded the IRI Medal , established by the Industrial Research Institute (IRI). [ 145 ] | https://en.wikipedia.org/wiki/Leroy_Hood |
The Les Houches Accords are agreements between particle physicists to standardize the interface between the matrix element programs and the event generators used to calculate different quantities. The original accord was initially formed in 2001, at a conference in Les Houches , in the French Alps , before it was subsequently expanded.
In experimental high energy physics , several levels of computing are used to simulate data runs, including programs that generate matrix elements and ones that generate events. However, there are several programs for each of these tasks, such as CompHEP and MadGraph to generate matrix elements, and PYTHIA and HERWIG for event generation. Depending on specific properties of the particle decay that physicists are interested in, they may desire to use a certain program for these tasks, but before the Les Houches Accords, there was no general interface for communicating between the programs. This enables physicists to choose more freely between different programs. The Accords also make it easier to generate parton distribution functions, which are datasets used to calculate cross sections , for events .
The original Accord defined a programmatic interface for transfer of event information, in terms of Fortran common blocks , but no data exchange file format was defined until 2006.
Events that conform to the formats described in the Les Houches Accords are said to be in Les Houches Event format, or more often, LHE format.
This computational physics -related article is a stub . You can help Wikipedia by expanding it .
This particle physics –related article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Les_Houches_Accords |
Lesley-Ann L. Dupigny-Giroux is the Vermont State Climatologist , president of the American Association of State Climatologists, [ 1 ] Inc., and a professor of Geography at the University of Vermont . [ 2 ]
Dupigny-Giroux was born in Trinidad . Her exploration of the small island gave her an early appreciation for place and geography, and their connections to history. [ 3 ]
Dupigny-Giroux earned her Bachelor of Science degree from the University of Toronto in 1989, double majoring in physical geography and development studies. She earned both her Master of Science (1992) and Doctor of Philosophy (1996) degrees from McGill University . [ 4 ] Her Master's degree was in climatology and hydrology , with a thesis on rainfall and runoff in drainage basins in Trinidad. Her doctoral degree was in climatology and geographic information systems (GIS) , with a thesis on drought and rainfall over northern Brazil . Early in her graduate studies, Dupigny-Giroux spent a summer at the National Center for Atmospheric Research (1990) analyzing rainfall and runoff data using spectral analysis methods with Warren Washington and Harry van Loon and later (1992) participated in the National Oceanic and Atmospheric Administration (NOAA) colloquium on operational and environmental prediction, where she learned techniques in climate monitoring, weathering analysis, and hydrologic and oceanographic prediction.
Dupigny-Giroux worked as a research assistant and lecturer while at McGill University and taught at the Southern Illinois University at Edwardsville as an assistant professor (1996-1997) before joining the University of Vermont and becoming Vermont State Climatologist in 1997. [ 5 ]
Dupigny-Giroux has served as Vermont State Climatologist and worked at the University of Vermont since 1997. She has authored more than 40 peer-reviewed publications and reports on hydrology, remote sensing , climate change and variability , extreme weather , and climate literacy. [ 2 ]
Notable publications include work with the US Global Change Research Program , where Dupigny-Giroux served as contributing author on Climate Change in the Northeast: A Sourcebook [ 6 ] , a technical input for the Northeast chapter [ 7 ] of the third National Climate Assessment (NCA3), and as chapter lead of the Northeast chapter [ 8 ] of the fourth National Climate Assessment (NCA4). [ 9 ] [ 10 ] The Northeast chapter of NCA4 included information on how climate change would affect rural economies, natural resources, and human health in the Northeast United States. [ 11 ] She also served as lead editor of the book Historical climate variability and impacts in North America , [ 12 ] which uses instrumental and historical data to reconstruct and analyze climate change in North America between the 17th and 19th centuries.
Dupigny-Giroux has also conducted research on North Atlantic Ocean tropical cyclones , including disaster mitigation research to reduce wind damage to residential infrastructure and construction in the Caribbean . [ 13 ] [ 14 ]
At the University of Vermont, Dupigny-Giroux served as an Assistant Professor from 1997 - 2003, Associate Professor from 2003 - 2014, Chair of the Department of Geography from 2015 - 2018, and Professor beginning in 2014, with secondary appointments in Department of Geology, the College of Education & Social Services, and Rubenstein School of Environment & Natural Resources. She teaches courses in meteorology, climatology, physical geography, remote sensing, and land-surface processes. [ citation needed ]
In her work as State Climatologist for Vermont, Dupigny-Giroux uses her expertise hydrology and extreme weather, such as floods, droughts, and storms, to keep the residents of Vermont informed on how climate change will affect their homes, health, and livelihoods. She assists other state agencies in preparing for and adapting to current and future impacts of climate change on Vermont's transportation system, emergency management planning, and agriculture and forestry industries. For example, she has published analyses of the impacts of climate change on the health of Vermont's sugar maples , a hardwood species of key economic and cultural importance to the state. [ 15 ] As co-chair of Vermont's State’s Drought Task Force, she played a key role in developing the 2018 Vermont State Hazard Mitigation Plan. [ 16 ]
Dupigny-Giroux served as Secretary for the American Association of State Climatologists from 2010-2011 and President Elect from 2019-2020. In June 2020, she was elected as President of the American Association of State Climatologists, which is a two-year term. [ 17 ]
In addition to her research on climate change , Dupigny-Giroux is known for her efforts to research and promote climate literacy. [ 18 ] [ 19 ] [ 20 ] [ 21 ] Climate literacy is an understanding of the influences of and influences on the climate system, including how people change the climate, how climate metrics are observed and modelled, and how climate change affects society. “Being climate literate is more critical than ever before,” Lesley-Ann Dupigny-Giroux stated for a 2020 article on climate literacy. [ 22 ] “If we do not understand weather, climate and climate change as intricate and interconnected systems, then our appreciation of the big picture is lost.”
Dupigny-Giroux is known for her climate literacy work with elementary and high school teachers and students. She co-founded the Satellites Weather and Climate (SWAC) [ 23 ] [ 24 ] project in 2008, which is a professional development program for K-12 teachers designed to promote climate literacy and interest in the STEM (Science, Technology, Engineering and Mathematics) careers. Dupigny-Giroux is also a founding member of the Climate Literacy and Energy Awareness Network (CLEAN; formerly Climate Literacy Network), [ 25 ] a community-based effort to support climate literacy and communication.
In a 2016 interview, Dupigny-Giroux stated: “Sharing knowledge and giving back to my community are my two axioms in life. Watching students mature and flourish in their four years with us is a great privilege and the best part about being a teacher-scholar here at UVM [University of Vermont].” [ 3 ]
Lesley-Ann Dupigny-Giroux is the co-founder of the Diversity Climate Network (D-ClimNet), [ 26 ] which was funded by a National Science Foundation ( NSF ) award (2009-2013) to enhance diversity, equity, and inclusion in the field of climatology. The Diversity Climate Network aims to train the next generation of racially and gender diverse scientists by providing mentoring and networking opportunities to high school students interested in climate science or geoscience. In 2010, Dupigny-Giroux was the Franklin Visiting Scholar for Inclusion and Diversity Leadership at the University of Georgia . | https://en.wikipedia.org/wiki/Lesley-Ann_L._Dupigny-Giroux |
Sir Leslie Fowden FRS [ 1 ] (1925–2008) was a British organic chemist and plant scientist , notable for his pioneering research on phytochemistry and plant amino acids , as well as for his role in promoting agricultural research in the UK.
Leslie Fowden was born at Birch Hill House, Wardle , Rochdale on 13 October 1925, the only child of Herbert Fowden, an iron turner, and Amy Dorothy (née Rabbich), a cotton minder. [ 2 ] He was a diligent student who excelled at mathematics and won a fee-paying scholarship to Rochdale Grammar School for Boys (now Balderstone Technology College ), where he studied from 1936 to 1943. He gained five distinctions in the School Certificate Examinations in 1940, including mathematics, physics and chemistry. In the 1942 Higher School Certificate (HSC) he was awarded distinctions for the same three subjects.
Fowden went on to read chemistry at University College (UCL) in a two-year intensive degree course (a special requirement for chemistry students in the war years). Another requirement was that he also had to participate in officer training. He was awarded a first class BSc degree in chemistry with honours, and told that he was the top student in chemistry in the University of London as a whole. He started his PhD in late 1945, supervised jointly by Professor Ingold and by Professor E. D. Hughes [ 3 ] of the University College of Wales, Bangor. Ingold was the UK authority on organic reaction mechanisms, and Fowden was set to work investigating nucleophilic substitution in alkyl halides as the alkyl group became progressively larger or more branched in structure. The degree was awarded in 1948, and the main findings were published in 1955. [ 4 ]
In 1947 Fowden accepted a post as scientific officer in the Human Nutrition Research Unit of the MRC in London. This was a key moment in his career, marking a move to work of more direct benefit to mankind. He was involved with two projects: (1) on kwashiorkor and a growth-retarding factor in maize bran ; and (2) a chromatographic study of peanut protein hydrolysates and their free amino acid content, as part of a scheme to improve post-war nutrition and the economy of Commonwealth countries in East Africa. [ 5 ]
Some aspects of the chromatographic work did not fit in with the MRC’s aims, so he accepted a lectureship in plant chemistry, back at UCL, where he had greater freedom. He set up a new lab where the main focus was on the identification and structural analysis of plant non-protein amino acids. He recruited PhD students and technical assistants; they, and later postdoctoral research fellows and foreign visitors, discovered several new plant amino and imino acids. [ 6 ] Fowden isolated and characterized non-protein amino acids from a growing number and variety of plants,
emphasizing their general importance in plant nitrogen metabolism.
"To isolate an unusual amino acid from the seeds of the lychee ( Litchi chinensis ) he had to buy large quantities of the fruit from Covent Garden . His UCL colleagues were invited to take home over the weekend as much of the fruit as they wished, provised that the washed stones were returned on the Monday morning". [ 7 ]
His researches were recognized by promotion to a readership in 1956.
On 31 January 1955, Leslie Fowden and his family sailed on the America from Southampton to New York, en route to Ithaca , where Fowden took up a Rockefeller Visiting Fellowship to work with Professor F. C. Steward at Cornell . Their work together “provided one of the earliest demonstrations of how chemical data could be used to establish phylogenetic relationships within and between plant families and their constituent genera”. [ 1 ] The Fowdens returned to the UK aboard the Queen Mary , arriving on 21 December 1955.
Leslie Fowden made several more trips in the coming years, including:
These trips strengthened his love of travel and languages.
In 1972 Fowden was invited to fill the post of Director of Rothamsted Experimental Station ; he took up the position on 1 April 1973. When he arrived the research being undertaken by some 500 scientists “needed reinvigoration—and new investment—to regain its past reputation for scientific excellence”. [ 1 ] Fragmented departments were combined into five new divisions. In 1986 Rothamsted itself was amalgamated with other Stations across the country to form the new Institute of Arable Crops Research (IACR), [ 2 ] and Fowden became its inaugural director. He retired in 1988, but did not slow down. He joined the council of the Royal Institution and became a trustee and then Director of the Foundation and Friends of Kew Gardens. He became a scientific adviser to several international agrochemical companies, and maintained visiting professorships at the University of London and the University of Wales Swansea .
Leslie Fowden married fellow chemistry student Margaret (Peggy) Oakes on 9 July 1949 at the Methodist chapel in East Ham. [ 2 ] They had two children:
Sir Leslie Fowden died from renal and heart failure at a care home in Histon on 16 December 2008 and was cremated in Cambridge on the 29th. | https://en.wikipedia.org/wiki/Leslie_Fowden |
Leslie Hicks is an American associate professor of analytical chemistry at the University of North Carolina at Chapel Hill . Her work primarily focuses on the study of proteomics and protein post-translational modifications using mass spectrometry , and identifying biologically active peptides in plants. [ 1 ]
Hicks earned her bachelor's degree at Marshall University in 2001, and went on to earn her doctorate at the University of Illinois Urbana-Champaign in 2005. She was an Assistant Member and Principal Investigator at the Donald Danforth Plant Science Center from 2006 to 2013, and an adjunct professor in the Department of Biology at Washington University in St. Louis before beginning her current position as a professor at UNC. [ 2 ] She was named Sherman Fairchild Foundation Chancellor’s Science Scholars Term Associate Professor in 2022. [ 3 ]
Hicks' research focuses largely on the development and implementation of mass spectrometric methods for protein identification and characterization. Recent work in the Hicks Lab has focused primarily on two areas. The first is the study of post-translational modifications and their role in regulation and development. The second involves a novel analytical pipeline for the discovery and characterization of antimicrobial peptides .
Hicks' research in post-translational modifications typically employs bottom-up proteomics using label-free quantification . Much of this research involves the model organism C. reinhardtii , an important organism in biofuel research due to its tendency to accumulate triacylglycerols . The Hicks Lab has studied the phosphoproteome of C. reinhardtii in order to examine underlying biological processes. [ 4 ] [ 5 ] Work has also been done to understand cell regulatory pathways, especially the algal analog of the mammalian TOR pathway. [ 6 ] To a similar end, Hicks' group has extended its work to examine how the reversible oxidation of thiols plays a role in signaling [ 7 ] and effector-triggered immunity . [ 8 ]
The increasing threat of antimicrobial resistance has produced a need for novel antimicrobial agents. [ 9 ] The Hicks Lab has investigated antimicrobial peptides as a potential source for new antibiotics. Recent work has involved the development of a comprehensive analytical approach using LC-MS for the identification of novel antimicrobial peptides from botanical, [ 10 ] [ 11 ] fungal , [ 12 ] and bacterial [ 13 ] sources. | https://en.wikipedia.org/wiki/Leslie_M._Hicks |
The reflected binary code ( RBC ), also known as reflected binary ( RB ) or Gray code after Frank Gray , is an ordering of the binary numeral system such that two successive values differ in only one bit (binary digit).
For example, the representation of the decimal value "1" in binary would normally be " 001 ", and "2" would be " 010 ". In Gray code, these values are represented as " 001 " and " 011 ". That way, incrementing a value from 1 to 2 requires only one bit to change, instead of two.
Gray codes are widely used to prevent spurious output from electromechanical switches and to facilitate error correction in digital communications such as digital terrestrial television and some cable TV systems. The use of Gray code in these devices helps simplify logic operations and reduce errors in practice. [ 3 ]
Many devices indicate position by closing and opening switches. If that device uses natural binary codes , positions 3 and 4 are next to each other but all three bits of the binary representation differ:
The problem with natural binary codes is that physical switches are not ideal: it is very unlikely that physical switches will change states exactly in synchrony. In the transition between the two states shown above, all three switches change state. In the brief period while all are changing, the switches will read some spurious position. Even without keybounce , the transition might look like 011 — 001 — 101 — 100 . When the switches appear to be in position 001 , the observer cannot tell if that is the "real" position 1, or a transitional state between two other positions. If the output feeds into a sequential system, possibly via combinational logic , then the sequential system may store a false value.
This problem can be solved by changing only one switch at a time, so there is never any ambiguity of position, resulting in codes assigning to each of a contiguous set of integers , or to each member of a circular list, a word of symbols such that no two code words are identical and each two adjacent code words differ by exactly one symbol. These codes are also known as unit-distance , [ 4 ] [ 5 ] [ 6 ] [ 7 ] [ 8 ] single-distance , single-step , monostrophic [ 9 ] [ 10 ] [ 7 ] [ 8 ] or syncopic codes , [ 9 ] in reference to the Hamming distance of 1 between adjacent codes.
In principle, there can be more than one such code for a given word length, but the term Gray code was first applied to a particular binary code for non-negative integers, the binary-reflected Gray code , or BRGC . Bell Labs researcher George R. Stibitz described such a code in a 1941 patent application, granted in 1943. [ 11 ] [ 12 ] [ 13 ] Frank Gray introduced the term reflected binary code in his 1947 patent application, remarking that the code had "as yet no recognized name". [ 14 ] He derived the name from the fact that it "may be built up from the conventional binary code by a sort of reflection process".
In the standard encoding of the Gray code the least significant bit follows a repetitive pattern of 2 on, 2 off (... 11001100 ...); the next digit a pattern of 4 on, 4 off; the i -th least significant bit a pattern of 2 i on 2 i off. The most significant digit is an exception to this: for an n -bit Gray code, the most significant digit follows the pattern 2 n −1 on, 2 n −1 off, which is the same (cyclic) sequence of values as for the second-most significant digit, but shifted forwards 2 n −2 places. The four-bit version of this is shown below:
For decimal 15 the code rolls over to decimal 0 with only one switch change. This is called the cyclic or adjacency property of the code. [ 15 ]
In modern digital communications , Gray codes play an important role in error correction . For example, in a digital modulation scheme such as QAM where data is typically transmitted in symbols of 4 bits or more, the signal's constellation diagram is arranged so that the bit patterns conveyed by adjacent constellation points differ by only one bit. By combining this with forward error correction capable of correcting single-bit errors, it is possible for a receiver to correct any transmission errors that cause a constellation point to deviate into the area of an adjacent point. This makes the transmission system less susceptible to noise .
Despite the fact that Stibitz described this code [ 11 ] [ 12 ] [ 13 ] before Gray, the reflected binary code was later named after Gray by others who used it. Two different 1953 patent applications use "Gray code" as an alternative name for the "reflected binary code"; [ 16 ] [ 17 ] one of those also lists "minimum error code" and "cyclic permutation code" among the names. [ 17 ] A 1954 patent application refers to "the Bell Telephone Gray code". [ 18 ] Other names include "cyclic binary code", [ 12 ] "cyclic progression code", [ 19 ] [ 12 ] "cyclic permuting binary" [ 20 ] or "cyclic permuted binary" (CPB). [ 21 ] [ 22 ]
The Gray code is sometimes misattributed to 19th century electrical device inventor Elisha Gray . [ 13 ] [ 23 ] [ 24 ] [ 25 ]
Reflected binary codes were applied to mathematical puzzles before they became known to engineers.
The binary-reflected Gray code represents the underlying scheme of the classical Chinese rings puzzle , a sequential mechanical puzzle mechanism described by the French Louis Gros in 1872. [ 26 ] [ 13 ]
It can serve as a solution guide for the Towers of Hanoi problem, based on a game by the French Édouard Lucas in 1883. [ 27 ] [ 28 ] [ 29 ] [ 30 ] Similarly, the so-called Towers of Bucharest and Towers of Klagenfurt game configurations yield ternary and pentary Gray codes. [ 31 ]
Martin Gardner wrote a popular account of the Gray code in his August 1972 "Mathematical Games" column in Scientific American . [ 32 ]
The code also forms a Hamiltonian cycle on a hypercube , where each bit is seen as one dimension.
When the French engineer Émile Baudot changed from using a 6-unit (6-bit) code to 5-unit code for his printing telegraph system, in 1875 [ 33 ] or 1876, [ 34 ] [ 35 ] he ordered the alphabetic characters on his print wheel using a reflected binary code, and assigned the codes using only three of the bits to vowels. With vowels and consonants sorted in their alphabetical order, [ 36 ] [ 37 ] [ 38 ] and other symbols appropriately placed, the 5-bit character code has been recognized as a reflected binary code. [ 13 ] This code became known as Baudot code [ 39 ] and, with minor changes, was eventually adopted as International Telegraph Alphabet No. 1 (ITA1, CCITT-1) in 1932. [ 40 ] [ 41 ] [ 38 ]
About the same time, the German-Austrian Otto Schäffler [ de ] [ 42 ] demonstrated another printing telegraph in Vienna using a 5-bit reflected binary code for the same purpose, in 1874. [ 43 ] [ 13 ]
Frank Gray , who became famous for inventing the signaling method that came to be used for compatible color television, invented a method to convert analog signals to reflected binary code groups using vacuum tube -based apparatus. Filed in 1947, the method and apparatus were granted a patent in 1953, [ 14 ] and the name of Gray stuck to the codes. The " PCM tube " apparatus that Gray patented was made by Raymond W. Sears of Bell Labs, working with Gray and William M. Goodall, who credited Gray for the idea of the reflected binary code. [ 44 ]
Gray was most interested in using the codes to minimize errors in converting analog signals to digital; his codes are still used today for this purpose.
Gray codes are used in linear and rotary position encoders ( absolute encoders and quadrature encoders ) in preference to weighted binary encoding. This avoids the possibility that, when multiple bits change in the binary representation of a position, a misread will result from some of the bits changing before others.
For example, some rotary encoders provide a disk which has an electrically conductive Gray code pattern on concentric rings (tracks). Each track has a stationary metal spring contact that provides electrical contact to the conductive code pattern. Together, these contacts produce output signals in the form of a Gray code. Other encoders employ non-contact mechanisms based on optical or magnetic sensors to produce the Gray code output signals.
Regardless of the mechanism or precision of a moving encoder, position measurement error can occur at specific positions (at code boundaries) because the code may be changing at the exact moment it is read (sampled). A binary output code could cause significant position measurement errors because it is impossible to make all bits change at exactly the same time. If, at the moment the position is sampled, some bits have changed and others have not, the sampled position will be incorrect. In the case of absolute encoders, the indicated position may be far away from the actual position and, in the case of incremental encoders, this can corrupt position tracking.
In contrast, the Gray code used by position encoders ensures that the codes for any two consecutive positions will differ by only one bit and, consequently, only one bit can change at a time. In this case, the maximum position error will be small, indicating a position adjacent to the actual position.
Due to the Hamming distance properties of Gray codes, they are sometimes used in genetic algorithms . [ 15 ] They are very useful in this field, since mutations in the code allow for mostly incremental changes, but occasionally a single bit-change can cause a big leap and lead to new properties.
Gray codes are also used in labelling the axes of Karnaugh maps since 1953 [ 45 ] [ 46 ] [ 47 ] as well as in Händler circle graphs since 1958, [ 48 ] [ 49 ] [ 50 ] [ 51 ] both graphical methods for logic circuit minimization .
In modern digital communications , 1D- and 2D-Gray codes play an important role in error prevention before applying an error correction . For example, in a digital modulation scheme such as QAM where data is typically transmitted in symbols of 4 bits or more, the signal's constellation diagram is arranged so that the bit patterns conveyed by adjacent constellation points differ by only one bit. By combining this with forward error correction capable of correcting single-bit errors, it is possible for a receiver to correct any transmission errors that cause a constellation point to deviate into the area of an adjacent point. This makes the transmission system less susceptible to noise .
Digital logic designers use Gray codes extensively for passing multi-bit count information between synchronous logic that operates at different clock frequencies. The logic is considered operating in different "clock domains". It is fundamental to the design of large chips that operate with many different clocking frequencies.
If a system has to cycle sequentially through all possible combinations of on-off states of some set of controls, and the changes of the controls require non-trivial expense (e.g. time, wear, human work), a Gray code minimizes the number of setting changes to just one change for each combination of states. An example would be testing a piping system for all combinations of settings of its manually operated valves.
A balanced Gray code can be constructed, [ 52 ] that flips every bit equally often. Since bit-flips are evenly distributed, this is optimal in the following way: balanced Gray codes minimize the maximal count of bit-flips for each digit.
George R. Stibitz utilized a reflected binary code in a binary pulse counting device in 1941 already. [ 11 ] [ 12 ] [ 13 ]
A typical use of Gray code counters is building a FIFO (first-in, first-out) data buffer that has read and write ports that exist in different clock domains. The input and output counters inside such a dual-port FIFO are often stored using Gray code to prevent invalid transient states from being captured when the count crosses clock domains. [ 53 ] The updated read and write pointers need to be passed between clock domains when they change, to be able to track FIFO empty and full status in each domain. Each bit of the pointers is sampled non-deterministically for this clock domain transfer. So for each bit, either the old value or the new value is propagated. Therefore, if more than one bit in the multi-bit pointer is changing at the sampling point, a "wrong" binary value (neither new nor old) can be propagated. By guaranteeing only one bit can be changing, Gray codes guarantee that the only possible sampled values are the new or old multi-bit value. Typically Gray codes of power-of-two length are used.
Sometimes digital buses in electronic systems are used to convey quantities that can only increase or decrease by one at a time, for example the output of an event counter which is being passed between clock domains or to a digital-to-analog converter. The advantage of Gray codes in these applications is that differences in the propagation delays of the many wires that represent the bits of the code cannot cause the received value to go through states that are out of the Gray code sequence. This is similar to the advantage of Gray codes in the construction of mechanical encoders, however the source of the Gray code is an electronic counter in this case. The counter itself must count in Gray code, or if the counter runs in binary then the output value from the counter must be reclocked after it has been converted to Gray code, because when a value is converted from binary to Gray code, [ nb 1 ] it is possible that differences in the arrival times of the binary data bits into the binary-to-Gray conversion circuit will mean that the code could go briefly through states that are wildly out of sequence. Adding a clocked register after the circuit that converts the count value to Gray code may introduce a clock cycle of latency, so counting directly in Gray code may be advantageous. [ 54 ]
To produce the next count value in a Gray-code counter, it is necessary to have some combinational logic that will increment the current count value that is stored. One way to increment a Gray code number is to convert it into ordinary binary code, [ 55 ] add one to it with a standard binary adder, and then convert the result back to Gray code. [ 56 ] Other methods of counting in Gray code are discussed in a report by Robert W. Doran , including taking the output from the first latches of the master-slave flip flops in a binary ripple counter. [ 57 ]
As the execution of program code typically causes an instruction memory access pattern of locally consecutive addresses, bus encodings using Gray code addressing instead of binary addressing can reduce the number of state changes of the address bits significantly, thereby reducing the CPU power consumption in some low-power designs. [ 58 ] [ 59 ]
The binary-reflected Gray code list for n bits can be generated recursively from the list for n − 1 bits by reflecting the list (i.e. listing the entries in reverse order), prefixing the entries in the original list with a binary 0 , prefixing the entries in the reflected list with a binary 1 , and then concatenating the original list with the reversed list. [ 13 ] For example, generating the n = 3 list from the n = 2 list:
The one-bit Gray code is G 1 = ( 0,1 ). This can be thought of as built recursively as above from a zero-bit Gray code G 0 = ( Λ ) consisting of a single entry of zero length. This iterative process of generating G n +1 from G n makes the following properties of the standard reflecting code clear:
These characteristics suggest a simple and fast method of translating a binary value into the corresponding Gray code. Each bit is inverted if the next higher bit of the input value is set to one. This can be performed in parallel by a bit-shift and exclusive-or operation if they are available: the n th Gray code is obtained by computing n ⊕ ⌊ n 2 ⌋ {\displaystyle n\oplus \left\lfloor {\tfrac {n}{2}}\right\rfloor } . Prepending a 0 bit leaves the order of the code words unchanged, prepending a 1 bit reverses the order of the code words. If the bits at position i {\displaystyle i} of codewords are inverted, the order of neighbouring blocks of 2 i {\displaystyle 2^{i}} codewords is reversed. For example, if bit 0 is inverted in a 3 bit codeword sequence, the order of two neighbouring codewords is reversed
If bit 1 is inverted, blocks of 2 codewords change order:
If bit 2 is inverted, blocks of 4 codewords reverse order:
Thus, performing an exclusive or on a bit b i {\displaystyle b_{i}} at position i {\displaystyle i} with the bit b i + 1 {\displaystyle b_{i+1}} at position i + 1 {\displaystyle i+1} leaves the order of codewords intact if b i + 1 = 0 {\displaystyle b_{i+1}={\mathtt {0}}} , and reverses the order of blocks of 2 i + 1 {\displaystyle 2^{i+1}} codewords if b i + 1 = 1 {\displaystyle b_{i+1}={\mathtt {1}}} . Now, this is exactly the same operation as the reflect-and-prefix method to generate the Gray code.
A similar method can be used to perform the reverse translation, but the computation of each bit depends on the computed value of the next higher bit so it cannot be performed in parallel. Assuming g i {\displaystyle g_{i}} is the i {\displaystyle i} th Gray-coded bit ( g 0 {\displaystyle g_{0}} being the most significant bit), and b i {\displaystyle b_{i}} is the i {\displaystyle i} th binary-coded bit ( b 0 {\displaystyle b_{0}} being the most-significant bit), the reverse translation can be given recursively: b 0 = g 0 {\displaystyle b_{0}=g_{0}} , and b i = g i ⊕ b i − 1 {\displaystyle b_{i}=g_{i}\oplus b_{i-1}} . Alternatively, decoding a Gray code into a binary number can be described as a prefix sum of the bits in the Gray code, where each individual summation operation in the prefix sum is performed modulo two.
To construct the binary-reflected Gray code iteratively, at step 0 start with the c o d e 0 = 0 {\displaystyle \mathrm {code} _{0}={\mathtt {0}}} , and at step i > 0 {\displaystyle i>0} find the bit position of the least significant 1 in the binary representation of i {\displaystyle i} and flip the bit at that position in the previous code c o d e i − 1 {\displaystyle \mathrm {code} _{i-1}} to get the next code c o d e i {\displaystyle \mathrm {code} _{i}} . The bit positions start 0, 1, 0, 2, 0, 1, 0, 3, ... [ nb 2 ] See find first set for efficient algorithms to compute these values.
The following functions in C convert between binary numbers and their associated Gray codes. While it may seem that Gray-to-binary conversion requires each bit to be handled one at a time, faster algorithms exist. [ 60 ] [ 55 ] [ nb 1 ]
On newer processors, the number of ALU instructions in the decoding step can be reduced by taking advantage of the CLMUL instruction set . If MASK is the constant binary string of ones ended with a single zero digit, then carryless multiplication of MASK with the grey encoding of x will always give either x or its bitwise negation.
In practice, "Gray code" almost always refers to a binary-reflected Gray code (BRGC). However, mathematicians have discovered other kinds of Gray codes. Like BRGCs, each consists of a list of words, where each word differs from the next in only one digit (each word has a Hamming distance of 1 from the next word).
It is possible to construct binary Gray codes with n bits with a length of less than 2 n , if the length is even. One possibility is to start with a balanced Gray code and remove pairs of values at either the beginning and the end, or in the middle. [ 61 ] OEIS sequence A290772 [ 62 ] gives the number of possible Gray sequences of length 2 n that include zero and use the minimum number of bits.
0 → 000 1 → 001 2 → 002 10 → 012 11 → 011 12 → 010 20 → 020 21 → 021 22 → 022 100 → 122 101 → 121 102 → 120 110 → 110 111 → 111 112 → 112 120 → 102 121 → 101 122 → 100 200 → 200 201 → 201 202 → 202 210 → 212 211 → 211 212 → 210 220 → 220 221 → 221
There are many specialized types of Gray codes other than the binary-reflected Gray code. One such type of Gray code is the n -ary Gray code , also known as a non-Boolean Gray code . As the name implies, this type of Gray code uses non- Boolean values in its encodings.
For example, a 3-ary ( ternary ) Gray code would use the values 0,1,2. [ 31 ] The ( n , k )- Gray code is the n -ary Gray code with k digits. [ 63 ] The sequence of elements in the (3, 2)-Gray code is: 00,01,02,12,11,10,20,21,22. The ( n , k )-Gray code may be constructed recursively, as the BRGC, or may be constructed iteratively . An algorithm to iteratively generate the ( N , k )-Gray code is presented (in C ):
There are other Gray code algorithms for ( n , k )-Gray codes. The ( n , k )-Gray code produced by the above algorithm is always cyclical; some algorithms, such as that by Guan, [ 63 ] lack this property when k is odd. On the other hand, while only one digit at a time changes with this method, it can change by wrapping (looping from n − 1 to 0). In Guan's algorithm, the count alternately rises and falls, so that the numeric difference between two Gray code digits is always one.
Gray codes are not uniquely defined, because a permutation of the columns of such a code is a Gray code too. The above procedure produces a code in which the lower the significance of a digit, the more often it changes, making it similar to normal counting methods.
See also Skew binary number system , a variant ternary number system where at most two digits change on each increment, as each increment can be done with at most one digit carry operation.
Although the binary reflected Gray code is useful in many scenarios, it is not optimal in certain cases because of a lack of "uniformity". [ 52 ] In balanced Gray codes , the number of changes in different coordinate positions are as close as possible. To make this more precise, let G be an R -ary complete Gray cycle having transition sequence ( δ k ) {\displaystyle (\delta _{k})} ; the transition counts ( spectrum ) of G are the collection of integers defined by
λ k = | { j ∈ Z R n : δ j = k } | , for k ∈ Z n {\displaystyle \lambda _{k}=|\{j\in \mathbb {Z} _{R^{n}}:\delta _{j}=k\}|\,,{\text{ for }}k\in \mathbb {Z} _{n}}
A Gray code is uniform or uniformly balanced if its transition counts are all equal, in which case we have λ k = R n n {\displaystyle \lambda _{k}={\tfrac {R^{n}}{n}}} for all k . Clearly, when R = 2 {\displaystyle R=2} , such codes exist only if n is a power of 2. [ 64 ] If n is not a power of 2, it is possible to construct well-balanced binary codes where the difference between two transition counts is at most 2; so that (combining both cases) every transition count is either 2 ⌊ 2 n 2 n ⌋ {\displaystyle 2\left\lfloor {\tfrac {2^{n}}{2n}}\right\rfloor } or 2 ⌈ 2 n 2 n ⌉ {\displaystyle 2\left\lceil {\tfrac {2^{n}}{2n}}\right\rceil } . [ 52 ] Gray codes can also be exponentially balanced if all of their transition counts are adjacent powers of two, and such codes exist for every power of two. [ 65 ]
For example, a balanced 4-bit Gray code has 16 transitions, which can be evenly distributed among all four positions (four transitions per position), making it uniformly balanced: [ 52 ]
whereas a balanced 5-bit Gray code has a total of 32 transitions, which cannot be evenly distributed among the positions. In this example, four positions have six transitions each, and one has eight: [ 52 ]
We will now show a construction [ 66 ] and implementation [ 67 ] for well-balanced binary Gray codes which allows us to generate an n -digit balanced Gray code for every n . The main principle is to inductively construct an ( n + 2)-digit Gray code G ′ {\displaystyle G'} given an n -digit Gray code G in such a way that the balanced property is preserved. To do this, we consider partitions of G = g 0 , … , g 2 n − 1 {\displaystyle G=g_{0},\ldots ,g_{2^{n}-1}} into an even number L of non-empty blocks of the form
{ g 0 } , { g 1 , … , g k 2 } , { g k 2 + 1 , … , g k 3 } , … , { g k L − 2 + 1 , … , g − 2 } , { g − 1 } {\displaystyle \left\{g_{0}\right\},\left\{g_{1},\ldots ,g_{k_{2}}\right\},\left\{g_{k_{2}+1},\ldots ,g_{k_{3}}\right\},\ldots ,\left\{g_{k_{L-2}+1},\ldots ,g_{-2}\right\},\left\{g_{-1}\right\}}
where k 1 = 0 {\displaystyle k_{1}=0} , k L − 1 = − 2 {\displaystyle k_{L-1}=-2} , and k L ≡ − 1 ( mod 2 n ) {\displaystyle k_{L}\equiv -1{\pmod {2^{n}}}} ). This partition induces an ( n + 2 ) {\displaystyle (n+2)} -digit Gray code given by
If we define the transition multiplicities
m i = | { j : δ k j = i , 1 ≤ j ≤ L } | {\displaystyle m_{i}=\left|\left\{j:\delta _{k_{j}}=i,1\leq j\leq L\right\}\right|}
to be the number of times the digit in position i changes between consecutive blocks in a partition, then for the ( n + 2)-digit Gray code induced by this partition the transition spectrum λ i ′ {\displaystyle \lambda '_{i}} is
λ i ′ = { 4 λ i − 2 m i , if 0 ≤ i < n L , otherwise {\displaystyle \lambda '_{i}={\begin{cases}4\lambda _{i}-2m_{i},&{\text{if }}0\leq i<n\\L,&{\text{ otherwise }}\end{cases}}}
The delicate part of this construction is to find an adequate partitioning of a balanced n -digit Gray code such that the code induced by it remains balanced, but for this only the transition multiplicities matter; joining two consecutive blocks over a digit i {\displaystyle i} transition and splitting another block at another digit i {\displaystyle i} transition produces a different Gray code with exactly the same transition spectrum λ i ′ {\displaystyle \lambda '_{i}} , so one may for example [ 65 ] designate the first m i {\displaystyle m_{i}} transitions at digit i {\displaystyle i} as those that fall between two blocks. Uniform codes can be found when R ≡ 0 ( mod 4 ) {\displaystyle R\equiv 0{\pmod {4}}} and R n ≡ 0 ( mod n ) {\displaystyle R^{n}\equiv 0{\pmod {n}}} , and this construction can be extended to the R -ary case as well. [ 66 ]
Long run (or maximum gap ) Gray codes maximize the distance between consecutive changes of digits in the same position. That is, the minimum run-length of any bit remains unchanged for as long as possible. [ 68 ]
Monotonic codes are useful in the theory of interconnection networks, especially for minimizing dilation for linear arrays of processors. [ 69 ] If we define the weight of a binary string to be the number of 1s in the string, then although we clearly cannot have a Gray code with strictly increasing weight, we may want to approximate this by having the code run through two adjacent weights before reaching the next one.
We can formalize the concept of monotone Gray codes as follows: consider the partition of the hypercube Q n = ( V n , E n ) {\displaystyle Q_{n}=(V_{n},E_{n})} into levels of vertices that have equal weight, i.e.
V n ( i ) = { v ∈ V n : v has weight i } {\displaystyle V_{n}(i)=\{v\in V_{n}:v{\text{ has weight }}i\}}
for 0 ≤ i ≤ n {\displaystyle 0\leq i\leq n} . These levels satisfy | V n ( i ) | = ( n i ) {\displaystyle |V_{n}(i)|=\textstyle {\binom {n}{i}}} . Let Q n ( i ) {\displaystyle Q_{n}(i)} be the subgraph of Q n {\displaystyle Q_{n}} induced by V n ( i ) ∪ V n ( i + 1 ) {\displaystyle V_{n}(i)\cup V_{n}(i+1)} , and let E n ( i ) {\displaystyle E_{n}(i)} be the edges in Q n ( i ) {\displaystyle Q_{n}(i)} . A monotonic Gray code is then a Hamiltonian path in Q n {\displaystyle Q_{n}} such that whenever δ 1 ∈ E n ( i ) {\displaystyle \delta _{1}\in E_{n}(i)} comes before δ 2 ∈ E n ( j ) {\displaystyle \delta _{2}\in E_{n}(j)} in the path, then i ≤ j {\displaystyle i\leq j} .
An elegant construction of monotonic n -digit Gray codes for any n is based on the idea of recursively building subpaths P n , j {\displaystyle P_{n,j}} of length 2 ( n j ) {\displaystyle 2\textstyle {\binom {n}{j}}} having edges in E n ( j ) {\displaystyle E_{n}(j)} . [ 69 ] We define P 1 , 0 = ( 0 , 1 ) {\displaystyle P_{1,0}=({\mathtt {0}},{\mathtt {1}})} , P n , j = ∅ {\displaystyle P_{n,j}=\emptyset } whenever j < 0 {\displaystyle j<0} or j ≥ n {\displaystyle j\geq n} , and
P n + 1 , j = 1 P n , j − 1 π n , 0 P n , j {\displaystyle P_{n+1,j}={\mathtt {1}}P_{n,j-1}^{\pi _{n}},{\mathtt {0}}P_{n,j}}
otherwise. Here, π n {\displaystyle \pi _{n}} is a suitably defined permutation and P π {\displaystyle P^{\pi }} refers to the path P with its coordinates permuted by π {\displaystyle \pi } . These paths give rise to two monotonic n -digit Gray codes G n ( 1 ) {\displaystyle G_{n}^{(1)}} and G n ( 2 ) {\displaystyle G_{n}^{(2)}} given by
G n ( 1 ) = P n , 0 P n , 1 R P n , 2 P n , 3 R ⋯ and G n ( 2 ) = P n , 0 R P n , 1 P n , 2 R P n , 3 ⋯ {\displaystyle G_{n}^{(1)}=P_{n,0}P_{n,1}^{R}P_{n,2}P_{n,3}^{R}\cdots {\text{ and }}G_{n}^{(2)}=P_{n,0}^{R}P_{n,1}P_{n,2}^{R}P_{n,3}\cdots }
The choice of π n {\displaystyle \pi _{n}} which ensures that these codes are indeed Gray codes turns out to be π n = E − 1 ( π n − 1 2 ) {\displaystyle \pi _{n}=E^{-1}\left(\pi _{n-1}^{2}\right)} . The first few values of P n , j {\displaystyle P_{n,j}} are shown in the table below.
These monotonic Gray codes can be efficiently implemented in such a way that each subsequent element can be generated in O ( n ) time. The algorithm is most easily described using coroutines .
Monotonic codes have an interesting connection to the Lovász conjecture , which states that every connected vertex-transitive graph contains a Hamiltonian path. The "middle-level" subgraph Q 2 n + 1 ( n ) {\displaystyle Q_{2n+1}(n)} is vertex-transitive (that is, its automorphism group is transitive, so that each vertex has the same "local environment" and cannot be differentiated from the others, since we can relabel the coordinates as well as the binary digits to obtain an automorphism ) and the problem of finding a Hamiltonian path in this subgraph is called the "middle-levels problem", which can provide insights into the more general conjecture. The question has been answered affirmatively for n ≤ 15 {\displaystyle n\leq 15} , and the preceding construction for monotonic codes ensures a Hamiltonian path of length at least 0.839 N , where N is the number of vertices in the middle-level subgraph. [ 70 ]
Another type of Gray code, the Beckett–Gray code , is named for Irish playwright Samuel Beckett , who was interested in symmetry . His play " Quad " features four actors and is divided into sixteen time periods. Each period ends with one of the four actors entering or leaving the stage. The play begins and ends with an empty stage, and Beckett wanted each subset of actors to appear on stage exactly once. [ 71 ] Clearly the set of actors currently on stage can be represented by a 4-bit binary Gray code. Beckett, however, placed an additional restriction on the script: he wished the actors to enter and exit so that the actor who had been on stage the longest would always be the one to exit. The actors could then be represented by a first in, first out queue , so that (of the actors onstage) the actor being dequeued is always the one who was enqueued first. [ 71 ] Beckett was unable to find a Beckett–Gray code for his play, and indeed, an exhaustive listing of all possible sequences reveals that no such code exists for n = 4. It is known today that such codes do exist for n = 2, 5, 6, 7, and 8, and do not exist for n = 3 or 4. An example of an 8-bit Beckett–Gray code can be found in Donald Knuth 's Art of Computer Programming . [ 13 ] According to Sawada and Wong, the search space for n = 6 can be explored in 15 hours, and more than 9500 solutions for the case n = 7 have been found. [ 72 ]
Snake-in-the-box codes, or snakes , are the sequences of nodes of induced paths in an n -dimensional hypercube graph , and coil-in-the-box codes, [ 73 ] or coils , are the sequences of nodes of induced cycles in a hypercube. Viewed as Gray codes, these sequences have the property of being able to detect any single-bit coding error. Codes of this type were first described by William H. Kautz in the late 1950s; [ 5 ] since then, there has been much research on finding the code with the largest possible number of codewords for a given hypercube dimension.
Yet another kind of Gray code is the single-track Gray code (STGC) developed by Norman B. Spedding [ 74 ] [ 75 ] and refined by Hiltgen, Paterson and Brandestini in Single-track Gray Codes (1996). [ 76 ] [ 77 ] The STGC is a cyclical list of P unique binary encodings of length n such that two consecutive words differ in exactly one position, and when the list is examined as a P × n matrix , each column is a cyclic shift of the first column. [ 78 ]
The name comes from their use with rotary encoders , where a number of tracks are being sensed by contacts, resulting for each in an output of 0 or 1 . To reduce noise due to different contacts not switching at exactly the same moment in time, one preferably sets up the tracks so that the data output by the contacts are in Gray code. To get high angular accuracy, one needs lots of contacts; in order to achieve at least 1° accuracy, one needs at least 360 distinct positions per revolution, which requires a minimum of 9 bits of data, and thus the same number of contacts.
If all contacts are placed at the same angular position, then 9 tracks are needed to get a standard BRGC with at least 1° accuracy. However, if the manufacturer moves a contact to a different angular position (but at the same distance from the center shaft), then the corresponding "ring pattern" needs to be rotated the same angle to give the same output. If the most significant bit (the inner ring in Figure 1) is rotated enough, it exactly matches the next ring out. Since both rings are then identical, the inner ring can be cut out, and the sensor for that ring moved to the remaining, identical ring (but offset at that angle from the other sensor on that ring). Those two sensors on a single ring make a quadrature encoder. That reduces the number of tracks for a "1° resolution" angular encoder to 8 tracks. Reducing the number of tracks still further cannot be done with BRGC.
For many years, Torsten Sillke [ 79 ] and other mathematicians believed that it was impossible to encode position on a single track such that consecutive positions differed at only a single sensor, except for the 2-sensor, 1-track quadrature encoder. So for applications where 8 tracks were too bulky, people used single-track incremental encoders (quadrature encoders) or 2-track "quadrature encoder + reference notch" encoders.
Norman B. Spedding, however, registered a patent in 1994 with several examples showing that it was possible. [ 74 ] Although it is not possible to distinguish 2 n positions with n sensors on a single track, it is possible to distinguish close to that many. Etzion and Paterson conjecture that when n is itself a power of 2, n sensors can distinguish at most 2 n − 2 n positions and that for prime n the limit is 2 n − 2 positions. [ 80 ] The authors went on to generate a 504-position single track code of length 9 which they believe is optimal. Since this number is larger than 2 8 = 256, more than 8 sensors are required by any code, although a BRGC could distinguish 512 positions with 9 sensors.
An STGC for P = 30 and n = 5 is reproduced here:
Each column is a cyclic shift of the first column, and from any row to the next row only one bit changes. [ 81 ] The single-track nature (like a code chain) is useful in the fabrication of these wheels (compared to BRGC), as only one track is needed, thus reducing their cost and size.
The Gray code nature is useful (compared to chain codes , also called De Bruijn sequences ), as only one sensor will change at any one time, so the uncertainty during a transition between two discrete states will only be plus or minus one unit of angular measurement the device is capable of resolving. [ 82 ]
Since this 30 degree example was added, there has been a lot of interest in examples with higher angular resolution. In 2008, Gary Williams, [ 83 ] [ user-generated source? ] based on previous work, [ 80 ] discovered a 9-bit single track Gray code that gives a 1 degree resolution. This Gray code was used to design an actual device which was published on the site Thingiverse . This device [ 84 ] was designed by etzenseep (Florian Bauer) in September 2022.
An STGC for P = 360 and n = 9 is reproduced here:
Two-dimensional Gray codes are used in communication to minimize the number of bit errors in quadrature amplitude modulation (QAM) adjacent points in the constellation . In a typical encoding the horizontal and vertical adjacent constellation points differ by a single bit, and diagonal adjacent points differ by 2 bits. [ 85 ]
Two-dimensional Gray codes also have uses in location identifications schemes, where the code would be applied to area maps such as a Mercator projection of the earth's surface and an appropriate cyclic two-dimensional distance function such as the Mannheim metric be used to calculate the distance between two encoded locations, thereby combining the characteristics of the Hamming distance with the cyclic continuation of a Mercator projection. [ 86 ]
If a subsection of a specific codevalue is extracted from that value, for example the last 3 bits of a 4-bit Gray code, the resulting code will be an "excess Gray code". This code shows the property of counting backwards in those extracted bits if the original value is further increased. Reason for this is that Gray-encoded values do not show the behaviour of overflow, known from classic binary encoding, when increasing past the "highest" value.
Example: The highest 3-bit Gray code, 7, is encoded as (0)100. Adding 1 results in number 8, encoded in Gray as 1100. The last 3 bits do not overflow and count backwards if you further increase the original 4 bit code.
When working with sensors that output multiple, Gray-encoded values in a serial fashion, one should therefore pay attention whether the sensor produces those multiple values encoded in 1 single Gray code or as separate ones, as otherwise the values might appear to be counting backwards when an "overflow" is expected.
The bijective mapping { 0 ↔ 00 , 1 ↔ 01 , 2 ↔ 11 , 3 ↔ 10 } establishes an isometry between the metric space over the finite field Z 2 2 {\displaystyle \mathbb {Z} _{2}^{2}} with the metric given by the Hamming distance and the metric space over the finite ring Z 4 {\displaystyle \mathbb {Z} _{4}} (the usual modular arithmetic ) with the metric given by the Lee distance . The mapping is suitably extended to an isometry of the Hamming spaces Z 2 2 m {\displaystyle \mathbb {Z} _{2}^{2m}} and Z 4 m {\displaystyle \mathbb {Z} _{4}^{m}} . Its importance lies in establishing a correspondence between various "good" but not necessarily linear codes as Gray-map images in Z 2 2 {\displaystyle \mathbb {Z} _{2}^{2}} of ring-linear codes from Z 4 {\displaystyle \mathbb {Z} _{4}} . [ 87 ] [ 88 ]
There are a number of binary codes similar to Gray codes, including:
The following binary-coded decimal (BCD) codes are Gray code variants as well: | https://en.wikipedia.org/wiki/Leslie–Russell_code |
The less-than sign is a mathematical symbol that denotes an inequality between two values. The widely adopted form of two equal-length strokes connecting in an acute angle at the left, < , has been found in documents dated as far back as the 1560s. In mathematical writing, the less-than sign is typically placed between two values being compared and signifies that the first number is less than the second number. Examples of typical usage include 1 < 4 and −2 < 0 .
Since the development of computer programming languages , the less-than sign and the greater-than sign have been repurposed for a range of uses and operations.
The less-than sign , < , is an original ASCII character (hex 3C, decimal 60).
In BASIC , Lisp -family languages, and C -family languages (including Java and C++ ), comparison operator < means "less than".
In Coldfusion , operator .lt. means "less than".
In Fortran , operator .LT. means "less than"; later versions allow < .
In Bourne shell (and many other shells), operator -lt means "less than". Less-than sign is used to redirect input from a file. Less-than plus ampersand ( <& ) is used to redirect from a file descriptor .
The double less-than sign , << , may be used for an approximation of the much-less-than sign ( ≪ ) or of the opening guillemet ( « ). ASCII does not encode either of these signs, though they are both included in Unicode .
In Bash , Perl , and Ruby , operator <<EOF (where "EOF" is an arbitrary string, but commonly "EOF" denoting "end of file") is used to denote the beginning of a here document .
In C and C++ , operator << represents a binary left shift .
In the C++ Standard Library , operator << , when applied on an output stream, acts as insertion operator and performs an output operation on the stream.
In Ruby , operator << acts as append operator when used between an array and the value to be appended.
In XPath the << operator returns true if the left operand precedes the right operand in document order; otherwise it returns false. [ 1 ]
In PHP , operator <<<OUTPUT is used to denote the beginning of a heredoc statement (where OUTPUT is an arbitrary named variable.)
In Bash, <<<word is used as a "here string", where word is expanded and supplied to the command on its standard input, similar to a heredoc.
The less-than sign with the equals sign, <= , may be used for an approximation of the less-than-or-equal-to sign , ≤ . ASCII does not have a less-than-or-equal-to sign, but Unicode defines it at code point U+2264.
In BASIC , Lisp -family languages, and C -family languages (including Java and C++ ), operator <= means "less than or equal to". In Sinclair BASIC it is encoded as a single-byte code point token.
In Prolog , =< means "less than or equal to" (as distinct from the arrow <= ).
In Fortran , operators .LE. and <= both mean "less than or equal to".
In Bourne shell and Windows PowerShell , the operator -le means "less than or equal to".
In the R programming language , the less-than sign is used in conjunction with a hyphen-minus to create an arrow ( <- ), this can be used as the left assignment operator.
The less-than sign is used in the spaceship operator .
In HTML (and SGML and XML ), the less-than sign is used at the beginning of tags. The less-than sign may be included with < . The less-than-or-equal-to sign, ≤ , may be included with ≤ .
Unicode provides various less than symbols: [ 2 ]
The less-than sign may be seen for an approximation of the opening angle bracket , ⟨ . True angle bracket characters, as required in linguistics notation , are expected in formal texts.
In an inequality, the less-than sign and greater-than sign always "point" to the smaller number. Put another way, the "jaws" (the wider section of the symbol) always direct to the larger number.
The less-than-sign is sometimes used to represent a total order , partial order or preorder . However, the symbol ≺ {\displaystyle \prec } is often used when it would be confusing or not convenient to use < . In mathematical writing using LaTeX , the TeX command is \prec . The Unicode code point is U+227A ≺ PRECEDES . | https://en.wikipedia.org/wiki/Less-than_sign |
LessWrong (also written Less Wrong ) is a community blog and forum focused on discussion of cognitive biases , philosophy , psychology , economics , rationality , and artificial intelligence , among other topics. [ 1 ] [ 2 ] It is associated with the rationalist community .
LessWrong describes itself as an online forum and community aimed at improving human reasoning, rationality, and decision-making, with the goal of helping its users hold more accurate beliefs and achieve their personal objectives. [ 3 ] The best known posts of LessWrong are "The Sequences", a series of essays which aim to describe how to avoid the typical failure modes of human reasoning with the goal of improving decision-making and the evaluation of evidence. [ 4 ] [ 5 ] One suggestion is the use of Bayes' theorem as a decision-making tool. [ 2 ] There is also a focus on psychological barriers that prevent good decision-making, including fear conditioning and cognitive biases that have been studied by the psychologist Daniel Kahneman . [ 6 ]
LessWrong is additionally concerned with artificial intelligence, transhumanism , existential threats , and the singularity . The New York Observer in 2012 noted that "Despite describing itself as a forum on 'the art of human rationality,' the New York Less Wrong group ... is fixated on a branch of futurism that would seem more at home in a 3D multiplex than a graduate seminar: the dire existential threat—or, with any luck, utopian promise—known as the technological Singularity ... Branding themselves as 'rationalists,' as the Less Wrong crew has done, makes it a lot harder to dismiss them as a ' doomsday cult '." [ 7 ]
LessWrong developed from Overcoming Bias , an earlier group blog focused on human rationality, which began in November 2006, with artificial intelligence researcher Eliezer Yudkowsky and economist Robin Hanson as the principal contributors. In February 2009, Yudkowsky's posts were used as the seed material to create the community blog LessWrong , and Overcoming Bias became Hanson's personal blog. [ 8 ] In 2013, a significant portion of the rationalist community shifted focus to Scott Alexander's Slate Star Codex . [ 4 ]
Discussions of AI within LessWrong include AI alignment , AI safety , [ 9 ] and machine consciousness . [ citation needed ] Articles posted on LessWrong about AI have been cited in the news media. [ 9 ] [ 10 ] LessWrong, and its surrounding movement work on AI are the subjects of the 2019 book The AI Does Not Hate You , written by former BuzzFeed science correspondent Tom Chivers. [ 11 ] [ 12 ] [ 13 ]
LessWrong played a significant role in the development of the effective altruism (EA) movement, [ 14 ] and the two communities are closely intertwined. [ 15 ] : 227 In a survey of LessWrong users in 2016, 664 out of 3,060 respondents, or 21.7%, identified as "effective altruists". A separate survey of effective altruists in 2014 revealed that 31% of respondents had first heard of EA through LessWrong , [ 15 ] though that number had fallen to 8.2% by 2020. [ 16 ]
In July 2010, LessWrong contributor Roko posted a thought experiment to the site in which an otherwise benevolent future AI system tortures people who heard of the AI before it came into existence and failed to work tirelessly to bring it into existence, in order to incentivise said work. This idea came to be known as " Roko's basilisk ", based on Roko's idea that merely hearing about the idea would give the hypothetical AI system an incentive to try such blackmail . [ 17 ] [ 18 ] [ 7 ]
After LessWrong split from Overcoming Bias , it attracted some individuals affiliated with neoreaction with discussions of eugenics and evolutionary psychology . [ 19 ] However, Yudkowsky has strongly rejected neoreaction. [ 20 ] [ 21 ] Additionally, in a survey among LessWrong users in 2016, only 28 out of 3060 respondents (0.92%) identified as "neoreactionary". [ 22 ]
According to the Community Survey 2023 , conducted among 558 users of the forum, the user base consists of 75% cis males and 9.6% cis females , with the rest describing themselves as trans or non-binary . Users are in most cases between 20 and 35 years old. Almost half of the users are from the United States and most of the remainder are from Western Europe or Canada . The ethnic makeup was 78.9% non-Hispanic White , 4.9% East Asian , 4.2% South Asian , 3.6% white Hispanic , 2.6% Middle Eastern , 0.7% Black and 5.1% others. LessWrong users are highly educated (with the majority having at least a Bachelor's degree ) and work primarily in IT , engineering or other STEM fields . A majority of 67% describe themselves as atheists and only 3.7% as convinced theists . In terms of political orientation, the most frequently mentioned answers were liberal (32.3%), libertarian (25.2%) and social democratic (22.3%). [ 23 ]
LessWrong has been associated with several influential contributors. Founder Eliezer Yudkowsky established the platform to promote rationality and raise awareness about potential risks associated with artificial intelligence. [ 24 ] Scott Alexander became one of the site's most popular writers before starting his own blog, Slate Star Codex, contributing discussions on AI safety and rationality. [ 24 ]
Further notable users on LessWrong include Paul Christiano , Wei Dai and Zvi Mowshowitz . A selection of posts by these and other contributors, selected through a community review process, [ 25 ] were published as parts of the essay collections "A Map That Reflects the Territory" [ 26 ] and "The Engines of Cognition". [ 27 ] [ 25 ] [ 28 ]
The Zizians formed within the community surrounding LessWrong , with many members, including founder Ziz LaSota, commenting frequently on the site. They were eventually banned from LessWrong and associated meetups and conferences due to an alleged pattern of aggressive behavior. [ 29 ] | https://en.wikipedia.org/wiki/LessWrong |
The Lessepsian migration (or Erythrean invasion ) is the migration of marine species along the Suez Canal , usually from the Red Sea to the Mediterranean Sea , and more rarely in the opposite direction. When the canal was completed in 1869, fish , crustaceans , mollusks , and other marine animals and plants were exposed to an artificial passage between the two naturally separate bodies of water, and cross-contamination was made possible between formerly isolated ecosystems . The phenomenon is still occurring today. It is named after Ferdinand de Lesseps , the French diplomat in charge of the canal's construction. The term was coined by Francis Dov Por in his 1978 book. [ 1 ]
The migration of invasive species through the Suez Canal from the Indo-Pacific region has been facilitated by many factors, both abiotic and anthropogenic , and presents significant implications for the ecological health and economic stability of the contaminated areas; of particular concern is the fisheries industry in the Eastern Mediterranean . Despite these threats, the phenomenon has allowed scientists to study an invasive event on a large scale in a short period of time, which usually takes hundreds of years in natural conditions.
The opening of the Suez Canal created the first saltwater passage between the Mediterranean Sea and the Red Sea. Constructed in 1869 to provide a more direct trade route from Europe to India and the Far East , the canal is 162.5 km (101.0 mi) long, with a depth of 10–15 m (33–49 ft) and a width varying between 200 and 300 m (660 and 980 ft). [ 2 ]
Because the surface of the Red Sea is slightly higher in elevation than the eastern Mediterranean, the canal serves as a tidal strait by which Red Sea water pours into the Mediterranean. The Bitter Lakes , which are natural hypersaline lakes that form part of the canal, blocked the migration of Red Sea species into the Mediterranean for many decades, but as the salinity of the lakes gradually equalized with that of the Red Sea, the barrier to migration was removed, and plants and animals from the Red Sea began to colonize the eastern Mediterranean. [ 3 ] The Red Sea, an extension of the Indian Ocean , is generally saltier and less nutrient-rich than the Mediterranean, an extension of the Atlantic Ocean , so Red Sea species, able to tolerate harsh environments, have advantages over Atlantic species in the conditions of the Eastern Mediterranean. Accordingly, most migrations between the two bodies of water are invasions of Red Sea species into the Mediterranean, and relatively few migrations occur in the opposite direction. The construction of the Aswan High Dam across the Nile River in the 1960s reduced the inflow of fresh water and nutrient-rich silt from the Nile into the eastern Mediterranean, making conditions in the eastern Mediterranean even more like those of the Red Sea, thereby increasing the impact of the invasions and facilitating the occurrence of new ones. [ 3 ]
The Red Sea is a profusely abundant tropical marine environment sharing species in common with the eastern Indo-Pacific region , while the Mediterranean is a temperate sea with much lower productivity; the two ecosystems are extremely different in terms of structure and ecology. [ 2 ] The Suez Canal quickly became the main pathway for the introduction of invasive species into the Eastern Mediterranean, having zoogeographic and ecological consequences far beyond what the designers foresaw. The Lessepsian migration includes hundreds of Red Sea and Indo-Pacific species that have colonized and established themselves in the Eastern Mediterranean system, causing biogeographic changes without precedent in human memory. [ 4 ] The trend is accelerating: to take just the fish, a long-term cross-Basin survey engaged by the Mediterranean Science Commission recently documented that in the first twenty years of our century more fish species from the Indo-Pacific Ocean had reached the Mediterranean than during the entire 20th century. [ 5 ]
As of about 2010, over 1,000 species — both vertebrates and invertebrates — native to the Red Sea had been identified in the Mediterranean Sea. It was thought that many others were as yet unidentified. From there they have spread even further afield, supplying 95% of Indo-Pacific species that have reached the Ponto-Caspian seas and increasingly rapidly. [ 6 ] In the late 20th and early 21st centuries, the Egyptian government announced its intentions to deepen and widen the canal, which raised concerns from marine biologists , fearing this would facilitate the crossing of the canal for additional species, accelerating the invasion of Red Sea species into the Mediterranean. [ 7 ] The extension was completed in 2015.
A wide-ranging species in the eastern Atlantic and Mediterranean, the meagre Argyrosomus regius is a species indigenous to the Eastern Mediterranean and was one of the most common commercial fish in the Levant . It has since disappeared from local catches, while the narrow-barred Spanish mackerel Scomberomorus commerson , a known Lessepsian migrant, has dramatically increased in population. Studies performed on this occurrence conclude that, due to similar life histories and diets, this may be an example of an invasive migrant outcompeting a native species and occupying its niche . [ 4 ]
Eight species of invasive prawns from the Erythraean Sea have been recorded in the Eastern Mediterranean. These prawns are considered highly prized in Levantine fisheries, and compose most of the prawn catch off the Mediterranean coast of Egypt, being 6% of total Egyptian landings. This high abundance of invasive prawns has led to the decline of a native penaeid prawn, Melicertus kerathurus , which supported a commercial Israeli fishery throughout the 1950s. Due to outcompetition and its habitat being overrun by these migrants, this native species has since disappeared, with resultant detrimental impacts on the commercial fishery. [ 9 ]
The invasion of new Red Sea species into the Mediterranean has facilitated the invasion of their associated parasites, for example the copepod Eudactylera aspera , which was found on a spinner shark, Carcharhinus brevipinna , taken off the coast of Tunisia . The copepod had originally been described from specimens taken from C. brevipinna off Madagascar and its finding in the Mediterranean has arguably confirmed the previously disputed status of C. brevipinna as a Lessepsian migrant. In addition, parasites originating in the Red Sea have shown an ability to use related native Mediterranean fish species as alternative hosts ; e.g. the copepod Nipergasilus bora was known to parasitise the grey mullets Mugil cephalus and Liza carinata in the Red Sea, both taxa having been recorded as Lessepsian migrants, and was subsequently found parasitising the native Mediterranean mullets Chelon aurata and Chelon labrosus . [ 10 ]
Sometimes, the invasion of parasites may reduce the competitive advantages that Red Sea invaders have in the Mediterranean. For example, the Indo-Pacific swimming crab Charybdis longicollis was first recorded in the Mediterranean in the mid-1950s and became dominant in silty and sandy substrates off the coast of Israel, making up to 70% of the total biomass in these habitats. Until 1992, none of the specimens collected was infected with the parasite Heterosaccus dollfusi , but in that year, a few infected crabs were collected. The parasite is a barnacle which desexes its host . Within three years, 77% of the crabs collected in Haifa Bay were infected, and the parasite had spread to southern Turkey . This rapid increase and high infection rate is attributed to the extremely high population density of the host and the year-round reproduction of the parasite. One effect of this was that the population of the Mediterranean native swimming crab Liocarcinus vernalis recovered somewhat. [ 11 ]
Fisheries have been heavily affected. The goldband goatfish, Upeneus moluccensis , was first recorded in the Eastern Mediterranean in the 1930s and has since established an abundant population. Following the warm winter of 1954–1955, it increased to 83% of the Israeli catch, replacing the native red mullet , which affected the Egyptian fishery, being 3% of their total landings. [ 12 ] The high water temperatures of this unusually warm winter may have resulted in the poor survival of red mullet juveniles, which may have allowed the goatfish population to expand into the opened niche. [ 9 ] Native mullet have since been displaced into deeper, cooler waters, where Lessepsian migrants consist of only 20% of the catch, whereas in shallower, warmer waters, this invasive species takes up 87% of the catch. [ 9 ] From these data, the Lessepsian migrants apparently have not adapted to the more temperate environment of the deeper areas of the basin, but have established dominant populations in the habitats most similar to the tropical sea habitats from which they came. The population of Caesio varilineata (a fusilier fish, Caesionidae), recently reported from the eastern Mediterranean Sea , [ 13 ] may develop in a similar fashion. As of 2006 [update] along the Mediterranean coast of Israel, over half of trawl catches are Lessepsians. Worse, full substitution has not occurred – total fishery productivity has been reduced by the invaders. [ 14 ]
The marbled spinefoot ( Siganus rivulatus ) and dusky spinefoot ( Siganus luridus ), both indigenous Red Sea rabbitfish , were first recorded off the coast of Mandate Palestine in 1924. In only a few decades, these schooling, herbivorous fish were able to settle in a range of habitats forming abundant populations, to the extent that George and Athanassiou, in a paper published in 1967, reported: "The millions of young abound over rocky outcropping grazing on the relatively abundant early summer algal cover". [ 15 ] By 2004, a study on these species found that they comprise 80% of the abundance of herbivorous fish in the shallow coastal sites of Lebanon . [ 9 ] They have been able to create marked phase shifts within the food web on multiple levels. Prior to the arrival of these Lessepsian migrants, the herbivores filled a small ecological role within the Eastern Mediterranean system. Therefore, with such a high influx of herbivorous species in a small period of time, this phenomenon has normalised the food web , increasing the rate at which algae are consumed and serving as a major prey item for large predators. [ 9 ] Further, these Red Sea migrants are affecting fisheries by outcompeting native fish of high commercial value, such as the seabream Boops boops . [ 9 ] A nonindigenous species of mussel – Brachidontes pharaonis – from the Indo-Pacific has also proliferated. This mussel, which has a thicker shell than that of the native mussel, has created a change in predation patterns, since they are more difficult for predators to handle. [ 9 ]
Only a comparatively few species have colonised the Red Sea from the Mediterranean; these are called anti-Lessepsian migrants. As the predominant flow of the canal is from south to north, this acts against the southward movement of Mediterranean species, and as stated above, the Red Sea has higher salinity, fewer nutrients, and a much more diverse biota than the Eastern Mediterranean. Some of the anti-Lessepsian migrants such as the sea star Sphaerodiscus placenta are found only in specialised habitats such as the lagoon of El Bilaiyim, which lies 180 km (110 mi) south of the southern entrance to the Suez Canal, but is much more saline than the surrounding waters of the Gulf of Suez . [ 3 ]
The sea slug Biuve fulvipunctata was described from waters around Japan and is widespread in the eastern Indian Ocean and western Pacific. It was first identified in the Mediterranean in 1961, and was seen in the Red Sea in 2005, most likely as a result of anti-Lessepsian migration. [ 16 ] Among the fish species that have been confirmed as anti-Lessepsian migrants are peacock blenny ( Salaria pavo ), [ 17 ] Solea aegyptiaca , Mediterranean moray ( Muraena helena ), the rock goby ( Gobius paganellus ), [ 18 ] the meagre ( Argyrosomus regius ), [ 19 ] the comber ( Serranus cabrilla ), [ 20 ] European seabass ( Dicentrarchus labrax ), and spotted seabass ( Dicentrarchus punctatus ). [ 21 ]
The sea lamprey reached Lake Ontario from the Atlantic Ocean through shipping canals and was recorded for the first time in Lake Ontario in the 1830s, but Niagara Falls was a barrier to their further spread. The deepening of the Welland Canal in 1919 allowed the sea lamprey to bypass the barrier created by the falls, and by 1938, sea lampreys had been recorded in all of the Great Lakes . [ 22 ]
The alewife ( Alosa pseudoharengus ), a species of shad from the Western Atlantic, invaded the Great Lakes by using the Welland Canal to bypass Niagara Falls. They colonised the Great Lakes and became abundant mostly in Lake Huron and Lake Michigan , reaching their peak abundance by the 1950s and 1980s. [ 23 ] [ 24 ]
The white-eye bream ( Ballerus sapa ) has invaded the Vistula River basin by migrating along the Dnieper–Bug Canal in Belarus , which connects the Vistula drainage basin with that of the Dnieper River . [ 25 ]
A small number of species have used the Panama Canal to move from the Atlantic Ocean to the Pacific Ocean, and vice versa. Six species of Atlantic fish were recorded on the Pacific side of the canal, and three species of Pacific fish were found on the Atlantic side of the canal. The Atlantic fish included Lupinoblennius dispar , Hypleurochilus aequipinnis , Barbulifer ceuthoecus , Oostethus lineatus and Lophogobius cyprinoides , while the Pacific species moving to the Atlantic included Gnathanodon speciosus . The Gatun Lake 's freshwater environment forms a barrier to the interchange of marine species. [ 26 ] | https://en.wikipedia.org/wiki/Lessepsian_migration |
In anatomy the Lesser Triangle is a region contained within the Submandibular triangle . Its boundaries are the Hypoglossal Nerve , and the Anterior and Posterior belly of the Digastric muscle . This triangle was named after a German surgeon named Ladislaus Leon Lesser , who lived from 1846 to 1925 [ 1 ]
This human musculoskeletal system article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Lesser_Triangle |
In toxicology , the lethal dose ( LD ) is an indication of the lethal toxicity of a given substance or type of radiation . Because resistance varies from one individual to another, the "lethal dose" represents a dose (usually recorded as dose per kilogram of subject body weight) at which a given percentage of subjects will die. The lethal concentration is a lethal dose measurement used for gases or particulates. The LD may be based on the standard person concept, a theoretical individual that has perfectly "normal" characteristics, and thus not apply to all sub-populations.
The median lethal dose, LD 50 (abbreviation for "lethal dose, 50%"), LC 50 (lethal concentration, 50%) or LCt 50 (lethal concentration and time) of a toxin , radiation , or pathogen is the dose required to kill half the members of a tested population after a specified test duration. LD 50 figures are frequently used as a general indicator of a substance's acute toxicity . [ 1 ] A lower LD 50 is indicative of increased toxicity.
The test was created by J.W. Trevan in 1927. [ 2 ] The term "semilethal dose" is occasionally used with the same meaning, in particular in translations from non-English-language texts, but can also refer to a sub lethal dose; because of this ambiguity, it is usually avoided. LD 50 is usually determined by tests on animals such as laboratory mice . In 2011 the US Food and Drug Administration approved alternative methods to LD 50 for testing the cosmetic drug Botox without animal tests. [ 3 ]
The LD 50 is usually expressed as the mass of substance administered per unit mass of test subject, typically as milligrams of substance per kilogram of body mass, but stated as nanograms (suitable for botulinum ), micrograms, milligrams, or grams (suitable for paracetamol ) per kilogram. Stating it this way allows the relative toxicity of different substances to be compared, and normalizes for the variation in the size of the animals exposed, although toxicity does not always scale simply with body mass.
The choice of 50% lethality as a benchmark avoids the potential for ambiguity of making measurements in the extremes and reduces the amount of testing required. However, this also means that LD 50 is not the lethal dose for all subjects; some may be killed by much less, while others survive doses far higher than the LD 50 . Measures such as "LD 1 " and "LD 99 " (dosage required to kill 1% or 99%, respectively, of the test population) are occasionally used for specific purposes. [ 4 ]
Lethal dosage often varies depending on the method of administration ; for instance, many substances are less toxic when administered orally than when intravenously administered. For this reason, LD 50 figures are often qualified with the mode of administration, e.g., "LD 50 i.v."
The related quantities LD 50 /30 or LD 50 /60 are used to refer to a dose that without treatment will be lethal to 50% of the population within (respectively) 30 or 60 days. These measures are used more commonly with radiation , as survival beyond 60 days usually results in recovery.
LD values for humans are best estimated by extrapolating results from human cell cultures . One form of measuring LD is to use model organisms , particularly animals like mice or rats, converting to dosage per kilogram of biomass, and extrapolating to human norms. The degree of error from animal-extrapolated LD values is large. The biology of test animals differs in important aspects to that of humans. For instance, mouse tissue is approximately fifty times less responsive than human tissue to the venom of the Sydney funnel-web spider [ citation needed ] . The square–cube law also complicates the scaling relationships involved. Researchers are shifting away from animal-based LD measurements in some instances. The U.S. Food and Drug Administration has begun to approve more non-animal methods in response to animal welfare concerns. [ 5 ]
The median infective dose (ID 50 ) is the number of organisms received by a person or test animal qualified by the route of administration (e.g., 1,200 org/man per oral). Because of the difficulties in counting actual organisms in a dose, infective doses may be expressed in terms of biological assay, such as the number of LD 50 's to some test animal. In biological warfare infective dosage is the number of infective doses per minute for a cubic meter (e.g., ICt 50 is 100 medium doses - min/m 3 ).)
The lowest lethal dose (LD Lo ) is the least amount of drug that can produce death in a given animal species under controlled conditions. [ 6 ] [ 7 ] The dosage is given per unit of bodyweight (typically stated in milligrams per kilogram ) of a substance known to have resulted in fatality in a particular species. When quoting an LD Lo , the particular species and method of administration ( e.g. ingested, inhaled, intravenous ) are typically stated.
For gases and aerosols, lethal concentration (given in mg/m 3 or ppm, parts per million) is the analogous concept, although this also depends on the duration of exposure, which has to be included in the definition. The term incipient lethal level is used to describe a LC 50 value that is independent of time. [ 8 ]
A comparable measurement is LCt 50 , which relates to lethal dosage from exposure, where C is concentration and t is time. It is often expressed in terms of mg-min/m 3. LCt 50 is the dose that will cause incapacitation rather than death. These measures are commonly used to indicate the comparative efficacy of chemical warfare agents, and dosages are typically qualified by rates of breathing (e.g., resting = 10 L/min) for inhalation, or degree of clothing for skin penetration. The concept of Ct was first proposed by Fritz Haber and is sometimes referred to as Haber's law , which assumes that exposure to 1 minute of 100 mg/m 3 is equivalent to 10 minutes of 10 mg/m 3 (1 × 100 = 100, as does 10 × 10 = 100). [ citation needed ]
Some chemicals, such as hydrogen cyanide , are rapidly detoxified by the human body, and do not follow Haber's Law. So, in these cases, the lethal concentration may be given simply as LC 50 and qualified by a duration of exposure (e.g., 10 minutes). The material safety data sheets for toxic substances frequently use this form of the term even if the substance does follow Haber's Law. [ citation needed ]
The LC Lo is the lowest concentration of a chemical, given over a period of time, that results in the fatality of an individual animal. LC Lo is typically for an acute (<24 hour) exposure. [ 9 ] [ 10 ] It is related to the LC 50 , the median lethal concentration. The LC Lo is used for gases and aerosolized material. [ 11 ]
As a measure of toxicity, lethal dose is somewhat unreliable and results may vary greatly between testing facilities due to factors such as the genetic characteristics of the sample population, animal species tested, environmental factors and mode of administration. [ 12 ]
There can be wide variability between species as well; what is relatively safe for rats may very well be extremely toxic for humans ( cf. paracetamol toxicity ), and vice versa. For example, chocolate, comparatively harmless to humans, is known to be toxic to many animals . When used to test venom from venomous creatures, such as snakes , LD 50 results may be misleading due to the physiological differences between mice, rats, and humans. Many venomous snakes are specialized predators of mice, and their venom may be adapted specifically to incapacitate mice; and mongooses may be exceptionally resistant. While most mammals have a very similar physiology, LD 50 results may or may not have equal bearing upon every mammal species, including humans.
Animal-rights and animal-welfare groups, such as Animal Rights International, [ 13 ] have campaigned against LD 50 testing on animals in particular as, in the case of some substances, causing the animals to die slow, painful deaths. Several countries, including the UK , have taken steps to ban the oral LD 50 , and the Organisation for Economic Co-operation and Development (OECD) abolished the requirement for the oral test in 2001. [ 14 ] | https://en.wikipedia.org/wiki/Lethal_dose |
Lethal synthesis , or suicide metabolism , [ 1 ] is the biosynthesis of a toxin from a precursor which is not itself toxic, such as the synthesis of fluorocitrate from fluoroacetate or the synthesis of methylglyoxal from glycerol . [ 2 ] [ 3 ] [ 4 ]
The term was first publicised by Rudolph Peters in his Croonian Lecture of 1951. [ 5 ] [ 3 ] [ 6 ]
A 1971 study published by the Harvard Medical School identified methylglyoxal , a form of glycerol, as a product of lethal synthesis in a specific E.coli mutant . [ 4 ] In E.coli, the synthesis of triose phosphate from glycerol is a reaction regulated by the synthesis rate of glycerol kinase and by feedback inhibition by fructose-1,6-bisphosphate . [ 4 ] The study demonstrated that, in E.coli mutants that had lost both control mechanisms, glycerol kinase no longer reacted to feedback regulation and instead produced the cytotoxic methylglyoxal. [ 4 ] A more recent review of research done on methylglyoxal metabolism concluded that the compound's cytotoxic nature is dependent on its ability to form advanced glycation end products (AGEs). [ 7 ] These compounds, which are thought to be factors in ageing and in the progression of degenerative diseases , have been shown to hinder the functions of the proteins they target. [ 7 ] | https://en.wikipedia.org/wiki/Lethal_synthesis |
María Leticia Carigi Delgado is a Venezuelan astronomer specializing in cosmochemistry , including the overall metallicity of galaxies and galactic halos , [ 1 ] and the evolution of galaxies . [ 2 ] She works in Mexico as a researcher and professor in the Institute of Astronomy of the National Autonomous University of Mexico (UNAM).
Carigi earned master's and doctoral degrees in astronomy through research in Venezuela's Centro de Investigaciones de Astronomia . [ 1 ] She completed her Ph.D. in 1994, at the Central University of Venezuela , with the dissertation Evolución química de la vecindad solar con rendimientos químicos estelares dependientes de la metalicidad [ Chemical evolution of the solar neighborhood with stellar chemical yields dependant on metallicity ], supervised by Gustavo Ramón Bruzual Alfonso. [ 3 ]
She came to the UNAM Institute of Astronomy as a postdoctoral researcher, working with Manuel Peimbert , [ 1 ] and has been a research professor there since 1995. [ 4 ]
Carigi is a member of the Mexican Academy of Sciences . [ 2 ] In 2010 UNAM gave her their Sor Juana Ines de la Cruz prize. [ 1 ] | https://en.wikipedia.org/wiki/Leticia_Carigi |
Leticia González Herrero (born in Madrid) is a theoretical chemist, known for her work on molecular excited states, especially ultrafast dynamics of DNA nucleobases [ 1 ] and highly accurate simulations of transition metal complexes. [ 2 ]
Leticia González was born in Madrid , Spain and studied chemistry from 1989 to 1994 at the Autonomous University of Madrid . In 1995, she earned her master's degree from King's College London . She returned to Autonomous University of Madrid for her PhD , which she earned in 1998. [ 3 ] She then moved to the Free University of Berlin and completed her Habilitation in 2004. [ 4 ] In 2007, she was appointed Professor for Theoretical and Physical Chemistry at the University of Jena . In 2011, she became Full Professor for Computational Chemistry, Theoretical Chemistry and
Scientific Computing at the University of Vienna . [ 5 ] | https://en.wikipedia.org/wiki/Leticia_González |
Leticia Myriam Torres Guerra (born September 9, 1955) is a Mexican chemist.
Her research work focuses on the development and synthesis of advanced materials such as semiconductors and their application as powders and films in renewable energy and sustainable decontamination projects.
In 2005, she was appointed head of the Faculty of Civil Engineering's Department of Ecomaterials and Energy at the Autonomous University of Nuevo León (UANL). As of 2019, she is the general director of the Advanced Materials Research Center [ es ] .
Leticia Myriam Torres Guerra was born in Monterrey on September 9, 1955. [ 1 ] She graduated from UANL with a licentiate in industrial chemistry in 1976. She earned her doctorate in advanced ceramic materials at the University of Aberdeen in 1984. [ 1 ] In 1985, she began her work as a research professor at UANL's Faculty of Chemical Sciences, and went on to receive the university's research award 15 times by 2010. She became a Level 3 member of the Sistema Nacional de Investigadores in 1986, the only woman to do so for ten years. [ 1 ] [ 2 ] [ 3 ]
Other positions she has held are deputy director of research of the UANL Faculty of Chemical Sciences from 1995 to 2001, and deputy director of scientific and technological development of the National Council of Science and Technology (CONACYT) from 2011 to 2013. [ 1 ] [ 2 ] During 2014 and 2015 she was a certified leader in renewable energies and energy efficiency at Harvard University . [ 1 ] She has been a member of the Mexican Academy of Sciences since 1999, the Mexican Materials Society since 2009, and the International Union of Materials Research Societies since 2017. [ 4 ] She is on four committees of Mexico's Presidential Advisory Council of Sciences [ es ] . [ 1 ]
Torres founded the Center for Research and Development of Ceramic Materials (active from 1990 to 1995) at UANL's Faculty of Chemical Sciences. [ 5 ] She has carried out technological developments in collaboration with the industrial sector, including an agreement with the Vitro Group in 1996 to teach a master of science program with a specialty oriented to glass, and one with Cemex to implement a special UNI-EMPRESA scholarship program. [ 1 ] [ 6 ]
In 2019, she was named general director of the Advanced Materials Research Center [ es ] . [ 7 ]
Torres' work has focused on materials science; she began her research with the synthesis of advanced ceramic materials and crystal chemistry . [ 4 ] Her most notable scientific investigations have focused on the synthesis and modification of semiconductors such as titanates , tantalates , and zirconates of alkali and alkaline earth metals for decontamination of air, soil, and water through photocatalysis , as well as their use in hydrogen production. The materials developed in her work group have shown high photoelectrocatalytic efficiency, allowing the development of prototypes of an " artificial leaf " to transform solar energy into chemical energy. [ 1 ] | https://en.wikipedia.org/wiki/Leticia_Myriam_Torres_Guerra |
Letitia Eva Takyibea Obeng FGA (10 January 1925 – 23 March 2023) was the first Ghanaian woman to obtain a degree in zoology and the first to be awarded a doctorate . [ 1 ] She is described as "the grandmother of female scientists in Ghana". [ 2 ]
Letitia Obeng was born at Anum in the Eastern Region on 10 January 1925. She attended a primary school in Abetifi , Kwahu and a middle school in Kyebi . Between 1939 and 1946, she had her secondary school education at Achimota College . While at school she took the London University International Examination to continue her education, courtesy of a government scholarship at the University of Birmingham (1948–1952), where she was the only African female student on the Edgbaston campus. [ 3 ] She graduated from the university with a degree in Zoology. [ 4 ] In her autobiography, she describes her experience of coming to study in the United Kingdom in the post-war years, including the prejudices she faced. [ 3 ]
Letitia Obeng was the first Ghanaian woman to be awarded a Bachelor of Science degree in Zoology and Botany (1952), a Master of Science degree in Parasitology (1962) and a PhD in Tropical Medicine (1964). [ 5 ] Her Bachelor and Master of Science degrees were both awarded by the University of Birmingham and her PhD was awarded by the Liverpool School of Tropical Medicine , where she studied the black fly and its relevance to river blindness . [ 1 ] She became very familiar with the freshwater courses in North Wales during her PhD studies and often brought her three children, who were 8, 6 and 3 at the time, to take samples in the area's rivers and streams. [ 6 ]
After her university education in the United Kingdom, she returned to her homeland Ghana and lectured at the University College of Science and Technology now known as the Kwame Nkrumah University of Science and Technology between 1952 and 1959. [ 7 ] In 1952, Letitia Obeng became the first female scientist at the Kwame Nkrumah University of Science and Technology (KNUST) where her husband also worked as a lecturer. [1] After her husband's death in 1959, Letitia Obeng moved to the Council for Scientific and Industrial Research (CSIR) (formerly known as National Research Council of Ghana) and in 1964, she established the Institute of Aquatic Biology within the same institution for research on Ghana's huge manmade Volta Lake and its inland water system. [ 8 ] [ 6 ] Letitia Obeng was the first scientist to be employed by the National Research Council of Ghana. [ 7 ] In 1965, Letitia Obeng became a fellow of the Ghana Academy of Arts and Sciences and in 2006, she became the academy's first female president. [ 9 ] [ 10 ] In 1972, Dr. Obeng delivered the Caroline Haslett Memorial Lecture to the Royal Society for the Encouragement of Arts, Manufactures and Commerce . Her lecture was titled “Nation Building and the African Woman [ 11 ] ”. Also in 1972, she was an invited participant in the United Nations Human Environment Conference in Stockholm . In 1974, she began work as the Officer in the United Nations Environment Programme (UNEP) . In 1980, she became the Director of the UNEP Regional Office for Africa and UNEP's Representative to Africa. Elected the first woman to the Fellowship of the Ghana Academy of Arts and Sciences , in 2008, she was unanimously chosen to be its first female President. [ 6 ]
Obeng launched her first book - Anthology of a Lifetime in July 2019. [ 12 ] It is a selection from the distinguished scientist's talks, speeches, writings and publications produced during the last 60 years. [ 13 ]
Letitia Obeng's research and publication focus on the environment, health and science education particularly in Africa. Her doctoral research investigated the aquatic stages of the Simuliidae identified as a major transmitter of the parasite for river blindness . Related to this research are her articles titled “Life-history and population studies on the Simuliidae of North Wales” [ 14 ] and “The identification of the aquatic stages of the British Simuliidae”. [ 15 ] In a paper titled "Environmental of Impacts of Four African Impoundments”, [ 16 ] Dr. Obeng considers the environmental effects of four African dams: Lake Volta , Lake Kariba , Lake Kainji and Lake Nasser . Some of her other research and publications include:
Obeng was also the author of Obeng, Letitia E. (1997). Parasites, the Sly and Sneaky Enemies inside You . Goldsear. ISBN 978-9988010171 . , a book written mainly for a non-scientific audience. Besides her science-related publications, Letitia Obeng is also the author of Obeng, Letitia Eva (2008). A Silent Heritage: an Autobiography . Goldsear. ISBN 9789988098834 .
Obeng was the sister of the late Madam Theodosia Okoh , the designer of the Ghana flag . [ 17 ] Her father, Very Reverend E.V. Asihene, was the Moderator of the Presbyterian Church of Ghana and her mother's name was Dora Asihene. She was married to George A. Obeng who died in 1959. They had three kids (two boys and a girl). [ 2 ] [ 3 ] The British Organizational theorists, professor and author Edward David Asihene " Eddie" Obeng (born 1959) is one of Letitia Obeng's children.
Obeng died on 23 March 2023, at the age of 98. [ 18 ]
From 1992 to 1993, Obeng was a Distinguished International Visitor fellow at Radcliff College . In 1997, she received the CSIR Award for Distinguished Career and Service to Science and Technology, the first female to receive such an award. Additionally, the CSIR Laboratory (known as The Letitia Obeng Block) was named after her in 1997. [ 19 ] Letitia Obeng received Ghana's highest national award, Order of the Star of Ghana in 2006. In 2017, she received an honorary Doctor of Science degree from KNUST. [ 20 ] | https://en.wikipedia.org/wiki/Letitia_Obeng |
LetterWise and WordWise were predictive text entry systems developed by Eatoni Ergonomics (Eatoni) for handheld devices with ambiguous keyboards / keypads, typically non-smart traditional cellphones and portable devices with keypads. All patents covering those systems have expired. [ citation needed ] LetterWise used a prefix based predictive disambiguation method and can be demonstrated to have some advantages over the non-predictive Multi-tap technique that was in widespread use at the time that system was developed. WordWise was not a dictionary-based predictive system, but rather an extension of the LetterWise system to predict whole words from their linguistic components. It was designed to compete with dictionary-based predictive systems such as T9 and iTap which were commonly used with mobile phones with 12-key telephone keypads.
The court dismissed a claim that Eatoni Ergonomics came into being in the Spring 1998 as an orally agreed partnership between Howard Gutowitz, David A. Kosower and Eugene Skepner; the former pair having met as social acquaintances and Skepner noted for programming skills. [ 1 ] The Eatoni project had the objective of developing reduced size keypads for portable devices. [ 1 ] By August 1999 Kosower stopped working on the project due to a disagreements with Gutowitz over terms for setting up the new company and patents Gutowitz had or intended to file which was eventually to result in a subsequent lawsuit. [ 1 ] In September 1999 Gutowitz went on to form Delaware limited liability company , Eatoni Ergonomics LLC and on 16 February 2000 formed the Delaware Corporation Eatoni Ergonomics Inc. [ 1 ] with Gutowitz as CEO .
Eatoni composed a conference paper for March 2001 on Linguistically Optimized Text Entry on a Mobile Phone but it was not accepted. [ 2 ] [ 3 ]
In November 2001 at the 14th annual ACM symposium on User interface software and technology a paper prepared by academic Scott MacKenzie and Hedy Kober [ a ] supported by three from Eatomi including Skepner described experimental results comparing LetterWise against other schemes though notably WordWise was for whatever reason absent from the presentation despite being announced over a year previously. [ 4 ] [ 5 ]
By May 2002 Gutowitz admitted adoption by established cell phone manufactures was proving difficult although Benq was taking the technology. [ 6 ] [ 7 ] [ 8 ]
Eatoni was involved in a series of lawsuits and countersuits mobile phone manufacturer BlackBerry (RIM) between 2005 and 2012 relative to alleged patent infringement and a settlement to jointly develop software for a reduced keyboard in 2007 and take Eatoni equity stock in 2007. [ 9 ] [ 10 ] [ 11 ] [ 12 ]
In the 2010s Eatoni have examined applying the cellphone keytap technology to threatened languages, in particular N'ko ; Gutowitz said he had eventually given up trying to get it supported by cellphone manufactures and begun to trial native language applications instead. [ 13 ] [ 14 ] [ 15 ]
Unlike most if not all other predictive text entry systems, LetterWise does not depend on a work dictionary but is a prefix based predictive system. For each letter in the word the user taps the key associated with that letter on the keypad. If the letter chosen is the one required the user simply repeats the process for the next letter in the word, other Next is tapped until the required letter appears. It is claimed this is a very simple and efficient system to use, with no Multi-tap style time-outs or dictionary limitations. [ citation needed ] In an instruction manual it can be described in the following single sentence: " Hit the key with the letter you want, if it doesn't come up, hit Next until it does. ".
Letterwise is not designed to be eyes-free , that is the associated device display must be monitored to perform the next action. This contrasts to Multi-tap and some two key systems where some skilled and expert users are able to input using whilst not referring to the screen. [ 3 ]
A word such as mama would be more favourable to Multi-tap where 4 taps and no timeouts would be required; far less than the 14 taps and 1 timeout required for sirs .
Despite not included as a system keyboard, LetterWise was available in Email / Twitter / SMS / LiveJournal clients for Symbian, iOS as well as Qualcomm's BREW platform (distributed by the Verizon Wireless Get It Now service). [ 17 ] [ 18 ]
Performance figures for predictive text examples typically depend on use of natural language. Use of SMS language abbreviations and slang can reduce any advantage. [ 3 ] [ b ] For the tests done by Scott Mackenzie a selection of words from the British National Corpus were used as a representative sample of the English language. [ 4 ]
LetterWise uses the probability of letters occurring in a particular sequence to achieve performance. [ 19 ]
One measure of performance for text entry systems is "key strokes per character" (kspc). As a baseline the full English PC keyboard has a kspc of 1 as precisely one key stroke is required per typed character. Scott Mackenzie and other academics presented with Eatoni that they had evaluated LetterWise to have a kspc of 1.15 for English. [ 4 ] [ 20 ] This typically relates to one extra tap per 6 letters compared to standard keyboard. In contrast multi-tap, where a key is repeatedly pressed until the desired letter is found whereupon no further taps are made until the cursor moves to the next letter, has been evaluated to have a kspc of about 2.03. [ citation needed ]
The pangram The quick brown fox jumps over the lazy dog is sometimes used for keyboard practice. The Eatoni website claims this 35 letter nine word phrase requires only 14 additional keystrokes with LetterWise compared to 42 additional keystrokes for MultiTap. [ 16 ]
Eatoni engineers claim LetterWise has relatively low storage requirements compared to dictionary based solutions. [ 5 ] The Eatoni website claims in the storage space typically required for a single dictionary database (30–100kb) it would be possible to fit LetterWise databases for 10–20 different languages. The website says device random-access memory requirements are similarly low, typically under 2kb, and there has been an implementation for 200 bytes of available memory. [ 21 ]
LetterWise was also used in TongueWise, [ 22 ] a tongue-computer interface for tetraplegics using the LetterWise engine . Clinical evaluations showed LetterWise could offer an almost 50% increase in throughput compared to Multi-tap for English language words. [ 23 ] [ 24 ]
The Chinese LetterWise can be loosely described as a two-level version of alphabetic LetterWise. A phonetic character (e.g. Pinyin or Bopomofo ) is entered on the first level which is converted automatically to Hanzi ready for the second level (Next Hanzi) key. [ 25 ] As of May 2019 [update] the Eatoni website showed three related cordless or answerphone physical devices from the same manufacture having adopted the technology. [ 26 ]
Eatoni Ergonomics also developed and patented the dictionary word based predictive text input system WordWise announcing it in September 2000 with claims it was even faster than LetterWise. [ 1 ] [ 5 ] Wigdor and Balakrishnan indicated WordWise performs similarly to earlier techniques but with subtle advantages, though as with all predictive techniques the efficiency relied essentially upon the use of natural language with techniques such as abbreviations tending to nullify any advantage. [ 3 ]
In addition to the standard version of WordWise Eatoni's website also notes they developed a more advanced version termed shift WordWise . [ c ] Shift-WordWise required use of a modified CHELNSTY keypad with those letters being selected by a shift key that could be allocated to the 1 button. [ 27 ]
From his lawsuit Kosover alleges he has some input into the development of the WordWise system during his time at Eatoni to August 1999. [ 1 ] It was designed to complement LetterWise and targeted for keyboards on mobile devices. [ citation needed ]
Eatoni's website indicates that it is possible for standard WordWise to add additional words to the dictionary on the device however this capability is no mentioned in Iridium satellite phone manuals so the capability might not be present on all versions of WordWise. [ 27 ] [ 28 ]
If WordWise is unable to suggest the required word either through it not being in the dictionary or due to a keying error the required word will need to be entered in another mode such as LetterWise which can be switched to relatively easily. [ citation needed ]
It has been suggested that WordWise is less sensitive to keystroke errors than competing T9 text prediction technology. [ 29 ] [ better source needed ]
A multilingual WordWise implementation is included in Iridium satellite phones. [ 28 ] [ 30 ] Eatoni's website also indicated it was included as their SMS , Twitter and e-mail downloadable client applications for certain Symbian and Apple IOS based products. [ 31 ]
Despite intensive marketing attempts in the early 2000s LetterWise and WordWise were not widely adopted by cell phone manufacturers with the Multi-tap and T9 system holding the market. [ 32 ] LetterWise did find some adoption for DECT cordless phones, which were typically constrained by more limited resources, with Eatoni claiming over 20 million devices capable of LetterWise being shipped. [ 26 ] From 2009 certain Iridium satellite phone models were shipped with both LetterWise and WordWise though not necessarily enabled by default; [ 28 ] [ 30 ] [ 31 ] as of May 2019 some of these models seem current. [ 33 ] | https://en.wikipedia.org/wiki/LetterWise |
Galileo Galilei 's " Letter to Benedetto Castelli " (1613) was his first statement on the authority of scripture and the Catholic Church in matters of scientific enquiry. [ 1 ] : 66 In a series of bold and innovative arguments, he undermined the claims for Biblical authority which the opponents of Copernicus used. The letter was the subject of the first complaint about Galileo to the Inquisition in 1615. [ 1 ] : 66
In 1610 Galileo had published Sidereus Nuncius ( The Starry Messenger ), which made him famous across Europe. This work prompted many debates as to whether the Earth really was the centre of the universe. [ 2 ] : 27 Galileo usually avoided referring to scripture in his arguments about the universe, while the Aristotelian scholars who opposed Copernicus cited the Bible in support of their views – for example Lodovico delle Colombe in his 1611 work Contra il Moto della Terra ( Against the Motion of the Earth ) explicitly challenged anyone defending Copernicus to answer the charge that he was going against what the Bible taught.
This presented Galileo with a dilemma – if he did not respond, he effectively conceded that the biblical text confirmed the Aristotelian view despite the fact that the Church had no firm position on the Copernican question; on the other hand if he tried to engage in arguments based on scripture, he allowed himself to be drawn into a field where the Church regarded its authority as absolute. [ 1 ] : 59–61 Indeed an earlier venture into this form of argument by Galileo had been stopped by the Church. In the manuscript for Letters on Sunspots (1613), he argued that "flaws" in the Sun demonstrated that the heavens were not immutable, as had previously been thought. A paragraph in which Galileo supported this by claiming that the scriptures supported the mutability of the heavens was removed by the Inquisition censors . [ 1 ] : 58–59
On 14 December 1613 Galileo's friend and former pupil Benedetto Castelli wrote to him to say that at a recent dinner in Pisa with the Grand Duke Cosimo II de' Medici a conversation had taken place in which Cosimo Boscaglia , a professor of philosophy , argued that the motion of the Earth could not be true, as it was contrary to the Bible . Castelli had disagreed with him and maintained, as Galileo held, that the Earth's motion was possible. After the dinner, Castelli had been called back by the Dowager Duchess Christina of Tuscany to answer points she raised from scriptural arguments against the motion of the Earth. Castelli had responded and Boscaglia had remained silent. [ 3 ] Castelli wished to alert Galileo to this exchange, and advised Galileo that their mutual friend Niccolò Arrighetti would come to Florence and explain matters further. This Arrighetti did. [ 4 ] : 57
Galileo felt that it was important for him to set out an argument to show how scripture could not be used as the basis for scientific enquiry. [ 2 ] : 27 He did so with great speed, replying with a letter to Castelli in less than a week, on 21 December 1613. [ 5 ] His Letter to Benedetto Castelli was not published, but was circulated widely in manuscript form. [ 1 ] : 66 As the debate about its arguments continued, Galileo thought it advisable to review and expand the arguments he had set out. This was the basis of his subsequent Letter to the Grand Duchess Christina , which expanded the eight pages of his letter to Castelli to forty pages. [ 2 ] : 29
In his letter to Benedetto Castelli, Galileo argues that using the Bible as evidence against the Copernican system involves three key errors. Firstly, claiming that the Bible shows the Earth to be static and concluding that the Earth therefore does not move is arguing from a false premise; whether the Earth moves or not is a thing which must be demonstrated (or not) through scientific enquiry. Secondly, the Bible is not even a source of authority on this kind of question, but only on matters of faith - thus if the Bible happens to say something about a natural phenomenon, this is not sufficient for us to say that it is so. Thirdly, he shows by deft argument that it is open to question whether the Bible, as his opponents claimed, even contradicted Copernicus' model of the universe. Indeed, Galileo argues, a key passage in the Bible which was held by his opponents to support the view that the Sun moves round the Earth supports his own views much better. [ 2 ] : 28
In the Bible Joshua 10:12 is an account of how God commanded the Sun to stand still so that Joshua could defeat his enemies. According to those opposed to Copernicus, this showed clearly that the Sun (and not the Earth) moved. Galileo argued that this passage could not be used to support the traditional Earth-centred view of the universe at all. If we assume the universe to be as it was described by Claudius Ptolemy , the Sun's annual motion was a slow movement towards the East, so if God had commanded it to stop, the daily movement towards the West would no longer have been counteracted and as a result the day would actually have got slightly shorter rather than longer. However if we assume the universe to be as Copernicus described it, the Sun is at the centre and its rotation drives the rotation of all the planets. Thus if God had ordered the Sun to stop turning, everything would have stopped and the day would have been longer, just as the Bible described. [ 1 ] : 68
Two aspects of Galileo's letter are particularly worthy of note. First, his boldness in venturing into the field of exegesis , where he was bound to upset many theologians who would not welcome his contributions. Second, his rhetorically brilliant argument was based on a fundamental contradiction; he began by arguing that faith and science were distinct, and that the Bible could not be used as the basis for arguments about science; he then went on to show, according to some novel and clever arguments, that actually the Bible supported his own scientific views. [ 6 ]
His letter argues a position on scriptural authority which is very similar in substance, if not in tone, to that set out by the Catholic Church itself centuries later, in Leo XIII 's 1893 encyclical , Providentissimus Deus . Emphasising that the Bible makes use of figurative language and is not meant to teach science, this argues:
"...here is the rule also laid down by St. Augustine, for the theologian: "Whatever they [i.e. scientists] can really demonstrate to be true of physical nature, we [i.e. theologians] must show to be capable of reconciliation with our Scriptures; and whatever they assert in their treatises which is contrary to these Scriptures of ours, that is to Catholic faith, we must either prove it as well as we can to be entirely false, or at all events we must, without the smallest hesitation, believe it to be so." [ 7 ]
Likewise, Galileo accepted that the Bible was infallible in matters of doctrine, but he agreed with Cardinal Baronius 's observation that it was "intended to teach us how to go to heaven, not how the heavens go." He also pointed out that both St. Augustine and St. Thomas Aquinas had taught that scripture had not been written to teach a system of astronomy, citing St. Augustine's comment that "One does not read in the Gospel that the Lord said: I will send you the Paraclete who will teach you about the course of the sun and moon. For He willed to make them Christians, not mathematicians." [ 8 ]
In late 1614 or early 1615, Niccolò Lorini obtained a copy of Galileo's letter, some parts of which he and his fellow Dominicans at the convent of San Marco in Florence adjudged to be "suspect or rash". [ 10 ] [ 11 ] He therefore forwarded it to Cardinal Paolo Emilio Sfondrati at the Congregation of the Index , together with a covering letter dated 7 February 1615, calling for the matter to be investigated. [ 12 ] [ 13 ] [ 1 ] : 70
The Holy Office examined Lorini's copy of Galileo's letter to Castelli on 25 February 1615 at the house of Robert Bellarmine . [ 4 ] : 61 It was clear to them that Lorini's version was not the complete letter, as it was obvious that an introductory section was missing. [ 1 ] : 71 Lorini's version also included the phrase 'Scripture does not refrain from perverting its most important dogmas...' whereas Galileo's original had said 'Scripture accommodates itself to the capacity of uncouth and uneducated people'. [ 1 ] : 197 For whatever reason, the Holy Office wished to make certain that it had an accurate version before proceeding with its investigation, so Cardinal Garzia Mellini , secretary of the Inquisition, wrote to the archbishop of Pisa, where Castelli taught at the university, and asked him to provide the original letter. [ 4 ] : 70
By now Galileo had apparently realised that some kind of investigation was underway, so he asked Castelli to return the original of the letter to him. He made a copy of it and sent this version to his friend Archbishop Piero Dini in Rome, protesting at the “wickedness and ignorance” of his enemies, and expressing concern that the Inquisition “may be in part deceived by this fraud which is going around under the cloak of zeal and charity”. [ 14 ]
The Holy Office submitted Galileo's letter to an unnamed theological adviser for examination. That adviser's report, undated, concluded that there were three places where Galileo had used language which was offensive, but 'although this document sometimes uses words improperly, it does not deviate from the narrow path of Catholic expression.' [ 1 ] : 72
Until 2018 two versions existed of the Letter to Benedetto Castelli – the Lorini version held in the Vatican archives and the Dini version. The general scholarly view was that Lorini's version was not authentic and that Lorini had amended it to show Galileo in the worst possible light, while the Dini version was generally held to be true.
In August 2018 the original manuscript of the letter was discovered in the archives of the Royal Society . This is the letter Galileo sent to Castelli and later asked Castelli to return to him. It shows the edits Galileo made in his own handwriting as he prepared the Dini version, replacing words and phrases that the Inquisition might object to with words less likely to offend. None of the arguments were changed, but the tone of the letter was altered considerably. [ 15 ] [ 14 ]
It is thus certain that the Lorini version was in most respects authentic, while the Dini version was not, as Galileo claimed, a true copy of his original letter. [ 15 ] [ 14 ] | https://en.wikipedia.org/wiki/Letter_to_Benedetto_Castelli |
A lettering guide template is a special type of template used to write uniform characters. It consists of a sheet of plastic or other material with cut-outs of letters, numbers, and other shapes used especially for creating technical drawings. For decades they have been essential for lettering a drawing nameplate so text and other designs could be made quickly and uniformly.
Although they have been superseded by the use of computers, during the greater part of the last century they were used to relatively ease the lettering process in the creation of technical drawings. They were an indispensable tool for architects and technical illustrators in general, for labeling their drawings and plans but also for the description of projects, in which it was good practice to use a lettering template to achieve uniform and well-written text.
A lettering template could also be used by people illiterate or semi-illiterate to learn to type, or improve their handwriting. [ 1 ] In the course of political history some politicians, such as Bettino Craxi , have used them to help people with writing difficulties. They distributed cardboard templates with the sequence of characters of their last name, so they could be easily written during the voting [ 2 ] process.
This design -related article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Lettering_guide |
Letters in Organic Chemistry (usually abbreviated as Lett. Org. Chem. ), is a peer-reviewed monthly scientific journal , published since 2004 by Bentham Science Publishers . [ 1 ] Letters in Organic Chemistry is indexed in: Chemical Abstracts Service (CAS), EBSCOhost , British Library , PubMed , Web of Science , and Scopus .
Letters in Organic Chemistry publishes letters and articles on all areas related to organic chemistry .
According to the Journal Citation Reports, the impact factor of this journal is 0.867 for the year 2020. [ 2 ] The Editor-in-Chief is Alberto Marra ( University of Montpellier , France ). who took over from Gwilherm Evano ( Université libre de Bruxelles , Belgium ) who resigned in February 2018 after a strong disagreement with Bentham on the scientific management of this journal. [ 3 ] | https://en.wikipedia.org/wiki/Letters_in_Organic_Chemistry |
Letters on Sunspots ( Istoria e Dimostrazioni intorno alle Macchie Solari ) was a pamphlet written by Galileo Galilei in 1612 and published in Rome by the Accademia dei Lincei in 1613. In it, Galileo outlined his recent observation of dark spots on the face of the Sun. [ 1 ] His claims were significant in undermining the traditional Aristotelian view that the Sun was both unflawed and unmoving. [ 2 ] The Letters on Sunspots was a continuation of Sidereus Nuncius , Galileo's first work where he publicly declared that he believed that the Copernican system was correct. [ 3 ]
Galileo was not the first person to observe sunspots . The earliest apparent reference to them appears in the I Ching of ancient China, [ 4 ] while the earliest recorded observation is also Chinese, dating to 364 BC. [ 5 ] Around the same time, the first European mention of sunspots is found, by Theophrastus . [ 6 ] There were reports from Islamic [ 7 ] and European astronomers of sunspots in the early ninth century; [ 8 ] [ 9 ] those occurring in 1129 were recorded by both Averroes [ 7 ] and John of Worcester , whose drawings of the phenomenon are the earliest surviving today. [ 10 ] Johannes Kepler observed a sunspot in 1607 but, like some earlier observers, believed he was watching the transit of Mercury . [ 11 ] The sunspot activity of December 1610 was the first to be observed using the newly invented telescope , by Thomas Harriot , who sketched what he saw but did not publish it. [ 12 ] In 1611 Johannes Fabricius saw them, and published a pamphlet entitled De Maculis in Sole Observatis , which Galileo was not aware of before he wrote the Letters on Sunspots. [ 13 ]
When Jesuit Christoph Scheiner first observed sunspots in March 1611, he ignored them until he saw them again in October. Then, under the pseudonym Apelles latens post tabulam (Apelles hiding behind the painting), [ 14 ] he presented his description and conclusions about them in three letters to the Augsburg banker and scholar Mark Welser . Scheiner wanted to remain anonymous to avoid involving the Jesuit order and the church generally in an area of controversy. [ 14 ] Welser published them on his own presses, sent copies to astronomers around Europe, and invited them to reply. [ 15 ] [ 16 ] [ 17 ] It was Welser's invitation which prompted Galileo to reply with two letters, arguing that the sunspots were not satellites, as Scheiner ('Apelles') maintained, but were features either on the Sun's surface or just above it.
In the meantime, Scheiner sent Welser two further letters on the subject, and after he had read Galileo's first letter, he responded with a sixth of his own. These later letters were different in tone from the first three, as they hinted that Galileo was claiming credit for having discovered the phases of Venus , when in fact proper credit was due to others. They also implied that Galileo had copied Scheiner's helioscope in order to do his research. [ 18 ]
Having published Scheiner's first three letters under the title Tres Epistolae de Maculis Solaribus ("Three Letters on Solar Spots") , Welser now published his second three, also in 1612, as De Maculis Solaribus et Stellis circa Iovis Errantibus Accuratior Disquisition ("A More Accurate Disquisition Concerning Solar Spots and Stars Wandering around Jupiter") . Having read these second three letters, Galileo replied with a third of his own, much sharper and more polemical in tone than his earlier ones. Welser declined to publish Galileo's letters, perhaps because of the sarcastic tone they took towards Apelles, although the reason he gave Galileo was the exorbitant cost of producing all the illustrations Galileo wanted. [ 19 ]
Publishing the Letters on Sunspots was a major financial and intellectual venture for the Accademia dei Lincei, and it was only the fourth title it had decided to issue. [ 20 ] Federico Cesi paid for the publication himself, and wanted to strike a careful balance between introducing extraordinary new ideas and avoiding causing offence to people who might find those views problematic. This was consistent with the Accademia's project of acting as a centre for the dissemination of radical new scientific ideas, issued with the agreement of the Church authorities. [ 21 ] Cesi tried to persuade Galileo to avoid an aggressive or polemical tone in his letters, to avoid antagonising the Jesuits (Scheiner's identity behind the pseudonym 'Apelles' was already suspected), [ 22 ] but having read Scheiner's apparent accusations of bad faith in his later letters, Galileo did not heed his advice. Indeed, the published version of his Letters on Sunspots contained a preface by Angelo de Filiis which uncompromisingly asserted Galileo's primacy in discovering sunspots. [ 18 ] The text was presented for censorship to the Roman Inquisition in order to obtain permission to print. The censors assigned were Cesare Fidelis, Luigi Ystella, Tommaso Pallavicini and Antonio Bucci. [ 20 ]
Ensuring the book was ready to print was a collaborative process involving the censors, Galileo, Cesi and others in working on the text until it was acceptable to the Inquisition, and the censors were well acquainted with the leading figures of the Accademia. [ 23 ] Antonio Bucci, for example, was a physician who had previously been involved in reviewing work by Giambattista della Porta , also published by Cesi. In the case of Letters on Sunspots his critical support appears to have been helpful in ensuring that publication was not prevented by influential Dominicans of the Sacred Palace . Indeed, in his comments Bucci praised Galileo's work, with which he was already familiar, as he had been invited to take part in the Accademia's discussions about it before the manuscript was presented for censorship. [ 24 ]
The censors insisted that Galileo remove from his text any reference to scripture or claims for divine guidance. Thus the pamphlet was to have opened with a quotation from Matthew 11:12 'The kingdom of heaven suffers violence, and men of violence take it by force.' The censors objected that this could be understood to mean that astronomers wanted to overpower theology. It was therefore amended to 'Already the minds of men assail the heavens, and the more valiant conquer them.' Further on in the text Galileo's claim that 'divine goodness' had led him to advocate the system of Copernicus was struck out, and replaced with 'favourable winds'. Galileo's text referred to the idea that the heavens were immutable as 'erroneous and repugnant to the indubitable truth of Scripture.' Like all other mentions of Scripture, the censors insisted that this too was removed. Galileo wanted to claim divine inspiration for his findings and show how they accorded with Holy Writ; the censors wanted to keep unusual new ideas at a safe distance from core tenets of the faith. [ 25 ] With these amendments Galileo was authorised to take his book to print. [ 26 ]
Half of the printed edition of 1400 copies of Letters on Sunspots contained both the Apelles Letters and Scheiner's illustrations as well as Galileo's replies. The other half contained Galileo's work only. [ 27 ] The total cost of the book was 258.70 scudi, of which 44 scudi was the cost of the illustrations and tables and 6 scudi was the cost of engraving the frontespiece. [ 28 ] : 249
Galileo describes how he has observed sunspots for eighteen months. His key conclusions are that sunspots were real and not merely optical illusions; and that they were not static, but moved. [ 29 ] The sunspots had a single motion, moving across the Sun in a uniform fashion. [ 3 ] Galileo argued that the Sun was a perfect sphere and that it moves by itself on its own center. The Sun carries these spots until they disappear from view at its rim in about one lunar month. [ 3 ]
Scheiner's view that the spots were satellites prompts Galileo to comment on the phases of Venus and how they supported a heliocentric view. [ 30 ] He develops his argument to show that sunspots were not permanent and did not have a regular pattern of movement as they would if they were heavenly bodies – they were nothing like the moons of Jupiter that he had himself discovered and described in Siderius Nuncius . 'The sun, turning on its axis, carries them around without necessarily showing us the same spots, or in the same order, or having the same shape.' [ 31 ] He noted the parallels between sunspots and clouds over the Earth, but did not assert that they were made of the same material. His comment on 'Apelles' (the pseudonym of Scheiner) was:
'It seems to me therefore that Apelles has a free, and not a servile mind; he is well able to grasp true teaching; and now, prompted by the strength of so many new ideas, he is beginning to listen and to assent to true and sound philosophy, especially as regards the arrangement of the universe. But he is not yet able to detach himself completely from the fantasies he absorbed in the past, to which his intellect sometimes returns and lends assent by force of long-established habit.' [ 32 ]
Much of Galileo's first letter is devoted to demonstrating weaknesses in Scheiner's arguments – inconsistencies, false analogies, and unlikely conclusions from the observations he had made.
Galileo's second letter restates the key propositions from his first letter, and is otherwise mostly concerned with geometric proofs that the spots are on the surface of the Sun rather than above it. To accompany these proofs Galileo provides 38 detailed illustrations, which allow the reader to see how his observations relate to his calculations.
While Galileo's First and Second Letters had been written in response to Scheiner's Tres Epistolae , his Third Letter responded to Accuratior Disquisitio . [ 28 ] : 234 Galileo was angry to see that once again Scheiner was making claims about the moons of Jupiter, since he regarded them as his own discovery. To demonstrate the falsehood of Scheiner's assertion that the moons of Jupiter were 'wandering stars', unpredictable in their movement, as well as to display his own clear superiority in observation and calculation of celestial movements, Galileo appended a complete set of Ephemerides for the Jovian moons to his third letter. [ 28 ] : 244 Galileo shows the critical flaws in Scheiner's geometry, his understanding of the authorities he cites, his reasoning, his observations and indeed his own drawings.
Galileo says there is no point in speculating about the 'essence' of sunspots, or indeed of other things, [ 28 ] : 254 but since writing his last letter he has spent time thinking about the uniform motion of the sunspots within a specific band around the Sun's surface. He asks, in passing, 'is there not still a controversy over whether the Earth itself remains immobile, or wanders?', which is an oblique reference to the idea, required by Copernicus' model of the universe, that the earth must rotate on its own axis every day. [ 28 ] : 254 Lastly, he humorously compares scholars who insist that every detail of Aristotle's writing must be true, whether it corresponds with reality or not, with those artists who draw portraits of people in fruit and vegetables. 'As long as these oddities are offered as jokes, they are nice and pleasing... but if someone, perhaps because he had consumed all his studies in a similar style of painting, then wanted to draw the general conclusion that every other method of imitating was imperfect and blameworthy, surely Cigoli and other celebrated painters would laugh at him.' [ 28 ] : 257
Galileo takes up once again the question of whether there is any relation between the transit of Venus and sunspots. He criticises 'Apelles' for setting out a long and complex demonstration of the movement of Venus across the face of the Sun, when it was superfluous to his purpose. [ 28 ] : 261 He criticises him further for giving an estimate of Venus's size as it crosses the Sun which is wrong, and for supporting this estimate with learned authorities from the past who did not have telescopes. [ 28 ] : 263 Furthermore, Galileo argues, some of the ancient astronomers, including Ptolemy, made more cogent arguments than 'Apelles' suggests.
Galileo notes that 'Apelles' has shifted his view on sunspots since his first letter. At first he insisted they were all spherical, like little moons; now he says they are irregular in shape, forming and dissolving. He previously said that the spots were at various distances from the Sun, wandering between it and Mercury, but he no longer maintains this view. [ 28 ] : 266 'Apelles' argues that the hardness and solidity of the Sun means that the fluid spots cannot be on its surface; but citing the authority of the ancients to confirm the Sun's solidity is pointless, since they had no idea of its structure; in any case the evidence of the spots themselves suggests the very opposite to the traditional view of the Sun's hardness. He agrees with 'Apelles' view that the spots are not chasms or pools on the Sun's surface, but nobody had ever argued that they were.
A large portion of the Third Letter is taken up with disproving Apelles' assertion that he had observed spots passing across the Sun at different speeds – one, on the diameter, taking sixteen days, and another, at a lower latitude, in just fourteen. (If sunspots moved at differential speeds, this tended to suggest they were moons moving independently of the Sun itself). Galileo says that in his own observations he has never seen this differential rate of movement, but that spots always move at a constant speed relative to each other. First Galileo demonstrates that points on two different sunspot trajectories at two different latitudes produce lines which maintain a constant proportion with each other at any point in the rotation. [ 28 ] : 269 Next he shows that the larger the sphere on which sunspots appear, the less differential there is in their transit times at the same two latitudes. [ 28 ] : 272 Finally, he shows that for a spot to move along the diameter of the Sun in a period 1 1 ⁄ 7 as long as another spot at a latitude 30° higher, the diameter of the Sun would need to be more than twice as great as observed. From this he concludes that Apelles is simply wrong, and it is not possible for one spot to traverse the Sun in sixteen days, while another takes only fourteen. [ 28 ] : 275
Now Galileo turns to Apelles' illustrations of sunspots, and begins to use them to show how his arguments about sunspot motion are false. He recalls how Apelles depicts them coming into view, foreshortened, before appearing at their full width. He then demonstrates that for the spots Apelles had observed to change in apparent size as they did, they would need to be on the face of the Sun, because if they were even a short distance above its surface the foreshortening effect would be remarkably different. [ 28 ] : 276 Galileo challenges Apelles' assertion that he had seen different spots moving at different speeds; particularly that he had seen spots on the Sun's diameter rotate more rapidly than those at higher latitudes. This, he says, is contradicted not only by observation but by Apelles' own statement in another place in his work that spots in the middle of the Sun remain longer than those passing nearer its limb. [ 28 ] : 279 Finally, Apelles' own illustrations clearly show spots transiting the Sun in around 14 1 ⁄ 2 days, and nothing in his illustrations supports his contention that some take 16, and others 9. [ 28 ] : 280
Having disproved Apelles' arguments on sunspots, Galileo addresses a number of his other errors. He briefly responds to Apelles' views on extraterrestrial life; then disposes of the idea that the Moon is translucent. He then returns to Apelles' analogy between sunspots and the moons of Jupiter, where he notes that Apelles has subtly moved from arguing that sunspots are like planets, to arguing that planets are like sunspots. 'Carried away by the desire to maintain what he had originally said, and unable to accommodate the spots exactly to the properties once associated with the other stars, [Apelles] has accommodated the stars to the properties that we know belong to the spots.' [ 28 ] : 286 To dispense once and for all with Apelles' claim that the moons of Jupiter 'appear and disappear', Galileo provides predictions for their positions for the next two months to prove the regularity of their motions. [ 28 ] : 287
To demonstrate that natural philosophy must always be led by observation and not try to fit new facts into preconceived frameworks, Galileo comments that the planet Saturn had recently and surprisingly changed its appearance. In his First Letter, he had argued that Saturn never changes its shape , and never will. Now, he agrees, it has changed shape. He does not try to prove his earlier views right in spite of new facts, but makes cautious predictions about how its appearance may change in future. [ 28 ] : 295
Galileo concludes his remarks by criticising those who doggedly adhere to Aristotle's views, and then, drawing together all he has said about sunspots, the moons of Jupiter, and Saturn, ends with the first explicit endorsement of Copernicus in his writings:
I think it is not the act of a true philosopher to persist – if I may say so – with such obstinacy in maintaining Peripatetic conclusions that have been found to be manifestly false, believing perhaps that if Aristotle were here today he would do likewise, as if defending what is false, rather than being persuaded by the truth, were the better index of perfect judgement... [and] I say to your Lordship that this star too [i.e. Saturn] and perhaps no less than the emergence of the horned Venus, agrees in a wondrous manner with the harmony of the great Copernican system, to whose universal relations we see such favourable breezes and bright escorts directing us. [ 28 ] : 296
The common belief until Galileo's time was that the heavens beyond the Moon were both perfect and unchanging. [ 33 ] Many of the arguments between Scheiner and Galileo were about things observed in the skies that appeared to be changing, and what the nature and significance of that change was. Although the behaviour of sunspots was the main topic of their debate, they also touched on other disputes, such as the phases of Venus and the moons of Jupiter . [ 34 ]
In a letter to Federico Cesi , Galileo said:
'I have finally concluded, and I believe I can demonstrate necessarily, that they [i.e. the sunspots] are contiguous to the surface of the solar body, where they are continually generated and dissolved, just like clouds around the earth, and are carried around by the sun itself, which turns on itself in a lunar month with a revolution similar [in direction] to those other of the planets... which news will be I think the funeral, or rather the extremity and Last Judgement of pseudophilosophy.... I wait to hear the spoutings of great things from the Peripatetics to maintain the immutability of the skies.' [ 35 ]
The cosmology of Galileo's time, based on Aristotle's Physics , held that the Sun was 'perfect' and unflawed. [ 36 ] [ 37 ] Only with the invention of the telescope was it possible for sunspots to be systematically observed. Many who had never seen them found the idea of them morally and philosophically repugnant. [ 38 ] Those who could see them, like Scheiner, wanted to find an explanation for them within the Aristotelian system. Galileo's arguments in Letters on Sunspots were intended to demonstrate these claims as false; and if they were false, Aristotelian assumptions about the universe could not be true.
Galileo had discovered the moons of Jupiter in 1609. [ 39 ] Scheiner argued that what appeared to be spots on the Sun were in fact clusters of small moons, thereby trying to deploy one of Galileo's own discoveries as an argument for the Aristotelian model. [ 40 ] [ 41 ] In his Letters on Sunspots Galileo showed how sunspots were nothing like the moons of Jupiter, and the comparison was false. Scheiner claimed that the sunspots, with their irregular movements, were like the moons of Jupiter whose positions were similarly hard to predict. To counter this argument, Galileo published tables of predictions for the future position of the moons of Jupiter, so that astronomers could easily distinguish between the regular, predictable movements they followed with the ephemeral and irregular sunspots. [ 23 ]
Showing that the Sun rotated had two effects. Firstly, it showed that the traditional Aristotelian model of the universe must be wrong, because that model assumed that the Sun had only a diurnal (daily) motion around the earth, and not a rotation on its own axis. Secondly, it showed that there was nothing necessarily unusual about rotation of a body in space. In the Aristotelian system, night and day were explained by the Sun moving round a static Earth. For Copernicus' system to work, there had to be an explanation for why half the Earth was not in permanent daylight, and the other in permanent darkness, as it completed its annual motion around the Sun. This explanation was that the Earth rotated on its own axis once every day. [ 42 ] However it was very difficult to prove that the Earth was rotating, so to show that the Sun rotated made the Copernican model at least more plausible. While the rotation of the Sun did not prove Copernicus right, it proved his opponents wrong and made his ideas more likely to be true.
In the Letters on Sunspots Galileo responded to claims by Scheiner about the phases of Venus , which were an important question in the astronomy of the time. There were different schools of thought about whether Venus had phases at all – to the naked eye, none were visible. [ 43 ] In 1610, using his telescope, Galileo had discovered in that Venus, like the Moon, had a full set of phases, [ 44 ] but only in Letters on Sunspots did he commit this finding to publication. The fact that there was a full phase of Venus, (similar to a full moon) when Venus was in the same direction in the sky as the Sun meant that at a certain point in its orbit, Venus was on the other side of the Sun to the Earth. This indicated that Venus went around the Sun, and not around the Earth. This provided important evidence in support of the Copernican model of the universe. [ 45 ]
At least as early as 1597, Galileo had concluded that the Copernican model of the universe was correct [ 46 ] [ 47 ] but had not publicly advocated this position. In Siderius Nuncius Galileo included in his dedication to the Grand Duke of Tuscany the words ' while all the while with one accord they [i.e. the planets] complete all together mighty revolutions every ten years round the centre of the universe, that is, round the Sun.' In the body of the text itself, he stated briefly that in a forthcoming work, 'I will prove that the Earth has motion', which is an indirect allusion to the Copernican system, but that is all. Copernicus is not mentioned by name. [ 48 ] [ 49 ] It is at the end of the Third Letter that Galileo explicitly declares his belief in the Copernican system.
Galileo remarks in one passage that the Sun might not be revolving, but in another he states more definitely that the Sun does have a motion, and wonders what causes it. Here he establishes a connection between cosmology and mechanics . [ 3 ] Galileo wrote, "I seem to have observed that physical bodies have physical inclination to some motion." [ 50 ] Letters in Sunspots is also the first of his works to mention the concept of inertia , which would later become Newton's first law of motion . [ 50 ]
While Scheiner wrote his letters in Latin, Galileo's reply was in Italian. Scheiner did not speak Italian, so Welser had to have Galileo's letters translated into Latin so he could read them. [ 51 ] [ 19 ] This was not the first time Galileo had published in Italian, and Galileo was not the first natural philosopher to publish in Italian (for example Lodovico delle Colombe 's account of the 1604 supernova was in Italian, as was Galileo's reply). However Letters on Sunspots was the first book the Accademia dei Lincei published in Italian. [ 20 ] Galileo later said of his preference for Italian over Latin:
'I wrote in Italian because I wished everyone to be able to read what I wrote.... I see young men.... who, although furnished.... with a decent set of brains, yet not being able to understand things written in gibberish [i.e. Latin], take it into their heads that in these crabbed folios there must be some grand hocus-pocus of logic and philosophy much too high up for them to think of jumping at. I want them to know, that as nature has given eyes to them, just as well as to philosophers, for the purpose of seeing her works, she has also given them brains for examining and understanding them.' [ 52 ]
While Scheiner's lack of Italian hindered his response to Galileo in 1612 while they corresponded through Welser, it also meant that when Galileo published Il Saggiatore in 1623, which accused Scheiner of plagiarism, Scheiner was unaware of this until he happened to visit Rome the following year. [ 11 ]
Most readers of the time did not have a telescope, so could not see sunspots for themselves – they relied on descriptions and illustrations to make clear what they looked like. [ 53 ] [ 54 ] For this reason the quality and number of illustrations was essential in building public understanding. Scheiner's book of letters had contained illustrations of sunspots which were mostly 2.5 cm in diameter, leaving little space for detail and portraying sunspots as solid, dark entities. Scheiner himself had described them as 'not terribly exact' and 'drawn without precise measurement'. He also indicated that his drawings were not to scale, and the spots in his illustration had been drawn disproportionately large 'so that they would be more conspicuous.' [ 40 ] A reader looking at these illustrations might be inclined to agree with Scheiner's view that sunspots were probably planets.
Although the sunspots were constantly changing position, Scheiner presented his observations over a period of six weeks in a single fold out plate. [ 14 ] All of his figures are small except for the observations in the top left corner. He admitted to his readers that his drawings were not made to scale, and that other factors such as variations in the weather, lack of time, or other impediments may have reduced their accuracy. [ 14 ] Scheiner also showed the formation of spots in different orientations. Sometimes the configurations of the spots were linear following consecutive days, but the orientations became more complex over time that there was a lack of an obvious pattern. [ 14 ]
For Galileo to persuade his readers that sunspots were not planets but a much more transient and nebulous phenomenon, he needed illustrations which were larger, more detailed, more nuanced, and more 'natural.' [ 55 ] Letters on Sunspots carried 38 engravings of sunspots, providing a visual narrative of the sun's appearance from 2 June – 8 July 1612, with some additional illustrations from August. This extensive visual representation, with its large scale and high-quality reproduction, allowed readers to see for themselves how sunspots waxed and waned as the sun rotated. [ 56 ] The impact of this series of illustrations was to create a near-photographic sense of reality. This sense undermined the claims made by Scheiner before any argument was mounted to refute them. [ 40 ]
Galileo and Prince Cesi selected Matthaeus Greuter to create the sunspot illustrations. Originally from Strasbourg and a convert from Protestantism, Greuter moved to Rome and set up as a printer specialising in work for the Jesuit order. His work ranged from devotional images of saints through to mathematical diagrams. This relationship may have recommended him as one whose involvement in a publication would perhaps ease its path through censorship; in addition his craftsmanship was outstanding, and he devised a novel etching technique specially in order to make the sunspot illustrations as realistic as possible. Galileo drew sunspots by projecting an image of the Sun through his helioscope onto a large piece of white paper, on which he had already used a compass to draw a circle. He then sketched the sunspots in as they appeared projected onto his sheet. To make his illustrations as realistic as possible, Greuter reproduced them at full size, even with the mark of the compass point from Galileo's original. Greuter worked from Galileo's original drawings, with the verso on the copperplate and the image traced through and etched. [ 57 ]
The cost of the thirty-eight copperplates was significant, amounting to fully half of the production costs of the edition. Because half the copies of the Letters also contained the Apelles Letters, Greuter reproduced the illustrations that Alexander Mair had done for Scheiner's book, allowing Galileo's readers to compare two distinct views of the sunspots. He reduced Mair's drawings further in size, and converted nine of the twelve from etchings or engravings into woodcuts, which lacked the subtlety of Mair's originals. Scheiner was evidently impressed by Greuter's work, as he commissioned him to create the illustrations for his own magnum opus Rosa Ursina in 1626. [ 57 ] The 1619 work Galileo co-wrote with Mario Guiducci , Discourse on Comets , mocked Scheiner for the 'badly colours and poorly-drawn images' in his work on Sunspots. [ 28 ] : 320
In modern science falsifiability is generally considered important. [ 58 ] [ 59 ] In De revolutionibus orbium coelestium Copernicus had published both a theoretical description of the universe and a set of tables and calculating methods for working out the future positions of the planets. In Letters on Sunspots Galileo did as Copernicus had done – he elaborated his ideas on the form and substance of sunspots, and accompanied this with tables of predictions for the position of the moons of Jupiter. In part this was to demonstrate that Scheiner was wrong in comparing sunspots with the moons. More generally, Galileo was using his predictions to establish the validity of his ideas – if he could be demonstrably right about the complex movements of many small moons, his readers could take that as a token of his wider credibility. This approach was the opposite of the method of Aristotelian astronomers, who did not build theoretical models based on data, but looked for ways of explaining how the available data could be accommodated within existing theory. [ 23 ] [ 40 ]
Some astronomers and philosophers, such as Kepler, did not publish views on the ideas in Galileo's Letters on Sunspots . Most scholars with an interest in the topic divided into those who supported Scheiner's view that sunspots were planets or other bodies above the surface of the Sun, or Galileo's that they were on or very near its surface. From the middle of the seventeenth century the debate about whether Scheiner or Galileo was right died down, partly because the number of sunspots was drastically reduced for several decades in the Maunder Minimum , making observation harder. [ 60 ] After the Paris Observatory was built in 1667, Jean-Dominique Cassini instituted a programme of systematic observations, but he and his colleagues could find little pattern in the appearance of sunspots after many years of observation. [ 61 ] However Cassini's observation did bear out Galileo's argument that sunspots indicated that the Sun was rotating, [ 62 ] and Cassini did discover the rotation of Mars and Jupiter, [ 63 ] which supported Galileo's contention that both the Earth and the Sun rotated.
As Cesi had feared, the hostile tone of the Letters on Sunspots towards Scheiner helped turn the Jesuits against Galileo. [ 64 ] [ 65 ] In 1619, Mario Guiducci published A Discourse on Comets , which was actually mostly written by Galileo, and which included an attack on Scheiner, although its focus was the work of another Jesuit, Orazio Grassi . In 1623, Galileo wrote Il Saggiatore ( The Assayer ) , which accused Scheiner of trying to steal Galileo's ideas. [ 66 ]
In 1624, on a visit to Rome, Scheiner discovered that in The Assayer , Galileo had accused him of plagiarism. Furious, he decided to stay in Rome and devote himself to proving his own expertise in sunspots. His major work on the topic was Rosa Ursina (1626–1630). [ 11 ] It is widely believed, though there is no direct evidence, that the bitter dispute with Scheiner was a factor in bringing Galileo to trial in 1633, and indeed that Scheiner may have worked behind the scenes to bring the trial about. [ 67 ] As a result of pursuing this dispute with Galileo and the years of research it entailed, Scheiner eventually became the world's leading expert on sunspots. [ 55 ]
Together with Niccolò Lorini and Tommaso Caccini , delle Colombe was one of three Florentine Dominicans who opposed Galileo. Along with Raffaelo's brother Lodovico delle Colombe they formed what Galileo called the 'Pigeon League'. Caccini and delle Colombe both used the pulpit to preach against Galileo and the ideas of Copernicus, but only delle Colombe is known to have preached, on two separate occasions, against Galileo's ideas about sunspots. The first occasion was 26 February 1613, when his sermon concluded with these words:
'That ingenious Florentine mathematician of ours [i.e. Galileo] laughs at the ancients who made the sun the most clear and clean of even the smallest spot, whence they formed the proverb 'to seek a spot on the sun.' But he, with the instrument called by him a telescope makes visible that it has regular spots, as by observation of days and months he had demonstrated. But this more truly God does, because 'the heavens are not of the world in His sight'. If spots are found in the suns of the just, do you think they will be found in the moons of the unjust?' [ 68 ]
The second sermon against sunspots was on 8 December 1615, when the Letters on Sunspots had already been referred to the Inquisition for review. The sermon was delivered in Florence cathedral on the Feast of the Immaculate Conception .
'an ingenious academic took for his device a mirror in the face of the sun with the motto 'it shows what is received'. That means he had carved in his spirit I do not know what kind of beloved sun. But what would be better for Mary? Who could fixedly look at the infinite light of the Divine Sun, were it not for this virginal mirror, that in itself conceives it [the light] and renders it to the world? 'Born to us, given to us from an intact virgin?' This is 'Let what is received, be shown'. For one who seeks defects where there are none, is it not to be said to him 'he seeks a spot in the sun?' The sun is without spot, and the mother of the sun is without spot, from where Jesus is born.' [ 69 ]
On 25 November 1615, the Inquisition decided to investigate the Letters on Sunspots because it had been mentioned by Tommaso Caccini and Gianozzo Attavanti in their complaint about Galileo. [ 70 ] Copies of the text were issued to the Inquisition's theological experts on 19 February 1616. On the morning of 23 February they met and agreed two propositions to be censured (that the Sun is the centre of the world, and that the Earth is not the centre of the world, but moves). Neither proposition is contained in Letters on Sunspots . [ 71 ] Shortly after the decision of the Inquisition, the Congregation of the Index placed Copernicus' De Revolutionibus on the Index. Letters on Sunspots was however not banned or required to undergo corrections. [ 72 ] This meant that while Catholic scholars could no longer discuss heliocentrism, they could discuss the nature and origin of sunspots freely.
In 1611, before the Letters on Sunspots appeared, Francesco Sizzi had published Dianoia Astronomica , attacking the ideas of Galileo's earlier work, Siderius Nuncius . In 1612 he went to Paris and devoted himself to the study of sunspots. In 1613 he wrote to Galileo's friend Orazio Morandi, confirming that his circle of colleagues in France agreed with Galileo that sunspots were not freshly generated with each revolution of the Sun, but could be observed passing round it several times. [ 35 ] Furthermore, Sizzi drew to Galileo's attention something he had not yet noticed – that the inclination of the path travelled by sunspots varied with the seasons. Thus in one part of the year the sunspots appeared to be travelling upwards across the face of the Sun; in another part of the year they appeared to be travelling downward. Galileo was to adopt this observation and deploy it in his Dialogue Concerning the Two Chief World Systems in 1632 to demonstrate that the Earth tilted on its axis as it orbited the Sun. [ 73 ]
In his work Phaenomenon singulare (1609) Kepler had described what he took to be the transit of Mercury, observed on 29 May 1607. However, after Michael Maestlin pointed out Galileo's work to him, he corrected himself in 1617 in his Ephemerides , recognising long after the event that what he had seen was sunspots. [ 74 ] Welser sent Kepler a copy of Scheiner's first three Apelles letters, and Kepler replied before Galileo, arguing, like him, that Sunspots must be on the surface of the Sun and not satellites. Kepler reached this conclusion only by studying the evidence Scheiner's had provided, without making any direct observations of his own. Kepler did not however engage with the claims of Galileo in "Letters on Sunspots" or have further involvement in public discussion on the question. [ 11 ]
In his treatise on the comet of 1618, Astronomischer Discurs von dem Cometen, so in Anno 1618 , Michael Maestlin made reference to the work of Fabricius and cited sunspots as evidence of the mutability of the heavens. He made no reference to the work of either Scheiner or Galileo, although he was aware of both. He concluded that sunspots are definitely on or near the Sun, and not a phenomenon of the Earth's atmosphere; that it is only thanks to the telescope that they can be studied, but that they are not a new phenomenon; and that whether they are on the surface of the Sun or move around it is a question to which there is no reliable answer. [ 75 ] [ page needed ]
The French churchman Jean Tarde visited Rome in 1615, and he also met Galileo in Florence and discussed sunspots with him, as well as Galileo's other work. He did not agree with Galileo's view that the sunspots were on or near the surface of the Sun, and held rather that they were small planets. On his return to France in 1615 he built an observatory at La Roque-Gageac where he studied sunspots further. In 1620 he published Borbonia Sidera , dedicated to Louis XIII , in which he declared the spots to be the 'Bourbon planets'. [ 76 ] [ 77 ]
The Belgian Jesuit Charles Malapert agreed with Tarde that the apparent sunspots were in fact planets. His book, published in 1633, was dedicated to Philip IV of Spain and christened them 'Austrian stars' in honour of the house of Habsburg . [ 78 ]
Pierre Gassendi made his own observations of sunspots between 1618 and 1638. [ 79 ] He agreed with Galileo that the spots were on the surface of the Sun, not satellites orbiting it. Like Galileo, he used observation of the spots to estimate the speed of the Sun's rotation, which he gave as 25–26 days. Most of his observations were not published however and his notes were not kept systematically. [ 80 ] He did however discuss his findings with Descartes.
René Descartes was interested in sunspots and his correspondence shows that he was actively gathering information about them when he was working on Le Monde . He was aware of Scheiner's Rosa Ursine published in 1630, which conceded Galileo's point that sunspots are actually on the face of the Sun. Whether he knew of Galileo's ideas primarily through Scheiner or whether he read Letters on Sunspots directly is not known, but in his Principles of Philosophy (1644) he refers to "spots which appear on the sun's surface also revolve around it in planes inclined to that of the ecliptic", which appears to indicate at least a knowledge of Galileo's argument. Descartes used sunspots as an illustration of his Vortex Theory . [ 79 ]
In his 1651 work Almagestum Novum , Giovanni Battista Riccioli set out 126 arguments against the Copernican model of the universe. In his 43rd argument, Riccioli considered the points Galileo had made in his Letters on Sunspots , and asserted that a heliocentric (Copernican) explanation of the phenomenon was more speculative, while a geocentric model allowed for a more parsimonious explanation and was thus more satisfactory (ref: Occam's Razor ). [ 81 ]
As Riccioli explained it, whether the Sun went round the Earth or the Earth round the Sun, three movements were necessary to explain the movement of sunspots. If the Earth moves around the Sun, the necessary movements were the annual motion of the Earth, the diurnal motion of the Earth, and the rotation of the Sun . However, if the Sun moved around the Earth, this accounted for the same movement as both the annual and diurnal motions in the Copernican model. In addition, the annual gyration of the Sun at its poles, and the rotation of the Sun had to be added to completely account for the movement of sunspots. While both models required three movements, the heliocentric model required the Earth to make two movements (annual and diurnal) which could not be demonstrated, while the geocentric model was based on three observable celestial movements, and was accordingly preferable. [ 82 ]
Athanasius Kircher succeeded Scheiner in the Chair of Mathematics at the Collegio Romano . In Mundus Subterraneus (1664), he rejected the views of both Scheiner and Galileo, reviving an earlier idea of Kepler's and arguing that sunspots were in fact smoke emanating from fires on the surface of the Sun, [ 83 ] and that the surface of the Sun was therefore indeed perfect as the Aristotelians believed, although apparently disfigured by blemishes. [ 84 ] Sunspots, he argued, just like the planets in astrology, had a profound influence on the Earth. [ 85 ]
In Il Saggiatore ( The Assayer ) (1623) Galileo was mostly concerned with faults in Orazio Grassi 's arguments about comets, but in the introductory section he wrote :
'How many men attacked my Letters on Sunspots, and under what disguises! The material contained therein ought to have opened to the minds eye much room for admirable speculation; instead it met with scorn and derision. Many people disbelieved it or failed to appreciate it. Others, not wanting to agree with my ideas, advanced ridiculous and impossible opinions against me; and some, overwhelmed and convinced by my arguments, attempted to rob me of that glory which was mine, pretending not to have seen my writings and trying to represent themselves as the original discoverers of these impressive marvels.' [ 86 ]
Christoph Scheiner took this to be an attack on him. He therefore used Rosa Ursina to mount a bitter riposte to Galileo, although he also conceded Galileo's main point, that sunspots exist on the Sun's surface or just above it, and thus that the Sun is not flawless. [ 27 ]
In 1632 Galileo published Dialogo sopra i due Massimi Sistemi del Mondo ( Dialogue Concerning the Two Chief World Systems ), a fictitious four day-long discussion about natural philosophy between the characters Salviati (who argued for Copernican ideas and was effectively a mouthpiece of Galileo), Sagredo, who represented the interested but less well-informed reader, and Simplicio, who argued for Aristotle, and whose arguments were possibly a parody of those made by Pope Urban VIII . [ 87 ] [ 88 ] The book was reviewed by the Roman Inquisition and in 1633 Galileo was interrogated and found 'vehemently suspect of heresy' because of it. He was forced to renounce his belief in heliocentrism, sentenced to house arrest and banned from publishing anything further. The Dialogue was placed on the Index . [ 89 ]
The Dialogue is a broad synthesis of Galileo's thinking about physics, planetary movement, how far we can rely on our senses in making judgements about the world, and how we make intelligent use of evidence. It drew together all his findings and recapitulated arguments made in earlier years on specific topics. [ 90 ] For this reason, there is no 'section on sunspots' in the Dialogue . Rather, they are referred to at various points in arguments about other topics. In the Dialogue , that sunspots are on the surface of the Sun and not planets was taken as established fact. The discussion concerned what inferences could be drawn about the universe from their rotation. Galileo did not argue that the existence of sunspots conclusively proved that the Copernican model was correct and the Aristotelian model wrong; he explained how the rotation of sunspots could be explained in both models, but that the Aristotelian explanation was much more complicated and suppositional. [ 91 ]
Day 1 The discussion opens with Salviati arguing that two key Aristotelian arguments are incompatible; either the heavens are perfect and unchanging, or that the evidence of the senses is preferable to argument and reasoning; either we should rely on the evidence of our senses when they tell us changes (such as sunspots) take place, or we should not. Holding both positions is not tenable. [ 92 ]
Day 2: Salviati argues that sunspots prove the rotation of the Sun on its axis. Aristotelians had previously held that it was impossible for a heavenly body to have more than one natural motion. Aristotelians must therefore choose between their determination that only one natural movement is possible (in which case the Sun is static, as Copernicus argued); or they must explain how a second natural motion occurs if they wish to maintain that the Sun makes a daily orbit of the Earth. This argument is resumed on Day 3 of the Dialogue. [ 93 ] | https://en.wikipedia.org/wiki/Letters_on_Sunspots |
The Letts nitrile synthesis is a chemical reaction of aromatic carboxylic acids with metal thiocyanates to form nitriles . The reaction includes the loss of carbon dioxide and potassium hydrosulfide . The polar basic substitution reaction was discovered in 1872 by Edmund A. Letts . [ 1 ] [ 2 ]
In 1857 Hugo Schiff observed that the reaction between benzoyl chloride with potassium cyanide produced the desired benzonitrile . [ 3 ] Work done later by British chemist Edmund A. Letts delved much deeper into the synthesis of nitriles. Attempting first to add cyano-groups to acetic acid , he obtained a mixture of acetamide and carbonyl sulfide . However, in 1872 he showed that treating a 2:1 molecular ratio of benzoic acid and potassium thiocyanate with heat for several hours also produced nitriles with only a small amount of amide with about 40% yield. [ 4 ]
G. Krüss expanded on Letts' work in 1884, producing better yields by utilizing lead(II) thiocyanate . [ 5 ] In 1916, E.E. Reid found that showed that dry distillation of the zinc (II) salt of the acid with a 20% excess of lead(II) thiocyanate gave an 86% conversion and 91% yield, almost double of that produced by Letts. [ 6 ]
Kekulé proposed the reaction mechanism in 1873. [ 7 ]
In this polar basic substitution reaction mechanism, thiocyanate ion extracts the acidic proton from benzoic acid while heated. This yields the conjugate base (stabilized by resonance structures ) and thiocyanic acid .
The next step involves the evolution of carbon dioxide, where a lone pair of electrons moves from the negatively charged oxygen to form a double bond with the carboxylic carbon. The sigma bond between the ring and carboxyl group is then severed, the electron pair moving to the ring and delocalized through resonance structures.
The final step of the mechanism involves the attack of the phenyl anion attacking the cyano-carbon, pushing the electron pair over to the sulfur, which readily diffuses the negative charge and is further stabilized by the potassium ion , resulting in the final benzonitrile product and potassium hydrosulfide.
Aromatic nitriles have a few applications, including polyrecombination to form polymers , [ 8 ] are sometimes studied as biologically active molecules [ 9 ] and undergoing Ritter reactions to form amides . [ 10 ]
Benzonitrile, the original product of Letts, has multiple uses as a versatile reagent and as a solvent . Substituted benzonitriles are important in many fields including pharmaceuticals. Benzonitrile is a precursor in the synthesis of Fadrozole , an aromatase inhibitor used in the treatment of breast cancer . [ 11 ] 4-(trifluoromethyl)benzonitrile, produced by the Nickel catalyzed cyanation of 4-chlorobenzotrifluoride is a precursor for the antidepressant Fluvoxamine . [ 12 ]
Benzonitrile can also act a ligand in asymmetric catalysis , coordinating to transition metals and forming Lewis acids . [ 13 ] [ 14 ]
For synthesis of nitriles:
For reactions of nitriles: | https://en.wikipedia.org/wiki/Letts_nitrile_synthesis |
Leu-enkephalin is an endogenous opioid peptide neurotransmitter with the amino acid sequence Tyr-Gly-Gly-Phe-Leu that is found naturally in the brains of many animals, including humans. [ 2 ] [ 3 ] It is one of the two forms of enkephalin ; the other is met-enkephalin . [ 2 ] The tyrosine residue at position 1 is thought to be analogous to the 3-hydroxyl group on morphine . [ 4 ] Leu-enkephalin has agonistic actions at both the μ- and δ-opioid receptors , with significantly greater preference for the latter. It has little to no effect on the κ-opioid receptor . [ 5 ] [ 6 ]
A nasal spray formulation of leu-enkephalin (developmental code names NES-100, NM-0127, NM-127, PES-200; proposed brand name Envelta) is under development by Virpax Pharmaceuticals for the treatment of pain and post-traumatic stress disorder (PTSD). [ 7 ] As of November 2023, it is up to the preclinical stage of development for these indications. [ 7 ]
This biochemistry article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Leu-enkephalin |
Leuckart's law is an empirical law in zoology that states that the size of the eye of an animal is related to its maximum speed of movement; fast-moving animals have larger eyes, after allowing for the effects of body mass . The hypothesis dates from 1876, [ 1 ] and in older literature is usually referred to as Leuckart's ratio . [ 2 ] It was proposed by Rudolf Leuckart in 1876. [ 3 ]
The principle was initially applied to birds; it has also been applied to mammals. [ 4 ]
A study of 88 bird species, published in 2011, found no useful correlation between flight speed and eye size. [ 5 ]
This animal anatomy –related article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Leuckart's_law |
The Leuckart reaction is the chemical reaction that converts aldehydes or ketones to amines . The reaction is an example of reductive amination . [ 1 ] The reaction, named after Rudolf Leuckart , uses either ammonium formate or formamide as the nitrogen donor and reducing agent . It requires high temperatures, usually between 120 and 130 °C; for the formamide variant, the temperature can be greater than 165 °C.
The Leuckart reaction is named in honor of its developer, the German chemist Rudolf Leuckart (1854–1899). He discovered that heating benzaldehyde with formamide does not produce benzylidenediformamide as anticipated, but benzylamine . [ 2 ] In 1891, a colleague of Leuckart at the University of Göttingen, Otto Wallach, performed further reactions using alicyclic and terpenoid ketones as well as aldehydes, demonstrating the general application. [ 2 ] Over the course of the past century, chemists have discovered several methods to improve the yield of the reaction and carry it out under less strenuous conditions. Pollard and Young summarized various ways in which amines can be formed: using either formamide or ammonium formate, or both, or adding formic acid to formamide. [ 3 ] However, using just ammonium formate as the reagent produces the best yields. [ 4 ] [ 3 ] Using formamide produces low yields compared to ammonium formate but yields can be increased by using large amount of formamide, or using ammonium formate, ammonium sulfate, and magnesium chloride as catalysts . [ 5 ]
Ammonium formate is a source of formic acid and ammonia . Starting with nucleophilic attack on the carbonyl by the ammonia, the carbonyl is converted to the iminium ion: [ 6 ]
The iminium is then reduced by the formate:
Formamide first nucleophilically attacks the carbonyl carbon. The oxygen is protonated by abstracting hydrogen from the nitrogen atom, subsequently forming a water molecule that leaves, forming N-formyl derivative, which is resonance stabilized. [ 3 ] Water hydrolyzes formamide to give ammonium formate, which acts as a reducing agent and adds on to the N-formyl derivative. Hydride shift occurs, resulting in loss of carbon dioxide. An ammonium ion is added forming an imine and releasing ammonia. The imine goes through hydrolysis to form the amine, which is depicted in the scheme below.
An example of the Leuckart reaction is its use in the synthesis of tetrahydro-1,4 benzodiazepin-5-one, a molecule that is part of the benzodiazepine family. [ 7 ] | https://en.wikipedia.org/wiki/Leuckart_reaction |
The Leuckart thiophenol reaction is the decomposition of a diazoxanthate, by gentle warming in a slightly acidic cuprous medium, to its corresponding aryl xanthates which give aryl thiols on alkaline hydrolysis and aryl thioethers on further warming. [ 1 ]
This reaction was first reported by Rudolf Leuckart in 1890. [ 2 ] [ 3 ] [ 4 ]
This chemical reaction article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Leuckart_thiophenol_reaction |
Leucopelargonidin is a colorless chemical compound related to leucoanthocyanins . It can be found in Albizia lebbeck (East Indian walnut), in the fruit of Anacardium occidentale (Cashew), in the fruit of Areca catechu (Areca nut), in the fruit of Hydnocarpus wightianus (Hindi Chaulmoogra), in the rhizome of Rumex hymenosepalus (Arizona dock), in Zea mays (Corn) and in Ziziphus jujuba (Chinese date). [ 1 ]
(+)-Leucopelargonidin can be synthesized from (+)- aromadendrin by sodium borohydride reduction. [ 2 ]
Dihydrokaempferol 4-reductase uses cis -3,4-leucopelargonidin and NADP + to produce (+)-aromadendrin, NADPH, and H + .
Leucoanthocyanidin reductase transforms cis -3,4-leucopelargonidin into afzelechin .
This biochemistry article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Leucopelargonidin |
Leucyl aminopeptidases ( EC 3.4.11.1 , leucine aminopeptidase , LAPs , leucyl peptidase , peptidase S , cytosol aminopeptidase , cathepsin III , L-leucine aminopeptidase , leucinaminopeptidase , leucinamide aminopeptidase , FTBL proteins , proteinates FTBL , aminopeptidase II , aminopeptidase III , aminopeptidase I ) are enzymes that preferentially catalyze the hydrolysis of leucine residues at the N-terminus of peptides and proteins . Other N-terminal residues can also be cleaved, however. LAPs have been found across superkingdoms . Identified LAPs include human LAP, bovine lens LAP, porcine LAP, Escherichia coli ( E. coli ) LAP (also known as PepA or XerB), and the solanaceous -specific acidic LAP (LAP-A) in tomato ( Solanum lycopersicum ).
The active sites in PepA and in bovine lens LAP have been found to be similar. [ 1 ] Shown in the picture below is the proposed model for the active site of LAP-A in tomato based on the work of Strater et al . [ 2 ] It is also known that the biochemistry of the LAPs from these three kingdoms is very similar. PepA, bovine lens LAP, and LAP-A preferentially cleave N-terminal leucine, arginine , and methionine residues. These enzymes are all metallopeptidases requiring divalent metal cations for their enzymatic activity [ 3 ] Enzymes are active in the presence of Mn +2 , Mg +2 and Zn +2 . These enzymes are also known to have high pH (pH 8) and temperature optima. At pH 8, the highest enzymatic activity is seen at 60 °C. PepA, bovine lens LAP and LAP-A are also known to form hexamers in vivo . The Gu et al. from 1999 demonstrated that six 55kDA enzymatically inactive LAP-A protomers come together to form the 353kDa bioactive LAP-A hexamer. Structures of the bovine lens LAP protomer and the biologically active hexamer have been constructed [ 4 ] can be found through Protein Data Bank (2J9A).
Historically, the mechanisms of carboxypeptidases and endoprotease have been much more well-studied and understood by researchers (Ref #6 Lipscomb 1990). Work within the past two decades has provided vital knowledge regarding the mechanisms of aminopeptidases. The mechanism of
bovine lens LAP and PepA have been elucidated (Ref 1 and 2), however, the exact mechanism of tomato LAP-A is unknown at this time. A search of current literature does not indicate that new research is underway to determine the exact mechanism of LAP-A. Based on the biochemical similarities of the LAPs between kingdoms, the mechanism of LAP-A may be similar to bovine lens LAP and PepA.
Once thought of as a housekeeping gene necessary only for protein turnover , studies have demonstrated that LAP-A has a regulatory role in the immune response in tomato.
In order to survive, plants must be able to respond to many biotic and abiotic stresses, including pathogen attack, piercing/sucking insects , herbivory , and mechanical wounding. These stresses activate specialized signal transduction pathways , which are specific to the stressor and the amount of tissue damage inflicted. Similar to mechanical wounding, chewing insects, such as the tobacco hornworm (Manduca sexta, one of the major pests of tomato), cause extensive tissue damage activating the jasmonic acid (JA)-mediated response (Walling 2000). This JA-mediated response revolves around the octadecanoid pathway , which is responsible for the synthesis of JA and several other potent signaling molecules, and ends in the regulation of two sets of genes whose expression changes over time. The early genes amplify the wounding signal and can be detected 30 minutes to 2 hours after damage (Ryan 2000). Late gene expression can be seen 4–24 hours after wounding. Products of late-response genes act as deterrents to chewing-insect feeding, often by decreasing the nutritional value of the food ingested or interfering with insect gut function (Walling 2000). For example, serine proteinase inhibitors (Pins) interfere with digestive proteases in the insect gut and polyphenol oxidases (PPO) act to decrease the nutritive value of plant leaves after ingestion by herbivores (Johnson et al. 1989; Ryan 2000; Orozco-Cardenas 2001). Please see the Picture 3 for a summary of the wound response in tomato.
The plant response in this octadecanoid pathway is similar to mammalian prostaglandin and leukotriene pathways (Ref Walling 2000). This particular pathway is inhibited by salicylic acid .
(LAP-A), a product of the octadecanoid pathway in some solanaceous plants, has been shown by Fowler et al. to have a regulatory role in the late wound response of tomato. Experiments were conducted using three genotypes of tomato plants: wildtype (WT), (LapA-SI) plants that were silenced for LAP-A, and LapA-OX that constitutively expressed LAP-A. Late-gene expression was inhibited in wounded LapA-SI plants, and the LapA-SI plants were also more susceptible to tobacco hornworm feeding, relative to wildtype (WT) plants. In comparison, the wounded LapA-OX leaves exhibited heightened levels of late gene RNA accumulation, an increased resistance to herbivory, and extended expression of late wound-response genes. These data suggest that LAP-A functions in regulating both the intensity and the persistence of the late wound response. However, unwounded LapA-OX did not accumulate late gene RNA transcripts, suggesting that presence of LAP-A alone is not sufficient to induce late gene expression. LAP-A is the first plant aminopeptidase shown to have a regulatory role in signal transduction pathway.
LAP proteins are expressed in a variety of marine organisms as a method of coping with the osmotic threat high salinity poses to the cell. During bouts of high salinity, LAP begins the catalysis of proteins in order to release amino acids into the cell in an attempt to balance the high ion concentrations in the external environment. [ 5 ] | https://en.wikipedia.org/wiki/Leucyl_aminopeptidase |
A leukocidin is a type of cytotoxin created by some types of bacteria ( Staphylococcus ). It is a type of pore-forming toxin . Leukocidins fall into the category of bacterial invasin . Invasins are enzymatic secretions that help bacteria invade the host tissue to which they are attached. Although similar to exotoxins , invasins are different in two respects: they work through much less specific mechanisms than exotoxins, and their actions are generally more localized.
Leukocidins get their names by killing ("-cide") leukocytes . Leukocidins target phagocytes , [ 1 ] natural killer cells , dendritic cells , and T lymphocytes , [ 2 ] and therefore affect both innate and adaptive immune responses.
Leukocidins are pore-forming toxins , and their model for pore formation is step-wise.
First, the cytotoxin's "S" subunit recognizes specific protein-containing receptors, typically G-protein coupled receptors , or an integrin on the host cell's surface. The S subunit then recruits a second, "F" subunit. The two subunits dimerize on the host cell surface. This dimerization is followed by oligomerization involving three additional leukocidin dimers, resulting in an octameric prepore complex.
The prepore undergoes a structural transition in which its prestem domain extends into the lipid bilayer , forming a beta barrel that pierces the target cell membrane, thereby disrupting the structure of the cell and leading to lysis. [ 1 ]
The F subunit stands for the "fast" subunit while the S subunit stands for the "slow" subunit. [ 3 ] The S subunit is the first to bind the lipid bilayer, recognizing the cell surface receptor. Once bound, the F subunit dimerizes with the S subunit to initiate pore assembly.
There are exceptions to the typical binding pattern of leukocidins. For example:
One notable type of leukocidin is the Panton-Valentine leukocidin .
This biochemistry article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Leukocidin |
Leukocyte-promoting factor , more commonly known as leukopoietin , is a category of substances produced by neutrophils when they encounter a foreign antigen . Leukopoietin stimulates the bone marrow to increase the rate of leukopoiesis in order to replace the neutrophils that will inevitably be lost when they begin to phagocytose the foreign antigens. [ citation needed ]
Leukocyte-promoting factors include colony stimulating factors (CSFs) (produced by monocytes and T lymphocytes ), interleukins (produced by monocytes, macrophages , and endothelial cells ), prostaglandins , and lactoferrin . [ 1 ]
This biochemistry article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Leukocyte-promoting_factor |
The leukocyte immunoglobulin-like receptors (LILR) are a family of receptors possessing extracellular immunoglobulin domains . [ 1 ] They are also known as CD85 , ILTs and LIR, and can exert immunomodulatory effects on a wide range of immune cells. [ 2 ] The human genes encoding these receptors are found in a gene cluster at chromosomal region 19q13.4.
They include
A subset of LILR recognise MHC class I (also known as HLA class I in humans). The LILR family is a cluster of paired receptors with both activating and inhibitory functions. [ 3 ] Of these, the inhibitory receptors LILRB1 and LILRB2 show a broad specificity for classical and non-classical MHC alleles with preferential binding to b2m -associated complexes. In contrast, the activating receptors LILRA1 and LILRA3 prefer b2m-independent free heavy chains of MHC class I, and in particular HLA-C alleles. [ 4 ]
This biochemistry article is a stub . You can help Wikipedia by expanding it .
This article about a biochemical receptor is a stub . You can help Wikipedia by expanding it .
This immunology article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Leukocyte_immunoglobulin-like_receptors |
Leukotrienes are a family of eicosanoid inflammatory mediators produced in leukocytes by the oxidation of arachidonic acid (AA) and the essential fatty acid eicosapentaenoic acid (EPA) by the enzyme arachidonate 5-lipoxygenase . [ 1 ] [ 2 ] [ 3 ]
Leukotrienes use lipid signaling to convey information to either the cell producing them ( autocrine signaling ) or neighboring cells ( paracrine signaling ) in order to regulate immune responses. The production of leukotrienes is usually accompanied by the production of histamine and prostaglandins , which also act as inflammatory mediators. [ 4 ]
One of their roles (specifically, leukotriene D 4 ) is to trigger contractions in the smooth muscles lining the bronchioles; their overproduction is a major cause of inflammation in asthma and allergic rhinitis . [ 5 ] Leukotriene antagonists are used to treat these disorders by inhibiting the production or activity of leukotrienes. [ 6 ]
The name leukotriene , introduced by Swedish biochemist Bengt Samuelsson in 1979, comes from the words leukocyte and triene (indicating the compound's three conjugated double bonds ).
What would be later named leukotriene C, "slow reaction smooth muscle-stimulating substance" ( SRS ) was originally described between 1938 and 1940 by Feldberg and Kellaway. [ 7 ] [ 8 ] [ 9 ] The researchers isolated SRS from lung tissue after a prolonged period following exposure to snake venom and histamine. [ 9 ]
LTC 4 , LTD 4 , LTE 4 and LTF 4 are often called cysteinyl leukotrienes due to the presence of the amino acid cysteine in their structure. The cysteinyl leukotrienes make up the slow-reacting substance of anaphylaxis (SRS-A). LTF 4 , like LTD 4 , is a metabolite of LTC 4 , but, unlike LTD 4 , which lacks the glutamic residue of glutathione , LTF 4 lacks the glycine residue of glutathione. [ 10 ]
LTB 4 is synthesized in vivo from LTA 4 by the enzyme LTA 4 hydrolase . Its primary function is to recruit neutrophils to areas of tissue damage, though it also helps promote the production of inflammatory cytokines by various immune cells. Drugs that block the actions of LTB 4 have shown some efficacy in slowing the progression of neutrophil-mediated diseases. [ 11 ]
There has also been postulated the existence of LTG 4 , a metabolite of LTE 4 in which the cysteinyl moiety has been oxidized to an alpha-keto-acid (i.e.—the cysteine has been replaced by a pyruvate ). Very little is known about this putative leukotriene. [ citation needed ]
Leukotrienes originating from the omega-3 class eicosapentanoic acid (EPA) have diminished inflammatory effects. In human subjects whose diets have been supplemented with eicosapentaenoic acid, leukotrine B5, along with leukotrine B4, is produced by neutrophils. [ 12 ] LTB 5 induces aggregation of rat neutrophils , chemokinesis of human polymorphonuclear neutrophils (PMN), lysosomal enzyme release from human PMN and potentiation of bradykinin-induced plasma exudation, although compared to LTB 4 , it has at least 30 times less potency. [ 13 ]
Leukotrienes are synthesized in the cell from arachidonic acid by arachidonate 5-lipoxygenase . The catalytic mechanism involves the insertion of an oxygen moiety at a specific position in the arachidonic acid backbone. [ citation needed ]
The lipoxygenase pathway is active in leukocytes and other immunocompetent cells, including mast cells , eosinophils , neutrophils , monocytes , and basophils . When such cells are activated, arachidonic acid is liberated from cell membrane phospholipids by phospholipase A2 , and donated by the 5-lipoxygenase-activating protein (FLAP) to 5-lipoxygenase. [ citation needed ]
5- Lipoxygenase (5-LO) uses FLAP to convert arachidonic acid into 5-hydroperoxyeicosatetraenoic acid (5-HPETE), which spontaneously reduces to 5-hydroxyeicosatetraenoic acid (5-HETE). The enzyme 5-LO acts again on 5-HETE to convert it into leukotriene A 4 (LTA 4 ), an unstable epoxide. 5-HETE can be further metabolized to 5-oxo-ETE and 5-oxo-15-hydroxy-ETE, all of which have pro-inflammatory actions similar but not identical to those of LTB 4 and mediated not by LTB 4 receptors but rather by the OXE receptor (see 5-Hydroxyeicosatetraenoic acid and 5-Oxo-eicosatetraenoic acid ). [ 14 ] [ 15 ]
In cells equipped with LTA hydrolase , such as neutrophils and monocytes, LTA 4 is converted to the dihydroxy acid leukotriene LTB 4 , which is a powerful chemoattractant for neutrophils acting at BLT 1 and BLT 2 receptors on the plasma membrane of these cells. [ citation needed ]
In cells that express LTC 4 synthase , such as mast cells and eosinophils, LTA 4 is conjugated with the tripeptide glutathione to form the first of the cysteinyl-leukotrienes, LTC 4 . Outside the cell, LTC 4 can be converted by ubiquitous enzymes to form successively LTD 4 and LTE 4 , which retain biological activity . [ citation needed ]
The cysteinyl-leukotrienes act at their cell-surface receptors CysLT1 and CysLT2 on target cells to contract bronchial and vascular smooth muscle, to increase permeability of small blood vessels, to enhance secretion of mucus in the airway and gut, and to recruit leukocytes to sites of inflammation. [ citation needed ]
Both LTB 4 and the cysteinyl-leukotrienes (LTC 4 , LTD 4 , LTE 4 ) are partly degraded in local tissues, and ultimately become inactive metabolites in the liver. [ citation needed ]
Leukotrienes act principally on a subfamily of G protein-coupled receptors . They may also act upon peroxisome proliferator-activated receptors . Leukotrienes are involved in asthmatic and allergic reactions and act to sustain inflammatory reactions. Several leukotriene receptor antagonists such as montelukast and zafirlukast are used to treat asthma . Recent research points to a role of 5-lipoxygenase in cardiovascular and neuropsychiatric illnesses. [ 16 ]
Leukotrienes are very important agents in the inflammatory response. Some such as LTB 4 have a chemotactic effect on migrating neutrophils, and as such help to bring the necessary cells to the tissue. Leukotrienes also have a powerful effect in bronchoconstriction and increase vascular permeability . [ 17 ]
Leukotrienes contribute to the pathophysiology of asthma , especially in patients with aspirin-exacerbated respiratory disease (AERD), and cause or potentiate the following symptoms : [ 18 ]
Cysteinyl leukotriene receptors CYSLTR1 and CYSLTR2 are present on mast cells, eosinophil, and endothelial cells. During cysteinyl leukotriene interaction, they can stimulate proinflammatory activities such as endothelial cell adherence and chemokine production by mast cells. As well as mediating inflammation, they induce asthma and other inflammatory disorders, thereby reducing the airflow to the alveoli . The levels of cysteinyl leukotrienes, along with 8-isoprostane , have been reported to be increased in the EBC of patients with asthma , correlating with disease severity. [ 19 ] Cysteinyl leukotrienes may also play a role in adverse drug reactions in general and in contrast medium induced adverse reactions in particular. [ 20 ]
In excess, the cysteinyl leukotrienes can induce anaphylactic shock . [ 21 ] | https://en.wikipedia.org/wiki/Leukotriene |
Leukotriene D 4 ( LTD 4 ) is one of the leukotrienes . Its main function in the body is to induce the contraction of smooth muscle , resulting in bronchoconstriction and vasoconstriction . It also increases vascular permeability . LTD 4 is released by basophils . Other leukotrienes that function in a similar manner are leukotrienes C 4 and E 4 . Pharmacological agents that inhibit the function of these leukotrienes are leukotriene receptor antagonists (e.g., zafirlukast , montelukast ) and are useful for asthmatic individuals . [ 1 ]
This biochemistry article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Leukotriene_D4 |
The leukotriene ( LT ) receptors are G protein-coupled receptors that bind and are activated by the leukotrienes . They include the following proteins :
The recently elucidated CysLT E , represented by GPR99/OXGR1 , may constitute a third CysLTR. [ 1 ]
This biochemistry article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Leukotriene_receptor |
Levacetylmethadol ( INN ), levomethadyl acetate ( USAN ), OrLAAM (trade name) or levo-α-acetylmethadol ( LAAM ) [ 1 ] [ 2 ] is a synthetic opioid similar in structure to methadone . It has a long duration of action due to its active metabolites .
LAAM is indicated as a second-line treatment for the treatment and management of opioid dependence if patients fail to respond to drugs like methadone or buprenorphine .
LAAM is used as an oral solution of LAAM hydrochloride at a concentration of 10 mg/mL in bottles of 120 and 500 mL under the brand name Orlaam. The first dose of LAAM for patients who have not started treatment with methadone is 20–40 mg. The first dose for patients who have been receiving methadone will be a little higher than the amount of methadone that was being taken every day, but not more than 120 mg. Afterwards, the dosage may be adjusted as needed. Unlike methadone, which requires daily administration, LAAM is administered two to three times a week.
LAAM acts as a μ-opioid receptor agonist . It also acts as a potent, noncompetitive α 3 β 4 neuronal nicotinic acetylcholine receptor antagonist . [ 3 ]
LAAM undergoes extensive first-pass metabolism to the active demethylated metabolite nor-LAAM, which is further demethylated to a second active metabolite, dinor-LAAM. These metabolites are more potent than the parent drug.
LAAM, or levomethadyl acetate, is the levo isomer of acetylmethadol , or α-methadyl acetate. The dextro isomer, d - alphacetylmethadol ( d -α-acetylmethadol), is more potent but shorter acting. The levo isomer is also less toxic with an LD 50 in mice of 110 mg/kg s.c. and 172.8 mg/kg orally as opposed to LD 50 s of 61 mg/kg s.c. and 118.3 mg/kg orally for dl -α-methadyl acetate. It has a melting point of 215 °C and a molecular weight of 353.50. β-methadyl acetate also exists, but is more toxic and less active than α-methadyl acetate and has no current medical use.
LAAM was approved in 1993 by the U.S. Food and Drug Administration for use in the treatment of opioid dependence . In 2001, LAAM was removed from the European market due to reports of life-threatening ventricular rhythm disorders . [ 4 ] In 2003, Roxane Laboratories, Inc. discontinued Orlaam in the US. [ 5 ]
Before August 1993, LAAM was classified as a schedule I drug in the United States. LAAM is not approved for use in Australia and Canada . At present, it is a Schedule II Narcotic controlled substance in the United States with a DEA ACSCN of 9648 and a national aggregate annual manufacturing quota of 4 grams as of 2013. [ needs update ] | https://en.wikipedia.org/wiki/Levacetylmethadol |
Levamlodipine ( INN ), also known as levoamlodipine or S -amlodipine is a pharmacologically active enantiomer of amlodipine . [ 1 ] Amlodipine belongs to the dihydropyridine group of calcium channel blocker used as an antihypertensive and antianginal agent. [ 2 ] It was approved by the U.S. FDA in December 2019 and is currently marketed under the brand name Conjupri . [ 3 ]
Amlodipine blocks the transmembrane influx of calcium into the vascular and cardiac smooth muscles resulting in vasodilation and hence a fall in blood pressure. Levamlodipine is an allosteric modulator and acts on the L-type of calcium channels . [ 4 ] [ 5 ] Receptor binding studies have shown that out of the two forms only the ( S )-enantiomer of amlodipine binds to and blocks L-type calcium channels whereas the ( R )-enantiomer has no activity on these channels. [ 6 ]
The precise mechanisms by which levamlodipine relieves angina have not been fully explored, but are thought to include the following:
Administration of levamlodipine (2.5 mg) as a single dose gives maximum plasma concentration ( C max ) of 8.3 to 9.3 ng/mL in 2 to 3 hrs ( T max ). It is extensively (about 90%) converted to inactive metabolites via hepatic metabolism with 10% of the parent compound and 60% of the metabolites excreted in the urine. Levamlodipine shows approximately 93% plasma protein binding in hypertensive patients. The mean AUC 0– t value ( t = 48 hrs) of levamlodipine tablets (2.5 mg) is 95 ± 14 ng·hr/mL . The plasma elimination half-life of levamlodipine has been found to be 31 ± 13 hrs . [ 7 ]
Various clinical studies have shown that levamlodipine has more selectivity and better efficacy than ( R )-amlodipine. In pooled data, from three comparative studies conducted in 200 patients with mild to moderate hypertension , 2.5 mg of levamlodipine was found to be equivalent in its blood pressure lowering efficacy to 5 mg of amlodipine. The average reduction in systolic BP was 19±3 vs 19±4, 20±2 vs 19±3 and 20±2 vs 19±3 mm of Hg recorded in standing, supine and sitting position respectively for levamlodipine compared to racemic amlodipine. The studies also reported a significant reduction in total cholesterol and triglyceride levels with levamlodipine, which was not seen with amlodipine. [ 8 ] [ 9 ] [ 10 ]
Efficacy and safety of levamlodipine (2.5 mg, once daily) has been evaluated in the patients with isolated systolic hypertension (ISH). Levamlodipine effectively reduced the systolic BP (mean reduction 22±14 mm of Hg) in all grades of ISH. After 28 days of the treatment, overall responder rate was 73%. It significantly reduced the systolic and diastolic BP within 4 weeks with a responder rate of 96.5%. [ 11 ]
Elderly hypertensives with diabetes mellitus exhibits higher response to levamlodipine therapy than non-diabetic patients. Levamlodipine is an effective switch-over option for the elderly patients who experience oedema and other adverse events with racemic amlodipine. [ 12 ]
The use of racemic amlodipine is commonly associated with adverse events like peripheral edema and other side effects like headache, dizziness, flushing and abdominal pain. [ 13 ] Controlled clinical trials showed that levamlodipine is rarely associated with these side effects. [ 14 ] No controlled clinical study of levamlodipine has been performed in patients with hepatic impairment and renal impairment. Clinical studies in patients with normal liver function have shown that there is no elevation in the hepatic enzymes with the use of levamlodipine. [ 2 ] However, caution should be taken while administering levamlodipine to such patients.
In a postmarketing surveillance study, levamlodipine (2.5/5 mg) was found to be well tolerated ( n = 1859) in patients with hypertension. Out of 314 patients, who reported peripheral edema with conventional amlodipine were switched over to levamlodipine and edema was resolved in 310 patients (98.72%) at the end of 4 weeks. Only in 4 patients was edema sustained. Only 30 patients (out of 1859) reported side effects. These side effects included vertigo , tachycardia , cough, headache, fever, mild difficulty in breathing and edema . Adverse events were mild in nature and no serious adverse events were reported. [ 14 ]
Aside from the U.S., levamlodipine is currently marketed in Brazil under the brand name Novanlo ( Biolab Sanus ) and in India as Eslo (Zuventus Healthcare Ltd.), Asomex ( Emcure Pharmaceutical Ltd. ) and Espin (Intas Pharmaceuticals Ltd.). [ 15 ] [ 16 ] | https://en.wikipedia.org/wiki/Levamlodipine |
Levdobutamine ( INN Tooltip International Nonproprietary Name ; developmental code name LY-206243 ; also known as ( S )-dobutamine ) is a sympathomimetic , selective β 1 -adrenergic receptor agonist , and positive inotrope which was never marketed. [ 1 ] [ 2 ] It is the ( S )- enantiomer of dobutamine . [ 1 ]
This drug article relating to the cardiovascular system is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Levdobutamine |
In science and engineering , a power level and a field level (also called a root-power level ) are logarithmic magnitudes of certain quantities referenced to a standard reference value of the same type.
The type of level and choice of units indicate the scaling of the logarithm of the ratio between the quantity and its reference value, though a logarithm may be considered to be a dimensionless quantity. [ 1 ] [ 2 ] [ 3 ] The reference values for each type of quantity are often specified by international standards.
Power and field levels are used in electronic engineering , telecommunications , acoustics and related disciplines. Power levels are used for signal power, noise power, sound power, sound exposure, etc. Field levels are used for voltage, current, sound pressure . [ 4 ] [ clarification needed ]
Level of a power quantity, denoted L P , is defined by
where
The level of a root-power quantity (also known as a field quantity), denoted L F , is defined by [ 5 ]
where
If the power quantity P is proportional to F 2 , and if the reference value of the power quantity, P 0 , is in the same proportion to F 0 2 , the levels L F and L P are equal.
The neper , bel , and decibel (one tenth of a bel) are units of level that are often applied to such quantities as power, intensity, or gain. [ 6 ] The neper, bel, and decibel are related by [ 7 ]
Level and its units are defined in ISO 80000-3 .
The ISO standard defines each of the quantities power level and field level to be dimensionless, with 1 Np = 1 . This is motivated by simplifying the expressions involved, as in systems of natural units .
Power and field quantities are part of a larger class, logarithmic ratio quantities.
ANSI/ASA S1.1-2013 defines a class of quantities it calls levels . It defines a level of a quantity Q , denoted L Q , as [ 8 ]
where
For the level of a root-power quantity, the base of the logarithm is r = e .
For the level of a power quantity, the base of the logarithm is r = e 2 . [ 9 ]
The logarithmic frequency ratio (also known as frequency level ) of two frequencies is the logarithm of their ratio, and may be expressed using the unit octave (symbol: oct) corresponding to the ratio 2 or the unit decade (symbol: dec) corresponding to the ratio 10: [ 7 ]
In music theory , the octave is a unit used with logarithm base 2 (called interval ). [ 10 ] A semitone is one twelfth of an octave. A cent is one hundredth of a semitone. In this context, the reference frequency is taken to be C 0 , four octaves below middle C . [ 11 ] | https://en.wikipedia.org/wiki/Level_(logarithmic_quantity) |
A level crossing is an intersection where a railway line crosses a road, path , or (in rare situations) airport runway, at the same level, [ 1 ] as opposed to the railway line or the road etc. crossing over or under using an overpass or tunnel . The term also applies when a light rail line with separate right-of-way or reserved track crosses a road in the same fashion. Other names include railway level crossing , [ 1 ] railway crossing (chiefly international), grade crossing or railroad crossing (chiefly American), [ 2 ] road through railroad , criss-cross , train crossing , and RXR (abbreviated).
There are more than 100,000 level crossings in Europe and more than 200,000 in North America.
Road-grade crossings are considered incompatible with high-speed rail [ 3 ] and are virtually non-existent in European high-speed train operations. [ 4 ]
The types of early level crossings varied by location, but often they had a flagman in a nearby booth who, on the approach of a train, would wave a red flag or lantern to stop all traffic and clear the tracks. This was a dangerous job that cost the lives of gatekeepers or their family members, as the train was not given enough time to stop. [ 5 ]
Gated crossings became commonplace in many areas, as they protected the railway from people trespassing and livestock, and they protected the users of the crossing when closed by the signalman/gateman. In the second quarter of the 20th century [ citation needed ] , manual or electrical closable gates that barricaded the roadway started to be introduced, intended to be a complete barrier against intrusion of any road traffic onto the railway. Automatic crossings are now commonplace in some countries as motor vehicles replaced horse-drawn vehicles and the need for animal protection diminished with time. Full-, half- or no-barrier crossings superseded gated crossings, although crossings of older types can still be found in places.
In rural regions with sparse traffic, the least expensive type of level crossing to operate is one without flagmen or gates, with only a warning sign posted. This type has been common across North America and in many developing countries.
Some international rules have helped to harmonise level crossing. For instance, the 1968 Vienna Convention states (chapter 3, article 23b) that:
This has been implemented in many countries, including countries which are not part of the Vienna Convention.
Trains have a much larger mass relative to their braking capability, and thus a far longer braking distance than road vehicles. With rare exceptions, trains do not stop at level crossings but rely on road vehicles and pedestrians to clear the tracks in advance. There have been several accidents in which a heavy load on a slow road transporter has not cleared the line in time, eg Dalfsen train crash and Hixon rail crash . At Hixon the police escort had received no training in their responsiblities.
Level crossings constitute a significant safety concern internationally. On average, each year around 400 people in the European Union [ 8 ] and over 300 in the United States [ 9 ] are killed in level crossing accidents. Collisions can occur with vehicles as well as pedestrians; pedestrian collisions are more likely to result in a fatality. [ 10 ] Among pedestrians, young people (5–19 years), older people (60 years and over), and males are considered to be higher risk users. [ 11 ] On some commuter lines most trains may slow to stop at a station, but express or freight trains will pass through stations at high speed without slowing.
As far as warning systems for road users are concerned, level crossings either have "passive" protection, in the form of various types of warning signs, or " active " protection, using automatic warning devices such as flashing lights, warning sounds, and barriers or gates. [ 8 ] In the 19th century and for much of the 20th, a sign warning "Stop, look, and listen" (or similar wording) was the sole protection at most level crossings. Fewer collisions take place at level crossings with active warning systems, and today active protection is widely available. [ 12 ] Modern radar sensor systems can detect if level crossings are free of obstructions as trains approach. These improve safety by not lowering crossing barriers that may trap vehicles or pedestrians on the tracks, while signalling trains to brake until the obstruction clears. However, they cannot prevent a vehicle from moving out onto the track once it is far too late for the locomotive to slow even slightly. [ 13 ]
Due to the increase in road and rail traffic as well as for safety reasons, level crossings are increasingly being removed. As an example, Melbourne is As of 2024 [update] planning to close 110 level crossings by 2030 and (due to the proximity of some stations) rebuild 51 stations. [ citation needed ]
At railway stations , a pedestrian level crossing is sometimes provided to allow passengers to reach other platforms in the absence of an underpass or bridge, or for disabled access. Where third rail systems have level crossings, there is a gap in the third rail over the level crossing, but this does not necessarily interrupt the power supply to trains since they may have current collectors on multiple cars.
Source: US Department of Transportation. [ 14 ] (1 mile=1.6 km)
Source: Eurostat : The rail accident data are provided to Eurostat by the European Railway Agency (ERA). The ERA manages and is responsible for the entire data collection. The Eurostat data constitute a part of the data collected by ERA and are part of the so-called Common Safety Indicators (CSIs).
Note: Since 2010, use of national definitions is no longer permitted: 2010 CSI data represent the first fully harmonized set of figures.
Traffic signal -controlled intersections next to level crossings on at least one of the roads in the intersection usually feature traffic signal preemption . [ 16 ] In the US, approaching trains activate a routine where, before the road lights and barriers are activated, all traffic signal phases go to red, except for the signal immediately after the crossing, which turns green (or flashing yellow) to allow traffic on the tracks to clear (in some cases, there are auxiliary traffic signals prior to the railroad crossing which will turn red, keeping new traffic from crossing the tracks. This is in addition to the flashing lights on the crossing barriers). After enough time to clear the crossing, the signal will turn. The crossing lights may begin flashing and the barriers lower immediately, or this might be delayed until after the traffic light turns red.
The operation of a traffic signal, while a train is present, may differ from municipality to municipality. There are a number of possible arrangements:
In France, cameras have been installed on some level crossings to obtain images to improve understanding of an incident when a technical investigation occurs. [ 17 ]
In England, cameras have been installed at some level crossings. [ 18 ] [ 19 ]
In South Australia, cameras have been installed at some level crossings to deter non-compliance with signals. [ 20 ]
Designs of level crossings vary between countries.
Level crossings present a significant risk of collisions between trains and road vehicles. This list is not a definitive list of the world's worst accidents and the events listed are limited to those where a separate article describes the event in question.
Aircraft runways sometimes cross roads or rail lines, and require signaling to avoid collisions.
Winston Churchill Avenue intersects the runway of Gibraltar International Airport at surface level; movable barricades close when aircraft land or take off.
As of March 2023, a tunnel under the runway opened to regular traffic, and the level crossing will only be available to pedestrians, cyclists and e-scooters. [ 47 ]
After the runway of Kai Tak Airport was extended in 1943, it intersected with the easternmost section of Prince Edward Road , so all road traffic had to be stopped during takeoffs and landings. The issue was relieved when the authorities constructed a new runway for replacement in September 1958. [ 48 ]
The Fianarantsoa-Côte Est railway crosses the runway at Manakara Airport . It is one of the few airports in the world that crosses an active railway line.
A level crossing near Gisborne , sees the Palmerston North - Gisborne Line cross one of Gisborne Airport 's runways . Aircraft landing on sealed 1310-metre runway 14L/32R are signalled with two red flashing lights on either side of the runway and a horizontal bar of flashing red lights to indicate the runway south of the railway line is closed, and may only land on the 866 metres (2,841 ft) section of the runway north of the railway line. When the full length of the runway is open, a vertical bar of green lights signal to the aircraft, with regular rail signals on either side of the runway indicating trains to stop. [ 49 ] [ 50 ]
The runway of Ometepe Airport crosses the highway NIC-64.
As of February 2023, there exists one road-runway crossing at Catarman Airport in Northern Samar. [ 51 ]
The Visby Lärbro Line between Visby and Lärbro crossed the runway of Visby Airport between 1956 and 1960. [ 52 ]
Two public roads cross the runway at Meiringen Air Base . Electrically operated gates close when aircraft land or take off. [ 53 ] | https://en.wikipedia.org/wiki/Level_crossing |
Level of invention (or degree of inventiveness , or level of solution , or rank of solution , or rank of invention ) is a relative degree of changes to the previous system (or solution) in the result of solution of inventive problem (one containing a contradiction ). Term was defined and introduced by TRIZ author G. S. Altshuller .
After initially reviewing 200,000 patent abstracts, Altshuller selected 40,000 as representatives of high level inventive solutions. The remainder involved direct improvements easily recognized within the specialty of the system.
Altshuller separated the patents' different degrees of inventiveness into five levels:
These levels of invention are applied to solutions rather than problems requiring a system of solution.
Also level of invention and the potential for innovation in any nation, geographical area or economic activity is as measurement in the concept of innovative capacity originally introduced by Prof. Suarez-Villa in 1990. [ 1 ]
This standards - or measurement -related article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Level_of_invention |
Level repulsion is the quantum mechanical equivalent to a repulsion effect in oscillators . [ 1 ] A system of two coupled oscillators has two natural frequencies. As the coupling strength between the oscillators increases, the lower frequency decreases and the higher increases. [ 2 ]
This quantum mechanics -related article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Level_repulsion |
A level spreader is an erosion control device designed to reduce water pollution by mitigating the impact of high-velocity stormwater surface runoff . It is used both on construction sites and for permanent applications such as drainage for roads and highways . The device reduces the energy level in high-velocity flow by converting it into sheet flow, and disperses the discharged water so that it may be infiltrated into soil . [ 1 ] [ 2 ]
Level spreaders may be used in conjunction with runoff infiltration devices such as bioretention systems, infiltration basins and percolation trenches . | https://en.wikipedia.org/wiki/Level_spreader |
A level staff , also called levelling rod , is a graduated wooden or aluminium rod, used with a levelling instrument to determine the difference in height between points or heights of points above a vertical datum .
When used for stadiametric rangefinding , the level staff is called a stadia rod .
Levelling rods can be one piece, but many are sectional and can be shortened for storage and transport or lengthened for use. Aluminum rods may be shortened by telescoping sections inside each other, while wooden rod sections can be attached to each other with sliding connections or slip joints , or hinged to fold when not in use.
There are many types of rods, with names that identify the form of the graduations and other characteristics. Markings can be in imperial or metric units. Some rods are graduated on one side only while others are marked on both sides. If marked on both sides, the markings can be identical or can have imperial units on one side and metric on the other.
In the photograph on the right, both a metric (left) and imperial (right) levelling rod are seen. This is a two-sided aluminum rod, coated white with markings in contrasting colours. The imperial side has a bright yellow background.
The metric rod has major numbered graduations in meters and tenths of meters (e.g. 18 is 1.8 m - there is a tiny decimal point between the numbers). Between the major marks are either a pattern of squares and spaces in different colours or an E shape (or its mirror image) with horizontal components and spaces between of equal size. In both parts of the pattern, the squares, lines or spaces are precisely one centimetre high. When viewed through an instrument's telescope, the observer can visually interpolate a 1 cm mark to a tenth of its height, yielding a reading with precision in mm. Usually readings are recorded with millimetre precision. On this side of the rod, the colours of the markings alternate between red and black with each meter of length.
The imperial graduations are in feet (large red numbers), tenths of a foot (small black numbers) and hundredths of a foot (unnumbered marks or spaces between the marks). The tenths of a foot point is indicated by the top of the long mark with the upward sloped end. The point halfway between tenths of a foot marks is indicated by the bottom of a medium length black mark with a downward sloped end. Each mark or space is approximately 3mm, yielding roughly the same accuracy as the metric rod.
Rods come in two classes:
Self-reading rods are rods that are read by the person viewing the rod through the telescope of the instrument. The graduations are sufficiently clear to read with good accuracy. Target rods, on the other hand, are equipped with a target. The target is a round or oval plate marked in quarters in contrasting colours such as red and white in opposite quarters. A hole in the centre allows the instrument user to see the rod's scale. The target is adjusted by the rodman according to the instructions from the instrument man. When the target is set to align with the crosshairs of the instrument, the rodman records the level value. The target may have a vernier to allow fractional increments of the graduation to be read.
Digital levels electronically read a bar-coded scale on the staff. These instruments usually include data recording capability. The automation removes the requirement for the operator to read a scale and write down the value, and so reduces blunders. It may also compute and apply refraction and curvature corrections.
Topographer's rods are special purpose rods used in topographical surveys. The rod has the zero mark at mid-height and the graduations increase in both directions away from the mid-height.
In use, the rod is adjusted so that the zero point is level with the instrument (or the surveyor's eye if he is using a hand level for low-resolution work). When placed at any point where the level is to be read, the value seen is the height above or below the viewer's position.
An alternative topographer's rod has the graduations numbered upwards from the base. | https://en.wikipedia.org/wiki/Level_staff |
Levelling or leveling ( American English ; see spelling differences ) is a branch of surveying , the object of which is to establish or verify or measure the height of specified points relative to a datum. It is widely used in geodesy and cartography to measure vertical position with respect to a vertical datum , and in construction to measure height differences of construction artifacts. In photolithography , the same term is used in a lithography machine calibration step measuring or calibrating wafer surface height with respect to a reference.
Optical levelling , also known as spirit levelling and differential levelling , employs an optical level , which consists of a precision telescope with crosshairs and stadia marks . The cross hairs are used to establish the level point on the target, and the stadia allow range-finding; stadia are usually at ratios of 100:1, in which case one metre between the stadia marks on the level staff (or rod ) represents 100 metres from the target.
The complete unit is normally mounted on a tripod , and the telescope can freely rotate 360° in a horizontal plane. The surveyor adjusts the instrument's level by coarse adjustment of the tripod legs and fine adjustment using three precision levelling screws on the instrument to make the rotational plane horizontal. The surveyor does this with the use of a bull's eye level built into the instrument mount.
The surveyor looks through the eyepiece of telescope while an assistant holds a vertical level staff which is graduated in inches or centimeters. The level staff is placed vertically using a level, with its foot on the point for which the level measurement is required. The telescope is rotated and focused until the level staff is plainly visible in the crosshairs. In the case of a high accuracy manual level, the fine level adjustment is made by an altitude screw, using a high accuracy bubble level fixed to the telescope. This can be viewed by a mirror whilst adjusting or the ends of the bubble can be displayed within the telescope, which also allows assurance of the accurate level of the telescope whilst the sight is being taken. However, in the case of an automatic level, altitude adjustment is done automatically by a suspended prism due to gravity, as long as the coarse levelling is accurate within certain limits. When level, the staff graduation reading at the crosshairs is recorded, and an identifying mark or marker placed where the level staff rested on the object or position being surveyed.
A typical procedure for a linear track of levels from a known datum is as follows. Set up the instrument within 100 metres (110 yards) of a point of known or assumed elevation. A rod or staff is held vertical on that point and the instrument is used manually or automatically to read the rod scale. This gives the height of the instrument above the starting (backsight) point and allows the height of the instrument (H.I.) above the datum to be computed.
The rod is then held on an unknown point and a reading is taken in the same manner, allowing the elevation of the new (foresight) point to be computed. The difference between these two readings equals the change in elevation, which is why this method is also called differential levelling . The procedure is repeated until the destination point is reached. It is usual practice to perform either a complete loop back to the starting point or else close the traverse on a second point whose elevation is already known. The closure check guards against blunders in the operation, and allows residual error to be distributed in the most likely manner among the stations.
Some instruments provide three crosshairs which allow stadia measurement of the foresight and backsight distances. These also allow use of the average of the three readings (3-wire leveling) as a check against blunders and for averaging out the error of interpolation between marks on the rod scale.
The two main types of levelling are single-levelling as already described, and double-levelling (double-rodding). In double-levelling, a surveyor takes two foresights and two backsights and makes sure the difference between the foresights and the difference between the backsights are equal, thereby reducing the amount of error. [ 1 ] Double-levelling costs twice as much as single-levelling. [ 2 ]
When using an optical level, the endpoint may be out of the effective range of the instrument. There may be obstructions or large changes of elevation between the endpoints. In these situations, extra setups are needed. Turning is a term used when referring to moving the level to take an elevation shot from a different location.
To "turn" the level, one must first take a reading and record the elevation of the point the rod is located on. While the rod is being kept in exactly the same location, the level is moved to a new location where the rod is still visible. A reading is taken from the new location of the level and the height difference is used to find the new elevation of the level gun. This is repeated until the series of measurements is completed.
The level must be horizontal to get a valid measurement. Because of this, if the horizontal crosshair of the instrument is lower than the base of the rod, the surveyor will not be able to sight the rod and get a reading. The rod can usually be raised up to 25 feet high, allowing the level to be set much higher than the base of the rod.
The other standard method of levelling in construction and surveying is called trigonometric levelling , which is preferred when levelling "out" to a number of points from one stationary point. This is done by using a total station , or any other instrument to read the vertical, or zenith angle to the rod, and the change in elevation is calculated using trigonometric functions (see example below). At greater distances (typically 1,000 feet and greater), the curvature of the Earth , and the refraction of the instrument wave through the air must be taken into account in the measurements as well (see section below).
Ex: an instrument at Point A reading to a rod at Point B a zenith angle of < 88°15'22" (degrees, minutes, seconds of arc ) and a slope distance of 305.50 feet not factoring rod or instrument height would be calculated thus:
meaning an elevation change of approximately 9.30 feet in elevation between Points A and B. So if Point A is at 1,000 feet of elevation, then Point B would be at approximately 1,009.30 feet of elevation, as the reference line (0°) for zenith angles is straight up going clockwise one complete revolution, and so an angle reading of less than 90 degrees (horizontal or flat) would be looking uphill and not down (and opposite for angles greater than 90 degrees), and so would gain elevation.
The curvature of the earth means that a line of sight that is horizontal at the instrument will be higher and higher above a spheroid at greater distances. The effect may be insignificant for some work at distances under 100 meters. The increase in height of a straight line with distance D is:
where R is the radius of the earth.
The line of sight is horizontal at the instrument, but is not a straight line because of atmospheric refraction . The change of air density with elevation causes the line of sight to bend toward the earth.
The combined correction for refraction and curvature is approximately: [ 3 ]
For precise work these effects need to be calculated and corrections applied. For most work it is sufficient to keep the foresight and backsight distances approximately equal so that the refraction and curvature effects cancel out. Refraction is generally the greatest source of error in leveling. For short level lines the effects of temperature and pressure are generally insignificant, but the effect of the temperature gradient dT / dh can lead to errors. [ 4 ]
Assuming error-free measurements, if the Earth's gravity field were completely regular and gravity constant, leveling loops would always close precisely:
around a loop. In the real gravity field of the Earth, this happens only approximately; on small loops typical of engineering projects, the loop closure is negligible, but on larger loops covering regions or continents it is not.
Instead of height differences, geopotential differences do close around loops:
where g i {\displaystyle g_{i}} stands for gravity at the leveling interval i . For precise leveling networks on a national scale, the latter formula should always be used.
should be used in all computations, producing geopotential values W i {\displaystyle W_{i}} for the benchmarks of the network.
High precision levelling, especially when conducted over long distances as used for the establishment and maintenance of vertical datums , is called geodetic levelling . [ 5 ]
The dumpy level was developed by English civil engineer William Gravatt , while surveying the route of a proposed railway line from London to Dover. More compact and hence both more robust and easier to transport, it is commonly believed that dumpy levelling is less accurate than other types of levelling, but such is not the case. Dumpy levelling requires shorter and therefore more numerous sights, but this fault is compensated by the practice of making foresights and backsights equal.
Precise level designs were often used for large leveling projects where utmost accuracy was required. They differ from other levels in having a very precise spirit level tube and a micrometer adjustment to raise or lower the line of sight so that the crosshair can be made to coincide with a line on the rod scale and no interpolation is required.
Automatic levels make use of a compensator that ensures that the line of sight remains horizontal once the operator has roughly leveled the instrument (to within maybe 0.05 degree). The compensator consists of small prisms suspended from wires inside of the level's chassis that are connected together in the shape of a pendulum. This allows for only horizontal light rays to enter, even in cases where the telescope of the instrument is not perfectly plumb. [ 6 ]
The surveyor sets the instrument up quickly and does not have to re-level it carefully each time they sight on a rod on another point. It also reduces the effect of minor settling of the tripod to the actual amount of motion instead of leveraging the tilt over the sight distance. Because the level of the instrument only needs to be adjusted once per setup, the surveyor can quickly and easily read as many side-shots as necessary between turns. Three level screws are used to level the instrument, as opposed to the four screws historically found in dumpy levels.
Laser levels [ 7 ] project a beam which is visible and/or detectable by a sensor on the leveling rod. This style is widely used in construction work but not for more precise control work. An advantage is that one person can perform the levelling independently, whereas other types require one person at the instrument and one holding the rod.
The sensor can be mounted on earth-moving machinery to allow automated grading . | https://en.wikipedia.org/wiki/Levelling |
A level staff , also called levelling rod , is a graduated wooden or aluminium rod, used with a levelling instrument to determine the difference in height between points or heights of points above a vertical datum .
When used for stadiametric rangefinding , the level staff is called a stadia rod .
Levelling rods can be one piece, but many are sectional and can be shortened for storage and transport or lengthened for use. Aluminum rods may be shortened by telescoping sections inside each other, while wooden rod sections can be attached to each other with sliding connections or slip joints , or hinged to fold when not in use.
There are many types of rods, with names that identify the form of the graduations and other characteristics. Markings can be in imperial or metric units. Some rods are graduated on one side only while others are marked on both sides. If marked on both sides, the markings can be identical or can have imperial units on one side and metric on the other.
In the photograph on the right, both a metric (left) and imperial (right) levelling rod are seen. This is a two-sided aluminum rod, coated white with markings in contrasting colours. The imperial side has a bright yellow background.
The metric rod has major numbered graduations in meters and tenths of meters (e.g. 18 is 1.8 m - there is a tiny decimal point between the numbers). Between the major marks are either a pattern of squares and spaces in different colours or an E shape (or its mirror image) with horizontal components and spaces between of equal size. In both parts of the pattern, the squares, lines or spaces are precisely one centimetre high. When viewed through an instrument's telescope, the observer can visually interpolate a 1 cm mark to a tenth of its height, yielding a reading with precision in mm. Usually readings are recorded with millimetre precision. On this side of the rod, the colours of the markings alternate between red and black with each meter of length.
The imperial graduations are in feet (large red numbers), tenths of a foot (small black numbers) and hundredths of a foot (unnumbered marks or spaces between the marks). The tenths of a foot point is indicated by the top of the long mark with the upward sloped end. The point halfway between tenths of a foot marks is indicated by the bottom of a medium length black mark with a downward sloped end. Each mark or space is approximately 3mm, yielding roughly the same accuracy as the metric rod.
Rods come in two classes:
Self-reading rods are rods that are read by the person viewing the rod through the telescope of the instrument. The graduations are sufficiently clear to read with good accuracy. Target rods, on the other hand, are equipped with a target. The target is a round or oval plate marked in quarters in contrasting colours such as red and white in opposite quarters. A hole in the centre allows the instrument user to see the rod's scale. The target is adjusted by the rodman according to the instructions from the instrument man. When the target is set to align with the crosshairs of the instrument, the rodman records the level value. The target may have a vernier to allow fractional increments of the graduation to be read.
Digital levels electronically read a bar-coded scale on the staff. These instruments usually include data recording capability. The automation removes the requirement for the operator to read a scale and write down the value, and so reduces blunders. It may also compute and apply refraction and curvature corrections.
Topographer's rods are special purpose rods used in topographical surveys. The rod has the zero mark at mid-height and the graduations increase in both directions away from the mid-height.
In use, the rod is adjusted so that the zero point is level with the instrument (or the surveyor's eye if he is using a hand level for low-resolution work). When placed at any point where the level is to be read, the value seen is the height above or below the viewer's position.
An alternative topographer's rod has the graduations numbered upwards from the base. | https://en.wikipedia.org/wiki/Levelling_rod |
Biological organization is the organization of complex biological structures and systems that define life using a reductionistic approach. [ 1 ] The traditional hierarchy, as detailed below, extends from atoms to biospheres . The higher levels of this scheme are often referred to as an ecological organizational concept, or as the field , hierarchical ecology .
Each level in the hierarchy represents an increase in organizational complexity , with each "object" being primarily composed of the previous level's basic unit. [ 2 ] The basic principle behind the organization is the concept of emergence —the properties and functions found at a hierarchical level are not present and irrelevant at the lower levels.
The biological organization of life is a fundamental premise for numerous areas of scientific research , particularly in the medical sciences . Without this necessary degree of organization, it would be much more difficult—and likely impossible—to apply the study of the effects of various physical and chemical phenomena to diseases and physiology (body function). For example, fields such as cognitive and behavioral neuroscience could not exist if the brain was not composed of specific types of cells, and the basic concepts of pharmacology could not exist if it was not known that a change at the cellular level can affect an entire organism. These applications extend into the ecological levels as well. For example, DDT 's direct insecticidal effect occurs at the subcellular level, but affects higher levels up to and including multiple ecosystems . Theoretically, a change in one atom could change the entire biosphere .
The simple standard biological organization scheme, from the lowest level to the highest level, is as follows: [ 1 ]
More complex schemes incorporate many more levels. For example, a molecule can be viewed as a grouping of elements , and an atom can be further divided into subatomic particles (these levels are outside the scope of biological organization). Each level can also be broken down into its own hierarchy, and specific types of these biological objects can have their own hierarchical scheme. For example, genomes can be further subdivided into a hierarchy of genes . [ 4 ]
Each level in the hierarchy can be described by its lower levels. For example, the organism may be described at any of its component levels, including the atomic, molecular, cellular, histological (tissue), organ and organ system levels. Furthermore, at every level of the hierarchy, new functions necessary for the control of life appear. These new roles are not functions that the lower level components are capable of and are thus referred to as emergent properties .
Every organism is organized, though not necessarily to the same degree. [ 5 ] An organism can not be organized at the histological (tissue) level if it is not composed of tissues in the first place. [ 6 ]
Biological organization is thought to have emerged in the early RNA world when RNA chains began to express the basic conditions necessary for natural selection to operate as conceived by Darwin (heritability, variation of type, and competition for limited resources). Fitness of an RNA replicator (its per capita rate of increase) would likely have been a function of adaptive capacities that were intrinsic (in the sense that they were determined by the nucleotide sequence) and the availability of resources. [ 7 ] [ 8 ] The three primary adaptive capacities may have been:
(1) the capacity to replicate with moderate fidelity (giving rise to both heritability and variation of type).
(2) the capacity to avoid decay.
(3) the capacity to acquire and process resources. [ 7 ] [ 8 ]
These capacities would have been determined initially by the folded configurations of the RNA replicators (see " Ribozyme ") that, in turn, would be encoded in their individual nucleotide sequences. Competitive success among different RNA replicators would have depended on the relative values of these adaptive capacities. Subsequently, among more recent organisms competitive success at successive levels of biological organization, presumably continued to depend, in a broad sense, on the relative values of these adaptive capacities.
Empirically, a large proportion of the (complex) biological systems we observe in nature exhibit hierarchical structure. On theoretical grounds we could expect complex systems to be hierarchies in a world in which complexity had to evolve from simplicity. System hierarchies analysis performed in the 1950s, [ 9 ] [ 10 ] laid the empirical foundations for a field that would be, from the 1980s, hierarchical ecology . [ 11 ] [ 12 ] [ 13 ] [ 14 ] [ 15 ]
The theoretical foundations are summarized by thermodynamics. When biological systems are modeled as physical systems , in its most general abstraction, they are thermodynamic open systems that exhibit self-organized behavior, [ 16 ] and the set/subset relations between dissipative structures can be characterized in a hierarchy.
A simpler and more direct way to explain the fundamentals of the "hierarchical organization of life", was introduced in Ecology by Odum and others as the " Simon 's hierarchical principle"; [ 17 ] Simon [ 18 ] emphasized that hierarchy " emerges almost inevitably through a wide variety of evolutionary processes, for the simple reason that hierarchical structures are stable ".
There once were two watchmakers, named Hora and Tempus, who made very fine watches. The phones in their workshops rang frequently; new customers were constantly calling them. However, Hora prospered while Tempus became poorer and poorer. In the end, Tempus lost his shop. What was the reason behind this?
The watches consisted of about 1000 parts each. The watches that Tempus made were designed such that, when he had to put down a partly assembled watch (for instance, to answer the phone), it immediately fell into pieces and had to be reassembled from the basic elements.
Hora had designed his watches so that he could put together subassemblies of about ten components each. Ten of these subassemblies could be put together to make a larger sub-assembly. Finally, ten of the larger subassemblies constituted the whole watch. Each subassembly could be put down without falling apart. | https://en.wikipedia.org/wiki/Levels_of_organization_(ecology) |
Levenshtein coding is a universal code encoding the non-negative integers developed by Vladimir Levenshtein . [ 1 ] [ 2 ]
The code of zero is "0"; to code a positive number :
The code begins:
To decode a Levenshtein-coded integer:
The Levenshtein code of a positive integer is always one bit longer than the Elias omega code of that integer. However, there is a Levenshtein code for zero, whereas Elias omega coding would require the numbers to be shifted so that a zero is represented by the code for one instead. | https://en.wikipedia.org/wiki/Levenshtein_coding |
In information theory , linguistics , and computer science , the Levenshtein distance is a string metric for measuring the difference between two sequences. The Levenshtein distance between two words is the minimum number of single-character edits (insertions, deletions or substitutions) required to change one word into the other. It is named after Soviet mathematician Vladimir Levenshtein , who defined the metric in 1965. [ 1 ]
Levenshtein distance may also be referred to as edit distance , although that term may also denote a larger family of distance metrics known collectively as edit distance . [ 2 ] : 32 It is closely related to pairwise string alignments .
The Levenshtein distance between two strings a , b {\displaystyle a,b} (of length | a | {\displaystyle |a|} and | b | {\displaystyle |b|} respectively) is given by lev ( a , b ) {\displaystyle \operatorname {lev} (a,b)} where
where the tail {\displaystyle \operatorname {tail} } of some string x {\displaystyle x} is a string of all but the first character of x {\displaystyle x} (i.e. tail ( x 0 x 1 … x n ) = x 1 x 2 … x n {\displaystyle \operatorname {tail} (x_{0}x_{1}\dots x_{n})=x_{1}x_{2}\dots x_{n}} ), and head ( x ) {\displaystyle \operatorname {head} (x)} is the first character of x {\displaystyle x} (i.e. head ( x 0 x 1 … x n ) = x 0 {\displaystyle \operatorname {head} (x_{0}x_{1}\dots x_{n})=x_{0}} ). Either the notation x [ n ] {\displaystyle x[n]} or x n {\displaystyle x_{n}} is used to refer to the n {\displaystyle n} th character of the string x {\displaystyle x} , counting from 0 , thus head ( x ) = x 0 = x [ 0 ] {\displaystyle \operatorname {head} (x)=x_{0}=x[0]} .
The first element in the minimum corresponds to deletion (from a {\displaystyle a} to b {\displaystyle b} ), the second to insertion and the third to replacement.
This definition corresponds directly to the naive recursive implementation .
For example, the Levenshtein distance between "kitten" and "sitting" is 3, since the following 3 edits change one into the other, and there is no way to do it with fewer than 3 edits:
A simple example of a deletion can be seen with "uninformed" and "uniformed" which have a distance of 1:
The Levenshtein distance has several simple upper and lower bounds. These include:
An example where the Levenshtein distance between two strings of the same length is strictly less than the Hamming distance is given by the pair "flaw" and "lawn". Here the Levenshtein distance equals 2 (delete "f" from the front; insert "n" at the end). The Hamming distance is 4.
In approximate string matching , the objective is to find matches for short strings in many longer texts, in situations where a small number of differences is to be expected. The short strings could come from a dictionary, for instance. Here, one of the strings is typically short, while the other is arbitrarily long. This has a wide range of applications, for instance, spell checkers , correction systems for optical character recognition , and software to assist natural-language translation based on translation memory .
The Levenshtein distance can also be computed between two longer strings, but the cost to compute it, which is roughly proportional to the product of the two string lengths, makes this impractical. Thus, when used to aid in fuzzy string searching in applications such as record linkage , the compared strings are usually short to help improve speed of comparisons. [ citation needed ]
In linguistics, the Levenshtein distance is used as a metric to quantify the linguistic distance , or how different two languages are from one another. [ 3 ] It is related to mutual intelligibility : the higher the linguistic distance, the lower the mutual intelligibility, and the lower the linguistic distance, the higher the mutual intelligibility.
There are other popular measures of edit distance , which are calculated using a different set of allowable edit operations. For instance,
Edit distance is usually defined as a parameterizable metric calculated with a specific set of allowed edit operations, and each operation is assigned a cost (possibly infinite). This is further generalized by DNA sequence alignment algorithms such as the Smith–Waterman algorithm , which make an operation's cost depend on where it is applied.
This is a straightforward, but inefficient, recursive Haskell implementation of a lDistance function that takes two strings, s and t , together with their lengths, and returns the Levenshtein distance between them:
This implementation is very inefficient because it recomputes the Levenshtein distance of the same substrings many times.
A more efficient method would never repeat the same distance calculation. For example, the Levenshtein distance of all possible suffixes might be stored in an array M {\displaystyle M} , where M [ i ] [ j ] {\displaystyle M[i][j]} is the distance between the last i {\displaystyle i} characters of string s and the last j {\displaystyle j} characters of string t . The table is easy to construct one row at a time starting with row 0. When the entire table has been built, the desired distance is in the table in the last row and column, representing the distance between all of the characters in s and all the characters in t .
This section uses 1-based strings rather than 0-based strings. If m is a matrix, m [ i , j ] {\displaystyle m[i,j]} is the i th row and the j th column of the matrix, with the first row having index 0 and the first column having index 0.
Computing the Levenshtein distance is based on the observation that if we reserve a matrix to hold the Levenshtein distances between all prefixes of the first string and all prefixes of the second, then we can compute the values in the matrix in a dynamic programming fashion, and thus find the distance between the two full strings as the last value computed.
This algorithm, an example of bottom-up dynamic programming , is discussed, with variants, in the 1974 article The String-to-string correction problem by Robert A. Wagner and Michael J. Fischer. [ 4 ]
This is a straightforward pseudocode implementation for a function LevenshteinDistance that takes two strings, s of length m , and t of length n , and returns the Levenshtein distance between them:
Two examples of the resulting matrix (hovering over a tagged number reveals the operation performed to get that number):
The invariant maintained throughout the algorithm is that we can transform the initial segment s [ 1. . i ] into t [ 1. . j ] using a minimum of d [ i , j ] operations. At the end, the bottom-right element of the array contains the answer.
It turns out that only two rows of the table – the previous row and the current row being calculated – are needed for the construction, if one does not want to reconstruct the edited input strings.
The Levenshtein distance may be calculated iteratively using the following algorithm: [ 5 ]
Hirschberg's algorithm combines this method with divide and conquer . It can compute the optimal edit sequence, and not just the edit distance, in the same asymptotic time and space bounds. [ 6 ]
Levenshtein automata efficiently determine whether a string has an edit distance lower than a given constant from a given string. [ 7 ]
The Levenshtein distance between two strings of length n can be approximated to within a factor
where ε > 0 is a free parameter to be tuned, in time O ( n 1 + ε ) . [ 8 ]
It has been shown that the Levenshtein distance of two strings of length n cannot be computed in time O ( n 2 − ε ) for any ε greater than zero unless the strong exponential time hypothesis is false. [ 9 ] | https://en.wikipedia.org/wiki/Levenshtein_distance |
A Levenspiel plot is a plot used in chemical reaction engineering to determine the required volume of a chemical reactor given experimental data on the chemical reaction taking place in it. It is named after the late chemical engineering professor Octave Levenspiel .
For a continuous stirred-tank reactor (CSTR), the following relationship applies: [ 1 ] [ 2 ]
V = F A o ( 1 − r A ) X {\displaystyle V=F_{Ao}\left({\frac {1}{-r_{A}}}\right)X}
where:
For a plug flow reactor (PFR), the following relationship applies:
V = F A o ∫ 0 X 1 − r A d X {\displaystyle V=F_{Ao}\int _{0}^{X}{\frac {1}{-r_{A}}}dX}
If F A o − r A {\displaystyle F_{Ao} \over -r_{A}} is plotted as a function of X {\displaystyle X} , the required volume to achieve a specific conversion can be determined given an entering molar flow rate.
The volume of a CSTR necessary to achieve a certain conversion at a given flow rate is equal to the area of the rectangle with height equal to F A o − r A {\displaystyle F_{Ao} \over -r_{A}} and width equal to X {\displaystyle X} .
The volume of a PFR necessary to achieve a certain conversion at a given flow rate is equal to the area under the curve of F A o − r A {\displaystyle F_{Ao} \over -r_{A}} plotted against X {\displaystyle X} . | https://en.wikipedia.org/wiki/Levenspiel_plot |
In chemistry , the lever rule is a formula used to determine the mole fraction ( x i ) or the mass fraction ( w i ) of each phase of a binary equilibrium phase diagram . It can be used to determine the fraction of liquid and solid phases for a given binary composition and temperature that is between the liquidus and solidus line. [ 1 ]
In an alloy or a mixture with two phases, α and β, which themselves contain two elements , A and B, the lever rule states that the mass fraction of the α phase is
where
all at some fixed temperature or pressure.
Suppose an alloy at an equilibrium temperature T consists of w B {\displaystyle w_{\rm {B}}} mass fraction of element B. Suppose also that at temperature T the alloy consists of two phases, α and β, for which the α consists of w B α {\displaystyle w_{\rm {B}}^{\alpha }} , and β consists of w B β {\displaystyle w_{\rm {B}}^{\beta }} . Let the mass of the α phase in the alloy be m α {\displaystyle m^{\alpha }} so that the mass of the β phase is m β = m − m α {\displaystyle m^{\beta }=m-m^{\alpha }} , where m {\displaystyle m} is the total mass of the alloy.
By definition, then, the mass of element B in the α phase is m B α = w B α m α {\displaystyle m_{\rm {B}}^{\alpha }=w_{\rm {B}}^{\alpha }m^{\alpha }} , while the mass of element B in the β phase is m B β = w B β ( m − m α ) {\displaystyle m_{\rm {B}}^{\beta }=w_{\rm {B}}^{\beta }\left(m-m^{\alpha }\right)} . Together these two quantities sum to the total mass of element B in the alloy, which is given by m B = w B m {\displaystyle m_{\rm {B}}=w_{\rm {B}}m} . Therefore,
By rearranging, one finds that
This final fraction is the mass fraction of the α phase in the alloy.
Before any calculations can be made, a tie line is drawn on the phase diagram to determine the mass fraction of each element; on the phase diagram to the right it is line segment LS. This tie line is drawn horizontally at the composition's temperature from one phase to another (here the liquid to the solid). The mass fraction of element B at the liquidus is given by w B l (represented as w l in this diagram) and the mass fraction of element B at the solidus is given by w B s (represented as w s in this diagram). The mass fraction of solid and liquid can then be calculated using the following lever rule equations: [ 1 ]
where w B is the mass fraction of element B for the given composition (represented as w o in this diagram).
The numerator of each equation is the original composition that we are interested in is +/- the opposite lever arm . That is if you want the mass fraction of solid then take the difference between the liquid composition and the original composition. And then the denominator is the overall length of the arm so the difference between the solid and liquid compositions. If you're having difficulty realising why this is so, try visualising the composition when w o approaches w l . Then the liquid concentration will start increasing.
There is now more than one two-phase region. The tie line drawn is from the solid alpha to the liquid and by dropping a vertical line down at these points the mass fraction of each phase is directly read off the graph, that is the mass fraction in the x axis element. The same equations can be used to find the mass fraction of alloy in each of the phases, i.e. w l is the mass fraction of the whole sample in the liquid phase. [ 2 ] | https://en.wikipedia.org/wiki/Lever_rule |
In petroleum engineering , the Leverett J -function is a dimensionless function of water saturation describing the capillary pressure , [ 1 ]
where S w {\displaystyle S_{w}} is the water saturation measured as a fraction, p c {\displaystyle p_{c}} is the capillary pressure (in pascal ), k {\displaystyle k} is the permeability (measured in m² ), ϕ {\displaystyle \phi } is the porosity (0-1), γ {\displaystyle \gamma } is the surface tension (in N/m) and θ {\displaystyle \theta } is the contact angle . The function is important in that it is constant for a given saturation within a reservoir, thus relating reservoir properties for neighboring beds.
The Leverett J -function is an attempt at extrapolating capillary pressure data for a given rock to rocks that are similar but with differing permeability, porosity and wetting properties. It assumes that the porous rock can be modelled as a bundle of non-connecting capillary tubes, where the factor k / ϕ {\displaystyle {\sqrt {k/\phi }}} is a characteristic length of the capillaries' radii.
This function is also widely used in modeling two-phase flow of proton-exchange membrane fuel cells . [ 2 ] A large degree of hydration is needed for good proton conductivity while large liquid water saturation in pores of catalyst layer or diffusion media will impede gas transport in the cathode.
This fluid dynamics –related article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Leverett_J-function |
The Leverhulme Centre for the Future of Intelligence ( CFI ) is an interdisciplinary research centre within the University of Cambridge that studies artificial intelligence . [ 1 ] [ 2 ] It is funded by the Leverhulme Trust . [ 3 ]
The Centre brings together academics from the fields of computer science, philosophy, social science and others. The centre works with the Oxford Martin School at the University of Oxford, Imperial College London , and the University of California, Berkeley [ 1 ] and has a memorandum of understanding with the Coral Bell School of Asia Pacific Affairs at the Australian National University . [ 4 ]
The CFI research is structured in a series of programmes and research exercises. The topics of the programmes range from algorithmic transparency to exploring the implications of AI for democracy. [ 5 ]
In July 2019, Leverhulme released the Animal-AI Olympics competition, featuring tests ordinarily used to test animal intelligence . [ 6 ] [ 7 ] [ 8 ]
This article relating to the University of Cambridge is a stub . You can help Wikipedia by expanding it .
This article about futures studies is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Leverhulme_Centre_for_the_Future_of_Intelligence |
Levetiracetam , sold under the brand name Keppra among others, is a novel antiepileptic drug [ 7 ] ( medication ) used to treat epilepsy . [ 8 ] It is used for partial-onset , myoclonic , or tonic–clonic seizures, [ 7 ] and is taken either by mouth as an immediate or extended release formulation or by injection into a vein . [ 8 ]
Levetiracetam was discovered in 1992 through screening in audiogenic seizure susceptible mice and, 3 years later, was reported to exhibit saturable, stereospecific binding in brain to a approximately 90 kDa protein, later identified as the ubiquitous synaptic vesicle glycoprotein SV2A." [ 9 ]
The discovery process identifying levetiracetam's antiepileptic potential was unique because it challenged several dogmas of antiepileptic drug discovery, and thereby encountered skepticism from the epilepsy community. [ 10 ]
Common side effects of levetiracetam include sleepiness, dizziness, feeling tired, and aggression. [ 8 ] Severe side effects may include psychosis , suicide , and allergic reactions such as Stevens–Johnson syndrome or anaphylaxis . [ 8 ] Levetiracetam is the S- enantiomer of etiracetam . [ 11 ] It acts as a synaptic vesicle glycoprotein 2A (SV2A) ligand . [ 12 ]
Levetiracetam was approved for medical use in the United States in 1999 [ 8 ] and is available as a generic medication . [ 13 ] In 2022, it was the 123rd most commonly prescribed medication in the United States, with more than 5 million prescriptions. [ 14 ] [ 15 ] It is on the World Health Organization's List of Essential Medicines . [ 16 ]
Levetiracetam is effective as single-drug treatment for newly diagnosed focal epilepsy in adults. [ 17 ] [ 18 ] It reduces focal seizures by 50% or more as an add-on medication. [ 19 ]
Levetiracetam is effective as add-on treatment for partial (focal) epilepsy. [ 20 ]
Levetiracetam is effective for treatment of generalized tonic-clonic epilepsy. [ 18 ] It has been approved in the United States as add-on treatment for myoclonic , and tonic-clonic seizures. [ 4 ] Levetiracetam has been approved in the European Union as a monotherapy treatment for epilepsy in the case of partial seizures or as an adjunctive therapy for partial, myoclonic, and tonic-clonic seizures. [ 21 ]
Levetiracetam is sometimes used off label to treat status epilepticus . [ 22 ] [ 23 ]
Based on low-quality evidence, levetiracetam is about as effective as phenytoin for prevention of early seizures after traumatic brain injury. [ 24 ] It may be effective for prevention of seizures associated with subarachnoid hemorrhages . [ 25 ]
Levetiracetam has not been found to be useful for treatment of neuropathic pain , [ 26 ] nor for treatment of essential tremors . [ 27 ] Levetiracetam has not been found to be useful for treating all developmental disorders within the autism spectrum ; [ 28 ] [ 29 ] studies have only proven to be an effective treatment for partial, myoclonic, or tonic-clonic seizures associated with autism spectrum disorder. [ 30 ]
Levetiracetam's efficacy and tolerability in individuals with intellectual disability is comparable to those without. [ 31 ]
Studies in female pregnant rats have shown minor fetal skeletal abnormalities when given maximum recommended human doses of levetiracetam orally throughout pregnancy and lactation. [ medical citation needed ]
Studies were conducted to look for increased adverse effects in the elderly population as compared to younger patients. One such study published in Epilepsy Research showed no significant increase in incidence of adverse symptoms experienced by young or elderly patients with disorders of the central nervous system. [ medical citation needed ]
The most common adverse effects of levetiracetam treatment include effects on the central nervous system such as somnolence, decreased energy, headache, dizziness, mood swings and coordination difficulties. These adverse effects are most pronounced in the first month of therapy. About 4% of patients dropped out of pre-approval clinical trials due to these side effects. [ 4 ]
About 13% of people taking levetiracetam experience adverse neuropsychiatric symptoms, which are usually mild. These include agitation, hostility, apathy, anxiety, emotional lability, and depression. Serious psychiatric adverse side effects that are reversed by drug discontinuation occur in about 1%. These include hallucinations, suicidal thoughts, or psychosis. These occur mostly within the first month of therapy, but can rarely develop at any time during treatment. [ 32 ]
Although rare, Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), which appears as a painful spreading rash with redness and blistering and/or peeling skin, have been reported in patients treated with levetiracetam. [ 33 ] The incidence of SJS following exposure to anti-epileptics such as levetiracetam is about 1 in 3,000. [ 34 ]
Levetiracetam should not be used in people who have previously shown hypersensitivity to levetiracetam or any of the inactive ingredients in the tablet or oral solution. Such hypersensitivity reactions include, but are not limited to, unexplained rash with redness or blistered skin, difficulty breathing, and tightness in the chest or airways. [ 4 ]
In a study, the incidence of decreased bone mineral density of patients on levetiracetam was significantly higher than for those on different epileptic medications. [ 35 ]
Levetiracetam, along with other anti-epileptic drugs, can increase the risk of suicidal behavior or thoughts. Patients taking levetiracetam should be monitored closely for signs of worsening depression, suicidal thoughts or tendencies, or any altered emotional or behavioral states. [ 4 ]
Kidney impairment decreases the rate of elimination of levetiracetam from the body. Individuals with reduced kidney function may require dose adjustments, guided by monitoring of kidney function . [ 4 ]
Dose adjustment of levetiracetam is not necessary in liver impairment. [ 4 ]
No significant pharmacokinetic interactions were observed between levetiracetam or its major metabolite and concomitant medications. [ 36 ] The pharmacokinetic profile of levetiracetam is not influenced by phenytoin , phenobarbital , primidone , carbamazepine , valproic acid , lamotrigine , gabapentin , digoxin , ethinylestradiol , or warfarin . [ 37 ]
The exact mechanism by which levetiracetam acts to treat epilepsy is unknown. Levetiracetam does not exhibit pharmacologic actions similar to that of classical anticonvulsants. It does not inhibit voltage-dependent Na+ channels, does not affect GABAergic transmission, and does not bind to GABAergic or glutamatergic receptors. [ 38 ] However, the drug binds to SV2A , [ 39 ] a synaptic vesicle glycoprotein , and inhibits presynaptic calcium channels , [ 40 ] reducing neurotransmitter release and acting as a neuromodulator . This is believed to impede impulse conduction across synapses. [ 41 ] As of 2024, this is widely accepted to be its mechanism of action. [ 12 ] However, the molecular basis of this action remains unknown. [ 12 ]
The FDA provided a detailed review of the pharmacology and biopharmaceutics of Levetiracetam in 2013. [ 42 ]
The absorption of levetiracetam tablets and oral solution is rapid and essentially complete. The bioavailability of levetiracetam is close to 100 percent, and the effect of food on absorption is minor. [ 4 ]
The volume of distribution of levetiracetam is similar to total body water. Levetiracetam modestly binds to plasma proteins (less than 10%). [ 4 ]
Levetiracetam does not undergo extensive metabolism, and the metabolites formed are not active and do not exert pharmacological activity. Metabolism of levetiracetam is not by liver cytochrome P450 enzymes, but through other metabolic pathways such as hydrolysis and hydroxylation. [ 4 ]
In persons with normal kidney function, levetiracetam is eliminated from the body primarily by the kidneys with about 66 percent of the original drug passed unchanged into urine. The plasma half-life of levetiracetam in adults is about 6 to 8 hours, [ 4 ] although the mean CSF half life of approx. 24 hours better reflects levels at site of action. [ 43 ]
Brivaracetam , a chemical analogue to levetiracetam, is a racetam derivative with similar properties.
Levetiracetam is available as regular and extended release oral formulations and as intravenous formulations. [ 44 ]
The immediate release tablet has been available as a generic in the United States since 2008, and in the UK since 2011. [ 45 ] [ 19 ] The patent for the extended release tablet will expire in 2028. [ 46 ]
The branded version Keppra is manufactured by UCB Pharmaceuticals S.A. [ 3 ] [ 4 ] [ 5 ] [ 6 ]
In 2015, Aprecia's orally disintegrating tablet form of the drug manufactured using pharmaceutical 3D printing techniques was approved by the FDA , under the trade name Spritam. [ 47 ] Some have said that the drug has been improved by 3D printing, as the formula used now has improved disintegration properties. [ 48 ]
Levetiracetam is a Schedule 4 substance in Australia under the Poisons Standard (February 2020) . [ 49 ] A Schedule 4 substance is classified as "Prescription Only Medicine, or Prescription Animal Remedy – Substances, the use or supply of which should be by or on the order of persons permitted by State or Territory legislation to prescribe and should be available from a pharmacist on prescription." [ 49 ]
Under Japanese law, levetiracetam and other racetams cannot be brought into the country except for personal use by a traveler for whom it has been prescribed. [ 50 ] Travelers who plan to bring more than a month's worth must apply for an import certificate, known as a Yakkan Shoumei ( 薬監証明 , yakkan shōmei ) . [ 51 ]
Levetiracetam has been studied in the past for treating symptoms of neurobiological conditions such as Tourette syndrome , [ 52 ] and anxiety disorder . [ 53 ] However, its most serious adverse effects are behavioral, and its benefit-risk ratio in these conditions is not well understood. [ 53 ]
Levetiracetam is being tested as a drug to reduce hyperactivity in the hippocampus in Alzheimer's disease . [ 54 ]
Additionally, Levetiracetam has been experimentally shown to reduce Levodopa-induced dyskinesia , [ 55 ] a type of movement disorder, or dyskinesia associated with the use of Levodopa , a medication used to treat Parkinson's disease .
Of the ten medications evaluated in a 2023 systematic review of the literature, levetiracetam was found to be the only medication with sufficient evidence showing that it may cause seizure freedom in some infants. [ 56 ] Further, adverse effects from levetiracetam were rarely severe enough for the medication to be discontinued in this age group. Because available research included only 2 published studies reporting seizure freedom rates, however, the strength of the evidence was judged to be low. [ 56 ] | https://en.wikipedia.org/wiki/Levetiracetam |
In theoretical computer science and mathematics , especially in the area of combinatorics on words , the Levi lemma states that, for all strings u , v , x and y , if uv = xy , then there exists a string w such that either
or
That is, there is a string w that is "in the middle", and can be grouped to one side or the other. Levi's lemma is named after Friedrich Wilhelm Levi , who published it in 1944. [ 1 ]
Levi's lemma can be applied repeatedly in order to solve word equations ; in this context it is sometimes called the Nielsen transformation by analogy with the Nielsen transformation for groups . For example, starting with an equation xα = yβ where x and y are the unknowns, we can transform it (assuming |x| ≥ |y| , so there exists t such that x = yt ) to ytα = yβ , thus to tα = β . This approach results in a graph of substitutions generated by repeatedly applying Levi's lemma. If each unknown appears at most twice, then a word equation is called quadratic; in a quadratic word equation the graph obtained by repeatedly applying Levi's lemma is finite, so it is decidable if a quadratic word equation has a solution . [ 2 ] A more general method for solving word equations is Makanin's algorithm . [ 3 ] [ 4 ]
The above is known as the Levi lemma for strings ; the lemma can occur in a more general form in graph theory and in monoid theory ; for example, there is a more general Levi lemma for traces originally due to Christine Duboc. [ 5 ] Several proofs of Levi's Lemma for traces can be found in The Book of Traces . [ 6 ]
A monoid in which Levi's lemma holds is said to have the equidivisibility property . [ 7 ] The free monoid of strings and string concatenation has this property (by Levi's lemma for strings), but by itself equidivisibility is not enough to guarantee that a monoid is free. However an equidivisible monoid M is free if additionally there exists a homomorphism f from M to the monoid of natural numbers (free monoid on one generator) with the property that the preimage of 0 contains only the identity element of M , i.e. f − 1 ( 0 ) = { 1 M } {\displaystyle f^{-1}(0)=\{1_{M}\}} . (Note that f simply being a homomorphism does not guarantee this latter property, as there could be multiple elements of M mapped to 0.) [ 8 ] A monoid for which such a homomorphism exists is also called graded (and the f is called a gradation). [ 9 ] | https://en.wikipedia.org/wiki/Levi's_lemma |
In mathematics, the Levi-Civita field , named after Tullio Levi-Civita , [ 1 ] is a non-Archimedean ordered field ; i.e., a system of numbers containing infinite and infinitesimal quantities. It is usually denoted R {\displaystyle {\mathcal {R}}} .
Each member a {\displaystyle a} can be constructed as a formal series of the form
where Q {\displaystyle \mathbb {Q} } is the set of rational numbers , the coefficients a q {\displaystyle a_{q}} are real numbers, and ε {\displaystyle \varepsilon } is to be interpreted as a fixed positive infinitesimal. We require that for every rational number r {\displaystyle r} , there are only finitely many q ∈ Q {\displaystyle q\in \mathbb {Q} } less than r {\displaystyle r} with a q ≠ 0 {\displaystyle a_{q}\neq 0} ; this restriction is necessary in order to make multiplication and division well defined and unique. Two such series are considered equal only if all their coefficients are equal. The ordering is defined according to the dictionary ordering of the list of coefficients, which is equivalent to the assumption that ε {\displaystyle \varepsilon } is an infinitesimal.
The real numbers are embedded in this field as series in which all of the coefficients vanish except a 0 {\displaystyle a_{0}} .
If a = ∑ q ∈ Q a q ε q {\displaystyle a=\sum \limits _{q\in \mathbb {Q} }a_{q}\varepsilon ^{q}} and b = ∑ q ∈ Q b q ε q {\displaystyle b=\sum \limits _{q\in \mathbb {Q} }b_{q}\varepsilon ^{q}} are two Levi-Civita series, then
(One can check that for every q ∈ Q {\displaystyle q\in \mathbb {Q} } the set { ( r , s ) ∈ Q × Q : r + s = q , a r ≠ 0 , b s ≠ 0 } {\displaystyle \{(r,s)\in \mathbb {Q} \times \mathbb {Q} :\ r+s=q,\ a_{r}\neq 0,\ b_{s}\neq 0\}} is finite, so that all the products are well-defined, and that the resulting series defines a valid Levi-Civita series.)
Equipped with those operations and order, the Levi-Civita field is indeed an ordered field extension of R {\displaystyle \mathbb {R} } where the series ε {\displaystyle \varepsilon } is a positive infinitesimal.
The Levi-Civita field is real-closed , meaning that it can be algebraically closed by adjoining an imaginary unit ( i ), or by letting the coefficients be complex . It is rich enough to allow a significant amount of analysis to be done, but its elements can still be represented on a computer in the same sense that real numbers can be represented using floating point .
It is the basis of automatic differentiation , a way to perform differentiation in cases that are intractable by symbolic differentiation or finite-difference methods. [ 2 ]
The Levi-Civita field is also Cauchy complete , meaning that relativizing the ∀ ∃ ∀ {\displaystyle \forall \exists \forall } definitions of Cauchy sequence and convergent sequence to sequences of Levi-Civita series, each Cauchy sequence in the field converges. Equivalently, it has no proper dense ordered field extension.
As an ordered field, it has a natural valuation given by the rational exponent corresponding to the first non zero coefficient of a Levi-Civita series. The valuation ring is that of series bounded by real numbers, the residue field is R {\displaystyle \mathbb {R} } , and the value group is ( Q , + ) {\displaystyle (\mathbb {Q} ,+)} . The resulting valued field is Henselian (being real closed with a convex valuation ring) but not spherically complete . Indeed, the field of Hahn series with real coefficients and value group ( Q , + ) {\displaystyle (\mathbb {Q} ,+)} is a proper immediate extension, containing series such as 1 + ε 1 / 2 + ε 2 / 3 + ε 3 / 4 + ε 4 / 5 + ⋯ {\displaystyle 1+\varepsilon ^{1/2}+\varepsilon ^{2/3}+\varepsilon ^{3/4}+\varepsilon ^{4/5}+\cdots } which are not in the Levi-Civita field.
The Levi-Civita field is the Cauchy-completion of the field P {\displaystyle \mathbb {P} } of Puiseux series over the field of real numbers, that is, it is a dense extension of P {\displaystyle \mathbb {P} } without proper dense extension. Here is a list of some of its notable proper subfields and its proper ordered field extensions: | https://en.wikipedia.org/wiki/Levi-Civita_field |
A Levich constant (B) is often used in order to simplify the Levich equation . [ 1 ] Furthermore, B is readily extracted from rotating disk electrode experimental data.
The B can be defined as: [ 2 ]
B = ( 0.620 ) n F A D 2 3 v − 1 6 C {\displaystyle B=(0.620)nFAD^{\frac {2}{3}}v^{\frac {-1}{6}}C}
where
This electrochemistry -related article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Levich_constant |
The Levich equation models the diffusion and solution flow conditions around a rotating disk electrode (RDE). It is named after Veniamin Grigorievich Levich who first developed an RDE as a tool for electrochemical research. It can be used to predict the current observed at an RDE, in particular, the Levich equation gives the height of the sigmoidal wave observed in rotating disk voltammetry. The sigmoidal wave height is often called the Levich current.
The Levich equation is written as:
where I L is the Levich current (A), n is the number of moles of electrons transferred in the half reaction (number), F is the Faraday constant (C/mol), A is the electrode area (cm 2 ), D is the diffusion coefficient (see Fick's law of diffusion ) (cm 2 /s), ω is the angular rotation rate of the electrode (rad/s), ν is the kinematic viscosity (cm 2 /s), C is the analyte concentration (mol/cm 3 ). In this form of the equation, the constant with a value of 0.620 has units of rad -1/2 .
The leading term 0.620 is from the calculation of the velocity profile near the surface of the electrode. [ 1 ] Using cylindrical coordinates, the von Karman and Cochran solution to the Navier-Stokes equations yields the two relevant profiles to electrochemical study:
The Levich equation can subsequently be derived by integrating the steady-state convection diffusion equation:
The leading numeric value varies with the units of ω : 0.621 is referred to ω in rad/s; other common values are 1.554 for ω in Hz, and 0.201 for ω in rpm. [ 2 ]
Whereas the Levich equation suffices for many purposes, improved forms based on derivations utilising more terms in the velocity expression are available. [ 3 ] [ 4 ]
The Levich equation is often simplified by defining a Levich constant B such that:
This electrochemistry -related article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Levich_equation |
The Levington Research Station is a fertiliser research institute in Suffolk .
It was opened by Fisons in 1957. [ 2 ] It received a Civic Trust Award in 1959. [ 3 ] Fisons sold the property in 1981.
Around three hundred people worked at the site and it was one of Europe's largest research institutes in the field of fertiliser.
On 1 January 1960, Fisons Horticulture and Fisons Fertilisers were formed. The research site worked with both. [ 4 ]
The horticultural division of Fisons was sold off for £25.4m in a management buy out in 1994 known as Levington Horticulture; the division had around 280 people and around 26% of the UK market, turning over £47m. [ 5 ] In 1997 this division was sold on again to the present ownership.
The research site developed the first specialist sports turf fertiliser; typical agricultural fertiliser was too concentrated: this is now found at all main golf courses across Europe under the Greensmaster brand. Levington Horticulture also made Turfclear herbicide, and had a Royal Warrant .
The site is known for developing Levington Compost in the 1960s. The compost was made in South Yorkshire and the fertiliser was made at Bramford , west of Ipswich, next to the Great Eastern Main Line .
Levington Multi-Purpose Compost (when owned by Fisons) had a 1984 television advert featuring Jack and the Beanstalk .
On Tuesday 1 May 1956, the site was visited by the Duke of Edinburgh. [ 6 ]
It is in the East Suffolk district of Suffolk. | https://en.wikipedia.org/wiki/Levington_Research_Station |
In mathematics , Levinson's inequality is the following inequality, due to Norman Levinson , involving positive numbers. Let a > 0 {\displaystyle a>0} and let f {\displaystyle f} be a given function having a third derivative on the range ( 0 , 2 a ) {\displaystyle (0,2a)} , and such that
for all x ∈ ( 0 , 2 a ) {\displaystyle x\in (0,2a)} . Suppose 0 < x i ≤ a {\displaystyle 0<x_{i}\leq a} and 0 < p i {\displaystyle 0<p_{i}} for i = 1 , … , n {\displaystyle i=1,\ldots ,n} . Then
The Ky Fan inequality is the special case of Levinson's inequality, where | https://en.wikipedia.org/wiki/Levinson's_inequality |
Levisoprenaline ( INN Tooltip International Nonproprietary Name ) is a sympathomimetic , β-adrenergic receptor agonist , and bronchodilator which was never marketed. [ 1 ] [ 2 ] [ 3 ] It is the levorotatory or ( R )- enantiomer of isoprenaline . [ 3 ]
This drug article relating to the cardiovascular system is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Levisoprenaline |
Levitated optomechanics is a field of mesoscopic physics which deals with the mechanical motion of mesoscopic particles which are optically or electrically or magnetically levitated . Through the use of levitation, it is possible to decouple the particle's mechanical motion exceptionally well from the environment. This in turn enables the study of high-mass quantum physics , out-of-equilibrium- and nano- thermodynamics [ 1 ] and provides the basis for precise sensing applications. [ 2 ]
In order to use mechanical oscillators in the regime of quantum physics or for sensing applications, low damping of the oscillator's motion and thus high quality factors are desirable. In nano and micromechanics , the Q-factor of a system is often limited by its suspension, which usually demands filigree structures. Nevertheless, the maximally achievable Q-factor usually correlates with the system's size, [ 3 ] requiring large systems for achieving high Q-factors.
Particle levitation in external fields can alleviate this constraint. This is one of the reasons why the field of levitated optomechanics has become attractive for research on the foundations in physics and for high-precision applications.
The interaction between a dielectric particle with polarizability α {\displaystyle \alpha } and an electric field E → {\displaystyle {\vec {E}}} is given by the gradient force F → g r a d = − α ∇ → E → 2 / 2 {\displaystyle {\vec {F}}_{grad}=-\alpha {\vec {\nabla }}{\vec {E}}^{2}/2} . When a particle is trapped and optically levitated in the focus of a Gaussian laser beam , the force can be approximated to first order by F g r a d , q = − k q q {\displaystyle F_{grad,q}=-k_{q}q} with q ∈ { x , y , z } {\displaystyle q\in \{x,y,z\}} , i.e. a harmonic oscillator with frequency ω q = k q / M {\displaystyle \omega _{q}={\sqrt {k_{q}/M}}} , where M {\displaystyle M} is the particle's mass. Including passive damping , active external feedback and coupling results in the Langevin equations of motion:
q ¨ ( t ) = − Γ C M q ˙ ( t ) ⏟ damping − ω q 2 q ( t ) ⏟ restoring force + 2 π S f f M ⏟ coupling + u f b ( t ) ⏟ feedback {\displaystyle {\ddot {q}}(t)=-\underbrace {\Gamma _{CM}{\dot {q}}(t)} _{\text{damping}}-\underbrace {\omega _{q}^{2}q(t)} _{\text{restoring force}}+\underbrace {\frac {\sqrt {2\pi S_{ff}}}{M}} _{\text{coupling}}+\underbrace {u_{fb}(t)} _{\text{feedback}}}
Here Γ C M {\displaystyle \Gamma _{CM}} is the total damping rate, which has usually two dominant contributions: collisions with atoms or molecules of the background gas and photon shot noise , which becomes dominant below pressures on the order of 10 −6 mbar.
The coupling term allows to model any coupling to an external heat bath .
The external feedback is usually used to cool and control the particle motion.
The approximation of a classical harmonic oscillator holds true until one reaches the regime of quantum mechanics, where the quantum harmonic oscillator is the superior approximation and the quantization of the energy levels becomes apparent. The QHO has a ground state of lowest energy where both position and velocity have a minimal variance, determined by the Heisenberg uncertainty principle .
Such quantum states are interesting starting conditions for preparing non-Gaussian quantum states, quantum enhanced sensing, matter-wave interferometry or the realization of entanglement in many-particle systems. [ 4 ]
The idea of feedback cooling is to apply a position and/or velocity dependent force on the particle in a way which produces a negative feedback loop .
One way to achieve that is by adding a feedback term, which is proportional to the particle's position ( u f b ( t ) ∝ q ˙ ( t ) {\displaystyle u_{fb}(t)\propto {\dot {q}}(t)} ). Since that mechanism provides damping, which cools down the mechanical motion, without the introduction of fluctuations, it is referred to as “cold damping”. The first experiment employing this type of cooling was done in 1977 by Arthur Ashkin , [ 5 ] who received the 2018 Nobel Prize in Physics for his pioneering work on trapping with optical tweezers .
Instead of applying a linear feedback signal, one can also combine position and velocity via u f b ∝ q ( t ) q ˙ ( t ) {\displaystyle u_{fb}\propto q(t){\dot {q}}(t)} to get a signal with twice the frequency of the particle's oscillation. This way the stiffness of the trap increases when the particle moves out of the trap and decreases when the particle is moving back. [ 6 ] | https://en.wikipedia.org/wiki/Levitated_optomechanics |
Wijsman convergence is a variation of Hausdorff convergence suitable for work with unbounded sets .
Intuitively, Wijsman convergence is to convergence in the Hausdorff metric as pointwise convergence is to uniform convergence .
The convergence was defined by Robert Wijsman . [ 1 ] The same definition was used earlier by Zdeněk Frolík . [ 2 ] Yet earlier, Hausdorff in his book Grundzüge der Mengenlehre defined so called closed limits ;
for proper metric spaces it is the same as Wijsman convergence.
Let ( X , d ) be a metric space and let Cl( X ) denote the collection of all d -closed subsets of X . For a point x ∈ X and a set A ∈ Cl( X ), set
A sequence (or net ) of sets A i ∈ Cl( X ) is said to be Wijsman convergent to A ∈ Cl( X ) if, for each x ∈ X ,
Wijsman convergence induces a topology on Cl( X ), known as the Wijsman topology . | https://en.wikipedia.org/wiki/Levi–Lechicki_theorem |
Levoamphetamine [ note 1 ] is a stimulant medication which is used in the treatment of certain medical conditions . [ 10 ] It was previously marketed by itself under the brand name Cydril , but is now available only in combination with dextroamphetamine in varying ratios under brand names like Adderall and Evekeo . [ 10 ] [ 5 ] The drug is known to increase wakefulness and concentration in association with decreased appetite and fatigue . [ 11 ] [ 12 ] Pharmaceuticals that contain levoamphetamine are currently indicated and prescribed for the treatment of attention deficit hyperactivity disorder (ADHD), obesity , and narcolepsy in some countries. [ 10 ] [ 5 ] [ 13 ] Levoamphetamine is taken by mouth . [ 10 ] [ 5 ]
Levoamphetamine acts as a releasing agent of the monoamine neurotransmitters norepinephrine and dopamine . [ 10 ] It is similar to dextroamphetamine in its ability to release norepinephrine and in its sympathomimetic effects but is a few times weaker than dextroamphetamine in its capacity to release dopamine and in its psychostimulant effects. [ 10 ] [ 14 ] [ 12 ] Levoamphetamine is the levorotatory stereoisomer of the racemic amphetamine molecule, whereas dextroamphetamine is the dextrorotatory isomer. [ 10 ] [ 5 ]
Levoamphetamine was first introduced in the form of racemic amphetamine under the brand name Benzedrine in 1935 and as an enantiopure drug under the brand name Cydril in the 1970s. [ 10 ] [ 15 ] While pharmaceutical formulations containing enantiopure levoamphetamine are no longer manufactured, [ 10 ] levomethamphetamine (levmetamfetamine) is still marketed and sold over-the-counter as a nasal decongestant . [ 16 ] In addition to being used in pharmaceutical drugs itself, levoamphetamine is a known active metabolite of certain other drugs, such as selegiline ( L -deprenyl). [ 17 ] [ 7 ]
Levoamphetamine has been used in the treatment of attention deficit hyperactivity disorder (ADHD) both alone and in combination with dextroamphetamine at different ratios. [ 10 ] [ 12 ] Levoamphetamine on its own has been found to be effective in the treatment of ADHD in multiple clinical studies conducted in the 1970s. [ 10 ] [ 12 ] The clinical dosages and potencies of levoamphetamine and dextroamphetamine in the treatment of ADHD have been fairly similar in these older studies. [ 10 ] [ 12 ]
The first patented amphetamine brand, Benzedrine , was a racemic (i.e., equal parts) mixture of the free bases or the more stable sulfate salts of both amphetamine enantiomers (levoamphetamine and dextroamphetamine) that was introduced in the United States in 1934 as an inhaler for treating nasal congestion . [ 2 ] It was later realized that the amphetamine enantiomers could treat obesity , narcolepsy , and ADHD . [ 2 ] [ 3 ] Because of the greater central nervous system effect of the dextrorotatory enantiomer (i.e., dextroamphetamine ), sold as Dexedrine, prescription of the Benzedrine brand fell and was eventually discontinued. [ 18 ] However, in 2012, racemic amphetamine sulfate was reintroduced as the Evekeo brand name. [ 3 ] [ 19 ]
Adderall is a 3.1:1 mixture of dextro- to levo- amphetamine base equivalent pharmaceutical that contains equal amounts (by weight) of four salts: dextroamphetamine sulfate, amphetamine sulfate, dextroamphetamine saccharate and amphetamine (D,L)-aspartate monohydrate. This result is a 76% dextroamphetamine to 24% levoamphetamine, or 3 ⁄ 4 to 1 ⁄ 4 ratio. [ 20 ] [ 21 ]
Evekeo is an FDA -approved medication that contains racemic amphetamine sulfate (i.e., 50% levoamphetamine sulfate and 50% dextroamphetamine sulfate). [ 3 ] It is approved for the treatment of narcolepsy , ADHD, and exogenous obesity. [ 3 ] The orally disintegrating tablets are approved for the treatment of attention deficit hyperactivity disorder (ADHD) in children and adolescents aged six to 17 years of age. [ 22 ]
Products using amphetamine base are now marketed. Dyanavel XR , a liquid suspension form became available in 2015, and contains about 24% levoamphetamine. [ 23 ] Adzenys XR , an orally dissolving tablet came to market in 2016 and contains 25% levoamphetamine. [ 24 ] [ 25 ]
Levoamphetamine can produce sympathomimetic side effects . [ 6 ]
Levoamphetamine, similarly to dextroamphetamine , acts as a reuptake inhibitor and releasing agent of norepinephrine and dopamine in vitro . [ 10 ] [ 14 ] However, there are differences in potency between the two compounds. [ 10 ] [ 14 ] Levoamphetamine is either similar in potency or somewhat more potent in inducing the release of norepinephrine than dextroamphetamine, whereas dextroamphetamine is approximately 4-fold more potent in inducing the release of dopamine than levoamphetamine. [ 10 ] In addition, as a reuptake inhibitor, levoamphetamine is about 3- to 7-fold less potent than dextroamphetamine in inhibiting dopamine reuptake but is only about 2-fold less potent in inhibiting norepinephrine reuptake. [ 10 ] Dextroamphetamine is very weak as a reuptake inhibitor of serotonin , whereas levoamphetamine is essentially inactive in this regard. [ 10 ] Levoamphetamine and dextroamphetamine are both also relatively weak reversible inhibitors of monoamine oxidase (MAO) and hence can inhibit catecholamine metabolism . [ 10 ] [ 35 ] [ 36 ] [ 37 ] However, this action may not occur significantly at clinical doses and may only be relevant to high doses. [ 35 ]
In rodent studies, both dextroamphetamine and levoamphetamine dose-dependently induce the release of dopamine in the striatum and norepinephrine in the prefrontal cortex . [ 10 ] Dextroamphetamine is about 3- to 5-fold more potent in increasing striatal dopamine levels as levoamphetamine in rodents in vivo , whereas the two enantiomers are about equally effective in terms of increasing prefrontal norepinephrine levels. [ 10 ] Dextroamphetamine has greater effects on dopamine levels than on norepinephrine levels, whereas levoamphetamine has relatively more balanced effects on dopamine and norepinephrine levels. [ 10 ] As with rodent studies, levoamphetamine and dextroamphetamine have been found to be similarly potent in elevating norepinephrine levels in cerebrospinal fluid in monkeys. [ 38 ] [ 39 ] By an uncertain mechanism , the striatal dopamine release of dextroamphetamine in rodents appears to be prolonged by levoamphetamine when the two enantiomers are administered at a 3:1 ratio (though not at a 1:1 ratio). [ 10 ]
The catecholamine -releasing effects of levoamphetamine and dextroamphetamine in rodents have a fast onset of action , with a peak of effect after about 30 to 45 minutes, are large in magnitude (e.g., 700–1,500% of baseline for dopamine and 400–450% of baseline for norepinephrine), and decline relatively rapidly after the effects reach their maximum. [ 10 ] The magnitudes of the effects of amphetamines are greater than those of classical reuptake inhibitors like atomoxetine and bupropion . [ 10 ] In addition, unlike with reuptake inhibitors, there is no dose–effect ceiling in the case of amphetamines. [ 10 ] Although dextroamphetamine is more potent than levoamphetamine, both enantiomers can maximally increase striatal dopamine release by more than 5,000% of baseline. [ 10 ] [ 40 ] This is in contrast to reuptake inhibitors like bupropion and vanoxerine , which have 5- to 10-fold smaller maximal impacts on dopamine levels and, in contrast to amphetamines, were not experienced as stimulating or euphoric . [ 10 ]
Dextroamphetamine has greater potency in producing stimulant-like effects in rodents and non-human primates than levoamphetamine. [ 10 ] Some rodent studies have found it to be 5- to 10-fold more potent in its stimulant-like effects than levoamphetamine. [ 14 ] [ 41 ] [ 42 ] Levoamphetamine is also less potent than dextroamphetamine in its anorectic effects in rodents. [ 14 ] [ 43 ] Dextroamphetamine is about 4-fold more potent than levoamphetamine in motivating self-administration in monkeys and is about 2- to 3-fold more potent than levoamphetamine in terms of positive reinforcing effects in humans. [ 10 ] [ 7 ] [ 44 ] Potency ratios of dextroamphetamine versus levoamphetamine with single doses of 5 to 80 mg in terms of psychological effects in humans including stimulation , wakefulness , activation, euphoria, reduction of hyperactivity , and exacerbation of psychosis have ranged from 1:1 to 4:1 in a variety of older clinical studies. [ 12 ] [ note 2 ] [ 45 ] With very large doses, ranging from 270 to 640 mg, the potency ratios of dextroamphetamine and levoamphetamine in stimulating locomotor activity and inducing amphetamine psychosis in humans have ranged from 1:1 to 2:1 in a couple studies. [ 12 ] The differences in potency and dopamine versus norepinephrine release between dextroamphetamine and levoamphetamine are suggestive of dopamine being the primary neurochemical mediator responsible for the stimulant and euphoric effects of these agents. [ 10 ]
In addition to inducing norepinephrine release in the brain, levoamphetamine and dextroamphetamine induce the release of epinephrine (adrenaline) in the peripheral sympathetic nervous system and this is related to their cardiovascular effects. [ 10 ] Although levoamphetamine is less potent than dextroamphetamine as a stimulant, it is approximately equipotent with dextroamphetamine in producing various peripheral effects, including vasoconstriction , vasopression , and other cardiovascular effects. [ 14 ]
Similarly to dextroamphetamine, levoamphetamine has been found to improve symptoms in an animal model of ADHD, the spontaneously hypertensive rat (SHR), including improving sustained attention and reducing overactivity and impulsivity . [ 46 ] [ 47 ] [ 48 ] [ 49 ] These findings parallel the clinical results in which both levoamphetamine and dextroamphetamine have been found to be effective in the treatment of ADHD in humans. [ 10 ] [ 12 ]
Unlike the case of dextroamphetamine versus dextromethamphetamine , in which the latter is more effective than the former, levoamphetamine is substantially more potent as a dopamine releaser and stimulant than levomethamphetamine . [ 35 ] [ 50 ] Conversely, levoamphetamine, levomethamphetamine, and dextroamphetamine are all similar in their potencies as norepinephrine releasers. [ 35 ] [ 50 ]
In addition to its catecholamine-releasing activity, levoamphetamine is also an agonist of the trace amine-associated receptor 1 (TAAR1). [ 51 ] [ 52 ] Levoamphetamine has also been found to act as a catecholaminergic activity enhancer (CAE), notably at much lower concentrations than its catecholamine releasing activity. [ 53 ] [ 54 ] [ 55 ] [ 56 ] It is similarly potent to selegiline and levomethamphetamine but is more potent than dextromethamphetamine and dextroamphetamine in this action. [ 55 ] The CAE effects of such agents may be mediated by TAAR1 agonism. [ 57 ] [ 56 ]
The pharmacokinetics of levoamphetamine have been studied. [ 5 ] [ 3 ] Usually this has been orally in combination with dextroamphetamine at different ratios. [ 5 ] [ 3 ] The pharmacokinetics of levoamphetamine have also been studied as a metabolite of selegiline . [ 7 ] [ 17 ]
The oral bioavailability of levoamphetamine has been found to be similar to that of dextroamphetamine. [ 58 ]
The time to peak levels of levoamphetamine with immediate-release (IR) formulations of amphetamine ranges from 2.5 to 3.5 hours and with extended-release (ER) formulations ranges from 5.3 to 8.2 hours depending on the formulation and the study. [ 5 ] [ 58 ] For comparison, the time to peak levels of dextroamphetamine with IR formulations ranges from 2.4 to 3.3 hours and with ER formulations ranges from 4.0 to 8.0 hours. [ 5 ] [ 58 ] The peak levels of levoamphetamine are proportionally similar to those of dextroamphetamine with administration of amphetamine at varying ratios. [ 5 ] With a single oral dose of 10 mg racemic amphetamine (a 1:1 ratio of enantiomers, or 5 mg dextroamphetamine and 5 mg levoamphetamine), peak levels of dextroamphetamine were 14.7 ng/mL and peak levels of levoamphetamine were 12.0 ng/mL in one study. [ 5 ]
Food does not affect the peak levels or overall exposure to levoamphetamine or dextroamphetamine with IR racemic amphetamine. [ 3 ] However, time to peak levels was delayed from 2.5 hours (range 1.5–6 hours) to 4.5 hours (range 2.5–8.0 hours). [ 3 ]
During oral selegiline therapy at a dosage of 10 mg/day, circulating levels of levoamphetamine have been found to be 6 to 8 ng/mL and levels of levomethamphetamine have been reported to be 9 to 14 ng/mL. [ 7 ] Although levels of levoamphetamine and levomethamphetamine are relatively low at typical doses of selegiline, they could be clinically relevant and may contribute to the effects and side effects of selegiline. [ 7 ]
The volume of distribution of both levoamphetamine and dextroamphetamine is about 3 to 4 L/kg. [ 58 ]
The plasma protein binding of levoamphetamine is 31.7%, whereas that of dextroamphetamine was 29.0% in the same study. [ 4 ]
Levoamphetamine and dextroamphetamine are metabolized via CYP2D6 -mediated hydroxylation to produce 4-hydroxyamphetamine and additionally via oxidative deamination . [ 3 ] There are several enzymes involved in the metabolism of amphetamine, of which CYP2D6 is one. [ 3 ] Levoamphetamine seems to be metabolized somewhat less efficiently than dextroamphetamine. [ 58 ]
The pharmacokinetics of levoamphetamine generated as a metabolite from selegiline have been found not to significantly vary in CYP2D6 poor metabolizers versus extensive metabolizers , suggesting that CYP2D6 may be minimally involved in the clinical metabolism of levoamphetamine. [ 17 ] [ 59 ]
The mean elimination half-life of levoamphetamine ranges from 11.7 to 15.2 hours in different studies. [ 5 ] [ 58 ] [ 3 ] Its half-life is somewhat longer than that of dextroamphetamine, with a difference of about 1 to 2 hours. [ 5 ] [ 6 ] [ 58 ] For comparison, in the same studies that reported the preceding values for levoamphetamine's half-life, the half-life of dextroamphetamine ranged from 10.0 to 12.4 hours. [ 5 ] [ 58 ] [ 3 ]
The elimination of amphetamine is highly dependent on urinary pH . [ 3 ] [ 6 ] Urinary acidifying agents like ascorbic acid and ammonium chloride increase amphetamine excretion and reduce its elimination half-life, whereas urinary alkalinizing agents like acetazolamide enhance renal tubular reabsorption and extend its half-life. [ 6 ] The urinary excretion of unchanged amphetamine is 70% on average with a urinary pH of 6.6 and 17 to 43% at a urinary pH of greater than 6.7. [ 3 ]
With selegiline at an oral dose of 10 mg, levoamphetamine and levomethamphetamine are eliminated in urine and recovery of levoamphetamine is 9 to 30% (or about 1–3 mg) while that of levomethamphetamine is 20 to 60% (or about 2–6 mg). [ 7 ]
Levoamphetamine is a substituted phenethylamine and amphetamine . It is also known as L -α-methyl-β-phenylethylamine or as (2 R )-1-phenylpropan-2-amine. [ 8 ] Levoamphetamine is the levorotatory stereoisomer of the amphetamine molecule. Racemic amphetamine contains two optical isomers in equal amounts, dextroamphetamine (the dextrorotatory enantiomer) and levoamphetamine. [ 20 ] [ 21 ]
The origin of the amphetamine psychostimulants comes from ephedra . [ 60 ] This plant, also known as "ma huang", is an herb which has been used for thousands of years in traditional Chinese medicine as a stimulant and antiasthmatic medicine . [ 61 ] [ 62 ] Ephedrine ((1 R ,2 S )-β-hydroxy- N -methylamphetamine), an analogue and derivative of amphetamine and the major pharmacologically active constituent of ephedra, was first isolated from the plant in 1885. [ 63 ] [ 60 ] Another plant, known as Catha edulis (khat), also naturally contains amphetamines, specifically cathine ((1 S ,2 S )-β-hydroxyamphetamine) and cathinone (β-ketoamphetamine). [ 62 ] [ 64 ] It has a long history of use for its stimulant effects in Eastern Africa and the Arabian Peninsula . [ 62 ] [ 64 ] However, cathine was not isolated from khat until 1930 and cathinone was not isolated from the plant until 1975. [ 64 ]
Amphetamine, which is a racemic mixture of dextroamphetamine and levoamphetamine, was first discovered in 1887, shortly after the isolation of ephedrine. [ 65 ] [ 60 ] However, it was not until 1927 that amphetamine was synthesized by Gordon Alles and was studied by him in animals and humans. [ 10 ] This led to the discovery of the stimulating effects of amphetamine in humans in 1929 after Alles injected himself with 50 mg of the drug. [ 65 ] [ 10 ] Levoamphetamine was first introduced in the form of racemic amphetamine (a 1:1 combination of levoamphetamine and dextroamphetamine) under the brand name Benzedrine in 1935. [ 10 ] It was indicated for the treatment of narcolepsy , mild depression , parkinsonism , and a variety of other conditions. [ 10 ] Dextroamphetamine was found to be the more potent of the two enantiomers of amphetamine and was introduced as an enantiopure drug under the brand name Dexedrine in 1937. [ 10 ] Consequent to its lower potency, levoamphetamine has received far less attention than racemic amphetamine or dextroamphetamine. [ 10 ]
Levoamphetamine was studied in the treatment of attention deficit hyperactivity disorder (ADHD) in the 1970s and was found to be clinically effective for this condition similarly to dextroamphetamine. [ 10 ] As a result, it was marketed as an enantiopure drug under the brand name Cydril for the treatment of ADHD in the 1970s. [ 10 ] [ 15 ] However, it was reported in 1976 that racemic amphetamine was less effective than dextroamphetamine in treating ADHD. [ 10 ] As a result of this study, use of racemic amphetamine in the treatment of ADHD dramatically declined in favor of dextroamphetamine. [ 10 ] Enantiopure levoamphetamine was eventually discontinued and is no longer available today. [ 10 ]
Levoamphetamine is a controlled substance in the Philippines . [ 66 ]
Misuse of enantiopure levoamphetamine and levomethamphetamine is reportedly not known. [ 17 ] However, rare cases of misuse of levomethamphetamine, which is available over-the-counter as a nasal decongestant , actually have been reported. [ 67 ] [ 68 ] [ 69 ] [ 70 ] Due to their lower efficacy in stimulating dopamine release and their reduced potency as psychostimulants , levoamphetamine and levomethamphetamine would theoretically be expected to have less misuse potential than the corresponding dextroamphetamine and dextromethamphetamine forms. [ 17 ]
Levoamphetamine as an enantiopure drug has been studied in the past in a variety of contexts. [ 11 ] These include its effects in and/or treatment of mood , [ 11 ] " minimal brain dysfunction ", [ 71 ] narcolepsy , [ 11 ] [ 72 ] " hyperkinetic syndrome " and aggression , [ 73 ] [ 15 ] sleep , [ 74 ] [ 75 ] schizophrenia , [ 76 ] wakefulness , [ 77 ] Tourette's syndrome , [ 78 ] and Parkinson's disease , among others. [ 11 ] [ 79 ] Levoamphetamine has been studied in the treatment of multiple sclerosis in more modern studies and has been reported to improve cognition and memory in this condition as well. [ 80 ] [ 81 ] [ 82 ] [ 83 ] [ 84 ] [ 85 ] It was under development for this indication under the name levafetamine and the developmental code name C-105 and reached phase 2 clinical trials , but development was discontinued sometime after 2008. [ 86 ]
Levoamphetamine is a major active metabolite of selegiline ( L -deprenyl; N -propargyl- L -methamphetamine). [ 7 ] [ 87 ] Selegiline is a monoamine oxidase inhibitor (MAOI), specifically a selective inhibitor of monoamine oxidase B (MAO-B) at lower doses and a dual inhibitor of both monoamine oxidase A (MAO-A) and MAO-B at higher doses. [ 7 ] [ 88 ] It also has additional activities, such as acting as a catecholaminergic activity enhancer (CAE), possibly via agonism of the TAAR1 , and having potential neuroprotective effects. [ 89 ] [ 88 ] [ 56 ] Selegiline is clinically used as an antiparkinsonian agent in the treatment of Parkinson's disease and as an antidepressant in the treatment of major depressive disorder . [ 89 ] [ 88 ]
In addition to levoamphetamine, selegiline also metabolizes into levomethamphetamine . [ 87 ] [ 7 ] With a 10 mg oral dose of selegiline, about 2 to 6 mg levomethamphetamine and 1 to 3 mg levoamphetamine is excreted in urine . [ 7 ] [ 90 ] [ 87 ] [ 91 ] As levoamphetamine and levomethamphetamine are norepinephrine and/or dopamine releasing agents , they may contribute to the effects and side effects of selegiline. [ 92 ] [ 93 ] [ 33 ] This may particularly include cardiovascular and sympathomimetic effects of selegiline. [ 92 ] [ 94 ] [ 95 ] [ 96 ] Other selective MAO-B inhibitors that do not metabolize into amphetamine metabolites or have associated cardiovascular effects, such as rasagiline , have also been developed and introduced. [ 92 ] [ 97 ]
Because selegiline metabolizes into levoamphetamine and levomethamphetamine, people taking selegiline can erroneously test positive for amphetamines on drug tests . [ 98 ] [ 99 ] | https://en.wikipedia.org/wiki/Levoamphetamine |
Levobetaxolol is a drug used to lower the pressure in the eye in treating conditions such as glaucoma . It is marketed as a 0.25 or 0.5% ophthalmic solution of levobetaxolol hydrochloride under the trade name Betaxon . Levobetaxolol is a beta-adrenergic receptor inhibitor ( beta blocker ).
It is indicated for intraocular pressure reduction in patients with open-angle glaucoma or ocular hypertension . [ 1 ]
Levobetaxolol inhibits the beta-1-adrenergic receptor. When applied topically, it reduces intra-ocular pressure (IOP) by 16-23% depending on time of day and the individual. It also has neuroprotective effects. [ 1 ] Levobetaxolol has fewer cardiovascular side effects than other beta blockers.
Levobetaxolol should not be used by people who have sinus bradycardia , atrioventricular block , cardiogenic shock, or overt cardiac failure. The drug has been associated with bradycardia and hypertension . [ citation needed ]
Levobetaxolol was developed in the 1980s. [ 1 ] It was FDA approved in 2000. [ 2 ] | https://en.wikipedia.org/wiki/Levobetaxolol |
(-)-bupivacaine
Levobupivacaine ( rINN ) is a local anaesthetic drug indicated for minor and major surgical anaesthesia and pain management . It is a long-acting amide -type local anaesthetic that blocks nerve impulses by inhibiting sodium ion influx into the nerve cells . [ 1 ] Levobupivacaine is the S- enantiomer of racemic bupivacaine and therefore similar in pharmacological effects. [ 2 ] The drug typically starts taking effect within 15 minutes and can last up to 16 hours depending on factors such as site of administration and dosage. [ 1 ]
Levobupivacaine was designed, in the late 1970s, to be a safer and more effective alternative to bupivacaine, which had been associated with a higher risk of cardiotoxicity. [ 1 ] [ 2 ] Compared to bupivacaine, levobupivacaine is associated with less vasodilation and has a longer duration of action. It is approximately 13 per cent less potent (by molarity) than racemic bupivacaine and has a longer motor block onset time. [ 3 ] Ropivacaine is, next to levobupivacaine, another less cardiotoxic alternative to bupivacaine. [ 4 ]
Levobupivacaine hydrochloride is commonly marketed by AbbVie under the trade name Chirocaine. [ 5 ] In Europe, Chirocaine is available – prescription only – in concentrations ranging from 0.625 mg/mL to 7.5 mg/mL. [ 6 ]
Levobupivacaine, the S(-)-enantiomer of bupivacaine has been developed as an alternative to the racemic mixture, as it has been shown to have a lower cardiotoxicity than bupivacaine. Under European Union advice, it can be applied for minor and major surgical anaesthesia , as well as (post-operative) pain management . [ 7 ] Particularly, it has been found suitable for multiple procedures, such as epidural block . It is effective for human patients who receive elective Caesarean section or lower body surgery, as it does not diverge dramatically in terms of sensory and/or motor block duration in comparison to bupivacaine. [ 7 ] Deserving of consideration is the fact that its enhanced motor blocking can be a downside for patients receiving an epidural injection during childbirth , as a certain level of movement may still be required. [ 7 ]
Other than childbirth, possible applications of levobupivacaine include upper and lower limb surgery, as well as eye surgery , where it blocks the extraocular muscle , highly efficient and convenient for patients undergoing vitreoretinal anterior segment or cataract surgery. [ 8 ]
Levobupivacaine can be combined with other analgesics, including opioids , for postoperative pain management. [ 9 ]
Using 0.75% (7.5 mg/mL) of levobupivacaine, similar to bupivacaine, is contraindicated in obstetric patients. Use in paracervical blocks in obstetrics is also contraindicated. Levobupivacaine is furthermore contraindicated in patients with known hypersensitivity to levobupivacaine or other amide-type local anaesthetics, in patients with severe hypotension (e.g. cardiac or hypovolemic shock ) and for use in intravenous regional anaesthesia (Bier’s block). [ 9 ] [ 10 ]
Possible adverse effects in the central nervous system caused by levobupivacaine usage are light-headedness , tinnitus , tongue numbness and convulsions , which may be due to the blockade of sodium, potassium and calcium channels in tissues that were not intended as targets. [ 11 ] Cardiotoxicity may be a result of indirect effects of the drug, such as the blockade of myocardial sympathetic nerves, thus leading to contractile delay, or by direct effects, such as the blockade of potassium channels. [ 7 ]
Effects of this nature lead to lowered contractile function and arrhythmogenic effects, which can potentially cause cardiovascular collapse and death. [ 11 ] It is to note that the drug also has vasoconstrictive activity, thereby increasing the duration of sensory blockage with a relatively low risk of central nervous system toxicity on one hand, and on the other, it can have the same effect on uteroplacental blood flow, which can harm the foetus . [ 7 ] Ultimately, levobupivacaine has been shown to have a lower risk of cardiovascular and central nervous system toxicity compared to bupivacaine in animal studies , not at the expense of potency and efficacy , and should be therefore considered as an alternative. [ 7 ]
Levobupivacaine has become a more favourable alternative for regional anaesthesia than bupivacaine due to its reduced toxicity. A plethora of non-human studies have established levobupivacaine’s lower risk of cardiac and neurotoxic adverse effects. [ 2 ] [ 12 ] [ 13 ] Most animal studies show that the lethal dose (LD 50 ) of levobupivacaine is approximately 50% higher than that of bupivacaine. [ 4 ] In general, laevorotatory isomers tend to cause significantly fewer adverse effects and are thus a safer pharmacological alternative. [ 12 ] [ 13 ] Levobupivacaine has a 97% protein binding rate which is 2% higher than what is observed in bupivacaine. [ 1 ] The faster protein binding rate contributes to its reduced toxicity level. [ 14 ]
In human volunteer studies, levobupivacaine consistently proved to have a safety advantage over bupivacaine. [ 15 ] [ 16 ] Risk factors for local anaesthetic toxicity depend on the administration of levobupivacaine to myocardial and cerebral tissue , as well as the predisposition of these tissues to levobupivacaine’s negative effects. [ 1 ]
Age is a relevant factor in vulnerability to levobupivacaine toxicity. Elderly patients are more likely to have pre-existing conditions impacting the cardiac , renal and hepatic systems , which contribute to the slower absorption rate and plasma concentrations below the toxic level compared to younger patients. [ 1 ] [ 17 ] On the other hand, homeostatic disbalance can exacerbate toxic effects. [ 7 ]
It is important to adjust the dosage of levobupivacaine in paediatric patients due to their underdeveloped metabolic processing to prevent reaching toxic levels. The dosage of local anaesthetics is calculated based on the patient’s weight and body mass index , however, the association power is stronger in children than in adults. Moreover, symptoms of systemic toxicity like paraesthesia are harder to notice in children. [ 1 ]
Levobupivacaine is a drug that has analgesic , motor blocking, and sensory blocking effects on the human body, whose properties are dictated by its chemical characteristics, such as pK a , which has a value of 8.1. [ 8 ] The pK a of a drug can be informative information that indicates its ionisation under physiological conditions . For example, drugs with a high pK a , such as that of levobupivacaine, tend to be their ionised form under physiological state, meaning that they would not easily cross the hydrophobic plasma membrane of cells. This, however, is counteracted by the high lipid solubility of levobupivacaine, which increases the ease with which it can diffuse through the phospholipid bilayer . [ 8 ] Additionally, high-protein binding quality (97%) is characteristic of levobupivacaine, which strengthens its binding to cell surface proteins, thereby lengthening the binding, and thus action time. [ 8 ]
The S(-)-enantiomer of levobupivacaine is a high- potency , long-acting anaesthetic with a relatively slow onset of action . Indeed, it has been found in certain studies that, as a surgical anaesthetic, it has a sensory ad motor blocking activity for over 90% of adult patients who received appropriate doses for their bodily composition, and duration of the surgery, with an onset time of 15 minutes. [ 7 ]
More specifically, levobupivacaine achieves its effects by acting on the neuronal voltage-sensitive sodium channels , where it prevents the transmission of nerve impulses . [ 18 ] The normal function of these sodium channels is halted temporarily, as the drug interferes with their opening, thereby inhibiting the conduction of action potentials in nerves involved in sympathetic, sensory, and motor activity. [ 7 ] This interruption results in decreased muscle control, and overall analgesic effects which allow for levobupivacaine to act as a local anaesthetic. [ 11 ]
Levobupivacaine varies slightly in its effects depending on the characteristics of the neuron in question. For example, in myelinated neurons, the nodes of Ranvier are targeted and more easily blocked than unmyelinated neurons, and small nerves are more easily blocked than large nerves. [ 7 ] [ 18 ]
When compared to the racemic bupivacaine mixture, levobupivacaine generally has been shown to have similar effects. As an anaesthetic, it is similar in nerve-blocking potency compared to its R(+)-enantiomer and racemic mixture, although its effects are affected by the route of administration and the concentration, however, they were ultimately similar among the three. [ 7 ] Some animal studies indicate that among the three, levobupivacaine shows an increased duration of anaesthesia and/or greater potency, and there is evidence that in humans it is as potent as bupivacaine. [ 7 ]
The plasma concentration of levobupivacaine is influenced by both the dosage and the method of administration . Additionally, absorption depends on the vascularity of the tissue. Maximum plasma concentration of 1.2 μg/mL is reached approximately 30 minutes post epidural injection.
Levobupivacaine undergoes biotransformation in the liver by the cytochrome P450 enzyme , specifically CYP1A2 and CYP3A isoforms as part of phase one biotransformation, thereby producing inactive metabolites. The major metabolite produced is 3-hydroxy-levobupivacaine and the minor one is desbutyl-levobupivacaine. Subsequently, levobupivacaine metabolites are further converted into glucuronic acid and sulphate ester conjugates as a part of phase two. [ 7 ] [ 16 ] Metabolic inversion of levobupivacaine is not observed. The extensive metabolism of levobupivacaine by the liver ensures that no unchanged drug is excreted via urine . As a result, in patients with renal dysfunction , only the inactive metabolites accumulate instead of the drug itself.
Research tracing radiolabelled levobupivacaine showed that 71% was recovered in urine and 24% was recovered in faecesl [ 9 ] After the intravenous administration of 40 mg of levobupivacaine, the half-life was approximately 80 minutes and the rate of clearance was 651 ± 221.5 mL/min. [ 10 ] [ 16 ]
Levobupivacaine is an amino - amide anaesthetic that is similar in structure to bupivacaine, namely the S-enantiomer of bupivacaine. A lipophilic aromatic ring is linked to a hydrocarbon chain by an amide bond. The lipophilic components of levobupivacaine allow it to cross cell membraness and exert its local anaesthetic effect by causing a reversible blockade of open neuronal sodium channels.
A 5-step process to synthesise levobupivacaine from N α -CBZ (S)-lysine, published in 1996, [ 19 ] is depicted in Scheme 1. The key steps in this process include oxidative de-animation and stereospecific ring closure to form the pipecolamide core structure. This method is claimed to be efficient, but showed to be dangerous for mass production due to the high risk of explosion of the diazonium salt intermediates.
A more recent patent from 2008, [ 20 ] consists of a 3-step process (see Scheme 2) to synthesise levobupivacaine hydrochloride of an optical purity of at least 99%. (S)-2,6-pipecocholxylide (I) is reacted with 1-bromobutane and a base (a), such as potassium carbonate , to obtain a solution of (S)-bupivacaine (II) and its enantiomers. Recrystallisation of this solution with a solvent (b), preferably cyclohexane , can lead to an optical purity of at least 98% levobupivacaine. Lastly, the addition of hydrochloride (c) is possible. | https://en.wikipedia.org/wiki/Levobupivacaine |
Levocetirizine , sold under the brand name Xyzal , among others, is a second-generation antihistamine used for the treatment of allergic rhinitis (hay fever) and long-term hives of unclear cause. [ 3 ] It is less sedating than older antihistamines. [ 4 ] It is taken by mouth . [ 3 ]
Common side effects include sleepiness, dry mouth, cough, vomiting, and diarrhea. [ 3 ] Use in pregnancy appears safe but has not been well studied and use when breastfeeding is of unclear safety. [ 5 ] It is classified as a second-generation antihistamine and works by blocking histamine H 1 -receptors . [ 6 ] [ 3 ]
Levocetirizine was approved for medical use in the United States in 2007, [ 3 ] and is available as a generic medication . [ 4 ] In 2022, it was the 152nd most commonly prescribed medication in the United States, with more than 3 million prescriptions. [ 7 ] [ 8 ]
Levocetirizine is used for allergic rhinitis. [ 9 ] This includes allergy symptoms such as watery eyes, runny nose, sneezing, hives, and itching. [ 10 ]
Levocetirizine is referred to as a non-sedating antihistamine as it does not enter the brain in significant amounts and is therefore unlikely to cause drowsiness. Cardiac safety with repolarization may be better than some other antihistamines, as levocetirizine does not significantly prolong the QT interval in healthy individuals. [ 11 ] [ 12 ] [ 13 ] However, some people may still experience some slight sleepiness , headache , mouth dryness , lightheadedness , vision problems (mainly blurred vision ), palpitations and fatigue . [ 14 ]
Levocetirizine is an antihistamine. It acts as an inverse agonist that decreases activity at histamine H1 receptors. This in turn prevents the release of other allergy chemicals and increases the blood supply to the area, providing relief from the typical symptoms of hay fever. Levocetirizine, ( R )-(-)-cetirizine, is essentially a chiral switch of (±)-cetirizine. This enantiomer, the eutomer , is more selective and the ( S )-counterpart, the distomer , is inactive. [ 15 ] [ 16 ]
Chemically, levocetirizine is the active levorotary enantiomer of cetirizine , also called the l -enantiomer of cetirizine. It is a member of the diphenylmethylpiperazine group of antihistamines. [ citation needed ]
Levocetirizine was first launched in 2001 by the Belgian pharmaceutical company UCB ( Union Chimique Belge ). [ citation needed ]
In January 2017, the US Food and Drug Administration approved an over-the-counter preparation. [ 17 ] Levocetirizine had previously received authorization by the FDA as a prescription drug in 2007, having already been brought to market throughout much of Europe. [ citation needed ] In India, a prescription-only drug containing levocetirizine hydrochloride and montelukast is sold as Crohist MK. [ citation needed ]
Preparations of levocetirizine are sold under the following brand names: | https://en.wikipedia.org/wiki/Levocetirizine |
Levodropropizine is a cough suppressant . It is the levo isomer of dropropizine . It acts as a peripheral antitussive, with no action in the central nervous system . [ 1 ] It does not cause side effects such as constipation or respiratory depression which can be produced by opioid antitussives such as codeine and its derivatives.
In September 2021, Korea United Pharm file lawsuits against 15 drug manufacturers as patent infringement protection for its 2017 registered antitussive drug Levotics CR Tab. (levodropropizine). The cases are anchored on violation of its patent for "Method for Preparing Sustained-Release Tablets Containing Levodropropizine." [ 2 ] In September 2023, KUP signed a five-year $52.1 million contract with MCQ, a Thai-based pharmaceutical company, for supply of its mucoactive drug, Levotics CR Tab (levodropropizine). [ 3 ]
This drug article relating to the respiratory system is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Levodropropizine |
Levofenfluramine ( INN ), or (−)-3-trifluoromethyl- N -ethylamphetamine , also known as (−)-fenfluramine or ( R )-fenfluramine , is a drug of the amphetamine family that, itself (i.e., in enantiopure form ), was never marketed alone. [ 1 ] It is the levorotatory enantiomer of fenfluramine , the racemic form of the compound, whereas the dextrorotatory enantiomer is dexfenfluramine . [ 2 ] Both fenfluramine and dexfenfluramine are anorectic agents that have been used clinically in the treatment of obesity (and hence, levofenfluramine has been as well since it is a component of fenfluramine). [ 2 ] However, they have since been discontinued due to reports of causing cardiovascular conditions such as valvular heart disease and pulmonary hypertension , [ 3 ] adverse effects that are likely to be caused by excessive stimulation of 5-HT 2B receptors expressed on heart valves . [ 4 ] [ 5 ]
Dexfenfluramine is believed to be solely responsible for the appetite suppressant properties of fenfluramine, [ 2 ] of which it has been demonstrated to mediate predominantly via activation of postsynaptic 5-HT 1B and 5-HT 2C receptors [ 6 ] through a combination of indirect serotonin releasing agent and direct serotonin receptor agonist activities (the latter of which are mediated fully by its active metabolite dexnorfenfluramine ). [ 7 ] [ 8 ] [ 9 ] Contrarily, levofenfluramine is thought to contribute only to unwanted side effects . [ 2 ] Paradoxically, however, it has been shown that levofenfluramine too acts as a relatively potent releaser of serotonin , [ 10 ] though with approximately 1/3 of the efficacy of dexfenfluramine. [ 10 ] As such, it would be expected to possess some degree of appetite suppressant properties as well, yet it does not. [ 2 ] [ 11 ] A potential explanation as to why levofenfluramine is not similarly an effective anorectic is that it has also been found to behave as a dopamine receptor antagonist , [ 12 ] which, as dopamine antagonists like atypical antipsychotics are associated with causing increased appetite and weight gain —effects that their actions on dopamine receptors have been implicated in playing a role in the development of, [ 13 ] is an action that could in theory cancel out the hypothetical serotonergically-mediated appetite suppressant effects of the compound. However, this is speculation and has not been proven.
Levonorfenfluramine , an active metabolite of levofenfluramine, is also a fairly potent serotonin releasing agent (with a potency of approximately 1/2 that of norfenfluramine and 1/6 that of dexfenfluramine) and, similarly to dexnorfenfluramine, is a 5-HT 2B and 5-HT 2C receptor agonist, as well as a somewhat less potent norepinephrine reuptake inhibitor (about 1/2 that of its efficacy as a serotonin releaser). [ 5 ] [ 7 ] [ 10 ] As such, it likely contributes significantly to the biological activity —though not necessarily appetite suppressant effects—of not only levofenfluramine but of racemic fenfluramine as well. In contrast to levonorfenfluramine, levofenfluramine is virtually inactive as a reuptake inhibitor or releaser of norepinephrine , [ 10 ] and neither compound has any effect on dopamine reuptake or release. [ 10 ] | https://en.wikipedia.org/wiki/Levofenfluramine |
Levofloxacin , sold under the brand name Levaquin among others, is a broad-spectrum antibiotic of the fluoroquinolone drug class. [ 5 ] It is the left-handed isomer of the medication ofloxacin . [ 5 ] [ 6 ] It is used to treat a number of bacterial infections including acute bacterial sinusitis , pneumonia , H. pylori (in combination with other medications), urinary tract infections , Legionnaires' disease , chronic bacterial prostatitis , and some types of gastroenteritis . [ 6 ] Along with other antibiotics it may be used to treat tuberculosis , meningitis , or pelvic inflammatory disease . [ 6 ] It is available by mouth, intravenously , [ 6 ] and in eye drop form. [ 7 ]
Common side effects include nausea , diarrhea , and trouble sleeping. [ 6 ] A warning concerning all fluoroquinolones was issued in 2016: "An FDA safety review has shown that fluoroquinolones when used systemically (i.e. tablets, capsules, and injectable) are associated with disabling and potentially permanent serious adverse effects that can occur together. These adverse effects can involve the tendons, muscles, joints, nerves, and central nervous system." [ 8 ]
Other serious side effects may include tendon rupture , tendon inflammation , seizures , psychosis , and potentially permanent peripheral nerve damage . [ 6 ] Tendon damage may appear months after treatment is completed. [ 6 ] People may also sunburn more easily . [ 6 ] In people with myasthenia gravis , muscle weakness and breathing problems may worsen. [ 6 ] While use during pregnancy is not recommended, risk appears to be low. [ 5 ] The use of other medications in this class appear to be safe while breastfeeding ; however, the safety of levofloxacin is unclear. [ 5 ]
Levofloxacin was patented in 1985 and approved for medical use in the United States in 1996. [ 6 ] [ 9 ] It is on the World Health Organization's List of Essential Medicines . [ 10 ] It is available as a generic medication . [ 6 ] In 2022, it was the 251st most commonly prescribed medication in the United States, with more than 1 million prescriptions. [ 11 ] [ 12 ]
Levofloxacin is used to treat infections including: respiratory tract infections , cellulitis , urinary tract infections , prostatitis , anthrax , endocarditis , meningitis , pelvic inflammatory disease , traveler's diarrhea , tuberculosis , and plague [ 6 ] [ 2 ] and is available by mouth, intravenously , [ 6 ] and in eye drop form. [ 7 ]
As of 2016, the US Food and Drug Administration (FDA) recommended that "serious side effects associated with fluoroquinolone antibacterial drugs generally outweigh the benefits for patients with acute sinusitis, acute bronchitis, and uncomplicated urinary tract infections who have other treatment options. For patients with these conditions, fluoroquinolones should be reserved for those who do not have alternative treatment options." [ 8 ]
Levofloxacin is used for the treatment of pneumonia, urinary tract infections, and abdominal infections. As of 2007 the Infectious Disease Society of America (IDSA) and the American Thoracic Society recommended levofloxacin and other respiratory fluoroquinolines as first line treatment for community acquired pneumonia when co-morbidities such as heart, lung, or liver disease are present or when in-patient treatment is required. [ 13 ] Levofloxacin also plays an important role in recommended treatment regimens for ventilator-associated and healthcare-associated pneumonia. [ 14 ]
As of 2010 it was recommended by the IDSA as a first-line treatment option for catheter-associated urinary tract infections in adults. [ 15 ] In combination with metronidazole it is recommended as one of several first-line treatment options for adult patients with community-acquired intra-abdominal infections of mild-to-moderate severity. [ 16 ] The IDSA also recommends it in combination with rifampicin as a first-line treatment for prosthetic joint infections. [ 17 ] The American Urological Association recommends levofloxacin as a first-line treatment to prevent bacterial prostatitis when the prostate is biopsied. [ 18 ] and as of 2004 it was recommended to treat bacterial prostatitis by the NIH research network studying the condition. [ 19 ]
Levofloxacin and other fluoroquinolones have also been widely used for the treatment of uncomplicated community-acquired respiratory and urinary tract infections, indications for which major medical societies generally recommend the use of older, narrower spectrum drugs to avoid fluoroquinolone resistance development. Due to its widespread use, common pathogens such as Escherichia coli and Klebsiella pneumoniae have developed resistance. In many countries as of 2013, resistance rates among healthcare-associated infections with these pathogens exceeded 20%. [ 20 ] [ 21 ]
Levofloxacin is also used as antibiotic eye drops to prevent bacterial infection. Usage of levofloxacin eye drops, along with an antibiotic injection of cefuroxime or penicillin during cataract surgery , has been found to lower the chance of developing endophthalmitis , compared to eye drops or injections alone. [ 22 ]
According to the FDA approved prescribing information, levofloxacin is pregnancy category C. [ 2 ] This designation indicates that animal reproduction studies have shown adverse effects on the fetus and there are no adequate and well-controlled studies in humans, but the potential benefit to the mother may in some cases outweigh the risk to the fetus. Available data point to a low risk for the unborn child. [ 5 ] Exposure to quinolones, including levofloxacin, during the first-trimester is not associated with an increased risk of stillbirths, premature births, birth defects, or low birth weight. [ 23 ]
Levofloxacin does penetrate into breastmilk, though the concentration of levofloxacin in the breastfeeding infant is expected to be low. [ 24 ] Due to potential risks to the baby, the manufacturer does not recommend that nursing mothers take levofloxacin. [ 2 ] However, the risk appears to be very low, and levofloxacin can be used in breastfeeding mothers with proper monitoring of the infant, combined with delaying breastfeeding for 4–6 hours after taking levofloxacin. [ 24 ]
Levofloxacin is not approved in most countries for the treatment of children except in unique and life-threatening infections because it is associated with an elevated risk of musculoskeletal injury in this population, a property it shares with other fluoroquinolones.
In the United States levofloxacin is approved for the treatment of anthrax and plague in children over six months of age. [ 2 ]
Levofloxacin is recommended by the Pediatric Infectious Disease Society and the Infectious Disease Society of America as a first-line treatment for pediatric pneumonia caused by penicillin-resistant Streptococcus pneumoniae , and as a second-line agent for the treatment of penicillin-sensitive cases. [ 25 ]
In one study, [ 2 ] [ 26 ] 1534 juvenile patients (age 6 months to 16 years) treated with levofloxacin as part of three efficacy trials were followed up to assess all musculoskeletal events occurring up to 12 months post-treatment. At 12 months follow-up the cumulative incidence of musculoskeletal adverse events was 3.4%, compared to 1.8% among 893 patients treated with other antibiotics. In the levafloxacin-treated group, approximately two-thirds of these musculoskeletal adverse events occurred in the first 60 days, 86% were mild, 17% were moderate, and all resolved without long-term sequelae.
Levofloxacin and later generation fluoroquinolones are collectively referred to as "respiratory quinolones" to distinguish them from earlier fluoroquinolones which exhibited modest activity toward the important respiratory pathogen Streptococcus pneumoniae . [ 27 ]
The drug exhibits enhanced activity against the important respiratory pathogen Streptococcus pneumoniae relative to earlier fluoroquinolone derivatives like ciprofloxacin . For this reason, it is considered a "respiratory fluoroquinolone" along with more recently developed fluoroquinolones such as moxifloxacin and gemifloxacin . It is less active than ciprofloxacin against Gram-negative bacteria, especially Pseudomonas aeruginosa , and lacks the anti- methicillin-resistant Staphylococcus aureus (MRSA) activity of moxifloxacin and gemifloxacin . [ 28 ] [ 29 ] [ 30 ] [ 31 ] Levofloxacin has shown moderate activity against anaerobes , and is about twice as potent as ofloxacin against Mycobacterium tuberculosis and other mycobacteria, including Mycobacterium avium complex . [ 32 ]
Its spectrum of activity includes most strains of bacterial pathogens responsible for respiratory, urinary tract, gastrointestinal, and abdominal infections, including Gram negative ( Escherichia coli , Haemophilus influenzae , Klebsiella pneumoniae , Legionella pneumophila , Moraxella catarrhalis , Proteus mirabilis , and Pseudomonas aeruginosa ), Gram positive ( methicillin -sensitive but not methicillin-resistant Staphylococcus aureus , Streptococcus pneumoniae , Staphylococcus epidermidis , Enterococcus faecalis , and Streptococcus pyogenes ), and atypical bacterial pathogens ( Chlamydophila pneumoniae and Mycoplasma pneumoniae ). Compared to earlier antibiotics of the fluoroquinoline class such as ciprofloxacin , levofloxacin exhibits greater activity towards Gram-positive bacteria [ 28 ] but lesser activity toward Gram-negative bacteria, [ 33 ] especially Pseudomonas aeruginosa .
Resistance to fluoroquinolones is common in staphylococcus and pseudomonas . Resistance occurs in multiple ways. One mechanism is by an alteration in topoisomerase IV enzyme. A double mutant form of S. pneumoniae Gyr A + Par C bearing Ser-81-->Phe and Ser-79-->Phe mutations were eight to sixteen times less responsive to ciprofloxacin. [ 34 ]
Package inserts mention that levofloxacin is to be avoided in patients with a known hypersensitivity to levofloxacin or other quinolone drugs. [ 2 ] [ 35 ]
Like all fluoroquinolines, levofloxacin is contraindicated in patients with epilepsy or other seizure disorders, and in patients who have a history of quinolone-associated tendon rupture. [ 2 ] [ 35 ]
Levofloxacin may prolong the QT interval in some people, especially the elderly, and levofloxacin should not be used for people with a family history of Long QT syndrome , or who have long QT, chronic low potassium , it should not be prescribed with other drugs that prolong the QT interval. [ 2 ]
Unlike ciprofloxacin, levofloxacin does not appear to deactivate the drug metabolizing enzyme CYP1A2 . Therefore, drugs that use that enzyme, like theophylline , do not interact with levofloxacin. It is a weak inhibitor of CYP2C9 , [ 36 ] suggesting potential to block the breakdown of warfarin and phenprocoumon . This can result in more action of drugs like warfarin, leading to more potential side effects, such as bleeding. [ 37 ]
The use of non-steroidal anti-inflammatory drugs (NSAIDs) in combination with high dose fluoroquinolone therapy may lead to seizures. [ 38 ]
When levofloxacin is taken with anti-acids containing magnesium hydroxide or aluminum hydroxide, the two combine to form insoluble salts that are difficult to absorb from the intestines. Peak serum concentrations of levofloxacin may be reduced by 90% or more, which can prevent the levofloxacin from working. Similar results have been reported when levofloxacin is taken with iron supplements and multi-vitamins containing zinc. [ 39 ] [ 40 ]
A 2011 review examining musculoskeletal complications of fluoroquinolones proposed guidelines with respect to administration to athletes, that called for avoiding all use of fluoroquinolone antibiotics if possible, and if they are used: ensure there is informed consent about the musculoskeletal risks, and inform coaching staff; do not use any corticosteroids if fluoroquinolones are used; consider dietary supplements of magnesium and antioxidants during treatment; reduce training until the course of antibiotic is finished and then carefully increase back to normal; and monitor for six months after the course is finished, and stop all athletic activity if symptoms emerge. [ 41 ]
Adverse effects are typically mild to moderate. However, severe, disabling, and potentially irreversible adverse effects sometimes occur, and for this reason it is recommended that use of fluoroquinolones be limited.
Prominent among these are adverse effects that became the subject of a black box warning by the FDA in 2016. [ 8 ] The FDA wrote: "An FDA safety review has shown that fluoroquinolones when used systemically (i.e. tablets, capsules, and injectable) are associated with disabling and potentially permanent serious adverse effects that can occur together. These adverse effects can involve the tendons, muscles, joints, nerves, and central nervous system." [ 8 ] Rarely, tendinitis or tendon rupture may occur due to fluoroquinolone antibiotics, including levofloxacin. [ 42 ] Such injuries, including tendon rupture, has been observed up to six months after cessation of treatment; higher doses of fluoroquinolones, being elderly, transplant patients, and those with a current or historical corticosteroid use are at elevated risk. [ 43 ] [ 44 ] The U.S. label for levofloxacin also contains a black box warning for the exacerbation of the symptoms of the neurological disease myasthenia gravis . [ 2 ] [ 45 ] Similarly, the UK Medicines and Healthcare Products Regulatory Agency recommendations warn of rare but disabling and potentially irreversible adverse effects, and to recommend limiting use of these drugs. [ 46 ] Increasing age and corticosteroid use appears to increase the risk of musculoskeletal complications. [ 41 ]
A wide variety of other uncommon but serious adverse events have been associated with fluoroquinolone use, with varying degrees of evidence supporting causation. These include anaphylaxis, hepatotoxicity, central nervous system effects including seizures and psychiatric effects, prolongation of the QT interval , blood glucose disturbances, and photosensitivity , among others. [ 2 ] [ 35 ] Levofloxacin may produce fewer of these rare serious adverse effects than other fluoroquinolones. [ 47 ]
There is some disagreement in the medical literature regarding whether and to what extent levofloxacin and other fluoroquinolones produce serious adverse effects more frequently than other broad spectrum antibacterial drugs. [ 48 ] [ 49 ] [ 50 ] [ 51 ]
Concerning more usual adverse effects, in pooled results from 7537 patients exposed to levofloxacin in 29 clinical trials, 4.3% discontinued treatment due to adverse drug reactions. The most common adverse reactions leading to discontinuation were gastrointestinal, including nausea, vomiting, and constipation. Overall, 7% of patients experienced nausea, 6% headache, 5% diarrhea, and 4% insomnia, along with other adverse reactions experienced at lower rates. [ 2 ]
Administration of levofloxacin or other broad-spectrum antibiotics is associated with Clostridioides difficile associated diarrhea which may range in severity from mild diarrhea to fatal colitis. Fluoroquinolone administration may be associated with the acquisition and outgrowth of a particularly virulent Clostridioides strain. [ 52 ]
More research is needed to determine the best dose and length of treatment. [ 53 ]
Overdosing experiments in animals showed loss of body control and drooping, difficulty breathing, tremors, and convulsions. Doses in excess of 1500 mg/kg orally and 250 mg/kg IV produced significant mortality in rodents. [ 2 ]
In the event of an acute overdosage, authorities recommend unspecific standard procedures such as emptying the stomach, observing the patient and maintaining appropriate hydration. Levofloxacin is not efficiently removed by hemodialysis or peritoneal dialysis . [ 2 ]
Levofloxacin is a broad-spectrum antibiotic that is active against both Gram-positive and Gram-negative bacteria. Like all quinolones, it functions by inhibiting the DNA gyrase and topoisomerase IV , two bacterial type IIA topoisomerases . [ 54 ] Topoisomerase IV is necessary to separate DNA that has been replicated (doubled) prior to bacterial cell division. With the DNA not being separated, the process is stopped, and the bacterium cannot divide. DNA gyrase, on the other hand, is responsible for supercoiling the DNA, so that it will fit in the newly formed cells. Both mechanisms amount to killing the bacterium. Levofloxacin acts as a bactericide . [ 55 ]
As of 2011, the mechanism of action for the drug's musculoskeletal complications were not clear. [ 41 ]
Levofloxacin is rapidly and essentially completely absorbed after oral administration, with a plasma concentration profile over time that is essentially identical to that obtained from intravenous administration of the same amount over 60 minutes. As such, the intravenous and oral formulations of levofloxacin are considered interchangeable. [ 2 ] Levofloxacin's ability to bind to proteins in the body ranges from 24 to 38%. [ 53 ]
The drug undergoes widespread distribution into body tissues. Peak levels in skin are achieved 3 hours after administration and exceed those in plasma by a factor of 2. Similarly, lung tissue concentrations range from two-fold to five-fold higher than plasma concentrations in the 24 hours after a single dose.
The mean terminal plasma elimination half-life of levofloxacin ranges from approximately 6 to 8 hours following single or multiple doses of levofloxacin given orally or intravenously. Elimination occurs mainly via excretion of unmetabolized drug in the urine. Following oral administration, 87% of an administered dose was recovered in the urine as unchanged drug within 2 days. Less than 5% was recovered in the urine as the desmethyl and N-oxide metabolites, the only metabolites identified in humans.
Like all fluoroquinolones, levofloxacin is a fluorinated quinolone carboxylic acid . It is a chiral molecule and the pure (−)-( S )- enantiomer of the racemic drug ofloxacin . [ 56 ] [ 57 ] [ 58 ] This enantiomer binds more effectively to the DNA gyrase enzyme and to topoisomerase IV than its (+)-( R )-counterpart. [ 53 ] Levofloxacin is referred to as a chiral switch : These are chiral drugs that have already been patent claimed , approved and marketed as racemates (or as mixtures of diastereomers [ 59 ] but have since been redeveloped as pure enantiomers. [ 60 ] Distinct functional groups on this molecules include a hydroxyl group, carbonyl group, and an aromatic ring. [ 61 ] [ failed verification ]
The substance is used as the hemi hydrate , which has the empirical formula C 18 H 20 FN 3 O 4 ·½H 2 O and a molecular mass of 370.38 g/mol. Levofloxacin is a light-yellowish-white to yellow-white crystal or crystalline powder. [ 2 ] A major issue in the synthesis of levofloxacin is identifying correct entries into the benzoxazine core in order to produce the correct chiral form. [ 62 ]
Levofloxacin is a third-generation fluoroquinolone , being one of the isomers of ofloxacin , which was a broader-spectrum conformationally locked analog of norfloxacin ; both ofloxacin and levofloxaxin were synthesized and developed by scientists at Daiichi Seiyaku . [ 63 ] The Daiichi scientists knew that ofloxacin was racemic, but tried unsuccessfully to separate the two isomers; in 1985 they succeeded in separately synthesizing the pure levo form and showed that it was less toxic and more potent than the other form. [ 64 ] [ 65 ]
It was first approved for marketing in Japan in 1993, for oral administration, and Daiichi marketed it there under the brand name Cravit. [ 65 ] Daiichi, working with Johnson & Johnson as it had with ofloxacin, obtained FDA approval in 1996 under the brand name Levaquin [ 64 ] to treat bacterial sinusitus, bacterial exacerbations of bronchitis, community-acquired pneumonia, uncomplicated skin infections, complicated urinary tract infections, and acute pyelonephritis. [ 2 ]
Levofloxacin had reached blockbuster status by this time; combined worldwide sales of levofloxacin and ofloxacin for J&J alone were US$1.6 billion in 2009. [ 66 ]
The term of the levofloxacin United States patent was extended by the U.S. Patent and Trademark Office 810 days under the provisions of the Hatch Waxman Amendment so that the patent would expire in 2010 instead of 2008. [ 64 ] This extension was challenged by generic drug manufacturer Lupin Pharmaceuticals, which did not challenge the validity of the patent, but only the validity of the patent extension, arguing that the patent did not cover a "product" and so Hatch-Waxman was not available for extensions. [ 64 ] The federal patent court ruled in favor of J&J and Daiichi, and generic versions of levofloxacin did not enter the U.S. market until 2009. [ 64 ] [ 66 ]
Levofloxacin is available in tablet form, injection,patches and oral solution. [ 2 ]
The US Food and Drug Administration estimated that in 2011, over 23 million outpatient prescriptions for fluoroquinolones, of which levofloxacin made up 28%, were filled in the United States. [ 67 ]
As of 2012, Johnson and Johnson was facing around 3400 state and federal lawsuits filed by people who claimed tendon damage from levofloxacin; about 1900 pending in a class action at the United States District Court in Minnesota [ 68 ] and about 1500 pending at a district court in New Jersey. [ 69 ] [ 70 ]
In October 2012, J&J settled 845 cases in the Minnesota action, after Johnson and Johnson prevailed in three of the first four cases to go to trial. By May 2014, all but 363 cases had been settled or adjudicated. [ 70 ] [ 71 ] [ 72 ]
Levofloxacin is marketed by Sanofi-Aventis under a license agreement signed with Daiichi in 1993, under the brand name Tavanic. [ 66 ] | https://en.wikipedia.org/wiki/Levofloxacin |
Levoglucosan (C 6 H 10 O 5 ) is an organic compound with a six- carbon ring structure formed from the pyrolysis of carbohydrates, such as starch and cellulose . [ 1 ] As a result, levoglucosan is often used as a chemical tracer for biomass burning in atmospheric chemistry studies, particularly with respect to airborne particulate matter .
Along with other tracers such as potassium, oxalate, and gaseous acetonitrile, [ 2 ] levoglucosan has been shown to be highly correlated with regional fires. This is because the gas emitted by the pyrolysis of wood (biomass) contains significant amounts of levoglucosan.
Levoglucosan has been described as "an unequivocal biomass burning tracer" in the context of forest and brush fires. [ 3 ] But the anhydrosugar has only been found detectable in low temperature samples (150-350 °C), meaning that its value as an indicator for smoke from controlled biomass combustion in, for instance, modern domestic wood stoves which operate at temperatures above 500 °C, is "very doubtful". [ 4 ] Levoglucosan is a marker for coal combustion as well as wood. [ 5 ]
The hydrolysis of levoglucosan generates the fermentable sugar glucose . Levoglucosan can be utilized in the synthesis of chiral polymers such as unhydrolysable glucose polymers . | https://en.wikipedia.org/wiki/Levoglucosan |
Levoketoconazole , sold under the brand name Recorlev , is a steroidogenesis inhibitor that is used for the treatment of Cushing's syndrome . [ 2 ] [ 3 ] [ 4 ] [ 5 ] Levoketoconazole was approved for medical use in the United States in December 2021. [ 6 ] [ 7 ]
Levoketoconazole is the levorotatory or (2 S ,4 R ) enantiomer of ketoconazole , [ 3 ] [ 4 ] [ 5 ] and it is an inhibitor of the enzymes CYP11B1 (11β-hydroxylase), CYP17A1 (17α-hydroxylase/17,20-lyase), and CYP21A2 (21-hydroxylase). [ 2 ] [ 3 ] [ 5 ] It inhibits glucocorticoid biosynthesis and hence circulating levels of glucocorticoids , thereby treating Cushing's syndrome. [ 2 ] [ 5 ] In addition to its increased potency, the drug is 12-fold less potent than racemic ketoconazole in inhibiting CYP7A1 (cholesterol 7α-hydroxylase), theoretically resulting in further reduced interference with bile acid production and metabolite elimination and therefore less risk of hepatotoxicity . [ 5 ] Levoketoconazole has also been found to inhibit CYP11A1 (cholesterol side-chain cleavage enzyme) and CYP51A1 (lanosterol-14α-demethylase), similarly but more potently relative to ketoconazole. [ 8 ]
In a systematic review of levoketoconazole, published in 2024, it was found to be effective in the management of Cushing Syndrome. [ 9 ] | https://en.wikipedia.org/wiki/Levoketoconazole |
Levomethamphetamine [ a ] ( INN : levmetamfetamine ) is an optical isomer of methamphetamine primarily used as a topical nasal decongestant . [ 2 ] Levomethamphetamine is used to treat nasal congestion from allergies and the common cold . [ 7 ] It was first used medically as decongestant beginning in 1958 and has been used for such purposes, primarily in the United States, since then. [ 8 ]
Levomethamphetamine is used to treat nasal congestion related to the common cold and allergic rhinitis. It is available in the form of an inhaler containing 50 mg total per inhaler and delivering between 0.04 and 0.15 mg of the drug per inhalation. [ 2 ] Inhalers with a total of 113 mg levomethamphetamine were previously marketed in the United States, but the total amount was eventually reduced to 50 mg. [ 2 ]
When the nasal decongestant is taken in excess, levomethamphetamine has potential side effects . These would be similar to those of other decongestants.
Levomethamphetamine acts as a selective norepinephrine releasing agent . [ 12 ] [ 16 ] [ 18 ] [ 4 ] The potencies of levomethamphetamine, levoamphetamine , dextromethamphetamine , and dextroamphetamine in terms of norepinephrine release in vitro and in vivo in rats are all similar. [ 19 ] [ 20 ] [ 21 ] [ 22 ] [ 16 ]
Conversely, whereas dextromethamphetamine and dextroamphetamine are relatively balanced releasers of dopamine and norepinephrine in vitro , levomethamphetamine is about 15- to 20-fold less potent in inducing dopamine release relative to norepinephrine release. [ 16 ] [ 18 ] [ 4 ] [ 12 ] [ 21 ] Moreover, whereas levoamphetamine is about 3- to 5-fold less potent in terms of dopamine release than dextroamphetamine in vivo , levomethamphetamine is dramatically less potent than dextromethamphetamine and substantially less potent than levoamphetamine in this regard. [ 20 ] [ 19 ] [ 22 ]
In accordance with the findings of catecholamine release studies, levomethamphetamine is 2- to 10-fold or more less potent than dextromethamphetamine in terms of psychostimulant -like effects in rodents. [ 23 ] [ 24 ] [ 25 ] For comparison, levoamphetamine is only 1- to 4-fold less potent than dextroamphetamine in its stimulating and reinforcing effects in monkeys and humans. [ 19 ] [ 26 ]
The effects of levomethamphetamine are qualitatively distinct relative to those of racemic methamphetamine and dextromethamphetamine and it does not possess the same potential for euphoria or addiction that these drugs possess. [ 2 ] [ 25 ] [ 27 ] [ 4 ] [ 22 ] In clinical studies, levomethamphetamine at oral doses of 1 to 10 mg has been found not to affect subjective drug responses, heart rate , blood pressure , core temperature , electrocardiography , respiration rate , oxygen saturation , or other clinical parameters. [ 2 ] [ 3 ] As such, doses of levomethamphetamine of less than or equal to 10 mg have no significant physiological or subjective effects. [ 2 ] [ 3 ] However, higher doses of levomethamphetamine, for instance 0.25 to 0.5 mg/kg (mean doses of ~18–37 mg) intravenously , have been reported to produce significant pharmacological effects, including increased heart rate and blood pressure, increased respiration rate, and subjective effects like intoxication and drug liking . [ 2 ] [ 4 ] On the other hand, in contrast to dextromethamphetamine, levomethamphetamine also produces subjective "bad" or aversive drug effects. [ 18 ] [ 4 ] Among the physiological effects of levomethamphetamine is vasoconstriction , which makes it useful for nasal decongestion. [ 28 ]
For comparison to levomethamphetamine, 5 to 60 mg oral doses of the related drug levoamphetamine have been used clinically and have been reported to produce significant pharmacological effects, for instance on wakefulness and mood . [ 29 ] [ 30 ] [ 31 ] [ 26 ] [ 32 ]
In addition to its norepinephrine-releasing activity, levomethamphetamine is also an agonist of the trace amine-associated receptor 1 (TAAR1). [ 33 ] [ 34 ] [ 35 ] Levomethamphetamine has also been found to act as a catecholaminergic activity enhancer (CAE), notably at much lower concentrations than its catecholamine releasing activity. [ 36 ] [ 37 ] [ 38 ] [ 39 ] [ 40 ] It is 1- to 10-fold less potent than selegiline but is 3- to 5-fold more potent than dextromethamphetamine in this action. [ 37 ] [ 38 ] [ 39 ] The CAE effects of such agents may be mediated by TAAR1 agonism. [ 41 ] [ 40 ]
The bioavailability of levomethamphetamine is approximately 100%. [ 2 ] [ 3 ] The peak levels of levomethamphetamine range from 3.3 to 31.4 ng/mL with single oral doses of 1 to 10 mg and from 65.4 to 125.9 ng/mL with single intravenous doses of 0.25 to 0.5 mg/kg. [ 2 ] [ 4 ] [ 42 ] The area-under-the-curve (AUC) levels of levomethamphetamine range from 73.0 to 694.7 ng⋅h/mL with single oral doses of 1 to 10 mg and from 1,190.7 to 2,368.1 mg/kg with single intravenous doses of 0.25 to 0.5 mg/kg. [ 2 ] [ 4 ] [ 42 ]
The volume of distribution of levomethamphetamine is 288.5 to 315.5 L or 4.15 to 4.17 L/kg. [ 2 ] [ 4 ] [ 3 ]
The pharmacokinetics of levomethamphetamine generated as a metabolite from selegiline have been found to be significantly different in CYP2D6 poor metabolizers versus extensive metabolizers . [ 5 ] [ 6 ] Area-under-the-curve (AUC) levels of levomethamphetamine were 46% higher and its elimination half-life was 33% longer in CYP2D6 poor metabolizers compared to extensive metabolizers. [ 5 ] [ 6 ] These findings suggest that CYP2D6 may be significantly involved in the metabolism of levomethamphetamine. [ 5 ] [ 6 ]
Levomethamphetamine is metabolized into levoamphetamine in small amounts. [ 2 ] [ 4 ] [ 3 ]
Levomethamphetamine is excreted in urine 40.8 to 49.0% as unchanged levomethamphetamine and 2.1 to 3.3% as levoamphetamine . [ 2 ] [ 4 ] [ 3 ] Levomethamphetamine can register on urine drug tests as either methamphetamine, amphetamine, or both, depending on the subject's metabolism and dosage. Levomethamphetamine metabolizes completely into levoamphetamine after a period of time. [ 43 ]
The mean elimination half-life of levomethamphetamine ranges between 10.2 and 15.0 hours. [ 2 ] [ 4 ] For comparison, the elimination half-life of dextromethamphetamine was around 10.2 to 10.7 hours in the same studies. [ 2 ] [ 4 ] The clearance of levomethamphetamine is 15.5 to 19.1 L/h or 0.221 L/h⋅kg. [ 2 ] [ 4 ] [ 3 ]
With selegiline at an oral dose of 10 mg, levomethamphetamine and levoamphetamine are eliminated in urine and recovery of levomethamphetamine is 20 to 60% (or about 2–6 mg) while that of levoamphetamine is 9 to 30% (or about 1–3 mg). [ 44 ]
Levomethamphetamine, also known as L -α, N -dimethyl-β-phenylethylamine or as L - N -methylamphetamine, is a substituted phenethylamine and amphetamine . [ 2 ] [ 45 ] It is the levorotatory enantiomer of methamphetamine . [ 2 ] Racemic methamphetamine contains two optical isomers in equal amounts, dextromethamphetamine (the dextrorotatory enantiomer) and levomethamphetamine. [ 2 ]
Methamphetamine , a racemic mixture of dextromethamphetamine and levomethamphetamine, was first discovered and synthesized in 1919. [ 46 ] [ 47 ] Methamphetamine was first introduced for medical use in 1938 in oral form under the brand name Pervitin in Germany . [ 46 ] [ 47 ] Over-the-counter nasal decongestant inhalers containing enantiopure levomethamphetamine, originally labeled with the chemical name l-desoxyephedrine , were first introduced in 1958 under the brand name Vicks Inhaler. [ 8 ] [ 48 ] [ 49 ] By 1995, the brand name was changed to Vicks Vapor Inhaler. [ 50 ] [ 51 ] In 1998, the United States Food and Drug Administration (FDA) required that the chemical name on the labeling be changed from l -desoxyephedrine to levmetamfetamine . [ 52 ]
Levomethamphetamine is a controlled substance in the Philippines . [ 53 ]
As of 2006, there were no studies demonstrating "drug liking" scores of oral levomethamphetamine that are similar to racemic methamphetamine or dextromethamphetamine in either recreational users or medicinal users. [ 4 ] In any case, misuse of levomethamphetamine at high doses has been reported. [ 54 ] [ 55 ] [ 56 ] [ 57 ]
In 2012, tighter controls in Mexico on certain methamphetamine precursors like ephedrine and pseudoephedrine led to a greater percentage of illicit methamphetamine from Mexican drug cartels consisting of a higher ratio of levomethamphetamine to dextromethamphetamine within batches of racemic methamphetamine. [ 58 ]
The manufacturing of levomethamphetamine products for therapeutic use is done according to government regulations and pharmacopeia monographs. The most recent change in Food and Drug Administration regulations for levomethamphetamine inhalers was in 1994, with the adoption of a final monograph. [ 59 ] | https://en.wikipedia.org/wiki/Levomethamphetamine |
Levomethorphan (LVM) ( INN , BAN ) is an opioid analgesic of the morphinan family that has never been marketed. [ 2 ] It is the L - stereoisomer of racemethorphan (methorphan). [ 2 ] The effects of the two isomers of racemethorphan are quite different, with dextromethorphan (DXM) being an antitussive at low doses and a dissociative hallucinogen at much higher doses. [ 3 ] Levomethorphan is about five times stronger than morphine. [ 4 ]
Levomethorphan is a prodrug to levorphanol , analogously to DXM acting as a prodrug to dextrorphan or codeine behaving as a prodrug to morphine . [ 5 ] As such, levomethorphan has similar effects to levorphanol but is less potent as it must be demethylated to the active form by liver enzymes before being able to produce its effects. [ 5 ] As a prodrug of levorphanol, levomethorphan functions as a potent agonist of all three of the opioid receptors , μ , κ (κ 1 and κ 3 but notably not κ 2 ), and δ , as an NMDA receptor antagonist , and as a serotonin-norepinephrine reuptake inhibitor . [ 5 ] Via activation of the κ-opioid receptor, levomethorphan can produce dysphoria and psychotomimetic effects such as dissociation and hallucinations . [ 6 ]
Levomethorphan is listed under the Single Convention on Narcotic Drugs 1961 and is regulated like morphine in most countries. In the United States it is a Schedule II Narcotic controlled substance with a DEA ACSCN of 9210 and a 2014 annual aggregate manufacturing quota of 195 grams, up from 6 grams the year before. The salts in use are the tartrate (free base conversion ratio 0.644) and hydrobromide (0.958). [ 7 ] At the current time [ when? ] , no levomethorphan pharmaceuticals are marketed in the United States. [ citation needed ] | https://en.wikipedia.org/wiki/Levomethorphan |
Levomilnacipran , sold under the brand name Fetzima , is an antidepressant , used for the treatment of major depressive disorder in adults. [ 4 ] It is the levorotatory enantiomer of milnacipran , and has similar effects and pharmacology , acting as a serotonin–norepinephrine reuptake inhibitor . [ 7 ] [ 8 ]
Levomilnacipran was approved for medical use in the United States in July 2013. [ 9 ]
Levomilnacipran is indicated for the treatment of major depressive disorder in adults. [ 4 ]
Side effects seen more often with levomilnacipran than with placebo in clinical trials included nausea , dizziness , sweating , constipation , insomnia , increased heart rate and blood pressure , urinary hesitancy , erectile dysfunction and delayed ejaculation in males, vomiting , tachycardia , and palpitations . [ 10 ] [ 11 ]
Relative to other serotonin and norepinephrine reuptake inhibitors, levomilnacipran, as well as milnacipran, differ in that they are much more balanced reuptake inhibitors of serotonin and norepinephrine . [ 12 ] [ 13 ] [ 14 ] To demonstrate, the serotonin:norepinephrine ratios of SNRIs are as follows: venlafaxine = 30:1, duloxetine = 10:1, desvenlafaxine = 14:1, milnacipran = 1.6:1, and levomilnacipran = 1:2. [ 12 ] The clinical implications of more balanced elevations of serotonin and norepinephrine are unclear, [ 12 ] but may include improved effectiveness, though also increased side effects. [ 13 ] [ 14 ] [ 15 ]
Levomilnacipran is selective for the serotonin and norepinephrine transporters , lacking significant affinity for over 23 off-target sites . [ 16 ] However, it does show some affinity for the dizocilpine (MK-801/ PCP Tooltip phencyclidine ) site of the NMDA receptor (K i = 1.7 μM), and has been found to inhibit NR2A and NR2B subunit -containing NMDA receptors with respective IC 50 values of 5.62 and 4.57 μM. [ 16 ] As such, levomilnacipran is an NMDA receptor antagonist at high concentrations. [ 16 ]
Levomilnacipran has a high oral bioavailability of 92% and a low plasma protein binding of 22%. [ 4 ] [ 5 ] It is metabolized in the liver by the cytochrome P450 enzyme CYP3A4 , [ 6 ] thereby making the medication susceptible to grapefruit-drug interactions . The drug has an elimination half-life of approximately 12 hours, allowing for once-daily administration. [ 6 ] Levomilnacipran is excreted in urine . [ 6 ]
Levomilnacipran was developed by Forest Laboratories and Pierre Fabre Group , and was approved by the US Food and Drug Administration in July 2013. [ 9 ] [ 10 ] The FDA approved levomilnacipran for treating major depressive disorder. The approval was based on the results of five clinical trials . The trials included one 10-week phase II and four 8-week phase III . Four of the five trials demonstrated a statistically significant superiority to placebo as measured by the Montgomery–Åsberg Depression Rating Scale . Superiority to placebo was also demonstrated by improvement in the Sheehan Disability Scale .
Levomilnacipran has been found to act as an inhibitor of beta-site amyloid precursor protein cleaving enzyme-1 (BACE-1), which is responsible for β-amyloid plaque formation, and hence may be a potentially useful drug in the treatment of Alzheimer's disease . [ 17 ] | https://en.wikipedia.org/wiki/Levomilnacipran |
Levonadifloxacin (trade name Emrok ) is an antibiotic drug of the fluoroquinolone class. [ 1 ] [ 2 ] Chemically, it is the ( S )- enantiomer of the racemic drug nadifloxacin .
It is approved in India for the treatment of skin and soft tissue infections of Gram-positive bacteria . [ 3 ] It is also being studied for potential use against resistant strains of bacteria including Streptococcus pneumoniae , Streptococcus pyogenes , Haemophilus influenzae , and Moraxella catarrhalis . [ 4 ]
Levonadifloxacin has poor oral bioavailability . A prodrug of levonadifloxacin with high oral bioavailability, alalevonadifloxacin , has been developed to mitigate this problem. [ 5 ] | https://en.wikipedia.org/wiki/Levonadifloxacin |
Levonorgestrel is a hormonal medication used in a number of birth control methods. [ 7 ] [ 11 ] It is combined with an estrogen to make combination birth control pills . [ 12 ] As an emergency birth control , sold under the brand names Plan B One-Step and Julie , among others, it is useful within 72 hours of unprotected sex . [ 7 ] [ 11 ] [ 13 ] The more time that has passed since sex, the less effective the medication becomes. [ 11 ] Levonorgestrel works by preventing or delaying ovulation so an egg cannot be released. The dosage used for emergency contraception is ineffective when ovulation has already occurred, and has been found to have no effect on implantation . [ 14 ] It decreases the chances of pregnancy by 57–93%. [ 15 ] In an intrauterine device (IUD), such as Mirena among others, it is effective for the long-term prevention of pregnancy . [ 11 ] A levonorgestrel-releasing implant is also available in some countries. [ 16 ]
Common side effects include nausea , breast tenderness , headaches , and increased , decreased , or irregular menstrual bleeding . [ 11 ] When used as an emergency contraceptive, if pregnancy occurs, there is no evidence that its use harms the fetus . [ 11 ] It is safe to use during breastfeeding . [ 11 ] Birth control that contains levonorgestrel will not change the risk of sexually transmitted infections . [ 11 ] It is a progestin and has effects similar to those of the hormone progesterone . [ 11 ] It works primarily by preventing ovulation and closing off the cervix to prevent the passage of sperm . [ 11 ]
Levonorgestrel was patented in 1960 and introduced for medical use together with ethinylestradiol in 1970. [ 17 ] [ 18 ] It is on the World Health Organization's List of Essential Medicines . [ 19 ] It is available as a generic medication . [ 20 ] In the United States, levonorgestrel-containing emergency contraceptives are available over the counter (OTC) for all ages. [ 21 ] In 2020, it was the 323rd most commonly prescribed medication in the United States, with more than 800 thousand prescriptions. [ 22 ]
At low doses, levonorgestrel is used in monophasic and triphasic formulations of combined oral contraceptive pills , with available monophasic doses ranging from 100 to 250 μg, and triphasic doses of 50 μg, 75 μg, and 125 μg. [ 23 ] It is combined with the estrogen ethinylestradiol in these formulations. [ 23 ]
At very low daily dose of 30 μg, levonorgestrel is used in some progestogen-only pill formulations . [ 23 ]
Levonorgestrel is the active ingredient in a number of intrauterine devices including Mirena and Skyla. [ 23 ] [ 24 ] It is also the active ingredient in the birth control implants Norplant and Jadelle . [ 23 ] [ 24 ]
One of the more common forms of contraception that contains only levonorgestrel is an IUD. One IUD, the Mirena, is a small hollow cylinder containing levonorgestrel and polydimethylsiloxane and covered with a release rate-controlling membrane. [ 25 ]
Levonorgestrel is used in emergency contraceptive pills (ECPs), both in a combined Yuzpe regimen which includes estrogen, and as a levonorgestrel-only method. The levonorgestrel-only method uses levonorgestrel 1.5 mg (as a single dose or as two 0.75 mg doses 12 hours apart) taken within three days of unprotected sex. One study indicated that beginning as late as 120 hours (5 days) after intercourse could be effective. [ medical citation needed ] However, taking more than one dose of emergency contraception does not increase the chance of pregnancy not happening. Planned Parenthood asserts "Taking the morning-after pill (also known as emergency contraception) multiple times doesn't change its effectiveness, and won't cause any long-term side effects." [ 26 ]
The primary mechanism of action of levonorgestrel as a progestogen-only emergency contraceptive pill is, according to International Federation of Gynecology and Obstetrics (FIGO), to prevent fertilization by inhibition of ovulation and thickening of cervical mucus. [ 27 ] [ 28 ] [ 29 ] [ 30 ] FIGO has stated that: "review of the evidence suggests that LNG [levonorgestreol] ECPs cannot prevent implantation of a fertilized egg. Language on implantation should not be included in LNG ECP product labeling." [ 31 ] [ 32 ] In November 2013, the European Medicines Agency (EMA) approved a change to the label saying it cannot prevent implantation of a fertilized egg. [ 33 ]
Other studies still find the evidence to be unclear. [ 34 ] While it is unlikely that emergency contraception affects implantation it is impossible to completely exclude the possibility of post-fertilization effect. [ 35 ]
In November 2013, the EMA also approved a change to the label for HRA Pharma 's NorLevo saying: "In clinical trials, contraceptive efficacy was reduced in women weighing 75 kg [165 pounds] or more, and levonorgestrel was not effective in women who weighed more than 80 kg [176 pounds]." [ 33 ] [ 36 ] [ 37 ] In November 2013 and January 2014, the FDA and the EMA said they were reviewing whether increased weight and body mass index (BMI) reduce the efficacy of emergency contraceptives. [ 33 ]
An analysis of four WHO randomised clinical trials, published in January 2017, showed pregnancy rates of 1.25% (68/5428) in women with BMI under 25, 0.61% (7/1140) in women with BMI between 25 and 30, and 2.03% (6/295) in women with BMI over 30. [ 38 ] These values yield an eight-fold reduction in efficacy for women with a BMI over 30 compared to women with a BMI under 25. However, emergency contraceptives remain effective regardless of BMI.
Levonorgestrel is used in combination with an estrogen in menopausal hormone therapy . [ 23 ] [ 39 ] It is used under the brand name Klimonorm as a combined oral tablet with estradiol valerate and under the brand name Climara Pro as a combined transdermal patch with estradiol . [ 23 ] [ 39 ]
As a type of emergency contraception, levonorgestrel is used after unprotected intercourse to reduce the risk of pregnancy. [ 40 ] However, it can serve different hormonal purposes in its different methods of delivery. It is available for use in a variety of forms:
Levonorgestrel can be taken by mouth as a form of emergency birth control. The typical dosage is either 1.5 mg taken once or 0.75 mg taken 12–24 hours apart. [ 41 ] The effectiveness in both methods is similar. [ 41 ] The most widely used form of oral emergency contraception is the progestin-only pill , which contains a 1.5 mg dosage of levonorgestrel. [ 40 ] Levonorgestrel-only emergency contraceptive pills are reported to have an 89% effectiveness rate if taken within the recommended 72 hours after sex. [ 42 ] The efficacy of the drug decreases by 50% for each 12-hour delay in taking the dose after the emergency contraceptive regimen has been started. [ 42 ]
Estradiol with levonorgestrel in the form of a skin patch is used under the brand name Climara Pro for hormone replacement therapy in postmenstrual women, treating symptoms such as hot flashes or osteoporosis . [ 43 ] The simultaneous delivery of a progestogen such as levonorgestrel is necessary for the protection of the endometrium . [ 44 ] [ 45 ]
The levonorgestrel intrauterine system (LNG-IUS) is a type of long-term birth control that releases the progestin into the uterine cavity. [ 46 ] [ 25 ] Levonorgestrel is released at a constant, gradual rate of 0.02 mg per day by the polydimethylsiloxane membrane of the device, which renders it effective for up to five years. [ 46 ] Because it is inserted directly into the uterus, levonorgestrel is present in the endometrium in much higher concentrations that would result from a LNG-containing oral pill; the LNG-IUS delivers 391 ng of levonorgestrel to the inner uterine region while a comparable oral contraceptive delivers only 1.35 ng. [ 46 ] This high level of levonorgestrel impedes the function of the endometrium, making it hostile for sperm transport, fertilization, and implantation of an ovum. [ 46 ]
Subcutaneous implants of levonorgestrel have been marketed as birth control implants under the brand names Norplant and Jadelle and are available for use in some countries. [ 47 ] [ 23 ]
Known or suspected pregnancy is a contraindication of levonorgestrel as an emergency contraceptive. [ 48 ]
After an intake of 1.5 mg levonorgestrel in clinical trials , very common side effects (reported by 10% or more) included: hives , dizziness , hair loss , headache , nausea , abdominal pain , uterine pain , delayed menstruation , heavy menstruation , uterine bleeding , and fatigue ; common side effects (reported by 1% to 10%) included diarrhea , vomiting , and painful menstruation ; these side effects usually disappeared within 48 hours. [ 49 ] [ 50 ] However, the long term side effects common with oral contraceptives such as arterial disease are lower with levonorgestrel than in combination pills. [ medical citation needed ]
Levonorgestrel as a contraceptive intrauterine device has been associated with a slightly higher risk of breast cancer than with non-use in select studies. [ 51 ]
Overdose of levonorgestrel as an emergency contraoceptive has not been described. [ 48 ] Nausea and vomiting might be expected. [ 48 ]
If taken together with drugs that induce the CYP3A4 cytochrome P450 liver enzyme , levonorgestrel may be metabolized faster and may have lower effectiveness. [ 52 ] These include, but are not limited to barbiturates, bosentan, carbamazepine, felbamate, griseofulvin, oxcarbazepine, phenytoin, rifampin, St. John's wort and topiramate. [ medical citation needed ]
Levonorgestrel is a progestogen with weak androgenic activity. [ 8 ] It has no other important hormonal activity, including no estrogenic , glucocorticoid , or antimineralocorticoid activity. [ 8 ] The lack of significant mineralocorticoid or antimineralocorticoid activity with levonorgestrel is in spite of it having relatively high affinity for the mineralocorticoid receptor , which is as much as 75% of that of aldosterone . [ 8 ]
Levonorgestrel is a progestogen ; that is, an agonist of the progesterone receptor (PR), the main biological target of the progestogen sex hormone progesterone . [ 8 ] It has effects similar to those of the hormone progesterone . [ 11 ] As a contraceptive, it works primarily by preventing ovulation and closing off the cervix to prevent the passage of sperm . [ 11 ] The endometrial transformation dose of levonorgestrel is 150 to 250 μg/day or 2.5 to 6 mg per cycle. [ 8 ] [ 53 ] [ 54 ] [ 55 ]
Due to its progestogenic activity, levonorgestrel has antigonadotropic effects and is able to suppress the secretion of the gonadotropins , luteinizing hormone and follicle-stimulating hormone , from the pituitary gland . [ 8 ] This in turn, results in suppression of gonadal activity, including reduction of fertility and gonadal sex hormone production in both women and men. [ 8 ] [ 56 ] The ovulation -inhibiting dose of levonorgestrel in premenopausal women is 50 to 60 μg/day. [ 8 ] [ 53 ] [ 57 ]
In men, levonorgestrel causes marked suppression of circulating testosterone levels secondary to its antigonadotropic effects. [ 58 ] In healthy young men, levonorgestrel alone at a dose of 120 to 240 μg/day orally for 2 weeks suppressed testosterone levels from ~450 ng/dL to ~248 ng/dL (–45%). [ 59 ] Because of its effects on testosterone levels, and due to its androgenic activity being only weak and hence insufficient for purposes of androgen replacement in males, levonorgestrel has potent functional antiandrogenic effects in men. [ 58 ] Consequently, it can produce adverse effects like decreased libido and erectile dysfunction , among others. [ 58 ] Levonorgestrel has been combined with an androgen like testosterone or dihydrotestosterone when it has been studied as a hormonal contraceptive in men . [ 56 ] [ 58 ]
Levonorgestrel is a weak agonist of the androgen receptor (AR), the main biological target of the androgen sex hormone testosterone . [ 8 ] It is a weakly androgenic progestin and in women may cause androgenic biochemical changes and side effects such as decreased sex hormone-binding globulin (SHBG) levels, decreased HDL cholesterol levels, weight gain , and acne . [ 8 ] [ 60 ]
In combination with a potent estrogen like ethinylestradiol however, all contraceptives containing androgenic progestins are negligibly androgenic in practice and in fact can be used to treat androgen-dependent conditions like acne and hirsutism in women. [ 60 ] This is because ethinylestradiol causes a marked increase in SHBG levels and thereby decreases levels of free and hence bioactive testosterone, acting as a functional antiandrogen . [ 60 ] Nonetheless, contraceptives containing progestins that are less androgenic increase SHBG levels to a greater extent and may be more effective for such indications. [ 60 ] Levonorgestrel is currently the most androgenic progestin that is used in contraceptives, and contraceptives containing levonorgestrel may be less effective for androgen-dependent conditions relative to those containing other progestins that are less androgenic. [ 61 ] [ 62 ] [ 63 ]
Levonorgestrel stimulates the proliferation of MCF-7 breast cancer cells in vitro , an action that is independent of the classical PRs and is instead mediated via the progesterone receptor membrane component-1 (PGRMC1). [ 64 ] [ 65 ] Certain other progestins act similarly in this assay, whereas progesterone acts neutrally. [ 64 ] [ 65 ] It is unclear if these findings may explain the different risks of breast cancer observed with progesterone and progestins in clinical studies . [ 66 ]
The bioavailability of levonorgestrel is approximately 95% (range 85 to 100%). [ 8 ] [ 9 ] The plasma protein binding of levonorgestrel is about 98%. [ 8 ] It is bound 50% to albumin and 48% to SHBG. [ 8 ] Levonorgestrel is metabolized in the liver , via reduction , hydroxylation , and conjugation (specifically glucuronidation and sulfation ). [ 8 ] [ 10 ] Oxidation occurs primarily at the C2α and C16β positions, while reduction occurs in the A ring. [ 10 ] 5α-Dihydrolevonorgestrel is produced as an active metabolite of levonorgestrel by 5α-reductase . [ 8 ] The elimination half-life of levonorgestrel is 24 to 32 hours, although values as short as 8 hours and as great as 45 hours have been reported. [ 8 ] [ 10 ] About 20 to 67% of a single oral dose of levonorgestrel is eliminated in urine and 21 to 34% in feces . [ 10 ]
Levonorgestrel, also known as 17α-ethynyl-18-methyl-19-nortestosterone or as 17α-ethynyl-18-methylestr-4-en-17β-ol-3-one, is a synthetic estrane steroid and a derivative of testosterone . [ 67 ] [ 68 ] It is the C13β or levorotatory stereoisomer and enantiopure form of norgestrel , the C13α or dextrorotatory isomer being inactive. [ 69 ] [ 70 ] Levonorgestrel is more specifically a derivative of norethisterone (17α-ethynyl-19-nortestosterone) and is the parent compound of the gonane (18-methylestrane or 13β-ethylgonane) subgroup of the 19-nortestosterone family of progestins. [ 71 ] Besides levonorgestrel itself, this group includes desogestrel , dienogest , etonogestrel , gestodene , norelgestromin , norgestimate , and norgestrel . [ 72 ] Levonorgestrel acetate and levonorgestrel butanoate are C17β esters of levonorgestrel. [ 73 ] [ 74 ] Levonorgestrel has a molecular weight of 312.45 g/mol and a partition coefficient (log P ) of 3.8. [ 75 ] [ 76 ]
Norgestrel ( rac -13-ethyl-17α-ethynyl-19-nortestosterone), the racemic mixture containing levonorgestrel and dextronorgestrel , was discovered by Hughes and colleagues at Wyeth in 1963 via structural modification of norethisterone (17α-ethynyl-19-nortestosterone). [ 77 ] [ 78 ] [ 79 ] [ 80 ] It was the first progestogen to be manufactured via total chemical synthesis . [ 79 ] [ 80 ] Norgestrel was introduced for medical use as a combined birth control pill with ethinylestradiol under the brand name Eugynon in Germany in 1966 and under the brand name Ovral in the United States 1968, and as a progestogen-only pill under the brand name Ovrette in the United States in 1973. [ 80 ] [ 81 ] [ 82 ] [ 83 ] Following its discovery, norgestrel had been licensed by Wyeth to Schering AG , which separated the racemic mixture into its two optical isomers and identified levonorgestrel (13β-ethyl-17α-ethynyl-19-nortestosterone) as the active component of the mixture. [ 18 ] [ 79 ] [ 80 ] Levonorgestrel was first studied in humans by 1970, and was introduced for medical use in Germany as a combined birth control pill with ethinylestradiol under the brand name Neogynon in August 1970. [ 18 ] [ 81 ] [ 82 ] [ 84 ] [ 85 ] [ 86 ] A more widely used formulation, containing lower doses of ethinylestradiol and levonorgestrel, was introduced under the brand name Microgynon by 1973. [ 23 ] [ 87 ] [ 88 ] In addition to combined formulations, levonorgestrel was introduced as a progestogen-only pill under the brand names Microlut by 1972 and Microval by 1974. [ 89 ] [ 90 ] Many other formulations and brand names of levonorgestrel-containing birth control pills have also been marketed. [ 23 ]
Levonorgestrel, taken alone in a single high dose, was first evaluated as a form of emergency contraception in 1973. [ 91 ] It was the second progestin to be evaluated for such purposes, following a study of quingestanol acetate in 1970. [ 91 ] [ 92 ] In 1974, the Yuzpe regimen , which consisted of high doses of a combined birth control pill containing ethinylestradiol and norgestrel, was described as a method of emergency contraception by A. Albert Yuzpe and colleagues, and saw widespread interest. [ 93 ] [ 94 ] Levonorgestrel-only emergency contraception was introduced under the brand name Postinor by 1978. [ 95 ] Ho and Kwan published the first study comparing levonorgestrel only and the Yuzpe regimen as methods of emergency contraception in 1993 and found that they had similar effectiveness but that levonorgestrel alone was better-tolerated. [ 96 ] [ 97 ] In relation to this, the Yuzpe regimen has largely been replaced as a method of emergency contraception by levonorgrestrel-only preparations. [ 98 ] Levonorgestrel-only emergency contraception was approved in the United States under the brand name Plan B in 1999, and has also been marketed widely elsewhere throughout the world under other brand names such as Levonelle and NorLevo in addition to Postinor . [ 23 ] [ 99 ] In 2013, the Food and Drug Administration approved Plan B One-Step for sale over-the-counter in the United States without a prescription or age restriction. [ 100 ]
Levonorgestrel has also been introduced for use as a progestogen-only intrauterine device under the brand names Mirena and Skyla among others, as a progestogen-only birth control implant under the brand names Norplant and Jadelle , as a combined oral tablet with estradiol valerate for menopausal hormone therapy under the brand name Klimonorm , and as a combined transdermal patch with estradiol for menopausal hormone therapy under the brand name Climara Pro . [ 23 ] [ 24 ] [ 39 ] Ester prodrugs of levonorgestrel such as levonorgestrel acetate and levonorgestrel butanoate have been developed and studied as other forms of birth control such as long-acting progestogen-only injectable contraceptives and contraceptive vaginal rings , but have not been marketed for medical use. [ 73 ] [ 74 ]
Levonorgestrel is the generic name of the drug and its INN Tooltip International Nonproprietary Name , USAN Tooltip United States Adopted Name , USP Tooltip United States Pharmacopeia , BAN Tooltip British Approved Name , DCIT Tooltip Denominazione Comune Italiana , and JAN Tooltip Japanese Accepted Name , while lévonorgestrel is its DCF Tooltip Dénomination Commune Française . [ 23 ] [ 67 ] [ 68 ] It is also known as d-norgestrel , d(–)-norgestrel , or D -norgestrel , as well as by its developmental code names WY-5104 ( Wyeth ) and SH-90999 ( Schering AG ). [ 23 ] [ 67 ] [ 68 ] [ 89 ]
Levonorgestrel is marketed alone or in combination with an estrogen (specifically ethinylestradiol , estradiol , or estradiol valerate ) under a multitude of brand names throughout the world, including Alesse , Altavera, Alysena, Amethia, Amethyst, Ashlyna, Aviane, Camrese, Chateal, Climara Pro , Cycle 21 , Daysee, Emerres, Enpresse, Erlibelle, Escapelle , Falmina, Introvale, Isteranda, Jadelle , Jaydess , Jolessa, Klimonorm , Kurvelo, Kyleena, Lessina, Levlen , Levodonna, Levonelle , Levonest, Levosert, Levora, Liletta, Loette , Logynon , LoSeasonique , Lutera, Lybrel, Marlissa, Microgynon , Microlut , Microvlar , Min-Ovral, Miranova , Mirena , My Way, Myzilra, Next Choice, Nordette , Norgeston, NorLevo, Norplant , One Pill, Option 2, Orsythia, Ovima, Ovranette, Plan B , Plan B One-Step , Portia, Postinor , Postinor-2 , Preventeza, Ramonna, Rigevidon , Quartette, Quasense, Seasonale , Seasonique , Skyla , Sronyx, Tri-Levlen, Trinordiol , Triphasil, Triquilar , Tri-Regol , Trivora, and Upostelle, among many others. [ 23 ] [ 68 ] [ 101 ] These formulations are used as emergency contraceptives, normal contraceptives, or in menopausal hormone therapy for the treatment of menopausal symptoms. [ medical citation needed ]
As an emergency contraceptive, levonorgestrel is often referred to colloquially as the "morning-after pill". [ 102 ] [ 103 ]
Levonorgestrel is very widely marketed throughout the world and is available in almost every country. [ 23 ] [ 68 ]
Levonorgestrel-containing emergency contraception is available over-the-counter in some countries, such as the United States. [ 100 ] On some college campuses, Plan B is available from vending machines. [ 104 ]
A policy update in 2015, required all pharmacies, clinics, and emergency departments run by Indian Health Services (for Native Americans) to have Plan B One-Step in stock, to distribute it to any woman (or her representative) who asked for it without a prescription, age verification, registration or any other requirement, to provide orientation training to all staff regarding the medication, to provide unbiased and medically accurate information about emergency contraception, and to make someone available at all times to distribute the pill in case the primary staffer objected to providing it on religious or moral grounds. [ 105 ]
Levonorgestrel has been studied in combination with androgens such as testosterone and dihydrotestosterone as a hormonal contraceptive for men . [ 56 ] [ 58 ]
Mechanism of action Copper-releasing IUCs When used as a regular or emergency method of contraception, copper-releasing IUCs act primarily to prevent fertilization. Emergency insertion of a copper IUC is significantly more effective than the use of ECPs, reducing the risk of pregnancy following unprotected intercourse by more than 99%. 2,3 This very high level of effectiveness implies that emergency insertion of a copper IUC must prevent some pregnancies after fertilization. Emergency contraceptive pills To make an informed choice, women must know that ECPs—like the birth control pill, patch, ring, shot, and implant, 76 and even like breastfeeding 77 —prevent pregnancy primarily by delaying or inhibiting ovulation and inhibiting fertilization, but may at times inhibit implantation of a fertilized egg in the endometrium. However, women should also be informed that the best available evidence indicates that ECPs prevent pregnancy by mechanisms that do not involve interference with post-fertilization events. ECPs do not cause abortion 78 or harm an established pregnancy. Pregnancy begins with implantation according to medical authorities such as the US FDA, the National Institutes of Health 79 and the American College of Obstetricians and Gynecologists (ACOG). 80 Ulipristal acetate (UPA). One study has demonstrated that UP can delay ovulation. 81 ... Another study found that UPA altered the endometrium, but whether this change would inhibit implantation is unknown. 82 p. 122: Progestin-only emergency contraceptive pills. Early treatment with ECPs containing only the progestin levonorgestrel has been shown to impair the ovulatory process and luteal function. 83–87 p. 123: Combined emergency contraceptive pills. Several clinical studies have shown that combined ECPs containing ethinyl estradiol and levonorgestrel can inhibit or delay ovulation. 107–110
How does EC work? In 2002, a judicial review ruled that pregnancy begins at implantation, not fertilisation. 8 The possible mechanisms of action should be explained to the patient as some methods may not be acceptable, depending on individual beliefs about the onset of pregnancy and abortion. Copper-bearing intrauterine device (Cu-IUD). Copper is toxic to the ovum and sperm and thus the copper-bearing intrauterine device (Cu-IUD) is effective immediately after insertion and works primarily by inhibiting fertilisation. 9–11 A systematic review on mechanisms of action of IUDs showed that both pre- and postfertilisation effects contribute to efficacy. 11 If fertilisation has already occurred, it is accepted that there is an anti-implantation effect, 12,13 Levonorgestrel (LNG). The precise mode of action of levonorgestrel (LNG) is incompletely understood but it is thought to work primarily by inhibition of ovulation. 16,17 Ulipristal acetate (UPA). UPA's primary mechanism of action is thought to be inhibition or delay of ovulation. 2
Can LNG ECPs cause an abortion? LNG ECPs do not interrupt an established pregnancy or harm a developing embryo. 15 The evidence available to date shows that LNG ECP use does not prevent a fertilized egg from attaching to the uterine lining. The primary mechanism of action is to stop or disrupt ovulation; LNG ECP use may also prevent the sperm and egg from meeting. 16
Emergency postcoital contraception Levonorgestrel Mechanism and efficacy
Levonorgestrel-only emergency contraceptive pills: • Interfere with the process of ovulation; • May possibly prevent the sperm and the egg from meeting. Implications of the research: • Inhibition or delay of ovulation is LNG ECPs principal and possibly only mechanism of action. • Review of the evidence suggests that LNG-ECs cannot prevent implantation of a fertilized egg. Language on implantation should not be included in LNG ECP product labeling. • The fact that LNG-ECs have no demonstrated effect on implantation explains why they are not 100% effective in preventing pregnancy and are less effective the later they are taken. Women should be given a clear message that LNG-ECs are more effective the sooner they are taken. • LNG ECPs do not interrupt a pregnancy (by any definition of the beginning of pregnancy). However, LNG ECPs can prevent abortions by reducing unwanted pregnancies.
Media related to Levonorgestrel at Wikimedia Commons | https://en.wikipedia.org/wiki/Levonorgestrel |
Levonorgestrel acetate ( LNG-A ), or levonorgestrel 17β-acetate , also known as 3-ketonorgestimate , is a progestin which was never marketed. [ 1 ] [ 2 ] [ 3 ] [ 4 ] It is a progestogen ester and is the C17β acetate ester and a prodrug of levonorgestrel . [ 2 ] Norgestimate is the C3 oxime of LNG-A. [ 1 ] [ 5 ] The drug is a minor active metabolite of norgestimate, which is a prodrug of norelgestromin and to a lesser extent of levonorgestrel and LNG-A. [ 2 ] LNG-A has high affinity for the progesterone receptor , about 135% of that of promegestone (relative to 150% for levonorgestrel). [ 2 ] [ 3 ] Along with levonorgestrel butanoate , LNG-A was investigated as a hormonal contraceptive by the Population Council . [ 6 ] [ 4 ]
This drug article relating to the genito-urinary system is a stub . You can help Wikipedia by expanding it .
This article about a steroid is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Levonorgestrel_acetate |
Levorphanol (brand name Levo-Dromoran ) is an opioid medication used to treat moderate to severe pain . [ 1 ] [ 3 ] [ 4 ] It is the levorotatory enantiomer of the compound racemorphan . Its dextrorotatory counterpart is dextrorphan .
It was first described in Germany in 1946. [ 5 ] The drug has been in medical use in the United States since 1953. [ 6 ]
Levorphanol acts predominantly as an agonist of the μ-opioid receptor (MOR), but is also an agonist of the δ-opioid receptor (DOR), κ-opioid receptor (KOR), and the nociceptin receptor (NOP), as well as an NMDA receptor antagonist and a serotonin-norepinephrine reuptake inhibitor (SNRI). [ 6 ] Levorphanol, similarly to certain other opioids, also acts as a glycine receptor antagonist and GABA receptor antagonist at very high concentrations. [ 7 ] As per the World Health Organization, levorphanol is a step 3 opioid and is considered eight times more potent than morphine at the MOR (2 mg levorphanol is equivalent to 15 mg morphine). [ citation needed ]
Relative to morphine, levorphanol lacks complete cross-tolerance [ 8 ] and possesses greater intrinsic activity at the MOR. [ 8 ] The duration of action is generally long compared to other comparable analgesics and varies from 4 hours to as much as 15 hours. For this reason levorphanol is useful in palliation of chronic pain and similar conditions. Levorphanol has an oral to parenteral effectiveness ratio of 2:1, one of the most favorable of the strong narcotics. Its antagonism of the NMDA receptor, similar to those of the phenylheptylamine open-chain opioids such as methadone or the phenylpiperidine ketobemidone , make levorphanol useful for types of pain that other analgesics may not be as effective against, such as neuropathic pain . [ 9 ] Levorphanol's exceptionally high analgesic efficacy in the treatment of neuropathic pain is also conferred by its action on serotonin and norepinephrine transporters , similar to the opioids tramadol and tapentadol , and mutually complements the analgesic effect of its NMDA receptor antagonism. [ 10 ]
Levorphanol shows a high rate of psychotomimetic side effects such as hallucinations and delirium , which have been attributed to its binding to and activation of the KOR. [ 11 ] At the same time however, activation of this receptor as well as of the DOR have been determined to contribute to its analgesic effects. [ 11 ]
Chemically, levorphanol belongs to the morphinan class and is (−)-3-hydroxy- N -methyl-morphinan. [ 8 ] It is the "left-handed" ( levorotatory ) stereoisomer of racemorphan , the racemic mixture of the two stereoisomers with differing pharmacology . The "right-handed" (dextrorotatory) enantiomer of racemorphan is dextrorphan (DXO), an antitussive , potent dissociative hallucinogen ( NMDA receptor antagonist ), and weakly active opioid. DXO is an active metabolite of the pharmaceutical drug dextromethorphan (DXM), which, analogously to DXO, is an enantiomer of the racemic mixture racemethorphan along with levomethorphan , the latter of which has similar properties to those of levorphanol.
Levorphanol is the INN , BAN , and DCF . [ 1 ] [ 3 ] [ 4 ] As the medically used tartrate salt , the drug is also known as levorphanol tartrate ( USAN , BANM ). [ 1 ] [ 4 ] The former developmental code name of levorphanol at Roche was Ro 1-5431 . [ 1 ] [ 4 ]
As the tartrate salt, levorphanol is marketed by Hikma Pharmaceuticals USA Inc. [ 12 ] and Virtus Pharmaceuticals in the U.S., and Canada under the brand name Levo-Dromoran . [ 3 ]
Levorphanol is listed under the Single Convention On Narcotic Drugs 1961 and is regulated like morphine in most countries. In the U.S., it is a Schedule II Narcotic controlled substance with a DEA ACSCN of 9220 and 2013 annual aggregate manufacturing quota of 4.5 kilograms. The salts in use are the tartrate (free base conversion ratio 0.58) and hydrobromide (0.76). [ 13 ] | https://en.wikipedia.org/wiki/Levorphanol |
Levosalbutamol , also known as levalbuterol , is a β 2 -adrenergic receptor agonist used in the treatment of bronchospasm. [ 1 ] Levosalbutamol is the ( R )-(−)- enantiomer of its prototype drug salbutamol . [ citation needed ]
Levosalbutamol is indicated for the treatment or prevention of bronchospasm in people aged four years of age and older with reversible obstructive airway disease. [ 1 ]
Evidence is inconclusive regarding the efficacy of levosalbutamol versus salbutamol (albuterol) or salbutamol-levosalbutamol combinations, though levosalbutamol is believed to have a better safety profile due to its more selective binding to β 2 receptors (primarily in the lungs) versus β 1 (primarily in heart muscle). [ 4 ] [ 5 ]
A 2013 systematic review of the use of levalbuterol as a treatment for acute asthma found that it "was not superior to albuterol regarding efficacy and safety in subjects with acute asthma." The review concluded: "We suggest that levalbuterol should not be used over albuterol for acute asthma." [ 4 ]
Generally, levosalbutamol is well tolerated. Common mild side effects include an elevated heart rate, muscle cramps, and gastric upset (including heartburn and diarrhea). [ 6 ]
Symptoms of overdose in particular include: collapse into a seizure ; chest pain (possible precursor of a heart attack ); fast, pounding heartbeat, which may cause raised blood pressure ( hypertension ); irregular heartbeat ( cardiac arrhythmia ), which may cause paradoxical lowered blood pressure ( hypotension ); nervousness and tremor ; headache; dizziness and nausea /vomiting; weakness or exhaustion ( medical fatigue ); dry mouth; and insomnia . [ 6 ]
Rarer side effects may indicate a dangerous allergic reaction. These include: paradoxical bronchospasm (shortness of breath and difficulty breathing); skin itching, rash, or hives ( urticaria ); swelling ( angioedema ) of any part of the face or throat (which can lead to voice hoarseness ), or swelling of the extremities. [ 6 ]
Activation of β 2 adrenergic receptors on airway smooth muscle leads to the activation of adenylate cyclase and to an increase in the intracellular concentration of 3',5'-cyclic adenosine monophosphate (cyclic AMP). The increase in cyclic AMP is associated with the activation of protein kinase A, which in turn, inhibits the phosphorylation of myosin and lowers intracellular ionic calcium concentrations, resulting in muscle relaxation.
Levosalbutamol relaxes the smooth muscles of all airways, from the trachea to the terminal bronchioles. Increased cyclic AMP concentrations are also associated with the inhibition of the release of mediators from mast cells in the airways. Levosalbutamol acts as a functional agonist that relaxes the airway irrespective of the spasmogen involved, thereby protecting against all bronchoconstrictor challenges.
While it is recognized that β 2 adrenergic receptors are the predominant receptors on bronchial smooth muscle, data indicate that there are beta receptors in the human heart, 10–50% of which are β 2 adrenergic receptors. The precise function of these receptors has not been established. However, all β adrenergic agonist drugs can produce a significant cardiovascular effect in some patients, as measured by pulse rate, blood pressure, and restlessness symptoms, and/or electrocardiographic (ECG).
Levosalbutamol is on the list of drugs banned by the World Anti-Doping Agency . [ 7 ]
Levalbuterol is more costly than salbutamol. [ 8 ] [ 9 ]
Levalbuterol was approved in the United States as a solution to be used with a nebulizer device in March 1999, [ 10 ] and in March 2005, became available in a formulation with a metered-dose inhaler under the brand name Xopenex HFA (levalbuterol tartrate inhalation aerosol). [ 11 ]
Levosalbutamol is the international nonproprietary name and levalbuterol is the United States Adopted Name .
It is available in Bangladesh as Purisal by Incepta Pharmaceuticals Ltd. | https://en.wikipedia.org/wiki/Levosalbutamol |
Levosulpiride , sold under the brand names Dislep and Sulpepta among others, is a dopamine antagonist medication which is used in the treatment of psychotic disorders like schizophrenia , major depressive disorder , nausea and vomiting , and gastroparesis . [ 1 ] [ 2 ] [ 3 ] [ 4 ] It is taken by mouth .
It is a selective antagonist of the dopamine D 2 receptor and an agonist of the serotonin 5-HT 4 receptor . [ 4 ] [ 5 ] Chemically, it is a benzamide and the ( S )-(−)- enantiomer of sulpiride . [ 4 ]
Levosulpiride is marketed widely throughout the world, including in Europe , South Korea , Latin America , India , and Pakistan . [ 2 ] It is not available in the United States or the United Kingdom . [ 2 ]
Levosulpiride is used in the treatment of: [ 3 ] [ 1 ]
Levosulpiride is not currently licensed for treatment of premature ejaculation in the United Kingdom or other European countries. [ 8 ]
Side effects of levosulpiride include amenorrhea , gynecomastia , galactorrhea , changes in libido , and neuroleptic malignant syndrome . [ 9 ] In the United States, as of 2013 only one case of adverse reaction to levosulpiride had been recorded on the FDA Adverse Event Reporting System Database. [ 8 ] A case of rapid-onset resistant dystonia caused by low-dose levosulpiride was reported in India. [ 10 ]
Levosulpiride is a selective dopamine D 2 receptor antagonist . [ 4 ] The drug has also been found to act as a moderate agonist of the serotonin 5-HT 4 receptor . [ 5 ] It is said to have antipsychotic , antidepressant , antiemetic , and gastroprokinetic effects. [ 4 ]
Levosulpiride is a substituted benzamide derivative . [ 4 ] It is the levorotatory enantiomer of sulpiride . [ 4 ] Other benzamide derivatives include amisulpride , metoclopramide , tiapride , sultopride , and veralipride , among others. | https://en.wikipedia.org/wiki/Levosulpiride |
Levoverbenone is an expectorant . It is the (−)- isomer of verbenone . [ 1 ]
This drug article relating to the respiratory system is a stub . You can help Wikipedia by expanding it .
This stereochemistry article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Levoverbenone |
The Levi–Mises equations (also called flow rules ) describe the relationship between stress and strain for an ideal plastic solid where the elastic strains are negligible.
The generalized Levy–Mises equation can be written as:
This applied mathematics –related article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Levy–Mises_equations |
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