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Mezen Basin The is a sedimentary basin located in northwestern Russia. It list southeast of the White Sea and bounds the Timanide Orogen to the north and west. The basin is classified as a pericratonic and epicratonic foreland basin within the East European Craton. The contains the following pre-Vendian sediments: the Ust-Nafta Group with a maximum thickness of 1200 meters, on top of this is rests the Safonovo Group made up of carbonates and siliciclastic sediments reminiscent of flysch. The Safonovo Group upward end is an unconformity that separates it from the poorly sorted sandstones of the Uftuga Formation. | https://en.wikipedia.org/wiki?curid=48036401 |
Madras Naturalists' Society is a non-governmental organization that promotes appreciation, education and conservation of Nature. It was founded by bird watchers from the city of Madras (now Chennai), India) on 17 May 1978. G. K. Bhat was the organization's first President. The logo of the society is a Blackbuck The society started publishing a monthly bulletin from December 1978 and a quarterly journal "Blackbuck" from January 1985 Blackbuck carries semi-technical articles and works of popular interest. The digitised Version of 'Blackbuck' and the monthly bulletin was unveiled on 2 July 2015 to the members. An anthology of writings from the "Blackbuck" titled "Sprint of the Blackbuck" was published in 2012. The volume was edited by noted Tamil film historian and member S. Theodore Baskaran. Starting from Madhavaiah Krishnan's birth centenary year in 2012, the society annual presents a "M. Krishnan Memorial Nature Writing Award" for young wildlife writers. | https://en.wikipedia.org/wiki?curid=48036893 |
NGC 6285 is an interacting spiral galaxy located in the constellation Draco. It is designated as S0-a in the galaxy morphological classification scheme and was discovered by the American astronomer Lewis A. Swift in 1886. is located at about 262 million light years away from earth. and NGC 6286 form a pair of interacting galaxies, with tidal distortions, categorized as Arp 293 in the Arp Atlas of Peculiar Galaxies<ref name="NASA/IPAC"></ref> | https://en.wikipedia.org/wiki?curid=48039287 |
NGC 6286 is an interacting spiral galaxy located in the constellation Draco. It is designated as Sb/P in the galaxy morphological classification scheme and was discovered by the American astronomer Lewis A. Swift on 13 August 1885. is located at about 252 million light years away from Earth. and NGC 6285 form a pair of interacting galaxies, with tidal distortions, categorized as Arp 293 in the Arp Atlas of Peculiar Galaxies.<ref name="NASA/IPAC"></ref> | https://en.wikipedia.org/wiki?curid=48040170 |
Maurits Lindström (10 May 1932 – 14 November 2009) was a Swedish geologist and paleontologist. Lindströms initial work was divided among two topics conodont paleontology and the structural geology of the Scandinavian Caledonides in Lappland. In 1970, he described the conodont families Cordylodontidae, Gondolellidae, Proconodontidae and Rhipidognathidae. In 1971, he described the conodont genera "Baltoniodus", "Microzarkodina" and "Paracordylodus". Lindström published conodont studies up to 1987 after which he only supervised students working with conodonts. In the late 1980s Lindström begun to study ancient impact craters in the Fennoscandian Shield. His studies have confirmed earlier speculations that Tvären and Lockne are craters. In 1985 he became member of the Royal Swedish Academy of Sciences and in 2009 he was awarded the prize "Årets geolog" (Geologist of the Year) by Geosektionen of Naturvetarna. He received the Pander Medal awarded by the Pander Society, an informal organisation founded in 1967 for the promotion of the study of conodont palaeontology. | https://en.wikipedia.org/wiki?curid=48040831 |
NGC 6300 is a barred Seyfert spiral galaxy located in the constellation Ara. It is designated as SB(rs)b in the galaxy morphological classification scheme and was discovered by the Scottish astronomer James Dunlop on 30 June 1826. is located at about 51 million light years away from earth. It is suspected that a massive black hole (300,000 times the mass of Sun) may be at its center, pulling all the nearby objects into it. In turn, it emits large amounts of X-rays.<ref name="NASA/IPAC"></ref><ref name="The NGC/IC Project"></ref> | https://en.wikipedia.org/wiki?curid=48043633 |
Henry Clay White (1848-1927) was an American chemist, notable for his contributions to agricultural science and higher education. He was also an early proponent of Darwin's theory of evolution. From 1872 to 1927, he was professor of chemistry at the University of Georgia. In 1893 he was elected as a member of the Royal Society of Chemistry. He died on November 30, 1927, in Athens, Georgia. | https://en.wikipedia.org/wiki?curid=48046115 |
Proglacial river A proglacial river is a river that flows from the margin of a glacier. These rivers are strongly affected by the highly-seasonal water supply from the glacier and by the large supply of sediment that arrives at the glacier terminus. This high sediment supply often makes them steep and braided. Many modern proglacial rivers drain glaciers in the mountain ranges of Alaska and the Himalayas. Past and present proglacial rivers in front of large ice sheets deposited large outwash plains of sediment. | https://en.wikipedia.org/wiki?curid=48047392 |
Microbial rhodopsin Microbial rhodopsins, also known as bacterial rhodopsins are retinal-binding proteins that provide light-dependent ion transport and sensory functions in halophilic This protein family includes light-driven proton pumps, ion pumps and ion channels, as well as light sensors. For example, the proteins from halobacteria include bacteriorhodopsin and archaerhodopsin, which are light-driven proton pumps; halorhodopsin, a light-driven chloride pump; and sensory rhodopsin, which mediates both photoattractant (in the red) and photophobic (in the ultra-violet) responses. Proteins from other bacteria include proteorhodopsin. Contrary to their name, microbial rhodopsins are found not only in Archaea and Bacteria, but also in Eukaryota (such as algae) and viruses; although they are rare in complex multicellular organisms. Rhodopsin was originally a synonym for "visual purple", a visual pigment (light-sensitive molecule) found in the retinas of frogs and other vertebrates, used for dim-light vision, and usually found in rod cells. This is still the meaning of rhodopsin in the narrow sense, any protein evolutionarily homologous to this protein. In a broad non-genetic sense, rhodopsin refers to any molecule, whether related by genetic descent or not (mostly not), consisting of an opsin and a chromophore (generally a variant of retinal) | https://en.wikipedia.org/wiki?curid=48050134 |
Microbial rhodopsin All animal rhodopsins arose (by gene duplication and divergence) late in the history of the large G-protein coupled receptor (GPCR) gene family, which itself arose after the divergence of plants, fungi, choanflagellates and sponges from the earliest animals. The retinal chromophore is found solely in the opsin branch of this large gene family, meaning its occurrence elsewhere represents convergent evolution, not homology. Microbial rhodopsins are, by sequence, very different from any of the GPCR families. The term bacterial rhodopsin originally referred to the first microbial rhodopsin discovered, known today as bacteriorhodopsin. The first bacteriorhodopsin turned out to be of archaeal origin, from "Halobacterium salinarum". Since then, other microbial rhodopsins have been discovered, rendering the term "bacterial rhodopsin" ambiguous. Below is a list of some of the more well-known microbial rhodopsins and some of their properties. The Ion-translocating Microbial Rhodopsin (MR) Family (TC# 3.E.1) is a member of the TOG Superfamily of secondary carriers. Members of the MR family catalyze light-driven ion translocation across microbial cytoplasmic membranes or serve as light receptors. Most proteins of the MR family are all of about the same size (250-350 amino acyl residues) and possess seven transmembrane helical spanners with their N-termini on the outside and their C-termini on the inside | https://en.wikipedia.org/wiki?curid=48050134 |
Microbial rhodopsin There are 9 subfamilies in the MR family: A phylogenetic analysis of microbial rhodopsins and a detailed analysis of potential examples of horizontal gene transfer have been published. Among the high resolution structures for members of the MR Family are the archaeal proteins, bacteriorhodopsin, sensory rhodopsin II, halorhodopsin, as well as an "Anabaena" cyanobacterial sensory rhodopsin (TC# 3.E.1.1.6) and others. The association of sensory rhodopsins with their transducer proteins appears to determine whether they function as transporters or receptors. Association of a sensory rhodopsin receptor with its transducer occurs via the transmembrane helical domains of the two interacting proteins. There are two sensory rhodopsins in any one halophilic archaeon, one (SRI) that responds positively to orange light but negatively to blue light, the other (SRII) that responds only negatively to blue light. Each transducer is specific for its cognate receptor. An x-ray structure of SRII complexed with its transducer (HtrII) at 1.94 Å resolution is available (). Molecular and evolutionary aspects of the light-signal transduction by microbial sensory receptors have been reviewed | https://en.wikipedia.org/wiki?curid=48050134 |
Microbial rhodopsin Homologues include putative fungal chaperone proteins, a retinal-containing rhodopsin from "Neurospora crassa", a H-pumping rhodopsin from "Leptosphaeria maculans", retinal-containing proton pumps isolated from marine bacteria, a green light-activated photoreceptor in cyanobacteria that does not pump ions and interacts with a small (14 kDa) soluble transducer protein and light-gated H channels from the green alga, "Chlamydomonas reinhardtii". The "N. crassa" NOP-1 protein exhibits a photocycle and conserved H translocation residues that suggest that this putative photoreceptor is a slow H pump. Most of the MR family homologues in yeast and fungi are of about the same size and topology as the archaeal proteins (283-344 amino acyl residues; 7 putative transmembrane α-helical segments), but they are heat shock- and toxic solvent-induced proteins of unknown biochemical function. They have been suggested to function as pmf-driven chaperones that fold extracellular proteins, but only indirect evidence supports this postulate. The MR family is distantly related to the 7 TMS LCT family (TC# 2.A.43). Representative members of MR family can be found in the Transporter Classification Database. Bacterio- and halorhodopsins pump 1 H and 1 Cl per photon absorbed, respectively. Specific transport mechanisms and pathways have been proposed | https://en.wikipedia.org/wiki?curid=48050134 |
Microbial rhodopsin The mechanism involves: Six structural models describe the transformations of the retinal and its interaction with water 402, Asp85, and Asp212 in atomic detail, as well as the displacements of functional residues farther from the Schiff base. The changes provide rationales for how relaxation of the distorted retinal causes movements of water and protein atoms that result in vectorial proton transfers to and from the Schiff base. Helix deformation is coupled to vectorial proton transport in the photocycle of bacteriorhodopsin. Most residues participating in the trimerization are not conserved in bacteriorhodopsin, a homologous protein capable of forming a trimeric structure in the absence of bacterioruberin. Despite a large alteration in the amino acid sequence, the shape of the intratrimer hydrophobic space filled by lipids is highly conserved between archaerhodopsin-2 and bacteriorhodopsin. Since a transmembrane helix facing this space undergoes a large conformational change during the proton pumping cycle, it is feasible that trimerization is an important strategy to capture special lipid components that are relevant to the protein activity. A marine bacterial rhodopsin has been reported to function as a proton pump. However, it also resembles sensory rhodopsin II of archaea as well as an Orf from the fungus "Leptosphaeria maculans" (AF290180). These proteins exhibit 20-30% identity with each other. Channelrhodopsin-1 (ChR1) or channelopsin-1 (Chop1; Cop3; CSOA) of "C | https://en.wikipedia.org/wiki?curid=48050134 |
Microbial rhodopsin reinhardtii" is closely related to the archaeal sensory rhodopsins. It has 712 aas with a signal peptide, followed by a short amphipathic region, and then a hydrophobic N-terminal domain with seven probable TMSs (residues 76-309) followed by a long hydrophilic C-terminal domain of about 400 residues. Part of the C-terminal hydrophilic domain is homologous to intersectin (EH and SH3 domain protein 1A) of animals (AAD30271). Chop1 serves as a light-gated proton channel and mediates phototaxis and photophobic responses in green algae. Based on this phenotype, Chop1 could be assigned to TC category #1.A, but because it belongs to a family in which well-characterized homologues catalyze active ion transport, it is assigned to the MR family. Expression of the "chop1" gene, or a truncated form of that gene encoding only the hydrophobic core (residues 1-346 or 1-517) in frog oocytes in the presence of all-trans retinal produces a light-gated conductance that shows characteristics of a channel passively but selectively permeable to protons. This channel activity probably generates bioelectric currents. A homologue of ChR1 in "C. reinhardtii" is channelrhodopsin-2 (ChR2; Chop2; Cop4; CSOB). This protein is 57% identical, 10% similar to ChR1. It forms a cation-selective ion channel activated by light absorption. It transports both monovalent and divalent cations. It desensitizes to a small conductance in continuous light. Recovery from desensitization is accelerated by extracellular H and a negative membrane potential | https://en.wikipedia.org/wiki?curid=48050134 |
Microbial rhodopsin It may be a photoreceptor for dark adapted cells. A transient increase in hydration of transmembrane α-helices with a t(1/2) = 60 μs tallies with the onset of cation permeation. Aspartate 253 accepts the proton released by the Schiff base (t(1/2) = 10 μs), with the latter being reprotonated by aspartic acid 156 (t(1/2) = 2 ms). The internal proton acceptor and donor groups, corresponding to D212 and D115 in bacteriorhodopsin, are clearly different from other microbial rhodopsins, indicating that their spatial positions in the protein were relocated during evolution. E90 deprotonates exclusively in the nonconductive state. The observed proton transfer reactions and the protein conformational changes relate to the gating of the cation channel. Archaerhodopsin-2 (aR2) was found in the claret membrane of "Halorubrum sp". It is a light-driven proton pump. Trigonal and hexagonal crystals revealed that trimers are arranged on a honeycomb lattice. In these crystals, the carotenoid bacterioruberin binds to crevices between the subunits of the trimer. Its polyene chain is inclined from the membrane normal by an angle of about 20 degrees and, on the cytoplasmic side, it is surrounded by helices AB and DE of neighboring subunits. This peculiar binding mode suggests that bacterioruberin plays a structural role for the trimerization of aR2. When compared with the aR2 structure in another crystal form containing no bacterioruberin, the proton release channel takes a more closed conformation in the P321 or P6(3) crystal; i.e | https://en.wikipedia.org/wiki?curid=48050134 |
Microbial rhodopsin , the native conformation of protein is stabilized in the trimeric protein-bacterioruberin complex. The generalized transport reaction for bacterio- and sensory rhodopsins is: That for halorhodopsin is: | https://en.wikipedia.org/wiki?curid=48050134 |
NGC 6328 is an intermediate spiral galaxy located in the constellation Ara. It is designated as SAB(s)ab in the galaxy morphological classification scheme and was discovered by the British astronomer John Herschel on 2 May 1835. is located at about 199 million light years away from earth.<ref name="NASA/IPAC"></ref> | https://en.wikipedia.org/wiki?curid=48060469 |
Heinrich Leonhards Skuja (1892–1972) was a botanist specialist of algae. | https://en.wikipedia.org/wiki?curid=48119533 |
Waulsortian mudmound A is a geographical feature formed in warm tropical waters in the Viséan geological age, now transposed to the temperate regions in Europe. It is a type of bioconstruction, rich in fossils. The rock comprises light grey, unbedded, micritic limestone, heavily jointed with calcite veining. There is some galena and sphalerite mineralisation in the joints. The fossils are mainly Crinoid ossicles together with gastropods and brachiopods. The term Waulsortian was first used in 1863 to describe an area of limestone near Waulsort in Namur, Belgium. Similar mudstone was recognised in the Clitheroe area of Lancashire England by Arthur Vaughan in 1916. On a firm bed of limestone, under the deep waters of the tropical sea, crinoids fixed themselves to the rock. The oceans gentle currents eroded the base rock creating a lime-rich mud which was propelled by the current. Where the water was too rapid, the crinoids were displaced, but where it was slower they formed a barrier which arrested the mud forming a micritic deposit. Further crinoids attached themselves, and the deposit thickened to an eventual depth of 200m. In the mudmound one finds fossils of the crinoids bone structure and the angle of deposit shows the direction and speed of mudflow | https://en.wikipedia.org/wiki?curid=48127400 |
Waulsortian mudmound There has been much debate on how the low micritic limestone hills in the Craven Basin were formed, one theory led to them being called reef knolls, knoll reefs, or bioherms but work in 1972 by Miller & Grayson identified them as mud mounds with the same fossil content as those near Waulsort. They include accessible geological sites at Clitheroe Castle, Salthill and Bellman quarries, Crow Hill and Worsaw, Gerna and Sykes. | https://en.wikipedia.org/wiki?curid=48127400 |
Primary direction is a term in astronomy for the reference meridian used in a celestial coordinate system for that system's longitude. | https://en.wikipedia.org/wiki?curid=48134895 |
Javier Pérez-Ramírez (born 28 October 1974) is a Professor of Catalysis and Chemical Engineering at ETH Zurich. (JPR) studied Chemical Engineering at the University of Alicante, and later obtained his PhD cum laude at TU Delft (2002). He worked for Norsk Hydro and Yara International and returned to academia as a ICREA research professor at the Institute of Chemical Research of Catalonia, related to the Rovira i Virgili University (2005-2009). Since 2010, he is Full Professor of Catalysis Engineering at the Institute for Chemical and Bioengineering at the Swiss Federal Institute of Technology Zurich. In 2018 he became visiting professor and director of the Flagship Green Energy Program at the National University of Singapore. He is associate editor of "Catalysis Science & Technology", and sits on the editorial board of Advanced Functional Materials, Applied Catalysis B: Environmental, ACS Catalysis, Energy Technology, and Catalysis Communications. Since 2018, Pérez-Ramírez is president of the Catalysis Section of the Swiss Chemical Society. He is Swiss representative of the European Federation of Catalysis. Pérez-Ramírez's central research focuses on the fundamental design and technical development of new heterogeneous catalysts and reactor engineering concepts, favoring the more efficient and sustainable manufacturing within the chemical industry | https://en.wikipedia.org/wiki?curid=48135307 |
Javier Pérez-Ramírez He has developed novel catalysts for the gas-phase oxidation of hydrogen chloride (Deacon process) and has done major and groundbreaking contributions in the rational design of hierarchical zeolites. Pérez-Ramírez's work of nearly 400 articles and 17 patents has been recognized by several major prizes, including the Paul H. Emmett Award in Fundamental Catalysis (2019), Xingda Lecturship of Peking University (2018), Sustainable Energy Award (2017), the Beilby Medal and Prize (2014), the EFCATS Young Researcher Award (2013), the DECHEMA Otto Roelen Medal (2012), the Andrew Main lectureship (2013), the UOP-Honeywell Invitational Lectureship (2012), and the KNCV Prijs voor Katalyse (2003). In 2013, he has been elected Fellow of the Royal Society of Chemistry. | https://en.wikipedia.org/wiki?curid=48135307 |
Specialty drugs in the United States Specialty drugs or specialty pharmaceuticals are a recent designation of pharmaceuticals that are classified as high-cost, high complexity and/or high touch. Specialty drugs are often biologics—"drugs derived from living cells" that are injectable or infused (although some are oral medications). They are used to treat complex or rare chronic conditions such as cancer, rheumatoid arthritis, hemophilia, H.I.V. psoriasis, inflammatory bowel disease and hepatitis C. In 1990 there were 10 specialty drugs on the market, in the mid-1990s there were fewer than 30, by 2008 there were 200, and by 2015 there were 300. Drugs are often defined as specialty because their price is much higher than that of non-specialty drugs. Medicare defines any drug for which the negotiated price is $670 per month or more, as a specialty drug which is placed in a specialty tier that requires a higher patient cost sharing. Drugs are also identified as specialty when there is a special handling requirement or the drug is only available via a limited distributions network. By 2015 "specialty medications accounted for one-third of all spending on drugs in the United States, up from 19 percent in 2004 and heading toward 50 percent in the next 10 years", according to IMS Health, which tracks prescriptions. According to a 2010 article in Forbes, specialty drugs for rare diseases became more expensive "than anyone imagined" and their success came "at a time when the traditional drug business of selling medicines to the masses" was "in decline" | https://en.wikipedia.org/wiki?curid=48172434 |
Specialty drugs in the United States In 2015 analysis by "The Wall Street Journal" suggested the large premium was due to the perceived value of rare disease treatments which usually are very expensive when compared to treatments for more common diseases. Medications must be either identified as high cost, high complexity or high touch to be classified as a specialty medication by Magellan Rx Management. Specialty pharmaceuticals are defined as "high-cost oral or injectable medications used to treat complex chronic conditions". According to a 2013 article in the "Journal of Managed Care & Specialty Pharmacy", on the increasingly important role of specialty drugs in the treatment of chronic conditions and their cost, drugs are most typically defined as specialty because they are expensive. Other criteria used to define a drug as specialty include "biologic drugs, the need to inject or infuse the drug, the requirement for special handling, or drug availability only via a limited distribution network". The price of specialty drugs compared to non-specialty drugs is very high, "more than $1,000 per 30-day supply". Specialty drugs cover over forty therapeutic categories and special disease states with over 500 drugs. Vogenberg claims that there is no standard definition of a specialty drug which is one of the reasons they are difficult to manage | https://en.wikipedia.org/wiki?curid=48172434 |
Specialty drugs in the United States "[T]hose pharmaceuticals that usually require special handling, administration, unique inventory management, and a high level of patient monitoring and support to consumers with specific chronic conditions, acute events, or complex therapies, and provides comprehensive patient education services and coordination with the patient and prescriber." Drugs are most typically defined as specialty because they are expensive. They are high cost "both in total and on a per-patient basis". High-cost medications are typically priced at more than $1,000 per 30-day supply. The Medicare Part D program "defines a specialty drug as one that costs more than $600 per month". Most of the prescriptions filled by Pennsylvania-licensed Philidor Rx Services, a specialty online mail-order pharmacy, which mainly sold Valeant Pharmaceuticals International Inc expensive drugs directly to patients and handled insurance claims on the customers' behalf, such as Solodyn, Jublia, and Tretinoin, would be considered specialty drugs. Specialty drugs are more complex to manufacture. They are "highly complex medications, typically biology-based, that structurally mimic compounds found within the body". Specialty drugs are often biologics—"drugs derived from living cells"—but biologics are "not always deemed to be specialty drugs". Biologics "may be produced by biotechnology methods and other cutting-edge technologies | https://en.wikipedia.org/wiki?curid=48172434 |
Specialty drugs in the United States Gene-based and cellular biologics, for example, often are at the forefront of biomedical research, and may be used to treat a variety of medical conditions for which no other treatments are available." According to the U.S. Food and Drug Administration (FDA) biologics, or Some specialty drugs can be oral medications or self-administered injectables. Others may be professionally administered or injectables/infusions. High-touch patient care management is usually required to control side effects and ensure compliance. Specialized handling and distribution are also necessary to ensure appropriate medication administration. Specialty drugs patient care management is meant to be both high technology and high touch care, or patient-centered care with "more face-to-face time, more personal connections". Patient-centered care is defined by the Institute of Medicine as "care that is respectful of and responsive to individual patient preferences, needs and values". Specialty drugs may be "difficult for patients to take without ongoing clinical support". Specialty drugs might have special requirements for handling procedures and administration including the necessity of having controlled environments such as highly specific temperature controls to ensure product integrity. They are often only available via a limited distributions network such as a special pharmacy. Specialty drugs may be "challenging for providers to manage" | https://en.wikipedia.org/wiki?curid=48172434 |
Specialty drugs in the United States Specialty drugs may be taken "by relatively small patient populations presenting with complex medical conditions". "Specialty pharmacies have their roots in the 1970s, when they began delivering temperature-controlled drugs to treat cancer, HIV, infertility and hemophilia." According to "The American Journal of Managed Care", in 1990 there were 10 specialty drugs on the market. According to the National Center for Biotechnology Information, by the mid-1990s, there were fewer than 30 specialty drugs on the market, but by 2008 that number had increased to 200. Specialty drugs may also be designated as orphan drugs or ultra-orphan drugs under the U. S. Orphan Drug Act of 1983. This was enacted to facilitate development of orphan drugs—drugs for rare diseases such as Huntington's disease, myoclonus, amyotrophic lateral sclerosis, Tourette syndrome and muscular dystrophy which affect small numbers of individuals residing in the United States. Not all specialty drugs are orphan drugs. According to Thomson Reuters in their 2012 publication "The Economic Power of Orphan Drugs", there has been increased investing in orphan drug research and development partly since the U.S. Congress enacted the Orphan Drug Act, giving an extra monopoly for drugs for "orphan diseases" that affected fewer than 200,000 people in the country. Similar acts came into existence in other regions of the world, many driven by "high-profile philanthropic funding" | https://en.wikipedia.org/wiki?curid=48172434 |
Specialty drugs in the United States According to a 2010 article in "Forbes", prior to 1983 drug companies largely ignored rare diseases and focused on drugs that affected millions of patients. The term "specialty drugs" was used as early as 1988 in a "New York Times" article about Eastman Kodak Company's acquisition of the New York-based Sterling Drug Inc., maker of specialty drugs along with many and diverse other products. When Shire Pharmaceuticals acquired BioChem Pharma in 2000 they created a specialty pharmaceuticals company. By 2001 Shire was one of the fastest growing specialty pharmaceutical companies in the world. By 2001 CVS's specialty pharmacy ProCare was the "largest integrated retail/mail provider of specialty pharmacy services" in the United States. It was consolidated with their pharmacy benefit management company PharmaCare in 2002. In their 2001 annual report, CVS anticipated that the "$16 billion specialty pharmacy market" would grow at "an even faster rate than traditional pharmacy due in large part to the robust pipeline of biotechnology drugs". By 2014 CVS Caremark, Express Scripts and Walgreens represented more than 50% of the specialty drug market in the United States. When an increasing number of oral oncology agents first entered the market between 2000 and 2010, most cancer care was provided in a community oncology practices. By 2008 many other drugs had been developed to treat cancer, and drug development had grown into a multibillion-dollar industry | https://en.wikipedia.org/wiki?curid=48172434 |
Specialty drugs in the United States In 2003 the Medicare Prescription Drug, Improvement, and Modernization Act was enacted—the largest overhaul of Medicare in the public health program's 38-year history—included Medicare Part D an entitlement benefit for prescription drugs, through tax breaks and subsidies. In 2004 the U. S. Centers for Medicare and Medicaid Services (CMS) prepared a report on final guidance regarding access to drug coverage enacted under in which they included the specialty drugs tier in the prescription drug formulary. At that time CMS guidelines included four tiers: tier 1 includes preferred generics, tier 2 includes preferred brands, tier 3 includes non-preferred brands and generics and tier 4 included specialty drugs. By January 1, 2006, the controversial Medicare Part D was put in effect. It was a massive expansion of the federal government's provision of prescription drug coverage to previously uninsured Americans, particularly seniors. In 2006 in the United States there was no standard nomenclature, so sellers could call the plan anything they wanted and cover whatever drugs they wanted. By 2008 most prescription medication plans in the United States used specialty drug tiers, and some had a separate benefit tier for injectable drugs. Beneficiary cost sharing was higher for drugs in these tiers | https://en.wikipedia.org/wiki?curid=48172434 |
Specialty drugs in the United States By 2011 in the United States a growing number of Medicare Part D health insurance plans—which normally include generic, preferred, and non-preferred tiers with an accompanying rate of cost-sharing or co-payment—had added an "additional tier for high-cost drugs which is referred to as a specialty tier". By 2014 in the United States, in the new Health Insurance Marketplace—following the implementation of the U.S. Affordable Care Act, also known as Obamacare—most health plans had a four- or five-tier prescription drug formulary with specialty drugs in the highest of the tiers. According to an AARP 2015 report, "All but 4 of the 46 therapeutic categories of specialty drug products had average annual retail price increases that exceeded the rate of general inflation in 2013. Price increases by therapeutic category ranged from 1.7 percent to 77.2 percent." On September 27, 2007 President George W. Bush amended the Food and Drug Administration Amendments Act of 2007 (FDAAA) to authorize the FDA to require Risk Evaluation and Mitigation Strategies (REMS) on medications if necessary to minimize the risks associated with some drugs". These medications were designated as specialty drugs and required specialty pharmacies. When the FDA approves a new drug they may require a REMS program which "may contain any combination of 5 criteria: Medication Guide, Communication Plan, Elements to Assure Safe Use, Implementation System, and Timetable for Submission of Assessments" | https://en.wikipedia.org/wiki?curid=48172434 |
Specialty drugs in the United States "In 2010, 48% of all new molecular entities, and 60% of all new specialty drug approvals, required a REMS program." Risk-reduction mechanisms can include the "use of specialized distribution partners", special pharmacy. In 2013 the FDA introduced the breakthrough therapy designation program which cut the development process of new therapies by several years. This meant that the FDA could "introduce important medicines to the market based on very promising phase 2 rather than phase 3 clinical trial results". Shortly after the law was enacted, Ivacaftor, in January 2013, became the first drug to receive the breakthrough therapy designation. On February 3, 2015 New York-based Pfizer's drug Ibrance was approved through the FDA's Breakthrough Therapy designation program as a treatment for advanced breast cancer. It can only be ordered through specialty pharmacies and sells for "$9,850 for a month or $118,200 per year". According to a statement by the New York-based Pfizer the price "is not the cost that most patients or payors pay" since most prescriptions are dispensed through health plans, which negotiate discounts for medicines or get government-mandated price concessions. According to Express Scripts, By 2015 "specialty medications account for one-third of all spending on drugs in the United States, up from 19 percent in 2004 and heading toward 50 percent in the next 10 years, according to IMS Health, which tracks prescriptions". The specialty pharmacy business had $20 billion in sales in 2005 | https://en.wikipedia.org/wiki?curid=48172434 |
Specialty drugs in the United States By 2014 it had grown to "$78 billion in sales". In Canada by 2013 "specialty drugs made up less than 1.3 percent of all Canadian prescriptions, but accounted for 24 percent of Canada's total spending on prescription drugs". When Randy Vogenberg of the Institute for Integrated Healthcare in Massachusetts and a co-leader of the Midwest Business Group initiative, began investigating specialty drugs in 2003, it "wasn't showing up on the radar". By 2009 specialty drugs had started doubling in cost and payers such as employers began to question. Vogenberg observed that by 2014 health care reform had changed the landscape for specialty drugs. There is a shift away from a marketplace based on a predominately clinical perspective, to one that puts economics first and clinical second. Many factors contribute to the continuing increase in price of specialty drugs. Development of specialty drugs not only costs more, but they also take longer to develop than other large market pharmaceuticals (See Drug development). In addition, there are often fewer drug choices for rare or hard-to-treat diseases. This results in less competition in the marketplace for these drugs due to patent protection, which allows these firms to act as monopolists (See Drug Price Competition and Patent Term Restoration Act). Due to this lack of competition, policies that serve to limit prices in other markets can be ineffective or even counter-productive when applied to specialty drugs | https://en.wikipedia.org/wiki?curid=48172434 |
Specialty drugs in the United States High prices for specialty drugs are a problem for both patients and payers. Patients frequently have difficulty paying for these medications, which can lead to lack of access to treatment. Specialty drugs are now so expensive that they are leading to increases in insurance premiums. Control of specialty drug prices will require research to identify effective policy options, which may include: decreasing regulation, limiting patent protection, allowing negotiation of drug prices by Medicare, or pricing drugs based on their effectiveness. In the United States, private insurance payers will favour a lower-cost agent preferring generics and biosimilars to the more expensive specialty drugs if there is no peer-reviewed or evidence-based justification for them. According to a 2012 report by Sun Life Financial the average cost of specialty drug claims was $10,753 versus $185 for non-specialty drugs and the cost of specialty drugs continues to rise. With such steep prices by 2012 specialty drugs represented 15-20% of prescription drug reimbursement claims. Patient advocacy groups that lobby for payment for specialty drugs include the Alliance for Patient Access (AfPA), formed in 2006 and which according to a 2014 article in the "Wall Street Journal" "represents physicians and is largely funded by the pharmaceutical industry. The contributors mostly include brand-name drug makers and biotechs, but some—such as Pfizer and Amgen—are also developing biosimilars | https://en.wikipedia.org/wiki?curid=48172434 |
Specialty drugs in the United States " In 2013 AfPA director David Charles published an article on specialty drugs in which he agreed with the findings of the Congressional Budget Office that spending on prescription medications "saves costs in other areas of healthcare spending". He observed that specialty drugs are so high priced that many patients do not fill prescriptions resulting in more serious health problems increasing. His article referred to specialty drugs such as "new cancer drugs specially formulated for patients with specific genetic markers". He explained the high cost of these "individualized medications based on diagnostic testing; and "biologics", or medicines created through biologic processes, rather than chemically synthesized like most pharmaceuticals". He argued that there should be a slight increase in co-pays for the more commonly using lower-tier medications to allow a lower co-pay for those who "require high-cost specialty tier medications". According to the 2014 Express Scripts Drug Trend Report, the most significant increase in prescription drugs in the United States in 2014 was due to "increased inflation and utilization of hepatitis C and compounded medications". "Excluding those two therapy classes, overall drug spend would have increased only 6.4%. The cost of "the top three specialty therapy classes—inflammatory conditions, multiple sclerosis and oncology—contributed 55.9% of the spend for all specialty medications billed through the pharmacy benefit in 2014. The U.S. spent 742 | https://en.wikipedia.org/wiki?curid=48172434 |
Specialty drugs in the United States 6% more on hepatitis C medications in 2014 than it did in 2013; this therapy class was not among the top 10 specialty classes in 2013. As the market demanded specialization in drug distribution and clinical management of complex therapies, specialized pharma (SP) evolved. By 2001 CVS' specialty pharmacy ProCare was the "largest integrated retail/mail provider of specialty pharmacy services" in the United States. It was consolidated with their pharmacy benefit management company, PharmaCare in 2002 to In their 2001 annual report CVS anticipated that the "$16 billion specialty pharmacy market" would grow at "an even faster rate than traditional pharmacy due in large part to the robust pipeline of biotechnology drugs". By 2014 CVS Caremark, Express Scripts and Walgreens represented more than 50% of the specialty drug market in the United States. The specialty pharmacy business had $20 billion in sales in 2005. By 2014 it had grown to "$78 billion in sales". Specialty pharmacies came into existence to as a result of unmet needs. According to the National Comprehensive Cancer Network the "primary goals of specialty pharmacies are to ensure the appropriate use of medications, maximize drug adherence, enhance patient satisfaction through direct interaction with healthcare professionals, minimize cost impact, and optimize pharmaceutical care outcomes and delivery of information" | https://en.wikipedia.org/wiki?curid=48172434 |
Specialty drugs in the United States McKesson Specialty Care Solutions, a division of McKesson Corporation, is "one of the largest distributors of specialty drugs, biologics and rheumatology drugs to community-based specialty practices". It is "a leader in the development, implementation and management of FDA-mandated Risk Evaluation and Mitigation Strategies (REMS) for manufacturers". For example, in order ProStrakan Group plc, an international pharmaceutical company based in the UK works with McKesson Specialty Care Solutions to administer its FDA-approved Risk Evaluation and Mitigation Strategy (REMS) program for Abstral. URAC's Specialty Pharmacy Accreditation "provides an external validation of excellence in Specialty Pharmacy Management and provides Continuous Quality Improvement (CQI) oriented processes that improve operations and enhance compliance". Specialty pharmaceuticals or biologics are a significant part of the treatment market, yet there is still additional work that should be done to manage costs. Defining biologics has been described as a matter of perspective, with variation between chemists, physicians, payers, microbiologists and regulators. A payer may define a biologic by cost, while a biochemist may look at composition and structure and a provider at means of delivery or action on the body. The FDA generally defines biologics as, "a wide range of products [that] ...can be composed of sugars, proteins, or nucleic acids or complex combinations of these substances, or may be living entities such as cells and tissues | https://en.wikipedia.org/wiki?curid=48172434 |
Specialty drugs in the United States Biologics are isolated from a variety of natural sources—human, animal, or microorganism—and may be produced by biotechnology methods and other cutting-edge technologies". Due to the complexity, risk of adverse events and allergic reactions associated with biologics, management is very important for the safety of patients. Management includes areas from patient education and adherence to the delivery of the medication. These medications often require very specific storage conditions and monitoring of temperature, the level of agitation and proper reconstitution of the drug . Because of the high risk of error and adverse events, provider management of delivery is required, especially for injection or infusion of some biologic medications. Such biologics are often coded in a way that ties reimbursement to delivery by a provider—either a specialty pharmacist or medical care provider with those skills. As more biologics are being designed to be self-administered pharmacists are supporting the management of these drugs. They make calls to remind patients of the need for refills, provide education to patients, monitor patients for adverse events and work with primary care provider offices to monitor the outcomes of the medication. The high cost of specialty pharmaceuticals is one of their defining characteristics; as such, cost-containment is high on the list of all the players in the arena | https://en.wikipedia.org/wiki?curid=48172434 |
Specialty drugs in the United States For physician-administered biologics, cost-containment is often handled by volume purchasing of biologic drugs for discounted pricing, formularies, step therapy to attempt other treatment before beginning biologics and administrative fees by insurers to keep physicians from artificially inflating requested reimbursement from insurance companies. Cost-containment for self-administered biologics tends to occur via requiring authorization to be prescribed those drugs and benefit design, such as coinsurance for cost-sharing. The 21st Century Cures Act which addressed fast-tracking approval of specialty pharmaceuticals was particularly beneficial for dealing with the development of 2nd run biologics (which might be more easily understood as "generic biologics", though they do not exist). Debate around the act raised some important questions about the efficacy of biologics and their continued high costs. Some call for insurers to pay only the cost of production to manufacturers until the benefit of these biologics can be proven long-term, stating that insurers should not bear the full cost of products that may be unreliable or have only limited efficacy. Achieving this would require conducting studies that assess value, such as comparative effectiveness studies and using those studies to determine pricing | https://en.wikipedia.org/wiki?curid=48172434 |
Specialty drugs in the United States Comparative effectiveness would examine all aspects of the use of biologics, from outcomes such as clinical benefits and potential harms, to efficiency of administration, public health benefits and patient productivity after treatment. This is a new direction in managing the high costs of specialty pharmaceuticals and not without challenges. One of the barriers is strict regulation by the Food and Drug Administration of what pharmaceutical manufacturers may communicate to the public, limiting that communication to formulary committees for managed care, for example. Additionally, studies tend to be constructed using observational design, instead of as randomized controlled trials, limiting their usefulness for real-world application. Difficulties experienced with patient adherence to specialty pharmaceuticals also limit the availability of real-world outcomes data for biologics. In 2016, real world data evaluating the efficacy of biologics was only publicly available for multiple myeloma through ICER (where biologics were found to be overpriced for their outcomes) and for hepatitis C treatment (which achieved high cure rates—90%—for patients co-infected with HIV and Hep C) through Curant Health. These studies show how useful value-based pricing may become for cost-containment in the field. The good news is that there are effectiveness studies on biologics currently underway aiming to provide more of this data | https://en.wikipedia.org/wiki?curid=48172434 |
Specialty drugs in the United States Biologics or biological products for human use are regulated by the Center for Biologics Evaluation and Research (CBER), overseen by the Office of Medical Products and Tobacco, within the U.S. Food and Drug Administration which includes the Public Health Service Act and the Federal Food, Drug and Cosmetic Act. "CBER protects and advances the public health by ensuring that biological products are safe and effective and available to those who need them. CBER also provides the public with information to promote the safe and appropriate use of biological products." There are multiple players in specialty drugs including the employer, the health plan, the pharmacy benefits manager and it is unclear who should be in charge of controlling costs and monitoring care. Pharmacies generally buy a product from a wholesaler and sell (Buy & Bill) it to the patient and provide basic drug use information and counseling. According to Maria Hardin, vice president of patient services for the National Organization for Rare Disorders, an alliance of voluntary health and patient advocacy groups working with rare diseases, "As the cost of drugs increases, management of the financial side has gotten more complex... The issues range from Medicare Part D to tiered benefits, prior authorizations, and no benefits. These patients need a pharmacy with the expertise and the clout to go to bat for them. If the patient doesn't get treated, the specialty pharmacy doesn't get paid | https://en.wikipedia.org/wiki?curid=48172434 |
Specialty drugs in the United States " Alexion Pharmaceuticals was one of the pioneers in the use of a business model of developing drugs to combat rare diseases. "Knowing the value of specialty drugs as well as its own stock is Alexion's business." Since other big pharmaceutical companies had tended to ignore these markets, Alexion had minimal competition at first. Insurance companies have generally been willing to pay high prices for such drugs; since few of their customers need the drugs, a high price does not significantly impact the insurance companies outlays. Alexion is thus seeking a stronger position in the lucrative rare disease market, and is willing to pay a premium to obtain that position. The rare disease market is seen as desirable because insurers have minimal motive to deny claims (due to small population sizes of patients) and are unable to negotiate better drug prices due to lack of competition. of May 2015, Alexion is currently seeking approval of its second drug, Strensiq. It will be used to treat hypophosphatasia, a rare metabolic disorder. In 2015 Alexion estimated that Synageva, its specialty drug for lysosomal acid lipase deficiency, a fatal genetic disorder, could eventually have annual sales of more than $1 billion. Companies like Magellan RX Management provide a "single source for high-touch patient care management to control side effects, patient support and education to ensure compliance or continued treatment, and specialized handling and distribution of medications directly to the patient or care provider | https://en.wikipedia.org/wiki?curid=48172434 |
Specialty drugs in the United States Specialty medications may be covered under either the medical or pharmacy benefit." According to an article published in 2014 in the journal "Pharmacoeconomics", "[s]pecialty pharmacies combine medication dispensing with clinical disease management. Their services have been used to improve patient outcomes and contain costs of specialty pharmaceuticals. These may be part of independent pharmacy businesses, retail pharmacy chains, wholesalers, pharmacy benefit managers, or health insurance companies. Over the last several years, payers have been transitioning to obligate beneficiaries to receive self-administered agents from contracted specialty pharmacies, limiting the choice of acceptable specialty pharmacy providers (SPPs) for patient services." Managed care organizations contract with Specialty Pharmacy vendors. "Managed care organizations (MCOs) are using varied strategies to manage utilization and costs. For example, 58% of 109 MCOs surveyed implement prior authorizations for MS specialty therapies." The Academy of Managed Care Pharmacy (AMCP) designates a product as a specialty drug if "[i]t requires a difficult or unusual process of delivery to the patient (preparation, handling, storage, inventory, distribution, Risk Evaluation and Mitigation Strategy (REMS) programs, data collection, or administration) or, Patient management prior to or following administration (monitoring, disease or therapeutic support systems)" | https://en.wikipedia.org/wiki?curid=48172434 |
Specialty drugs in the United States Health plans consider "high cost" (on average a minimum monthly costs of $US1,200) to be is a determining factor in identifying a specialty drug. Tom Westrich, of St. Louis, Missouri-based Centric Health Resources, a specialty pharmacy, described how their specialty drugs treat ultra-orphan diseases with a total patient population of 20,000 nationwide. The top ten specialty pharmacies in 2014 were CVS Specialty parent company CVS Health with $20.5B in sales, Express Scripts's Accredo at $15B, Walgreens Boots Alliance's Walgreens Specialty at $8.5B, UnitedHealth Group's OptumRx at $2.4B, Diplomat Pharmacy at $2.1B, Catamaran's BriovaRx at $2.0B, Specialty Prime Therapeutics's Prime Therapeutics at $1.8B, Omnicare's Advanced Care Scripts at $1.3B, Humana's RightsourceRx at $1.2B, Avella at $0.8B. All the other specialty pharmacies accounted for $22.4B of sales in 2014 with a total of $78B. In 2010 the United States enacted a new health law which had unintended consequences. Because of the 2010 law, drug companies like Genentech informed children's hospitals that they would no longer get discounts for certain cancer medicines such as the orphan drugs Avastin, Herceptin, Rituxan, Tarceva, or Activase. This cost hospitals millions of dollars. There is a debate about whether specialty drugs should be managed as a medical benefit or a pharmaceutical benefit. Infused or injected medications are usually covered under the medical benefit and oral medications are covered under the pharmacy benefit | https://en.wikipedia.org/wiki?curid=48172434 |
Specialty drugs in the United States Self-injected medications may be either. "Many biologics, such as chemotherapy drugs, are administered in a doctor's office and require extensive monitoring, further driving up costs." Chemotherapy is usually delivered intravenously, although a number of agents can be administered orally (e.g. specialty drugs, melphalan (trade name Alkeran), busulfan, capecitabine). Delcath Systems, Inc. (NASDAQ: DCTH) a specialty pharmaceutical and medical device company manufactures melphalan. By 2011 the oral medications for cancer patients represented approximately 35% of cancer medications. Prior to the increase in cancer oral drugs community cancer centers were used to managing office-administered chemotherapy treatments. At that time "the majority of community oncology practices were unfamiliar with the process of prescribing and obtaining drugs that are covered under the pharmacy benefit" and "conventional retail pharmacy chains were ill-prepared to stock oral oncology agents, and were not set up to deliver the counseling that often accompanies these medications". According to IMS Health "Specialty pharmaceutical spending is on the rise and is expected to increase from approximately $55 billion in 2005 to $1.7 trillion in 2030, according to the Pharmaceutical Care Management Association. That reflects an increase from 24% of total drug spend in 2005 to an estimated 44% of a health plan's total drug expenditure in 2030 | https://en.wikipedia.org/wiki?curid=48172434 |
Specialty drugs in the United States " While CVS, Accredo, and Walgreens led the Specialty Pharmacies (SP) market in revenue in 2014, there are constant changes through mergers and acquisitions in terms of SPs and specialty distributors (SDs). The SP/SD network faces common strengths such as "in-depth clinical management, coordinated/comprehensive care, and early limited distribution network success" and common weaknesses, "lack of ability to customize services, poor integration experience and outcomes, and strained pharma relations". BioScrip was acquired by Walgreens in 2012. Specialty companies like Genzyme and MedImmune were acquired and are transitioning to a new business model. According to Nicolas Basta, by 2013 there was "a spate of new entities" called hub services, "mechanisms by which manufacturers can keep a grip on the marketplace" in specialty pharma. The "biggest and oldest of these organizations" are "offshoots of insurance companies or [Pharmacy benefit managers] PBMs, such as Express Scripts' combination of Accredo and CuraScript (both specialty pharmacies) and HealthBridge (physician and patient support). UnitedHealth, an insurance company, operates OptumRx, a PBM, which has a specialty unit within it. Cigna has Tel-Drug, a mail-order pharmacy and support system | https://en.wikipedia.org/wiki?curid=48172434 |
Specialty drugs in the United States " Basta described how Hubs have been around since about 2002 "starting out as "reimbursement hubs"", usually provided as a service by manufacturers to help patients and providers navigate the process of obtaining permission to use, and reimbursement for, expensive specialty therapies". Industry observers look to pioneering efforts by Genentech and Genzyme under the tenure of Henri Termeer, "when some of their earliest biotech products entered the marketplace". Specialty hubs provide reimbursement support to physicians and patients as well as patient education including medical hotlines. There is a voluntary program enrollment and registry intake with Patient Assistance Program management. According to a 2007 study by employees of Express Scripts or its wholly owned subsidiary CuraScript on specialty pharmacy costs, if payers manage cost control through copayments with patients, there is an increased risk that patients will forego essential but expensive specialty drugs. and health outcomes were compromised. In 2007 these researchers suggested in the adoption of formularies and other traditional drug-management tools. They also recommended specialty drug utilization management programs that guide treatment plans and improve outpatient compliance. By 2010 Alexion Pharmaceuticals's Soliris, was considered to be the most expensive drug in the world. In a 2012 article in the "New York Times," journalist Andrew Pollack described how Don M | https://en.wikipedia.org/wiki?curid=48172434 |
Specialty drugs in the United States Bailey, a mechanical engineer by training who became interim president of Questcor Pharmaceuticals, Inc. (Questcor) in May 2007, initiated a new pricing model for Acthar in August 2007 when it was classified by FDA as an orphan drug and a specialty drug to treat infantile spasms. Questcor, a biopharmaceutical company, focuses on the treatment of patients with "serious, difficult-to-treat autoimmune and inflammatory disorders". Its primary product is FDA-approved Acthar, an injectable drug that is used for the treatment of 19 indications. At the same time Questcor created "an expanded safety net for patients using Acthar", provided a "group of Medical Science Liaisons to work with health care providers who are administering Acthar" and limited distribution to its sole specialty distributor, Curascript. The 2007 pricing model brought "Acthar in line with the cost of treatments for other very rare diseases". The cost for a course of treatment in 2007 was estimated at about "$80,000–$100,000". Acthar is now manufactured through a contractor on Prince Edward Island, Canada. The price increased from $40 a vial to $700 and continued to increase. By 2012 the price of a vial of Acthar was $28,400. and was considered to be one of the world's most expensive drugs in 2013. By 2014 the price of Gilead's specialty drug for hepatitis C, Sovaldi or "sofosbuvir", was $84,000 to $168,000 for a course of treatment in the U.S., £35,000 in the UK for 12 weeks | https://en.wikipedia.org/wiki?curid=48172434 |
Specialty drugs in the United States Sovaldi is on the World Health Organization's most important medications needed in a basic health system and the steep price is highly controversial. In 2014 the U.S. spent 742.6% more on hepatitis C medications than it did in 2013. In September 2015, Martin Shkreli was criticized by several health organizations for obtaining manufacturing licenses on old, out-of-patent, life-saving medicines including pyrimethamine (brand name "Daraprim"), which is used to treat patients with toxoplasmosis, malaria, some cancers, and AIDS, and then increasing the price of the drug in the US from $13.50 to $750 per pill, a 5,455% increase. In an interview with "Bloomberg News", Shkreli claimed that despite the price increase, patient co-pays would be lower, that many patients would get the drug at no cost, that the company has expanded its free drug program, and that it sells half of the drugs for one dollar. In 2015 Bloomberg News used the term 'captive pharmacies' to describe the alleged exclusive agreements such as that between the specialty mail-order pharmacy Philodor and Valeant, mail-order pharmacy Linden Care and Horizon Pharma Plc. In November 2015 Express Scripts Holding Co.—the largest U.S. manager of prescription drug benefits—"removed the mail-order pharmacy Linden Care LLC from its network after concluding it dispensed a large portion of its medications from Horizon Pharma Plc and didn't fulfill its contractual agreements" | https://en.wikipedia.org/wiki?curid=48172434 |
Specialty drugs in the United States Express Scripts was "evaluating other 'captive pharmacies' that it said are mostly distributing Horizon drugs". In 2015 specialty pharmacies like "Philidor drew attention for the lengths they went to fill prescriptions with brand-name drugs and then secure insurance reimbursement. According to Pfenex, a clinical-stage biotechnology company, the proposed terms in the Trans-Pacific Partnership, a trade agreement between twelve Pacific Rim countries, meant that all participating countries had to adopt the United States' lengthy drug patent exclusivity protection period of 12 years for biologics and specialty drugs. In 1981 an episode of the television series "Quincy, M.E." starring star, Jack Klugman as Quincy, entitled "Seldom Silent, Never Heard" brought the plight of children with orphan diseases to public attention. In the episode, Jeffrey, a young boy with Tourette syndrome, died after falling from a building. Dr. Arthur Ciotti (Michael Constantine), a medical doctor who had been researching Tourette syndrome for years wanted to study Jeffrey's brain to discover the cause and cure for the rare disease. He explained to Quincy that drug companies, like the one where he worked, were not interested in doing the research because so few people were afflicted with them that it was not financially viable. In 1982 another episode "Give Me Your Weak" Klugman as Quincy testified before Congress in an effort to get the Orphan Drug Act passed. He was moved by the dilemma of a young mother with myoclonus. | https://en.wikipedia.org/wiki?curid=48172434 |
Alla Masevich Alla Genrikhovna Masevich (October 9, 1918 — May 6, 2008) was a Soviet astronomer. She graduated from Moscow State Pedagogical University. She served as deputy chairman of the Astronomical Council of the Academy of Sciences of the USSR in 1952, and worked closely with Victor Ambartsumian. She became a professor of space geodesy at the Moscow Institute of Geodesy and Cartography in 1972. She is known for her work in organizing groups to observe some of the first Russian satellites (1956–57). Masevitch was the Russian delegate to the International Astronautical Federation Congress following the 1957 Sputnik launch and presented a paper on optical tracking of satellites. From 1952 to 1987 she held the prestigious position of Deputy Chairman of the Astronomical Council of the Akademiya Nauk Sovestskogo Soyuza. During her tenure at the Academy, she led a team in 1957 to monitor Soviet satellites which included Sputnik. In 1987 she left the Academy to become Chairman of the Astrosoviets, the Astronomical Council of the Academy of Sciences USSR. (or Massevitch) was born in Tbilisi as the eldest child of Natalia A. Zhgenti, a Georgian nurse, and Genrikh C. Massevitch, a lawyer. Masevich married Josif N. Friedlander and they had one daughter together, Natasha Josifovna Friedlander. | https://en.wikipedia.org/wiki?curid=48201018 |
List of the physiographic regions of the world The landforms of the Earth are generally divided into physiographic divisions, consisting of physiographic provinces, which in turn consist of physiographic sections, though some others use different terminology, such as realms, regions and sub-regions. Some areas have further categorized their respective areas into more detailed sub-sections. | https://en.wikipedia.org/wiki?curid=48201744 |
Collage (geology) In geology a collage is a tectonostratigraphic unit characterized by its heterogeneity in terms of its lithology, rock ages, or both. The term is usually applied to Precambrian tectonostratigraphic units. Collages form by plate tectonic processes like accretion and continental collision. | https://en.wikipedia.org/wiki?curid=48215783 |
NGC 120 is a lenticular galaxy of type SB0? pec? with an apparent magnitude of 13.4 located in the constellation Cetus. It was descovered on 27 September 1880 by Wilhelm Tempel. | https://en.wikipedia.org/wiki?curid=48221740 |
William Andrew Clark Dr FRSE (1911-1983) was a Scottish botanist known for collections largely in the Outer Hebrides. He was an expert on spermatophytes and the flora of north-east England. He was born in Girvan in Ayrshire the son of Thomas Clark. He attended Alva Academy 1916-1923 and then Harris Academy in Dundee 1923–1929. He attended St Andrews University gaining a BSc in 1932 and a PhD in 1936. He lectured in Botany firstly at Liverpool University then at Newcastle University until retiring in 1976. He was elected a Fellow of the Royal Society of Edinburgh in 1957. He died in Ryton, Tyne and Wear on 19 November 1983. He married Helena Heslop-Harrison, daughter of John William Heslop-Harrison FRSE in 1941. | https://en.wikipedia.org/wiki?curid=48246659 |
Chromogen The term chromogen is applied in chemistry to a colourless (or weakly coloured) chemical compound that can be converted by chemical reaction into a compound which can be described as "coloured". There is no universally agreed definition of the term. Various dictionaries give the following definitions: In biochemistry the term has a rather different meaning. The following are found in various dictionaries. | https://en.wikipedia.org/wiki?curid=48248326 |
Phase stretch transform (PST) is a computational approach to signal and image processing. One of its utilities is for feature detection and classification. PST is related to time stretch dispersive Fourier transform. It transforms the image by emulating propagation through a diffractive medium with engineered 3D dispersive property (refractive index). The operation relies on symmetry of the dispersion profile and can be understood in terms of dispersive eigenfunctions or stretch modes. PST performs similar functionality as phase-contrast microscopy, but on digital images. PST can be applied to digital images and temporal (time series) data. Here the principle is described in the context of feature enhancement in digital images. The image is first filtered with a spatial kernel followed by application of a nonlinear frequency-dependent phase. The output of the transform is the phase in the spatial domain. The main step is the 2-D phase function which is typically applied in the frequency domain. The amount of phase applied to the image is frequency dependent, with higher amount of phase applied to higher frequency features of the image. Since sharp transitions, such as edges and corners, contain higher frequencies, PST emphasizes the edge information. Features can be further enhanced by applying thresholding and morphological operations. PST is a pure phase operation whereas conventional edge detection algorithms operate on amplitude | https://en.wikipedia.org/wiki?curid=48249441 |
Phase stretch transform Photonic time stretch technique can be understood by considering the propagation of an optical pulse through a dispersive fiber. By disregarding the loss and non-linearity in fiber, the non-linear Schrödinger equation governing the optical pulse propagation in fiber upon integration reduces to: formula_1 (1) where formula_2 =GVD parameter, z is propagation distance, formula_3 is the reshaped output pulse at distance z and time t. The response of this dispersive element in the time-stretch system can be approximated as a phase propagator as presented in formula_4 (2) <br> Therefore, Eq. 1 can be written as following for a pulse that propagates through the time-stretch system and is reshaped into a temporal signal with a complex envelope given by <br> formula_5 (3) <br> The time stretch operation is formulated as generalized phase and amplitude operations, <br> formula_6 (4) where formula_7 is the phase filter and formula_8is the amplitude filter. Next the operator is converted to discrete domain, <br> formula_9 (5) <br> where formula_10 is the discrete frequency, formula_11 is the phase filter, formula_12 is the amplitude filter and FFT is Fast Fourier Transform. The Stretch operator formula_13 for a digital image is then <br> formula_14 (6) In the above equations, formula_15 is the input image, formula_16 and formula_17 are the spatial variables, formula_18 is the two dimensional Fast Fourier Transform, and formula_19 and formula_20 are spatial frequency variables | https://en.wikipedia.org/wiki?curid=48249441 |
Phase stretch transform The function formula_21 is the warped phase kernel and the function formula_22 is a localization kernel implemented in frequency domain. PST operator is defined as the phase of the Warped Stretch Transform output as follows formula_23 (7) where formula_24is the angle operator. PST has been used for edge detection in biological and biomedical images as well as synthetic-aperture radar (SAR) image processing. PST has also been applied to improve the point spread function for single molecule imaging in order to achieve super-resolution. The transform exhibits intrinsic superior properties compared to conventional edge detectors for feature detection in low contrast visually impaired images. The PST function can also be performed on 1-D temporal waveforms in the analog domain to reveal transitions and anomalies in real time. On February 9, 2016, a UCLA Engineering research group has made public the computer code for PST algorithm that helps computers process images at high speeds and "see" them in ways that human eyes cannot. The researchers say the code could eventually be used in face, fingerprint, and iris recognition systems for high-tech security, as well as in self-driving cars' navigation systems or for inspecting industrial products. Matlab and Python implementation for PST is available for free download from our Github Repository. The Matlab implementation for PST can also be downloaded from Matlab Files Exchange | https://en.wikipedia.org/wiki?curid=48249441 |
Phase stretch transform However, it is provided for research purposes only, and a license must be obtained for any commercial applications. The software is protected under a US patent. | https://en.wikipedia.org/wiki?curid=48249441 |
Pursuit predation is a form of predation in which predators give chase to fleeing prey. The chase can be initiated either by the predator or by the prey, should the prey be alerted to a predator's presence and attempt to flee before the predator gives chase. The chase ends when either the predator captures and consumes the prey, or the prey escapes. is typically observed in carnivorous species within the kingdom Animalia, with some iconic examples being cheetahs, lions, and wolves. is an alternate predation strategy to ambush predation. While pursuit predators use a detection and pursuit phase in order to obtain prey, ambush predators use stealth to capture prey. Strength and speed are important to pursuit predators, whereas ambush predators ignore these in favor of surprise from a typically concealed location. While the two patterns of predation are not mutually exclusive, morphological differences in body plan can create a bias in an organism towards each type of predation. One particular form of pursuit predation is persistence hunting, and some animals are examples of both types of predator. There is still uncertainty as to whether predators behave with a general tactic or strategy while preying. However, among pursuit predators, there are several common behaviors. Often, predators will scout potential prey, assessing prey quantity and density prior to engaging in a pursuit. Certain predators choose to pursue prey primarily in a group of conspecifics; such animals are known as pack hunters or group pursuers | https://en.wikipedia.org/wiki?curid=48264022 |
Pursuit predation Other species choose to hunt alone. These two behaviors are typically due to differences in hunting success, where some groups are very successful in groups and others are more successful alone. Pursuit predators may also choose to either exhaust their metabolic resources rapidly or pace themselves during a chase. This choice can be influenced by prey species, seasonal settings, or temporal settings. Predators that rapidly exhaust their metabolic resources during a chase tend to first stalk their prey, slowly approaching their prey to decrease chase distance and time. When the predator is at a closer distance (one that would lead to easier prey capture), it finally gives chase. Pacing pursuit is more commonly seen in group pursuit, as individual animals do not need to exert as much energy to capture prey. However, this type of pursuit requires group coordination, which may have varying degrees of success. Since groups can engage in longer chases, they often focus on separating a weaker or slower prey item during pursuit. Morphologically speaking, while ambush predation requires stealth, pursuit predation requires speed; pursuit predators are proportionally long-limbed and equipped with cursorial adaptations. Current theories suggest that this proportionally long-limbed approach to body plan was an evolutionary countermeasure to prey adaptation. Group pursuers hunt with a collection of conspecifics | https://en.wikipedia.org/wiki?curid=48264022 |
Pursuit predation Group pursuit is usually seen in species of relatively high sociality; in vertebrates, individuals often seem to have defined roles in pursuit. African wild dog ("Lycaon pictus") packs have been known to split into several smaller groups while in pursuit; one group initiates the chase, while the other travels ahead of the prey's escape path. The group of chase initiators coordinate their chase to lead the prey towards the location of the second group, where the prey's escape path will be effectively cut off. Bottlenose dolphins ("Tursiops") have been shown exhibiting similar behaviors of pursuit role specialization. One group within the dolphin pod, known as the drivers, give chase to the fish - forcing the fish into a tight circle formation, while the other group of the pod, the barriers, approach the fish from the opposite direction. This two-pronged attack leaves the fish with only the option of jumping out of the water to escape the dolphins. However, the fish are completely vulnerable in the air; it is at this point when the dolphins leap out and catch the fish. In lion ("Panthera leo") pack hunting, each member of the hunting group is assigned a position, from left wing to right wing, in order to better obtain prey. Such specializations in roles within the group are thought to increase sophistication in technique; lion wing members are faster, and will drive prey toward the center where the larger, stronger, killing members of the pride will take down the prey | https://en.wikipedia.org/wiki?curid=48264022 |
Pursuit predation Many observations of group pursuers note an optimal hunting size in which certain currencies (mass of prey killed or number of prey killed) are maximized with respect to costs (kilometers covered or injuries sustained). Groups size is often dependent on aspects of the environment: number of prey, prey density, number of competitors, seasonal changes, etc. While birds are generally believed to be individual hunters, there are a few examples of birds that cooperate during pursuits. Harris's hawks ("Parabuteo unicinctus") have two cooperative strategies for hunting: Surrounding and cover penetration, and long chase relay attack. The first strategy involves a group of hawks surrounding prey hidden under some form of cover, while another hawk attempts to penetrate the prey's cover. The penetration attempt flushes the prey out from its cover where it is swiftly killed by one of the surrounding hawks. The second strategy is less commonly used: It involves a "relay attack" in which a group of hawks, led by a "lead" hawk, engage in a long chase for prey. The "lead" hawk will dive in order to kill the prey. If the dive is unsuccessful, the role of the "lead" shifts to another hawk who will then dive in another attempt to kill the prey. During one observed relay attack, 20 dives and hence 20 lead switches were exhibited | https://en.wikipedia.org/wiki?curid=48264022 |
Pursuit predation As in vertebrates, there are many species of invertebrates which actively pursue prey in groups and exhibit task specialization, but while the vertebrates change their behavior based on their role in hunting, invertebrate task delegation is usually based on actual morphological differences. The vast majority of eusocial insects have castes within a population which tend to differ in size and have specialized structures for different tasks. This differentiation is taken to the extreme in the groups isoptera and hymenoptera, or termites and ants, bees, and wasps respectively. Termite-hunting ants of the genus "Pachycondyla", also known as Matabele ants, form raiding parties consisting of ants of different castes, such as soldier ants and worker ants. Soldier ants are much larger than worker ants, with more powerful mandibles and more robust exoskeletons, and so they make up the front lines of raiding parties and are responsible for killing prey. Workers usually butcher and carry off the killed prey, while supporting the soldiers. The raiding parties are highly mobile and move aggressively into the colonies of termites, often breaking through their outer defenses and entering their mounds. The ants do not completely empty the mound of termites, instead they only take a few, allowing the termites to recover their numbers so that the ants have a steady stream of prey. Asian giant hornets, "Vespa mandarinia", form similar raiding parties to hunt their prey, which usually consists of honeybees | https://en.wikipedia.org/wiki?curid=48264022 |
Pursuit predation The giant hornets group together and as a team can decimate an entire honeybee colony, especially those of non-native European honeybees. Alone, the hornets are subject to attack by the smaller bees, who swarm the hornet and vibrate their abdomens to generate heat, collectively cooking the hornet until it dies. By hunting in groups, the hornets avoid this problem. While most big cat species are individual, ambush predators, Cheetahs ("Acinonyx jubatus") are pursuit predators. Widely known as the fastest terrestrial animal, with speeds reaching 61–64 miles per hour, cheetahs take advantage of their speed during chases. However, their speed and acceleration also have disadvantages, as both can only be sustained for short periods of time. Studies show that cheetahs can maintain maximum speed for a distance of approximately 500 yards. Due to these limitations, cheetahs are often observed running at moderate speeds during chases. There are claims that the key to cheetahs' pursuit success may not be just their speed. Cheetahs are extremely agile, able to maneuver and change directions at very high speeds in very short amounts of time. This extensive maneuverability can make up for unsustainable high speed pursuit, as it allows cheetahs to quickly close the distance between prey without decreasing their speed when prey change direction. The Painted redstart ("Myioborus pictus") is one of the most well documented flush pursuers | https://en.wikipedia.org/wiki?curid=48264022 |
Pursuit predation When flies, prey for redstarts, are alerted of the presence of predators, they respond by fleeing. Redstarts take advantage of this anti-predator response by spreading and orienting their easily noticeable wings and tails, alerting the flies, but only when they are in a position where the flies' escape path intersects with the redstart's central field of vision. When prey's path are in this field of vision, the redstart's prey capture rate is at its maximum. Once the flies begin to flee, the redstart begins to chase. It has been proposed that redstarts exploit two aspects of the visual sensitivity of their prey: sensitivity to the location of the stimulus in the prey's visual field and sensitivity to the direction of stimulus environment. The effectiveness of this pursuit can also be explained by "rare enemy effect", an evolutionary consequence of multi-species predator-prey interactions. Dragonflies are skilled aerial pursuers; they have a 97% success rate for prey capture. This success rate is a consequence of the "decision" on which prey to pursue, based on initial conditions. Observations of several species of perching dragonflies show more pursuit initiations at larger starting distances for larger size prey species than for much smaller prey. Further evidence points to a potential bias towards larger prey, due to more substantial metabolic rewards. This bias is in spite of the fact that larger prey are typically faster and choosing them results in less successful pursuits | https://en.wikipedia.org/wiki?curid=48264022 |
Pursuit predation Dragonflies high success rate for prey capture may also be due to their interception foraging method. Unlike classical pursuit, in which the predator aims for the current position of their prey, dragonflies predict the prey's direction of motion, as in parallel navigation. Perching dragonflies (Libellulidae family), have been observed "staking out" high density prey spots prior to pursuit. There are no noticeable distinctions in prey capture efficiency between males and females. Further, percher dragonflies are bound by their visual range. They are more likely to engage in pursuit when prey come within a subtended angle of around 1-2 degrees. Angles greater than this are outside of a dragonflies visual range. Current theory on the evolution of pursuit predation suggests that the behavior is an evolutionary countermeasure to prey adaptation. Prey animals vary in their likelihood to avoid predation, and it is predation failure that drives evolution of both prey and predator. Predation failure rates vary wildly across the animal kingdom; raptorial birds can fail anywhere from 20% to 80% of the time in predation, while predatory mammals usually fail more than half the time. Prey adaptation drives these low rates in three phases: the detection phase, the pursuit phase, and the resistance phase. The pursuit phase drove the evolution of distinct behaviors for pursuit predation | https://en.wikipedia.org/wiki?curid=48264022 |
Pursuit predation As selective pressure on prey is higher than on predators adaptation usually occurs in prey long before the reciprocal adaptations in predators. Evidence in the fossil record supports this, with no evidence of modern pursuit predators until the late Tertiary period. Certain adaptations, like long limbs in ungulates, that were thought to be adaptive for speed against predatory behavior have been found to predate predatory animals by over 20 million years. Because of this, modern pursuit predation is an adaptation that may have evolved separately and much later as a need for more energy in colder and more arid climates. Longer limbs in predators, the key morphological adaptation required for lengthy pursuit of prey, is tied in the fossil record to the late Tertiary. It is now believed that modern pursuit predators like the wolf and lion evolved this behavior around this time period as a response to ungulates increasing feeding range. As ungulate prey moved into a wider feeding range to discover food in response to changing climate, predators evolved the longer limbs and behavior necessary to pursue prey across larger ranges. In this respect, pursuit predation is not co-evolutionary with prey adaptation, but a direct response to prey. Prey's adaptation to climate is the key formative reason for evolving the behavior and morphological necessities of pursuit predation | https://en.wikipedia.org/wiki?curid=48264022 |
Pursuit predation In addition to serving as a countermeasure to prey adaptation, pursuit predation has evolved in some species as an alternative, facultative mechanism for foraging. For example, polar bears typically act as specialized predators of seal pups and operate in a manner closely predicted by the optimal foraging theory. However, they have been seen to occasionally employ more energy-inefficient pursuit predation tactics on flightless geese. This alternative predatory strategy may serve as a back-up resource when optimal foraging is circumstantially impossible, or may even be a function of filling dietary needs. revolves around a distinct movement interaction between predator and prey; as prey move to find new foraging areas, predators should move with them. Predators congregate in areas of high prey density, and prey should therefore avoid these areas. However, dilution factor may be a reason to stay in areas of high density due to a decreased risk of predation. Given the movements of predators over ranges in pursuit predation, though, dilution factor seems a less important cause for predation avoidance. Because of these interactions, spatial patterns of predators and prey are important in preserving population size. Attempts by prey to avoid predation and find food are coupled with predator attempts to hunt and compete with other predators. These interactions act to preserve populations | https://en.wikipedia.org/wiki?curid=48264022 |
Pursuit predation Models of spatial patterns and synchrony of predator-prey relationships can be used as support for the evolution of pursuit predation as one mechanism to preserve these population mechanics. By pursuing prey over long distances, predators actually improve longterm survival of both their own population and prey population through population synchrony. acts to even out population fluctuations by moving predatory animals from areas of high predator density to low predator density, and low prey density to high prey density. This keeps migratory populations in synchrony, which increases metapopulation persistence. Pursuit predation’s effect on population persistence is more marked over larger travel ranges. Predator and prey levels are usually more synchronous in predation over larger ranges, as population densities have more ability to even out. can then be supported as an adaptive mechanism for not just individual feeding success but also metapopulation persistence. Just as the evolutionary arms race has led to the development of pursuit behavior of predators, so too has it led to the anti-predator adaptations of prey. Alarm displays such as eastern swamphen's tail flicking, white-tailed deer's tail flagging, and Thomson's gazelles' stotting have been observed deterring pursuit. These tactic are believed to signal that a predator's presence is known and, therefore, pursuit will be much more difficult. These displays are more frequent when predators are at an intermediate distance away | https://en.wikipedia.org/wiki?curid=48264022 |
Pursuit predation Alarm displays are used more often when prey believe predators are more prone to change their decision to pursue. For instance, cheetahs, common predators of Thomson's gazelles, are less likely to change their choice to pursue. As such, gazelles stott less when cheetahs are present than when other predators are present. In addition to behavioral adaptations, there are also morphological anti-predator adaptations to pursuit predators. For example, many birds have evolved rump feathers that fall off with much less force than the feathers of their other body parts. This allows for easier escape from predator birds, as avian predators often approach prey from their rump. In many species that fall prey to pursuit predation, gregariousness on a massive scale has evolved as a protective behavior. Such herds can be conspecific (all individuals are of one species) or heterospecific. This is primarily due to the confusion effect, which states that if prey animals congregate in large groups, predators will have more difficulty identifying and tracking specific individuals. This effect has greater influence when individuals are visually similar and less distinguishable. In groups where individuals are visually similar, there is a negative correlation between group size and predator success rates. This may mean that the overall number of attacks decreases with larger group size or that the number of attacks per kill increases with larger group size | https://en.wikipedia.org/wiki?curid=48264022 |
Pursuit predation This is especially true in open habitats, such as grasslands or open ocean ecosystems, where view of the prey group is unobstructed, in contrast to a forest or reef. Prey species in these open environments tend to be especially gregarious, with notable examples being starlings and sardines. When individuals of the herd are visually dissimilar, however, the success rate of predators increases dramatically. In one study, wildebeest on the African Savannah were selected at random and had their horns painted white. This introduced a distinction, or oddity, into the population; researchers found that the wildebeest with white horns were preyed upon at substantially higher rates. By standing out, individuals are not as easily lost in the crowd, and so predators are able to track and pursue them with higher fidelity. This has been proposed as the reason why many schooling fish show little to no sexual dimorphism, and why many species in heterospecific schools bear a close resemblance to other species in their school. | https://en.wikipedia.org/wiki?curid=48264022 |
Roger J. Thomas was a solar physicist who worked at NASA for many years. He was an internationally recognized expert on the design of extreme ultraviolet spectrographs, and received the prestigious NASA Exceptional Service Medal in 2009. | https://en.wikipedia.org/wiki?curid=48284793 |
List of bacterial disulfide oxidoreductases Bacterial "thiol disulfide oxidoreductases (TDOR)" are bacterial enzymes which, along with unfolded proteins, are pumped out of a bacterial cell that allow for adhesion and biofilm development, and generally disease development. | https://en.wikipedia.org/wiki?curid=48317392 |
Yttrogummite is a yttrium-bearing variety of gummite mineral. It is a rare earth mineral containing relatively large amounts of the yttrium earths. It is an alteration product of yttrian uraninite. It was first described by Adolf Erik Nordenskiöld, who discovered it in Arendal, Norway in 1870s. | https://en.wikipedia.org/wiki?curid=48374150 |
Mahendra Verma Mahendra Kumar Verma (born 27 May 1966) is an Indian physicist and professor at the Indian Institute of Technology Kanpur who works on fluid dynamics, turbulence, and nonlinear dynamics. Verma earned his bachelor's degree in computer science from the Indian Institute of Technology Madras in 1988, and a Ph.D. in physics from the University of Maryland, College Park in 1994. He was awarded the Swarnajayanti Fellowship by the Department of Science and Technology, Government of India in 2006, and the Dr. A. P. J. Abdul Kalam Cray HPC award, which honors high-performance computing contributions from India, in 2018. He is also an elected fellow of the Indian National Science Academy and the Indian Academy of Sciences. | https://en.wikipedia.org/wiki?curid=48382174 |
Irina Veretennicoff is a physicist, honorary professor of the Vrije Universiteit Brussel. Veretennicoff graduated in Physics from the Vrije Universiteit Brussel (VUB) in 1973 with a doctorate under the guidance of Radu Balescu of Université libre de Bruxelles (ULB). has been an honorary member of the Class of Natural Sciences Royal Flemish Academy of Belgium for Science and the Arts since 1998. | https://en.wikipedia.org/wiki?curid=48388763 |
Structure function The structure function (also known as the proton structure function), like the fragmentation function, is a probability density function. It is somewhat analogous to the structure factor in solid-state physics, and the form factor (quantum field theory). The nucleon (proton and neutron) electromagnetic form factors describe the spatial distributions of electric charge and current inside the nucleon and thus are intimately related to its internal structure; these form factors are among the most basic observables of the nucleon. (Nucleons are the building blocks of almost all ordinary matter in the universe. The challenge of understanding the nucleon's structure and dynamics has occupied a central place in nuclear physics.) The structure functions are important in the study of deep inelastic scattering. The fundamental understanding of structure functions in terms of QCD is one of the outstanding problems in hadron physics. Why do quarks form colourless hadrons with only two stable configurations, proton and neutron? One important step towards answering this question is to characterize the internal structure of the nucleon. High energy electron scattering provides one of the most powerful tools to investigate this structure. | https://en.wikipedia.org/wiki?curid=48407985 |
Shobhana Narasimhan is a Professor of Theoretical Sciences at the Jawaharlal Nehru Centre for Advanced Scientific Research in Bangalore, India. Her main area of interest is computational nanoscience. Her research examines how the lowering of dimensionality and reduction of size affect material properties. She is a Fellow of the National Academy of Sciences, India. Narasimhan earned her B.Sc. in Physics from St. Xavier's College, Mumbai in 1983 and her M.Sc. in Physics from IIT Bombay in 1985. She received her Ph.D. in Theoretical Physics from Harvard University in 1991. Subsequently, she did her postdoctoral work at Brookhaven National Laboratory, USA and at Fritz-Haber-Institut of the Max Planck Society in Berlin, Germany. She joined the Theoretical Sciences Unit of Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore, India as a faculty member in 1996. She was formerly Chair of the Theoretical Sciences Unit and Dean of Academic Affairs at JNCASR. Narasimhan has a strong interest in innovative teaching methods and has organized and participated in many interactive workshops in several countries. She is also keen on promoting women in science causes. She is a member of the Standing Committee on Women in Science of the Government of India and was formerly a panel Member of the Women in Science initiative of the Indian Academy of Sciences, and has also organized several Career Development Workshops for Women in Physics at the International Centre for Theoretical Physics in Trieste, Italy | https://en.wikipedia.org/wiki?curid=48412394 |
Shobhana Narasimhan and at the East African Institute for Fundamental Research in Kigali, Rwanda. Narasimhan became a Fellow of the National Academy of Sciences, India in 2011. She also received the Stree Shakti Samman Science Award in 2010 and the Kalpana Chawla Woman Scientist Award of the Government of Karnataka in 2010. | https://en.wikipedia.org/wiki?curid=48412394 |
M. S. Ramakumar Mallasamudram Subramanyam Ramakumar was an Indian mechanical engineer, outstanding scientist and roboticist, known for developing robotic and automation technologies for Indian nuclear and defence purposes. He was the director of Nuclear Fuels, Automation and Manufacturing Group of the Bhabha Atomic Research Centre (BARC), Trombay. He was the first Head of Division of Remote Handling of Robotics (DRHR) at the organization. He pioneered robotic technology in India. Ramakumar was one of the key persons behind the Pokhran-II test, conducted by India in 1998. It was his team, which developed the online fuelling and coolant channel inspection systems for the power reactors for the 1998 tests. Ramakumar published several articles on Robotics and Remote handling technologies and peer reviewed a few journals of international repute. He was a member of the advisory board of the "Indian Conference on Computer Vision, Graphics and Image Processing", organised by Space Applications Centre of the Indian Space Research Organization (ISRO) at Ahmedabad, in 2002 and was an external examiner of the Indian Institute of Technology, Mumbai. Government of India awarded him the fourth highest civilian award of the Padmashri in 1999. | https://en.wikipedia.org/wiki?curid=48442415 |
Biconcave disc A biconcave disc — also referred to as a discocyte — is a geometric shape resembling an oblate spheroid with two concavities on the top and on the bottom. It is meta-stable, and involves the continuous adjustment of the asymmetric transbilayer lipid distribution, which is correlated with ATP depletion. A biconcave disc can be described mathematically by where is the height of the surface as a function of radius , is the diameter of the disc, and are coefficients describing the shape. The above model describes a smooth surface; actual cells can be much more irregular. Erythrocytes are in the shape of a biconcave disc. | https://en.wikipedia.org/wiki?curid=48444540 |
Maitree Bhattacharyya is a Professor and the Director of Jagadis Bose National Science Talent Search (JBNSTS), Kolkata, which works for the propagation of scientific temperament among the young students of the country. She graduated from Presidency College with Honours in Physics and obtained M.Sc degree from the Science college campus of University of Calcutta. She started her research career in the Department of Biophysics and Molecular Biology, University of Calcutta with a PhD degree in 1991. She pursued research with a Research associateship from CSIR and in 1994 joined University of Calcutta as an Assistant Professor. Later, she was awarded a DBT Overseas fellowship and worked as Visiting Scientist in UCSD, USA. Now she is the Professor, Department of Biochemistry in University of Calcutta. Bhattacharyya joined as director at Jagadis Bose National Science Talent Search (JBNSTS), Kolkata from January 2015. Fourteen students have been awarded PhD degree under her supervision and in 2015 she is leading a group of ten research scholars which comprises PhD and post doctoral students. She has published several research articles and chapters in books of International repute. During 2016 Bhattacharyya has been bestowed the fellow of the West Bengal Academy of Science and Technology. | https://en.wikipedia.org/wiki?curid=48446984 |
Timeline of plastic development This is a timeline of the development of plastics, comprising key discoveries and developments in the production of plastics. | https://en.wikipedia.org/wiki?curid=48458437 |
Jo-Anne H. Young (née van Burik) is an American physician, scientist, and Editor-in-Chief of "Clinical Microbiology Reviews", published by the American Society for Microbiology. Her expertise is in the areas of transplantation, infectious diseases, infections of the immune compromised host, and clinical mycology and virology. She is Medical Director of the Adult Transplant Infectious Disease Program at the University of Minnesota. Other responsibilities that Young has with the University of Minnesota include the Institutional Review Board, Co-chair of the Supportive Care/Infectious Disease/Toxicities Site Team for the Cancer Center, Physician Informatics Committee at the Medical Center, and Clinical Service Unit Board in the Department of Medicine. Before coming to the University of Minnesota in 1999, she worked at the Fred Hutchinson Cancer Research Center with the University of Washington in Seattle, from 1993 to 1998. She completed an internal medicine residency at Vanderbilt University Medical Center in Nashville, Tennessee, from 1990 to 1993. She completed her M.D. degree at Case Western Reserve University in Cleveland, Ohio, in 1990. | https://en.wikipedia.org/wiki?curid=48461272 |
Sofia Romanskaya (1886–1969) was a Soviet astronomer known as one the first Russian women to have a significant role in the field. Sofia (also spelled Sofya) Vasilievna Voroshilova-Romanskaya was born in St. Petersburg. She graduated from the Bestuzhev Courses, a prominent women's educational institution of the Russian Empire. Romanskaya worked at the Pulkovo Observatory from 1908 to 1959. There, she carried out over 20,000 latitude observations in her studies of polar motion. She was a member of the International Astronomical Union and attended the organization's 1958 General Assembly in Moscow. The asteroid , discovered by Grigory Neujmin in 1936, was named after Romanskaya. A crater on Venus also bears her name. | https://en.wikipedia.org/wiki?curid=48461396 |
Mandar Madhukar Deshmukh (born 20 October 1974) is an Indian physicist specialising in nanoscale and mesoscopic physics and affiliated to Tata Institute of Fundamental Research, Mumbai. He was awarded the Shanti Swarup Bhatnagar Prize for Science and Technology in 2015, the highest science award in India, in the physical sciences category. He obtained BTech degree from Indian Institute of Technology Bombay in 1996 and PhD degree from Cornell University under the guidance of D.C. Ralph in 2002. Before coming to Tata Institute of Fundamental Research, he was a postdoctoral researcher in the group of Hongkun Park at Harvard University. His wife Prita Pant also Ph.D. from Cornell University is an Associate Professor at IIT Bombay. | https://en.wikipedia.org/wiki?curid=48465317 |
Teodor Bordeianu (February 16 1902 – March 19 1969) was a Romanian agronomist and pomologist who was a member of the Romanian Academy. He was born in the village of Marșenița, which is today in Ukraine, and died in Bucharest, Romania. | https://en.wikipedia.org/wiki?curid=48477239 |
Encapsulin nanocompartment Encapsulin nanocompartments, or encapsulin protein cages, are spherical bacterial organelle-like compartments roughly 25-30 nm in diameter that are involved in various aspects of metabolism, in particular protecting bacteria from oxidative stress. Encapsulin nanocompartments are structurally similar to the HK97 bacteriophage and their function depends on the proteins loaded into the nanocompartment. The sphere is formed from 60 (for a 25 nm sphere) or 180 (for a 30 nm sphere) copies of a single protomer, termed encapsulin. Their structure has been studied in great detail using X-ray crystallography and cryo-electron microscopy. A number of different types of proteins have been identified as being loaded into encapsulin nanocompartments. Peroxidases or proteins similar to ferritins are the two most common types of cargo proteins. While most encapsulin nanocompartments contain only one type of cargo protein, in some species two or three types of cargo proteins are loaded. Encapsulins purified from "Rhodococcus jostii" can be assembled and disassembled with changes in pH. In the assembled state, the compartment enhances the activity of its cargo, a peroxidase enzyme. Recently, encapsulin nanocompartments have begun to receive considerable interest from bioengineers because of their potential to allow the targeted delivery of drugs, proteins, and mRNAs to specific cells of interest. | https://en.wikipedia.org/wiki?curid=48483838 |
993–994 carbon-14 spike The was a rapid increase in carbon-14 content from tree rings, and followed the 774–775 carbon-14 spike. This event is also confirmed by a sharp increase of beryllium-10 and hence considered as solar-origin. It may have come from a massive solar storm as a series of auroral observations are known to be observed in late 992. | https://en.wikipedia.org/wiki?curid=48508353 |
Ligia Gargallo is a Chilean chemist and university professor of the Pontifical Catholic University of Chile. She works at the University of Tarapacá (Arica) and at the Pontifical Catholic University of Chile, in Santiago. She received a bachelor's degree in chemical pharmaceutical at the University of Chile in 1959, degrees in chemistry from Paris Dauphine University and Katholieke Universiteit Leuven, a doctorate in chemical sciences at the University of Liège in Belgium in 1972, and a doctorate in chemistry from Katholieke Universiteit Leuven. Her areas of investigation are focused in Polymers and Macromolecules. Her work has aided drug designers. She is the winner of the Prize L'Oréal-UNESCO to Women in Science 2007 and Chile's National Prize for Natural Sciences in 2014 because of the "pioneering work in the development of the chemistry of polymers and macromolecules". | https://en.wikipedia.org/wiki?curid=48514474 |
Computational anatomy is an interdisciplinary field of biology focused on quantitative investigation and modelling of anatomical shapes variability. It involves the development and application of mathematical, statistical and data-analytical methods for modelling and simulation of biological structures. The field is broadly defined and includes foundations in anatomy, applied mathematics and pure mathematics, machine learning, computational mechanics, computational science, biological imaging, neuroscience, physics, probability, and statistics; it also has strong connections with fluid mechanics and geometric mechanics. Additionally, it complements newer, interdisciplinary fields like bioinformatics and neuroinformatics in the sense that its interpretation uses metadata derived from the original sensor imaging modalities (of which Magnetic Resonance Imaging is one example). It focuses on the anatomical structures being imaged, rather than the medical imaging devices. It is similar in spirit to the history of Computational linguistics, a discipline that focuses on the linguistic structures rather than the sensor acting as the transmission and communication medium(s). In computational anatomy, the diffeomorphism group is used to study different coordinate systems via coordinate transformations as generated via the Lagrangian and Eulerian velocities of flow in formula_1 | https://en.wikipedia.org/wiki?curid=48520204 |
Computational anatomy The flows between coordinates in computational anatomy are constrained to be geodesic flows satisfying the principle of least action for the Kinetic energy of the flow. The kinetic energy is defined through a Sobolev smoothness norm with strictly more than two generalized, square-integrable derivatives for each component of the flow velocity, which guarantees that the flows in formula_2 are diffeomorphisms. It also implies that the diffeomorphic shape momentum taken pointwise satisfying the Euler-Lagrange equation for geodesics is determined by its neighbors through spatial derivatives on the velocity field. This separates the discipline from the case of incompressible fluids for which momentum is a pointwise function of velocity. intersects the study of Riemannian manifolds and nonlinear global analysis, where groups of diffeomorphisms are the central focus. Emerging high-dimensional theories of shape are central to many studies in computational anatomy, as are questions emerging from the fledgling field of shape statistics. The metric structures in computational anatomy are related in spirit to morphometrics, with the distinction that focuses on an infinite-dimensional space of coordinate systems transformed by a diffeomorphism, hence the central use of the terminology , the metric space study of coordinate systems via diffeomorphisms. At computational anatomy's heart is the comparison of shape by recognizing in one shape the other | https://en.wikipedia.org/wiki?curid=48520204 |
Computational anatomy This connects it to D'Arcy Wentworth Thompson's developments On Growth and Form which has led to scientific explanations of morphogenesis, the process by which patterns are formed in Biology. Albrecht Durer's Four Books on Human Proportion were arguably the earliest works on computational anatomy. The efforts of Noam Chomsky in his pioneering of Computational Linguistics inspired the original formulation of computational anatomy as a generative model of shape and form from exemplars acted upon via transformations. Due to the availability of dense 3D measurements via technologies such as magnetic resonance imaging (MRI), computational anatomy has emerged as a subfield of medical imaging and bioengineering for extracting anatomical coordinate systems at the morphome scale in 3D. The spirit of this discipline shares strong overlap with areas such as computer vision and kinematics of rigid bodies, where objects are studied by analysing the groups responsible for the movement in question. departs from computer vision with its focus on rigid motions, as the infinite-dimensional diffeomorphism group is central to the analysis of Biological shapes. It is a branch of the image analysis and pattern theory school at Brown University pioneered by Ulf Grenander. In Grenander's general Metric Pattern Theory, making spaces of patterns into a metric space is one of the fundamental operations since being able to cluster and recognize anatomical configurations often requires a metric of close and far between shapes | https://en.wikipedia.org/wiki?curid=48520204 |
Computational anatomy The diffeomorphometry metric of measures how far two diffeomorphic changes of coordinates are from each other, which in turn induces a metric on the shapes and images indexed to them. The models of metric pattern theory, in particular group action on the orbit of shapes and forms is a central tool to the formal definitions in Computational anatomy. is the study of shape and form at the morphome or gross anatomy millimeter, or morphology scale, focusing on the study of sub-manifolds of formula_3 points, curves surfaces and subvolumes of human anatomy. An early modern computational neuro-anatomist was David Van Essen performing some of the early physical unfoldings of the human brain based on printing of a human cortex and cutting. Jean Talairach's publication of Talairach coordinates is an important milestone at the morphome scale demonstrating the fundamental basis of local coordinate systems in studying neuroanatomy and therefore the clear link to charts of differential geometry. Concurrently, virtual mapping in computational anatomy across high resolution dense image coordinates was already happening in Ruzena Bajcy's and Fred Bookstein's earliest developments based on Computed axial tomography and Magnetic resonance imagery. The earliest introduction of the use of flows of diffeomorphisms for transformation of coordinate systems in image analysis and medical imaging was by Christensen, Joshi, Miller, and Rabbitt | https://en.wikipedia.org/wiki?curid=48520204 |
Computational anatomy The first formalization of computational anatomy as an orbit of exemplar templates under diffeomorphism group action was in the original lecture given by Grenander and Miller with that title in May 1997 at the 50th Anniversary of the Division of Applied Mathematics at Brown University, and subsequent publication. This was the basis for the strong departure from much of the previous work on advanced methods for spatial normalization and image registration which were historically built on notions of addition and basis expansion. The structure preserving transformations central to the modern field of Computational Anatomy, homeomorphisms and diffeomorphisms carry smooth submanifolds smoothly. They are generated via Lagrangian and Eulerian flows which satisfy a law of composition of functions forming the group property, but are not additive. The original model of computational anatomy was as the triple, formula_4 the group formula_5, the orbit of shapes and forms formula_6, and the probability laws formula_7 which encode the variations of the objects in the orbit. The template or collection of templates are elements in the orbit formula_8 of shapes | https://en.wikipedia.org/wiki?curid=48520204 |
Computational anatomy The Lagrangian and Hamiltonian formulations of the equations of motion of computational anatomy took off post 1997 with several pivotal meetings including the 1997 Luminy meeting organized by the Azencott school at Ecole-Normale Cachan on the "Mathematics of Shape Recognition" and the 1998 Trimestre at Institute Henri Poincaré organized by David Mumford "Questions Mathématiques en Traitement du Signal et de l'Image" which catalyzed the Hopkins-Brown-ENS Cachan groups and subsequent developments and connections of to developments in global analysis. The developments in computational anatomy included the establishment of the Sobelev smoothness conditions on the diffeomorphometry metric to insure existence of solutions of variational problems in the space of diffeomorphisms, the derivation of the Euler-Lagrange equations characterizing geodesics through the group and associated conservation laws, the demonstration of the metric properties of the right invariant metric, the demonstration that the Euler-Lagrange equations have a well-posed initial value problem with unique solutions for all time, and with the first results on sectional curvatures for the diffeomorphometry metric in landmarked spaces. Following the Los Alamos meeting in 2002, Joshi's original large deformation singular "Landmark" solutions in were connected to peaked "Solitons" or "Peakons" as solutions for the Camassa-Holm equation | https://en.wikipedia.org/wiki?curid=48520204 |
Computational anatomy Subsequently, connections were made between Computational anatomy's Euler-Lagrange equations for momentum densities for the right-invariant metric satisfying Sobolev smoothness to Vladimir Arnold's characterization of the Euler equation for incompressible flows as describing geodesics in the group of volume preserving diffeomorphisms. The first algorithms, generally termed LDDMM for large deformation diffeomorphic mapping for computing connections between landmarks in volumes and spherical manifolds, curves, currents and surfaces, volumes, tensors, varifolds, and time-series have followed. These contributions of computational anatomy to the global analysis associated to the infinite dimensional manifolds of subgroups of the diffeomorphism group is far from trivial. The original idea of doing differential geometry, curvature and geodesics on infinite dimensional manifolds goes back to Bernhard Riemann's Habilitation (Ueber die Hypothesen, welche der Geometrie zu Grunde liegen); the key modern book laying the foundations of such ideas in global analysis are from Michor. The applications within medical imaging of computational anatomy continued to flourish after two organized meetings at the Institute for Pure and Applied Mathematics conferences at University of California, Los Angeles. has been useful in creating accurate models of the atrophy of the human brain at the morphome scale, as well as Cardiac templates, as well as in modeling biological systems | https://en.wikipedia.org/wiki?curid=48520204 |
Computational anatomy Since the late 1990s, computational anatomy has become an important part of developing emerging technologies for the field of medical imaging. Digital atlases are a fundamental part of modern Medical-school education and in neuroimaging research at the morphome scale. Atlas based methods and virtual textbooks which accommodate variations as in deformable templates are at the center of many neuro-image analysis platforms including Freesurfer, FSL, MRIStudio, SPM. Diffeomorphic registration, introduced in the 1990s, is now an important player with existing codes bases organized around ANTS,<ref name="stnava/ANTs"></ref> DARTEL, DEMONS, LDDMM,<ref name="NITRC: LDDMM: Tool/Resource Info"></ref> StationaryLDDMM, FastLDDMM, are examples of actively used computational codes for constructing correspondences between coordinate systems based on sparse features and dense images. Voxel-based morphometry (VBM) is an important technology built on many of these principles. The model of human anatomy is a deformable template, an orbit of exemplars under group action. Deformable template models have been central to Grenander's Metric Pattern theory, accounting for typicality via templates, and accounting for variability via transformation of the template. An orbit under group action as the representation of the deformable template is a classic formulation from differential geometry | https://en.wikipedia.org/wiki?curid=48520204 |
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