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publishes his new measurements of the mass–velocity dependence, and claims to disprove the formula of Lorentz and Einstein. At the same time, he accepts that both the old model of Abraham (1902) and the later model of Bucherer & Langevin (1904) are consistent with the data. 1907 – Max Von Laue describes how the relativistic velocity-addition formula recreates the Fresnel drag coefficients. 1908 – Hermann Minkowski publishes his spacetime formalism of special relativity. 1908 – Frederick Thomas Trouton and Alexander Rankine conduct an experiment with electric circuit, proving that the length contraction is not the only relativistic effect and some form of time dilation is present – similarly to the previous experiments by Rayleigh (1902) and Brace (1904). 1908 – Walther Ritz publishes his ballistic theory of light as an alternative to special relativity and Maxwell’s electrodynamics. 1909 – Paul Ehrenfest publishes the Ehrenfest paradox about rigidity in special relativity. 1909 – Gilbert N. Lewis and Richard Tolman coin the disputed term relativistic mass. === 1910s === 1910 – Vladimir Ignatowski makes the first derivations of Lorentz transformations that rely mostly – and almost entirely – on the relativity principle, without appealing to Maxwell’s equations; such derivations are sometimes called single-postulate. 1910 – Edmund Taylor Whittaker and Vladimir Varićak introduce the idea of rapidity, but without using this name. 1911 – Alfred Robb coins the term rapidity. 1911 – Paul Langevin presents the twin paradox implied by time dilation. 1911 – Max von Laue writes that special relativity and Lorentz aether theory predict the Sagnac effect, absent in Ritz's ballistic theory or in Stokes's theory of aether drag. 1913 – Georges Sagnac observes the effect named after him, disproving Ritz's ballistic theory or aether drag. However, he favours Lorentz's model and even claims – incorrectly – to contradict SR. 1913
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"page_id": 69602684,
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"title": "Timeline of special relativity and the speed of light"
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|
– Willem de Sitter describes how the light of double stars contradicts Ritz’s ballistic theory of light. 1914 – Ludwik Silberstein gives the first description of Thomas–Wigner rotation, then underappreciated. 1914 – Günther Neumann measures the mass–velocity dependence for electrons. His result favours the formula of Lorentz & Einstein over the one by Abraham. 1915 – Charles-Eugène Guye and Charles Lavanchy make their own measurements of the inertia of cathode rays, much more exact than the earlier research by Kaufmann. Their conclusion is opposite to Kaufmann’s – again, the formula of Lorentz and Einstein is correct and Abraham’s model is disproved. === 1920s and 1930s === 1924 – Hans Thirring notices that ballistic theories of light contradict spectroscopic observations of the Sun. 1924 – Anton Lampa predicts a relativistic effect later known as Penrose–Terrell rotation. 1925 – the Michelson–Gale–Pearson experiment tests the Sagnac effect caused by the Earth’s rotation. The result disproves any aether drag; in combination with other experiments – disproving the stationary aether like the Michelson–Morley experiment – it proves the Lorentz transformations correct. 1925 – Llewelyn Thomas discovers Thomas precession, which can be explained by the effect described earlier by Silberstein and later by Wigner. 1928 – Paul Dirac describes the general energy–momentum relation, extending the equivalence of mass and energy. 1932 – Kennedy–Thorndike experiment confirms the Lorentz transformations in a new way, complementary to the Michelson–Morley experiment. These two results, if combined, prove some form of time dilation. 1932 – John Cockcroft and Ernest Walton prove the mass–energy equivalence via a nuclear reaction. 1933 – Dayton Miller conducts an improved form of the Michelson–Morley experiment, claiming to contradict special relativity. It would be later explained consistently with SR in the 1950s. 1935 – the Hammar experiment is another refutation of aether drag and evidence for special
|
{
"page_id": 69602684,
"source": null,
"title": "Timeline of special relativity and the speed of light"
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relativity. 1938 – Ives–Stilwell experiment measures time dilation via the relativistic Doppler effect. For the first time, the Lorentz transformations can be derived directly from empirical data, as would be noticed by Robertson in 1949. 1939 – Eugene Wigner rediscovers that SR predicts the Thomas–Wigner rotation. === After 1930s === 1940 – Bruno Rossi and D.B. Hall observe time dilation in cosmic rays, i.e. in the decay of muons. 1949 – Howard P. Robertson notices that the Lorentz transformations can be deduced (extracted) from three key experiments: Michelson–Morley, Kennedy–Thorndike and Ives–Stillwell. 1954 – Gerhart Lüders and Wolfgang Pauli prove that the Lorentz invariance in quantum field theories implies the CPT symmetry, allowing for new tests of special relativity. 1955 – Robert S. Shankland and others explain Miller’s experimental result from 1933 in a way consistent with special relativity. 1959 – Roger Penrose and James Terrell independently publish their rediscovery that SR predicts the Penrose–Terrell effect. 1959 – E. Dewan and M. Beran publish the thought experiment known as Bell's spaceship paradox. 1960 – Vernon W. Hughes et al. perform a spectroscopic experiment, later interpreted as evidence for the Lorentz invariance of particle interactions. 1961 – Ronald Drever independently conducts a similar experiment with the same conclusions. 1961 – Wolfgang Rindler presents and solves the ladder paradox. 1967 – Gerald Feinberg introduces the term tachyon for hypothetical particles with speeds higher than that of light in vacuum (c). 1971 – The Hafele–Keating experiment confirms time dilation predicted by special & general relativity. 1974 – Stefan Marinov claims to contradict special relativity by measuring a variation in c. His results are noted by the scientific community but rejected as incorrect. 1983 – the speed of light in vacuum (c) is used to define the metre in the SI system of units; the
|
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"page_id": 69602684,
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"title": "Timeline of special relativity and the speed of light"
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definition does not mention any frame of reference, assuming this speed is universal, and implicitly that special relativity is correct. == 21st century == 2011 – Faster-than-light neutrino anomaly is reported by CERN. 2012 – the anomaly in neutrino speed is explained by a failure of the equipment; this reason is officially reported. == See also == History of Lorentz transformations Timeline of gravitational physics and relativity == References == == Further reading == Andrzej Kajetan Wróblewski, Einstein and Physics hundred years ago, Acta Physica Polonica B, Vol. 37 (2006). Retrieved 2021-12-28.
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"page_id": 69602684,
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The following is a partial list of the "D" codes for Medical Subject Headings (MeSH), as defined by the United States National Library of Medicine (NLM). This list continues the information at List of MeSH codes (D12.776). Codes following these are found at List of MeSH codes (D20). For other MeSH codes, see List of MeSH codes. The source for this content is the set of 2006 MeSH Trees from the NLM. == MeSH D13 – nucleic acids, nucleotides, and nucleosides == === MeSH D13.150 – antisense elements (genetics) === ==== MeSH D13.150.200 – DNA, antisense ==== MeSH D13.150.200.640 – oligodeoxyribonucleotides, antisense ==== MeSH D13.150.480 – oligonucleotides, antisense ==== MeSH D13.150.480.640 – oligodeoxyribonucleotides, antisense MeSH D13.150.480.645 – oligoribonucleotides, antisense ==== MeSH D13.150.650 – rna, antisense ==== MeSH D13.150.650.319 – micrornas MeSH D13.150.650.640 – oligoribonucleotides, antisense MeSH D13.150.650.700 – rna, small interfering === MeSH D13.400 – nucleic acid precursors === ==== MeSH D13.400.730 – rna precursors ==== === MeSH D13.444 – nucleic acids === ==== MeSH D13.444.308 – DNA ==== MeSH D13.444.308.135 – DNA adducts MeSH D13.444.308.142 – DNA, a-form MeSH D13.444.308.148 – DNA, algal MeSH D13.444.308.150 – DNA, antisense MeSH D13.444.308.150.640 – oligodeoxyribonucleotides, antisense MeSH D13.444.308.180 – DNA, archaeal MeSH D13.444.308.212 – DNA, bacterial MeSH D13.444.308.227 – DNA, c-form MeSH D13.444.308.243 – DNA, catalytic MeSH D13.444.308.283 – DNA, circular MeSH D13.444.308.283.084 – DNA, catenated MeSH D13.444.308.283.170 – DNA, chloroplast MeSH D13.444.308.283.225 – DNA, mitochondrial MeSH D13.444.308.283.225.200 – DNA, kinetoplast MeSH D13.444.308.283.250 – DNA, superhelical MeSH D13.444.308.291 – DNA, concatenated MeSH D13.444.308.295 – DNA, cruciform MeSH D13.444.308.300 – DNA, fungal MeSH D13.444.308.315 – DNA, helminth MeSH D13.444.308.324 – DNA, intergenic MeSH D13.444.308.324.230 – DNA, ribosomal spacer MeSH D13.444.308.425 – DNA, neoplasm MeSH D13.444.308.435 – DNA, plant MeSH D13.444.308.435.275 – DNA, chloroplast MeSH D13.444.308.442 – DNA, protozoan MeSH D13.444.308.442.200 – DNA, kinetoplast
|
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"page_id": 5115261,
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MeSH D13.444.308.460 – DNA, recombinant MeSH D13.444.308.475 – DNA, ribosomal MeSH D13.444.308.475.230 – DNA, ribosomal spacer MeSH D13.444.308.480 – DNA, satellite MeSH D13.444.308.497 – DNA, single-stranded MeSH D13.444.308.497.220 – DNA, complementary MeSH D13.444.308.520 – DNA transposable elements MeSH D13.444.308.568 – DNA, viral MeSH D13.444.308.574 – DNA, z-form MeSH D13.444.308.580 – isochores MeSH D13.444.308.760 – retroelements ==== MeSH D13.444.500 – nucleic acid heteroduplexes ==== ==== MeSH D13.444.600 – nucleic acid probes ==== MeSH D13.444.600.150 – antisense elements (genetics) MeSH D13.444.600.150.200 – DNA, antisense MeSH D13.444.600.150.200.640 – oligodeoxyribonucleotides, antisense MeSH D13.444.600.150.640 – oligonucleotides, antisense MeSH D13.444.600.150.640.640 – oligodeoxyribonucleotides, antisense MeSH D13.444.600.150.640.645 – oligoribonucleotides, antisense MeSH D13.444.600.150.760 – rna, antisense MeSH D13.444.600.150.760.640 – oligoribonucleotides, antisense MeSH D13.444.600.223 – DNA probes MeSH D13.444.600.223.500 – DNA, complementary MeSH D13.444.600.223.550 – DNA probes, hla MeSH D13.444.600.223.555 – DNA probes, hpv MeSH D13.444.600.601 – oligonucleotide probes MeSH D13.444.600.723 – rna probes MeSH D13.444.600.723.480 – rna, complementary ==== MeSH D13.444.625 – peptide nucleic acids ==== ==== MeSH D13.444.735 – rna ==== MeSH D13.444.735.130 – rna, algal MeSH D13.444.735.150 – rna, antisense MeSH D13.444.735.150.319 – micrornas MeSH D13.444.735.150.640 – oligoribonucleotides, antisense MeSH D13.444.735.150.700 – rna, small interfering MeSH D13.444.735.300 – rna, archaeal MeSH D13.444.735.473 – rna, bacterial MeSH D13.444.735.476 – rna, chloroplast MeSH D13.444.735.480 – rna, complementary MeSH D13.444.735.490 – rna, double-stranded MeSH D13.444.735.500 – rna, fungal MeSH D13.444.735.520 – rna, helminth MeSH D13.444.735.544 – rna, messenger MeSH D13.444.735.544.355 – codon MeSH D13.444.735.544.355.225 – codon, initiator MeSH D13.444.735.544.355.250 – codon, terminator MeSH D13.444.735.544.355.250.235 – codon, nonsense MeSH D13.444.735.544.500 – rna caps MeSH D13.444.735.544.500.710 – rna cap analogs MeSH D13.444.735.544.527 – rna, messenger, stored MeSH D13.444.735.544.550 – rna splice sites MeSH D13.444.735.544.875 – untranslated regions MeSH D13.444.735.544.875.880 – 3' untranslated regions MeSH D13.444.735.544.875.885 – 5' untranslated regions MeSH D13.444.735.615 – rna, neoplasm MeSH D13.444.735.628 – rna, nuclear MeSH D13.444.735.628.806 –
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rna, heterogeneous nuclear MeSH D13.444.735.628.818 – rna, small nuclear MeSH D13.444.735.628.818.800 – rna, small nucleolar MeSH D13.444.735.635 – rna, plant MeSH D13.444.735.635.575 – rna, chloroplast MeSH D13.444.735.640 – rna precursors MeSH D13.444.735.650 – rna, protozoan MeSH D13.444.735.686 – rna, ribosomal MeSH D13.444.735.686.650 – rna, ribosomal, 5s MeSH D13.444.735.686.660 – rna, ribosomal, 5.8s MeSH D13.444.735.686.670 – rna, ribosomal, 16s MeSH D13.444.735.686.675 – rna, ribosomal, 18s MeSH D13.444.735.686.680 – rna, ribosomal, 23s MeSH D13.444.735.686.690 – rna, ribosomal, 28s MeSH D13.444.735.686.845 – rna, ribosomal, self-splicing MeSH D13.444.735.721 – rna, satellite MeSH D13.444.735.721.250 – cucumber mosaic virus satellite MeSH D13.444.735.757 – rna, transfer MeSH D13.444.735.757.286 – anticodon MeSH D13.444.735.757.700 – rna, transfer, amino acid-specific MeSH D13.444.735.757.700.050 – rna, transfer, ala MeSH D13.444.735.757.700.075 – rna, transfer, arg MeSH D13.444.735.757.700.085 – rna, transfer, asn MeSH D13.444.735.757.700.090 – rna, transfer, asp MeSH D13.444.735.757.700.200 – rna, transfer, cys MeSH D13.444.735.757.700.400 – rna, transfer, gln MeSH D13.444.735.757.700.410 – rna, transfer, glu MeSH D13.444.735.757.700.420 – rna, transfer, gly MeSH D13.444.735.757.700.450 – rna, transfer, his MeSH D13.444.735.757.700.480 – rna, transfer, ile MeSH D13.444.735.757.700.500 – rna, transfer, leu MeSH D13.444.735.757.700.510 – rna, transfer, lys MeSH D13.444.735.757.700.525 – rna, transfer, met MeSH D13.444.735.757.700.650 – rna, transfer, phe MeSH D13.444.735.757.700.660 – rna, transfer, pro MeSH D13.444.735.757.700.700 – rna, transfer, ser MeSH D13.444.735.757.700.725 – rna, transfer, thr MeSH D13.444.735.757.700.740 – rna, transfer, trp MeSH D13.444.735.757.700.750 – rna, transfer, tyr MeSH D13.444.735.757.700.900 – rna, transfer, val MeSH D13.444.735.757.715 – rna, transfer, amino acyl MeSH D13.444.735.790 – rna, untranslated MeSH D13.444.735.790.099 – micrornas MeSH D13.444.735.790.149 – regulatory sequences, ribonucleic acid MeSH D13.444.735.790.199 – rna, catalytic MeSH D13.444.735.790.400 – rna, guide MeSH D13.444.735.790.530 – rna, small cytoplasmic MeSH D13.444.735.790.537 – rna, small interfering MeSH D13.444.735.790.545 – rna, small nuclear MeSH D13.444.735.790.545.800 – rna, small nucleolar MeSH D13.444.735.790.560 – rna, spliced leader MeSH D13.444.735.790.878 – untranslated regions MeSH D13.444.735.790.878.880
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– 3' untranslated regions MeSH D13.444.735.790.878.885 – 5' untranslated regions MeSH D13.444.735.828 – rna, viral === MeSH D13.570 – nucleosides === ==== MeSH D13.570.065 – arabinonucleosides ==== MeSH D13.570.065.090 – arabinofuranosyluracil MeSH D13.570.065.300 – cytarabine MeSH D13.570.065.300.050 – ancitabine MeSH D13.570.065.950 – vidarabine ==== MeSH D13.570.230 – deoxyribonucleosides ==== MeSH D13.570.230.229 – deoxyadenosines MeSH D13.570.230.229.075 – cladribine MeSH D13.570.230.229.105 – dideoxyadenosine MeSH D13.570.230.229.650 – puromycin aminonucleoside MeSH D13.570.230.329 – deoxycytidine MeSH D13.570.230.329.100 – bromodeoxycytidine MeSH D13.570.230.329.950 – zalcitabine MeSH D13.570.230.329.950.500 – lamivudine MeSH D13.570.230.360 – deoxyguanosine MeSH D13.570.230.430 – deoxyuridine MeSH D13.570.230.430.196 – bromodeoxyuridine MeSH D13.570.230.430.432 – floxuridine MeSH D13.570.230.430.609 – idoxuridine MeSH D13.570.230.500 – dideoxynucleosides MeSH D13.570.230.500.090 – didanosine MeSH D13.570.230.500.105 – dideoxyadenosine MeSH D13.570.230.500.850 – stavudine MeSH D13.570.230.500.925 – zalcitabine MeSH D13.570.230.500.925.500 – lamivudine MeSH D13.570.230.500.950 – zidovudine MeSH D13.570.230.677 – pentostatin MeSH D13.570.230.855 – thymidine MeSH D13.570.230.855.875 – stavudine MeSH D13.570.230.855.900 – trifluridine MeSH D13.570.230.855.950 – zidovudine ==== MeSH D13.570.583 – purine nucleosides ==== MeSH D13.570.583.138 – adenosine MeSH D13.570.583.138.025 – adenosine-5'-(n-ethylcarboxamide) MeSH D13.570.583.138.240 – s-adenosylhomocysteine MeSH D13.570.583.138.264 – s-adenosylmethionine MeSH D13.570.583.138.300 – 2-chloroadenosine MeSH D13.570.583.138.300.200 – cladribine MeSH D13.570.583.138.325 – deoxyadenosines MeSH D13.570.583.138.325.075 – cladribine MeSH D13.570.583.138.325.105 – dideoxyadenosine MeSH D13.570.583.138.325.800 – puromycin aminonucleoside MeSH D13.570.583.138.500 – isopentenyladenosine MeSH D13.570.583.138.630 – phenylisopropyladenosine MeSH D13.570.583.138.711 – puromycin MeSH D13.570.583.138.711.650 – puromycin aminonucleoside MeSH D13.570.583.138.900 – vidarabine MeSH D13.570.583.454 – guanosine MeSH D13.570.583.454.240 – deoxyguanosine MeSH D13.570.583.454.500 – nucleoside q MeSH D13.570.583.616 – inosine MeSH D13.570.583.616.130 – didanosine MeSH D13.570.583.616.450 – inosine pranobex MeSH D13.570.583.616.900 – thioinosine MeSH D13.570.583.616.900.500 – methylthioinosine MeSH D13.570.583.910 – tubercidin ==== MeSH D13.570.685 – pyrimidine nucleosides ==== MeSH D13.570.685.245 – cytidine MeSH D13.570.685.245.217 – azacitidine MeSH D13.570.685.245.453 – cytarabine MeSH D13.570.685.245.453.050 – ancitabine MeSH D13.570.685.245.500 – deoxycytidine MeSH D13.570.685.245.500.250 – bromodeoxycytidine MeSH D13.570.685.245.500.950 – zalcitabine MeSH D13.570.685.245.500.950.500 – lamivudine MeSH D13.570.685.350 – formycins
|
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"page_id": 5115261,
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MeSH D13.570.685.350.200 – coformycin MeSH D13.570.685.350.200.700 – pentostatin MeSH D13.570.685.705 – thymidine MeSH D13.570.685.705.875 – stavudine MeSH D13.570.685.705.900 – trifluridine MeSH D13.570.685.705.950 – zidovudine MeSH D13.570.685.725 – tunicamycin MeSH D13.570.685.852 – uridine MeSH D13.570.685.852.150 – arabinofuranosyluracil MeSH D13.570.685.852.176 – azauridine MeSH D13.570.685.852.250 – 3-deazauridine MeSH D13.570.685.852.300 – deoxyuridine MeSH D13.570.685.852.300.150 – bromodeoxyuridine MeSH D13.570.685.852.300.350 – floxuridine MeSH D13.570.685.852.300.400 – idoxuridine MeSH D13.570.685.852.628 – pseudouridine MeSH D13.570.685.852.800 – tetrahydrouridine MeSH D13.570.685.852.829 – thiouridine ==== MeSH D13.570.800 – ribonucleosides ==== MeSH D13.570.800.096 – adenosine MeSH D13.570.800.096.250 – adenosine-5'-(n-ethylcarboxamide) MeSH D13.570.800.096.262 – s-adenosylhomocysteine MeSH D13.570.800.096.264 – s-adenosylmethionine MeSH D13.570.800.096.300 – 2-chloroadenosine MeSH D13.570.800.096.300.200 – cladribine MeSH D13.570.800.096.500 – isopentenyladenosine MeSH D13.570.800.096.630 – phenylisopropyladenosine MeSH D13.570.800.286 – cytidine MeSH D13.570.800.286.300 – azacitidine MeSH D13.570.800.330 – dichlororibofuranosylbenzimidazole MeSH D13.570.800.410 – formycins MeSH D13.570.800.410.200 – coformycin MeSH D13.570.800.453 – guanosine MeSH D13.570.800.453.500 – nucleoside q MeSH D13.570.800.573 – inosine MeSH D13.570.800.573.130 – didanosine MeSH D13.570.800.573.450 – inosine pranobex MeSH D13.570.800.573.900 – thioinosine MeSH D13.570.800.573.900.500 – methylthioinosine MeSH D13.570.800.790 – ribavirin MeSH D13.570.800.810 – showdomycin MeSH D13.570.800.840 – toyocamycin MeSH D13.570.800.850 – tubercidin MeSH D13.570.800.892 – uridine MeSH D13.570.800.892.176 – azauridine MeSH D13.570.800.892.250 – 3-deazauridine MeSH D13.570.800.892.628 – pseudouridine MeSH D13.570.800.892.800 – tetrahydrouridine MeSH D13.570.800.892.829 – thiouridine ==== MeSH D13.570.900 – thionucleosides ==== MeSH D13.570.900.800 – thioinosine MeSH D13.570.900.800.500 – methylthioinosine MeSH D13.570.900.829 – thiouridine === MeSH D13.695 – nucleotides === ==== MeSH D13.695.065 – arabinonucleotides ==== MeSH D13.695.065.200 – arabinofuranosylcytosine triphosphate MeSH D13.695.065.900 – vidarabine phosphate ==== MeSH D13.695.201 – deoxyribonucleotides ==== MeSH D13.695.201.100 – deoxyadenine nucleotides MeSH D13.695.201.150 – deoxycytosine nucleotides MeSH D13.695.201.150.200 – deoxycytidine monophosphate MeSH D13.695.201.175 – deoxyguanine nucleotides MeSH D13.695.201.200 – deoxyuracil nucleotides MeSH D13.695.201.200.270 – fluorodeoxyuridylate MeSH D13.695.201.486 – nucleoside diphosphate sugars MeSH D13.695.201.789 – thymine nucleotides MeSH D13.695.201.789.788 – thymidine monophosphate ==== MeSH D13.695.250 – dinucleoside phosphates ==== ==== MeSH
|
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"page_id": 5115261,
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|
D13.695.462 – nucleotides, cyclic ==== MeSH D13.695.462.200 – cyclic amp MeSH D13.695.462.200.225 – 8-bromo cyclic adenosine monophosphate MeSH D13.695.462.200.250 – bucladesine MeSH D13.695.462.250 – cyclic cmp MeSH D13.695.462.275 – cyclic gmp MeSH D13.695.462.275.325 – dibutyryl cyclic gmp MeSH D13.695.462.300 – cyclic imp ==== MeSH D13.695.578 – polynucleotides ==== MeSH D13.695.578.424 – oligonucleotides MeSH D13.695.578.424.224 – aptamers, nucleotide MeSH D13.695.578.424.450 – oligodeoxyribonucleotides MeSH D13.695.578.424.450.275 – DNA primers MeSH D13.695.578.424.480 – oligonucleotides, antisense MeSH D13.695.578.424.480.640 – oligodeoxyribonucleotides, antisense MeSH D13.695.578.424.480.645 – oligoribonucleotides, antisense MeSH D13.695.578.424.500 – oligoribonucleotides MeSH D13.695.578.424.600 – pyrimidine dimers MeSH D13.695.578.500 – polydeoxyribonucleotides MeSH D13.695.578.500.050 – apurinic acid MeSH D13.695.578.500.300 – poly da-dt MeSH D13.695.578.500.600 – poly t MeSH D13.695.578.550 – polyribonucleotides MeSH D13.695.578.550.050 – apurinic acid MeSH D13.695.578.550.500 – poly a MeSH D13.695.578.550.500.510 – poly a-u MeSH D13.695.578.550.530 – poly adenosine diphosphate ribose MeSH D13.695.578.550.560 – poly c MeSH D13.695.578.550.560.600 – poly i-c MeSH D13.695.578.550.600 – poly g MeSH D13.695.578.550.650 – poly i MeSH D13.695.578.550.650.600 – poly i-c MeSH D13.695.578.550.750 – poly u MeSH D13.695.578.550.750.510 – poly a-u ==== MeSH D13.695.667 – purine nucleotides ==== MeSH D13.695.667.138 – adenine nucleotides MeSH D13.695.667.138.124 – adenosine diphosphate MeSH D13.695.667.138.124.070 – adenosine diphosphate sugars MeSH D13.695.667.138.124.070.075 – adenosine diphosphate glucose MeSH D13.695.667.138.124.070.125 – adenosine diphosphate ribose MeSH D13.695.667.138.124.070.125.040 – o-acetyl-adp-ribose MeSH D13.695.667.138.124.070.125.195 – cyclic adp-ribose MeSH D13.695.667.138.180 – adenosine monophosphate MeSH D13.695.667.138.180.080 – adenosine phosphosulfate MeSH D13.695.667.138.236 – adenosine triphosphate MeSH D13.695.667.138.236.050 – adenylyl imidodiphosphate MeSH D13.695.667.138.236.250 – ethenoadenosine triphosphate MeSH D13.695.667.138.382 – coenzyme a MeSH D13.695.667.138.382.300 – acyl coenzyme a MeSH D13.695.667.138.382.300.020 – acetyl coenzyme a MeSH D13.695.667.138.382.300.500 – malonyl coenzyme a MeSH D13.695.667.138.382.300.700 – palmitoyl coenzyme a MeSH D13.695.667.138.395 – cyclic amp MeSH D13.695.667.138.395.225 – 8-bromo cyclic adenosine monophosphate MeSH D13.695.667.138.395.250 – bucladesine MeSH D13.695.667.138.410 – deoxyadenine nucleotides MeSH D13.695.667.138.506 – flavin-adenine dinucleotide MeSH D13.695.667.138.694 – nad MeSH D13.695.667.138.749
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}
|
– nadp MeSH D13.695.667.138.850 – phosphoadenosine phosphosulfate MeSH D13.695.667.138.925 – vidarabine phosphate MeSH D13.695.667.454 – guanine nucleotides MeSH D13.695.667.454.160 – cyclic gmp MeSH D13.695.667.454.160.325 – dibutyryl cyclic gmp MeSH D13.695.667.454.200 – deoxyguanine nucleotides MeSH D13.695.667.454.340 – guanosine diphosphate MeSH D13.695.667.454.340.350 – guanosine diphosphate sugars MeSH D13.695.667.454.340.350.400 – guanosine diphosphate fucose MeSH D13.695.667.454.340.350.500 – guanosine diphosphate mannose MeSH D13.695.667.454.440 – guanosine pentaphosphate MeSH D13.695.667.454.480 – guanosine tetraphosphate MeSH D13.695.667.454.504 – guanosine triphosphate MeSH D13.695.667.454.504.380 – guanosine 5'-o-(3-thiotriphosphate) MeSH D13.695.667.454.504.400 – guanylyl imidodiphosphate MeSH D13.695.667.454.525 – 5'-guanylic acid MeSH D13.695.667.454.700 – rna caps MeSH D13.695.667.454.700.710 – rna cap analogs MeSH D13.695.667.616 – inosine nucleotides MeSH D13.695.667.616.300 – cyclic imp MeSH D13.695.667.616.400 – inosine diphosphate MeSH D13.695.667.616.500 – inosine monophosphate MeSH D13.695.667.616.800 – inosine triphosphate ==== MeSH D13.695.740 – pyrimidine nucleotides ==== MeSH D13.695.740.050 – apurinic acid MeSH D13.695.740.246 – cytosine nucleotides MeSH D13.695.740.246.050 – arabinofuranosylcytosine triphosphate MeSH D13.695.740.246.115 – cyclic cmp MeSH D13.695.740.246.150 – cytidine diphosphate MeSH D13.695.740.246.150.180 – cytidine diphosphate choline MeSH D13.695.740.246.150.210 – cytidine diphosphate diglycerides MeSH D13.695.740.246.370 – cytidine monophosphate MeSH D13.695.740.246.370.250 – cytidine monophosphate n-acetylneuraminic acid MeSH D13.695.740.246.400 – cytidine triphosphate MeSH D13.695.740.246.425 – deoxycytosine nucleotides MeSH D13.695.740.246.425.300 – deoxycytidine monophosphate MeSH D13.695.740.600 – pyrimidine dimers MeSH D13.695.740.706 – thymine nucleotides MeSH D13.695.740.706.788 – thymidine monophosphate MeSH D13.695.740.850 – uracil nucleotides MeSH D13.695.740.850.210 – deoxyuracil nucleotides MeSH D13.695.740.850.210.200 – fluorodeoxyuridylate MeSH D13.695.740.850.600 – uridine diphosphate MeSH D13.695.740.850.600.677 – uridine diphosphate sugars MeSH D13.695.740.850.600.677.100 – uridine diphosphate n-acetylgalactosamine MeSH D13.695.740.850.600.677.120 – uridine diphosphate n-acetylglucosamine MeSH D13.695.740.850.600.677.150 – uridine diphosphate n-acetylmuramic acid MeSH D13.695.740.850.600.677.300 – uridine diphosphate galactose MeSH D13.695.740.850.600.677.350 – uridine diphosphate glucose MeSH D13.695.740.850.600.677.375 – uridine diphosphate glucuronic acid MeSH D13.695.740.850.600.677.800 – uridine diphosphate xylose MeSH D13.695.740.850.877 – uridine monophosphate MeSH D13.695.740.850.950 – uridine triphosphate ==== MeSH D13.695.827 – ribonucleotides ==== MeSH D13.695.827.068 – adenine nucleotides MeSH D13.695.827.068.124
|
{
"page_id": 5115261,
"source": null,
"title": "List of MeSH codes (D13)"
}
|
– adenosine diphosphate MeSH D13.695.827.068.124.070 – adenosine diphosphate sugars MeSH D13.695.827.068.124.070.075 – adenosine diphosphate glucose MeSH D13.695.827.068.124.070.125 – adenosine diphosphate ribose MeSH D13.695.827.068.124.070.125.040 – o-acetyl-adp-ribose MeSH D13.695.827.068.124.070.125.195 – cyclic adp-ribose MeSH D13.695.827.068.180 – adenosine monophosphate MeSH D13.695.827.068.180.080 – adenosine phosphosulfate MeSH D13.695.827.068.236 – adenosine triphosphate MeSH D13.695.827.068.236.050 – adenylyl imidodiphosphate MeSH D13.695.827.068.236.250 – ethenoadenosine triphosphate MeSH D13.695.827.068.382 – coenzyme a MeSH D13.695.827.068.382.300 – acyl coenzyme a MeSH D13.695.827.068.382.300.020 – acetyl coenzyme a MeSH D13.695.827.068.382.300.500 – malonyl coenzyme a MeSH D13.695.827.068.382.300.700 – palmitoyl coenzyme a MeSH D13.695.827.068.395 – cyclic amp MeSH D13.695.827.068.395.225 – 8-bromo cyclic adenosine monophosphate MeSH D13.695.827.068.395.250 – bucladesine MeSH D13.695.827.068.506 – flavin-adenine dinucleotide MeSH D13.695.827.068.694 – nad MeSH D13.695.827.068.749 – nadp MeSH D13.695.827.068.850 – phosphoadenosine phosphosulfate MeSH D13.695.827.232 – cytosine nucleotides MeSH D13.695.827.232.115 – cyclic cmp MeSH D13.695.827.232.150 – cytidine diphosphate MeSH D13.695.827.232.150.180 – cytidine diphosphate choline MeSH D13.695.827.232.150.210 – cytidine diphosphate diglycerides MeSH D13.695.827.232.370 – cytidine monophosphate MeSH D13.695.827.232.370.250 – cytidine monophosphate n-acetylneuraminic acid MeSH D13.695.827.232.400 – cytidine triphosphate MeSH D13.695.827.349 – flavin mononucleotide MeSH D13.695.827.426 – guanine nucleotides MeSH D13.695.827.426.160 – cyclic gmp MeSH D13.695.827.426.160.325 – dibutyryl cyclic gmp MeSH D13.695.827.426.340 – guanosine diphosphate MeSH D13.695.827.426.340.350 – guanosine diphosphate sugars MeSH D13.695.827.426.340.350.400 – guanosine diphosphate fucose MeSH D13.695.827.426.340.350.500 – guanosine diphosphate mannose MeSH D13.695.827.426.440 – guanosine pentaphosphate MeSH D13.695.827.426.480 – guanosine tetraphosphate MeSH D13.695.827.426.504 – guanosine triphosphate MeSH D13.695.827.426.504.380 – guanosine 5'-o-(3-thiotriphosphate) MeSH D13.695.827.426.504.400 – guanylyl imidodiphosphate MeSH D13.695.827.426.525 – 5'-guanylic acid MeSH D13.695.827.426.700 – rna caps MeSH D13.695.827.426.700.710 – rna cap analogs MeSH D13.695.827.519 – inosine nucleotides MeSH D13.695.827.519.300 – cyclic imp MeSH D13.695.827.519.400 – inosine diphosphate MeSH D13.695.827.519.500 – inosine monophosphate MeSH D13.695.827.519.800 – inosine triphosphate MeSH D13.695.827.648 – nicotinamide mononucleotide MeSH D13.695.827.708 – nucleoside diphosphate sugars MeSH D13.695.827.708.070 – adenosine diphosphate sugars MeSH D13.695.827.708.070.075 – adenosine diphosphate glucose MeSH D13.695.827.708.070.125 – adenosine diphosphate
|
{
"page_id": 5115261,
"source": null,
"title": "List of MeSH codes (D13)"
}
|
ribose MeSH D13.695.827.708.070.125.040 – o-acetyl-adp-ribose MeSH D13.695.827.708.070.125.195 – cyclic adp-ribose MeSH D13.695.827.708.070.125.600 – poly adenosine diphosphate ribose MeSH D13.695.827.708.260 – cytidine diphosphate diglycerides MeSH D13.695.827.708.400 – guanosine diphosphate sugars MeSH D13.695.827.708.400.410 – guanosine diphosphate fucose MeSH D13.695.827.708.400.500 – guanosine diphosphate mannose MeSH D13.695.827.708.727 – uridine diphosphate sugars MeSH D13.695.827.708.727.100 – uridine diphosphate n-acetylgalactosamine MeSH D13.695.827.708.727.120 – uridine diphosphate n-acetylglucosamine MeSH D13.695.827.708.727.150 – uridine diphosphate n-acetylmuramic acid MeSH D13.695.827.708.727.300 – uridine diphosphate galactose MeSH D13.695.827.708.727.350 – uridine diphosphate glucose MeSH D13.695.827.708.727.375 – uridine diphosphate glucuronic acid MeSH D13.695.827.708.727.800 – uridine diphosphate xylose MeSH D13.695.827.919 – uracil nucleotides MeSH D13.695.827.919.600 – uridine diphosphate MeSH D13.695.827.919.600.677 – uridine diphosphate sugars MeSH D13.695.827.919.600.677.100 – uridine diphosphate n-acetylgalactosamine MeSH D13.695.827.919.600.677.120 – uridine diphosphate n-acetylglucosamine MeSH D13.695.827.919.600.677.150 – uridine diphosphate n-acetylmuramic acid MeSH D13.695.827.919.600.677.300 – uridine diphosphate galactose MeSH D13.695.827.919.600.677.350 – uridine diphosphate glucose MeSH D13.695.827.919.600.677.375 – uridine diphosphate glucuronic acid MeSH D13.695.827.919.600.677.800 – uridine diphosphate xylose MeSH D13.695.827.919.877 – uridine monophosphate MeSH D13.695.827.919.950 – uridine triphosphate ==== MeSH D13.695.900 – thionucleotides ==== MeSH D13.695.900.380 – guanosine 5'-o-(3-thiotriphosphate) The list continues at List of MeSH codes (D20).
|
{
"page_id": 5115261,
"source": null,
"title": "List of MeSH codes (D13)"
}
|
The molecular formula C19H23N3 (molar mass: 293.41 g/mol, exact mass: 293.1892 u) may refer to: Amitraz Binedaline, or binodaline
|
{
"page_id": 36834690,
"source": null,
"title": "C19H23N3"
}
|
A primary standard in metrology is a standard that is sufficiently accurate such that it is not calibrated by or subordinate to other standards. Primary standards are defined via other quantities like length, mass and time. Primary standards are used to calibrate other standards referred to as working standards. See Hierarchy of Standards. == In chemistry == Standards are used in analytical chemistry. Here, a primary standard is typically a reagent which can be weighed easily, and which is so pure that its weight is truly representative of the number of moles of substance contained. Features of a primary standard include: High purity Stability (low reactivity) Low hygroscopicity (to minimize weight changes due to humidity) High equivalent weight (to minimize weighing errors) Long lasting molar solution i.e. concentration remains unchanged for long periods of time Non-toxicity Ready and cheap availability (The last two are not as essential as the first four.) Some examples of primary standards for titration of solutions, based on their high purity, are provided: Arsenic trioxide for making sodium arsenite solution for standardisation of sodium periodate solution (until Ph. Eur. 3, Appendix 2001 also for iodine and cerium(IV) sulfate solutions, since Ph. Eur. 4, 2002 standardised by sodium thiosulfate) Benzoic acid for standardisation of waterless basic solutions: ethanolic sodium and potassium hydroxide, TBAH, and alkali methanolates in methanol, isopropanol, or DMF Potassium bromate (KBrO3) for standardisation of sodium thiosulfate solutions Potassium hydrogen phthalate (usually called KHP) for standardisation of aqueous base and perchloric acid in acetic acid solutions Sodium carbonate for standardisation of aqueous acids: hydrochloric, sulfuric acid and nitric acid solutions (but not acetic acid) Sodium chloride for standardisation of silver nitrate solutions Sulfanilic acid for standardisation of sodium nitrite solutions Zinc powder, after being dissolved in sulfuric or hydrochloric acid, for standardization of EDTA solutions
|
{
"page_id": 200069,
"source": null,
"title": "Primary standard"
}
|
Such standards are often used to make standard solutions. These primary standards are used in titration and are essential for determining unknown concentrations or preparing working standards. == See also == Technical standard == References == == External links == Analytical Standards. Department of Chemistry, University of Adelaide, Australia.
|
{
"page_id": 200069,
"source": null,
"title": "Primary standard"
}
|
The molecular formula C20H34O (molar mass: 290.48 g/mol, exact mass: 290.2610 u) may refer to: Cembratrienol (CBTol) Geranylgeraniol Isotuberculosinol, also known as nosyberkol or edaxadiene
|
{
"page_id": 33230216,
"source": null,
"title": "C20H34O"
}
|
The Horner–Wadsworth–Emmons (HWE) reaction is a chemical reaction used in organic chemistry of stabilized phosphonate carbanions with aldehydes (or ketones) to produce predominantly E-alkenes. In 1958, Leopold Horner published a modified Wittig reaction using phosphonate-stabilized carbanions. William S. Wadsworth and William D. Emmons further defined the reaction. In contrast to phosphonium ylides used in the Wittig reaction, phosphonate-stabilized carbanions are more nucleophilic but less basic. Likewise, phosphonate-stabilized carbanions can be alkylated. Unlike phosphonium ylides, the dialkylphosphate salt byproduct is easily removed by aqueous extraction. Several reviews have been published. == Reaction mechanism == The Horner–Wadsworth–Emmons reaction begins with the deprotonation of the phosphonate to give the phosphonate carbanion 1. Nucleophilic addition of the carbanion onto the aldehyde 2 (or ketone) producing 3a or 3b is the rate-limiting step. If R2 = H, then intermediates 3a and 4a and intermediates 3b and 4b can interconvert with each other. The final elimination of oxaphosphetanes 4a and 4b yield (E)-alkene 5 and (Z)-alkene 6, with the by-product being a dialkyl-phosphate. The ratio of alkene isomers 5 and 6 is not dependent upon the stereochemical outcome of the initial carbanion addition and upon the ability of the intermediates to equilibrate. The electron-withdrawing group (EWG) alpha to the phosphonate is necessary for the final elimination to occur. In the absence of an electron-withdrawing group, the final product is the β-hydroxyphosphonate 3a and 3b. However, these β-hydroxyphosphonates can be transformed to alkenes by reaction with diisopropylcarbodiimide. == Stereoselectivity == The Horner–Wadsworth–Emmons reaction favours the formation of (E)-alkenes. In general, the more equilibration amongst intermediates, the higher the selectivity for (E)-alkene formation. === Disubstituted alkenes === Thompson and Heathcock have performed a systematic study of the reaction of methyl 2-(dimethoxyphosphoryl)acetate with various aldehydes. While each effect was small, they had a cumulative effect making it possible to
|
{
"page_id": 3804552,
"source": null,
"title": "Horner–Wadsworth–Emmons reaction"
}
|
modify the stereochemical outcome without modifying the structure of the phosphonate. They found greater (E)-stereoselectivity with the following conditions: Increasing steric bulk of the aldehyde Higher reaction temperatures (23 °C over −78 °C) Li > Na > K salts In a separate study, it was found that bulky phosphonate and bulky electron-withdrawing groups enhance E-alkene selectivity. === Trisubstituted alkenes === The steric bulk of the phosphonate and electron-withdrawing groups plays a critical role in the reaction of α-branched phosphonates with aliphatic aldehydes. Aromatic aldehydes produce almost exclusively (E)-alkenes. In case (Z)-alkenes from aromatic aldehydes are needed, the Still–Gennari modification (see below) can be used. === Olefination of ketones === The stereoselectivity of the Horner–Wadsworth–Emmons reaction of ketones is poor to modest. == Variations == === Base sensitive substrates === Since many substrates are not stable to sodium hydride, several procedures have been developed using milder bases. Masamune and Roush have developed mild conditions using lithium chloride and DBU. Rathke extended this to lithium or magnesium halides with triethylamine. Several other bases have been found effective. === Gennari-Still modification === W. Clark Still and C. Gennari have developed conditions that give Z-alkenes with excellent stereoselectivity. Using phosphonates with electron-withdrawing groups (trifluoroethyl) together with strongly dissociating conditions (KHMDS and 18-crown-6 in THF) nearly exclusive Z-alkene production can be achieved. Ando has suggested that the use of electron-deficient phosphonates accelerates the elimination of the oxaphosphetane intermediates. == See also == Wittig reaction Michaelis–Arbuzov reaction Michaelis–Becker reaction Peterson reaction Tebbe olefination == References ==
|
{
"page_id": 3804552,
"source": null,
"title": "Horner–Wadsworth–Emmons reaction"
}
|
Burton Richter (March 22, 1931 – July 18, 2018) was an American physicist. He led the Stanford Linear Accelerator Center (SLAC) team which co-discovered the J/ψ meson in 1974, alongside the Brookhaven National Laboratory (BNL) team led by Samuel Ting for which they won Nobel Prize for Physics in 1976. This discovery was part of the November Revolution of particle physics. He was the SLAC director from 1984 to 1999. == Life and work == A native of New York City, Richter was born into a Jewish family in Brooklyn, and was raised in the Queens neighborhood of Far Rockaway. His parents were Fanny (Pollack) and Abraham Richter, a textile worker. He graduated from Far Rockaway High School, a school that also produced fellow laureates Baruch Samuel Blumberg and Richard Feynman. He attended Mercersburg Academy in Pennsylvania, then continued on to study at the Massachusetts Institute of Technology, where he received his bachelor's degree in 1952 and his PhD in 1956. He then joined the faculty of Stanford University, becoming a full professor in 1967. Richter was director of the Stanford Linear Accelerator Center (SLAC) from 1984 to 1999. He was a senior fellow of the Freeman Spogli Institute for International Studies and Paul Pigott Professor in the Physical Sciences Emeritus of Stanford University. As a professor at Stanford, Richter designed the SPEAR (Stanford Positron-Electron Asymmetric Ring) particle accelerator with the help of another Stanford physics professor, David Ritson. When eventually resources were secured, Richter led the building of SPEAR, with the support of the U.S. Atomic Energy Commission. With it he led a team that discovered a new subatomic particle he called a ψ (psi). This discovery was also made by the team led by Samuel Ting at Brookhaven National Laboratory, but he called the particle J. The particle
|
{
"page_id": 396684,
"source": null,
"title": "Burton Richter"
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|
thus became known as the J/ψ meson. Richter and Ting were jointly awarded the 1976 Nobel Prize in Physics for their work. During 1975 Richter spent a sabbatical year at CERN where he worked on the ISR experiment R702. In 1987, Richter received the Golden Plate Award of the American Academy of Achievement. Richter was a member of the JASON advisory group and served on the board of directors of Scientists and Engineers for America, an organization focused on promoting sound science in American government. Richter was elected to the American Philosophical Society in 2003. In May 2007, he visited Iran and Sharif University of Technology. Richter is one of the 20 American recipients of the Nobel Prize in Physics to sign a letter addressed to President George W. Bush in May 2008, urging him to "reverse the damage done to basic science research in the Fiscal Year 2008 Omnibus Appropriations Bill" by requesting additional emergency funding for the Department of Energy’s Office of Science, the National Science Foundation, and the National Institute of Standards and Technology. In 2012, President Barack Obama announced that Burton Richter was a co-recipient of the Enrico Fermi Award, along with Mildred Dresselhaus. In 2014, President Obama also awarded Richter the 2012 National Medal of Science. His citation read, "For pioneering contributions to the development of electron accelerators, including circular and linear colliders, synchrotron light sources, and for discoveries in elementary particle physics and contributions to energy policy." In 2013, Richter commented on an open letter from Tom Wigley, Kerry Emanuel, Ken Caldeira, and James Hansen, that Angela Merkel was "wrong to shut down nuclear". In 2014, Richter was among the residents of a continuing care retirement center who filed an unsuccessful lawsuit against a continuing care retirement home's financial practices. Richter died on July
|
{
"page_id": 396684,
"source": null,
"title": "Burton Richter"
}
|
18, 2018, in Stanford, California, at the age 87. == See also == List of Jewish Nobel laureates List of independent discoveries == References == == Publications == Barber, W. C.; Richter, B.; Panofsky, W. K. H.; O'Neill, G. K. & B. Gittelman. "An Experiment on the Limits of Quantum Electro-dynamics", High-Energy Physics Laboratory at Stanford University, Princeton University, United States Department of Energy (through predecessor agency the Atomic Energy Commission), Office of Naval Research, (June 1959). Richter, B. "Design Considerations for High Energy Electron – Positron Storage Rings", Stanford Linear Accelerator Center, Stanford University, United States Department of Energy (through predecessor agency the Atomic Energy Commission), (November 1966). Boyarski, A. M.; Coward, D.; Ecklund, S.; Richter, B.; Sherden, D.; Siemann, R. & C. Sinclair. "Inclusive Yields of pi{sup +}, pi{sup -}, K{sup +}, and K{sup -} from H{sub 2} Photoproduced at 18 GeV at Forward Angles", Stanford Linear Accelerator Center, Stanford University, United States Department of Energy (through predecessor agency the Atomic Energy Commission), (1971). Richter, B. "Total Hadron Cross Section, New Particles, and Muon Electron Events in e{sup +}e{sup -} Annihilation at SPEAR", Stanford Linear Accelerator Center, Stanford University, United States Department of Energy (through predecessor agency the U.S. Energy Research and Development Administration (ERDA)), (January 1976). Richter, B. "Forty-five Years of e{sup +}e{sup -} Annihilation Physics: 1956 to 2001", Stanford Linear Accelerator Center, United States Department of Energy, (August 1984). Richter, B. "Charting the Course for Elementary Particle Physics", Stanford Linear Accelerator Center, United States Department of Energy, (February 16, 2007). Richter, B. Beyond Smoke and Mirrors: Climate Changes and Energy in the 21st Century. Second Edition. Cambridge University Press, 2014. ISBN 978-1-107-67372-4 == External links == Burton Richter on Nobelprize.org including the Nobel Lecture, December 11, 1976 From the Psi to Charm – The Experiments of
|
{
"page_id": 396684,
"source": null,
"title": "Burton Richter"
}
|
1975 and 1976 The Nobel Prize in Physics 1976 Richter Burton, Nobel Luminaries Project, The Museum of the Jewish People at Beit Hatfutsot SLAC Flickr album Historical photos of Burton Richter NIF Secretary of Energy Board Honoring Burton Richter at APS April 2019 Persis Drell, Vera Luth, and Maury Tigner, "Burton Richter", Biographical Memoirs of the National Academy of Sciences (2022)
|
{
"page_id": 396684,
"source": null,
"title": "Burton Richter"
}
|
Dichloroethane can refer to either of two isomeric organochlorides with the molecular formula C2H4Cl2: 1,1-Dichloroethane (ethylidene chloride) 1,2-Dichloroethane (ethylene dichloride) == See also == Dichloroethene Difluoroethane
|
{
"page_id": 3018125,
"source": null,
"title": "Dichloroethane"
}
|
A total internal reflection fluorescence microscope (TIRFM) is a type of microscope with which a thin region of a specimen, usually less than 200 nanometers can be observed. TIRFM is an imaging modality which uses the excitation of fluorescent cells in a thin optical specimen section that is supported on a glass slide. The technique is based on the principle that when excitation light is totally internally reflected in a transparent solid coverglass at its interface with a liquid medium, an electromagnetic field, also known as an evanescent wave, is generated at the solid-liquid interface with the same frequency as the excitation light. The intensity of the evanescent wave exponentially decays with distance from the surface of the solid so that only fluorescent molecules within a few hundred nanometers of the solid are efficiently excited. Two-dimensional images of the fluorescence can then be obtained, although there are also mechanisms in which three-dimensional information on the location of vesicles or structures in cells can be obtained. == History == Widefield fluorescence was introduced in 1910 which was an optical technique that illuminates the entire sample. Confocal microscopy was then introduced in 1960 which decreased the background and exposure time of the sample by directing light to a pinpoint and illuminating cones of light into the sample. In the 1980s, the introduction of TIRFM further decreased background and exposure time by only illuminating the thin section of the sample being examined. == Background == There are two common methods for producing the evanescent wave for TIRFM. The first is the prism method which uses a prism to direct the laser toward the interface between the coverglass and the media/cells at an incident angle sufficient to cause total internal reflection. This configuration has been applied to cellular microscopy for over 30 years but
|
{
"page_id": 1183118,
"source": null,
"title": "Total internal reflection fluorescence microscope"
}
|
has never become a mainstream tool due to several limitations. Although there are many variations of the prism configuration, most restrict access to the specimen which makes it difficult to perform manipulations, inject media into the specimen space, or carry out physiological measurements. Another disadvantage is that in most configurations based on the inverted microscope designs, the illumination is introduced on the specimen side opposite of the objective optics which requires imaging of the evanescent field region through the bulk of the specimen. There is great complexity and precision required in imaging this system which meant that the prism method was not used by many biologists but rather limited to use by physicists. The other method is known as the objective lens method which has increased the use of TIRFM in cellular microscopy and increased furthermore since a commercial solution became available. In this mechanism, one can easily switch between standard widefield fluorescence and TIRF by changing the off-axis position of the beam focus at the objective's back focal plane. There are several developed ways to change the positions of the beam such as using an actuator that can change the position in relation to the fluorescence illuminator that is attached to the microscope. == Application == In cell and molecular biology, a large number of molecular events in cellular surfaces such as cell adhesion, binding of cells by hormones, secretion of neurotransmitters, and membrane dynamics have been studied with conventional fluorescence microscopes. However, fluorophores that are bound to the specimen surface and those in the surrounding medium exist in an equilibrium state. When these molecules are excited and detected with a conventional fluorescence microscope, the resulting fluorescence from those fluorophores bound to the surface is often overwhelmed by the background fluorescence due to the much larger population of non-bound
|
{
"page_id": 1183118,
"source": null,
"title": "Total internal reflection fluorescence microscope"
}
|
molecules. TIRFM allows for selective excitation of the surface-bound fluorophores, while non-bound molecules are not excited and do not fluoresce. Due to the fact of sub-micron surface selectivity, TIRFM has become a method of choice for single molecule detection. There are many applications of TIRFM in cellular microscopy. Some of these applications include: Measuring the kinetics of receptor endocytosis in response to ligand binding and receptor movement Observing exocytic events through the loading of vesicles undergoing exocytosis with fluorescent dyes Qualitatively and quantitatively describing the roles different proteins play in endocytosis/exocytosis Observing the size, movement, and distance apart of the regions of contact between a cell and a solid substrate With the ability to resolve individual vesicles optically and follow the dynamics of their interactions directly, TIRFM provides the capability to study the vast number of proteins involved in neurobiological processes in a manner that was not possible before. === Benefits === TIRFM provides several benefits over standard widefield and confocal fluorescence microscopy such as: The background is substantially decreased so structures can be seen clearly There is virtually no out-of-focus fluorescence collected which decrease blurring effects Cells are exposed to a significantly smaller amount of light which limits phototoxicity to cells == Overview == The idea of using total internal reflection to illuminate cells contacting the surface of glass was first described by E.J. Ambrose in 1956. This idea was then extended by Daniel Axelrod at the University of Michigan, Ann Arbor in the early 1980s as TIRFM. A TIRFM uses an evanescent wave to selectively illuminate and excite fluorophores in a restricted region of the specimen immediately adjacent to the glass-water interface. The evanescent electromagnetic field decays exponentially from the interface, and thus penetrates to a depth of only approximately 100 nm into the sample medium. Thus the
|
{
"page_id": 1183118,
"source": null,
"title": "Total internal reflection fluorescence microscope"
}
|
TIRFM enables a selective visualization of surface regions such as the basal plasma membrane (which are about 7.5 nm thick) of cells. Note, however, that the region visualized is at least a few hundred nanometers wide, so the cytoplasmic zone immediately beneath the plasma membrane is necessarily visualized in addition to the plasma membrane during TIRF microscopy. The selective visualization of the plasma membrane renders the features and events on the plasma membrane in living cells with high axial resolution. TIRF can also be used to observe the fluorescence of a single molecule, making it an important tool of biophysics and quantitative biology. TIRF microscopy has also been applied in the single molecule detection of DNA biomarkers and SNP discrimination. Cis-geometry (through-objective TIRFM) and trans-geometry (prism- and lightguide based TIRFM) have been shown to provide different quality of the effect of total internal reflection. In the case of trans-geometry, the excitation lightpath and the emission channel are separated, while in the case of objective-type TIRFM they share the objective and other optical elements of the microscope. Prism-based geometry was shown to generate clean evanescent wave, which exponential decay is close to theoretically predicted function. In the case of objective-based TIRFM, however, the evanescent wave is contaminated with intense stray light. The intensity of stray light was shown to amount 10–15% of the evanescent wave, which makes it difficult to interpret data obtained by objective-type TIRFM == Mechanism == The basic components of the TIRFM device include: Excitation beam light source Cover slip and immersion oil Objective lens Sample specimen Detector === Objective-based vs prism-based === Key differences between objective-based (cis) and prism-based (trans) TIRFM are that prism based TIRFM requires usage of a prism/solution interface to generate the evanescent field, while objective-based TIRFM does not require a prism and utilizes
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"page_id": 1183118,
"source": null,
"title": "Total internal reflection fluorescence microscope"
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a cover slip/solution interface to generate the evanescent field. Typically objective-based TIRFM are more popularly used, however have lowered imaging quality due to stray light noise within the evanescent wave. ==== Prism-based ==== Less extraneous scattering Much cheaper (hundreds instead of thousands of dollars) Best for low-mid range magnification and water immersion objectives Easiest with free collimated laser sources Larger range of incidence angles Desirable to achieve smallest evanescent field depth ==== Objective-based ==== High magnification and aperture Stable, easy to set up and align Works with free collimated laser, optical fiber, or conventional arc sources == Methodology == === Fundamental physics === TIRFM is predicated on the optical phenomena of total internal reflection, in which waves arriving at a medium interface do not transmit into medium 2 but are completely reflected back into medium 1. Total internal reflection requires medium 2 to have a lower refractive index than medium 1, and for the waves must be incident at sufficiently oblique angles on the interface. An observed phenomena accompanying total internal reflection is the evanescent wave, which spatially extends away perpendicularly from the interface into medium 2, and decays exponentially, as a factor of wavelength, refractive index, and incident angle. It is the evanescent wave which is used to achieve increased excitation of the fluorophores close to the surface of the sample, and diminished excitation of superfluous fluorophores within solution. For practical purposes, in objective based TIRF, medium 1 is typically a high refractive index glass coverslip, and medium 2 is the sample in solution with a lower refractive index. There may be immersion oil between the lens and the glass coverslip to prevent significant refraction through air. === Evanescent wave === The critical angle for excitatory light incidence can be derived from Snell's law: θ c = sin −
|
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"page_id": 1183118,
"source": null,
"title": "Total internal reflection fluorescence microscope"
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1 ( n 1 n 2 ) {\displaystyle \theta _{c}=\sin ^{-1}\left({\frac {n_{1}}{n_{2}}}\right)} For n 1 {\displaystyle n_{1}} the refractive index of sample, n 2 {\displaystyle n_{2}} the refractive index of the cover slip. Thus, as the angle of incidence reaches θ c {\displaystyle \theta _{c}} , we begin observing effects of total internal reflection and evanescent wave, and as it surpasses θ c {\displaystyle \theta _{c}} these effects are more prevalent. The intensity of the evanescent wave is given by: I ( Z ) = I 0 e − z / d {\displaystyle I(Z)=I_{0}e^{-z/d}} With penetration depth d {\displaystyle d} given by: d = λ 0 4 π ( n 2 2 sin 2 θ − n 1 2 ) − 1 / 2 {\displaystyle d={\frac {\lambda _{0}}{4\pi }}\left(n_{2}^{2}\sin ^{2}\theta -n_{1}^{2}\right)^{-1/2}} Typically, d {\displaystyle d} ≤~100 nanometers, which is typically much smaller than the wavelength of light, and much thinner than a slice from confocal microscopes. For TIRFM imaging the wavelength of the excitation beam λ 0 {\displaystyle \lambda _{0}} within the sample can be selected for by filtering. Additionally, the range of incident angles θ {\displaystyle \theta } is determined by the numerical aperture (NA) of the objective, and requires that NA > n {\displaystyle n} . This parameter can be adjusted by changing the angle the excitation beam enters the objective lens. Finally, the reflective indices ( n {\displaystyle n} ) of the solution and cover slip can be experimentally found or reported by manufacturers. === Excitation beam === For complex fluoroscope microscopy techniques, lasers are the preferred light source as they are highly uniform, intense, and near-monochromatic. However, it is noted that ARC LAMP light sources and other types of sources may also work. Typically the wavelength of excitation beam is designated by the requirements
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{
"page_id": 1183118,
"source": null,
"title": "Total internal reflection fluorescence microscope"
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of the fluorophores within the sample, with most common excitation wavelengths being in the 400–700 nm range for biological samples. In practice, a lightbox will generate a high intensity multichromatic laser, which will then be filtered to allow the desired wavelengths through to excite the sample. For objective-based TIRFM, the excitation beam and fluoresced emission beam will be captured via the same objective lens. Thus, to split the beams, a dichromatic mirror is used to reflect the incoming excitation beam towards the objective lens, and allow the emission beam to pass through into the detector. Additional filtering may be required to further separate emission and excitation wavelengths. === Emission beam === When excited with specific wavelengths of light, fluorophore dyes will reemit light at longer wavelengths (which contain less energy). In the context of TIRFM, only fluorophores close to the interface will be readily excited by the evanescent field, while those past ~100 nm will be highly attenuated. Light emitted by the fluorophores will be undirected, and thus will pass through the objective lens at varying locations with varying intensities. This signal will then pass through the dichromatic mirror and onward to the detector. === Cover slip and immersion oil === Glass cover slips typically have a reflective index around n = 1.52 {\displaystyle n=1.52} , while the immersion oil refractive index is a comparable n = 1.51 {\displaystyle n=1.51} . The medium of air, which has a refractive index of n = 1.00 {\displaystyle n=1.00} , would cause refraction of the excitation beam between the objective and the coverslip, thus the oil is used to buffer the region and prevent superfluous interface interactions before the beam reaches the interface between coverslip and sample. === Objective lens === The objective lens numerical aperture (NA) specifies the range of angles over
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"page_id": 1183118,
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"title": "Total internal reflection fluorescence microscope"
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which the system can accept or emit light. To achieve the greatest incident angles, it is desirable to pass light at an off-axis angle through the peripheries of the lens. ==== Back focal plane (BPF) ==== The back focal plane (also called "aperture plane") is the plane through which the excitatory beam is focused before passing through the objective. Adjusting the distance between the objective and BPF can yield different imaging magnification, as the incident angle will become less or more steep. The beam must be passed through the BPF off-axis in order to pass through the objective at its ends, allowing for the angle to be sufficiently greater than the critical angle. The beam must also be focused at the BPF because this ensures that the light passing through the objective is collimated, interacting with the cover slip at the same angle and thus all totally internally reflecting. === Sample === The sample should be adsorbed to the surface of the glass cover slide and stained with appropriate fluorophores to resolve the features desired within the sample. This is in protocol with any other fluorescent microscopy technique. === Dichroic (dichromatic) filter === The dichroic filter is an edge filter used at an oblique angle of incidence (typically 45°) to efficiently reflect light in the excitation band and to transmit light in the emission band. The 45° angle of the filter separates the path of the excitation and emission beam. The filter is composed of a complex system of multiple layers of metals, metal salts and dielectrics which have been vacuum-deposited onto thin glass. This coating is designed to have high reflectivity for shorter wavelengths and high transmission for longer wavelengths. While the filter transmits the selected excitation light (shorter wavelength) through the objective and onto the plane of the
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"page_id": 1183118,
"source": null,
"title": "Total internal reflection fluorescence microscope"
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specimen, it also passes emission fluorescence light (longer wavelength) to the barrier filter and reflecting any scattered excitation light back in the direction of the laser source. This maximizes the amount of exciting radiation passing through the filter and emitted fluorescence beam that is detected by the detector. === Barrier filter === The barrier filter mainly blocks off undesired wavelengths, especially shorter excitation light wavelengths. It is typically a bandpass filter that passes only the wavelengths emitted by the fluorophore and blocks all undesired light outside this band. More modern microscopes enable the barrier filter to be changed according to the wavelength of the fluorophore's specific emission. == Image detection and resolution == The image is detected by a charged-coupled device (CCD) digital camera. CCD cameras have photon detectors, which are thin silicon wafers, assembled into 2D arrays of light-sensitive regions. The detector arrays capture and store image information in the form of localized electrical charge that varies with incident light intensity. As shown in the schematic the photons are transform to electrons by the detectors and the electrons are converted to readable electrical signal in the circuit board. The electrical signal is then convoluted with a point spread function (PSF) to sample the original signal. As such, image resolution is highly dependent on the number of detectors and the point spread function will determine the image resolution. === Image artifact and noise === Most fluorescence imaging techniques exhibit background noise due to illuminating and reconstructing large slices (in the z-direction) of the samples. Since TIRFM uses an evanescent wave to fluoresce a thin slice of the sample, there is inherently less background noise and artifacts. However, there are still other noises and artifacts such as poisson noise, optical aberrations, photobleaching, and other fluorescence molecules. Poissonian noise are fundamental uncertainties
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"page_id": 1183118,
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"title": "Total internal reflection fluorescence microscope"
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with the measurement of light. This will cause uncertainties during the detection of fluorescence photons. If N photons are measured in a particular measurement, there is a 63% probability that the true average value is in the range between N +√N and N −√N. This noise may cause misrepresentation of the object at incorrect pixel locations. Optical aberrations can arise from diffraction of fluorescence light or microscope and objective misalignment. Diffraction of light on the sample slide can spread the fluorescence signal and result in blurring in the convoluted images. Similarly, if there is a misalignment between the objective lens, filter, and detector, the excitation or emission beam may not be in focus and can cause blurring in the images. Photobleaching can occur when the covalent or noncovalent bonds in the fluorophores are destructed by the excitation light and can no longer fluoresce. The fluorescing substances will always degrade to some extent by the energy of the exciting radiation and will cause the fluorescence to fade and result in a dark blurry image. Photobleaching is inevitable but can be minimized by avoiding unwanted light exposure and using immersion oils to minimize light scattering. Autofluorescence can occur in certain cell structures where the natural compound in the structure would fluoresce after being excited at relatively shorter wavelengths (similar to that of the excitation wavelength). Induced fluorescence can also occur when certain non-autofluorescent compounds become fluorescent after binding to certain chemicals (such as formaldehyde). These fluorescence can result in artifacts or background noise in the image. Noise from other fluorescence compounds can be effectively eliminated by using filters to capture the desired fluorescence wavelength, or by making sure the autofluorescence compounds are not present in the sample. === Current and future work === Modern fluorescence techniques attempt to incorporate methods to eliminate
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some blurring and noises. Optical aberrations are generally deterministic (it is constant throughout the image process and across different samples). Deterministic blurring can be eliminated by deconvoluting the signal and subtracting the known artifact. The deconvolution technique is simply using an inverse fourier transform to obtain the original fluorescence signal and remove the artifact. Nevertheless, deconvolution has only been shown to work if there is a strong fluorescence signal or when the noise is clearly identified. In addition, deconvolution performs poorly because it does not include statistical information and can not reduce non-deterministic noise such as poissonian noise. To obtain better image resolution and quality, researchers have used statistical techniques to model the probability where photons may be distributed on the detector. This technique, called the maximum likelihood method, is being further improved by algorithms to improve its performance speed. == References == Axelrod, Daniel (1 November 2001). "Total Internal Reflection Fluorescence Microscopy in Cell Biology" (PDF). Traffic. 2 (11): 764–774. doi:10.1034/j.1600-0854.2001.21104.x. hdl:2027.42/72779. PMID 11733042. S2CID 15202097. == External links == Interactive Fluorescence Dye and Filter Database Carl Zeiss Interactive Fluorescence Dye and Filter Database. TIRF Microscopy: Introduction and Applications TIRF Tutorial from Microscopy U TIRF Microscopy: Overview TIRF Tutorial from Olympus Microscopy Resource Center Olympus TIRFM Microscopes commercial TIRF microscope systems Carl Zeiss Laser TIRF 3 commercial TIRF microscope systems Lightguide- and prism-based TIRF microscopy TIRF-Labs.com :Commercial TIRF Microscopy and Spectroscopy. Selecting TIRFM geometry for your application TIRF FLIM microscopy Lambert Instruments TIRF - FLIM microscopy Schwartz Research Group, CU-Boulder Single Molecule Imaging Research Group
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In biological nomenclature, organisms often receive scientific names that honor a person. A taxon (e.g. species or genus; plural: taxa) named in honor of another entity is an eponymous taxon, and names specifically honoring a person or persons are known as patronyms. Scientific names are generally formally published in peer-reviewed journal articles or larger monographs along with descriptions of the named taxa and ways to distinguish them from other taxa. Following rules of Latin grammar, species or subspecies names derived from a man's name often end in -i or -ii if named for an individual, and -orum if named for a group of men or mixed-sex group, such as a family. Similarly, those named for a woman often end in -ae, or -arum for two or more women. This list is part of the List of organisms named after famous people, and includes organisms named after famous individuals born between 1 January 1800 and 31 December 1899. It also includes ensembles in which at least one member was born within those dates; but excludes companies, institutions, ethnic groups or nationalities, and populated places. It does not include organisms named for fictional entities (which can be found in the List of organisms named after works of fiction), for biologists, paleontologists or other natural scientists, nor for associates or family members of researchers who were not otherwise notable; exceptions are made, however, for natural scientists who are much more famous for other aspects of their lives, such as, for example, writers Vladimir Nabokov or Beatrix Potter. Organisms named after famous people born earlier can be found in: List of organisms named after famous people (born before 1800) Organisms named after famous people born later can be found in: List of organisms named after famous people (born 1900–1949) List of organisms named after
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{
"page_id": 69275023,
"source": null,
"title": "List of organisms named after famous people (born 1800–1899)"
}
|
famous people (born 1950–present) The scientific names are given as originally described (their basionyms); subsequent research may have placed species in different genera, or rendered them taxonomic synonyms of previously described taxa. Some of these names may be unavailable in the zoological sense or illegitimate in the botanical sense due to senior homonyms already having the same name. == List (people born 1800–1899) == == See also == List of bacterial genera named after personal names List of rose cultivars named after people List of taxa named by anagrams List of organisms named after the Harry Potter series == Notes == == References ==
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{
"page_id": 69275023,
"source": null,
"title": "List of organisms named after famous people (born 1800–1899)"
}
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The spermatheca (pronounced pl.: spermathecae ), also called receptaculum seminis (pl.: receptacula seminis), is an organ of the female reproductive tract in insects, e.g. ants, bees, some molluscs, Oligochaeta worms and certain other invertebrates and vertebrates. Its purpose is to receive and store sperm from the male or, in the case of hermaphrodites, the male component of the body. Spermathecae can sometimes be the site of fertilisation when the oocytes are sufficiently developed. Some species of animal have multiple spermathecae. For example, certain species of earthworms have four pairs of spermathecae—one pair each in the 6th, 7th, 8th, and 9th segments. The spermathecae receive and store the spermatozoa of another earthworm during copulation. They are lined with epithelium and are variable in shape: some are thin, heavily coiled tubes, while others are vague outpocketings from the main reproductive tract. It is one of the many variations in sexual reproduction. The nematode Caenorhabditis elegans has two spermathecae, one at the end of each gonad. The C. elegans spermatheca is made up of 24 smooth muscle-like cells that form a stretchable tubular structure. Actin filaments line the spermatheca in a circumferential manner. The C. elegans spermatheca is used as a model to study mechanotransduction. An apiculturist may examine the spermatheca of a dead queen bee to find out whether it had received sperm from a male. In many species of stingless bees, especially Melipona bicolor, the queen lays her eggs during the provisioning and oviposition process and the spermatheca fertilizes the egg as it passes along the oviduct. The haplo-diploid system of sex determination makes it possible for the queen to choose the sex of the egg. == See also == Cyphopods, sperm receptacles in female millipedes Female sperm storage Reproductive system of gastropods == References ==
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{
"page_id": 2100624,
"source": null,
"title": "Spermatheca"
}
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Specialty drugs or specialty pharmaceuticals are a recent designation of pharmaceuticals classified as high-cost, high complexity and/or high touch. Specialty drugs are often biologics—"drugs derived from living cells" that are injectable or infused (although some are oral medications). They are used to treat complex or rare chronic conditions such as cancer, rheumatoid arthritis, hemophilia, H.I.V. psoriasis, inflammatory bowel disease and hepatitis C. In 1990 there were 10 specialty drugs on the market, around five years later nearly 30, by 2008 200, and by 2015 300. Drugs can be defined as specialty because of their high price. Medicare defines any drug with a negotiated price of $670 per month or more as a specialty drug. These drugs are placed in a specialty tier requiring a higher patient cost sharing. Drugs are also identified as specialty when there is a special handling requirement or the drug is only available via a limited distributions network. By 2015 "specialty medications accounted for one-third of all spending on drugs in the United States, up from 19 percent in 2004 and heading toward 50 percent in the next 10 years", according to IMS Health. According to a 2010 article in Forbes, specialty drugs for rare diseases became more expensive "than anyone imagined" and their success came "at a time when the traditional drug business of selling medicines to the masses" was "in decline". In 2015 analysis by The Wall Street Journal suggested the large premium was due to the perceived value of rare disease treatments which usually are very expensive when compared to treatments for more common diseases. == Definition and common characteristics == Medications must be either identified as high cost, high complexity or high touch to be classified as a specialty medication by Magellan Rx Management. Specialty pharmaceuticals are defined as "high-cost oral or
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"page_id": 48172434,
"source": null,
"title": "Specialty drugs in the United States"
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injectable medications used to treat complex chronic conditions". According to a 2013 article in the Journal of Managed Care & Specialty Pharmacy, on the increasingly important role of specialty drugs in the treatment of chronic conditions and their cost, drugs are most typically defined as specialty because they are expensive. Other criteria used to define a drug as specialty include "biologic drugs, the need to inject or infuse the drug, the requirement for special handling, or drug availability only via a limited distribution network". The price of specialty drugs compared to non-specialty drugs is very high, "more than $1,000 per 30-day supply". Specialty drugs cover over forty therapeutic categories and special disease states with over 500 drugs. Vogenberg claims that there is no standard definition of a specialty drug which is one of the reasons they are difficult to manage. "[T]hose pharmaceuticals that usually require special handling, administration, unique inventory management, and a high level of patient monitoring and support to consumers with specific chronic conditions, acute events, or complex therapies, and provides comprehensive patient education services and coordination with the patient and prescriber." === High cost === Drugs are most typically defined as specialty because they are expensive. They are high cost "both in total and on a per-patient basis". High-cost medications are typically priced at more than $1,000 per 30-day supply. The Medicare Part D program "defines a specialty drug as one that costs more than $600 per month". Most of the prescriptions filled by Pennsylvania-licensed Philidor Rx Services, a specialty online mail-order pharmacy, which mainly sold Valeant Pharmaceuticals International Inc expensive drugs directly to patients and handled insurance claims on the customers' behalf, such as Solodyn, Jublia, and Tretinoin, would be considered specialty drugs. === High complexity === Specialty drugs are more complex to manufacture. They are
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{
"page_id": 48172434,
"source": null,
"title": "Specialty drugs in the United States"
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"highly complex medications, typically biology-based, that structurally mimic compounds found within the body". Specialty drugs are often biologics—"drugs derived from living cells"—but biologics are "not always deemed to be specialty drugs". Biologics "may be produced by biotechnology methods and other cutting-edge technologies. Gene-based and cellular biologics, for example, often are at the forefront of biomedical research, and may be used to treat a variety of medical conditions for which no other treatments are available." "In contrast to most drugs that are chemically synthesized and their structure is known, most biologics are complex mixtures that are not easily identified or characterized. Biological products, including those manufactured by biotechnology, tend to be heat sensitive and susceptible to microbial contamination. Therefore, it is necessary to use aseptic principles from initial manufacturing steps, which is also in contrast to most conventional drugs. Biological products often represent the cutting-edge of biomedical research and, in time, may offer the most effective means to treat a variety of medical illnesses and conditions that presently have no other treatments available." According to the U.S. Food and Drug Administration (FDA) biologics, or "Biological products include a wide range of products such as vaccines, blood and blood components, allergenics, somatic cells, gene therapy, tissues, and recombinant therapeutic proteins. Biologics can be composed of sugars, proteins, or nucleic acids or complex combinations of these substances, or may be living entities such as cells and tissues. Biologics are isolated from a variety of natural sources—human, animal, or microorganism..." === High touch === Some specialty drugs can be oral medications or self-administered injectables. Others may be professionally administered or injectables/infusions. High-touch patient care management is usually required to control side effects and ensure compliance. Specialized handling and distribution are also necessary to ensure appropriate medication administration. Specialty drugs patient care management is meant
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{
"page_id": 48172434,
"source": null,
"title": "Specialty drugs in the United States"
}
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to be both high technology and high touch care, or patient-centered care with "more face-to-face time, more personal connections". Patient-centered care is defined by the Institute of Medicine as "care that is respectful of and responsive to individual patient preferences, needs and values". Specialty drugs may be "difficult for patients to take without ongoing clinical support". === Limited availability === Specialty drugs might have special requirements for handling procedures and administration including the necessity of having controlled environments such as highly specific temperature controls to ensure product integrity. They are often only available via a limited distributions network such as a special pharmacy. Specialty drugs may be "challenging for providers to manage". === Rare and complex diseases === Specialty drugs may be taken "by relatively small patient populations presenting with complex medical conditions". == History == "Specialty pharmacies have their roots in the 1970s, when they began delivering temperature-controlled drugs to treat cancer, HIV, infertility and hemophilia." "The business grew as more drugs became available for patients to inject themselves and as insurers sought to manage expenses for patients with chronic conditions, according to areport from IMS Health. Manufacturers have increasingly relied on these pharmacies when it comes to fragile medicines that need special handling or have potentially dangerous side effects that require them to be taken under a management program." According to The American Journal of Managed Care, in 1990 there were 10 specialty drugs on the market. According to the National Center for Biotechnology Information, by the mid-1990s, there were fewer than 30 specialty drugs on the market, but by 2008 that number had increased to 200. Specialty drugs may also be designated as orphan drugs or ultra-orphan drugs under the U. S. Orphan Drug Act of 1983. This was enacted to facilitate development of orphan drugs—drugs for
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"page_id": 48172434,
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rare diseases such as Huntington's disease, myoclonus, amyotrophic lateral sclerosis, Tourette syndrome and muscular dystrophy which affect small numbers of individuals residing in the United States. Not all specialty drugs are orphan drugs. According to Thomson Reuters in their 2012 publication "The Economic Power of Orphan Drugs", there has been increased investing in orphan drug research and development partly since the U.S. Congress enacted the Orphan Drug Act, giving an extra monopoly for drugs for "orphan diseases" that affected fewer than 200,000 people in the country. Similar acts came into existence in other regions of the world, many driven by "high-profile philanthropic funding". According to a 2010 article in Forbes, prior to 1983 drug companies largely ignored rare diseases and focused on drugs that affected millions of patients. The term specialty drugs was used as early as 1988 in a New York Times article about Eastman Kodak Company's acquisition of the New York-based Sterling Drug Inc., maker of specialty drugs along with many and diverse other products. When Shire Pharmaceuticals acquired BioChem Pharma in 2000 they created a specialty pharmaceuticals company. By 2001 Shire was one of the fastest growing specialty pharmaceutical companies in the world. By 2001 CVS's specialty pharmacy ProCare was the "largest integrated retail/mail provider of specialty pharmacy services" in the United States.: 10 It was consolidated with their pharmacy benefit management company PharmaCare in 2002. In their 2001 annual report, CVS anticipated that the "$16 billion specialty pharmacy market" would grow at "an even faster rate than traditional pharmacy due in large part to the robust pipeline of biotechnology drugs". By 2014 CVS Caremark, Express Scripts and Walgreens represented more than 50% of the specialty drug market in the United States.: 4 When an increasing number of oral oncology agents first entered the market between 2000
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"page_id": 48172434,
"source": null,
"title": "Specialty drugs in the United States"
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and 2010, most cancer care was provided in a community oncology practices. By 2008 many other drugs had been developed to treat cancer, and drug development had grown into a multibillion-dollar industry. In 2003 the Medicare Prescription Drug, Improvement, and Modernization Act was enacted—the largest overhaul of Medicare in the public health program's 38-year history—included Medicare Part D an entitlement benefit for prescription drugs, through tax breaks and subsidies. In 2004 the U. S. Centers for Medicare and Medicaid Services (CMS) prepared a report on final guidance regarding access to drug coverage enacted under in which they included the specialty drugs tier in the prescription drug formulary. At that time CMS guidelines included four tiers: tier 1 includes preferred generics, tier 2 includes preferred brands, tier 3 includes non-preferred brands and generics and tier 4 included specialty drugs. By January 1, 2006, the controversial Medicare Part D was put in effect. It was a massive expansion of the federal government's provision of prescription drug coverage to previously uninsured Americans, particularly seniors.: 69 In 2006 in the United States there was no standard nomenclature, so sellers could call the plan anything they wanted and cover whatever drugs they wanted. By 2008 most prescription medication plans in the United States used specialty drug tiers, and some had a separate benefit tier for injectable drugs. Beneficiary cost sharing was higher for drugs in these tiers. By 2011 in the United States a growing number of Medicare Part D health insurance plans—which normally include generic, preferred, and non-preferred tiers with an accompanying rate of cost-sharing or co-payment—had added an "additional tier for high-cost drugs which is referred to as a specialty tier".: 1 By 2014 in the United States, in the new Health Insurance Marketplace—following the implementation of the U.S. Affordable Care Act, also
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{
"page_id": 48172434,
"source": null,
"title": "Specialty drugs in the United States"
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known as Obamacare—most health plans had a four- or five-tier prescription drug formulary with specialty drugs in the highest of the tiers. == AARP == According to an AARP 2015 report, "All but 4 of the 46 therapeutic categories of specialty drug products had average annual retail price increases that exceeded the rate of general inflation in 2013. Price increases by therapeutic category ranged from 1.7 percent to 77.2 percent." === Risk evaluation and mitigation strategies (REMS) === On September 27, 2007 President George W. Bush amended the Food and Drug Administration Amendments Act of 2007 (FDAAA) to authorize the FDA to require Risk Evaluation and Mitigation Strategies (REMS) on medications if necessary to minimize the risks associated with some drugs". These medications were designated as specialty drugs and required specialty pharmacies. When the FDA approves a new drug they may require a REMS program which "may contain any combination of 5 criteria: Medication Guide, Communication Plan, Elements to Assure Safe Use, Implementation System, and Timetable for Submission of Assessments". "In 2010, 48% of all new molecular entities, and 60% of all new specialty drug approvals, required a REMS program." Risk-reduction mechanisms can include the "use of specialized distribution partners", special pharmacy. === Breakthrough therapy === In 2013 the FDA introduced the breakthrough therapy designation program which cut the development process of new therapies by several years. This meant that the FDA could "introduce important medicines to the market based on very promising phase 2 rather than phase 3 clinical trial results". Shortly after the law was enacted, Ivacaftor, in January 2013, became the first drug to receive the breakthrough therapy designation. On February 3, 2015 New York-based Pfizer's drug Ibrance was approved through the FDA's Breakthrough Therapy designation program as a treatment for advanced breast cancer. It can only
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"page_id": 48172434,
"source": null,
"title": "Specialty drugs in the United States"
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be ordered through specialty pharmacies and sells for "$9,850 for a month or $118,200 per year". According to a statement by the New York-based Pfizer the price "is not the cost that most patients or payors pay" since most prescriptions are dispensed through health plans, which negotiate discounts for medicines or get government-mandated price concessions. === Trends in spending in the United States === According to Express Scripts, "[T]he pharmacy landscape [in the United States] underwent a seismic change, and the budgetary impact to healthcare payers was significant. U.S. prescription drug spend increased 13.1% in 2014 – the largest annual increase since 2003 – and this was largely driven by an unprecedented 30.9% increase in spending on specialty medications. Utilization of traditional medications stayed flat (-0.1%), while the use of specialty drugs increased 5.8%. The largest factors contributing to the increased spending, however, were the price increases for these medication categories – 6.5% for traditional and 25.2% for specialty. While specialty medications represent only 1% of all U.S. prescriptions, these medications represented 31.8% of all 2014 drug spend – an increase from 27.7% in 2013." By 2015 "specialty medications account for one-third of all spending on drugs in the United States, up from 19 percent in 2004 and heading toward 50 percent in the next 10 years, according to IMS Health, which tracks prescriptions". The specialty pharmacy business had $20 billion in sales in 2005. By 2014 it had grown to "$78 billion in sales". In Canada by 2013 "specialty drugs made up less than 1.3 percent of all Canadian prescriptions, but accounted for 24 percent of Canada's total spending on prescription drugs". When Randy Vogenberg of the Institute for Integrated Healthcare in Massachusetts and a co-leader of the Midwest Business Group initiative, began investigating specialty drugs in 2003, it
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"page_id": 48172434,
"source": null,
"title": "Specialty drugs in the United States"
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"wasn't showing up on the radar". By 2009 specialty drugs had started doubling in cost and payers such as employers began to question. Vogenberg observed that by 2014 health care reform had changed the landscape for specialty drugs. There is a shift away from a marketplace based on a predominately clinical perspective, to one that puts economics first and clinical second.: 15 Many factors contribute to the continuing increase in price of specialty drugs. Development of specialty drugs not only costs more, but they also take longer to develop than other large market pharmaceuticals (See Drug development). In addition, there are often fewer drug choices for rare or hard-to-treat diseases. This results in less competition in the marketplace for these drugs due to patent protection, which allows these firms to act as monopolists (See Drug Price Competition and Patent Term Restoration Act). Due to this lack of competition, policies that serve to limit prices in other markets can be ineffective or even counter-productive when applied to specialty drugs. High prices for specialty drugs are a problem for both patients and payers. Patients frequently have difficulty paying for these medications, which can lead to lack of access to treatment. Specialty drugs are now so expensive that they are leading to increases in insurance premiums. Control of specialty drug prices will require research to identify effective policy options, which may include: decreasing regulation, limiting patent protection, allowing negotiation of drug prices by Medicare, or pricing drugs based on their effectiveness. === Insurance payer definition === In the United States, private insurance payers will favour a lower-cost agent preferring generics and biosimilars to the more expensive specialty drugs if there is no peer-reviewed or evidence-based justification for them. According to a 2012 report by Sun Life Financial the average cost of specialty drug
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claims was $10,753 versus $185 for non-specialty drugs and the cost of specialty drugs continues to rise. With such steep prices by 2012 specialty drugs represented 15-20% of prescription drug reimbursement claims. Patient advocacy groups that lobby for payment for specialty drugs include the Alliance for Patient Access (AfPA), formed in 2006 and which according to a 2014 article in the Wall Street Journal "represents physicians and is largely funded by the pharmaceutical industry. The contributors mostly include brand-name drug makers and biotechs, but some—such as Pfizer and Amgen—are also developing biosimilars." In 2013 AfPA director David Charles published an article on specialty drugs in which he agreed with the findings of the Congressional Budget Office that spending on prescription medications "saves costs in other areas of healthcare spending". He observed that specialty drugs are so high priced that many patients do not fill prescriptions resulting in more serious health problems increasing. His article referred to specialty drugs such as "new cancer drugs specially formulated for patients with specific genetic markers". He explained the high cost of these "individualized medications based on diagnostic testing; and "biologics", or medicines created through biologic processes, rather than chemically synthesized like most pharmaceuticals". He argued that there should be a slight increase in co-pays for the more commonly using lower-tier medications to allow a lower co-pay for those who "require high-cost specialty tier medications". === Top specialty therapy classes and average prescription costs === According to the 2014 Express Scripts Drug Trend Report, the most significant increase in prescription drugs in the United States in 2014 was due to "increased inflation and utilization of hepatitis C and compounded medications". "Excluding those two therapy classes, overall drug spend would have increased only 6.4%. The cost of "the top three specialty therapy classes—inflammatory conditions, multiple sclerosis
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and oncology—contributed 55.9% of the spend for all specialty medications billed through the pharmacy benefit in 2014. The U.S. spent 742.6% more on hepatitis C medications in 2014 than it did in 2013; this therapy class was not among the top 10 specialty classes in 2013. == Specialty pharmacies == As the market demanded specialization in drug distribution and clinical management of complex therapies, specialized pharma (SP) evolved. By 2001 CVS' specialty pharmacy ProCare was the "largest integrated retail/mail provider of specialty pharmacy services" in the United States.: 10 It was consolidated with their pharmacy benefit management company, PharmaCare in 2002 to In their 2001 annual report CVS anticipated that the "$16 billion specialty pharmacy market" would grow at "an even faster rate than traditional pharmacy due in large part to the robust pipeline of biotechnology drugs". By 2014 CVS Caremark, Express Scripts and Walgreens represented more than 50% of the specialty drug market in the United States.: 4 The specialty pharmacy business had $20 billion in sales in 2005. By 2014 it had grown to "$78 billion in sales". Specialty pharmacies came into existence to as a result of unmet needs. According to the National Comprehensive Cancer Network the "primary goals of specialty pharmacies are to ensure the appropriate use of medications, maximize drug adherence, enhance patient satisfaction through direct interaction with healthcare professionals, minimize cost impact, and optimize pharmaceutical care outcomes and delivery of information". McKesson Specialty Care Solutions, a division of McKesson Corporation, is "one of the largest distributors of specialty drugs, biologics and rheumatology drugs to community-based specialty practices". It is "a leader in the development, implementation and management of FDA-mandated Risk Evaluation and Mitigation Strategies (REMS) for manufacturers". For example, in order ProStrakan Group plc, an international pharmaceutical company based in the UK works with
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McKesson Specialty Care Solutions to administer its FDA-approved Risk Evaluation and Mitigation Strategy (REMS) program for Abstral. URAC's Specialty Pharmacy Accreditation "provides an external validation of excellence in Specialty Pharmacy Management and provides Continuous Quality Improvement (CQI) oriented processes that improve operations and enhance compliance". Specialty pharmaceuticals or biologics are a significant part of the treatment market, yet there is still additional work that should be done to manage costs. Defining biologics has been described as a matter of perspective, with variation between chemists, physicians, payers, microbiologists and regulators. A payer may define a biologic by cost, while a biochemist may look at composition and structure and a provider at means of delivery or action on the body. The FDA generally defines biologics as, "a wide range of products [that] ...can be composed of sugars, proteins, or nucleic acids or complex combinations of these substances, or may be living entities such as cells and tissues. Biologics are isolated from a variety of natural sources—human, animal, or microorganism—and may be produced by biotechnology methods and other cutting-edge technologies". Due to the complexity, risk of adverse events and allergic reactions associated with biologics, management is very important for the safety of patients. Management includes areas from patient education and adherence to the delivery of the medication. These medications often require very specific storage conditions and monitoring of temperature, the level of agitation and proper reconstitution of the drug . Because of the high risk of error and adverse events, provider management of delivery is required, especially for injection or infusion of some biologic medications. Such biologics are often coded in a way that ties reimbursement to delivery by a provider—either a specialty pharmacist or medical care provider with those skills. As more biologics are being designed to be self-administered pharmacists are supporting
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the management of these drugs. They make calls to remind patients of the need for refills, provide education to patients, monitor patients for adverse events and work with primary care provider offices to monitor the outcomes of the medication. The high cost of specialty pharmaceuticals is one of their defining characteristics; as such, cost-containment is high on the list of all the players in the arena. For physician-administered biologics, cost-containment is often handled by volume purchasing of biologic drugs for discounted pricing, formularies, step therapy to attempt other treatment before beginning biologics and administrative fees by insurers to keep physicians from artificially inflating requested reimbursement from insurance companies. Cost-containment for self-administered biologics tends to occur via requiring authorization to be prescribed those drugs and benefit design, such as coinsurance for cost-sharing. The 21st Century Cures Act which addressed fast-tracking approval of specialty pharmaceuticals was particularly beneficial for dealing with the development of 2nd run biologics (which might be more easily understood as "generic biologics", though they do not exist). Debate around the act raised some important questions about the efficacy of biologics and their continued high costs. Some call for insurers to pay only the cost of production to manufacturers until the benefit of these biologics can be proven long-term, stating that insurers should not bear the full cost of products that may be unreliable or have only limited efficacy. Achieving this would require conducting studies that assess value, such as comparative effectiveness studies and using those studies to determine pricing. Comparative effectiveness would examine all aspects of the use of biologics, from outcomes such as clinical benefits and potential harms, to efficiency of administration, public health benefits and patient productivity after treatment. This is a new direction in managing the high costs of specialty pharmaceuticals and not without challenges.
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One of the barriers is strict regulation by the Food and Drug Administration of what pharmaceutical manufacturers may communicate to the public, limiting that communication to formulary committees for managed care, for example. Additionally, studies tend to be constructed using observational design, instead of as randomized controlled trials, limiting their usefulness for real-world application. Difficulties experienced with patient adherence to specialty pharmaceuticals also limit the availability of real-world outcomes data for biologics. In 2016, real world data evaluating the efficacy of biologics was only publicly available for multiple myeloma through ICER (where biologics were found to be overpriced for their outcomes) and for hepatitis C treatment (which achieved high cure rates—90%—for patients co-infected with HIV and Hep C) through Curant Health. These studies show how useful value-based pricing may become for cost-containment in the field. The good news is that there are effectiveness studies on biologics currently underway aiming to provide more of this data. == Regulation == Biologics or biological products for human use are regulated by the Center for Biologics Evaluation and Research (CBER), overseen by the Office of Medical Products and Tobacco, within the U.S. Food and Drug Administration which includes the Public Health Service Act and the Federal Food, Drug and Cosmetic Act. "CBER protects and advances the public health by ensuring that biological products are safe and effective and available to those who need them. CBER also provides the public with information to promote the safe and appropriate use of biological products." == Specialty market participants == There are multiple players in specialty drugs including the employer, the health plan, the pharmacy benefits manager and it is unclear who should be in charge of controlling costs and monitoring care. Pharmacies generally buy a product from a wholesaler and sell (Buy & Bill) it to the
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patient and provide basic drug use information and counseling. According to Maria Hardin, vice president of patient services for the National Organization for Rare Disorders, an alliance of voluntary health and patient advocacy groups working with rare diseases, "As the cost of drugs increases, management of the financial side has gotten more complex... The issues range from Medicare Part D to tiered benefits, prior authorizations, and no benefits. These patients need a pharmacy with the expertise and the clout to go to bat for them. If the patient doesn't get treated, the specialty pharmacy doesn't get paid." Alexion Pharmaceuticals was one of the pioneers in the use of a business model of developing drugs to combat rare diseases. "Knowing the value of specialty drugs as well as its own stock is Alexion's business." Since other big pharmaceutical companies had tended to ignore these markets, Alexion had minimal competition at first. Insurance companies have generally been willing to pay high prices for such drugs; since few of their customers need the drugs, a high price does not significantly impact the insurance companies outlays. Alexion is thus seeking a stronger position in the lucrative rare disease market, and is willing to pay a premium to obtain that position. The rare disease market is seen as desirable because insurers have minimal motive to deny claims (due to small population sizes of patients) and are unable to negotiate better drug prices due to lack of competition. of May 2015, Alexion is currently seeking approval of its second drug, Strensiq. It will be used to treat hypophosphatasia, a rare metabolic disorder. In 2015 Alexion estimated that Synageva, its specialty drug for lysosomal acid lipase deficiency, a fatal genetic disorder, could eventually have annual sales of more than $1 billion. Companies like Magellan RX Management provide
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a "single source for high-touch patient care management to control side effects, patient support and education to ensure compliance or continued treatment, and specialized handling and distribution of medications directly to the patient or care provider. Specialty medications may be covered under either the medical or pharmacy benefit." According to an article published in 2014 in the journal Pharmacoeconomics, "[s]pecialty pharmacies combine medication dispensing with clinical disease management. Their services have been used to improve patient outcomes and contain costs of specialty pharmaceuticals. These may be part of independent pharmacy businesses, retail pharmacy chains, wholesalers, pharmacy benefit managers, or health insurance companies. Over the last several years, payers have been transitioning to obligate beneficiaries to receive self-administered agents from contracted specialty pharmacies, limiting the choice of acceptable specialty pharmacy providers (SPPs) for patient services." === Health plans and pharmacy benefit managers === Managed care organizations contract with Specialty Pharmacy vendors. "Managed care organizations (MCOs) are using varied strategies to manage utilization and costs. For example, 58% of 109 MCOs surveyed implement prior authorizations for MS specialty therapies." The Academy of Managed Care Pharmacy (AMCP) designates a product as a specialty drug if "[i]t requires a difficult or unusual process of delivery to the patient (preparation, handling, storage, inventory, distribution, Risk Evaluation and Mitigation Strategy (REMS) programs, data collection, or administration) or, Patient management prior to or following administration (monitoring, disease or therapeutic support systems)". Health plans consider "high cost" (on average a minimum monthly costs of $US1,200) to be is a determining factor in identifying a specialty drug. === Independent specialty pharmacies === Tom Westrich, of St. Louis, Missouri-based Centric Health Resources, a specialty pharmacy, described how their specialty drugs treat ultra-orphan diseases with a total patient population of 20,000 nationwide. === Retail pharmacies === The top ten specialty pharmacies
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in 2014 were CVS Specialty parent company CVS Health with $20.5B in sales, Express Scripts's Accredo at $15B, Walgreens Boots Alliance's Walgreens Specialty at $8.5B, UnitedHealth Group's OptumRx at $2.4B, Diplomat Pharmacy at $2.1B, Catamaran's BriovaRx at $2.0B, Specialty Prime Therapeutics's Prime Therapeutics at $1.8B, Omnicare's Advanced Care Scripts at $1.3B, Humana's RightsourceRx at $1.2B, Avella at $0.8B. All the other specialty pharmacies accounted for $22.4B of sales in 2014 with a total of $78B. === Hospitals and physicians === In 2010 the United States enacted a new health law which had unintended consequences. Because of the 2010 law, drug companies like Genentech informed children's hospitals that they would no longer get discounts for certain cancer medicines such as the orphan drugs Avastin, Herceptin, Rituxan, Tarceva, or Activase. This cost hospitals millions of dollars. There is a debate about whether specialty drugs should be managed as a medical benefit or a pharmaceutical benefit. Infused or injected medications are usually covered under the medical benefit and oral medications are covered under the pharmacy benefit. Self-injected medications may be either. "Many biologics, such as chemotherapy drugs, are administered in a doctor's office and require extensive monitoring, further driving up costs." Chemotherapy is usually delivered intravenously, although a number of agents can be administered orally (e.g. specialty drugs, melphalan (trade name Alkeran), busulfan, capecitabine). Delcath Systems, Inc. (NASDAQ: DCTH) a specialty pharmaceutical and medical device company manufactures melphalan. By 2011 the oral medications for cancer patients represented approximately 35% of cancer medications. Prior to the increase in cancer oral drugs community cancer centers were used to managing office-administered chemotherapy treatments. At that time "the majority of community oncology practices were unfamiliar with the process of prescribing and obtaining drugs that are covered under the pharmacy benefit" and "conventional retail pharmacy chains were ill-prepared
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to stock oral oncology agents, and were not set up to deliver the counseling that often accompanies these medications". == U.S. national market share == According to IMS Health "Specialty pharmaceutical spending is on the rise and is expected to increase from approximately $55 billion in 2005 to $1.7 trillion in 2030, according to the Pharmaceutical Care Management Association. That reflects an increase from 24% of total drug spend in 2005 to an estimated 44% of a health plan's total drug expenditure in 2030." === Mergers and acquisitions among specialty pharmacies === While CVS, Accredo, and Walgreens led the Specialty Pharmacies (SP) market in revenue in 2014, there are constant changes through mergers and acquisitions in terms of SPs and specialty distributors (SDs). The SP/SD network faces common strengths such as "in-depth clinical management, coordinated/comprehensive care, and early limited distribution network success" and common weaknesses, "lack of ability to customize services, poor integration experience and outcomes, and strained pharma relations". BioScrip was acquired by Walgreens in 2012. Specialty companies like Genzyme and MedImmune were acquired and are transitioning to a new business model.: 12 === Specialty hubs === According to Nicolas Basta, by 2013 there was "a spate of new entities" called hub services, "mechanisms by which manufacturers can keep a grip on the marketplace" in specialty pharma. The "biggest and oldest of these organizations" are "offshoots of insurance companies or [Pharmacy benefit managers] PBMs, such as Express Scripts' combination of Accredo and CuraScript (both specialty pharmacies) and HealthBridge (physician and patient support). UnitedHealth, an insurance company, operates OptumRx, a PBM, which has a specialty unit within it. Cigna has Tel-Drug, a mail-order pharmacy and support system." Basta described how Hubs have been around since about 2002 "starting out as "reimbursement hubs"", usually provided as a service by manufacturers to
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help patients and providers navigate the process of obtaining permission to use, and reimbursement for, expensive specialty therapies". Industry observers look to pioneering efforts by Genentech and Genzyme under the tenure of Henri Termeer, "when some of their earliest biotech products entered the marketplace". Specialty hubs provide reimbursement support to physicians and patients as well as patient education including medical hotlines. There is a voluntary program enrollment and registry intake with Patient Assistance Program management. === Affordability of specialty drugs and patient compliance with care plan === According to a 2007 study by employees of Express Scripts or its wholly owned subsidiary CuraScript on specialty pharmacy costs, if payers manage cost control through copayments with patients, there is an increased risk that patients will forego essential but expensive specialty drugs.: 6 and health outcomes were compromised.: 69 In 2007 these researchers suggested in the adoption of formularies and other traditional drug-management tools. They also recommended specialty drug utilization management programs that guide treatment plans and improve outpatient compliance.: 88 ==== Price inflation controversies ==== By 2010 Alexion Pharmaceuticals's Soliris, was considered to be the most expensive drug in the world. In a 2012 article in the New York Times, journalist Andrew Pollack described how Don M. Bailey, a mechanical engineer by training who became interim president of Questcor Pharmaceuticals, Inc. (Questcor) in May 2007, initiated a new pricing model for Acthar in August 2007 when it was classified by FDA as an orphan drug and a specialty drug to treat infantile spasms. Questcor, a biopharmaceutical company, focuses on the treatment of patients with "serious, difficult-to-treat autoimmune and inflammatory disorders". Its primary product is FDA-approved Acthar, an injectable drug that is used for the treatment of 19 indications. At the same time Questcor created "an expanded safety net for patients using
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Acthar", provided a "group of Medical Science Liaisons to work with health care providers who are administering Acthar" and limited distribution to its sole specialty distributor, Curascript. The 2007 pricing model brought "Acthar in line with the cost of treatments for other very rare diseases". The cost for a course of treatment in 2007 was estimated at about "$80,000–$100,000". Acthar is now manufactured through a contractor on Prince Edward Island, Canada. The price increased from $40 a vial to $700 and continued to increase. By 2012 the price of a vial of Acthar was $28,400. and was considered to be one of the world's most expensive drugs in 2013. By 2014 the price of Gilead's specialty drug for hepatitis C, Sovaldi or sofosbuvir, was $84,000 to $168,000 for a course of treatment in the U.S., £35,000 in the UK for 12 weeks. Sovaldi is on the World Health Organization's most important medications needed in a basic health system and the steep price is highly controversial. In 2014 the U.S. spent 742.6% more on hepatitis C medications than it did in 2013. In September 2015, Martin Shkreli was criticized by several health organizations for obtaining manufacturing licenses on old, out-of-patent, life-saving medicines including pyrimethamine (brand name Daraprim), which is used to treat patients with toxoplasmosis, malaria, some cancers, and AIDS, and then increasing the price of the drug in the US from $13.50 to $750 per pill, a 5,455% increase. In an interview with Bloomberg News, Shkreli claimed that despite the price increase, patient co-pays would be lower, that many patients would get the drug at no cost, that the company has expanded its free drug program, and that it sells half of the drugs for one dollar. === Captive pharmacies === In 2015 Bloomberg News used the term 'captive pharmacies'
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to describe the alleged exclusive agreements such as that between the specialty mail-order pharmacy Philodor and Valeant, mail-order pharmacy Linden Care and Horizon Pharma Plc. In November 2015 Express Scripts Holding Co.—the largest U.S. manager of prescription drug benefits—"removed the mail-order pharmacy Linden Care LLC from its network after concluding it dispensed a large portion of its medications from Horizon Pharma Plc and didn't fulfill its contractual agreements". Express Scripts was "evaluating other 'captive pharmacies' that it said are mostly distributing Horizon drugs". In 2015 specialty pharmacies like "Philidor drew attention for the lengths they went to fill prescriptions with brand-name drugs and then secure insurance reimbursement. == Trans-Pacific Partnership == According to Pfenex, a clinical-stage biotechnology company, the proposed terms in the Trans-Pacific Partnership, a trade agreement between twelve Pacific Rim countries, meant that all participating countries had to adopt the United States' lengthy drug patent exclusivity protection period of 12 years for biologics and specialty drugs. == Popular culture == In 1981 an episode of the television series Quincy, M.E. starring star, Jack Klugman as Quincy, entitled "Seldom Silent, Never Heard" brought the plight of children with orphan diseases to public attention. In the episode, Jeffrey, a young boy with Tourette syndrome, died after falling from a building. Dr. Arthur Ciotti (Michael Constantine), a medical doctor who had been researching Tourette syndrome for years wanted to study Jeffrey's brain to discover the cause and cure for the rare disease. He explained to Quincy that drug companies, like the one where he worked, were not interested in doing the research because so few people were afflicted with them that it was not financially viable. In 1982 another episode "Give Me Your Weak" Klugman as Quincy testified before Congress in an effort to get the Orphan Drug Act passed. He
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was moved by the dilemma of a young mother with myoclonus. == Further reading == Pharmaceutical Market Size, Share, Growth, and Industry Analysis". Report from The Market Intelligence. Oct 24, 2024. == References ==
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Dichloropropane can refer to any of several chemical compounds: 1,1-Dichloropropane 1,2-Dichloropropane 1,3-Dichloropropane 2,2-Dichloropropane == See also == Dichloropropene
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{
"page_id": 3018131,
"source": null,
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== Disorders of the skin == Athlete's foot Callus and Corns of the Skin Onychocryptosis (Ingrown Toenail) Keratosis palmaris et plantaris == Disorders of the joints == Arthritis mutilans Hallux valgus (bunion) Hallux varus Diabetic Arthropathy (Charcot Foot) Rheumatoid arthritis Osteoarthritis == Disorders of the bones == Fracture Jones Fracture Dupuytren fracture or Pott's fracture Osteomyelitis Bone cancer == Disorders of the nerves == Tarsal tunnel syndrome Neuroma Metatarsalgia Nerve entrapment == Combined disorders == Pes cavus (Cavus foot) Club foot == Genetic disorders == Polydactyly == Specific manifestations of systemic disease == Diabetic foot Rheumatoid foot Neuropathy Plantar fasciitis
|
{
"page_id": 7671190,
"source": null,
"title": "List of disorders of foot and ankle"
}
|
Sir Nevill Francis Mott (30 September 1905 – 8 August 1996) was a British physicist who won the Nobel Prize for Physics in 1977 for his work on the electronic structure of magnetic and disordered systems, especially amorphous semiconductors. The award was shared with Philip W. Anderson and J. H. Van Vleck. The three had conducted loosely related research. Mott and Anderson clarified the reasons why magnetic or amorphous materials can sometimes be metallic and sometimes insulating. == Education and early life == Mott was born in Leeds to Charles Francis Mott and Lilian Mary Reynolds, a granddaughter of Sir John Richardson, and great granddaughter of Sir John Henry Pelly, 1st Baronet. Miss Reynolds was a Cambridge Mathematics Tripos graduate and at Cambridge was the best woman mathematician of her year. His parents met in the Cavendish Laboratory, when both were engaged in physics research under J.J. Thomson. Nevill grew up first in the village of Giggleswick, in the West Riding of Yorkshire, where his father was Senior Science Master at Giggleswick School. His mother also taught Maths at the School. The family moved (due to his father's jobs) first to Staffordshire, then to Chester and finally Liverpool, where his father had been appointed Director of Education. Mott was at first educated at home by his mother. At age ten, he began formal education at Clifton College in Bristol, followed by study at St John's College, Cambridge, where he read the Mathematics Tripos, supervised by R.H. Fowler. == Career and research == Mott was appointed a Lecturer in the Physics Department at the University of Manchester in 1929. He returned to Cambridge in 1930 as a Fellow and lecturer of Gonville and Caius College, and in 1933 moved to the University of Bristol as Melville Wills Professor in Theoretical Physics.
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In 1948 he became Henry Overton Wills Professor of Physics and Director of the Henry Herbert Wills Physical Laboratory at Bristol. In 1954 he was appointed Cavendish Professor of Physics at Cambridge, a post he held until 1971. He was instrumental in the painful cancellation of the planned particle accelerator because of its very high cost. He also served as Master of Gonville and Caius College, 1959–1966. His early works were on the theoretical analysis of collisions in gases, notably the collision with spin flip of an electron against a hydrogen atom, which would stimulate subsequent works by André Blandin and Jun Kondo about similar effects between conduction electrons, as well as magnetic properties in metals. This sort of activity led Mott to writing two books. The first one, which was edited together with Ian Sneddon, gives a simple and clear description of quantum mechanics, with an emphasis on the Schrödinger equation in real space. The second describes atomic and electronic collisions in gases, using the rotational symmetry of electronic states in the Hartree–Fock method. But already in the middle of the 1930s, Mott's interests had broadened to include solid states, leading to two more books that would have a great impact on the development of the field in the years prior and after World War II. In 1936, Theory of the Properties of Metals and Alloys (written together with H. Jones) describes a simplified framework which led to rapid progress. The concept of nearly free valence electrons in metallic alloys explained the special stability of the Hume-Rothery phases if the Fermi sphere of the sp valence electron, treated as free, would be scattered by the Brillouin zone boundaries of the atomic structure. The description of the impurities in metals by the Thomas Fermi approximation would explain why such impurities
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"page_id": 396697,
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would not interact at long range. Finally the delocalisation of the valence d electrons in transitional metals and alloys would explain the possibility for the magnetic moments of atoms to be expressed as fractions of Bohr magnetons, leading to ferro or antiferromagnetic coupling at short range. This last contribution, produced at the first international conference on magnetism, held in Strasbourg in May 1939, reinforced similar points of view defended at the time in France by the future Nobel laureate Louis Néel. In 1949, Mott suggested to Jacques Friedel to use the approach developed together with Marvey for a more accurate description of the electric-field screening of the impurity in a metal, leading to the characteristic long range charge oscillations. Friedel also used the concept developed in that book of virtual bound level to describe a situation when the atomic potential considered is not quite strong enough to create a (real) bound level of symmetry e ≠ o. The consequences of these remarks on the more exact approaches of cohesion in rp as well as d metals were mostly developed by his students in Orsay. The second book, with Ronald Wilfred Gurney, On the Physical Chemistry of Solids was more wide-ranging. It treated notably of the oxidation of metals at low temperatures, where it described the growth of the oxide layer as due to the electric field developed between the metal and absorbed oxygen ions, which could force the way of metallic or oxygen ions through a disordered oxide layer. The book also analysed the photographic reactions in ionic silver compound in terms of precipitation of silver ions into metallic clusters. This second field had a direct and long lasting consequence on the research activity of John (Jack) Mitchell. Mott's accomplishments include explaining theoretically the effect of light on a photographic
|
{
"page_id": 396697,
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emulsion (see latent image). His work on oxidation, besides fostering new research in the field (notably by J. Bénard and Nicolás Cabrera), was the root of the concept of the band gap produced in semiconductors by gradients in the distribution of donor and acceptor impurities. During World War II, Mott joined the "Army Cell" of radar researchers. He was put in charge of getting the Army's GL Mk. II radar working in the presence of serious calibration problems that caused the measurements to change as the antenna tracked its targets. He solved this problem by designing a large metal wire mat that was built around the radars to provide a very flat reference plane. During the war Mott worked on the role of plastic deformation in the progression of fracture cracks. When he returned to Bristol after the war, his having met and hired Charles Frank enabled the two of them to make considerable advances in the study of dislocations, with the help of others such as Frank Nabarro and Alan Cottrell. Bristol became an important centre of research in this topic, especially at the end of the 1940s. If Mott only produced early and somewhat minor contributions to that field, notably on alloy hardening with Nabarro and on the topology of a dislocation network lowering the apparent elastic constants of a crystal, there is no doubt that Mott's enthusiasm played its role in the three major steps forward in the field by Frank on crystal growth and plasticity and later, in Cambridge, by Peter Hirsch on thin film electron microscopy. At the same time, however, Mott gave a lot of thought to electronic correlations and their possible role in Verwey's compounds such as nickel oxides which could switch from metals to nonmetallic insulators under various physical conditions - this
|
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is known as the Mott transition. The term Mott insulator is also named for him, as well as the Mott polynomials, which he introduced. === Publications === N. F. Mott revived the old Philosophical Magazine and transformed it into a lively publication essentially centred on the then-new field of solid state physics, attracting writers, readers and general interest on a wide scale. After receiving a paper on point defects in crystals by Frederick Seitz that was obviously too long for the journal, Mott decided to create a new publication, Advances in Physics, for such review papers. Both publications are still active in 2017. N. F. Mott, "The Wave Mechanics of α-Ray Tracks", Proceedings of the Royal Society (1929) A126, pp. 79–84, doi:10.1098/rspa.1929.0205. (reprinted as Sec. I-6 of Quantum Theory and Measurement, J. A. Wheeler. and W. H. Zurek, (1983) Princeton). N. F. Mott, Metal-Insulator Transitions, second edition (Taylor & Francis, London, 1990). ISBN 0-85066-783-6, ISBN 978-0-85066-783-7 N. F. Mott, A Life in Science (Taylor & Francis, London, 1986). ISBN 0-85066-333-4, ISBN 978-0-85066-333-4 N. F. Mott, H. Jones, The Theory of Properties of Metals and Alloys, (Dover Publications Inc., New York, 1958) Brian Pippard, Nevill Francis Mott, Physics Today, March 1997, pp. 95 and 96: (pdf). == Awards and honours == In 1977, Nevill Mott was awarded the Nobel Prize in Physics, together with Philip Warren Anderson and John Hasbrouck Van Vleck "for their fundamental theoretical investigations of the electronic structure of magnetic and disordered systems." The news of having won the Nobel Prize received Mott while having lunch at restaurant Die Sonne in Marburg, Germany, during a visit to fellow solid state scientist at Marburg University. Mott was elected a Fellow of the Royal Society (FRS) in 1936. Mott served as president of the Physical Society in 1957. In the
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early 1960s he was chairman of the British Pugwash group. He was knighted in 1962. Mott received an honorary Doctorate from Heriot-Watt University in 1972. In 1981, Mott became a founding member of the World Cultural Council. He continued to work until he was about ninety. He was made a Member of the Order of the Companions of Honour in 1995. In 1995, Mott visited the Loughborough University Department of Physics and presented a lecture entitled "65 Years in Physics". The University continues to host the annual Sir Nevill Mott Lecture. == Personal life == Mott was married to Ruth Eleanor Horder, and had two daughters, Elizabeth and Alice. Alice was an educationist who worked with Claus Moser and married the mathematician Mike Crampin who was a Professor of Mathematics at The Open University. Neville Mott retired to live near the Crampins in Aspley Guise, Milton Keynes, where he died on 8 August 1996 at the age of 90. His autobiography, A Life in Science, was published in 1986 by Taylor & Francis. His great grandfather was Sir John Richardson , the arctic explorer. == References == == External links == Media related to Nevill Francis Mott at Wikimedia Commons Quotations related to Nevill Mott at Wikiquote Nevill Mott on Nobelprize.org including the Nobel Lecture, 8 December 1977 Electrons in Glass
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"page_id": 396697,
"source": null,
"title": "Nevill Mott"
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Graviton (Franklin Hall) is a supervillain appearing in American comic books published by Marvel Comics. Created by writer Jim Shooter and artist Sal Buscema, he first appeared in The Avengers #158, dated April 1977. Over the years, he has mainly opposed the Avengers in their various incarnations. Originally a gravity researcher, Franklin Hall gains the ability to control gravity. Corrupted by this power, he becomes a supervillain using the name "Graviton". He is confronted and defeated by the Avengers as he tried to destroy the facility where he did his original research. In subsequent appearances Graviton seems to struggle with control of his powers and often loses because of this. More than one storyline has depicted Graviton's apparent death, only for him to return subsequently through various means. He later becomes part of Advanced Idea Mechanics' High Council as "Minister of Science". Graviton has appeared in Marvel television series, such as The Avengers: Earth's Mightiest Heroes, voiced by Fred Tatasciore. Additionally, Franklin Hall appeared in the Marvel Cinematic Universe (MCU) television series Agents of S.H.I.E.L.D., portrayed by Ian Hart, while the Graviton identity is filled by Glenn Talbot, portrayed by Adrian Pasdar. == Publication history == Graviton first appears in The Avengers #158 (April 1977) and was created by Jim Shooter and Sal Buscema. == Fictional character biography == Franklin Hall is a Canadian physicist involved in an experiment in a private research facility in the Canadian Rockies. A mistake in Hall's calculations causes graviton particles to be merged with his own molecules, and Hall later discovers that he can mentally control gravity. Hall at first tries to hide his newfound ability, but becomes tempted by the potential power, and donning a costume adopts the alias "Graviton". When Graviton takes over the research facility and forbids all communications with the
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outside world, a fellow scientist sends a distress signal to the superhero team the Avengers. A furious Graviton then lifts the facility several thousands of feet into the sky and threatens to kill the scientist. The Avengers then arrive and attack but are all defeated when trapped in a gravity field. Graviton then proceeds to bring the facility to New York, and demands the U.N. to hand over world power or he will destroy the world's cities. At Avengers Mansion a returning Black Panther learns of their plight and joins with Thor, having also been on leave from the team, and the two head to the facility. As Thor battles Graviton with Iron Man's help, the Panther frees the captive Avengers, but Graviton defeats them again until he is tricked into thinking a fellow scientist he cares for has committed suicide. Graviton then panics and causes the entire facility to collapse on him, forming a giant stone sphere that is dropped into a river by the Avengers. Graviton later reappears, although is suffering from amnesia and is flickering in and out of existence. Somehow guided to the female scientist he has feelings for, Graviton attempts to abduct her but is stopped by the Thing and Black Bolt. During the battle, Graviton describes himself as becoming a "living black hole" and morphs into a colossal humanoid. Graviton is then attacked until he loses concentration, implodes, and is presumed dead. Graviton is eventually able to reform his body, and decides to seek a bride. Elevating a Bloomingdale's store into the sky, he takes several women hostage until tricked by Thor. Thor then maroons a defeated Graviton in an alternate dimension. Graviton is able to return when an anomaly opens a portal to Earth. Arriving in Los Angeles, Graviton attempts to unite all
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"page_id": 1510811,
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"title": "Graviton (comics)"
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criminal elements under his leadership, but is defeated by the West Coast Avengers. Graviton was among the villains recruited by Mister Bitterhorn into Mephisto's Legion Accursed. They were used in part of a plot to kill the Beyonder with Mephisto's Beyondersbane weapon, but were delayed by the Thing until the weapon melted down. Graviton then recruits the supervillains Halflife, Quantum, and Zzzax as allies, but they are once again defeated by the West Coast Avengers. Graviton then defeats Spider-Man, and after a skirmish with the Fantastic Four, is defeated in turn by a cosmic-powered Spider-Man. Graviton then attacks the Avengers again, but is defeated when they overload his powers, banishing him to yet another alternate dimension. He then sends out a distress signal, which is noticed by the villains Techno and Baron Zemo. Graviton is eventually freed and attacks the teams the Thunderbolts and Great Lakes Avengers, but is persuaded by Moonstone to rethink his priorities. Desiring still more power, Graviton recruited a team of criminals and looted San Francisco, until eventually defeated by the Thunderbolts – currently aided by Angel – with the use of technology from Machine Man, whose flight capabilities cancel gravity, allowing them to use arm-bands based on his technology to shut down Graviton's powers. Banished once again to the same alternate dimension, Graviton becomes insane from the constant defeats and exile from Earth, and returns with the goal of total world conquest, accompanied by an adult-level P'tah named M'reel. Seeking revenge on the Thunderbolts, Graviton storms their headquarters to discover they have disbanded and been replaced by the Redeemers. Graviton kills almost the entire team before being defeated by a reformed Thunderbolts. Discovering that M'reel was channeling his power to create a dimensional warp enabling the P'tah to invade Earth a furious Graviton apparently dies
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stopping the alien invasion and saves the Thunderbolts. Under unrevealed circumstances, Graviton returned to Earth once more and was rendered powerless long enough to be imprisoned on the Raft with other superhuman criminals. However, when Electro shorted out the Raft's defenses to free Sauron, Graviton and dozens of other inmates escaped, only to be confronted by the heroes who would soon organize as the latest incarnation of the Avengers. Although recaptured, Graviton evidently sustained a head injury that somehow greatly dampened his powers, making him much less powerful than at his previous encounter with the Thunderbolts. He also was more megalomaniacal than ever during his next escape, declaring himself capable of forgiving and punishing sins. The reorganized Avengers again fought him at Ryker's, and after wounding Captain America and Spider-Man, Graviton was downed and almost killed by an Extremis-enhanced Iron Man. After battling Iron Man once again, having been framed for murder by an associate of the Mandarin who possessed similar gravity-manipulating powers to his own – he uses his powers to trigger an aneurysm in his brain, concluding that he will never receive a fair trial and wanting to end things on his terms. A 2010 storyline reveals that Graviton has a son with the same powers as he has, a criminal named Singularity, but he was revealed to be a normal child unrelated to Graviton, who had been brainwashed and mutated by the evil son of the Leader called Superior. Graviton turns up alive as part of the new High Council of A.I.M. (alongside Andrew Forson, Jude the Entropic Man, Mentallo, Superia and an undercover Taskmaster) as the Minister of Science. When the Secret Avengers attempted to assassinate Andrew Forson, Graviton attacked them but was quickly stopped by an attack by sentient Iron Patriot armors led by the
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Hulk. In "Avengers: Standoff!", Graviton was shown in a training video for the S.H.I.E.L.D. Cadets working in the gated community Pleasant Hill being subjected to Kobik, which turned him into a mild-mannered Pleasant Hill chef named Howie Howardson. In "Secret Empire", Graviton joins Helmut Zemo's Army of Evil. == Powers and abilities == Franklin Hall was a normal human until empowered by an explosion that intermingled his molecules with sub-nuclear graviton particles generated by a nearby particle generator, which gave him the ability to manipulate gravity. He can immobilize others by increasing their gravity, levitate himself by lowering his own gravity, and generate concussive energy blasts. Graviton's abilities are potent enough to move islands and reshape mountains. == In other media == === Television === Graviton appears in The Avengers: Earth's Mightiest Heroes two-part episode "Breakout", voiced by Fred Tatasciore. This version is a physicist hired by S.H.I.E.L.D. to help recreate the super-soldier serum that created Captain America. However, Hall caused an accident that gave himself near-limitless gravitational powers. Soon after, when it became clear that he had become dangerous, S.H.I.E.L.D. Director Nick Fury placed Hall into an unconscious state and imprisoned him in the Raft. A decade later, a technological malfunction enables Hall to escape and seek revenge on Fury, only to be foiled by Thor, the Wasp, Iron Man, the Hulk, and Ant-Man. Several characters inspired by Graviton appear in Agents of S.H.I.E.L.D., set in the Marvel Cinematic Universe (MCU). Franklin Hall appears in the first season episode "The Asset", portrayed by Ian Hart. This version is a Canadian physicist who was abducted by his former partner, Ian Quinn (portrayed by David Conrad), to finish work on a gravity manipulator powered by a liquid metal-esque, gravity-manipulating substance called gravitonium. Believing it is dangerous, Hall attempts to destroy the
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substance. S.H.I.E.L.D. agent Phil Coulson tries to save Hall, but the latter is pulled into the gravitonium, where he got trapped. The substance reappears in the episode "Providence", when Hydra agents release it before their leader John Garrett gives the gravitonium back to Quinn. In a flashback depicted in the fifth season episode "Inside Voices", Quinn is absorbed by the gravitonium following Garrett's defeat. During the fifth season, Ruby Hale (portrayed by Dove Cameron), a genetically-engineered Hydra agent, invades a subterranean Hydra facility and infuses herself with 8% of the gravitonium, seeking to become the "Destroyer of Worlds". However, she fails to control her newly acquired powers and kills one of Hydra's leaders, Werner von Strucker, before she is killed by S.H.I.E.L.D. agent Elena Rodriguez and S.H.I.E.L.D. recovers the remaining gravitonium. Later that season, when S.H.I.E.L.D. comes under attack by alien warriors sent by the Confederacy, Glenn Talbot (portrayed by Adrian Pasdar) infuses himself with the remaining gravitonium, along with Hall and Quinn's consciousnesses, and uses his new abilities to kill the warriors before taking Coulson to confront the Confederacy, who they learn intend to stop Thanos. Becoming increasingly narcissistic and unhinged under the corrupting influence of the gravitonium however, Talbot forces his way into the group and attempts to absorb more gravitonium until he is defeated by Daisy Johnson. Graviton appears in Marvel Disk Wars: The Avengers voiced by Mitsuaki Madano in the Japanese version and by Patrick Seitz in the English dub. This version is a member of the Masters of Evil. === Film === Graviton appears in Avengers Confidential: Black Widow & Punisher. === Video games === Graviton appears as a boss in The Amazing Spider-Man 2. Graviton appears as a boss in Marvel: Avengers Alliance 2. == References == == External links == Graviton at Marvel.com
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"page_id": 1510811,
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Internal conversion is a transition from a higher to a lower electronic state in a molecule or atom. It is sometimes called "radiationless de-excitation", because no photons are emitted. It differs from intersystem crossing in that, while both are radiationless methods of de-excitation, the molecular spin state for internal conversion remains the same, whereas it changes for intersystem crossing. The energy of the electronically excited state is given off to vibrational modes of the molecule. The excitation energy is transformed into heat. == Examples == A classic example of this process is the quinine sulfate fluorescence, which can be quenched by the use of various halide salts. The excited molecule can de-excite by increasing the thermal energy of the surrounding solvated ions. Several natural molecules perform a fast internal conversion. This ability to transform the excitation energy of photon into heat can be a crucial property for photoprotection by molecules such as melanin. Fast internal conversion reduces the excited state lifetime, and thereby prevents bimolecular reactions. Bimolecular electron transfer always produces a reactive chemical species, free radicals. Nucleic acids (precisely the single, free nucleotides, not those bound in a DNA/RNA strand) have an extremely short lifetime due to a fast internal conversion. Both melanin and DNA have some of the fastest internal conversion rates. In applications that make use of bimolecular electron transfer the internal conversion is undesirable. For example, it is advantageous to have a long-lived excited state in Grätzel cells (Dye-sensitized solar cells). == See also == Fluorescence spectroscopy Förster resonance energy transfer == References ==
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{
"page_id": 2362780,
"source": null,
"title": "Internal conversion (chemistry)"
}
|
In quantum and theoretical chemistry, an intruder state is a particular situation arising in perturbative evaluations, where the energy of the perturbers is comparable in magnitude to the energy associated to the zero order wavefunction. In this case, a divergent behavior occurs, due to the nearly zero denominator in the expression of the perturbative correction. Multi-reference wavefunction methods are not immune. There are ways to identity them. The natural orbitals of the perturbation expansion are a useful diagnostic for detecting intruder state effects. Sometimes what appears to be an intruder state is simply a change in basis. == References ==
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{
"page_id": 4525469,
"source": null,
"title": "Intruder state"
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Joaquim da Costa Ribeiro (Rio de Janeiro, July 8th 1906 - July 29th, 1960) was a Brazilian physicist and university professor in Brazil. He discovered the thermodielectric effect, also known as the Workman-Reynolds in the US. Ribeiro was a member of the Brazilian Academy of Sciences and was the first Scientific Director of CNPq. He is the father of anthropologist Yvonne Maggie and grandfather of movie author Ana Costa Ribeiro, who directed "Termodielétrico", a memoir film about him and his legacy. == Biography == Costa Ribeiro was born at his family's house, on Barão de Itapejipe street, 82, in what was then the federal district of Brazil. His parents were Antonio Marques da Costa Ribeiro and Maria Constança Alburquerque da Costa Ribeiro. His father and grandfather, after whom Joaquim was named, were judges. Costa Ribeiro studied in a Jesuit school called Santo Inácio, until 1923, enrolling in the National School of Engineering the next year at the University of Brazil. Ten years later, he got tenure at the same university. In 1940, Costa Ribeiro started researching new methods to measure radioactivity, and later studied the production of electret using several dielectric materials Costa Ribeiro observed that, during electret formation, electric current was unnecessary: the dielectric's natural freezing was enough to electrify the end material, provided that one of the cooling phases was solid. The phenomenom was named "thermodielectric effect" by Costa Ribeiro and fully described by him in a 1944 article in the Annals of the Brazilian Academy of Sciences (ABC) that gathered siginificant attention at home and abroad. This marked the first physical phenomenom completely observed and described by a Brazilian researcher. Two years later, he got a permanent position in general and experimental Physics at the National Philosophy College, at the same university. === Naming Controversy === In
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may 1950, six years after the complete description of the phenomenom, two american scientists, Everly J. Workman and Steve E. Reynolds, published an article on Physical Review describing the observation of the thermodielectric effect in ice and water, without acknowledging Costa Ribeiro's findings. Despite attempts by the Brazilian scientific community to warn authors of the precedence, several papers still mention the thermodielectric effect as the "Workman-Reynolds effect". == Death == Costa Ribeiro died in July 29th, 1960 at 54 years of age, at the Casa de Saúde Santa Lúcia. He was survived by his nine children. == Awards == Costa RIbeiro received the Einstein Prize by the ABC. He was also the first Brazilian delegate of UN for the peaceful use of nuclear energy. Costa Ribeiro also helped to found CNPq, and was its first director. Since he was a pioneer of condensed matter physics in Brazil, the Brazilian Physical Society created the Joaquim da Costa Ribeiro prize, awarded to "researchers with meaningful contributions to condensed matter science in Brazil". == References ==
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{
"page_id": 79826334,
"source": null,
"title": "Joaquim da Costa Ribeiro"
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The Volcano Ranch experiment was an array of particle detectors in Volcano Ranch, New Mexico, used to measure ultra-high-energy cosmic rays. The array was built by John Linsley and Livio Scarsi in 1959. On February 22, 1962, Linsley observed an air shower at Volcano Ranch created by a primary particle with an energy greater than 1020 eV, the highest energy cosmic ray particle ever detected at the time. Linsley continued to operate Volcano Ranch until 1978, when it was closed due to lack of funding. == References == "Finding Aid to the John Linsley Papers". Fermilab History and Archives Project, Fermi National Accelerator Laboratory. 2012. Retrieved 21 September 2012. Nagano, M.; Watson, A. A. (July 2000). "Observations and implications of the ultrahigh-energy cosmic rays". Rev. Mod. Phys. 72 (3): 689–732. Bibcode:2000RvMP...72..689N. CiteSeerX 10.1.1.1029.7236. doi:10.1103/RevModPhys.72.689.
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{
"page_id": 33885598,
"source": null,
"title": "Volcano Ranch experiment"
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Vat Yellow 1 is a vat dye, yellow in appearance under some conditions used in cloth dyeing. == References ==
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{
"page_id": 42208674,
"source": null,
"title": "Vat Yellow 1"
}
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Absolute molar mass is a process used to determine the characteristics of molecules. == History == The first absolute measurements of molecular weights (i.e. made without reference to standards) were based on fundamental physical characteristics and their relation to the molar mass. The most useful of these were membrane osmometry and sedimentation. Another absolute instrumental approach was also possible with the development of light scattering theory by Albert Einstein, Chandrasekhara Venkata Raman, Peter Debye, Bruno H. Zimm, and others. The problem with measurements made using membrane osmometry and sedimentation was that they only characterized the bulk properties of the polymer sample. Moreover, the measurements were excessively time consuming and prone to operator error. In order to gain information about a polydisperse mixture of molar masses, a method for separating the different sizes was developed. This was achieved by the advent of size exclusion chromatography (SEC). SEC is based on the fact that the pores in the packing material of chromatography columns could be made small enough for molecules to become temporarily lodged in their interstitial spaces. As the sample makes its way through a column the smaller molecules spend more time traveling in these void spaces than the larger ones, which have fewer places to "wander". The result is that a sample is separated according to its hydrodynamic volume V h {\displaystyle V_{h}} . As a consequence, the big molecules come out first, and then the small ones follow in the eluent. By choosing a suitable column packing material it is possible to define the resolution of the system. Columns can also be combined in series to increase resolution or the range of sizes studied. The next step is to convert the time at which the samples eluted into a measurement of molar mass. This is possible because if the
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{
"page_id": 16977319,
"source": null,
"title": "Absolute molar mass"
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molar mass of a standard were known, the time at which this standard eluted should be equal to a specific molar mass. Using multiple standards, a calibration curve of time versus molar mass can be developed. This is significant for polymer analysis because a single polymer could be shown to have many different components, and the complexity and distribution of which would also affect the physical properties. However this technique has shortcomings. For example, unknown samples are always measured in relation to known standards, and these standards may or may not have similarities to the sample of interest. The measurements made by SEC are then mathematically converted into data similar to that found by the existing techniques. The problem was that the system was calibrated according to the Vh characteristics of polymer standards that are not directly related to the molar mass. If the relationship between the molar mass and Vh of the standard is not the same as that of the unknown sample, then the calibration is invalid. Thus, to be accurate, the calibration must use the same polymer, of the same conformation, in the same eluent and have the same interaction with the solvent as the hydration layer changes Vh. Benoit et al. showed that taking into account the hydrodynamic volume would solve the problem. In his publication, Benoit showed that all synthetic polymers elutes on the same curve when the log of the intrinsic viscosity multiplied by the molar mass was plotted against the elution volume. This is the basis of universal calibration which requires a viscometer to measure the intrinsic viscosity of the polymers. Universal calibration was shown to work for branched polymers, copolymers as well as starburst polymers. For good chromatography, there must be no interaction with the column other than that produced by size.
|
{
"page_id": 16977319,
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"title": "Absolute molar mass"
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As the demands on polymer properties increased, the necessity of getting absolute information on the molar mass and size also increased. This was especially important in pharmaceutical applications where slight changes in molar mass (e.g. aggregation) or shape may result in different biological activity. These changes can actually have a harmful effect instead of a beneficial one. To obtain molar mass, light scattering instruments need to measure the intensity of light scattered at zero angle. This is impractical as the laser source would outshine the light scattering intensity at zero angle. The 2 alternatives are to measure very close to zero angle or to measure at many angle and extrapolate using a model (Rayleigh, Rayleigh–Gans–Debye, Berry, Mie, etc.) to zero degree angle. Traditional light scattering instruments worked by taking readings from multiple angles, each being measured in series. A low angle light scattering system was developed in the early 1970s that allowed a single measurement to be used to calculate the molar mass. Although measurements at low angles are better for fundamental physical reasons (molecules tend to scatter more light in lower angle directions than in higher angles), low angle scattering events caused by dust and contamination of the mobile phase easily overwhelm the scattering from the molecules of interest. When the low-angle laser light scattering (LALLS) became popular in the 1970s and mid-1980s, good quality disposable filters were not readily available and hence multi-angle measurements gained favour. Multi-angle light scattering was invented in the mid-1980s and instruments like that were able to make measurements at the different angles simultaneously but it was not until the later 1980s (10-12) that the connection of multi-angle laser light scattering (MALS) detectors to SEC systems was a practical proposition enabling both molar mass and size to be determined from each slice of the
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{
"page_id": 16977319,
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polymer fraction. == Applications == Light scattering measurements can be applied to synthetic polymers, proteins, pharmaceuticals and particles such as liposomes, micelles, and encapsulated proteins. Measurements can be made in one of two modes which are un-fractionated (batch mode) or in continuous flow mode (with SEC, HPLC or any other flow fractionation method). Batch mode experiments can be performed either by injecting a sample into a flow cell with a syringe or with the use of discrete vials. These measurements are most often used to measure timed events like antibody-antigen reactions or protein assembly. Batch mode measurements can also be used to determine the second virial coefficient (A2), a value that gives a measure of the likelihood of crystallization or aggregation in a given solvent. Continuous flow experiments can be used to study material eluting from virtually any source. More conventionally, the detectors are coupled to a variety of different chromatographic separation systems. The ability to determine the mass and size of the materials eluting then combines the advantage of the separation system with an absolute measurement of the mass and size of the species eluting. The addition of an SLS detector coupled downstream to a chromatographic system allows the utility of SEC or similar separation combined with the advantage of an absolute detection method. The light scattering data is purely dependent on the light scattering signal times the concentration; the elution time is irrelevant and the separation can be changed for different samples without recalibration. In addition, a non-size separation method such as HPLC or IC can also be used. As the light scattering detector is mass dependent, it becomes more sensitive as the molar mass increases. Thus it is an excellent tool for detecting aggregation. The higher the aggregation number, the more sensitive the detector becomes. == Low-angle
|
{
"page_id": 16977319,
"source": null,
"title": "Absolute molar mass"
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|
(laser)-light scattering (LALS) method == LALS measurements are measuring at a very low angle where the scattering vector is almost zero. LALS does not need any model to fit the angular dependence and hence is giving more reliable molecular weights measurements for large molecules. LALS alone does not give any indication of the root mean square radius. == Multi-angle (laser)-light scattering (MALS) method == MALS measurements work by calculating the amount of light scattered at each angle detected. The calculation is based on the intensity of light measured and the quantum efficiency of each detector. Then a model is used to approximate the intensity of light scattered at zero angle. The zero angle light scattered is then related to the molar mass. As previously noted, the MALS detector can also provide information about the size of the molecule. This information is the Root Mean Square radius of the molecule (RMS or Rg). This is different from the Rh mentioned above who is taking the hydration layer into account. The purely mathematical root mean square radius is defined as the radii making up the molecule multiplied by the mass at that radius. == Bibliography == A. Einstein, Ann. Phys. 33 (1910), 1275 C.V. Raman, Indian J. Phys. 2 (1927), 1 P.Debye, J. Appl. Phys. 15 (1944), 338 B.H. Zimm, J. Chem. Phys. 13 (1945), 141 B.H. Zimm, J. Chem. Phys. 16 (1948), 1093 B.H. Zimm, R.S. Stein and P. Dotty, Pol. Bull. 1,(1945), 90 M. Fixman, J. Chem. Phys. 23 (1955), 2074 A.C. Ouano and W. Kaye J. Poly. Sci. A1(12) (1974), 1151 Z. Grubisic, P. Rempp, and H. Benoit, J. Polym. Sci., 5 (1967), 753 Flow Through MALS detector, DLS 800, Science Spectrum Inc. P.J. Wyatt, C. Jackson and G.K. Wyatt Am. Lab 20(6) (1988), 86 P.J. Wyatt, D. L.
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{
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|
Hicks, C. Jackson and G.K. Wyatt Am. Lab. 20(6) (1988), 106 C. Jackson, L.M. Nilsson and P.J. Wyatt J. Appl. Poly. Sci. 43 (1989), 99
|
{
"page_id": 16977319,
"source": null,
"title": "Absolute molar mass"
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|
FI6 is an antibody that targets a protein found on the surface of all influenza A viruses called hemagglutinin. FI6 is the only known antibody found to bind all 16 subtypes of the influenza A virus hemagglutinin and is hoped to be useful for universal influenza virus therapy. The antibody binds to the F domain HA trimer, and prevents the virus from attaching to the host cell. The antibody has been refined in order to remove any excess, unstable mutations that could negatively affect its neutralising ability, and this new version of the antibody has been termed "FI6v3" == Research == Researchers from Britain and Switzerland have previously found antibodies that work in Group 1 influenza A viruses or against most Group 2 viruses (CR8020), but not against both. This team developed a method using single-cell screening to test very large numbers of human plasma cells, to increase their odds of finding an antibody even if it was extremely rare. When they identified FI6, they injected it into mice and ferrets and found that it protected the animals against infection by either a Group 1 or Group 2 influenza A virus. Scientists screened 104,000 peripheral-blood plasma cells from eight recently infected or vaccinated donors for antibodies that recognize each of three diverse influenza strains: H1N1 (swine-origin) and H5N1 and H7N7 (highly pathogenic avian influenzas.) From one donor, they isolated four plasma cells that produced an identical antibody, which they called FI6. This antibody binds all 16 HA subtypes, neutralizes infection, and protects mice and ferrets from lethal infection. The most broadly reactive antibodies that had previously been discovered recognized either one group of HA subtypes or the other, highlighting how remarkable FI6 is in its ability to target the gamut of influenza subtypes. == Clinical implication == Researchers determined the
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{
"page_id": 32574888,
"source": null,
"title": "FI6 (antibody)"
}
|
crystal structure of the FI6 antibody when it was bound to H1 and H3 HA proteins. Sitting atop the HA spike is a globular head domain that binds to cellular receptors during viral entry and contains the major antigenic sites targeted by the immune system. Because of this selective pressure, the sequence in the head domain drifts enough to require an updated seasonal vaccine most years. A stalk domain connects the head to the viral membrane and is responsible for fusing viral and host membranes so that the pathogen can invade human cells. The immune system usually does not have a strong response to the partially hidden stalk domain, so portions of the stalk remain highly conserved across all influenza subtypes. The FI6 antibody makes extensive contact with conserved parts of the stalk, thereby blocking HA from harpooning a sticky fusion peptide into the host membrane during viral entry. The FI6 provides scientists with a broadly neutralizing antibody that recognizes all 16 HA subtypes, including emerging ones, such as H5N1. But, because the replication of the influenza virus is somewhat error-prone, the virus evolves as a quasispecies, and widespread use of antiviral drugs can lead to resistant strains. Such has been the case for oseltamivir and for the M2 ion channel blocker amantadine. Therefore, before considering FI6 as a long-term prophylactic or therapeutic agent against seasonal influenza, we would first have to determine whether the influenza virus could quickly mutate the epitope targeted by FI6 and escape recognition by FI6 after exposure. A more important clinical implication of this work is the identification of a universal neutralizing epitope in the HA stalk at the atomic level an important intellectual landmark for the development of a universal influenza vaccine. In the absence of the immunodominant head domain, isolated portions of the
|
{
"page_id": 32574888,
"source": null,
"title": "FI6 (antibody)"
}
|
HA stalk that include the FI6 epitope and have already been shown to stimulate broad, but not universal, protective effects against H1N1 and H3N2 strains in vaccinated animals. Using protein engineering and adjuvants to focus the immune system on the FI6 epitope may be the critical next step along the path to a universal vaccine. == See also == Universal flu vaccine == References == == External links == Science Magazine: A Neutralizing Antibody Selected from Plasma Cells That Binds to Group 1 and Group 2 Influenza A Hemagglutinins GenBank accession: heavy chain variable region: JN234430, JN234435, JN234436, JN234437 (FI6VHv3), JN234438 (FI6VHv2), JN234439 (FI6VH) Identical group AEL31297: JN234431, JN234432, JN234433, JN234434 kappa light chain variable region: Identical group AEL31306: JN234440, JN234441, JN234442, JN234443 JN234444, JN234445, JN234446 (FI6VKv2), JN234447 (FI6VKv1), JN234448 (FI6VK)
|
{
"page_id": 32574888,
"source": null,
"title": "FI6 (antibody)"
}
|
The UCSF Industry Documents Library (IDL) is a digital archive of internal tobacco, drug, food, chemical and fossil fuel corporate documents, acquired largely through litigation, which illustrate industry efforts to influence policies and regulations meant to protect public health. Created and maintained by the UCSF Library, the mission of the UCSF Industry Documents Library is to "identify, collect, curate, preserve, and make freely accessible internal documents created by industries and their partners which have an impact on public health, for the benefit and use of researchers, clinicians, educators, students, policymakers, media, and the general public at UCSF and internationally". == Collections == The IDL includes the following archives: the Truth Tobacco Industry Documents the Drug Industry Documents Archive the Food Industry Documents Archive the Chemical Industry Documents Archive the Fossil Fuel Industry Document Archive == References == == External links == Official site
|
{
"page_id": 48827817,
"source": null,
"title": "Industry Documents Library"
}
|
Terpenoidallyltransferase may refer to: All-trans-octaprenyl-diphosphate synthase, an enzyme All-trans-decaprenyl-diphosphate synthase, an enzyme
|
{
"page_id": 38866348,
"source": null,
"title": "Terpenoidallyltransferase"
}
|
Rhizochromulinales is an order of Dictyochophyceae. The order includes the genus, Rhizochromulina. Ciliophrys is also sometimes included in this group. == References ==
|
{
"page_id": 23203246,
"source": null,
"title": "Rhizochromulinales"
}
|
Terpenyl pyrophosphate synthetase may refer to: All-trans-octaprenyl-diphosphate synthase, an enzyme All-trans-decaprenyl-diphosphate synthase, an enzyme
|
{
"page_id": 38866350,
"source": null,
"title": "Terpenyl pyrophosphate synthetase"
}
|
When placed into solution, salts begin to dissolve and form ions. This is not always in equal proportion, due to the preference of an ion to be dissolved in a given solution. The ability of an ion to preferentially dissolve (as a result of unequal activities) over its counterion is classified as the potential determining ion. The properties of this ion are strongly related to the surface potential present on a corresponding solid. This unequal property between corresponding ions results in a net surface charge. In some cases this arises because one of the ions freely leaves a corresponding solid and the other does not or it is bound to the solid by some other means. Adsorption of an ion to the solid may result in the solid acting as an electrode. (e.g., H+ and OH− on the surfaces of clays). In a colloidal dispersed system, ion dissolution arises, where the dispersed particles exist in equilibrium with their saturated counterpart, for example: NaCl(s) ⇌ Na+(aq) + Cl−(aq) The behavior of this system is characterised by the components activity coefficients and solubility product: aNa+ · aCl− = Ksp In clay-aqueous systems the potential of the surface is determined by the activity of ions which react with the mineral surface. Frequently this is the hydrogen ion H+ in which case the important activity is determined by pH. The simultaneous adsorption of protons and hydroxyls as well as other potential determining cations and anions, leads to the concept of point of zero charge or PZC, where the total charge from the cations and anions at the surface is equal to zero. The charge must be zero, and this does not necessarily mean the number of cations versus anions in the solution are equal. For clay minerals the potential determining ions are H+ and
|
{
"page_id": 7867823,
"source": null,
"title": "Potential determining ion"
}
|
OH− and complex ions formed by bonding with H+ and OH−. == References == == Further reading == Patrick Brezonik; William Arnold (22 March 2011). Water Chemistry: An Introduction to the Chemistry of Natural and Engineered Aquatic Systems. Oxford University Press. p. 540. ISBN 978-0-19-973072-8. Retrieved 3 February 2014. Robert J. Stokes; D. Fennell Evans (1997). Fundamentals of Interfacial Engineering. John Wiley & Sons. p. 157. ISBN 978-0-471-18647-2. Retrieved 3 February 2014. Terence Cosgrove (16 February 2010). Colloid Science: Principles, Methods and Applications. John Wiley & Sons. p. 25. ISBN 978-1-4443-2018-3. Retrieved 3 February 2014.
|
{
"page_id": 7867823,
"source": null,
"title": "Potential determining ion"
}
|
ESyPred3D is an automated homology modeling program. Alignments are obtained by combining, weighting and screening the results of several multiple alignment programs. The final three-dimensional structure is built using the modeling package MODELLER. == Method == To perform homology modeling, the ESyPred3D program first searches for a template (a similar sequence of known structure), before aligning the query and template sequences. EsyPred3D then build the 3D models using the alignment and the template structure, before assessing the final 3D model. The query and the template sequences are aligned using a consensus alignment method. Different multiple sequence alignments are built using different alignment programs on two sets of sequences including the query and the template sequence. The consensus method uses a neural network to find the best aligned residues and analyzing all possible combinations using a dead end elimination algorithm. The final 3D model is built from the target-template alignment and the 3D structure of the template using MODELLER. MODELLER is also used to build the missing loops. == See also == List of protein structure prediction software Protein structure prediction Homology modeling == References == == External links == ESyPred3D web server
|
{
"page_id": 18615729,
"source": null,
"title": "ESyPred3D"
}
|
A trajectory or flight path is the path that an object with mass in motion follows through space as a function of time. In classical mechanics, a trajectory is defined by Hamiltonian mechanics via canonical coordinates; hence, a complete trajectory is defined by position and momentum, simultaneously. The mass might be a projectile or a satellite. For example, it can be an orbit — the path of a planet, asteroid, or comet as it travels around a central mass. In control theory, a trajectory is a time-ordered set of states of a dynamical system (see e.g. Poincaré map). In discrete mathematics, a trajectory is a sequence ( f k ( x ) ) k ∈ N {\displaystyle (f^{k}(x))_{k\in \mathbb {N} }} of values calculated by the iterated application of a mapping f {\displaystyle f} to an element x {\displaystyle x} of its source. == Physics of trajectories == A familiar example of a trajectory is the path of a projectile, such as a thrown ball or rock. In a significantly simplified model, the object moves only under the influence of a uniform gravitational force field. This can be a good approximation for a rock that is thrown for short distances, for example at the surface of the Moon. In this simple approximation, the trajectory takes the shape of a parabola. Generally when determining trajectories, it may be necessary to account for nonuniform gravitational forces and air resistance (drag and aerodynamics). This is the focus of the discipline of ballistics. One of the remarkable achievements of Newtonian mechanics was the derivation of Kepler's laws of planetary motion. In the gravitational field of a point mass or a spherically-symmetrical extended mass (such as the Sun), the trajectory of a moving object is a conic section, usually an ellipse or a hyperbola. This
|
{
"page_id": 200115,
"source": null,
"title": "Trajectory"
}
|
agrees with the observed orbits of planets, comets, and artificial spacecraft to a reasonably good approximation, although if a comet passes close to the Sun, then it is also influenced by other forces such as the solar wind and radiation pressure, which modify the orbit and cause the comet to eject material into space. Newton's theory later developed into the branch of theoretical physics known as classical mechanics. It employs the mathematics of differential calculus (which was also initiated by Newton in his youth). Over the centuries, countless scientists have contributed to the development of these two disciplines. Classical mechanics became a most prominent demonstration of the power of rational thought, i.e. reason, in science as well as technology. It helps to understand and predict an enormous range of phenomena; trajectories are but one example. Consider a particle of mass m {\displaystyle m} , moving in a potential field V {\displaystyle V} . In physical terms, mass represents inertia, and the field V {\displaystyle V} represents external forces of a particular kind known as "conservative". Given V {\displaystyle V} at every relevant position, there is a way to infer the associated force that would act at that position, say from gravity. Not all forces can be expressed in this way, however. The motion of the particle is described by the second-order differential equation m d 2 x → ( t ) d t 2 = − ∇ V ( x → ( t ) ) with x → = ( x , y , z ) . {\displaystyle m{\frac {\mathrm {d} ^{2}{\vec {x}}(t)}{\mathrm {d} t^{2}}}=-\nabla V({\vec {x}}(t)){\text{ with }}{\vec {x}}=(x,y,z).} On the right-hand side, the force is given in terms of ∇ V {\displaystyle \nabla V} , the gradient of the potential, taken at positions along the trajectory. This is
|
{
"page_id": 200115,
"source": null,
"title": "Trajectory"
}
|
the mathematical form of Newton's second law of motion: force equals mass times acceleration, for such situations. == Examples == === Uniform gravity, neither drag nor wind === The ideal case of motion of a projectile in a uniform gravitational field in the absence of other forces (such as air drag) was first investigated by Galileo Galilei. To neglect the action of the atmosphere in shaping a trajectory would have been considered a futile hypothesis by practical-minded investigators all through the Middle Ages in Europe. Nevertheless, by anticipating the existence of the vacuum, later to be demonstrated on Earth by his collaborator Evangelista Torricelli, Galileo was able to initiate the future science of mechanics. In a near vacuum, as it turns out for instance on the Moon, his simplified parabolic trajectory proves essentially correct. In the analysis that follows, we derive the equation of motion of a projectile as measured from an inertial frame at rest with respect to the ground. Associated with the frame is a right-hand coordinate system with its origin at the point of launch of the projectile. The x {\displaystyle x} -axis is tangent to the ground, and the y {\displaystyle y} axis is perpendicular to it ( parallel to the gravitational field lines ). Let g {\displaystyle g} be the acceleration of gravity. Relative to the flat terrain, let the initial horizontal speed be v h = v cos ( θ ) {\displaystyle v_{h}=v\cos(\theta )} and the initial vertical speed be v v = v sin ( θ ) {\displaystyle v_{v}=v\sin(\theta )} . It will also be shown that the range is 2 v h v v / g {\displaystyle 2v_{h}v_{v}/g} , and the maximum altitude is v v 2 / 2 g {\displaystyle v_{v}^{2}/2g} . The maximum range for a given initial
|
{
"page_id": 200115,
"source": null,
"title": "Trajectory"
}
|
speed v {\displaystyle v} is obtained when v h = v v {\displaystyle v_{h}=v_{v}} , i.e. the initial angle is 45 ∘ {\displaystyle ^{\circ }} . This range is v 2 / g {\displaystyle v^{2}/g} , and the maximum altitude at the maximum range is v 2 / ( 4 g ) {\displaystyle v^{2}/(4g)} . ==== Derivation of the equation of motion ==== Assume the motion of the projectile is being measured from a free fall frame which happens to be at (x,y) = (0,0) at t = 0. The equation of motion of the projectile in this frame (by the equivalence principle) would be y = x tan ( θ ) {\displaystyle y=x\tan(\theta )} . The co-ordinates of this free-fall frame, with respect to our inertial frame would be y = − g t 2 / 2 {\displaystyle y=-gt^{2}/2} . That is, y = − g ( x / v h ) 2 / 2 {\displaystyle y=-g(x/v_{h})^{2}/2} . Now translating back to the inertial frame the co-ordinates of the projectile becomes y = x tan ( θ ) − g ( x / v h ) 2 / 2 {\displaystyle y=x\tan(\theta )-g(x/v_{h})^{2}/2} That is: y = − g sec 2 θ 2 v 0 2 x 2 + x tan θ , {\displaystyle y=-{g\sec ^{2}\theta \over 2v_{0}^{2}}x^{2}+x\tan \theta ,} (where v0 is the initial velocity, θ {\displaystyle \theta } is the angle of elevation, and g is the acceleration due to gravity). ==== Range and height ==== The range, R, is the greatest distance the object travels along the x-axis in the I sector. The initial velocity, vi, is the speed at which said object is launched from the point of origin. The initial angle, θi, is the angle at which said object is released.
|
{
"page_id": 200115,
"source": null,
"title": "Trajectory"
}
|
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