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Plastic magnet The plastic magnet was made from a polymer made of tetracyanoethylene (TCNE) combined with manganese (Mn) ions – atoms of the metal manganese with electrons removed. The magnet functioned up to a temperature of . | https://en.wikipedia.org/wiki?curid=950025 |
Classical XY model The classical XY model (sometimes also called classical rotor (rotator) model or O(2) model) is a lattice model of statistical mechanics. It is the special case of the "n"-vector model for . Given a -dimensional lattice , per each lattice site there is a two-dimensional, unit-length vector The spin configuration, is an assignment of the angle for each . Given a "translation-invariant" interaction and a point dependent external field formula_1, the configuration energy is The case in which except for nearest neighbor is called "nearest neighbor" case. The configuration probability is given by the Boltzmann distribution with inverse temperature : where is the normalization, or partition function. The notation formula_4 indicates the expectation of the random variable in the infinite volume limit, after "periodic boundary conditions" have been imposed. The fact that at high temperature correlations decay exponentially fast, while at low temperatures decay with power law, even though in both regimes , is called Kosterlitz–Thouless transition. The continuous version of the XY model is often used to model systems that possess order parameters with the same kinds of symmetry, e.g. superfluid helium, hexatic liquid crystals. This is what makes them peculiar from other phase transitions which are always accompanied with a symmetry breaking. Topological defects in the XY model lead to a vortex-unbinding transition from the low-temperature phase to the high-temperature disordered phase | https://en.wikipedia.org/wiki?curid=954006 |
Classical XY model Independently of the range of the interaction, at low enough temperature the magnetization is positive. In general, the XY model can be seen as a specialization of Stanley's "n"-vector model | https://en.wikipedia.org/wiki?curid=954006 |
The Great Devonian Controversy began in 1834 when Roderick Murchison disagreed with Henry De la Beche as to the dating of certain petrified plants found in coals in the Greywacke strata in North Devon, England. De La Beche was claiming that since Carboniferous fossils were found deep in the Greywacke strata, which itself was older than the Carboniferous period, this method of dating rocks was not viable. Murchison, on the other hand, claimed that De La Beche did not place the fossils correctly, as they were occurring quite near the top of the strata as opposed to deep within it. De La Beche soon agreed with Murchison's argument as to the placing of fossils but maintained that since a layer of Old Red Sandstone, present in other formations, was missing between the layer of older rock and this new formation, there was still insufficient evidence to suggest the formation was not part of the older Silurian strata. There followed much debate and some extensive investigations which ranged as far as Russia, where in 1840 Murchison discovered a layer similar to the one found in Devon placed between well-defined Silurian and Carboniferous deposits. This discovery put an end to the controversy and led to the definition of a new period called Devonian. | https://en.wikipedia.org/wiki?curid=960678 |
ACES (computational chemistry) Aces II (Advanced Concepts in Electronic Structure Theory) is an ab initio computational chemistry package for performing high-level quantum chemical ab initio calculations. Its major strength is the accurate calculation of atomic and molecular energies as well as properties using many-body techniques such as many-body perturbation theory (MBPT) and, in particular coupled cluster techniques to treat electron correlation. The development of ACES II began in early 1990 in the group of Professor Rodney J. Bartlett at the Quantum Theory Project (QTP) of the University of Florida in Gainesville. There, the need for more efficient codes had been realized and the idea of writing an entirely new program package emerged. During 1990 and 1991 John F. Stanton, Jürgen Gauß, and John D. Watts, all of them at that time postdoctoral researchers in the Bartlett group, supported by a few students, wrote the backbone of what is now known as the ACES II program package. The only parts which were not new coding efforts were the integral packages (the MOLECULE package of J. Almlöf, the VPROP package of P.R. Taylor, and the integral derivative package ABACUS of T. Helgaker, P. Jorgensen J. Olsen, and H.J. Aa. Jensen). The latter was modified extensively for adaptation with Aces II, while the others remained very much in their original forms. Ultimately, two different versions of the program evolved | https://en.wikipedia.org/wiki?curid=961605 |
ACES (computational chemistry) The first was maintained by the Bartlett group at the University of Florida, and the other (known as ACESII-MAB) was maintained by groups at the University of Texas, Universitaet Mainz in Germany, and ELTE in Budapest, Hungary. The latter has recently been renamed as CFOUR. Aces III is a parallel implementation that was released in the fall of 2008. The effort led to definition of a new architecture for scalable parallel software called the super instruction architecture. The design and creation of software is divided into two parts: The ACES III program consists of 580,000 lines of SIAL code of which 200,000 lines are comments, and 230,000 lines of C/C++ and Fortran of which 62,000 lines are comments. | https://en.wikipedia.org/wiki?curid=961605 |
NGC 3628 NGC 3628, also known as the Hamburger Galaxy or Sarah's Galaxy, is an unbarred spiral galaxy about 35 million light-years away in the constellation Leo. It was discovered by William Herschel in 1784. It has an approximately 300,000 light-years long tidal tail. Along with M65 and M66, forms the Leo Triplet, a small group of galaxies. Its most conspicuous feature is the broad and obscuring band of dust located along the outer edge of its spiral arms, effectively transecting the galaxy to the view from Earth. Due to the presence of an x-shaped bulge, visible in multiple wavelengths, it has been argued that is instead a barred spiral galaxy with the bar seen end-on. Simulations have shown that bars often form in disk galaxies during interactions and mergers, and is known to be interacting with its two large neighbors. | https://en.wikipedia.org/wiki?curid=964170 |
Henry Charles Gordon (December 23, 1925 – September 24, 1996), (Col, USAF), was an American aeronautical engineer, U.S. Air Force officer, test pilot, and astronaut in the X-20 Dyna-Soar program. Gordon was born in Valparaiso, Indiana, on December 23, 1925. In 1950 he earned his Bachelor of Science degree in Aeronautical Engineering from Purdue University, and in 1966 he earned his Master of Business Administration degree from the University of Southern California. He is married and has four children. Gordon was in the Air Force, and flew combat missions in the Korean and Vietnam wars. He was selected as an astronaut in the X-20 Dyna-Soar program in April 1962 and began training at the Air Force Flight Test Center, Edwards Air Force Base, California. He retired as an astronaut when the Dyna-Soar program was cancelled on December 10, 1963, having never flown in space. He remained in the U.S. Air Force after the Dyna-Soar program was cancelled and retired from the Air Force with the rank of Colonel. Gordon died in Peoria, Arizona on September 24, 1996, age 70. | https://en.wikipedia.org/wiki?curid=970716 |
Small telescope A small telescope is generally considered by professional astronomers to be any reflecting telescope with a primary mirror that is less than in diameter. By amateur standards, a small telescope can have a primary mirror/aperture less than in diameter. Little if any professional-level research is performed with refracting telescopes in the modern era of astronomy. Small telescopes dominate astronomical research in the fields of asteroid/comet discovery/observation, variable star photometry, supernova/nova discovery, and colorimetry/polarimetry of the Solar System's planets. Because of their limited light-gathering capability, small telescopes are usually not well-suited to spectroscopy, although some useful spectroscopic work can be performed with reflecting telescopes with a primary mirror as small as when equipped with the increasingly sophisticated CCD imaging and spectroscopic instrumentation that has become available to amateur astronomers in the 21st century. Most telescopes within the field of amateur astronomy are considered to be small, ranging in general from achromatic refracting types, to reflecting telescopes featuring primary mirrors up to or more in diameter. Most small telescopes are dedicated to visual observation, although many are used for astrophotography or to gather scientific data. The range of amateur astronomers' telescopes is wide, with numerous types and designs. Refracting designs include achromatic and apochromatic types | https://en.wikipedia.org/wiki?curid=971612 |
Small telescope Some reflecting types are Newtonian, Schmidt–Cassegrain, Maksutov-Cassegrain, and Maksutov-Newtonian. Even sophisticated designs, such as the Ritchey–Chrétien and (corrected) Dall–Kirkham, which have traditionally been the preserve of large professional-grade instruments, have become available to amateurs. | https://en.wikipedia.org/wiki?curid=971612 |
Russell L. Rogers Russell Lee Rogers (April 12, 1928 – September 13, 1967), (Lt Col, USAF), was an American electrical engineer, U.S. Air Force officer, test pilot, and astronaut in the X-20 Dyna-Soar program. He was born on April 12, 1928 in Lawrence, Kansas. He received a Bachelor of Science degree in Electrical Engineering from the University of Colorado in 1958. He was married with five children. As a USAF Test Pilot School graduate, Rogers was an experimental test pilot at Edwards AFB, California when selected for the X-20 program in April, 1960. He left the program on December 10, 1963 when it was cancelled. After the X-20 program, he remained in the U.S. Air Force on active flight duty as a pilot with the rank of Lt. Colonel at the time of his death. Rogers was killed when the engine of his F-105 fighter plane failed near Kadena AFB, Okinawa, Japan on September 13, 1967. He ejected from his aircraft, but his parachute failed to deploy properly. He was 39 years old. | https://en.wikipedia.org/wiki?curid=972042 |
James W. Wood James Wayne Wood (August 9, 1924 – January 1, 1990), (Col, USAF), was an American aeronautical engineer, U.S. Air Force officer, test pilot, and astronaut in the X-20 Dyna-Soar program. He was born on August 9, 1924, in Paragould, Arkansas, to Henry P. Wood (1894–1983) and Alfreda Wood ("née" Lowrie; 1900–1993). Wood earned a Bachelor of Science degree in Aeronautical Engineering from the U.S. Air Force Institute of Technology in 1954. He was married and had three children. Wood served in the U.S. Army Air Corps during World War II, and flew 10 combat missions. In the Korean War, he flew more than 100 combat missions. As a USAF Test Pilot School graduate, he was serving as an experimental test pilot at the Air Force Flight Test Center, Edwards AFB, California when selected for the X-20 Dyna-Soar program. However, before his selection, he had an unsuccessful application for NASA astronaut group 1. Wood was the senior test pilot on the Dyna-Soar project and was slated to be the pilot on its first sub-orbital mission. If the program had not been cancelled, the first drop test would have been in July 1964. After the Dyna-Soar program was cancelled on December 10, 1963, he remained with the U.S. Air Force and served as Commander of Test Operations at Edwards Air Force Base until 1978. He retired from the U.S. Air Force with the rank of colonel. Wood later was test pilot and Director of Operations, Tracor Flight Systems Inc., in Newport Beach, California | https://en.wikipedia.org/wiki?curid=972753 |
James W. Wood He died in Melbourne, Florida, on January 1, 1990, of natural causes, aged 65. | https://en.wikipedia.org/wiki?curid=972753 |
Tong Dizhou (; May 28, 1902 － March 30, 1979) was a Chinese embryologist known for his contributions to the field of cloning. He was a vice president of Chinese Academy of Science. Born in Yinxian, Zhejiang province, Tong graduated from Fudan University in 1924 with a degree in psychology, and received a PhD in 1930 from Free University Brussels (ULB). From 1950 to 1956, he was a supporter of Lysenkoism. In 1963, Tong inserted DNA of a male carp into the egg of a female carp and became the first to successfully clone a fish. He is regarded as "the father of China's clone". Tong was also an academician at the Chinese Academy of Sciences and the first director of its Institute of Oceanology from its founding in 1950 until 1978. Tong died in 30 March 1979 at Beijing Hospital in Beijing. | https://en.wikipedia.org/wiki?curid=973296 |
True longitude In celestial mechanics true longitude is the ecliptic longitude at which an orbiting body could actually be found if its inclination were zero. Together with the inclination and the ascending node, the true longitude can tell us the precise direction from the central object at which the body would be located at a particular time. The true longitude can be calculated as follows: where: | https://en.wikipedia.org/wiki?curid=976840 |
Leo Buss Leo W. Buss (born 1953) is a retired Professor at Yale University's departments of geology, geophysics, and ecology and evolutionary biology. He graduated from Johns Hopkins University with a B.A., M.A., and Ph.D in 1979. His evolutionary developmental biology book approaches the subject of the evolution of metazoan development from a cell lineage selection point of view. He reevaluates August Weismann's model of the cell compartmentalization of somatic and germline cell lineages (see Weismann barrier), and argues that the vision of the individual taken by the modern synthesis is insufficient to explain the early evolution of development or ontogeny. He collaborated with Walter Fontana in producing some of the first papers on artificial chemistries. | https://en.wikipedia.org/wiki?curid=977351 |
Justus Ludwig Adolf Roth (September 15, 1818, Hamburg – April 1, 1892) was a German geologist and mineralogist. In 1844 he obtained his doctorate from the University of Jena and spent the next few years working as a pharmacist in Hamburg. In 1848 he relocated to Berlin, where he came under the influence of Gustav Rose and Heinrich Ernst Beyrich. In 1867 he became an associate professor of mineralogy at the University of Berlin. He may be regarded as one of the founders of petrographical science. In his published papers he dealt with metamorphism and crystalline schists, discussed the origin of serpentine, and wrote on the rocks of Mount Vesuvius and Ponza Island. His separate works included: | https://en.wikipedia.org/wiki?curid=977546 |
HCG 87 is a compact group of galaxies listed in the Hickson Compact Group Catalogue. This group is about 400 million light-years away in the constellation Capricornus. The group distinguishes itself as one of the most compact groups of galaxies, hosting two active galactic nuclei and a starburst among its three members, all of which show signs of interaction. This interaction, which astronomers have called visually, and scientifically, intriguing is being examined to understand the influence of active nuclei on star formation histories. | https://en.wikipedia.org/wiki?curid=977799 |
Non-inclined orbit A non-inclined orbit is an orbit coplanar with a plane of reference. The orbital inclination is 0° for prograde orbits, and π (180°) for retrograde ones. If the plane of reference is a massive spheroid body's equatorial plane, these orbits are called equatorial; if the plane of reference is the ecliptic plane, they are called ecliptic. As these orbits lack nodes, the ascending node is usually taken to lie in the reference direction (usually the vernal equinox), and thus the longitude of the ascending node is taken to be zero. Also, the argument of periapsis is undefined. Geostationary orbit is a geosynchronous example of an equatorial orbit. | https://en.wikipedia.org/wiki?curid=978733 |
Gilead Sciences Gilead Sciences, Inc. , is an American biopharmaceutical company that researches, develops and commercializes drugs. The company focuses primarily on antiviral drugs used in the treatment of HIV, hepatitis B, hepatitis C, and influenza, including Harvoni and Sovaldi. Headquartered and founded in Foster City, California, Gilead is a member of the NASDAQ Biotechnology Index and the S&P 500. In June 1987, was originally founded under the name Oligogen by Michael L. Riordan, a medical doctor. Riordan graduated from Washington University in St. Louis, the Johns Hopkins School of Medicine and the Harvard Business School. Three scientific advisers worked with Riordan to create the company: Peter Dervan of Caltech, Doug Melton of Harvard, and Harold M. Weintraub of the Fred Hutchinson Cancer Research Center. Riordan served as CEO from the company's founding until 1996. Menlo Ventures, a venture capital firm where Riordan had previously worked, made the first investment in Gilead of $2 million. Riordan also recruited scientific advisers including Harold Varmus, a Nobel laureate who later became Director of the National Institutes of Health, and Jack Szostak, recipient of the Nobel Prize for Physiology or Medicine in 2009. The company's primary therapeutic focus was in antiviral medicines, a field that interested Riordan after he contracted dengue fever. Riordan recruited Donald Rumsfeld to join the board of directors in 1988, followed by Benno C. Schmidt, Sr., Gordon Moore, and George P. Shultz | https://en.wikipedia.org/wiki?curid=978997 |
Gilead Sciences Riordan tried to recruit Warren Buffett as an investor and board member, but was unsuccessful. The company focused its early research on making small strands of DNA (oligomers, or more particularly, oligonucleotides) to target specific genetic code sequences – that is, antisense therapy, a form of gene therapy. Because of the expected healing potential of such research, Oligogen soon changed its name to Gilead Sciences, after the reputed healing properties of the ancient Balm of Gilead. By 1988, the company had moved its headquarters to Foster City's Vintage Park neighborhood, where it has been based ever since. The company began to develop small molecule antiviral therapeutics in 1991, when the company in-licensed a group of nucleotide compounds including tenofovir. Gilead's antisense intellectual property portfolio was sold to Ionis Pharmaceuticals. Gilead debuted on the NASDAQ in January 1992. Its initial public offering raised $86.25 million in proceeds. In June 1996, Gilead launched Vistide (cidofovir injection) for the treatment of cytomegalovirus (CMV) retinitis in patients with AIDS. In January 1997, Donald Rumsfeld was appointed Chairman, but left the board in January 2001 when he was appointed United States Secretary of Defense during George W. Bush's first term as President. In March 1999, Gilead acquired NeXstar Pharmaceuticals of Boulder, Colorado | https://en.wikipedia.org/wiki?curid=978997 |
Gilead Sciences At the time, NeXstar's annual sales of $130 million was three times Gilead's sales; it sold AmBisome, an injectable fungal treatment, and DaunoXome, an oncology drug taken by HIV patients. That same year, Roche announced FDA approval of Tamiflu (oseltamivir) for the treatment of influenza. Tamiflu was originally discovered by Gilead and licensed to Roche for late-phase development and marketing. One reason for entering into the Tamiflu licensing agreement was that with only 350 employees, Gilead still did not yet have the capability to sell its drugs directly to overseas buyers. To avoid having to license future drugs in order to access international markets, Gilead simply acquired the 480-employee NeXstar, which had already built its own sales force in Europe to market AmBisome there. Viread (tenofovir) achieved first approval in 2001 for the treatment of HIV. In 2002 Gilead changed its corporate strategy to focus exclusively on antivirals, and sold its cancer assets to OSI Pharmaceuticals for $200 million. In December 2002, Gilead and Triangle Pharmaceuticals announced that Gilead would acquire Triangle for around $464 million; Triangle's lead drug was emtricitabine that was near FDA approval, and it had two other antivirals in its pipeline. The company also announced its first full year of profitability. Later that year Hepsera (adefovir) was approved for the treatment of chronic hepatitis B, and Emtriva (emtricitabine) for the treatment of HIV | https://en.wikipedia.org/wiki?curid=978997 |
Gilead Sciences During this era, Gilead completed its gradual evolution from a biotech startup into a pharmaceutical company. The "San Francisco Chronicle" noted that by 2003, the Gilead corporate campus in Foster City had expanded to "seven low-slung sand-colored buildings around a tiny lake on which ducks happily paddle." Like many startups, Gilead originally leased its space, but in 2004, the company paid $123 million to buy all its headquarters buildings from its landlords. However, even as Gilead developed its ability to distribute and sell its own drugs, it remained distinct from most pharmaceutical companies in terms of its strong reliance on subcontracting most of its manufacturing to contract manufacturing organizations. In 2004, Gilead launched Truvada. Years later, through efforts of activists and other groups, Gilead was convinced that a fixed-dose combination of tenofovir and emtricitabine could be used as a pre-exposure prophylactic against the transmission of HIV. In 2006, Gilead completed two acquisitions that allowed the company to branch out from its historical antiviral franchise into the cardiovascular and respiratory therapeutic arenas. Under an agreement with GlaxoSmithKline, Myogen marketed Flolan (epoprostenol sodium) in the United States for the treatment of primary pulmonary hypertension. Additionally, Myogen was developing (in Phase 3 studies) darusentan, also an endothelin receptor antagonist, for the potential treatment of resistant hypertension. In 2006, the company acquired Corus Pharma, Inc | https://en.wikipedia.org/wiki?curid=978997 |
Gilead Sciences for $365 million. The acquisition of Corus signaled Gilead's entry into the respiratory arena. Corus was developing aztreonam lysine for the treatment of patients with cystic fibrosis who are infected with "Pseudomonas aeruginosa". In July 2006, the U.S. Food and Drug Administration (FDA) approved Atripla, a once a day single tablet regimen for HIV, combining Sustiva (efavirenz), a Bristol-Myers Squibb product, and Truvada (emtricitabine and tenofovir disoproxil), a Gilead product. Gilead purchased Raylo Chemicals, Inc. in November 2006 for a price of $133.3 million. Raylo Chemical, based in Edmonton, Alberta, was a wholly owned subsidiary of Degussa AG, a German company. Raylo Chemical was a custom manufacturer of active pharmaceutical ingredients and advanced intermediates for the pharmaceutical and biopharmaceutical industries. Later in the same year Gilead acquired Myogen, Inc. for $2.5 billion (then its largest acquisition). With two drugs in development (ambrisentan and darusentan), and one marketed product (Flolan) for pulmonary diseases, the acquisition of Myogen has solidified Gilead's position in this therapeutic arena. Gilead expanded its move into respiratory therapeutics in 2007 by entering into a licensing agreement with Parion for an epithelial sodium channel inhibitor for the treatment of pulmonary diseases, including cystic fibrosis, chronic obstructive pulmonary disease and bronchiectasis. In 2009, the company acquired CV Therapeutics, Inc. for $1 | https://en.wikipedia.org/wiki?curid=978997 |
Gilead Sciences 4 billion, bringing Ranexa and Lexiscan into Gilead. Ranexa is a cardiovascular drug used to treat chest pain related to coronary artery disease, with both of these products and pipeline building out Gilead's cardiovascular franchise. Later that year, the company was named one of the Fastest Growing Companies by "Fortune". In the same year, they were also named as one America's Top Companies to work for by "Forbes". In 2010, the company acquired CGI Pharmaceuticals for $120 million, expanding Gilead's research expertise into kinase biology and chemistry. Later that year, the company acquired Arresto Biosciences, Inc. for $225 million, obtaining developmental-stage research for treating fibrotic diseases and cancer. In February 2011, the company acquired Calistoga Pharmaceuticals for $375 million ($225 million plus milestone payments). The acquisition boosted Gilead's oncology and inflammation areas. Later that year, Gilead made its most important acquisition – and by then most expensive – with the $10.4 billion purchase of Pharmasset, Inc. This transaction helped cement Gilead as the leader in treatment of the hepatitis C virus by giving it control of sofosbuvir (see below). In October 2011, Gilead broke ground on a massive multi-year expansion of its 17-building headquarters campus in Foster City. By replacing eight one or two-story buildings with seven new structures ranging as tall as 10 stories, Gilead nearly doubled its headquarters real estate footprint from about 620,000 square feet to about 1 | https://en.wikipedia.org/wiki?curid=978997 |
Gilead Sciences 2 million square feet. On July 16, 2012, the FDA approved Gilead's Truvada for prevention of HIV infection (it was already approved for treating HIV). The pill was a preventive measure (PrEP) for people at high risk of getting HIV through sexual activity. In 2013, the company acquired YM Biosciences, Inc. for $510 million. The acquisition brings drug candidate CYT387, an orally-administered, once-daily, selective inhibitor of the Janus kinase (JAK) family, specifically JAK1 and JAK2, into Gilead's oncology pipeline. The JAK enzymes have been implicated in myeloproliferative diseases, inflammatory disorders, and certain cancers. In 2015, the company made a trio of acquisitions: In 2016, the company acquired Nimbus Apollo, Inc. for $400 million, giving Gilead control of the compound NDI-010976 (an ACC inhibitor) and other preclinical ACC inhibitors for the treatment of non-alcoholic steatohepatitis and for the potential treatment of hepatocellular carcinoma. Also in 2016, the company was named the most generous company on the 2016 Fortune list of The Most Generous Companies of the Fortune 500. Charitable donations to HIV/AIDS and liver disease organizations totaled over 440 million in 2015. In August 2017, the company announced it would acquire Kite Pharma for $11.9 billion, equating to $180 cash per share, a 29% premium over the closing price of the shares. The deal will add the promising CAR-T candidate to the companys existing portfolio | https://en.wikipedia.org/wiki?curid=978997 |
Gilead Sciences In November, the company announced it will acquire Cell Design Labs for up to $567 million, after it indirectly acquired a stake of 12.2% via the Kite Pharma deal. On May 9, 2019, the U.S. Department of Health and Human Services announced that will donate Truvada, the only drug approved to prevent infection with H.I.V., for free to 200,000 patients annually for 11 years. On December 3, 2019, HHS explained how the government would distribute the donated drugs. The new program called Ready, Set, PrEP is accepting applications from any patient who doesn't have health insurance, has a valid prescription for PrEP and has had a recent negative H.I.V. test. To apply, patients can call 855-477-8410, online at www.getyourprep.com or in person at participating health care provider. HHS Secretary Alex Azar explained that the U.S. government will pay Gilead $200 per bottle for 30 pills for costs associated with getting the drug from factories into the eventual hands of patients. In March 2020, the company announced it would acquire Forty Seven Inc. for $95.50 a share ($4.9 billion in total). On April 7, 2020, Gilead completed acquisition of Forty Seven, Inc. for "$95.50 per share, net to the seller in cash, without interest, or approximately $4.9 billion in the aggregate." The drug sofosbuvir had been part of the 2011 acquisition of Pharmasset. In 2013, the FDA approved this drug, under the trade name Sovaldi, as a treatment for the hepatitis C virus | https://en.wikipedia.org/wiki?curid=978997 |
Gilead Sciences "Forbes" magazine ranked Gilead its number 4 drug company, citing a market capitalization of US$113 billion and stock appreciation of 100%, and describing their 2011 purchase of Pharmasset for $11 billion as "one of the best pharma acquisitions ever". Deutsche Bank estimated Sovaldi sales in the year's final quarter would be $53 million, and "Barron's" noted the FDA approval and subsequent strong sales of the "potentially revolutionary" drug as a positive indicator for the stock. On July 11, 2014, the United States Senate Committee on Finance investigated Sovaldi's high price ($1,000 per pill; $84,000 for the full 12-week regimen). Senators questioned the extent to which the market was operating "efficiently and rationally", and committee chairman Ron Wyden (D-Oregon) and ranking minority member Chuck Grassley (R-Iowa) wrote to CEO John C. Martin asking Gilead to justify the price for this drug. The committee hearings did not result in new law, but in 2014 and 2015, due to negotiated and mandated discounts, Sovaldi was sold well below the list price. For poorer countries, Gilead licensed multiple companies to produce generic versions of Sovaldi; in India, a pill's price was as low as $4.29. Gilead later combined Sovaldi with other antivirals in single-pill combinations. First, Sovaldi was combined with ledipasvir and marketed as Harvoni. This treatment for hepatitis C cures the patient in 94% to 99% of cases (HCV genotype 1) | https://en.wikipedia.org/wiki?curid=978997 |
Gilead Sciences By 2017, Gilead was reporting drastic drops in Sovaldi revenue from year to year, not only because of pricing pressure but because the number of suitable patients decreased. Later single-pill combinations were Epclusa (with velpatasvir) and Vosevi (with velpatasvir and voxilaprevir). For the fiscal year 2017, reported earnings of US$4.628 billion and annual revenue of US$26.107 billion, a decline of 14.1% over the previous fiscal cycle. Gilead Sciences's shares traded at over $70 per share, and its market capitalization was valued at US$93.4 billion in October 2018. As of 2017, Gilead's challenge is to develop or acquire new blockbuster drugs before its current revenue-producers wane or their patent protection expires. Gilead benefited from the expansion of Medicaid in the ACA; Leerink analyst Geoffrey Porges wrote that Gilead's HIV drugs could face funding pressure under reform proposals. Gilead has $32 billion in cash, but $27.4 billion is outside the U.S. and is unavailable for acquisitions unless Gilead pays U.S. tax on it, though it could borrow against it. Gilead would benefit from proposals to let companies repatriate offshore capital with minimal further taxation. Gilead's Entospletinib has shown a 90% complete response rate for MLL type AML. On December 26, 2018, "The Times" reported that Gilead had used the Double Irish arrangement to avoid U.S. corporate taxes on non–U.S | https://en.wikipedia.org/wiki?curid=978997 |
Gilead Sciences profits, reporting that "A US pharmaceutical firm used a controversial tax loophole arrangement to shift almost €20 billion in profits through an Irish entity in just two years". Several class-action lawsuits have been filed against Gilead over allegations that the company deliberately delayed development of antiretroviral drugs based on tenofovir alafenamide fumarate (TAF) in order to maximize profits from previous-generation medications containing tenofovir disoproxil fumarate (TDF). Plaintiffs allege that Gilead suspended TAF in 2004 despite clear evidence indicating that TAF-based medications were safer than TDF, a compound whose long-term use was associated with adverse side effects such as nephrotoxicity and bone density loss. Gilead intentionally withheld results of clinical trials demonstrating TAF's relative safety and efficacy and shelved TAF-based therapies until 2010, when the Food and Drug Administration approved Gilead's application to patent TAF. Gilead's first TAF medication, marketed under the trade name Genvoya, came out in 2015. In the interim period, many HIV patients who continuously took Gilead's older TDF-based drugs suffered permanent, debilitating kidney and bone damage, often developing conditions such as Fanconi syndrome and osteomalacia. Gilead has come under intense criticism for its high pricing of its patented drug sofosbuvir. In the US, for instance, it was launched at $1,000 per pill or $84,000 for the standard 84-day course | https://en.wikipedia.org/wiki?curid=978997 |
Gilead Sciences Gilead has also tried to eliminate competition in lucrative markets by entering voluntary licensing agreements (VLA) with companies from developing countries such as India, which mandated the limitation of the latter's operations to less lucrative markets. The company has also been criticized for creating harsh restrictions within countries where they have been denied rights, or are engaged in VLAs. For example, in India, they tried to create an 'anti-diversion' program to determine who could buy the drug, which was considered a coercive and policing move by Médecins Sans Frontières since it could lead to the exclusion of vulnerable groups like refugees and migrants from accessing the medicines. On January 21 2020, the Wuhan Institute of Virology applied for a Chinese "use patent" on remdesivir, for the novel use of treating COVID-19. Gilead sought and obtained "orphan drug" status for remdesivir from the US Food and Drug Administration on March 23rd, 2020. This provision is intended to encourage the development of drugs affecting fewer than 200,000 Americans by granting strengthened and extended legal monopoly rights to the manufacturer, along with waivers on taxes and government fees. Remdesivir is a candidate for treating COVID-19; at the time the status was granted, fewer than 200,000 Americans had COVID-19, but numbers were climbing rapidly as the COVID-19 pandemic reached the US, and crossing the threshold soon was considered inevitable. Remdesivir was developed by Gilead with over $79 million in U.S | https://en.wikipedia.org/wiki?curid=978997 |
Gilead Sciences government funding. After facing strong reactions, Gilead gave up the "orphan drug" status for remdesivir on March 25th. Gilead retains 20-year remdesivir patents in more than 70 countries. Gilead has also been accused of price-gouging on other medications developed with public funding, including AIDS PrEP drug Tenofovir and hepatitis C drug Sofosbuvir. | https://en.wikipedia.org/wiki?curid=978997 |
Working range Each instrument used in analytical chemistry has a useful working range. This is the range of concentration (or mass) that can be adequately determined by the instrument, where the instrument provides a useful signal that can be related to the concentration of the analyte. All instruments have an upper and a lower working limit. Concentrations below the working limit do not provide enough signal to be useful, and concentrations above the working limit provide too much signal to be useful. When calibrating an instrument for use, the experimenter must be familiar with both the lower and upper working range of the chosen instrument. | https://en.wikipedia.org/wiki?curid=979229 |
Philipp Ludwig Statius Müller (April 25, 1725 – January 5, 1776) was a German zoologist. Statius Müller was born in Esens, and was a professor of natural science at Erlangen. Between 1773 and 1776, he published a German translation of Linnaeus's "Natursystem". The supplement in 1776 contained the first scientific classification for a number of species, including the dugong, guanaco, potto, tricolored heron, umbrella cockatoo, red-vented cockatoo, and the enigmatic hoatzin. He was also an entomologist. Müller died in Erlangen. He is not to be confused with Salomon Müller (1804–1864), also an ornithologist, or with Otto Friedrich Müller. | https://en.wikipedia.org/wiki?curid=981615 |
William Ogilby (1808–1873) was an Irish barrister and naturalist. Ogilby was honorary secretary of the Zoological Society of London from 1839 to 1846. | https://en.wikipedia.org/wiki?curid=981797 |
L ring The L-ring of the bacterial flagellum is the ring in the lipid outer cell membrane through which the axial filament (rod, hook, and flagellum) passes. | https://en.wikipedia.org/wiki?curid=983400 |
NGC 3 is a lenticular galaxy in the Pisces constellation. It was discovered on November 29, 1864 by Albert Marth. | https://en.wikipedia.org/wiki?curid=983406 |
NGC 5078 is a spiral galaxy in the Hydra constellation, approximately 94 million light-years away from Earth. It has a diameter of 127,000 light-years and is probably a member of the NGC 5061 group. The dust lane of is warped, probably by interaction with the nearby galaxy IC 879, which is itself distorted into an 'S' shape by the interaction. At the presumed distance the two galaxies would have a minimal separation of about 61,000 light-years. For comparison, the Large Magellanic Cloud is about 160,000 light-years from the Milky Way. | https://en.wikipedia.org/wiki?curid=983463 |
Clay Riddell Clayton Howard Riddell, OC (July 13, 1937 – September 15, 2018) was a Canadian billionaire businessman who was the founder, president and CEO of Paramount Resources, based in Calgary, Alberta. He was born on a farm near Treherne, Manitoba on July 13, 1937, the youngest child of Cecil Howard Riddell and Bertha Maude Riddell nee Taylor. Riddell earned with a bachelor's degree in geology from the University of Manitoba. He also was part owner of the Calgary Flames and high-end Calgary restaurant Catch. With an estimated net worth of $US 2.5 billion (as of March 2011), he was ranked by Forbes as the 12th wealthiest Canadian and 459th in the world. Riddell was a president of the Canadian Society of Petroleum Geologists and Chair of the Canadian Association of Petroleum Producers. The Clayton H. Riddell Faculty of Environment, Earth, and Resources at the University of Manitoba is named in his honour. He donated $10 million to create an endowment fund for the faculty, which combines the Department of Environment and Geography, the Department of Geological Sciences and the Natural Resources Institute. In 2008, Riddell was made an Officer of the Order of Canada for his leadership and philanthropy. In May 2010, Carleton University announced the creation of Canada's first graduate program in political management, Clayton H. Riddell Graduate Program in Political Management, made possible through a donation from Riddell that is the largest in Carleton's history | https://en.wikipedia.org/wiki?curid=983668 |
Clay Riddell He was married to Vi Thorarinson, a nurse for 49 years until her death from leukemia in 2012. They had three daughters and a son together, Lynne, Sue, Jim and Brenda. Riddell died on September 15, 2018, after a short illness. | https://en.wikipedia.org/wiki?curid=983668 |
Sol (colloid) A sol is a colloid made out of very small solid particles in a continuous liquid medium. Sols are quite stable and show the Tyndall effect. Examples include blood, pigmented ink, cell fluids, paint, antacids and mud. Artificial sols may be prepared by dispersion or condensation. Dispersion techniques include grinding solids to colloidal dimensions by ball milling and Bredig's arc method. The stability of sols may be maintained by using dispersing agents. Sols are commonly used as part of the sol–gel process. A sol generally has a liquid as the dispersing medium and solid as a dispersed phase. Properties of a Colloid (applicable to sols) | https://en.wikipedia.org/wiki?curid=991054 |
NGC 7320 is a spiral galaxy in the Stephan's Quintet. However, it is not an actual member of the galaxy group, but a much closer line-of-sight galaxy at a distance of about 40 million light years. Other galaxies of Stephan's Quintet are some 300 million light-year distant. | https://en.wikipedia.org/wiki?curid=992044 |
Earth (historical chemistry) Earths were defined by the Ancient Greeks as "materials that could not be changed further by the sources of heat then available". Several oxides were thought to be earths, such as aluminum oxide and magnesium oxide. It wasn't until 1808 that these weren't elements but metallic oxides. | https://en.wikipedia.org/wiki?curid=992733 |
Orbiting body In astrodynamics, an orbiting body is any physical body that orbits a more massive one, called the primary body. The orbiting body is properly referred to as the secondary body (formula_1), which is less massive than the primary body (formula_2). Thus, formula_3 or formula_4. Under standard assumptions in astrodynamics, the barycenter of the two bodies is a focus of both orbits. An orbiting body may be a spacecraft (i.e. an artificial satellite) or a natural satellite, such as a planet, dwarf planet, moon, moonlet, asteroid, or comet. A system of two orbiting bodies is modeled by the Two-Body Problem and a system of three orbiting bodies is modeled by the Three-Body Problem. These problems can be generalized to an N-body problem. While there are a few analytical solutions to the n-body problem, it can be reduced to a 2-body system if the secondary body stays out of other bodies Sphere of Influence and remains in the primary bodies sphere of influence . | https://en.wikipedia.org/wiki?curid=996828 |
Relative angular momentum In celestial mechanics, the relative angular momentum (formula_1) of an orbiting body (formula_2) relative to a central body (formula_3) is the moment of (formula_2)'s relative linear momentum: where: For a body in an unperturbed orbit about a central body, the orbital plane is stationary, and the relative angular momentum (formula_1) is perpendicular to the orbital plane. <br> For perturbed orbits where the orbital plane is in motion, the relative angular momentum vector is perpendicular to the (osculating) orbital plane at only two points in the orbit. In astrodynamics relative angular momentum is usually used to derive specific relative angular momentum (formula_10): where: | https://en.wikipedia.org/wiki?curid=997253 |
Bioequivalence is a term in pharmacokinetics used to assess the expected in vivo biological equivalence of two proprietary preparations of a drug. If two products are said to be bioequivalent it means that they would be expected to be, for all intents and purposes, the same. Birkett (2003) defined bioequivalence by stating that, "two pharmaceutical products are bioequivalent if they are pharmaceutically equivalent and their bioavailabilities (rate and extent of availability) after administration in the same molar dose are similar to such a degree that their effects, with respect to both efficacy and safety, can be expected to be essentially the same. Pharmaceutical equivalence implies the same amount of the same active substance(s), in the same dosage form, for the same route of administration and meeting the same or comparable standards." For The World Health Organization (WHO) "two pharmaceutical products are bioequivalent if they are pharmaceutically equivalent or pharmaceutical alternatives, and their bioavailabilities, in terms of rate (Cmax and tmax) and extent of absorption (area under the curve), after administration of the same molar dose under the same conditions, are similar to such a degree that their effects can be expected to be essentially the same" | https://en.wikipedia.org/wiki?curid=998103 |
Bioequivalence The United States Food and Drug Administration (FDA) has defined bioequivalence as, "the absence of a significant difference in the rate and extent to which the active ingredient or active moiety in pharmaceutical equivalents or pharmaceutical alternatives becomes available at the site of drug action when administered at the same molar dose under similar conditions in an appropriately designed study." In determining bioequivalence, for example, between two products such as a commercially available Brand product and a potential to-be-marketed Generic product, pharmacokinetic studies are conducted whereby each of the preparations are administered in a cross-over study to volunteer subjects, generally healthy individuals but occasionally in patients. Serum/plasma samples are obtained at regular intervals and assayed for parent drug (or occasionally metabolite) concentration. Occasionally, blood concentration levels are neither feasible or possible to compare the two products (e.g. inhaled corticosteroids), then pharmacodynamic endpoints rather than pharmacokinetic endpoints (see below) are used for comparison. For a pharmacokinetic comparison, the plasma concentration data are used to assess key pharmacokinetic parameters such as area under the curve (AUC), peak concentration ("C"), time to peak concentration ("T"), and absorption lag time ("t"). Testing should be conducted at several different doses, especially when the drug displays non-linear pharmacokinetics | https://en.wikipedia.org/wiki?curid=998103 |
Bioequivalence In addition to data from bioequivalence studies, other data may need to be submitted to meet regulatory requirements for bioequivalence. Such evidence may include: The World Health Organization considers two formulation bioequivalent if the 90% confidence interval for the ratio multisource (generic) product/comparator lie within 80.00-125.00% acceptance range for AUC and C. For high variable finished pharmaceutical products, the applicable acceptance range for C can be 69.84-143.19%. In Australia, the Therapeutics Goods Administration (TGA) considers preparations to be bioequivalent if the 90% confidence intervals (90% CI) of the rate ratios, between the two preparations, of "C" and AUC lie in the range 0.80–1.25. "T" should also be similar between the products. There are tighter requirements for drugs with a narrow therapeutic index and/or saturable metabolism – thus no generic products exist on the Australian market for digoxin or phenytoin for instance. According to regulations applicable in the European Economic Area two medicinal products are bioequivalent if they are pharmaceutically equivalent or pharmaceutical alternatives and if their bioavailabilities after administration in the same molar dose are similar to such a degree that their effects, with respect to both efficacy and safety, will be essentially the same. This is considered demonstrated if the 90% confidence intervals (90% CI) of the ratios for AUC and "C" between the two preparations lie in the range 80–125% | https://en.wikipedia.org/wiki?curid=998103 |
Bioequivalence The FDA considers two products bioequivalent if the 90% CI of the relative mean C, AUC and AUC of the test (e.g. generic formulation) to reference (e.g. innovator brand formulation) should be within 80% to 125% in the fasting state. Although there are a few exceptions, generally a bioequivalent comparison of Test to Reference formulations also requires administration after an appropriate meal at a specified time before taking the drug, a so-called "fed" or "food-effect" study. A food-effect study requires the same statistical evaluation as the fasting study, described above. While the FDA maintains that approved generic drugs are equivalent to their branded counterparts, bioequivalence problems have been reported by physicians and patients for many drugs. Certain classes of drugs are suspected to be particularly problematic because of their chemistry. Some of these include chiral drugs, poorly absorbed drugs, and cytotoxic drugs. In addition, complex delivery mechanisms can cause bioequivalence variances. Physicians are cautioned to avoid switching patients from branded to generic, or between different generic manufacturers, when prescribing anti-epileptic drugs, warfarin, and levothyroxine. Major issues were raised in the verification of bioequivalence when multiple generic versions of FDA-approved generic drug were found not to be equivalent in efficacy and side effect profiles. In 2007, two providers of consumer information on nutritional products and supplements, ConsumerLab | https://en.wikipedia.org/wiki?curid=998103 |
Bioequivalence com and The People's Pharmacy, released the results of comparative tests of different brands of bupropion. The People's Pharmacy received multiple reports of increased side effects and decreased efficacy of generic bupropion, which prompted it to ask ConsumerLab.com to test the products in question. The tests showed that some generic versions of Wellbutrin XL 300 mg didn't perform the same as the brand-name pill in laboratory tests. The FDA investigated these complaints and concluded that the generic version is equivalent to Wellbutrin XL in regard to bioavailability of bupropion and its main active metabolite hydroxybupropion. The FDA also said that coincidental natural mood variation is the most likely explanation for the apparent worsening of depression after the switch from Wellbutrin XL to Budeprion XL. After several years of denying patient reports, in 2012 the FDA reversed this opinion, announcing that "Budeprion XL 300 mg fails to demonstrate therapeutic equivalence to Wellbutrin XL 300 mg." The FDA did not test the bioequivalence of any of the other generic versions of Wellbutrin XL 300 mg, but requested that the four manufacturers submit data on this question to the FDA by March 2013. As of October 2013, the FDA has made determinations on the formulations from some manufacturers not being bioequivalent. In 2004, Ranbaxy was revealed to have been falsifying data regarding the generic drugs they were manufacturing | https://en.wikipedia.org/wiki?curid=998103 |
Bioequivalence As a result, 30 products were removed from US markets and Ranbaxy paid $500 million in fines. The FDA investigated many Indian drug manufacturers after this was discovered, and as a result at least 12 companies have been banned from shipping drugs to the US. | https://en.wikipedia.org/wiki?curid=998103 |
Tuberous receptor Tuberous receptors are electroreceptors that are specialized to respond to high-frequency electrical fields (electric organ discharges or EODs), and hence are found only in fish with an active electrical sense that can generate their own electrical fields. They are mostly found on weakly electric fishes such as gymnotiforms and mormyrids. These receptors are particularly receptive to their own electrical fields, and can detect perturbations caused by foreign objects. There are two types of tuberous receptors, t-type and p-type. Species which use tuberous receptors include the glass knife fish ("Eigenmannia virescens"), a gymnotiform. | https://en.wikipedia.org/wiki?curid=1005964 |
Biorobotics is an interdisciplinary science that combines the fields of biomedical engineering, cybernetics, and robotics to develop new technologies that integrate biology with mechanical systems to develop more efficient communication, alter genetic information, and create machines that imitate biological systems. Cybernetics focuses on the communication and system of living organisms and machines that can be applied and combined with multiple fields of study such as biology, mathematics, computer science, engineering, and much more. This discipline falls under the branch of biorobotics because of its combined field of study between biological bodies and mechanical systems. Studying these two systems allow for advanced analysis on the functions and processes of each system as well as the interactions between them. Cybernetic theory is a concept that has existed for centuries, dating back to the era of Plato where he applied the term to refer to the “governance of people”. The term ‘cybernetique’ is seen in the mid 1800’s used by physicist André-Marie Ampère. The term “cybernetics” was popularized in the late 1940’s to refer to a discipline that touched on, but was separate, from established disciplines, such as electrical engineering, mathematics, and biology. Cybernetics is often misunderstood because of the breadth of disciplines it covers. In the early 20th century, it was coined as an interdisciplinary field of study that combines biology, science, network theory, and engineering | https://en.wikipedia.org/wiki?curid=1006293 |
Biorobotics Today, it covers all scientific fields with system related processes. The goal of cybernetics is to analyze systems and processes of any system or systems in an attempt to make them more efficient and effective. Cybernetics is used as an umbrella term so applications extend to all systems related scientific fields such as biology, mathematics, computer science, engineering, management, psychology, sociology, art, and more. Cybernetics is used amongst several fields to discover principles of systems, adaptation of organisms, information analysis and much more. Genetic engineering is a field that uses advances in technology to modify biological organisms. Through different methods, scientists are able to alter the genetic material of microorganisms, plants and animals to provide them with desirable traits. Genetic engineering is included in biorobotics because it uses new technologies to alter biology and change an organism’s DNA for their and society’s benefit. Although humans have been modifying genetic material of animals and plants through artificial selection for millenia (such as the genetic mutations that developed teosinte into corn and wolves into dogs), genetic engineering refers to the deliberate alteration or insertion of specific genes to an organism's DNA. The first successful case of genetic engineering occurred in 1973 when Herbert Boyer and Stanley Cohen were able to transfer a gene with antibiotic resistance to a bacteria | https://en.wikipedia.org/wiki?curid=1006293 |
Biorobotics There are three main techniques used in genetic engineering: The plasmid method, the vector method and the biolistic method. This technique is used mainly for microorganisms such as bacteria. Through this method, DNA molecules called plasmids are extracted from bacteria and placed in a lab where restriction enzymes break them down. As the enzymes break the molecules down, some develop a rough edge that resembles that of a staircase which is considered ‘sticky’ and capable of reconnecting. These ‘sticky’ molecules are inserted into another bacteria where they will connect to the DNA rings with the altered genetic material. The vector method is considered a more precise technique than the plasmid method as it involves the transfer of a specific gene instead of a whole sequence. In the vector method, a specific gene from a DNA strand is isolated through restriction enzymes in a laboratory and is inserted into a vector. Once the vector accepts the genetic code, it is inserted into the host cell where the DNA will be transferred. The biolistic method is typically used to alter the genetic material of plants. This method embeds the desired DNA with a metallic particle such as gold or tungsten in a high speed gun. The particle is then bombarded into the plant. Due to the high velocities and the vacuum generated during bombardment, the particle is able to penetrate the cell wall and inserts the new DNA into the cell. Genetic engineering has many uses in the fields of medicine, research and agriculture | https://en.wikipedia.org/wiki?curid=1006293 |
Biorobotics In the medical field, genetically modified bacteria are used to produce drugs such as insulin, human growth hormones and vaccines. In research, scientists genetically modify organisms to observe physical and behavioral changes to understand the function of specific genes. In agriculture, genetic engineering is extremely important as it is used by farmers to grow crops that are resistant to herbicides and to insects such as BTCorn. Bionics is a medical engineering field and a branch of biorobotics consisting of electrical and mechanical systems that imitate biological systems, such as prosthetics and hearing aids. It’s a portmanteau that combines biology and electronics. The history of bionics goes as far back in time as ancient Egypt. A prosthetic toe made out of wood and leather was found on the foot of a mummy. The time period of the mummy corpse was estimated to be from around the fifteenth century B.C. Bionics can also be witnessed in ancient Greece and Rome. Prosthetic legs and arms were made for amputee soldiers. In the early 16th century, a French military surgeon by the name of Ambroise Pare became a pioneer in the field of bionics. He was known for making various types of upper and lower prosthetics. One of his most famous prosthetics, Le Petit Lorrain, was a mechanical hand operated by catches and springs. During the early 19th century, Alessandro Volta further progressed bionics. He set the foundation for the creation of hearing aids with his experiments | https://en.wikipedia.org/wiki?curid=1006293 |
Biorobotics He found that electrical stimulation could restore hearing by inserting an electrical implant to the saccular nerve of a patient’s ear. In 1945, the National Academy of Sciences created the Artificial Limb Program, which focused on improving prosthetics since there were a large number of World War II amputee soldiers. Since this creation, prosthetic materials, computer design methods, and surgical procedures have improved, creating modern-day bionics. The important components that make up modern-day prosthetics are the pylon, the socket, and the suspension system. The pylon is the internal frame of the prosthetic that is made up of metal rods or carbon-fiber composites. The socket is the part of the prosthetic that connects the prosthetic to the person’s missing limb. The socket consists of a soft liner that makes the fit comfortable, but also snug enough to stay on the limb. The suspension system is important in keeping the prosthetic on the limb. The suspension system is usually a harness system made up of straps, belts or sleeves that are used to keep the limb attached. The operation of a prosthetic could be designed in various ways. The prosthetic could be body-powered, externally-powered, or myoelectrically-powered. Body-powered prosthetics consist of cables attached to a strap or harness, which is placed on the person’s functional shoulder, allowing the person to manipulate and control the prosthetic as he or she deems fit | https://en.wikipedia.org/wiki?curid=1006293 |
Biorobotics Externally-powered prosthetics consist of motors to power the prosthetic and buttons and switches to control the prosthetic. Myoelectrically-powered prosthetics are new, advanced forms of prosthetics where electrodes are placed on the muscles above the limb. The electrodes will detect the muscle contractions and send electrical signals to the prosthetic to move the prosthetic. Four major components make up the hearing aid: the microphone, the amplifier, the receiver, and the battery. The microphone takes in outside sound, turns that sound to electrical signals, and sends those signals to the amplifier. The amplifier increases the sound and sends that sound to the receiver. The receiver changes the electrical signal back into sound and sends the sound into the ear. Hair cells in the ear will sense the vibrations from the sound, convert the vibrations into nerve signals, and send it to the brain so the sounds can become coherent to the person. The battery simply powers the hearing aid. Cochlear implants are a type of hearing aid for those who are deaf. Cochlear implants send electrical signals straight to the auditory nerve, the nerve responsible for sound signals, instead of just sending the signals to the ear canal like normal hearing aids. These hearing aids are also used for people with severe hearing loss. Baha hearing aids attach to the bones of the middle ear to create the sound vibrations in the skull and send those vibrations to the cochlea | https://en.wikipedia.org/wiki?curid=1006293 |
Biorobotics This artificial sensing skin detects any pressure put on it and is meant for people who have lost any sense of feeling on parts of their bodies, such as diabetics with peripheral neuropathy. The bionic eye is a bioelectronic implant that restores vision for people with blindness. Orthopedic bionics consist of advanced bionic limbs that use a person’s neuromuscular system to control the bionic limb. These robotics can remove a polyp during a colonoscopy. | https://en.wikipedia.org/wiki?curid=1006293 |
Arthur Urquhart Arthur Torrane Urquhart (1839–1919) was an arachnologist and naturalist based in New Zealand. Urquhart was born in Switzerland in 1839. In 1856, he migrated to New Zealand and lived in a farm in Karaka. He produced eighteen taxonomic papers between 1882 and 1897. | https://en.wikipedia.org/wiki?curid=62040174 |
NGC 4380 is a spiral galaxy located in the constellation of Virgo . | https://en.wikipedia.org/wiki?curid=62056938 |
Osebury Rock (also spelt Oseberrow or Rosebury) is a cliff on the River Teme where fragmentary rocks of the Haffield Breccia layer are revealed. Its woodland and vegetation include some restricted varieties including the large-leaved lime and narrow-leaved bitter-cress. It was registered as a Site of Special Scientific Interest in 1990. The place is traditionally associated with fairies and Bate's Bush was said to be haunted. Bate's Bush was a maple tree at the nearby crossroads which was said to have sprung from a stake used to impale the body of a suicide. | https://en.wikipedia.org/wiki?curid=62060919 |
Richard Heaton (priest) Richard Heaton, DD was a Church of Ireland priest in Ireland during the Seventeenth Century. Heaton was educated at Trinity College, Dublin. He was appointed Prebendary of Kilrush in Killaloe Cathedral in 1633 and Dean of Clonfert in 1662, holding both positions until his death in 1666. He was an amateur botanist. | https://en.wikipedia.org/wiki?curid=62067487 |
Stephen Eales is a professor of astrophysics at Cardiff University, where he is currently head of the Astronomy Group. In 2015, he was awarded the Herschel Medal from the Royal Astronomical Society for outstanding contributions to observational astrophysics. He also writes articles and books about astronomy. His main research field is the new field of submillimetre astronomy, in particular using submillimetre observations to investigate the origin and evolution of galaxies. He has led a number of large submillimetre observing programmes. In particular, with Loretta Dunne he led the Herschel ATLAS the largest survey of the extragalactic sky carried out with the Herschel Space Observatory. | https://en.wikipedia.org/wiki?curid=62067518 |
Vicarious Hypothesis The Vicarious Hypothesis, or hypothesis vicaria, was a planetary hypothesis proposed by Johannes Kepler to describe the motion of Mars. The hypothesis adopted the circular orbit and equant of Ptolemy's planetary model as well as the heliocentrism of the Copernican model. Calculations using the did not support a circular orbit for Mars, leading Kepler to propose elliptical orbits as one of three laws of planetary motion in "Astronomia Nova". In 1600, Johannes Kepler met and began working with Tycho Brahe at Benátky, a town north of Prague where Brahe's new observatory was being built. Brahe assigned Kepler the task of modeling the motion of Mars using only data that Brahe had collected himself. Upon the death of Brahe in 1601, all of Brahe's data was willed to Kepler. Brahe's observational data was among the most accurate of his time, which Kepler used in the construction of the Vicarious Hypothesis. Claudius Ptolemy's planetary model consisted of a stationary earth surrounded by fixed circles, called deferents, which carried smaller, rotating circles called epicycles. Planets rotated on the epicycles as the epicycles traveled along the deferent. Ptolemy shifted the Earth away from the center of the deferent and introduced another point, the equant, equidistant to the deferent's center on the opposite side of the Earth. The uses a circular orbit for Mars and reintroduces a form of the equant to describe the motion of Mars with constant angular speed | https://en.wikipedia.org/wiki?curid=62081079 |
Vicarious Hypothesis Nicolaus Copernicus broke from the geocentric model of Ptolemy by placing the Sun at the center of his planetary model. However, Copernicus retained circular orbits for the planets and added an orbit for the Earth, insisting that the Earth revolved around the Sun. The Sun was positioned off-center of the orbits but was still contained within all orbits. Kepler adopted Copernican heliocentrism in the construction of the so that his measurements of the distances to Mars were taken relative to the Sun. Kepler's construction of the was based on a circular orbit for Mars and a heliocentric model for the planets. After receiving longitudinal observation data from Tycho Brahe, Kepler had twelve observations, two being his own, in which Mars was at opposition to the Sun. From these twelve observations, Kepler chose four to form the basis of the because they had a relatively uniform distribution across his proposed circular orbit for Mars. In this sense, the functions as a fit to observational data. Kepler used these four observations to determine the eccentricities of the Sun and equant of his proposed orbit. Unlike the Ptolemaic System, in which the Earth and equant were assumed equidistant to the center of the orbit, the placed the equant where the time and location of the observation would match. Using the Vicarious Hypothesis, Kepler determined the eccentricities of the Sun and equant to be 11,332 and 7,232 arbitrary units, respectively, for the Martian orbital radius of 100,000 units | https://en.wikipedia.org/wiki?curid=62081079 |
Vicarious Hypothesis Using these positions for the Sun and equant, the model constructed using the agreed with the twelve observations within 2' of arc, a level of accuracy better than any other previous model. While the heliocentric longitudes of this model proved to be accurate, distances from the Sun to Mars, or latitudes of Mars, challenged the model. In his book, "Astronomia Nova", Kepler determined that the eccentricity of the Sun, based on latitudinal oppositions, should be between a range of 8,000 and 9,943, conflicting with the eccentricity of 11,332 determined by the Vicarious Hypothesis. To accommodate the latitudinal data, Kepler modified the to include a bisected eccentricity, making the Sun and equant equidistant to the center of the orbit. This resolved the error in the latitudes of Mars but introduced a longitudinal error of 8' of arc in some parts of the Mars orbit. While an 8' error still had better accuracy than previous models, corresponding to approximately one-fourth the diameter of the Moon, Kepler rejected the because he did not believe it was accurate enough to model the true orbit of Mars. The errors in latitude and longitude of the Mars orbit made Kepler realize that false assumptions were made using the Vicarious Hypothesis. In particular, Kepler amended the hypothesis to exclude the circular orbit. Kepler realized that he could fix the error by reducing the spread of the central region of the circular orbit, creating an ellipse | https://en.wikipedia.org/wiki?curid=62081079 |
Vicarious Hypothesis He used calculations previously made with the to confirm the elliptical orbit for Mars. Kepler published his results in "Astronomia Nova", in which he introduces the elliptical orbit for planets as his first law of planetary motion. | https://en.wikipedia.org/wiki?curid=62081079 |
Anthropocene Working Group The (AWG) is an interdisciplinary research group dedicated to the study of the Anthropocene as a geological time unit. It was established in 2009 as part of the Subcommission on Quaternary Stratigraphy (SQS), a constituent body of the International Commission on Stratigraphy (ICS). As for 2019, the research program features 35 members (including the Nobel Prize-winning Paul Crutzen, who popularized the word 'Anthropocene' in 2000), including a working group convener and a Secretary, respectively the palaeobiologist Jan Zalasiewicz and the geologist Colin Neil Waters. The main goal of the AWG is providing scientific evidence robust enough for the Anthropocene to be formally ratified by the International Union of Geological Sciences (IUGS) as an Epoch within the Geologic time scale. Prior to the establishment of the in 2009, no research program dedicated to the formalization of the Anthropocene in the geologic time scale existed. The idea of naming the current epoch 'Anthropocene' rather than using its formal time unit, the Holocene, became popular after Paul Crutzen and Eugene Stoermer published in May 2000 an article on the "IGBP Global Change Newsletter" called "The 'Anthropocene' | https://en.wikipedia.org/wiki?curid=62084284 |
Anthropocene Working Group " Later in 2002, Crutzen published a commentary on "Nature" titled "Geology of Mankind" where he further stressed the idea "to assign the term ‘Anthropocene’ to the present, in many ways human-dominated, geological epoch, supplementing the Holocene," with starting date in the late 18th century (at the onset of the Industrial Revolution). Soon after Paul Crutzen published his influential articles, a debate over the beginning of the Anthropocene took place between supporters of the Early Anthropocene Hypothesis, an thesis originally promoted in 2003 by the palaeoclimatologist William Ruddiman dating the beginning of the Anthropocene as far back as the neolithic revolution, and supporters of more recent starting dates, from the late 18th century to the post-WWII Great Acceleration. The discussion over the beginning of the Anthropocene was crucial for the 'stratigraphic turn' that the Anthropocene debate took in the following years. In February 2008, Jan Zalasiewicz and other members of the Stratigraphy Commission of the Geological Society of London published a paper that considered the possibility to "amplify and extend the discussion of the effects referred to by Crutzen and then apply the same criteria used to set up new epochs to ask whether there really is justification or need for a new term, and if so, where and how its boundary might be placed." The article raised the possibility of studying the Anthropocene as a discrete geological unit—a possibility that later led to the establishment of the AWG | https://en.wikipedia.org/wiki?curid=62084284 |
Anthropocene Working Group In 2009, the Subcommission on Quaternary Stratigraphy established an to "examine the status, hierarchical level and definition of the Anthropocene as a potential new formal division of the Geological Time Scale." Some authors have labelled this moment as 'stratigraphic turn' or 'geological turn', in that the establishment of the AWG acknowledged the Anthropocene as an object of geological interest in the scientific community. The AWG has been actively publishing ever since then. The is one of four workings groups part of the Subcommission on Quaternary Stratigraphy (the other three being the Pleistocene–Holocene boundary working group, Middle/Late Pleistocene boundary working group, and Early/Middle Pleistocene boundary working group). The AWG members (including Paul Crutzen, who was awarded the Nobel prize for chemistry in 1995 for his researcher on ozone depletion; John McNeill, a pioneering researcher in the field of environmental history; and Naomi Oreskes, author of the influential book "Merchants of Doubt") have diverse disciplinary backgrounds, ranging from international law, archaeology, and history to philosophy, natural science, and geography. Since no direct funding supports the research program, communication among members happens mostly through email, whereas meetings are usually founded by hosting institutions | https://en.wikipedia.org/wiki?curid=62084284 |
Anthropocene Working Group As for most of the epochs in the Phanerozoic (the current Eon, starting 541 million years ago), determining the beginning of the Anthropocene by locating and agreeing upon its lower boundary is a necessary step in its process of formalization. A lower boundary is defined by locating a GSSP (informally known as 'golden spike') in the stratigraphic section of a stage, the chronostratigraphic taxonomic equivalent of an Epoch. Alternatively, if a 'golden spike' cannot be located, a GSSA can be agreed upon, although this methodology is usually implemented for Precambrian boundaries. There is a specific set of rules that a GSSP must fulfill in order to be recognized as a valid primary geologic marker. A central object of research for the AWG is establishing "when", "where", and "how" to locate the lower boundary of the Anthropocene. This means assigning a starting date to the Anthropocene (and an end to the Holocene), locating primary as well as auxiliary markers defining Anthropocene geologic record, and determining the proper methodology to implement in the overall process of formalization (GSSP or GSSA, what proxies to use as markers, etc.). Although debates on the taxonomical level of the Anthropocene in the chronostratigraphic chart / geologic time scale (Stage/Age, Series/Epoch, or System/Period) have occurred, the AWG has been considering the Anthropocene to best fit the requirements to be taxonomically recognized as an Epoch | https://en.wikipedia.org/wiki?curid=62084284 |
Anthropocene Working Group In January 2014, the Geological Society of London published "A Stratigraphical Basis for the Anthropocene," a collection of scientific essays dedicated to assessing and analyzing the anthropogenic signatures defining the Anthropocene, and its requirements to be recognized as a distinct chronostratigraphic unit from the Holocene. The volume constitutes a landmark publication for the AWG, collecting a preliminary body of scientific evidence for the Anthropocene, and establishing research areas and trajectories retraced in the following years. In February 2019, the AWG published "The Anthropocene as a Geological Time Unit: A Guide to the Scientific Evidence and Current Debate." It represents an extensive summary of evidence collected supporting the case of formalization of the Anthropocene as a geological time unit. The synthesis comprehends evidence ranging from stratigraphy, lithostratigraphy, mineralogy, biostratigraphy, chemostratigraphy, to climatology, Earth system science, and archaeology. The monograph also links the Anthropocene to the question concerning anthropogenic climate change, and the role of human technology and the technosphere in impacting the functioning of the Earth system. In the first chapter, the authors also provide a genealogy of the term 'Anthropocene,' and a statement of the role of the AWG as a scientific research program | https://en.wikipedia.org/wiki?curid=62084284 |
Anthropocene Working Group In May, 2019, the AWG completed a binding vote determining two major research questions: Both questions received a positive response, with 29 votes in favor, 4 votes against, and no abstention (33 votes received out of 34 potential voting members). | https://en.wikipedia.org/wiki?curid=62084284 |
Genome sequencing of endangered species is the application of Next Generation Sequencing (NGS) technologies in the field of conservative biology, with the aim of generating life history, demographic and phylogenetic data of relevance to the management of endangered wildlife. In the context of conservation biology, genomic technologies such as the production of large-scale sequencing data sets via DNA sequencing can be used to highlight the relevant aspects of the biology of wildlife species for which management actions may be required. This may involve the estimation of recent demographic events, genetic variations, divergence between species and population structure. Genome-wide association studies (GWAS) are useful to examine the role of natural selection at the genome level, to identify the loci associated with fitness, local adaptation, imbreeding, depression or disease susceptibility. The access to all these data and the interrogation of genome-wide variation of SNP markers can help the identification of the genetic changes that influence the fitness of wild species and are also important to evaluate the potential respond to changing environments. NGS projects are expected to rapidly increase the number of threatened species for which assembled genomes and detailed information on sequence variation are available and the data will advance investigations relevant to the conservation of biological diversity. The traditional approaches in the preservation of endangered species are captive breeding and the private farming | https://en.wikipedia.org/wiki?curid=62084317 |
Genome sequencing of endangered species In some cases those methods led to great results, but some problems still remain. For example, by inbreeding only few individuals, the genetic pool of a sub-population remains limited or may decrease. Genetic analyses can remove subjective elements from the determination of the phyliogenetic relationship between organisms. Considering the great variety of information provided by living organisms, it is clear that the type of data will affect both the method of treatment and validity of the results: the higher the correlation of data and genotype, the greater is the validity likely to be. The data analysis can be used to compared different sequencing database and find similar sequences, or similar protein in different species. The comparison can be done using informatic software based on alignment to know the divergence between different species and evaluate the similarities. Since whole-genome sequencing is generally very data-intensive, techniques for reduced representation genomic approaches are sometimes used for practical applications. For example, restriction site-associated DNA sequencing (RADseq) and double digest RADseq are being developed. With those techniques researchers can target different numbers of loci. With a statistical and bioinformatic approach scientists can make considerations about big genomes, by just focusing on a small representative part of it | https://en.wikipedia.org/wiki?curid=62084317 |
Genome sequencing of endangered species While solving biological problems, one encounters multiple types of genomic data or sometimes an aggregate of same type of data across multiple studies and decoding such huge amount of data manually is unfeasible and tedious. Therefore, integrated analysis of genomic data using statistical methods has become popular. The rapid advancement in high throughput technologies allows researchers to answer more complex biological questions enabling the development of statistical methods in integrated genomics to establish more effective therapeutic strategies for human disease. While studying the genome, there are some crucial aspects that should be taken in consideration. Gene prediction is the identification of genetic elements in a genomic sequence. This study is based on a combination of approaches: de novo, homology prediction, and transcription. Tools such as EvidenceModeler are used to merge the different results. Gene structure also have been compared, including mRNA length, exon length, intron length, exon number, and non-coding RNA. Analysis of repeated sequences has been found useful in reconstructing species divergence timelines. In order to preserve a specie, knowledge of the mating system is crucial: scientists can stabilize wild populations through captive breeding, followed by the release in the environment of new individuals. This task is particularly difficult by considering the species with homomorphic sex chromosomes and a large genome | https://en.wikipedia.org/wiki?curid=62084317 |
Genome sequencing of endangered species For example, in the case of amphibians, there are multiple transitions among male and/or female heterogamety. Sometimes even variation of sex chromosomes within amphibian populations of the same specie were reported. The multiple transitions among XY and ZW systems that occur in amphibians determine the sex chromosome systems to be labile in salamanders populations. By understanding the chromosomal basis of sex of those species, it is possible to reconstruct the phylogenetic history of those families and use more efficient strategies in their conservation. By using the ddRADseq method scientists find new sex-related loci in a 56 Gb genome of "Cryptobranchidae" family. Their results support the hypothesis of female heterogamety of this species. These loci were confirmed through the bioinformatic analysis of presence/absence of that genetic locus in sex-knowing individuals. Their sex was determined previously by ultrasound, laparoscopy and by measuring serum calcium level differences. The determination of those candidate sexual loci was performed considering valid both the female-heterogametic and the male-heterogametic. Finally to evaluate the validity of those loci, they were amplified through PCR directly from samples of known-sex individuals. This final step led to the demonstration of female-heterogametic of several divergent populations of "Cryptobranchidae" family | https://en.wikipedia.org/wiki?curid=62084317 |
Genome sequencing of endangered species A recent study used whole-genome sequencing data to demonstrate the sister lineage between the Dryas monkey and vervet monkey and their divergence with additional bidirectional gene flow approximately 750,000 to approximately 500,000 years ago. With <250 remaining adult individuals, the study showed high genetic diversity and low levels of inbreeding and genetic load in the studied Dryas monkey individuals. Another study used several techniques such as single-molecule real time sequencing, paired-end sequencing, optical maps, and high-throughput chromosome conformation capture to obtain a high quality chromosome assembly from already constructed incomplete and fragmented genome assembly for the golden snub-nosed monkey. The modern techniques used in this study represented 100-fold improvement in the genome with 22,497 protein-coding genes, of which majority were functionally annotated. The reconstructed genome showed a close relationship between the species and the Rhesus macaque, indicating a divergence approximately 13.4 million years ago. Plants species identified as PSESP ("plant species with extremely small population") have been the focus of genomic studies, with the aim of determining the most endangered populations. The DNA genome can be sequenced starting from the fresh leaves by doing a DNA extraction. The combination of different sequencing techniques together can be used to obtain a high quality data that can be used to assembly the genome | https://en.wikipedia.org/wiki?curid=62084317 |
Genome sequencing of endangered species The RNA extraction is essential for the transcriptome assembly and the extraction process start from stem, roots, fruits, buds and leaves. The "de novo" genome assembly can be performed using software to optimize assembly and scaffolding. The software can also be used to fill the gaps and reduce the interaction between chromosome. The combination of different data can be used for the identification of orthologous gene with different species, phylogenetic tree construction, and interspecific genome comparisons. The development of indirect sequencing methods has to some degree mitigated the lack of efficient DNA sequencing technologies. These techniques allowed researchers to increase scientific knowledge in fields like ecology and evolution. Several genetic markers, more or less well suited for the purpose, were developed helping researchers to address many issues among which demography and mating systems, population structures and phylogeography, speciational processes and species differences, hybridization and introgression, phylogenetics at many temporal scales. However, all these approaches had a primary deficiency: they were all limited only to a fraction of the entire genome so that genome-wide parameters were inferred from a tiny amount of genetic material. The invention and rising of DNA sequencing methods brought a huge contribution in increasing available data potentially useful to improve the field of conservation biology | https://en.wikipedia.org/wiki?curid=62084317 |
Genome sequencing of endangered species The ongoing development of cheaper and high throughput allowed the production of a wide array of information in several disciplines providing conservation biologists a very powerful databank from which was possible to extrapolate useful information about, for example, population structure, genetic connections, identification of potential risks due to demographic changes and inbreeding processes through population-genomic approaches that rely on the detection of SNPs, indel or CNV. From one side of the coin, data derived from high throughput sequencing of whole genomes were potentially a massive advance in the field of species conservation, opening wide doors for future challenges and opportunities. On the other side all these data brought researchers to face two main issues. First, how to process all these information. Second, how to translate all the available information into conservation's strategies and practice or, in other words, how to fill the gap between genomic researches and conservation application. Unfortunately, there are many analytical and practical problems to consider using approaches involving genome-wide sequencing. Availability of samples is a major limiting factor: sampling procedures may disturb an already fragile population or may have a big impact in individual animals itself putting limitations to samples' collection | https://en.wikipedia.org/wiki?curid=62084317 |
Genome sequencing of endangered species For these reasons several alternative strategies where developed: constant monitoring, for example with radio collars, allow us to understand the behaviour and develop strategies to obtain genetic samples and management of the endangered populations. The samples taken from those species are then used to produce primary cell culture from biopsies. Indeed, this kind of material allow us to grow in vitro cells, and allow us to extract and study genetic material without constantly sampling the endangered populations. Despite a faster and easier data production and a continuous improvement of sequencing technologies, there is still a marked delay of data analysis and processing techniques. Genome-wide analysis and big genomes studies require advances in bioinformatics and computational biology. At the same time improvements in the statistical programs and in the population genetics are required to make better conservation strategies. This last aspect work in parallel with prediction strategies which should take in consideration all features that determine fitness of a species. | https://en.wikipedia.org/wiki?curid=62084317 |
Kurt Lohwag (1913 – 1970) was a Bohemian-born Austrian botanist and mycologist. The son of the mycologist Heinrich Lohwag, he was educated at the University of Vienna. For much of his career, he worked at the Hochschule für Bodenkultur, Vienna. | https://en.wikipedia.org/wiki?curid=62088523 |
Marta Catellani is an Italian chemist known for her discovery of the eponymous Catellani reaction in 1997. She was elected to the European Academy of Sciences in 2016. Catellani earned her Ph.D. in chemistry in 1971 from the University of Parma, where, as of 2019, she is a professor and chairs the Department of Organic Chemistry. Catellani completed her postdoctoral education at the University of Chicago. She has served as a visiting professor at Moscow State University (1992), Beijing Institute of Technology (2004), and University of Xi'an (2004). She was awarded a fellowship at the Japan Society for the Promotion of Science in 2012. Her research focuses on palladium as a catalyst for multistep organic reactions. | https://en.wikipedia.org/wiki?curid=62096452 |
Katarina Cicak is a physicist. She is a researcher in the advanced microwave photonics group at the National Institute of Standards and Technology. | https://en.wikipedia.org/wiki?curid=62115342 |
Prime editing is a ‘search-and-replace’ genome editing technology in molecular biology by which the genome of living organisms may be modified. The technology directly writes new genetic information into a targeted DNA site. It uses a fusion protein, consisting of a catalytically impaired Cas9 endonuclease fused to an engineered reverse transcriptase enzyme, and a prime editing guide RNA (pegRNA), capable of identifying the target site and provide the new genetic information to replace the target DNA nucleotides. It mediates targeted insertions, deletions, and base-to-base conversions without the need for double strand breaks (DSBs) or donor DNA templates. The technology is an early-stage, experimental genome editing method that has received mainstream press attention due to its potential uses in medical genetics. It utilizes similar methodologies to precursor genome editing technologies, including CRISPR/Cas9 and base editors. As of 2019, it remains a scientific proof of concept, with no therapeutic applications. involves three major components: Genomic editing takes place by transfecting cells with the pegRNA and the fusion protein. Transfection is often accomplished by introducing vectors into a cell. Once internalized, the fusion protein nicks the target DNA sequence, exposing a 3’-hydroxyl group that can be used to initiate (prime) the reverse transcription of the RT template portion of the pegRNA | https://en.wikipedia.org/wiki?curid=62129266 |
Prime editing This results in a branched intermediate that contains two DNA flaps: a 3’ flap that contains the newly synthesized (edited) sequence, and a 5’ flap that contains the dispensable, unedited DNA sequence. The 5’ flap is then cleaved by structure-specific endonucleases or 5’ exonucleases. This process allows 3’ flap ligation, and creates a heteroduplex DNA composed of one edited strand and one unedited strand. The reannealed double stranded DNA contains nucleotide mismatches at the location where editing took place. In order to correct the mismatches, the cells exploit the intrinsic mismatch repair mechanism, with two possible outcomes: (i) the information in the edited strand is copied into the complementary strand, permanently installing the edit; (ii) the original nucleotides are re-incorporated into the edited strand, excluding the edit. During the development of this technology, several modifications were done to the components, in order to increase its effectiveness. In the first system, a wild-type Moloney Murine Leukemia Virus (M-MLV) reverse transcriptase was fused to the Cas9 H840A nickase C-terminus. Detectable editing efficiencies were observed. In order to enhance DNA-RNA affinity, enzyme processivity, and thermostability, five amino acid substitutions were incorporated into the M-MLV reverse transcriptase. The mutant M-MLV RT was then incorporated into PE1 to give rise to (Cas9 (H840A)-M-MLV RT(D200N/L603W/T330P/T306K/W313F)). Efficiency improvement was observed over PE1 | https://en.wikipedia.org/wiki?curid=62129266 |
Prime editing Despite its increased efficacy, the edit inserted by PE2 might still be removed due to DNA mismatch repair of the edited strand. To avoid this problem during DNA heteroduplex resolution, an additional single guide RNA (sgRNA) is introduced. This sgRNA is designed to match the edited sequence introduced by the pegRNA, but not the original allele. It directs the Cas9 nickase portion of the fusion protein to nick the unedited strand at a nearby site, opposite to the original nick. Nicking the non-edited strand causes the cell’s natural repair system to copy the information in the edited strand to the complementary strand, permanently installing the edit. Although additional research is required to improve the efficiency of prime editing, the technology offers promising scientific improvements over other gene editing tools. The prime editing technology has the potential to correct the vast majority of pathogenic alleles that cause genetic diseases, as it can repair insertions, deletions, and nucleotide substitutions. The prime editing tool offers advantages over traditional gene editing technologies. CRISPR/Cas9 edits rely on non-homologous end joining (NHEJ) or homology-directed repair (HDR) to fix DNA breaks, while the prime editing system employs DNA mismatch repair. This is an important feature of this technology given that DNA repair mechanisms such as NHEJ and HDR, generate unwanted, random insertions or deletions (INDELs) byproducts which complicate the retrieval of cells carrying the correct edit | https://en.wikipedia.org/wiki?curid=62129266 |
Prime editing The prime system introduces single-stranded DNA breaks instead of the double-stranded DNA breaks observed in other editing tools, such as base editors. Collectively, base editing and prime editing offer complementary strengths and weaknesses for making targeted transition mutations. Base editors offer higher editing efficiency and fewer INDEL byproducts if the desired edit is a transition point mutation and a PAM sequence exists roughly 15 bases from the target site. However, because the prime editing technology does require a precisely positioned PAM sequence to target a nucleotide sequence, it offers more flexibility and editing precision. Remarkably, prime editors allow all types of substitutions, transitions and transversions to be inserted into the target sequence. Because the prime system involves three separate DNA binding events (between (i) the guide sequence and the target DNA, (ii) the primer binding site and the target DNA, and (iii) the 3’ end of the nicked DNA strand and the pegRNA), it has been suggested to have fewer undesirable off-target effects than CRISPR/Cas9. There is considerable interest in applying gene editing methods to the treatment of diseases with a genetic component. However, there are multiple challenges associated with this approach. An effective treatment would require editing of a large number of target cells, which in turn would require an effective method of delivery and a great level of tissue specificity | https://en.wikipedia.org/wiki?curid=62129266 |
Prime editing As of 2019, prime editing looks promising for relatively small genetic alterations, but more research needs to be conducted to evaluate whether the technology is efficient in making larger alterations, such as targeted insertions and deletions. Larger genetic alterations would require a longer RT template, which could hinder the efficient delivery of pegRNA to target cells. Furthermore, a pegRNA containing a long RT template could become vulnerable to damage caused by cellular enzymes. Overall, much research will be needed before prime editing could be used to correct pathogenic alleles in human diseases. Base editors used for prime editing require delivery of both a protein and RNA molecule into living cells. Introducing exogenous gene editing technologies into living organisms is a significant challenge. One potential way to introduce a base editor into animals and plants would be to package the base editor into a viral capsid. The target organism can then be transduced by the virus to synthesize the base editor "in vivo". Common laboratory vectors of transduction such as lentivirus cause immune responses in humans, so proposed human therapies often centered around adeno-associated virus (AAV) because AAV infections are largely asymptomatic. Unfortunately, the effective packaging capacity of AAV vectors is small, approximately 4.4kb not including inverted terminal repeats. As a comparison, an SpCas9-reverse transcriptase fusion protein is 6 | https://en.wikipedia.org/wiki?curid=62129266 |
Prime editing 3kb, which doesn't even account for the lengthened guide RNA necessary for targeting and priming the site of interest. Images created with Biorender. | https://en.wikipedia.org/wiki?curid=62129266 |
Elsa Matilde Zardini (born 1949) is an Argentinian/Paraguayan botanist, teacher, curator, and explorer. She has made botanical expeditions in the US, Brazil, Argentina, Paraguay. Three botanical taxon names were authored by Zardini. Her specialization is the flora of the Plata basin, with an emphasis on that of Paraguay. In 1973 Zardini earned a Masters in Science, and in 1974 a PhD, both at the National University of La Plata in Buenos Aires, Argentina. Zardini is one of the disciples of the Argentinian botanist Ángel Lulio Cabrera among them: Genoveva Dawson, Otto Solbrig, Jorge Morello, Humberto A. Fabris (1924-1976), Delia Abbiatti, Noemí Correa, Delia Añón Suárez, Cristina Orsi, Amelia Torres, Aída Pontiroli, Jorge Crisci, Roberto Kiesling and Fernando Zuloaga. 2011: she became associate curator of the Missouri Botanical Garden. Spermatophytes was an area of interest for her. Flora of the Guianas Onagraceae. . Zardini, Elsa M,j. Jansen-Jacobs, peter h. Raven. 1991."e". Vol. 10. Ed. Koeltz "American Cucurbitaceae useful to man:" Whitaker, Thomas of the United States Department of Agriculture, Zardini, E.M. La Plata, October 7 to 14, 1980. Ed. Province of Buenos Aires Commission of Investigations Scientists, List of . Lulia, Lulia nervosa, and Trichocline deserticola | https://en.wikipedia.org/wiki?curid=62132271 |
Thierry Chopin Thierry B.R. Chopin is a phycologist and professor of aquaculture at the University of New Brunswick, Saint John. | https://en.wikipedia.org/wiki?curid=62134509 |
3MM-1 is a star-forming galaxy about 12.5 billion light-years away that is obscured by clouds of dust. It was first detected in spectroscopic data on rotational transitions of carbon monoxide obtained using the Atacama Large Millimeter Array from 23-24 December 2018, as detailed in an article that was published on 22 October 2019. The authors of this article described the discovery as "serendipitous", since was found at a redshift of about 5.5, while the focus of their planned observations had been on galaxies at redshifts near 1.5 that are quiescent, i.e. do not form stars, and directly observable. In the same dataset, another dust-obscured star-forming galaxy, 3MM-2, was found at a redshift of about 3.3. has a mass of about 10 solar masses, and stars form in it at about 100 times the rate as in the Milky Way. | https://en.wikipedia.org/wiki?curid=62134998 |
John Diffley (biologist) John Francis Xavier Diffley (born 1958 in New York City) is a molecular biologist who specializes in studying eukaryotic DNA replication. He was awarded the 2019 Canada Gairdner International Award for his "pioneering research on the eukaryotic DNA replication cycles including initiation, regulation and responses to DNA damage". He is associate research director at the Francis Crick Institute. | https://en.wikipedia.org/wiki?curid=62145523 |
Victoria Leong is a developmental cognitive neuroscientist whose research into the neural synchrony between mothers and infants has been widely reported. Leong's PhD thesis won the Robert J. Glushko Prize of the Cognitive Science Society in 2014 "in recognition of outstanding cross-disciplinary work integrating neuroscience, psychology, linguistics and computational modelling." She has a dual appointment at Nanyang Technological University and the University of Cambridge and is head of the Baby-LINC Lab at the Department of Psychology at Cambridge. | https://en.wikipedia.org/wiki?curid=62165769 |
Sebeș Formation The is a geological formation in Romania. It is of Maastrichtian age. It is laterally equivalent to the Sard Formation. The base of the formation consists of claystones interbedded with sandstones and conglmerates. It is well known for its fossils which form a component of the Hațeg Island fauna. | https://en.wikipedia.org/wiki?curid=62168119 |
Glacier head A glacier head is the top of a glacier. Although glaciers seem motionless to the observer they are in constant motion and the terminus is always either advancing or retreating. On a glacier, the accumulation zone is the area above the firn line, where snowfall accumulates and exceeds the losses from ablation, (melting, evaporation, and sublimation). The annual equilibrium line separates the accumulation and ablation zone annually. The accumulation zone is also defined as the part of a glacier's surface, usually at higher elevations, on which there is net accumulation of snow, which subsequently turns into firn and then glacier ice. Part of the glacier where snow builds up and turns to ice moves outward from there. The glacier head is the highest upslope edge of an alpine glacier or the upslope end of the zone of accumulation. The head of the glacier comes up against a steep bedrock cliff called a cirque headwall The head can come away from the cirque in a downslope movement which can create a large crevasse called a bergschrund. This crevasse can be a major obstacle for mountaineers. The existence of a bergschrund is evidence that ice mass has pulled away from the cirque. A shrinking glacier thins faster near the terminus than near the head, which explains why glaciers retreat up-valley and the glacier head stays in place The speed of erosion or accumulation is partly dependent on a shape factor which is the ratio of the change in thickness at the glacier head to the change in the thickness at the terminus | https://en.wikipedia.org/wiki?curid=62175198 |
Glacier head "attribution":Contains text copied from Accumulation zone and Bergschrund and Terminus. | https://en.wikipedia.org/wiki?curid=62175198 |
NGC 4746 is an edge-on spiral galaxy located 107 million light-years away in the constellation Virgo. It was discovered by John Herschel during a sky-survey on March 29, 1830. | https://en.wikipedia.org/wiki?curid=62176999 |
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