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Eutectic system The eutectic solidification is defined as follows: This type of reaction is an invariant reaction, because it is in thermal equilibrium; another way to define this is the change in Gibbs free energy equals zero. Tangibly, this means the liquid and two solid solutions all coexist at the same time and are in chemical equilibrium. There is also a thermal arrest for the duration of the change of phase during which the temperature of the system does not change. The resulting solid macrostructure from a eutectic reaction depends on a few factors. The most important factor is how the two solid solutions nucleate and grow. The most common structure is a lamellar structure, but other possible structures include rodlike, globular, and acicular. Compositions of eutectic systems that are not at the eutectic composition can be classified as "hypoeutectic" or "hypereutectic". Hypoeutectic compositions are those with a smaller percent composition of species β and a greater composition of species α than the eutectic composition (E) while hypereutectic solutions are characterized as those with a higher composition of species β and a lower composition of species α than the eutectic composition. As the temperature of a non-eutectic composition is lowered the liquid mixture will precipitate one component of the mixture before the other. In a hypereutectic solution, there will be a proeutectoid phase of species β whereas a hypoeutectic solution will have a proeutectic α phase | https://en.wikipedia.org/wiki?curid=152969 |
Eutectic system Eutectic alloys have two or more materials and have a eutectic composition. When a non-eutectic alloy solidifies, its components solidify at different temperatures, exhibiting a plastic melting range. Conversely, when a well-mixed, eutectic alloy melts, it does so at a single, sharp temperature. The various phase transformations that occur during the solidification of a particular alloy composition can be understood by drawing a vertical line from the liquid phase to the solid phase on the phase diagram for that alloy. Some uses include: When the solution above the transformation point is solid, rather than liquid, an analogous eutectoid transformation can occur. For instance, in the iron-carbon system, the austenite phase can undergo a eutectoid transformation to produce ferrite and cementite, often in lamellar structures such as pearlite and bainite. This eutectoid point occurs at and about 0.76% carbon. A "peritectoid" transformation is a type of isothermal reversible reaction that has two solid phases reacting with each other upon cooling of a binary, ternary, ..., formula_2-ary alloy to create a completely different and single solid phase. The reaction plays a key role in the order and decomposition of quasicrystalline phases in several alloy types. Peritectic transformations are also similar to eutectic reactions. Here, a liquid and solid phase of fixed proportions react at a fixed temperature to yield a single solid phase | https://en.wikipedia.org/wiki?curid=152969 |
Eutectic system Since the solid product forms at the interface between the two reactants, it can form a diffusion barrier and generally causes such reactions to proceed much more slowly than eutectic or eutectoid transformations. Because of this, when a peritectic composition solidifies it does not show the lamellar structure that is found with eutectic solidification. Such a transformation exists in the iron-carbon system, as seen near the upper-left corner of the figure. It resembles an inverted eutectic, with the δ phase combining with the liquid to produce pure austenite at and 0.17% carbon. At the peritectic decomposition temperature the compound, rather than melting, decomposes into another solid compound and a liquid. The proportion of each is determined by the lever rule. In the Al-Au phase diagram, for example, it can be seen that only two of the phases melt congruently, AuAl and AuAl , while the rest peritectically decompose. The composition and temperature of a eutectic can be calculated from enthalpy and entropy of fusion of each components | https://en.wikipedia.org/wiki?curid=152969 |
Eutectic system The Gibbs free energy "G" depends on its own differential: Thus, the "G"/"T" derivative at constant pressure is calculated by the following equation: The chemical potential formula_5 is calculated if we assume that the activity is equal to the concentration: At the equilibrium, formula_7, thus formula_8 is obtained as Using and integrating gives The integration constant "K" may be determined for a pure component with a melting temperature formula_11 and an enthalpy of fusion formula_12: We obtain a relation that determines the molar fraction as a function of the temperature for each component: The mixture of "n" components is described by the system which can be solved by | https://en.wikipedia.org/wiki?curid=152969 |
First Point of Aries The First Point of Aries, also known as the Cusp of Aries, is the location of the vernal equinox, used as a reference point in celestial coordinate systems. In diagrams using such coordinate systems, it is often indicated with the symbol ♈︎. Named for the constellation of Aries, it is one of the two points on the celestial sphere at which the celestial equator crosses the ecliptic, the other being the First Point of Libra, located exactly 180° from it. Due to precession of the equinoxes since the position was originally named in antiquity, the position of the Sun on the March equinox is now in Pisces, while that on the September equinox is in Virgo (as of J2000). Along its yearly path through the zodiac, the Sun meets the celestial equator from south to north at the First Point of Aries, and from north to south at the First Point of Libra. The is considered to be the celestial "prime meridian" from which right ascension is calculated. The choice of starting position from which to measure the Sun's motion across celestial sphere is arbitrary. The equinoxes are preferred as an equinox marks the point in time when the Sun has neither northern nor southern declination but is crossing the celestial equator. Of the two possible equinoxes the ancient Greeks chose the March equinox as the starting point. This coincided with the festival of Hilaria, a time of optimism and beginnings where farmers began to sow or observed the first growth and blossoming of trees and summer crops | https://en.wikipedia.org/wiki?curid=153774 |
First Point of Aries The naming of Aries is late in the Babylonian zodiac where the equinox was in its earliest tradition marked as in the early Middle Bronze Age by actual coincidence with the Pleiades. The time also corresponds to the time of castration of male calves, mules and donkeys, "Sanguia" on the vernal equinox and marked the start of spring proper. The is so called because, when Hipparchus defined it in 130 BCE, it was located in the western extreme of the constellation of Aries, near its border with Pisces and the star γ Arietis. Due to the Sun's eastward movement across the sky throughout the year, this western end of Aries was the point at which the Sun entered the constellation, hence the name "First Point" of Aries. Due to Earth's axial precession, this point gradually moves westwards at a rate of about one degree every 72 years. This means that, since the time of Hipparchus, it has shifted across the sky by about 30°, and is currently located within Pisces, near its border with Aquarius. The Sun now appears in Aries from late April until mid-May, though the constellation is still associated with the beginning of the northern spring. The is important to the fields of astronomy, nautical navigation and astrology. Navigational ephemeris tables record the geographic position of the as the reference for position of navigational stars | https://en.wikipedia.org/wiki?curid=153774 |
First Point of Aries Due to the slow precession of the equinoxes, the Zenith view (above a location) of constellations at a time of year from a given location have slowly moved west (by using solar epochs the drift is known). The tropical Zodiac is similarly affected and no longer corresponds with the constellations (the Cusp of Libra today is located within Virgo). In sidereal astrology, by contrast, the first point of Aries remains aligned with the Aries constellation. | https://en.wikipedia.org/wiki?curid=153774 |
Shortwave radiation (SW) is radiant energy with wavelengths in the visible (VIS), near-ultraviolet (UV), and near-infrared (NIR) spectra. There is no standard cut-off for the near-infrared range; therefore, the shortwave radiation range is also variously defined. It may be broadly defined to include all radiation with a wavelength of 0.1μm and 5.0μm or narrowly defined so as to include only radiation between 0.2μm and 3.0μm. There is little radiation flux (in terms of W/m²) to the Earth's surface below 0.2μm or above 3.0μm, although photon flux remains significant as far as 6.0μm, compared to shorter wavelength fluxes. UV-C radiation spans from 0.1μm to .28μm, UV-B from 0.28μm to 0.315μm, UV-A from 0.315μm to 0.4μm, the visible spectrum from 0.4μm to 0.7μm, and NIR arguably from 0.7μm to 5.0μm, beyond which the infrared is thermal. is distinguished from longwave radiation. Downward shortwave radiation is sensitive to solar zenith angle, cloud cover. | https://en.wikipedia.org/wiki?curid=154581 |
Novartis International AG is a Swiss multinational pharmaceutical company based in Basel, Switzerland. It is one of the largest pharmaceutical companies by both market capitalization and sales. manufactures the drugs clozapine (Clozaril), diclofenac (Voltaren), carbamazepine (Tegretol), valsartan (Diovan), imatinib mesylate (Gleevec/Glivec), cyclosporine (Neoral/Sandimmune), letrozole (Femara), methylphenidate (Ritalin), terbinafine (Lamisil), deferasirox (Exjade), and others. In 1996, Ciba-Geigy merged with Sandoz; the pharmaceutical and agrochemical divisions of both companies formed as an independent entity. Ciba-Geigy and Sandoz businesses were sold, or, like Ciba Specialty Chemicals, spun off as independent companies. The Sandoz brand disappeared for three years, but was revived in 2003 when consolidated its generic drugs businesses into a single subsidiary and named it Sandoz. divested its agrochemical and genetically modified crops business in 2000 with the spinout of Syngenta in partnership with AstraZeneca, which also divested its agrochemical business. is a full member of the European Federation of Pharmaceutical Industries and Associations (EFPIA), the International Federation of Pharmaceutical Manufacturers and Associations (IFPMA), and the Pharmaceutical Research and Manufacturers of America (PhRMA). AG is a publicly traded Swiss holding company that operates through the Group. AG owns, directly or indirectly, all companies worldwide that operate as subsidiaries of the Group | https://en.wikipedia.org/wiki?curid=159284 |
Novartis Novartis's businesses are divided into three operating divisions: Innovative Medicines, Sandoz (generics) and Alcon (eyecare). In April 2019, spun off Alcon into a separate company. The Innovative Medicines division comprises two business units: Pharmaceuticals and Oncology. operates directly through subsidiaries, each of which fall under one of the divisions, and that categorizes as fulfilling one or more of the following functions: Holding/Finance, Sales, Production, and Research AG also holds 33.3% of the shares of Roche however, it does not exercise control over Roche. also has two significant license agreements with Genentech, a Roche subsidiary. One agreement is for Lucentis; the other is for Xolair. In 2014, established a center in Hyderabad, India, in order to offshore several of its R&D, clinical development, medical writing and administrative functions. The center supports the drug major's operations in the pharmaceuticals (Novartis), eye care (Alcon) and generic drugs segments (Sandoz). Overall, was the world's second largest pharmaceutical company in 2011. Alcon: At the time bought Alcon, they had annual sales of $6.5 billion and a net income of $2 billion. In April 2019, completed the spin-off of Alcon as a separate commercial entity. Sandoz: , Sandoz has been recognized as the world's second-largest generic drug company. Sandoz' biosimilars lead its field, getting the first biosimilar approvals in the EU. In 2018, Sandoz reported US$9.9 billion in net sales | https://en.wikipedia.org/wiki?curid=159284 |
Novartis Vaccines and Diagnostics Division: In 2013, announced it was considering selling the vaccines and diagnostics division off. This sale was completed in late 2015, and the division was integrated into CSL's BioCSL operation, with the combined entity trading as Seqirus. In 2018, sold its consumer healthcare joint venture vaccines division to GlaxoSmithKline for US$13.0 billion. Consumer: is not a leader in the over-the-counter or animal health segments; its leading OTC brands are Excedrin and Theraflu, but sales have been slowed by problems at its key US manufacturing plant. In 2018, ranked 2nd on the Access to Medicine Index, which "ranks companies on how readily they make their products available to the world's poor." For the fiscal year 2019, reported earnings of US$11.732 billion, with an annual revenue of US$48.677 billion, an increase of 5.59% over the previous fiscal cycle. shares traded at over $88.14 per share, and its market capitalization was valued at $205.32B as of April 28, 2020. was created in 1996 from the merger of Ciba-Geigy and Sandoz Laboratories, both Swiss companies. Ciba-Geigy was formed in 1970 by the merger of J. R. Geigy Ltd (founded in Basel in 1758) and CIBA (founded in Basel in 1859). Ciba began in 1859, when Alexander Clavel (1805–1873) took up the production of fuchsine in his factory for silk-dyeing works in Basel. By 1873, he sold his dye factory to the company Bindschedler and Busch | https://en.wikipedia.org/wiki?curid=159284 |
Novartis In 1884, Bindschedler and Busch was transformed into a joint-stock company named "Gesellschaft für Chemische Industrie Basel" (Company for Chemical Industry Basel). The acronym, CIBA, was adopted as the company's name in 1945. The foundation for Geigy was established in 1857, when Johann Rudolf Geigy-Merian (1830–1917) and Johann Muller-Pack acquired a site in Basel, where they built a dyewood mill and a dye extraction plant. Two years later, they began the production of synthetic fuchsine. In 1901, they formed the public limited company Geigy, and the name of the company was changed to J. R. Geigy Ltd in 1914. CIBA and Geigy merged in 1970 to form Ciba‑Geigy Ltd. . In the mid-1990s, state and federal health and environmental agencies identified an increased incidence of childhood cancers in Toms River from the 1970–1995 period. Multiple investigations by state and federal environmental and health agencies indicated that the likely source of the increased cancer risk was contamination from Toms River Chemical Plant (then operated by Ciba-Geigy), which had been in operation since 1952. The area was designated a United States Environmental Protection Agency Superfund site in 1983 after an underground plume of toxic chemicals was identified. The following year, a discharge pipe was shut down after a sinkhole at the corner of Bay Avenue and Vaughn Avenue revealed that it had been leaking. The plant ceased operation in 1996 | https://en.wikipedia.org/wiki?curid=159284 |
Novartis A follow up study from the 1996–2000 period indicated that while there were more cancer cases than expected, rates had significantly fallen and the difference was statistically insignificant compared to normal statewide cancer rates. Since 1996, the Toms River water system has been subject to the most stringent water testing in the state and is considered safe for consumption. Dan Fagin's Toms River: A Story of Science and Salvation, the 2014 Pulitzer Prize winning book, examined the issue of industrial pollution at the site in detail. Before the 1996 merger with Ciba-Geigy to form Novartis, Sandoz Pharmaceuticals (Sandoz AG) was a pharmaceutical company headquartered in Basel, Switzerland (as was Ciba-Geigy), and was best known for developing drugs such as Sandimmune for organ transplantation, the antipsychotic Clozaril, Mellaril Tablets and Serentil Tablets for treating psychiatric disorders, and Cafergot Tablets and Torecan Suppositories for treating migraine headaches. The "Chemiefirma Kern und Sandoz" ("Kern and Sandoz Chemistry Firm") was founded in 1886 by Alfred Kern (1850–1893) and Edouard Sandoz (1853–1928). The first dyes manufactured by them were alizarinblue and auramine. After Kern's death, the partnership became the corporation "Chemische Fabrik vormals Sandoz" in 1895. The company began producing the fever-reducing drug antipyrin in the same year. In 1899, the company began producing the sugar substitute saccharin | https://en.wikipedia.org/wiki?curid=159284 |
Novartis Further pharmaceutical research began in 1917 under Arthur Stoll (1887–1971), who is the founder of Sandoz's pharmaceutical department in 1917. In 1918, Arthur Stoll isolated ergotamine from ergot; the substance was eventually used to treat migraine and headaches and was introduced under the trade name Gynergen in 1921. Between the World Wars, Gynergen (1921) and Calcium-Sandoz (1929) were brought to market. Sandoz also produced chemicals for textiles, paper, and leather, beginning in 1929. In 1939, the company began producing agricultural chemicals. The psychedelic effects of lysergic acid diethylamide (LSD) were discovered at the Sandoz laboratories in 1943 by Arthur Stoll and Albert Hofmann. Sandoz began clinical trials and marketed the substance, from 1947 through the mid-1960s, under the name "Delysid" as a psychiatric drug, thought useful for treating a wide variety of mental ailments, ranging from alcoholism to sexual deviancy. Sandoz suggested in its marketing literature that psychiatrists take LSD themselves, to gain a better subjective understanding of the schizophrenic experience, and many did exactly that and so did other scientific researchers. The Sandoz product received mass publicity as early as 1954, in a Time Magazine feature. Research on LSD peaked in the 1950s and early 1960s. Sandoz withdrew the drug from the market in 1965 | https://en.wikipedia.org/wiki?curid=159284 |
Novartis The drug became a cultural novelty of the 1960s after psychologist Timothy Leary at Harvard University began to promote its use for recreational and spiritual experiences among the general public. Sandoz opened its first foreign offices in 1964. In 1967, Sandoz merged with Wander AG (known for Ovomaltine and Isostar). Sandoz acquired the companies Delmark, Wasabröd (a Swedish manufacturer of crisp bread), and Gerber Products Company (a baby food company). On 1 November 1986, a fire broke out in a production plant storage room, which led to the Sandoz chemical spill and a large amount of pesticide being released into the upper Rhine river. This exposure killed many fish and other aquatic life. In 1995, Sandoz spun off its specialty chemicals business to form Clariant. In 1997, Clariant merged with the specialty chemicals business that was spun off from Hoechst AG in Germany. In 1996 Ciba-Geigy merged with Sandoz, with the pharmaceutical and agrochemical divisions of both staying together to form Novartis. Other Ciba-Geigy and Sandoz businesses were spun off as independent companies., notably Ciba Specialty Chemicals. Sandoz's Master Builders Technologies, a producer of chemicals for the construction industry, was sold off to SKW Trostberg A.G., a subsidiary of the German energy company VIAG, while its North American corn herbicide business became part of the German chemical maker BASF | https://en.wikipedia.org/wiki?curid=159284 |
Novartis In 1998, the company entered into a biotechnology licensing agreement with the University of California at Berkeley Department of Plant and Microbial Biology. Critics of the agreement expressed concern over prospects that the agreement would diminish academic objectivity, or lead to the commercialization of genetically modified plants. The agreement expired in 2003. In 2000, and AstraZeneca combined their agrobusiness divisions to create a new company, Syngenta. In 2003, organized all its generics businesses into one division, and merged some of its subsidiaries into one company, reusing the predecessor brand name of Sandoz. In 2005, expanded its subsidiary Sandoz significantly through the US$8.29 billion acquisition of Hexal, one of Germany's leading generic drug companies, and Eon Labs, a fast-growing United States generic pharmaceutical company. In 2006, acquired the California-based Chiron Corporation. Chiron had been divided into three units: Chiron Vaccines, Chiron Blood Testing, and Chiron BioPharmaceuticals. The biopharmaceutical unit was integrated into Pharmaceuticals, while the vaccines and blood testing units were made into a new Vaccines and Diagnostics division. Also in 2006, Sandoz became the first company to have a biosimilar drug approved in Europe with its recombinant human growth hormone drug. In 2007, sold the Gerber Products Company to Nestlé as part of its continuing effort to shed old Sandoz and Ciba-Geigy businesses and focus on healthcare | https://en.wikipedia.org/wiki?curid=159284 |
Novartis In 2009, reached an agreement to acquire an 85% stake in the Chinese vaccines company Zhejiang Tianyuan Bio-Pharmaceutical Co., Ltd. as part of a strategic initiative to build a vaccines industry leader in this country and expand the group's limited presence in this fast-growing market segment. This proposed acquisition will require government and regulatory approvals in China. In 2010, offered to pay US$39.3 billion to fully acquire Alcon, the world's largest eye-care company, including a majority stake held by Nestlé. had bought 25% of Alcon in 2008. created a new division and called it Alcon, under which it placed its CIBA VISION subsidiary and Ophthalmics, which became the second-largest division of Novartis. The total cost for Alcon amounted to $60 billion. In 2011, acquired the medical laboratory diagnostics company Genoptix to "serve as a strong foundation for our (Novartis') individualized treatment programs". In 2012, the Company cut ~2000 positions in the United States, most in sales, in response to anticipated revenue downturns from the hypertension drug Diovan, which was losing patent protection, and the realization that the anticipated successor to Diovan, Rasilez, was failing in clinical trials. The 2012 personnel reductions follow ~2000 cut positions in Switzerland and the United States in 2011, ~1400 cut positions in the United States in 2010, and a reduction of "thousands" and several site closures in previous years | https://en.wikipedia.org/wiki?curid=159284 |
Novartis Also in 2012, became the biggest manufacturer of generic skin care medicine, after agreeing to buy Fougera Pharmaceuticals for $1.525 billion in cash. In 2013, the Indian Supreme Court issued a decision rejecting Novartis' patent application in India on the final form of Gleevec, Novartis's cancer drug; the case caused great controversy. In 2013, was sued again by the US government, this time for allegedly bribing doctors for a decade so that their patients are steered towards the company's drugs. In January 2014, announced plans to cut 500 jobs from its pharmaceuticals division. In February 2014, announced that it acquired CoStim Pharmaceuticals. In May 2014, bought the rights to market Ophthotech's Fovista (an anti-PDGF aptamer, also being investigated for use in combination with anti-VEGF treatments) outside the United States for up to $1 billion. will acquire exclusive rights to market the eye drug outside of America while retaining US marketing rights. The company agreed to pay Ophthotech $200 million upfront, and $130 million in milestone payments relating to Phase III trials. Ophthotech is also eligible to receive up to $300 million dependent upon future marketing approval milestones outside of America and up to $400 million relating to sales milestones. In September 2014, Ophthotech received its first $50 million phase III trial milestone payment from Novartis | https://en.wikipedia.org/wiki?curid=159284 |
Novartis In April 2014, announced that it would acquire GlaxoSmithKline's cancer drug business for $16 billion as well as selling its vaccines business to GlaxoSmithKline for $7.1 billion. In August 2014 "Genetic Engineering & Biotechnology News" reported that had acquired a 15% stake in Gamida Cell for $35 million, with the option to purchase the whole company for approximately $165 million. In October 2014, announced its intention to sell its influenza vaccine business (inclusive of its development pipeline), subject to regulatory approval, to CSL for $275 million. In March 2015, the company announced BioPharma had completed its acquisition of two Phase III cancer-drug candidates; the MEK inhibitor binimetinib (MEK 162) and the BRAF inhibitor encorafenib (LGX818), for $85 million. Further, the company sold its RNAi portfolio to Arrowhead Research for $10 million and $25 million in stock. In June, the company announced it would acquire Spinifex Pharmaceuticals for more than $200 million. In August, the company acquired the remaining rights to the CD20 monoclonal antibody Ofatumumab from GlaxoSmithKline for up to $1 billion. In October the company acquired Admune Therapeutics for an undisclosed sum, as well as licensing PBF-509, an adenosine A2A receptor antagonist which is in Phase I clinical trials for non-small cell lung cancer, from Palobiofarma. In November 2016, the company announced it would acquire Selexys Pharmaceuticals for $665 million | https://en.wikipedia.org/wiki?curid=159284 |
Novartis In December, the company acquired Encore Vision, gaining the company's principle compound, EV06, is a first-in-class topical therapy for presbyopia. In December acquired Ziarco Group Limited, bolstering its presence in eczema treatments. In late October 2017, "Reuters" announced that would acquire Advanced Accelerator Applications for $3.9 billion, paying $41 per ordinary share and $82 per American depositary share representing a 47 percent premium. In March 2018, GlaxoSmithKline announced that it has reached an agreement with to acquire Novartis' 36.5% stake in their Consumer Healthcare Joint Venture for $13 billion (£9.2 billion). In April of the same year, the business utilised some of the proceeds from the aforementioned GlaxoSmithKline deal to acquire Avexis for $218 per share or $8.7 billion in total, gaining the lead compound AVXS-101 used to treat spinal muscular atrophy. In August 2018, signed a deal with Laekna-a Shanghai-based pharmaceutical company for its two clinical-stage cancer drugs. gave Laekna the exclusive international rights for the drugs that are oral pan-Akt kinase inhibitors namely; afuresertib (ASB138) and uprosertib (UPB795). In mid-October, the company announced it would acquire Endocyte Inc for $2.1 billion ($24 per share) merging it with a newly created subsidiary. Endocyte will bolster Novartis' offering in its radiopharmaceuticals business, with Endocyte's first in class candidate Lu-PSMA-617 being targeted against metastatic castration-resistant prostate cancer | https://en.wikipedia.org/wiki?curid=159284 |
Novartis In late December the company announced it would acquire France-based contract manufacturer, CellforCure from LFB - boosting its capacity to produce cell and gene therapies. On 9 April 2019, announced that it had completed the spin-off of Alcon as a separate commercial entity. Alcon was listed on the SIX exchange in Switzerland and NYSE exchange in the USA. announced during late 2019 a five-year artificial intelligence "alliance" with Microsoft. The companies aim to create applications for "Microsoft's AI capabilities", in turn improving the other's drug development processes. Microsoft seeks to "test AI products it is already working on in 'real-life' situations". The deal will pursue solutions for "organizing and using" data generated from Novartis' laboratory experiments, clinical trials, and manufacturing plants. It will also look at improving manufacturing of Chimeric antigen receptor T cell (CAR T cells). Finally, the deal "will also apply AI to generative chemistry to enhance drug design". In November 2019, Sandoz announced it would acquire the Japanese business of Aspen Global inc for €300 million (around $330 million), boosting the business' presence in Asia. In late November 2019, the business announced it would acquire The Medicines Company for ($85 per share) in order to acquire amongst other assets, the cholesterol lowering therapy; inclisiran. In April 2020 the company announced it would acquire Amblyotech | https://en.wikipedia.org/wiki?curid=159284 |
Novartis The company's global research operations, called "Institutes for BioMedical Research (NIBR)" have their global headquarters in Cambridge, Massachusetts, United States. Two research institutes reside within NIBR that focus on diseases in the developing world: Institute for Tropical Diseases, which works on tuberculosis, dengue, and malaria, and Vaccines Institute for Global Health, which works on salmonella typhi (typhoid fever) and shigella. is also involved in publicly funded collaborative research projects, with other industrial and academic partners. One example in the area of non-clinical safety assessment is the InnoMed PredTox project. The company is expanding its activities in joint research projects within the framework of the Innovative Medicines Initiative of EFPIA and the European Commission. is working with Science 37 in order to allow video based telemedicine visits instead of physical traveling to clinics for patients. It is planning for ten clinical trials over three years using mobile technology to help free patients from burdensome hospital trips. In January 2009, the United States Department of Health and Human Services awarded a $486 million contract for construction of the first US plant to produce cell-based influenza vaccine, to be located in Holly Springs, North Carolina. The stated goal of this program is the capability of producing 150,000,000 doses of pandemic vaccine within six months of declaring a flu pandemic | https://en.wikipedia.org/wiki?curid=159284 |
Novartis In April 2014, divested its consumer health section with $3,5 billion worth of assets into a new joint venture with GlaxoSmithkline, named GSK Consumer Healthcare, of which will hold a 36,5% stake. In March 2018, GSK announced that it has reached an agreement with to acquire Novartis' 36.5% stake in their Consumer Healthcare Joint Venture for $13 billion (£9.2 billion). fought a seven-year, controversial battle to patent Gleevec in India, and took the case all the way to the Indian Supreme Court, where the patent application was finally rejected. The patent application at the center of the case was filed by in India in 1998, after India had agreed to enter the World Trade Organization and to abide by worldwide intellectual property standards under the TRIPS agreement. As part of this agreement, India made changes to its patent law; the biggest of which was that prior to these changes, patents on products were not allowed, while afterwards they were, albeit with restrictions. These changes came into effect in 2005, so Novartis' patent application waited in a "mailbox" with others until then, under procedures that India instituted to manage the transition. India also passed certain amendments to its patent law in 2005, just before the laws came into effect, which played a key role in the rejection of the patent application. The patent application claimed the final form of Gleevec (the beta crystalline form of imatinib mesylate) | https://en.wikipedia.org/wiki?curid=159284 |
Novartis In 1993, before India allowed patents on products, had patented imatinib, with salts vaguely specified, in many countries but could not patent it in India. The key differences between the two patent applications were that the 1998 patent application specified the counterion (Gleevec is a specific salt - imatinib mesylate) while the 1993 patent application did not claim any specific salts nor did it mention mesylate, and the 1998 patent application specified the solid form of Gleevec - the way the individual molecules are packed together into a solid when the drug itself is manufactured (this is separate from processes by which the drug itself is formulated into pills or capsules) - while the 1993 patent application did not. The solid form of imatinib mesylate in Gleevec is beta crystalline. As provided under the TRIPS agreement, applied for Exclusive Marketing Rights (EMR) for Gleevec from the Indian Patent Office and the EMR was granted in November 2003. made use of the EMR to obtain orders against some generic manufacturers who had already launched Gleevec in India. set the price of Gleevec at US$2666 per patient per month; generic companies were selling their versions at US$177 to 266 per patient per month. also initiated a program to assist patients who could not afford its version of the drug, concurrent with its product launch | https://en.wikipedia.org/wiki?curid=159284 |
Novartis When examination of Novartis' patent application began in 2005, it came under immediate attack from oppositions initiated by generic companies that were already selling Gleevec in India and by advocacy groups. The application was rejected by the patent office and by an appeal board. The key basis for the rejection was the part of Indian patent law that was created by amendment in 2005, describing the patentability of new uses for known drugs and modifications of known drugs. That section, Paragraph 3d, specified that such inventions are patentable only if "they differ significantly in properties with regard to efficacy." At one point, went to court to try to invalidate Paragraph 3d; it argued that the provision was unconstitutionally vague and that it violated TRIPS. lost that case and did not appeal. did appeal the rejection by the patent office to India's Supreme Court, which took the case. The Supreme Court case hinged on the interpretation of Paragraph 3d. The Supreme Court decided that the substance that sought to patent was indeed a modification of a known drug (the raw form of imatinib, which was publicly disclosed in the 1993 patent application and in scientific articles), that did not present evidence of a difference in therapeutic efficacy between the final form of Gleevec and the raw form of imatinib, and that therefore the patent application was properly rejected by the patent office and lower courts | https://en.wikipedia.org/wiki?curid=159284 |
Novartis Although the court ruled narrowly, and took care to note that the subject application was filed during a time of transition in Indian patent law, the decision generated widespread global news coverage and reignited debates on balancing public good with monopolistic pricing, innovation with affordability etc. Had won and had its patent issued, it could not have prevented generics companies in India from selling generic Gleevec, but it could have obliged them to pay a reasonable royalty under a grandfather clause included in India's patent law. In reaction to the decision, Ranjit Shahani, vice-chairman and managing director of India Ltd was quoted as saying "This ruling is a setback for patients that will hinder medical progress for diseases without effective treatment options." He also said that companies like would invest less money in research in India as a result of the ruling. also emphasised that it continues to be committed to good access to its drugs; according to Novartis, by 2013, "95% of patients in India—roughly 16,000 people—receive Glivec free of charge... and it has provided more than $1.7 billion worth of Glivec to Indian patients in its support program since it was started.. | https://en.wikipedia.org/wiki?curid=159284 |
Novartis " On 17 May 2010, a jury in the United States District Court for the Southern District of New York awarded $3,367,250 in compensatory damages against Novartis, finding that the company had committed sexual discrimination against twelve female sales representatives and entry-level managers since 2002, in matters of pay, promotion, and treatment after learning that the employees were pregnant. Two months later the company settled with the remaining plaintiffs for $152.5 million plus attorney fees. In September 2008, the US Food and Drug Administration (FDA) sent a notice to Pharmaceuticals regarding its advertising of Focalin XR, an ADHD drug, in which the company overstated its efficacy while marketing to the public and medical professionals. In 2005, federal prosecutors opened an investigation into Novartis' marketing of several drugs: Trileptal, an antiseizure drug; three drugs for heart conditions - Diovan (the company's top-selling product), Exforge, and Tekturna; Sandostatin, a drug to treat a growth hormone disorder; and Zelnorm, a drug for irritable bowel syndrome. In September 2010, agreed to pay US$422.5 million in criminal and civil claims and to enter into a corporate integrity agreement with the US Office of the Inspector General. According to "The New York Times", "Federal prosecutors accused of paying illegal kickbacks to health care professionals through speaker programs, advisory boards, entertainment, travel and meals | https://en.wikipedia.org/wiki?curid=159284 |
Novartis But aside from pleading guilty to one misdemeanor charge of mislabeling in an agreement that announced in February, the company denied wrongdoing." In the same New York Times article, Frank Lichtenberg, a Columbia professor who receives pharmaceutical financing for research on innovation in the industry, said off-label prescribing was encouraged by the American Medical Association and paid for by insurers, but off-label marketing was clearly illegal. "So it's not surprising that they would settle because they don't have a legal leg to stand on." In April 2013, federal prosecutors filed two lawsuits against under the False Claims Act for off-label marketing and kickbacks; in both suits, prosecutors are seeking treble damages. The first suit "accused of inducing pharmacies to switch thousands of kidney transplant patients to its immunosuppressant drug Myfortic in exchange for kickbacks disguised as rebates and discounts". In the second, the Justice Department joined a "qui tam", or whistleblower, lawsuit brought by a former sales rep over off-label marketing of three drugs: Lotrel and Valturna (both hypertension drugs), and the diabetes drug, Starlix. Twenty-seven states, the District of Columbia and Chicago and New York also joined. Outside the US, markets the drug ranibizumab (trade name Lucentis), which is a monoclonal antibody fragment derived from the same parent mouse antibody as bevacizumab (Avastin) | https://en.wikipedia.org/wiki?curid=159284 |
Novartis Both Avastin and Lucentis were created by Genentech which is owned by Roche; Roche markets Avastin worldwide, and also markets Lucentis in the US. Lucentis has been approved worldwide as a treatment for wet macular degeneration and other retinal disorders; Avastin is used to treat certain cancers. Because the price of Lucentis is much higher than Avastin, many ophthalmologists began having compounding pharmacies formulate Avastin for administration to the eye, and began treating their patients with Avastin. In 2011, four trusts of the National Health Service in the UK issued policies approving use and payment for administering Avastin for macular degeneration, in order to save money, even though Avastin had not been approved for that indication. In April 2012, after failing to persuade the trusts that it was uncertain whether Avastin was as safe and effective as Lucentis, and in order to retain the market for Lucentis, announced it would sue the trusts. However, in July offered significant discounts (kept confidential) to the trusts, and the trusts agreed to change their policy, and in November, dropped the litigation | https://en.wikipedia.org/wiki?curid=159284 |
Novartis In the summer of 2013, two Japanese universities retracted several publications of clinical trials that purported to show that Valsartan (branded as Diovan) had cardiovascular benefits, when it was found that statistical analysis had been manipulated, and that a employee had participated in the statistical analysis but had not disclosed his relationship with but only his affiliation with Osaka City University, where he was a lecturer. In January 2018, began being investigated by Greek authorities for allegedly bribing public officials in the 2006-2015 period. Two former prime ministers, a series of former ministers served in the ministries of health and economy, such as bankers are included in the case, while the current manager of is banned from leaving the country. The minister's deputy described the allegations as "the biggest scandal since the creation of the Greek state", which caused "annual state expenditure on medicine to explode". Most of the ministers involved in the scandal have denied the allegations, calling the case "political targeting" and "bullying", created by Syriza party. Besides bribery that involves artificial increases in the price of several medicines, the case also involves money laundering, with suspicions of "illegal funds of more than four billion euros ($4.2 billion)" were involved. paid $1.2 million to Essential Consultants, an entity owned by Michael Cohen, following the 2017 inauguration of Donald Trump. Cohen was paid monthly, with each payment just under $100,000 | https://en.wikipedia.org/wiki?curid=159284 |
Novartis claims it paid Cohen to help it understand and influence the new administration's approach to drug pricing and regulation. In July 2018, the US Senate committee report "White House Access for Sale" revealed that Ag's relationship with Cohen was "longer and more detailed". initially stated that the relationship ceased a month after entering the US$1.2 million contract with Cohen's consulting firm since the consultants were not able to provide the information the pharmaceutical company needed. Later, it became clear, however, that then-CEO Joseph Jimenez and Cohen communicated via email multiple times during 2017, which included ideas to lower drug prices to be discussed with the president. According to the report, several of the ideas appeared later in Trump's drug pricing plan, released in early 2018, in which pharmaceutical companies were protected from reduced revenues. Having already received approval for Zolgensma in May 2019, on June 28 AveXis (a company) voluntarily disclosed to the FDA that some data previously submitted to the agency as part of the Biologics License Application (BLA) package was inaccurate. Specifically, the data manipulation related to an "in vivo" murine potency assay used in the early development of the product but the issue the FDA and wider community has taken is that AveXis was aware of the data manipulation as early as 14 March 2019, almost two months before the BLA was approved | https://en.wikipedia.org/wiki?curid=159284 |
Novartis To compound the problem in early August it emerged a senior manager sold almost $1 million worth of stock immediately before the FDA probe became public on August 6, but after the company had informed the FDA of the problem. As of September 2019 the FDA was still preparing its response to the scandal. | https://en.wikipedia.org/wiki?curid=159284 |
Heterogamy is a term applied to a variety of distinct phenomena in different scientific domains. Usually having to do with some kind of difference, "hetero", in reproduction, "gamy". See below for more specific senses. In reproductive biology, heterogamy is the alternation of differently organized generations, applied to the alternation between parthenogenetic and a sexual generation. This type of heterogamy occurs for example in some aphids. Alternately, "heterogamy" or "heterogamous" is often used as a synonym of heterogametic, meaning the presence of two unlike chromosomes in a sex. For example, XY males and ZW females are called the heterogamous sex. In cell biology, heterogamy is a synonym of anisogamy, the condition of having differently sized male and female gametes produced by different sexes or mating types in a species. In botany, a plant is heterogamous when it carries at least two different types of flowers in regard to their reproductive structures, for example male and female flowers or bisexual and female flowers. Stamens and carpels are not regularly present in each flower or floret. In sociology, heterogamy refers to a marriage between two individuals that differ in a certain criterion, and is contrasted with homogamy for a marriage or union between partners that match according to that criterion. For example, ethnic heterogamy refers to marriages involving individuals of different ethnic groups. Age heterogamy refers to marriages involving partners of significantly different ages | https://en.wikipedia.org/wiki?curid=162736 |
Heterogamy and homogamy are also used to describe marriage or union between people of unlike and like sex (or gender) respectively. | https://en.wikipedia.org/wiki?curid=162736 |
Secondary circulation In fluid dynamics, a secondary circulation is a weak circulation that plays a key maintenance role in sustaining a stronger primary circulation that contains most of the kinetic energy and inertia of a flow. For example, a (horizontally swirling), but their evolution and maintenance against friction involves an in-up-out flow that is important to its clouds and rain. On a planetary scale, Earth's winds are mostly east-west or zonal, but that flow is maintained against friction by the Coriolis force acting on a small north-south or meridional secondary circulation. | https://en.wikipedia.org/wiki?curid=164321 |
Annual cycle An annual cycle refers to a set of changes or events that uniformly, or consistently, take place at the same time of year. In biology, the annual cycle for plants and animals details behavioral and chemical changes that take place as the seasons advance. In business, a business cycle refers to the way modelling and analysis is applied to the periodic development and marketing of new products and services. In religion, the annual cycle refers to the various celebrations or memorials that occur in the same sequence from year to year. For example, in Christianity the liturgical year is an annual cycle, which for some Christian denominations is composed of the "temporal cycle" that tracks the events in the life of Christ, and the "sanctoral cycle" which tracks the various saint's days. Some Christian churches only observe the "temporal cycle". In climatology, an annual cycle is the part of a measured quantity's fluctuation that is attributed to Earth's changing position in orbit over the course of the year. Such quantities might be influenced directly (e.g. incoming solar radiation at a point at the surface) or indirectly (e.g. stratospheric westerlies and easterlies over the winter and summer hemispheres, respectively) by orbital position. Mathematically, the climatological annual cycle is commonly estimated from observational data or model output by taking the average of all Januaries, all Februaries, and so forth. If the observational record is long enough and conditions are stationary (i.e | https://en.wikipedia.org/wiki?curid=164548 |
Annual cycle there is no significant long-term trend), a meaningful annual cycle will result that can be used to calculate an anomaly time series. | https://en.wikipedia.org/wiki?curid=164548 |
Storm track Storm tracks are the relatively narrow zones in seas and oceans where storms travel driven by the prevailing winds. The Atlantic and Pacific have storm tracks along which most Atlantic or Pacific extratropical cyclones or tropical cyclones travel. The storm tracks usually begin in the westernmost parts of Atlantic and Pacific, where the large temperature contrasts between land and sea cause cyclones to form, particularly in winter. Surface friction cause these cyclones to quickly fill up and decay as soon as they reach land at the eastern end of the basins, accounting for the easternmost edges of the storm tracks. Storm tracks can shift position, causing important climatic patterns. As an example, during La Niña the Atlantic storm track shifts north causing droughts in Israel, while during El Niño it shifts south bringing heavy rains to the same region. Another example of a storm track is the circumpolar storm track in the Antarctic, however land-sea contrasts play no role in its formation. Given a grid point field of geopotential height, storm tracks can be visualized by contouring its average standard deviation, after the data has been band-pass filtered. | https://en.wikipedia.org/wiki?curid=164596 |
Mean flow In fluid dynamics, the fluid flow is often decomposed into a mean flow – and deviations from the mean. The averaging can be done either in space or in time, or by ensemble averaging. Calculation of the mean flow may often be as simple as the mathematical mean: simply add up the given flow rates and then divide the final figure by the number of initial readings. For example, given two discharges ("Q") of 3 m³/s and 5 m³/s, we can use these flow rates "Q" to calculate the mean flow rate "Q". Which in this case is "Q" = 4 m³/s. | https://en.wikipedia.org/wiki?curid=164597 |
Prognostic variable In the context of prognostics, a prognostic variable is a measured or estimated variable that is correlated with the health condition of a system, and may be used to predict its residual useful life. An ideal prognostic variable is easily measured or calculated, and provides an exact estimation of how long time the system can continue to operate before maintenance or replacement will be required. Real prognostic variables are usually either known with some uncertainty, may be difficult to measure, and their correlation to the state of health of the system may not be exact. Examples of prognostic variables are the age of a vehicle and its odometer reading: the older a car is, and the longer it has been driven, the more worn it can be expected to be. These prognostic variables are useful, but not ideal, since they do not consider other aspects such as the regularity of the maintenance that was applied on the vehicle, how they were driven, in which weather conditions, etc; they do, however, have the advantage of being easily measured, understood and verified, whereas an in-depth analysis of the mechanical condition of the vehicle would be expensive to perform, require specific skills to be understood and would be difficult to verify. In climate science, the term indicates a variable that a computer model predicts by integration of a physical equation, typically vorticity, divergence, temperature, surface pressure, and water vapour concentration in atmospheric models | https://en.wikipedia.org/wiki?curid=164681 |
Prognostic variable The term "prognostic" is given to some values or variables that are directly predicted by the model, such as temperature, water vapour, salinity, depth in atmospheric or ocean models; i.e., variables that can be directly obtained as a model outcome. On the other hand, there are some other variables that need to be calculated separately as derived variables, such as relative humidity, which may be a diagnostic variable obtained from the model's prognostic variables, temperature and water vapour. | https://en.wikipedia.org/wiki?curid=164681 |
Natural history is a domain of inquiry involving organisms, including animals, fungi and plants, in their natural environment, leaning more towards observational than experimental methods of study. A person who studies natural history is called a naturalist or natural historian. encompasses scientific research but is not limited to it. It involves the systematic study of any category of natural objects or organisms. So while it dates from studies in the ancient Greco-Roman world and the mediaeval Arabic world, through to European Renaissance naturalists working in near isolation, today's natural history is a cross discipline umbrella of many specialty sciences; e.g., geobiology has a strong multi-disciplinary nature. The meaning of the English term "natural history" (a calque of the Latin "historia naturalis") has narrowed progressively with time; while, by contrast, the meaning of the related term "nature" has widened (see also History below). In antiquity, "natural history" covered essentially anything connected with nature, or which used materials drawn from nature, such as Pliny the Elder's encyclopedia of this title, published circa 77 to 79 AD, which covers astronomy, geography, humans and their technology, medicine, and superstition, as well as animals and plants. Medieval European academics considered knowledge to have two main divisions: the humanities (primarily what is now known as classics) and divinity, with science studied largely through texts rather than observation or experiment | https://en.wikipedia.org/wiki?curid=166380 |
Natural history The study of nature revived in the Renaissance, and quickly became a third branch of academic knowledge, itself divided into descriptive natural history and natural philosophy, the analytical study of nature. In modern terms, natural philosophy roughly corresponded to modern physics and chemistry, while natural history included the biological and geological sciences. The two were strongly associated. During the heyday of the gentleman scientists, many people contributed to both fields, and early papers in both were commonly read at professional science society meetings such as the Royal Society and the French Academy of Sciences—both founded during the seventeenth century. had been encouraged by practical motives, such as Linnaeus' aspiration to improve the economic condition of Sweden. Similarly, the Industrial Revolution prompted the development of geology to help find useful mineral deposits. Modern definitions of natural history come from a variety of fields and sources, and many of the modern definitions emphasize a particular aspect of the field, creating a plurality of definitions with a number of common themes among them. For example, while natural history is most often defined as a type of observation and a subject of study, it can also be defined as a body of knowledge, and as a craft or a practice, in which the emphasis is placed more on the observer than on the observed | https://en.wikipedia.org/wiki?curid=166380 |
Natural history Definitions from biologists often focus on the scientific study of individual organisms in their environment, as seen in this definition by Marston Bates: "is the study of animals and Plants—of organisms. ... I like to think, then, of natural history as the study of life at the level of the individual—of what plants and animals do, how they react to each other and their environment, how they are organized into larger groupings like populations and communities" and this more recent definition by D.S. Wilcove and T. Eisner: "The close observation of organisms—their origins, their evolution, their behavior, and their relationships with other species". This focus on organisms in their environment is also echoed by H.W. Greene and J.B. Losos: "focuses on where organisms are and what they do in their environment, including interactions with other organisms. It encompasses changes in internal states insofar as they pertain to what organisms do". Some definitions go further, focusing on direct observation of organisms in their environment, both past and present, such as this one by G.A. Bartholomew: "A student of natural history, or a naturalist, studies the world by observing plants and animals directly | https://en.wikipedia.org/wiki?curid=166380 |
Natural history Because organisms are functionally inseparable from the environment in which they live and because their structure and function cannot be adequately interpreted without knowing some of their evolutionary history, the study of natural history embraces the study of fossils as well as physiographic and other aspects of the physical environment". A common thread in many definitions of natural history is the inclusion of a descriptive component, as seen in a recent definition by H.W. Greene: "Descriptive ecology and ethology". Several authors have argued for a more expansive view of natural history, including S. Herman, who defines the field as "the scientific study of plants and animals in their natural environments. It is concerned with levels of organization from the individual organism to the ecosystem, and stresses identification, life history, distribution, abundance, and inter-relationships. It often and appropriately includes an esthetic component", and T. Fleischner, who defines the field even more broadly, as "A practice of intentional, focused attentiveness and receptivity to the more-than-human world, guided by honesty and accuracy". These definitions explicitly include the arts in the field of natural history, and are aligned with the broad definition outlined by B. Lopez, who defines the field as the "Patient interrogation of a landscape" while referring to the natural history knowledge of the Eskimo (Inuit) | https://en.wikipedia.org/wiki?curid=166380 |
Natural history A slightly different framework for natural history, covering a similar range of themes, is also implied in the scope of work encompassed by many leading natural history museums, which often include elements of anthropology, geology, paleontology and astronomy along with botany and zoology, or include both cultural and natural components of the world. The plurality of definitions for this field has been recognized as both a weakness and a strength, and a range of definitions have recently been offered by practitioners in a recent collection of views on natural history. begins with Aristotle and other ancient philosophers who analyzed the diversity of the natural world. was understood by Pliny the Elder to cover anything that could be found in the world, including living things, geology, astronomy, technology, art and humanity. "De Materia Medica" was written between 50 and 70 AD by Pedanius Dioscorides, a Roman physician of Greek origin. It was widely read for more than 1,500 years until supplanted in the Renaissance, making it one of the longest-lasting of all natural history books. From the ancient Greeks until the work of Carl Linnaeus and other 18th century naturalists, a major concept of natural history was the "scala naturae" or Great Chain of Being, an arrangement of minerals, vegetables, more primitive forms of animals, and more complex life forms on a linear scale of supposedly increasing perfection, culminating in our species | https://en.wikipedia.org/wiki?curid=166380 |
Natural history was basically static through the Middle Ages in Europe—although in the Arabic and Oriental world it proceeded at a much brisker pace. From the thirteenth century, the work of Aristotle was adapted rather rigidly into Christian philosophy, particularly by Thomas Aquinas, forming the basis for natural theology. During the Renaissance, scholars (herbalists and humanists, particularly) returned to direct observation of plants and animals for natural history, and many began to accumulate large collections of exotic specimens and unusual monsters. Leonhart Fuchs was one of the three founding fathers of botany, along with Otto Brunfels and Hieronymus Bock. Other important contributors to the field were Valerius Cordus, Konrad Gesner ("Historiae animalium"), Frederik Ruysch, and Gaspard Bauhin. The rapid increase in the number of known organisms prompted many attempts at classifying and organizing species into taxonomic groups, culminating in the system of the Swedish naturalist Carl Linnaeus. A significant contribution to English natural history was made by parson-naturalists such as Gilbert White, William Kirby, John George Wood, and John Ray, who wrote about plants, animals, and other aspects of nature. Many of these men wrote about nature to make the natural theology argument for the existence or goodness of God. Since early modern times, however, a great number of women made contributions to natural history, particularly in the field of botany, be it as authors, collectors, or illustrators | https://en.wikipedia.org/wiki?curid=166380 |
Natural history In modern Europe, professional disciplines such as botany, geology, mycology, palaeontology, physiology and zoology were formed. "Natural history", formerly the main subject taught by college science professors, was increasingly scorned by scientists of a more specialized manner and relegated to an "amateur" activity, rather than a part of science proper. In Victorian Scotland it was believed that the study of natural history contributed to good mental health. Particularly in Britain and the United States, this grew into specialist hobbies such as the study of birds, butterflies, seashells (malacology/conchology), beetles and wildflowers; meanwhile, scientists tried to define a unified discipline of biology (though with only partial success, at least until the modern evolutionary synthesis). Still, the traditions of natural history continue to play a part in the study of biology, especially ecology (the study of natural systems involving living organisms and the inorganic components of the Earth's biosphere that support them), ethology (the scientific study of animal behavior), and evolutionary biology (the study of the relationships between life-forms over very long periods of time), and re-emerges today as integrative organismal biology. Amateur collectors and natural history entrepreneurs played an important role in building the world's large natural history collections, such as the Natural History Museum, London, and the National Museum of Natural History in Washington D.C | https://en.wikipedia.org/wiki?curid=166380 |
Natural history Three of the greatest English naturalists of the nineteenth century, Henry Walter Bates, Charles Darwin, and Alfred Russel Wallace—who all knew each other—each made natural history travels that took years, collected thousands of specimens, many of them new to science, and by their writings both advanced knowledge of "remote" parts of the world—the Amazon basin, the Galápagos Islands, and the Malay archipelago, among others—and in so doing helped to transform biology from a descriptive to a theory based science. The understanding of "Nature" as "an organism and not as a mechanism" can be traced to the writings of Alexander von Humboldt (Prussia, 1769–1859). Humboldt's copious writings and research were seminal influences for Charles Darwin, Simón Bolívar, Henry David Thoreau, Ernst Haeckel, and John Muir. museums, which evolved from cabinets of curiosities, played an important role in the emergence of professional biological disciplines and research programs. Particularly back in the 19th century, scientists began to use their natural history collections as teaching tools for advanced students and the basis for their own morphological research. The term "natural history" alone, or sometimes together with archaeology, forms the name of many national, regional and local natural history societies that maintain records for animals (including birds (ornithology), insects (entomology) and mammals (mammalogy)), fungi (mycology), plants (botany) and other organisms | https://en.wikipedia.org/wiki?curid=166380 |
Natural history They may also have geological and microscopical sections. Examples of these societies in Britain include the Natural History Society of Northumbria founded in 1829, London Natural History Society (1858), Birmingham Natural History Society (1859), British Entomological and Natural History Society founded in 1872, Glasgow Natural History Society, Manchester Microscopical and Natural History Society established in 1880, Whitby Naturalists' Club founded in 1913, Scarborough Field Naturalists' Society and the Sorby Natural History Society, Sheffield, founded in 1918. The growth of natural history societies was also spurred due to the growth of British colonies in tropical regions with numerous new species to be discovered. Many civil servants took an interest in their new surroundings, sending specimens back to museums in Britain. (See also: Indian natural history) Societies in other countries include the American Society of Naturalists and Polish Copernicus Society of Naturalists. | https://en.wikipedia.org/wiki?curid=166380 |
Windsock A windsock is a conical textile tube that resembles a giant sock. Windsocks can be used as a basic guide to wind direction and speed, or as decoration. Windsocks are used to tell wind speed and the direction of the wind speed itself. Windsocks typically are used at airports to indicate the direction and strength of the wind to pilots and at chemical plants where there is risk of gaseous leakage. They are sometimes located alongside highways at windy locations. At many airports, windsocks are lit at night, either by floodlights on top surrounding it or with one mounted on the pole shining inside it. Wind direction is the opposite of the direction in which the windsock is pointing (note that wind directions are conventionally specified as being the compass point from which the wind originates; so a windsock pointing due north indicates a southerly wind). Wind speed is indicated by the windsock's angle relative to the mounting pole; in low winds, the windsock droops; in high winds it flies horizontally. Alternating stripes of high visibility orange and white were initially used to help to estimate the speed of wind. Each stripe adds up 3 knots to the estimated wind speed. However, some circle frames mountings cause windsocks to be held open at one end, indicating a velocity of 3 knots, even though anemometers would show no wind speed. A fully extended windsock suggests a wind speed of or greater | https://en.wikipedia.org/wiki?curid=166760 |
Windsock Per FAA standards, a properly-functioning windsock will orient itself to a breeze of at least and will be fully extended by a wind of . Per Transport Canada standards: a wind will fully extend the wind sock, a wind will cause the wind sock to be 5° below the horizontal, a wind will cause the wind sock to be 30° below the horizontal. | https://en.wikipedia.org/wiki?curid=166760 |
Protein production is the biotechnological process of generating a specific protein. It is typically achieved by the manipulation of gene expression in an organism such that it expresses large amounts of a recombinant gene. This includes the transcription of the recombinant DNA to messenger RNA (mRNA), the translation of mRNA into polypeptide chains, which are ultimately folded into functional proteins and may be targeted to specific subcellular or extracellular locations. systems (in lab jargon also referred to as 'expression systems') are used in the life sciences, biotechnology, and medicine. Molecular biology research uses numerous proteins and enzymes, many of which are from expression systems; particularly DNA polymerase for PCR, reverse transcriptase for RNA analysis, restriction endonucleases for cloning, and to make proteins that are screened in drug discovery as biological targets or as potential drugs themselves. There are also significant applications for expression systems in industrial fermentation, notably the production of biopharmaceuticals such as human insulin to treat diabetes, and to manufacture enzymes. Commonly used protein production systems include those derived from bacteria, yeast,baculovirus/insect, mammalian cells, and more recently filamentous fungi such as "Myceliophthora thermophila". When biopharmaceuticals are produced with one of these systems, process-related impurities termed host cell proteins also arrive in the final product in trace amounts | https://en.wikipedia.org/wiki?curid=167540 |
Protein production The oldest and most widely used expression systems are cell-based and may be defined as the ""combination of an expression vector, its cloned DNA, and the host for the vector that provide a context to allow foreign gene function in a host cell, that is, produce proteins at a high level"". Overexpression is an abnormally and excessively high level of gene expression which produces a pronounced gene-related phenotype. There are many ways to introduce foreign DNA to a cell for expression, and many different host cells may be used for expression — each expression system has distinct advantages and liabilities. Expression systems are normally referred to by the host and the DNA source or the delivery mechanism for the genetic material. For example, common hosts are bacteria (such as "E.coli", "B. subtilis"), yeast (such as "S.cerevisiae") or eukaryotic cell lines. Common DNA sources and delivery mechanisms are viruses (such as baculovirus, retrovirus, adenovirus), plasmids, artificial chromosomes and bacteriophage (such as lambda). The best expression system depends on the gene involved, for example the "Saccharomyces cerevisiae" is often preferred for proteins that require significant posttranslational modification. Insect or mammal cell lines are used when human-like splicing of mRNA is required. Nonetheless, bacterial expression has the advantage of easily producing large amounts of protein, which is required for X-ray crystallography or nuclear magnetic resonance experiments for structure determination | https://en.wikipedia.org/wiki?curid=167540 |
Protein production Because bacteria are prokaryotes, they are not equipped with the full enzymatic machinery to accomplish the required post-translational modifications or molecular folding. Hence, multi-domain eukaryotic proteins expressed in bacteria often are non-functional. Also, many proteins become insoluble as inclusion bodies that are difficult to recover without harsh denaturants and subsequent cumbersome protein-refolding. To address these concerns, expressions systems using multiple eukaryotic cells were developed for applications requiring the proteins be conformed as in, or closer to eukaryotic organisms: cells of plants (i.e. tobacco), of insects or mammalians (i.e. bovines) are transfected with genes and cultured in suspension and even as tissues or whole organisms, to produce fully folded proteins. Mammalian "in vivo" expression systems have however low yield and other limitations (time-consuming, toxicity to host cells..). To combine the high yield/productivity and scalable protein features of bacteria and yeast, and advanced epigenetic features of plants, insects and mammalians systems, other protein production systems are developed using unicellular eukaryotes (i.e. non-pathogenic '"Leishmania"' cells). "E. coli" is one of the most widely used expression hosts, and DNA is normally introduced in a plasmid expression vector. The techniques for overexpression in "E | https://en.wikipedia.org/wiki?curid=167540 |
Protein production coli" are well developed and work by increasing the number of copies of the gene or increasing the binding strength of the promoter region so assisting transcription. For example, a DNA sequence for a protein of interest could be cloned or subcloned into a high copy-number plasmid containing the "lac" (often LacUV5) promoter, which is then transformed into the bacterium "E. coli". Addition of IPTG (a lactose analog) activates the lac promoter and causes the bacteria to express the protein of interest. "E. coli" strain BL21 and BL21(DE3) are two strains commonly used for protein production. As members of the B lineage, they lack "lon" and "OmpT" proteases, protecting the produced proteins from degradation. The DE3 prophage found in BL21(DE3) provides T7 RNA polymerase (driven by the LacUV5 promoter), allowing for vectors with the T7 promoter to be used instead. Non-pathogenic species of the gram-positive "Corynebacterium" are used for the commercial production of various amino acids. The "C. glutamicum" species is widely used for producing glutamate and lysine, components of human food, animal feed and pharmaceutical products. Expression of functionally active human epidermal growth factor has been done in "C. glutamicum", thus demonstrating a potential for industrial-scale production of human proteins. Expressed proteins can be targeted for secretion through either the general, secretory pathway (Sec) or the twin-arginine translocation pathway (Tat) | https://en.wikipedia.org/wiki?curid=167540 |
Protein production Unlike gram-negative bacteria, the gram-positive "Corynebacterium" lack lipopolysaccharides that function as antigenic endotoxins in humans. The non-pathogenic and gram-negative bacteria, "Pseudomonas fluorescens", is used for high level production of recombinant proteins; commonly for the development bio-therapeutics and vaccines. " P. fluorescens" is a metabolically versatile organism, allowing for high throughput screening and rapid development of complex proteins. "P. fluorescens" is most well known for its ability to rapid and successfully produce high titers of active, soluble protein. Expression systems using either "S. cerevisiae" or "Pichia pastoris" allow stable and lasting production of proteins that are processed similarly to mammalian cells, at high yield, in chemically defined media of proteins. Filamentous fungi, especially "Aspergillus" and "Trichoderma", but also more recently "Myceliophthora thermophila" C1 have been developed into expression platforms for screening and production of diverse industrial enzymes. The expression system C1 shows a low viscosity morphology in submerged culture, enabling the use of complex growth and production media. Baculovirus-infected insect cells (Sf9, Sf21, High Five strains) or mammalian cells (HeLa, HEK 293) allow production of glycosylated or membrane proteins that cannot be produced using fungal or bacterial systems. It is useful for production of proteins in high quantity | https://en.wikipedia.org/wiki?curid=167540 |
Protein production Genes are not expressed continuously because infected host cells eventually lyse and die during each infection cycle. Non-lytic insect cell expression is an alternative to the lytic baculovirus expression system. In non-lytic expression, vectors are transiently or stably transfected into the chromosomal DNA of insect cells for subsequent gene expression. This is followed by selection and screening of recombinant clones. The non-lytic system has been used to give higher protein yield and quicker expression of recombinant genes compared to baculovirus-infected cell expression. Cell lines used for this system include: Sf9, Sf21 from "Spodoptera frugiperda" cells, Hi-5 from "Trichoplusia ni" cells, and Schneider 2 cells and Schneider 3 cells from "Drosophila melanogaster" cells. With this system, cells do not lyse and several cultivation modes can be used. Additionally, protein production runs are reproducible. This system gives a homogeneous product. A drawback of this system is the requirement of an additional screening step for selecting viable clones. "Leishmania tarentolae" (cannot infect mammals) expression systems allow stable and lasting production of proteins at high yield, in chemically defined media. Produced proteins exhibit fully eukaryotic post-translational modifications, including glycosylation and disulfide bond formation. The most common mammalian expression systems are Chinese Hamster ovary (CHO) and Human embryonic kidney (HEK) cells | https://en.wikipedia.org/wiki?curid=167540 |
Protein production Cell-free production of proteins is performed "in vitro" using purified RNA polymerase, ribosomes, tRNA and ribonucleotides. These reagents may be produced by extraction from cells or from a cell-based expression system. Due to the low expression levels and high cost of cell-free systems, cell-based systems are more widely used. | https://en.wikipedia.org/wiki?curid=167540 |
Glycogen is a multibranched polysaccharide of glucose that serves as a form of energy storage in animals, fungi, and bacteria. The polysaccharide structure represents the main storage form of glucose in the body. functions as one of two forms of energy reserves, glycogen being for short-term and the other form being triglyceride stores in adipose tissue (i.e., body fat) for long-term storage. In humans, glycogen is made and stored primarily in the cells of the liver and skeletal muscle. In the liver, glycogen can make up 5–6% of the organ's fresh weight, and the liver of an adult weighing 1.5 kg can store roughly 100–120 grams of glycogen. In skeletal muscle, glycogen is found in a low concentration (1–2% of the muscle mass) and the skeletal muscle of an adult weighing 70 kg stores roughly 400 grams of glycogen. The amount of glycogen stored in the body—particularly within the muscles and liver—mostly depends on physical training, basal metabolic rate, and eating habits. Small amounts of glycogen are also found in other tissues and cells, including the kidneys, red blood cells, white blood cells, and glial cells in the brain. The uterus also stores glycogen during pregnancy to nourish the embryo. Approximately 4 grams of glucose are present in the blood of humans at all times; in fasted individuals, blood glucose is maintained constant at this level at the expense of glycogen stores in the liver and skeletal muscle | https://en.wikipedia.org/wiki?curid=168986 |
Glycogen stores in skeletal muscle serve as a form of energy storage for the muscle itself; however, the breakdown of muscle glycogen impedes muscle glucose uptake from the blood, thereby increasing the amount of blood glucose available for use in other tissues. Liver glycogen stores serve as a store of glucose for use throughout the body, particularly the central nervous system. The human brain consumes approximately 60% of blood glucose in fasted, sedentary individuals. is the analogue of starch, a glucose polymer that functions as energy storage in plants. It has a structure similar to amylopectin (a component of starch), but is more extensively branched and compact than starch. Both are white powders in their dry state. is found in the form of granules in the cytosol/cytoplasm in many cell types, and plays an important role in the glucose cycle. forms an energy reserve that can be quickly mobilized to meet a sudden need for glucose, but one that is less compact than the energy reserves of triglycerides (lipids). As such it is also found as storage reserve in many parasitic protozoa. is a branched biopolymer consisting of linear chains of glucose residues with an average chain length of approximately 8–12 glucose units. Glucose units are linked together linearly by α(1→4) glycosidic bonds from one glucose to the next. Branches are linked to the chains from which they are branching off by α(1→6) glycosidic bonds between the first glucose of the new branch and a glucose on the stem chain | https://en.wikipedia.org/wiki?curid=168986 |
Glycogen Due to the way glycogen is synthesised, every glycogen granule has at its core a glycogenin protein. in muscle, liver, and fat cells is stored in a hydrated form, composed of three or four parts of water per part of glycogen associated with 0.45 millimoles (18 mg) of potassium per gram of glycogen. Glucose is an osmotic molecule, and can have profound effects on osmotic pressure in high concentrations possibly leading to cell damage or death if stored in the cell without being modified. is a non-osmotic molecule, so it can be used as a solution to storing glucose in the cell without disrupting osmotic pressure. As a meal containing carbohydrates or protein is eaten and digested, blood glucose levels rise, and the pancreas secretes insulin. Blood glucose from the portal vein enters liver cells (hepatocytes). Insulin acts on the hepatocytes to stimulate the action of several enzymes, including glycogen synthase. Glucose molecules are added to the chains of glycogen as long as both insulin and glucose remain plentiful. In this postprandial or "fed" state, the liver takes in more glucose from the blood than it releases. After a meal has been digested and glucose levels begin to fall, insulin secretion is reduced, and glycogen synthesis stops. When it is needed for energy, glycogen is broken down and converted again to glucose. phosphorylase is the primary enzyme of glycogen breakdown | https://en.wikipedia.org/wiki?curid=168986 |
Glycogen For the next 8–12 hours, glucose derived from liver glycogen is the primary source of blood glucose used by the rest of the body for fuel. Glucagon, another hormone produced by the pancreas, in many respects serves as a countersignal to insulin. In response to insulin levels being below normal (when blood levels of glucose begin to fall below the normal range), glucagon is secreted in increasing amounts and stimulates both glycogenolysis (the breakdown of glycogen) and gluconeogenesis (the production of glucose from other sources). Muscle cell glycogen appears to function as an immediate reserve source of available glucose for muscle cells. Other cells that contain small amounts use it locally, as well. As muscle cells lack glucose-6-phosphatase, which is required to pass glucose into the blood, the glycogen they store is available solely for internal use and is not shared with other cells. This is in contrast to liver cells, which, on demand, readily do break down their stored glycogen into glucose and send it through the blood stream as fuel for other organs. was discovered by Claude Bernard. His experiments showed that the liver contained a substance that could give rise to reducing sugar by the action of a "ferment" in the liver. By 1857, he described the isolation of a substance he called ""la matière glycogène"", or "sugar-forming substance". Soon after the discovery of glycogen in the liver, A. Sanson found that muscular tissue also contains glycogen | https://en.wikipedia.org/wiki?curid=168986 |
Glycogen The empirical formula for glycogen of () was established by Kekulé in 1858. synthesis is, unlike its breakdown, endergonic—it requires the input of energy. Energy for glycogen synthesis comes from uridine triphosphate (UTP), which reacts with glucose-1-phosphate, forming UDP-glucose, in a reaction catalysed by UTP—glucose-1-phosphate uridylyltransferase. is synthesized from monomers of UDP-glucose initially by the protein glycogenin, which has two tyrosine anchors for the reducing end of glycogen, since glycogenin is a homodimer. After about eight glucose molecules have been added to a tyrosine residue, the enzyme glycogen synthase progressively lengthens the glycogen chain using UDP-glucose, adding α(1→4)-bonded glucose to the reducing end of the glycogen chain. The glycogen branching enzyme catalyzes the transfer of a terminal fragment of six or seven glucose residues from a nonreducing end to the C-6 hydroxyl group of a glucose residue deeper into the interior of the glycogen molecule. The branching enzyme can act upon only a branch having at least 11 residues, and the enzyme may transfer to the same glucose chain or adjacent glucose chains. is cleaved from the nonreducing ends of the chain by the enzyme glycogen phosphorylase to produce monomers of glucose-1-phosphate: In vivo, phosphorolysis proceeds in the direction of glycogen breakdown because the ratio of phosphate and glucose-1-phosphate is usually greater than 100 | https://en.wikipedia.org/wiki?curid=168986 |
Glycogen Glucose-1-phosphate is then converted to glucose 6-phosphate (G6P) by phosphoglucomutase. A special debranching enzyme is needed to remove the α(1-6) branches in branched glycogen and reshape the chain into a linear polymer. The G6P monomers produced have three possible fates: The most common disease in which glycogen metabolism becomes abnormal is diabetes, in which, because of abnormal amounts of insulin, liver glycogen can be abnormally accumulated or depleted. Restoration of normal glucose metabolism usually normalizes glycogen metabolism, as well. In hypoglycemia caused by excessive insulin, liver glycogen levels are high, but the high insulin levels prevent the glycogenolysis necessary to maintain normal blood sugar levels. Glucagon is a common treatment for this type of hypoglycemia. Various inborn errors of metabolism are caused by deficiencies of enzymes necessary for glycogen synthesis or breakdown. These are collectively referred to as glycogen storage diseases. Long-distance athletes, such as marathon runners, cross-country skiers, and cyclists, often experience glycogen depletion, where almost all of the athlete's glycogen stores are depleted after long periods of exertion without sufficient carbohydrate consumption. This phenomenon is referred to as "hitting the wall". depletion can be forestalled in three possible ways. First, during exercise, carbohydrates with the highest possible rate of conversion to blood glucose (high glycemic index) are ingested continuously | https://en.wikipedia.org/wiki?curid=168986 |
Glycogen The best possible outcome of this strategy replaces about 35% of glucose consumed at heart rates above about 80% of maximum. Second, through endurance training adaptations and specialized regimens (e.g. fasting low-intensity endurance training), the body can condition type I muscle fibers to improve both fuel use efficiency and workload capacity to increase the percentage of fatty acids used as fuel, sparing carbohydrate use from all sources. Third, by consuming large quantities of carbohydrates after depleting glycogen stores as a result of exercise or diet, the body can increase storage capacity of intramuscular glycogen stores. This process is known as carbohydrate loading. In general, glycemic index of carbohydrate source does not matter since muscular insulin sensitivity is increased as a result of temporary glycogen depletion. When experiencing glycogen debt, athletes often experience extreme fatigue to the point that it is difficult to move. As a reference, the very best professional cyclists in the world will usually finish a 4- to 5-hr stage race right at the limit of glycogen depletion using the first three strategies. When athletes ingest both carbohydrate and caffeine following exhaustive exercise, their glycogen stores tend to be replenished more rapidly; however, the minimum dose of caffeine at which there is a clinically significant effect on glycogen repletion has not been established. | https://en.wikipedia.org/wiki?curid=168986 |
Twig A twig is a thin branch of a tree or bush. The buds on the twig are an important diagnostic characteristic, as are the abscission scars where the leaves have fallen away. The color, texture, and patterning of the twig bark are also important, in addition to the thickness and nature of any pith of the twig. There are two types of twig, vegetative twigs and fruiting spurs. Fruiting spurs are specialized twigs that generally branch off the sides of branches and are stubby and slow-growing, with many annular ring markings from seasons past. The age and rate of growth of a twig can be determined by counting the winter terminal bud scale scars, or annular ring marking, down the length of the twig. | https://en.wikipedia.org/wiki?curid=169193 |
Binary phase In materials chemistry, a binary phase or binary compound is a chemical compound containing two different elements. Some binary phase compounds are molecular, e.g. carbon tetrachloride (CCl). More typically binary phase refers to extended solids. Famous examples zinc sulfide, which contains zinc and sulfur, and tungsten carbide, which contains tungsten and carbon. Phases with higher degrees of complexity feature more elements, e.g. three elements in ternary phases, four elements in quaternary phases. | https://en.wikipedia.org/wiki?curid=175638 |
Lignotuber A lignotuber is a woody swelling of the root crown possessed by some plants as a protection against destruction of the plant stem, such as by fire. The crown contains buds from which new stems may sprout, as well as stores of starch that can support a period of growth in the absence of photosynthesis. The term "lignotuber" was coined in 1924 by Australian botanist Leslie R. Kerr. Plants possessing lignotubers include "Eucalyptus marginata" (Jarrah), "Eucalyptus brevifolia" (snappy gum) and "Eucalyptus ficifolia" (scarlet gum) all of which can have lignotubers ten feet (3 meters) wide and three feet (one meter) deep as well as most mallees, and many "Banksia" species. Lignotubers develop from the cotyledonary bud in seedlings of several oak species including cork oak "Quercus suber", but do not develop in several other oak species, and are not apparent in mature cork oak trees. The largest known lignotubers (also called "root collar burls") are those of the Coast Redwood "(Sequoia sempervirens)" of central and northern California and extreme southwestern Oregon. A lignotuber washed into Big Lagoon (30 miles (48 km) north of Eureka, California) by the full gale storm of 1977 was 41 feet (12.5 meters) in diameter and about half as tall and estimated to weigh 525 short tons (476.3 metric tonnes). The largest dicot lignotubers are those of the Chinese Camphor Tree, or Kusu "(Cinnamomum camphora)" of Japan, China and the Koreas | https://en.wikipedia.org/wiki?curid=179211 |
Lignotuber Ones at the Vergelegen Estate in Cape Town, South Africa which were planted in the late 1600s have muffin-shaped lignotubers up to six feet (2 meters) high and about thirty feet (9 meters) in diameter. Perhaps the largest lignotuber in Australia would be that of "Old Bottle Butt", a Red Bloodwood Tree (Corymbia gummifera) near Wauchope, New South Wales that has a lignotuber about eight feet (2.5 meters) in height and seventeen feet thick (16.3 meters circumference) at breast height. Many plants with lignotubers grow in a shrubby habit, but with multiple stems arising from the lignotuber. The term lignotuberous shrub is used to describe this habit. | https://en.wikipedia.org/wiki?curid=179211 |
Pharmaceutical Research and Manufacturers of America (PhRMA, pronounced ), formerly known as the Pharmaceutical Manufacturers Association, is a trade group representing companies in the pharmaceutical industry in the United States. Founded in 1958, PhRMA's stated mission is advocacy for public policies that encourage the discovery of new medicines for patients by companies engaged in pharmaceutical and biopharmaceutical research. Steve Ubl became PhRMA's chairman in September 2015. PhRMA is headquartered in Washington, DC. In 2017, the organization had revenue of $455 million, $128 million of which was spent on lobbying activities. George A. Scangos, CEO of Biogen, is chairman of the PhRMA board. Joaquin Duato, chairman of Johnson & Johnson's pharmaceutical division, is chairman-elect and Joseph Jimenez, CEO of Novartis, is board treasurer. Previous leadership includes: John J. Castellani, formerly head of the Business Roundtable, a U.S. advocacy and lobbying group and Billy Tauzin, a former Republican congressman from Louisiana. The company has notably opposed market pricing strategies of Valeant Pharmaceuticals, deriding the firm as having a strategy "reflective of a hedge fund". SMARxT Disposal is a joint program run by the U.S. Fish and Wildlife Service, the American Pharmacists Association, and PhRMA to encourage consumers to properly dispose of unused medicines to avoid harm to the environment | https://en.wikipedia.org/wiki?curid=179628 |
Pharmaceutical Research and Manufacturers of America The Partnership for Prescription Assistance is a program by PhRMA and its member companies that connects patients in-need with information on low-cost and free prescription medication. PhRMA has in 2017 raised concerns over price increases for generic drugs out of patent by the company Marathon Pharmaceuticals over Duchenne muscular dystrophy treatment. The company has advocated abroad in South Africa regarding pharmaceutical drug intellectual property rules. In January 2018, the organization introduced the "Let's Talk About Cost" website, which makes the argument that much of the cost of medication goes to middlemen unassociated with pharmaceutical companies. | https://en.wikipedia.org/wiki?curid=179628 |
Lithification (from the Ancient Greek word "lithos" meaning 'rock' and the Latin-derived suffix "-ific") is the process in which sediments compact under pressure, expel connate fluids, and gradually become solid rock. Essentially, lithification is a process of porosity destruction through compaction and cementation. includes all the processes which convert unconsolidated sediments into sedimentary rocks. Petrifaction, though often used as a synonym, is more specifically used to describe the replacement of organic material by silica in the formation of fossils. | https://en.wikipedia.org/wiki?curid=182735 |
Sedimentology encompasses the study of modern sediments such as sand, silt, and clay, and the processes that result in their formation (erosion and weathering), transport, deposition and diagenesis. Sedimentologists apply their understanding of modern processes to interpret geologic history through observations of sedimentary rocks and sedimentary structures. Sedimentary rocks cover up to 75% of the Earth's surface, record much of the Earth's history, and harbor the fossil record. is closely linked to stratigraphy, the study of the physical and temporal relationships between rock layers or strata. The premise that the processes affecting the earth today are the same as in the past is the basis for determining how sedimentary features in the rock record were formed. By comparing similar features today to features in the rock record—for example, by comparing modern sand dunes to dunes preserved in ancient aeolian sandstones—geologists reconstruct past environments. There are four primary types of sedimentary rocks: clastics, carbonates, evaporites, and chemical. Sedimentary rocks provide a multitude of products which modern and ancient society has come to utilise. The aim of sedimentology, studying sediments, is to derive information on the depositional conditions which acted to deposit the rock unit, and the relation of the individual rock units in a basin into a coherent understanding of the evolution of the sedimentary sequences and basins, and thus, the Earth's geological history as a whole | https://en.wikipedia.org/wiki?curid=182779 |
Sedimentology The scientific basis of this is the principle of uniformitarianism, which states that the sediments within ancient sedimentary rocks were deposited in the same way as sediments which are being deposited at the Earth's surface today. Sedimentological conditions are recorded within the sediments as they are laid down; the form of the sediments at present reflects the events of the past and all events which affect the sediments, from the source of the sedimentary material to the stresses enacted upon them after diagenesis are available for study. The principle of superposition is critical to the interpretation of sedimentary sequences, and in older metamorphic terrains or fold and thrust belts where sediments are often intensely folded or deformed, recognising younging indicators or graded bedding is critical to interpretation of the sedimentary section and often the deformation and metamorphic structure of the region. Folding in sediments is analysed with the principle of original horizontality, which states that sediments are deposited at their angle of repose which, for most types of sediment, is essentially horizontal. Thus, when the younging direction is known, the rocks can be "unfolded" and interpreted according to the contained sedimentary information. The principle of lateral continuity states that layers of sediment initially extend laterally in all directions unless obstructed by a physical object or topography | https://en.wikipedia.org/wiki?curid=182779 |
Sedimentology The principle of cross-cutting relationships states that whatever cuts across or intrudes into the layers of strata is younger than the layers of strata. The methods employed by sedimentologists to gather data and evidence on the nature and depositional conditions of sedimentary rocks include; The longstanding understanding of how some mudstones form has been challenged by geologists at Indiana University (Bloomington) and the Massachusetts Institute of Technology. The research, which appears in the December 14th, 2007, edition of "Science", counters the prevailing view of geologists that mud only settles when water is slow-moving or still, instead showing that "muds will accumulate even when currents move swiftly." The research shows that some mudstones may have formed in fast-moving waters: "Mudstones can be deposited under more energetic conditions than widely assumed, requiring a reappraisal of many geologic records." Macquaker and Bohacs, in reviewing the research of Schieber et al., state that "these results call for critical reappraisal of all mudstones previously interpreted as having been continuously deposited under still waters. Such rocks are widely used to infer past climates, ocean conditions, and orbital variations." Considerable recent research into mudstones has been driven by the recent effort to commercially produce hydrocarbons from them, in both the Shale gas and Tight Oil (or Light Tight Oil) plays. | https://en.wikipedia.org/wiki?curid=182779 |
Petuntse (from 白墩子 in pinyin: bai2 dun1 zi0), also spelled petunse and bai dunzi, baidunzi, is a historic term for a wide range of micaceous or feldspathic rocks. However, all will have been subject to geological decomposition processes that result in a material which, after processing, is suitable as an ingredient in some ceramic formulations. The name means "little white bricks", referring to the form in which it was transported to the potteries (compare ball clay). It was, and to some extent continues to be, an important raw material for Chinese porcelain, although the terms "porcelain stone", or "pottery stone", are now used. The equivalent term in Chinese is "cishi". It is mixed with kaolin in proportions varying according to the grade of porcelain to be produced; equal quantities for the best and two thirds petuntse to one third kaolin for everyday ware. There are large deposits of high quality stone in Jiangxi province in south-eastern China, which became a centre for porcelain production, especially in Jingdezhen ware. While sharing some similarities to the material known as China stone, which is found uniquely in southwestern England, they differ in mineralogy. However both are derived from the alteration of igneous rocks. | https://en.wikipedia.org/wiki?curid=186138 |
Intermontane is a physiographic adjective formed from the prefix "inter-" (""signifying among, between, amid, during, within, mutual, reciprocal") and the adjective "montane" (""inhabiting, or growing in mountainous regions, especially cool, moist upland slopes below the timberline."") The corresponding "physiographic" noun is intermountain, while the noun "intermontane" is an "ecologic" noun meaning "among, between, amid, or within "flora and fauna of a montane habitat."" As an example, an alpine region would be an intermontane for a species that migrates between a glacial region and a subalpine region. In palaeogeography, intermontane may refer to | https://en.wikipedia.org/wiki?curid=186446 |
Nikolaas Tinbergen Nikolaas "Niko" Tinbergen (; ; 15 April 1907 – 21 December 1988) was a Dutch biologist and ornithologist who shared the 1973 Nobel Prize in Physiology or Medicine with Karl von Frisch and Konrad Lorenz for their discoveries concerning organization and elicitation of individual and social behavior patterns in animals. He is regarded as one of the founders of modern ethology, the study of animal behavior. In 1951, he published "The Study of Instinct", an influential book on animal behaviour. In the 1960s, he collaborated with filmmaker Hugh Falkus on a series of wildlife films, including "The Riddle of the Rook" (1972) and "Signals for Survival" (1969), which won the Italia prize in that year and the American blue ribbon in 1971. Born in The Hague, Netherlands, he was one of five children of Dirk Cornelis Tinbergen and his wife Jeannette van Eek. His brother, Jan Tinbergen, won the first Bank of Sweden Prize in Economic Sciences in Memory of Alfred Nobel in 1969. They are the only siblings to each win a Nobel Prize. Another brother, Luuk Tinbergen was also a noted biologist. Tinbergen's interest in nature manifested itself when he was young. He studied biology at Leiden University and was a prisoner of war during World War II. Tinbergen's experience as a prisoner of the Nazis led to some friction with longtime intellectual collaborator Konrad Lorenz, and it was several years before the two reconciled | https://en.wikipedia.org/wiki?curid=188094 |
Nikolaas Tinbergen After the war, Tinbergen moved to England, where he taught at the University of Oxford and was a fellow first at Merton College, Oxford and later at Wolfson College, Oxford. Several of his graduate students went on to become prominent biologists including Richard Dawkins, Marian Dawkins, Desmond Morris, Iain Douglas-Hamilton, and Tony Sinclair. In 1951 Tinbergen's "The Study of Instinct" was published. Behavioural ecologists and evolutionary biologists still recognise the contribution this book offered the field of behavioural science studies. "The Study of Instinct" summarises Tinbergen's ideas on innate behavioural reactions in animals and the adaptiveness and evolutionary aspects of these behaviours. By behaviour, he means the total movements made by the intact animal; innate behaviour is that which is not changed by the learning process. The major question of the book is the role of internal and external stimuli in controlling the expression of behaviour. In particular, he was interested in explaining 'spontaneous' behaviours: those that occurred in their complete form the first time they were performed and that seemed resistant to the effects of learning. He explains how behaviour can be considered a combination of these spontaneous behaviour patterns and as set series of reactions to particular stimuli. Behaviour is a reaction in that to a certain extent it is reliant on external stimuli, however it is also spontaneous since it is also dependent upon internal causal factors | https://en.wikipedia.org/wiki?curid=188094 |
Nikolaas Tinbergen His model for how certain behavioural reactions are provoked was based on work by Konrad Lorenz. Lorenz postulated that for each instinctive act there is a specific energy which builds up in a reservoir in the brain. In this model, Lorenz envisioned a reservoir with a spring valve at its base that an appropriate stimulus could act on, much like a weight on a scale pan pulling against a spring and releasing the reservoir of energy, an action which would lead an animal to express the desired behaviour. Tinbergen added complexity to this model, a model now known as Tinbergen's hierarchical model. He suggested that motivational impulses build up in nervous centres in the brain which are held in check by blocks. The blocks are removed by an innate releasing mechanism that allows the energy to flow to the next centre (each centre containing a block that needs to be removed) in a cascade until the behaviour is expressed. Tinbergen's model shows multiple levels of complexity and that related behaviours are grouped. An example is in his experiments with foraging honey bees. He showed that honey bees show curiosity for yellow and blue paper models of flowers, and suggested that these were visual stimuli causing the buildup of energy in one specific centre. However, the bees rarely landed on the model flowers unless the proper odour was also applied. In this case, the chemical stimuli of the odour allowed the next link in the chain to be released, encouraging the bee to land | https://en.wikipedia.org/wiki?curid=188094 |
Nikolaas Tinbergen The final step was for the bee to insert its mouthparts into the flower and initiate suckling. Tinbergen envisioned this as concluding the reaction set for honey bee feeding behaviour. In 1973 Tinbergen, along with Konrad Lorenz and Karl von Frisch, were awarded the Nobel Prize in Physiology or Medicine "for their discoveries concerning organization and elicitation of individual and social behaviour patterns". The award recognised their studies on genetically programmed behaviour patterns, their origins, maturation and their elicitation by key stimuli. In his Nobel Lecture, Tinbergen addressed the somewhat unconventional decision of the Nobel Foundation to award the prize for Physiology or Medicine to three men who had until recently been regarded as "mere animal watchers". Tinbergen stated that their revival of the "watching and wondering" approach to studying behaviour could indeed contribute to the relief of human suffering. The studies performed by the trio on fish, insects and birds laid the foundation for further studies on the importance of specific experiences during critical periods of normal development, as well as the effects of abnormal psychosocial situations in mammals. At the time, these discoveries were stated to have caused "a breakthrough in the understanding of the mechanisms behind various symptoms of psychiatric disease, such as anguish, compulsive obsession, stereotypic behaviour and catatonic posture" | https://en.wikipedia.org/wiki?curid=188094 |
Nikolaas Tinbergen Tinbergen's contribution to these studies included the testing of the hypotheses of Lorenz/von Frisch by means of "comprehensive, careful, and ingenious experiments" as well as his work on supernormal stimuli. The work of Tinbergen during this time was also regarded as having possible implications for further research in child development and behaviour. He also caused some intrigue by dedicating a large part of his acceptance speech to FM Alexander, originator of the Alexander technique, a method which investigates postural reflexes and responses in human beings. In 1950 Tinbergen became member of the Royal Netherlands Academy of Arts and Sciences. He was elected a Fellow of the Royal Society (FRS) in 1962. He was also awarded the Godman-Salvin Medal in 1969 by the British Ornithologists' Union, and in 1973 received the Swammerdam Medal and Wilhelm Bölsche Medal (from the Genootschap ter bervordering van Natuur-, Genees- en Heelkunde of the University of Amsterdam and the Kosmos-Gesellschaft der Naturfreunde respectively). Tinbergen described four questions he believed should be asked of any animal behaviour, which were: In ethology and sociobiology, causation and ontogeny are summarised as the "proximate mechanisms", while adaptation and phylogeny are the "ultimate mechanisms". They are still considered as the cornerstone of modern ethology, sociobiology and transdisciplinarity in Human Sciences. A major body of Tinbergen's research focused on what he termed the supernormal stimulus | https://en.wikipedia.org/wiki?curid=188094 |
Nikolaas Tinbergen This was the concept that one could build an artificial object which was a stronger stimulus or releaser for an instinct than the object for which the instinct originally evolved. He constructed plaster eggs to see which a bird preferred to sit on, finding that they would select those that were larger, had more defined markings, or more saturated colour—and a dayglo-bright one with black polka dots would be selected over the bird's own pale, dappled eggs. Tinbergen found that territorial male three-spined stickleback (a small freshwater fish) would attack a wooden fish model more vigorously than a real male if its underside was redder. He constructed cardboard dummy butterflies with more defined markings that male butterflies would try to mate with in preference to real females. The superstimulus, by its exaggerations, clearly delineated what characteristics were eliciting the instinctual response. Among the modern works calling attention to Tinbergen's classic work is Deirdre Barrett's 2010 book, "Supernormal Stimuli". Tinbergen applied his observational methods to the problems of autistic children. He recommended a "holding therapy" in which parents hold their autistic children for long periods of time while attempting to establish eye contact, even when a child resists the embrace. However, his interpretations of autistic behaviour, and the holding therapy that he recommended, lacked scientific support and the therapy is described as controversial and potentially abusive | https://en.wikipedia.org/wiki?curid=188094 |
Nikolaas Tinbergen Some of the publications of Tinbergen are: Publications about Tinbergen and his work: Tinbergen was a member of the advisory committee to the Anti-Concorde Project and was also an atheist. Tinbergen married Elisabeth Rutten (1912-1990) and they had five children. Later in life he suffered depression and feared he might, like his brother Luuk, commit suicide. He was treated by his friend, whose ideas he had greatly influenced, John Bowlby. Tinbergen died on 21 December 1988, after suffering a stroke at his home in Oxford, England. | https://en.wikipedia.org/wiki?curid=188094 |
GlaxoSmithKline The company has a primary listing on the London Stock Exchange and is a constituent of the FTSE 100 Index. , it had a market capitalisation of £81 billion (about US$107 billion), the fourth largest on the London Stock Exchange. It has a secondary listing on the New York Stock Exchange. The company developed the first malaria vaccine, RTS,S, which it said in 2014, it would make available for five percent above cost. Legacy products developed at GSK include several listed in the World Health Organization's List of Essential Medicines, such as amoxicillin, mercaptopurine, pyrimethamine, and zidovudine. In 2012, GSK pleaded guilty to promotion of drugs for unapproved uses, failure to report safety data, and kickbacks to physicians in the United States and agreed to pay a US$3billion (£1.9bn) settlement. It was the largest health-care fraud case to date in that country and the largest settlement by a drug company. Joseph Nathan and Co. was founded in 1873, as a general trading company in Wellington, New Zealand, by a Londoner, Joseph Edward Nathan. In 1904, it began producing a dried-milk baby food from excess milk produced on dairy farms near Bunnythorpe. The resulting product was first known as Defiance, then as Glaxo (from "lacto"), and sold with the slogan "Glaxo builds bonny babies." The Glaxo Laboratories sign is still visible "(right)" on what is now a car repair shop on the main street of Bunnythorpe. The company's first pharmaceutical product, released in 1924, was vitamin D | https://en.wikipedia.org/wiki?curid=192517 |
GlaxoSmithKline Glaxo Laboratories was incorporated as a distinct subsidiary company in London in 1935. Joseph Nathan's shareholders reorganised the group's structure in 1947, making Glaxo the parent and obtained a listing on the London Stock Exchange. Glaxo acquired Allen & Hanburys in 1958. The Scottish pharmacologist David Jack was hired as a researcher for Allen & Hanburys a few years after Glaxo took it over; he went on to lead the company's R&D until 1987. After Glaxo bought Meyer Laboratories in 1978, it began to play an important role in the US market. In 1983, the American arm, Glaxo Inc., moved to Research Triangle Park (US headquarters/research) and Zebulon (US manufacturing) in North Carolina. Burroughs Wellcome & Company was founded in 1880, in London by the American pharmacists Henry Wellcome and Silas Burroughs. The Wellcome Tropical Research Laboratories opened in 1902. In the 1920s Burroughs Wellcome established research and manufacturing facilities in Tuckahoe, New York, which served as the US headquarters until the company moved to Research Triangle Park in North Carolina in 1971. The Nobel Prize winning scientists Gertrude B. Elion and George H. Hitchings worked there and invented drugs still used many years later, such as mercaptopurine. In 1959, the Wellcome Foundation bought Cooper, McDougall & Robertson Inc to become more active in animal health. Glaxo and Wellcome merged in 1995, to form Glaxo Wellcome plc | https://en.wikipedia.org/wiki?curid=192517 |
GlaxoSmithKline Glaxo Wellcome restructured its R&D operation that year, cutting 10,000 jobs worldwide, closing its R&D facility in Beckenham, Kent, and opening a Medicines Research Centre in Stevenage, Hertfordshire. Also that year, Glaxo Wellcome acquired the California-based Affymax, a leader in the field of combinatorial chemistry. By 1999, Glaxo Wellcome had become the world's third-largest pharmaceutical company by revenues (behind Novartis and Merck), with a global market share of around 4 per cent. Its products included Imigran (for the treatment of migraine), salbutamol (Ventolin) (for the treatment of asthma), Zovirax (for the treatment of coldsores), and Retrovir and Epivir (for the treatment of AIDS). In 1999, the company was the world's largest manufacturer of drugs for the treatment of asthma and HIV/AIDS. It employed 59,000 people, including 13,400 in the UK, had 76 operating companies and 50 manufacturing facilities worldwide, and seven of its products were among the world's top 50 best-selling pharmaceuticals. The company had R&D facilities in Hertfordshire, Kent, London and Verona (Italy), and manufacturing plants in Scotland and the north of England. It had R&D centres in the US and Japan, and production facilities in the US, Europe and the Far East. In 1848, Thomas Beecham launched his Beecham's Pills laxative in England, giving birth to the Beecham Group. In 1859, Beecham opened its first factory in St Helens, Lancashire | https://en.wikipedia.org/wiki?curid=192517 |
GlaxoSmithKline By the 1960s Beecham was extensively involved in pharmaceuticals and consumer products such as Macleans toothpaste, Lucozade and synthetic penicillin research. John K. Smith opened his first pharmacy in Philadelphia in 1830. In 1865, Mahlon Kline joined the business, which 10 years later became Smith, Kline & Co. In 1891, it merged with French, Richard and Company, and in 1929, changed its name to Smith Kline & French Laboratories as it focused more on research. Years later it bought Norden Laboratories, a business doing research into animal health, and Recherche et Industrie Thérapeutiques in Belgium in 1963, to focus on vaccines. The company began to expand globally, buying seven laboratories in Canada and the United States in 1969. In 1982, it bought Allergan, a manufacturer of eye and skincare products. SmithKline & French merged with Beckman Inc. in 1982, and changed its name to "SmithKline Beckman". In 1988, it bought International Clinical Laboratories, and in 1989, merged with Beecham to form "SmithKline Beecham P.L.C.". The headquarters moved from the United States to England. To expand R&D in the United States, the company bought a new research center in 1995; another opened in 1997, in England at New Frontiers Science Park, Harlow. Glaxo Wellcome and SmithKline Beecham announced their intention to merge in January 2000. The merger was completed in December that year, forming (GSK) | https://en.wikipedia.org/wiki?curid=192517 |
GlaxoSmithKline The company's global headquarters are at GSK House, Brentford, London, officially opened in 2002, by then-Prime Minister Tony Blair. The building was erected at a cost of £300million and was home to 3,000 administrative staff. GSK completed the acquisition of New Jersey-based Block Drug in 2001, for . In 2006, GSK acquired the US-based consumer healthcare company CNS Inc., whose products included Breathe Right nasal strips and FiberChoice dietary supplements, for US$566million in cash. Chris Gent, previously CEO of Vodafone, was appointed chairman of the board in 2005. GSK opened its first R&D centre in China in 2007, in Shanghai, initially focused on neurodegenerative diseases. Andrew Witty became the chief executive officer in 2008. Witty joined Glaxo in 1985, and had been president of GSK's Pharmaceuticals Europe since 2003. In 2009, GSK acquired Stiefel Laboratories, then the world's largest independent dermatology drug company, for . In November 2009, the FDA approved GSK's vaccine for 2009 H1N1 influenza protection, manufactured by the company's ID Biomedical Corp in Canada. Also in November 2009, GSK formed a joint venture with Pfizer to create ViiV Healthcare, which specializes in HIV research. In 2010, the company acquired Laboratorios Phoenix, an Argentine pharmaceutical company, for US$253m, and the UK-based sports nutrition company Maxinutrition for £162million (US$256million) | https://en.wikipedia.org/wiki?curid=192517 |
GlaxoSmithKline In 2011, in a US$660-million deal, Prestige Brands Holdings took over 17 GSK brands with sales of US$210million, including BC Powder, Beano, Ecotrin, Fiber Choice, Goody's Powder, Sominex and Tagamet. In 2012, the company announced that it would invest £500million in manufacturing facilities in Ulverston, northern England, designating it as the site for a previously announced biotech plant. In May that year it acquired CellZome, a German biotech company, for US$98million, and in June worldwide rights to alitretinoin (Toctino), an eczema drug, for US$302million. In 2013, GSK acquired Human Genome Sciences (HGS) for US$3billion; the companies had collaborated on developing the lupus drug Belimumab (Benlysta), albiglutide for type 2 diabetes, and darapladib for atherosclerosis, and in September, sold its beverage division to Suntory. This included the brands Lucozade and Ribena; however, the deal did not include Horlicks. In March 2014, GSK paid US$1billion to raise its stake in its Indian pharmaceutical unit, Pharmaceuticals, to 75 percent as part of a move to focus on emerging markets. In April 2014, Novartis and Glaxo agreed on more than US$20billion in deals, with Novartis selling its vaccine business to GSK and buying GSK's cancer business. In February 2015, GSK announced that it would acquire GlycoVaxyn, a Swiss pharmaceutical company, for US$190million, and in June that year that it would sell two meningitis drugs to Pfizer, Nimenrix and Mencevax for around US$130million | https://en.wikipedia.org/wiki?curid=192517 |
GlaxoSmithKline Philip Hampton, at that time chair of the Royal Bank of Scotland, became GSK chairman in September 2015. On 31 March 2017, Emma Walmsley became CEO. She is the first female CEO of the company. In December 2017, Reuters reported that Glaxo had increased its stake in its Saudi Arabian unit to 75% (from 49%) taking over control from its Saudi partner Banaja KSA Holding Company. With respect to rare diseases, the company divested its portfolio of gene therapy drugs to Orchard Therapeutics in April 2018. In November 2018, Reuters reported that Unilever was in prime position to acquire GSK's interest in its Indian unit, Consumer Healthcare Ltd, in a sale that could generate around US$4billion for the company. Nestlé and Coca-Cola have also been reported to be interested in the business unit as they look to strengthen their presence in India. On 3 December 2018, GSK announced that Unilever would acquire the Indian-listed Consumer Healthcare business for US$3.8billion (£2.98billion). Unilever will pay the majority of the deal in cash, with the remaining being paid in shares in its Ondian operation, Hindustan Unilever Limited. Upon completion, GSK will then own around 5.7% of Hindustan Unilever Limited, selling those shares in a number of tranches. The same day, the company also announced it would acquire oncology specialist, Tesaro, for US$5.1billion. The deal will give GSK control of ovarian cancer treatment, Zejula - a member of the class of poly ADP ribose polymerase (PARP) inhibitors | https://en.wikipedia.org/wiki?curid=192517 |
GlaxoSmithKline In October 2019, GSK agreed to sell its rabies vaccine, RabAvert, and its tick-borne encephalitis vaccine, Encepur, to Bavarian Nordic for US$1.06billion (€955million). In March 2018, GSK announced that it has reached an agreement with Novartis to acquire Novartis's 36.5% stake in their Consumer Healthcare Joint Venture for US$13billion (£9.2billion). In December 2018, GSK announced that it, along with Pfizer, had reached an agreement to merge and combine their consumer healthcare divisions into a single entity. The combined entity would have sales of around £9.8billion ($12.7billion), with GSK maintaining a 68% controlling stake in the joint venture. Pfizer would own the remaining 32% shareholding. The deal builds on an earlier 2018 deal where GSK bought out Novartis' stake in the GSK-Novartis consumer healthcare joint business. The culmination of the Consumer Healthcare string of deals will result in GSK splitting into two separate companies, via a demerger and subsequent listing of the joint venture. This will create two publicly traded companies, one focusing on pharmaceuticals and research & development, the other on consumer healthcare. SR One was established in 1985, by SmithKline Beecham to invest in new biotechnology companies and continued operating after GSK was formed; by 2003, GSK had formed another subsidiary, GSK Ventures, to out-license or start new companies around drug candidates that it did not intend to develop further | https://en.wikipedia.org/wiki?curid=192517 |
GlaxoSmithKline , SR One tended to invest only if the company aligned with GSK's business. In September 2019, GSK announced it would acquire Sitari Pharmaceuticals and its transglutaminase 2 small molecule program for the treatment of celiac disease. GSK manufactures products for major disease areas such as asthma, cancer, infections, diabetes and mental health. Medicines historically discovered or developed at GSK and its legacy companies and now sold as generics include amoxicillin and amoxicillin-clavulanate, ticarcillin-clavulanate, mupirocin, and ceftazidime for bacterial infections, zidovudine for HIV infection, valacyclovir for herpes virus infections, albendazole for parasitic infections, sumatriptan for migraine, lamotrigine for epilepsy, bupropion and paroxetine for major depressive disorder, cimetidine and ranitidine for gastroesophageal reflux disorder, mercaptopurine and thioguanine for the treatment of leukemia, allopurinol for gout, pyrimethamine for malaria, and the antibacterial trimethoprim. Among these, albendazole, amoxicillin, amoxicillin-clavulanate, allopurinol, mercaptopurine, mupirocin, pyrimethamine, ranitidine, thioguanine, trimethoprim, and zidovudine are on the World Health Organization's List of Essential Medicines, the safest and most effective medicines needed in a health system. In 2014, GSK applied for regulatory approval for the first malaria vaccine. Malaria is responsible for over 650,000 deaths annually, mainly in Africa | https://en.wikipedia.org/wiki?curid=192517 |
GlaxoSmithKline Known as RTS,S, the vaccine was developed as a joint project with the PATH vaccines initiative and the Bill and Melinda Gates Foundation. The company has committed to making the vaccine available in developing countries for five percent above the cost of production. , RTS,S, which uses GSK's proprietary AS01 adjuvant, was being examined in a Phase 3 trial in eight African countries. PATH reported that "[i]n the 12-month period following vaccination, RTS,S conferred approximately 50% protection from clinical Plasmodium falciparum disease in children aged 5-17 months, and approximately 30% protection in children aged 6-12 weeks when administered in conjunction with Expanded Program for Immunization (EPI) vaccines." In 2014, Glaxo said it had spent more than US$350million and expected to spend an additional US$260million before seeking regulatory approval. GSK's consumer healthcare division, which earned £5.2billion in 2013, sells oral healthcare, including Aquafresh, Maclean's and Sensodyne toothpastes; and drinks such as Horlicks, Boost and a chocolate-flavoured malt drink sold in India. GSK also previously owned the Lucozade and Ribena brands of soft drinks, but they were sold in 2013, to Suntory for £1.35bn. Other products include Abreva to treat cold sores; Night Nurse, a cold remedy; Breathe Right nasal strips; and Nicoderm and Nicorette nicotine replacements | https://en.wikipedia.org/wiki?curid=192517 |
GlaxoSmithKline In March 2014, it recalled Alli, an over-the-counter weight-loss drug, in the United States and Puerto Rico because of possible tampering, following customer complaints. , GSK had offices in over 115 countries and employed over 99,000 people, 12,500 in R&D. The company's single largest market is the United States. Its US headquarters are in The Navy Yard, Philadelphia, and Research Triangle Park, North Carolina; its consumer-products division is in Moon Township, Pennsylvania. Four scientists have been recognized by the Nobel Committee for their contributions to basic medical science and/or therapeutics development. Since 2010, has several times ranked first among pharmaceutical companies on the Global Access to Medicines Index, which is funded by the Bill and Melinda Gates Foundation. In 2014, the Human Rights Campaign, an LGBT-rights advocacy group gave GSK a score of 100 percent in its Corporate Equality Index. GSK has been active, with the World Health Organization (WHO), in the Global Alliance to Eliminate Lymphatic Filariasis (GAELF). Around 120million people globally are believed to be infected with lymphatic filariasis. In 2012, the company endorsed the London Declaration on Neglected Tropical Diseases; it agreed to donate 400million albendazole tablets to the WHO each year to fight soil-transmitted helminthiasis and to provide 600million albendazole tablets every year for lymphatic filariasis until the disease is eradicated | https://en.wikipedia.org/wiki?curid=192517 |
GlaxoSmithKline , over 5billion treatments had been delivered, and 18 of 73 countries in which the disease is considered endemic had progressed to the surveillance stage. In 2009, the company said it would cut drug prices by 25 percent in 50 of the poorest nations, release intellectual property rights for substances and processes relevant to neglected disease into a patent pool to encourage new drug development, and invest 20 percent of profits from the least-developed countries in medical infrastructure for those countries. Médecins Sans Frontières welcomed the decision, but criticized GSK for failing to include HIV patents in its patent pool and for not including middle-income countries in the initiative. In 2013, GSK licensed its HIV portfolio to the Medicines Patent Pool for use in children, and agreed to negotiate a license for dolutegravir, an integrase inhibitor then in clinical development. In 2014, this license was extended to include dolutegravir and adults with HIV. The licenses include countries in which 93 percent of adults and 99 percent of children with HIV live. Also in 2013 GSK joined AllTrials, a British campaign to ensure that all clinical trials are registered and the results reported. The company said it would make its past clinical-trial reports available and future ones within a year of the studies' end. In July 2012, GSK pleaded guilty in the United States to criminal charges, and agreed to pay US$3billion, in what was the largest settlement until then between the Justice Department and a drug company | https://en.wikipedia.org/wiki?curid=192517 |
GlaxoSmithKline The US$3billion included a criminal fine of US$956,814,400 and forfeiture of US$43,185,600. The remaining US$2billion covered a civil settlement with the government under the False Claims Act. The investigation was launched largely on the basis of information from four whistleblowers who filed qui tam (whistleblower) lawsuits against the company under the False Claims Act. The charges stemmed from GSK's promotion of the anti-depressants Paxil (paroxetine) and Wellbutrin (bupropion) for unapproved uses from 1998–2003, specifically as suitable for patients under the age of 18, and from its failure to report safety data about Avandia (rosiglitazone), both in violation of the Federal Food, Drug, and Cosmetic Act. Other drugs promoted for unapproved uses were two inhalers, Advair (fluticasone/salmeterol) and Flovent (fluticasone propionate), as well as Zofran (ondansetron), Imitrex (sumatriptan), Lotronex (alosetron) and Valtrex (valaciclovir). The settlement also covered reporting false best prices and underpaying rebates owed under the Medicaid Drug Rebate Program, and kickbacks to physicians to prescribe GSK's drugs. There were all-expenses-paid spa treatments and hunting trips for doctors and their spouses, speakers' fees at conferences, and payment for articles ghostwritten by the company and placed by physicians in medical journals. The company set up a ghostwriting programme called CASPPER, initially to produce articles about Paxil but which was extended to cover Avandia | https://en.wikipedia.org/wiki?curid=192517 |
GlaxoSmithKline As part of the settlement GSK signed a five-year corporate integrity agreement with the Department of Health and Human Services, which obliged the company to make major changes in the way it did business, including changing its compensation programmes for its sales force and executives, and to implement and maintain transparency in its research practices and publication policies. It announced in 2013, that it would no longer pay doctors to promote its drugs or attend medical conferences, and that its sales staff would no longer have prescription targets. The 2012 settlement included a criminal fine of US$242,612,800 for failing to report safety data to the FDA about Avandia (rosiglitazone), a diabetes drug approved in 1999, and a civil settlement of US$657million for making false claims about it. The Justice Department said GSK had promoted rosiglitazone to physicians with misleading information, including that it conferred cardiovascular benefits despite an FDA-mandated label warning of cardiovascular risks. In 1999, John Buse, a diabetes specialist, told medical conferences that rosiglitazone might carry an increased risk of cardiovascular problems. GSK threatened to sue him, called his university head of department, and persuaded him to sign a retraction. GSK raised questions internally about the drug's safety in 2000, and in 2002, the company ghostwrote an article in "Circulation" describing a GSK funded clinical trial that suggested rosiglitazone might have a beneficial effect on cardiovascular risk | https://en.wikipedia.org/wiki?curid=192517 |
GlaxoSmithKline From 2001, reports began to link the thiazolidinediones (the class of drugs to which rosiglitazone belongs) to heart failure. In April that year, GSK began a six-year, open-label, randomized trial, known as RECORD, to examine rosiglitazone and cardiovascular events. Two GSK meta-analyses in 2005, and 2006, showed an increased risk of cardiovascular problems with rosiglitazone; the information was passed to the FDA and posted on the company website, but not otherwise published. By December 2006, rosiglitazone had become the top-selling diabetes drug, with annual sales of US$3.3billion. In June 2007, "The New England Journal of Medicine" published a meta-analysis that associated the drug with an increased risk of heart attack. GSK had reportedly tried to persuade one of the authors, Steven Nissen, not to publish it, after receiving an advance copy from one of the journal's peer reviewers, a GSK consultant. In July 2007, FDA scientists suggested that rosiglitazone had caused 83,000 excess heart attacks between 1999, and 2007. The FDA placed restrictions on the drug, including adding a boxed warning, but did not withdraw it. (In 2013, the FDA rejected that the drug had caused excess heart attacks.) A Senate Finance Committee inquiry concluded in 2010, that GSK had sought to intimidate scientists who had concerns about rosiglitazone. In February that year the company tried to halt publication of an editorial about the controversy by Nissen in the "European Heart Journal" | https://en.wikipedia.org/wiki?curid=192517 |
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