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The Lucifer Principle is a 1995 book by American author Howard Bloom, in which he argues that social groups, not individuals, are the primary "unit of selection" on genes and human psychological development. He states that both competition between groups and competition between individuals shape the evolution of the genome. Bloom "explores the intricate relationships among genetics, human behavior, and culture" and argues that "evil is a by-product of nature's strategies for creation and that it is woven into our most basic biological fabric". It sees selection (e.g., through violent competition) as central to the creation of the "superorganism" of society. It also focuses on competition between individuals for position in the "pecking order" and competition between groups for standing in pecking orders of groups. The Lucifer Principle shows how ideas are vital in creating cohesion and cooperation in these pecking order battles. In the book, Bloom writes: "Superorganism, ideas and the pecking order...these are the primary forces behind much of human creativity and earthly good." == Reception of the book == Reviews of the book saw it as "ambitious" and "disturbing" in its conclusions that societies based on individual freedom might succumb to systems such as bureaucratic Communism or Islamic fundamentalism. The Washington Post said that "Readers will be mesmerized by the mirror Bloom holds to the human condition... He draws on a dozen years of research into a jungle of scholarly fields...and meticulously supports every bit of information...." while Chet Raymo in The Boston Globe termed it "a string of rhetorical firecrackers that challenge our many forms of self-righteousness". == Bloom responds to Islamic issues == Bloom later wrote that he and his publisher had been threatened by Islamic groups who objected to aspects of the book. He claimed that "Arab pressure groups asked ever so politely that
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"page_id": 14946407,
"source": null,
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The Lucifer Principle be withdrawn from print and that nothing that I write be published again. They offered to boycott my publisher's products—all of them—worldwide. And they backed their warning with a call for my punishment in seventeen Islamic countries." Bloom states that the attorney for the Authors Guild wrote to his publishers, warning of an author boycott if the book was pulled from the shelves. The publishers asked Bloom to rewrite a chapter on Islamic violence, which led to the creation of 358 lines of footnotes attesting to the facts he presented within it, documenting that what Bloom wrote about Islam in The Lucifer Principle is based on expertise. == References == == External links == Official website "Muslim protests against The Lucifer Principle". Archived from the original on October 23, 2007. Retrieved December 30, 2007.
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{
"page_id": 14946407,
"source": null,
"title": "The Lucifer Principle"
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The Crich β-mannosylation in organic chemistry is a synthetic strategy which is used in carbohydrate synthesis to generate a 1,2-cis-glycosidic bond. This type of linkate is generally very difficult to make, and specific methods like the Crich β-mannosylation are used to overcome these issues. The technique takes its name from its developer, Professor David Crich. == Background == The development of facile chemical glycosylation protocols is essential to synthesizing complex oligosaccharides. Among many diverse type of glycosidic linkages, the 1,2-cis-β-glycoside, which exists in many biologically relevant glycoconjugates and oligosaccharides, is arguably one of the most difficult to synthesize. The challenges in constructing β-mannose linkage have been well documented in several reviews. To date, a few laboratories have devised efficient methodologies to overcome these synthetic hurdles, and achieved varying degrees of success. Of those elegant approaches, a highly stereoselective β-mannosylation protocol developed by Crich and co-workers was realized as a breakthrough in β-mannoside synthesis. This strategy is based on the initial activation of α-mannosyl sulfoxides 1 with triflic anhydride (Tf2O) using DTBMP (2,6-di-tert-butyl-4-methylpyridine) as a base, followed by nucleophilic substitution of glycosyl acceptors (HOR3) to provide the 1,2-cis-β-glycoside 2 in good yield and selectivity (Scheme 1). == Mechanistic Studies == The mechanistic details of this reaction have been extensively explored by Crich’s laboratories. Low-temperature 1H, 13C, and 19F NMR spectroscopic investigations revealed that anomeric triflate 3 derived from 1 is the intermediate glycosyl donor. Moreover, the mechanism of glycosidic bond forming reaction (3→2) was examined thoroughly by the determination of kinetic isotopic effects (KIEs) and NMR spectroscopy. Consequently, the magnitude of KIEs indicated that the displacement of the triflate from 3 proceeded with the development of significant oxacarbenium ion character at the anomeric position. This might be rationalized either by (1) a dissociative mechanism involving the intermediacy of either a transient
|
{
"page_id": 22483052,
"source": null,
"title": "Crich beta-mannosylation"
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contact ion pair (CIP) 4 or a solvent-separated ion pair (SSIP) 5, or (2) a mechanistically variant transition state 7 (Scheme 2). For the intermediate CIP 4, the triflate anion is closely associated with face where it just departed thus shields that side against nucleophilic attack. For the alternative intermediate SSIP 5 which is in equilibrium with an initial CIP, the anomeric center could presumably be attacked by incoming alcohol from either face, giving β-mannoside 2 along with the undesired α-anomer 6. Along these lines, the presence of the 4,6-O-benzylidene protecting group, which serves to rigidify the pyranoside against rehybridization at the anomeric carbon, is essential in shifting the equilibrium toward the covalent triflate, thus reducing α-glycoside formation. Additionally, the only intermediate observed by NMR spectroscopy is the covalent triflate 3, indicating that the complete set of equilibria between 3, the CIP 4, and SSIP 5 set is very heavily biased towards 3. == Reaction Scope == Some representative examples of Crich’s β-mannosylation are shown in Scheme 3. It is noteworthy that, with this method in hand, primary, secondary, and tertiary alcohols (9, 12, and 13) all serve as glycosyl acceptors effectively in terms of yields and selectivity. In a recent version, the β-mannosylation of thioglycoside 14 and its analogues were examined to prepare sterically hindered glycosides, in which PhSOTf (or other newly developed sulfur-type oxidants) served as a convenient reagent for the in situ generation of the glycosyl triflate from 14, thus facilitating the reaction. == Solid-Phase Synthesis == The polymer-supported synthesis of β-mannosides based on the Crich’s protocol has also been studied in the same laboratories. As shown in Scheme 4, diol 17 was first reacted with polystyrylboronic acid (18) to offer the bound donor 19, in which 4,6-O-phenylboronates served as the torsionally disarming protecting group. With that,
|
{
"page_id": 22483052,
"source": null,
"title": "Crich beta-mannosylation"
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activation of the thioglycoside 19 was readily achieved, and the coupling reaction with the acceptor alcohol underwent smoothly to provide the bound β-mannoside 20. After removal of the excess reagents and byproducts from the resin, 20 was then treated with aqueous acetone to release 4,6-diol 21. Overall, this is a powerful method for solid-phase synthesis of β-mannosides, which has great potential to be further extended, was established. == See also == Carbohydrate synthesis Difficult linkages Carbohydrate chemistry == References ==
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{
"page_id": 22483052,
"source": null,
"title": "Crich beta-mannosylation"
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William Webster (1855–1910) was an English chemical engineer credited with developments in gas detection, sewage treatment and medical use of x-rays. A gifted artist and musician, Webster also helped found the Blackheath Concert Halls and the adjacent Conservatoire in Blackheath in south-east London during the 1890s. == Career == Webster was the son of William Webster, a successful building contractor who grew wealthy from constructing major civil engineering and building projects in London. The family lived from 1869 in Wyberton House in Lee Terrace, Blackheath. The younger William Webster trained as a chemical engineer. A fellow of the Chemical Society, he patented a system to detect hydrogenous gases in mines in 1876, and later developed a system for the electrolytic purification of sewage (patent application filed on 22 December 1887; US patent awarded on 19 February 1889), trialled in 1888 at the Crossness Southern Outfall works which had been built by his father's firm in the 1860s. Webster was also a pioneer in x-ray research and a founder member of the Röntgen Society (since 1927 part of the British Institute of Radiology), assisting surgeon Thomas Moore in producing radiographs in 1896, after which Moore set up an x-ray unit at the Miller General Hospital in Greenwich High Road. Webster is also believed to be the first person to experience radiation 'sunburn', suffered on his right hand. He wrote a letter on the subject of x-ray photography published in the journal Nature in 1897. Webster was an accomplished violinist, singer, and artist - his paintings were exhibited in the Summer Exhibition at the Royal Academy. In 1881 local residents formed the Blackheath Conservatoire of Music, and Webster founded the company which funded the building of a concert hall, today Blackheath Halls, and its neighbouring schools for art and music, the Blackheath
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{
"page_id": 57413744,
"source": null,
"title": "William Webster (chemical engineer)"
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Conservatoire. The Conservatoire of Music opened in 1896 and the School of Art in 1897. == References ==
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{
"page_id": 57413744,
"source": null,
"title": "William Webster (chemical engineer)"
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The Professorship of Physiology, also known as the Chair of Physiology (1883), is a chair at the University of Cambridge. In 2006, the Department of Physiology was merged with the Department of Anatomy to form the Department of Physiology, Development and Neuroscience where the chair is now based. == List of Professors of Physiology == Michael Foster (1883–1903) John Newport Langley (1903–1925) Joseph Barcroft (1926–1937) Edgar Adrian (1937–1951) Bryan Harold Cabot Matthews (1952–1973) Richard Darwin Keynes (1973–1987) Ian Michael Glynn (1986–1995) Roger Christopher Thomas (1996–2006) Ole Paulsen (2010–present)
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{
"page_id": 32051313,
"source": null,
"title": "Professor of Physiology (Cambridge)"
}
|
Mesoxantha is a genus of nymphalid butterflies. It is monotypic, containing only Mesoxantha ethosea, the Drury's delight. It is found in Sierra Leone, Guinea, Liberia, Ivory Coast, Ghana, Togo, Nigeria, Cameroon, Gabon, the Republic of the Congo, the Central African Republic, Angola, the Democratic Republic of the Congo, Sudan, Uganda, Tanzania and Mozambique. The habitat consists of lowland forests, including secondary forests. The larvae feed on Tragia brevipes and Malacantha alnifolia. == Description == Upperside: Antennae black. Thorax, abdomen, and wings deep brown, almost black; the disk of the anterior being white, and extending to the shoulders, all the middle part of the posterior being white likewise. Underside: Palpi grey. Breast and abdomen brown. Anterior wings next the body yellowish brown, but towards the tips inclining to grey; nerves black; the disk white, with a round black spot near the body, and another of a smaller size below it. The middle of the posterior wings is white, surrounded with brown, that part along the lower edges being darkest; next the body are five distinct black round spots, and an irregular shaped one at the middle of the upper edge; along the lower edges are a number of small triangular white spots. Margins of the posterior wings slightly dentated. Wingspan 2+1⁄4 inches (57 mm). == Subspecies == Mesoxantha ethosea ethosea (Sierra Leone, Guinea, Liberia, Ivory Coast, Ghana, Togo) Mesoxantha ethosea ethoseoides Rebel, 1914 (Nigeria: south and the Cross River loop, Cameroon, Gabon, Congo, Central African Republic, Angola, eastern and southern Democratic Republic of the Congo) Mesoxantha ethosea reducta Rothschild, 1918 (southern Sudan, Uganda, western Tanzania, possibly Mozambique) == References == Seitz, A. Die Gross-Schmetterlinge der Erde 13: Die Afrikanischen Tagfalter. Plate XIII 49
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{
"page_id": 35131505,
"source": null,
"title": "Mesoxantha"
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LacED, also known as The Lactamase Engineering Database, is a database that identifies and corrects inconsistencies in already existing databases, namely Beta-lactamases. It integrates such information as mutations, sequence alignments, and structures in order to accomplish the task. As of the publication of the primary literature, LacED provides 2399 sequences entries and 37 structure entries. Example of this database in action is shown when 89 proteins from the microbial organisms and 35 proteins from cloning or expression vectors had new mutation profiles. Additionally, 55 proteins had inconsistent annotations in their TEM assignments or mutation profiles. == See also == Antimicrobial resistance databases == References ==
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{
"page_id": 61149297,
"source": null,
"title": "LacED"
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Prephytoene-diphosphate synthase may refer to: All-trans-phytoene synthase, an enzyme Phytoene synthase, an enzyme
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{
"page_id": 38867060,
"source": null,
"title": "Prephytoene-diphosphate synthase"
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Gray's Paradox is a paradox posed in 1936 by British zoologist Sir James Gray. The paradox was to figure out how dolphins can obtain such high speeds and accelerations with what appears to be a small muscle mass. Gray made an estimate of the power a dolphin could exert based on its physiology, and concluded the power was insufficient to overcome the drag forces in water. He hypothesized that Dolphin's skin must have special anti-drag properties. In 2008, researchers from Rensselaer Polytechnic Institute, West Chester University and the University of California, Santa Cruz used digital particle image velocimetry to prove that Gray's assumptions oversimplified the relationship between muscle power and drag force. Timothy Wei, professor and acting dean of Rensselaer's School of Engineering, videotaped two bottlenose dolphins, Primo and Puka, as they swam through a section of water populated with hundreds of thousands of tiny air bubbles. Computer software and force measurement tools developed for aerospace were then used to study the particle-image velocimetry which was captured at 1,000 frames per second (fps). This allowed the team to measure the force exerted by a dolphin. Results showed the dolphin to exert approximately 200 lb of force every time it thrust its tail – 10 times more than Gray hypothesized – and at peak force can exert between 300 and 400 lb. Wei also used this technique to film dolphins as they were doing tail-stands, a trick where the dolphins “walk” on water by holding most of their bodies vertical above the water while supporting themselves with short, powerful thrusts of their tails. In 2009, researchers from the National Chung Hsing University in Taiwan introduced new concepts of “kidnapped airfoils” and “circulating horsepower” to explain the swimming capabilities of the swordfish. Swordfish swim at even higher speeds and accelerations than dolphins.
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"page_id": 25038967,
"source": null,
"title": "Gray's paradox"
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The researchers claim their analysis also "solves the perplexity of dolphin’s Gray paradox". == Gray's flawed assumption == The prior research efforts to refute Gray's paradox only looked at the drag reducing aspect of dolphin's skin, but never questioned the basic assumption of Gray "that drag cannot be greater than muscle work" which led to paradox in the first place. In 2014, a team of theoretical mechanical engineers from Northwestern University proved the underlying hypothesis of Gray's paradox wrong. They showed mathematically that drag on undulatory swimmers (such as dolphins) can indeed be greater than the muscle power it generates to propel itself forward, without being paradoxical. They introduced the concept of "energy cascade" to show that during steady swimming all of the generated muscle power is dissipated in the wake of the swimmer (through viscous dissipation). A swimmer uses muscle power to undulate its body, which causes it to experience both drag and thrust simultaneously. Muscle power generated should be equated to power needed to deform the body, rather than equating it to the drag power. On the contrary drag power should be equated to thrust power. This is because during steady swimming, drag and thrust are equal in magnitude but opposite in direction. Their findings can be summarized in a simple power balance equation: P m u s c l e + P t h r u s t = P d r a g + P d e f o r m a t i o n {\displaystyle \mathbf {P} _{muscle}+\mathbf {P} _{thrust}=\mathbf {P} _{drag}+\mathbf {P} _{deformation}} in which, P m u s c l e = P d e f o r m a t i o n and P t h r u s t = P d r a g {\displaystyle \mathbf {P} _{muscle}=\mathbf
|
{
"page_id": 25038967,
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"title": "Gray's paradox"
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{P} _{deformation}{\text{ and }}\mathbf {P} _{thrust}=\mathbf {P} _{drag}} . It is important to acknowledge the fact that a swimmer does not have to spend energy to overcome drag all through its muscle work; it is also assisted by the thrust force in this task. Their research also shows that defining drag on the body is definitional and many definitions of drag on the swimming body are prevalent in literature. Some of these definitions can give higher value than the muscle power. However, this does not lead to any paradox because higher drag also means higher thrust in the power balance equation, and this does not violate any energy balance principles. == References == == Notes == Fish, Frank (2005) A porpoise for power The Journal of Experimental Biology, Classics, 208: 977–978. doi:10.1242/jeb.01513 == External links == Gray's Paradox on Science Daily
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{
"page_id": 25038967,
"source": null,
"title": "Gray's paradox"
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The Virginia Institute for Psychiatric and Behavioral Genetics (abbreviated VIPBG) is a human genetics research center, located at Virginia Commonwealth University (VCU), that aims to study the role played by genetic factors in the etiology of psychiatric conditions and substance abuse. It was co-founded in 1996 by VCU psychiatry professors Kenneth Kendler and Lindon Eaves. Kendler serves as the Institute's director and the director of its Psychiatric Genetics Research Program (abbreviated PGRP), while Eaves is the director of the Institute's Genetic Epidemiology Research Group (abbreviated GERG). The PGRP and GERG are subsidiaries of the Department of Psychiatry and the Department of Human and Molecular Genetics, respectively, at the VCU School of Medicine. The Institute's associate director is Michael Neale. In 2017, the Virginia General Assembly passed a bill commending Kendler and the VIPBG, describing the latter as "...an exciting, highly collaborative research environment with a strong record of funding, research, and training, including more than 140 predoctoral and postdoctoral students over the past decade". == References == == External links == Official Website Law Of Attraction
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{
"page_id": 57872517,
"source": null,
"title": "Virginia Institute for Psychiatric and Behavioral Genetics"
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The cell is the basic structural and functional unit of all forms of life. Every cell consists of cytoplasm enclosed within a membrane; many cells contain organelles, each with a specific function. The term comes from the Latin word cellula meaning 'small room'. Most cells are only visible under a microscope. Cells emerged on Earth about 4 billion years ago. All cells are capable of replication, protein synthesis, and motility. Cells are broadly categorized into two types: eukaryotic cells, which possess a nucleus, and prokaryotic cells, which lack a nucleus but have a nucleoid region. Prokaryotes are single-celled organisms such as bacteria, whereas eukaryotes can be either single-celled, such as amoebae, or multicellular, such as some algae, plants, animals, and fungi. Eukaryotic cells contain organelles including mitochondria, which provide energy for cell functions, chloroplasts, which in plants create sugars by photosynthesis, and ribosomes, which synthesise proteins. Cells were discovered by Robert Hooke in 1665, who named them after their resemblance to cells inhabited by Christian monks in a monastery. Cell theory, developed in 1839 by Matthias Jakob Schleiden and Theodor Schwann, states that all organisms are composed of one or more cells, that cells are the fundamental unit of structure and function in all living organisms, and that all cells come from pre-existing cells. == Cell types == Cells are broadly categorized into two types: eukaryotic cells, which possess a nucleus, and prokaryotic cells, which lack a nucleus but have a nucleoid region. Prokaryotes are single-celled organisms, whereas eukaryotes can be either single-celled or multicellular. === Prokaryotic cells === Prokaryotes include bacteria and archaea, two of the three domains of life. Prokaryotic cells were the first form of life on Earth, characterized by having vital biological processes including cell signaling. They are simpler and smaller than eukaryotic cells, and lack
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{
"page_id": 4230,
"source": null,
"title": "Cell (biology)"
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a nucleus, and other membrane-bound organelles. The DNA of a prokaryotic cell consists of a single circular chromosome that is in direct contact with the cytoplasm. The nuclear region in the cytoplasm is called the nucleoid. Most prokaryotes are the smallest of all organisms, ranging from 0.5 to 2.0 μm in diameter.: 78 A prokaryotic cell has three regions: Enclosing the cell is the cell envelope, generally consisting of a plasma membrane covered by a cell wall which, for some bacteria, may be further covered by a third layer called a capsule. Though most prokaryotes have both a cell membrane and a cell wall, there are exceptions such as Mycoplasma (bacteria) and Thermoplasma (archaea) which only possess the cell membrane layer. The envelope gives rigidity to the cell and separates the interior of the cell from its environment, serving as a protective filter. The cell wall consists of peptidoglycan in bacteria and acts as an additional barrier against exterior forces. It also prevents the cell from expanding and bursting (cytolysis) from osmotic pressure due to a hypotonic environment. Some eukaryotic cells (plant cells and fungal cells) also have a cell wall. Inside the cell is the cytoplasmic region that contains the genome (DNA), ribosomes and various sorts of inclusions. The genetic material is freely found in the cytoplasm. Prokaryotes can carry extrachromosomal DNA elements called plasmids, which are usually circular. Linear bacterial plasmids have been identified in several species of spirochete bacteria, including members of the genus Borrelia notably Borrelia burgdorferi, which causes Lyme disease. Though not forming a nucleus, the DNA is condensed in a nucleoid. Plasmids encode additional genes, such as antibiotic resistance genes. On the outside, some prokaryotes have flagella and pili that project from the cell's surface. These are structures made of proteins that facilitate movement
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{
"page_id": 4230,
"source": null,
"title": "Cell (biology)"
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and communication between cells. === Eukaryotic cells === Plants, animals, fungi, slime moulds, protozoa, and algae are all eukaryotic. These cells are about fifteen times wider than a typical prokaryote and can be as much as a thousand times greater in volume. The main distinguishing feature of eukaryotes as compared to prokaryotes is compartmentalization: the presence of membrane-bound organelles (compartments) in which specific activities take place. Most important among these is a cell nucleus, an organelle that houses the cell's DNA. This nucleus gives the eukaryote its name, which means "true kernel (nucleus)". Some of the other differences are: The plasma membrane resembles that of prokaryotes in function, with minor differences in the setup. Cell walls may or may not be present. The eukaryotic DNA is organized in one or more linear molecules, called chromosomes, which are associated with histone proteins. All chromosomal DNA is stored in the cell nucleus, separated from the cytoplasm by a membrane. Some eukaryotic organelles such as mitochondria also contain some DNA. Many eukaryotic cells are ciliated with primary cilia. Primary cilia play important roles in chemosensation, mechanosensation, and thermosensation. Each cilium may thus be "viewed as a sensory cellular antennae that coordinates a large number of cellular signaling pathways, sometimes coupling the signaling to ciliary motility or alternatively to cell division and differentiation." Motile eukaryotes can move using motile cilia or flagella. Motile cells are absent in conifers and flowering plants. Eukaryotic flagella are more complex than those of prokaryotes. Many groups of eukaryotes are single-celled. Among the many-celled groups are animals and plants. The number of cells in these groups vary with species; it has been estimated that the human body contains around 37 trillion (3.72×1013) cells, and more recent studies put this number at around 30 trillion (~36 trillion cells in the
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{
"page_id": 4230,
"source": null,
"title": "Cell (biology)"
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male, ~28 trillion in the female). == Subcellular components == All cells, whether prokaryotic or eukaryotic, have a membrane that envelops the cell, regulates what moves in and out (selectively permeable), and maintains the electric potential of the cell. Inside the membrane, the cytoplasm takes up most of the cell's volume. Except red blood cells, which lack a cell nucleus and most organelles to accommodate maximum space for hemoglobin, all cells possess DNA, the hereditary material of genes, and RNA, containing the information necessary to build various proteins such as enzymes, the cell's primary machinery. There are also other kinds of biomolecules in cells. This article lists these primary cellular components, then briefly describes their function. === Cell membrane === The cell membrane, or plasma membrane, is a selectively permeable biological membrane that surrounds the cytoplasm of a cell. In animals, the plasma membrane is the outer boundary of the cell, while in plants and prokaryotes it is usually covered by a cell wall. This membrane serves to separate and protect a cell from its surrounding environment and is made mostly from a double layer of phospholipids, which are amphiphilic (partly hydrophobic and partly hydrophilic). Hence, the layer is called a phospholipid bilayer, or sometimes a fluid mosaic membrane. Embedded within this membrane is a macromolecular structure called the porosome the universal secretory portal in cells and a variety of protein molecules that act as channels and pumps that move different molecules into and out of the cell. The membrane is semi-permeable, and selectively permeable, in that it can either let a substance (molecule or ion) pass through freely, to a limited extent or not at all. Cell surface membranes also contain receptor proteins that allow cells to detect external signaling molecules such as hormones. === Cytoskeleton === The cytoskeleton
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"page_id": 4230,
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"title": "Cell (biology)"
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acts to organize and maintain the cell's shape; anchors organelles in place; helps during endocytosis, the uptake of external materials by a cell, and cytokinesis, the separation of daughter cells after cell division; and moves parts of the cell in processes of growth and mobility. The eukaryotic cytoskeleton is composed of microtubules, intermediate filaments and microfilaments. In the cytoskeleton of a neuron the intermediate filaments are known as neurofilaments. There are a great number of proteins associated with them, each controlling a cell's structure by directing, bundling, and aligning filaments. The prokaryotic cytoskeleton is less well-studied but is involved in the maintenance of cell shape, polarity and cytokinesis. The subunit protein of microfilaments is a small, monomeric protein called actin. The subunit of microtubules is a dimeric molecule called tubulin. Intermediate filaments are heteropolymers whose subunits vary among the cell types in different tissues. Some of the subunit proteins of intermediate filaments include vimentin, desmin, lamin (lamins A, B and C), keratin (multiple acidic and basic keratins), and neurofilament proteins (NF–L, NF–M). === Genetic material === Two different kinds of genetic material exist: deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). Cells use DNA for their long-term information storage. The biological information contained in an organism is encoded in its DNA sequence. RNA is used for information transport (e.g., mRNA) and enzymatic functions (e.g., ribosomal RNA). Transfer RNA (tRNA) molecules are used to add amino acids during protein translation. Prokaryotic genetic material is organized in a simple circular bacterial chromosome in the nucleoid region of the cytoplasm. Eukaryotic genetic material is divided into different, linear molecules called chromosomes inside a discrete nucleus, usually with additional genetic material in some organelles like mitochondria and chloroplasts (see endosymbiotic theory). A human cell has genetic material contained in the cell nucleus (the nuclear genome)
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{
"page_id": 4230,
"source": null,
"title": "Cell (biology)"
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and in the mitochondria (the mitochondrial genome). In humans, the nuclear genome is divided into 46 linear DNA molecules called chromosomes, including 22 homologous chromosome pairs and a pair of sex chromosomes. The mitochondrial genome is a circular DNA molecule distinct from nuclear DNA. Although the mitochondrial DNA is very small compared to nuclear chromosomes, it codes for 13 proteins involved in mitochondrial energy production and specific tRNAs. Foreign genetic material (most commonly DNA) can also be artificially introduced into the cell by a process called transfection. This can be transient, if the DNA is not inserted into the cell's genome, or stable, if it is. Certain viruses also insert their genetic material into the genome. === Organelles === Organelles are parts of the cell that are adapted and/or specialized for carrying out one or more vital functions, analogous to the organs of the human body (such as the heart, lung, and kidney, with each organ performing a different function). Both eukaryotic and prokaryotic cells have organelles, but prokaryotic organelles are generally simpler and are not membrane-bound. There are several types of organelles in a cell. Some (such as the nucleus and Golgi apparatus) are typically solitary, while others (such as mitochondria, chloroplasts, peroxisomes and lysosomes) can be numerous (hundreds to thousands). The cytosol is the gelatinous fluid that fills the cell and surrounds the organelles. ==== Eukaryotic ==== Cell nucleus: A cell's information center, the cell nucleus is the most conspicuous organelle found in a eukaryotic cell. It houses the cell's chromosomes, and is the place where almost all DNA replication and RNA synthesis (transcription) occur. The nucleus is spherical and separated from the cytoplasm by a double membrane called the nuclear envelope, space between these two membrane is called perinuclear space. The nuclear envelope isolates and protects a
|
{
"page_id": 4230,
"source": null,
"title": "Cell (biology)"
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cell's DNA from various molecules that could accidentally damage its structure or interfere with its processing. During processing, DNA is transcribed, or copied into a special RNA, called messenger RNA (mRNA). This mRNA is then transported out of the nucleus, where it is translated into a specific protein molecule. The nucleolus is a specialized region within the nucleus where ribosome subunits are assembled. In prokaryotes, DNA processing takes place in the cytoplasm. Mitochondria and chloroplasts: generate energy for the cell. Mitochondria are self-replicating double membrane-bound organelles that occur in various numbers, shapes, and sizes in the cytoplasm of all eukaryotic cells. Respiration occurs in the cell mitochondria, which generate the cell's energy by oxidative phosphorylation, using oxygen to release energy stored in cellular nutrients (typically pertaining to glucose) to generate ATP (aerobic respiration). Mitochondria multiply by binary fission, like prokaryotes. Chloroplasts can only be found in plants and algae, and they capture the sun's energy to make carbohydrates through photosynthesis. Endoplasmic reticulum: The endoplasmic reticulum (ER) is a transport network for molecules targeted for certain modifications and specific destinations, as compared to molecules that float freely in the cytoplasm. The ER has two forms: the rough ER, which has ribosomes on its surface that secrete proteins into the ER, and the smooth ER, which lacks ribosomes. The smooth ER plays a role in calcium sequestration and release and also helps in synthesis of lipid. Golgi apparatus: The primary function of the Golgi apparatus is to process and package the macromolecules such as proteins and lipids that are synthesized by the cell. Lysosomes and peroxisomes: Lysosomes contain digestive enzymes (acid hydrolases). They digest excess or worn-out organelles, food particles, and engulfed viruses or bacteria. Peroxisomes have enzymes that rid the cell of toxic peroxides, Lysosomes are optimally active in an acidic
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{
"page_id": 4230,
"source": null,
"title": "Cell (biology)"
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environment. The cell could not house these destructive enzymes if they were not contained in a membrane-bound system. Centrosome: the cytoskeleton organizer: The centrosome produces the microtubules of a cell—a key component of the cytoskeleton. It directs the transport through the ER and the Golgi apparatus. Centrosomes are composed of two centrioles which lie perpendicular to each other in which each has an organization like a cartwheel, which separate during cell division and help in the formation of the mitotic spindle. A single centrosome is present in the animal cells. They are also found in some fungi and algae cells. Vacuoles: Vacuoles sequester waste products and in plant cells store water. They are often described as liquid filled spaces and are surrounded by a membrane. Some cells, most notably Amoeba, have contractile vacuoles, which can pump water out of the cell if there is too much water. The vacuoles of plant cells and fungal cells are usually larger than those of animal cells. Vacuoles of plant cells are surrounded by a membrane which transports ions against concentration gradients. ==== Eukaryotic and prokaryotic ==== Ribosomes: The ribosome is a large complex of RNA and protein molecules. They each consist of two subunits, and act as an assembly line where RNA from the nucleus is used to synthesise proteins from amino acids. Ribosomes can be found either floating freely or bound to a membrane (the rough endoplasmatic reticulum in eukaryotes, or the cell membrane in prokaryotes). Plastids: Plastid are membrane-bound organelle generally found in plant cells and euglenoids and contain specific pigments, thus affecting the colour of the plant and organism. And these pigments also helps in food storage and tapping of light energy. There are three types of plastids based upon the specific pigments. Chloroplasts contain chlorophyll and some carotenoid pigments
|
{
"page_id": 4230,
"source": null,
"title": "Cell (biology)"
}
|
which helps in the tapping of light energy during photosynthesis. Chromoplasts contain fat-soluble carotenoid pigments like orange carotene and yellow xanthophylls which helps in synthesis and storage. Leucoplasts are non-pigmented plastids and helps in storage of nutrients. == Structures outside the cell membrane == Many cells also have structures which exist wholly or partially outside the cell membrane. These structures are notable because they are not protected from the external environment by the cell membrane. In order to assemble these structures, their components must be carried across the cell membrane by export processes. === Cell wall === Many types of prokaryotic and eukaryotic cells have a cell wall. The cell wall acts to protect the cell mechanically and chemically from its environment, and is an additional layer of protection to the cell membrane. Different types of cell have cell walls made up of different materials; plant cell walls are primarily made up of cellulose, fungi cell walls are made up of chitin and bacteria cell walls are made up of peptidoglycan. === Prokaryotic === ==== Capsule ==== A gelatinous capsule is present in some bacteria outside the cell membrane and cell wall. The capsule may be polysaccharide as in pneumococci, meningococci or polypeptide as Bacillus anthracis or hyaluronic acid as in streptococci. Capsules are not marked by normal staining protocols and can be detected by India ink or methyl blue, which allows for higher contrast between the cells for observation.: 87 ==== Flagella ==== Flagella are organelles for cellular mobility. The bacterial flagellum stretches from cytoplasm through the cell membrane(s) and extrudes through the cell wall. They are long and thick thread-like appendages, protein in nature. A different type of flagellum is found in archaea and a different type is found in eukaryotes. ==== Fimbriae ==== A fimbria (plural fimbriae
|
{
"page_id": 4230,
"source": null,
"title": "Cell (biology)"
}
|
also known as a pilus, plural pili) is a short, thin, hair-like filament found on the surface of bacteria. Fimbriae are formed of a protein called pilin (antigenic) and are responsible for the attachment of bacteria to specific receptors on human cells (cell adhesion). There are special types of pili involved in bacterial conjugation. == Cellular processes == === Replication === Cell division involves a single cell (called a mother cell) dividing into two daughter cells. This leads to growth in multicellular organisms (the growth of tissue) and to procreation (vegetative reproduction) in unicellular organisms. Prokaryotic cells divide by binary fission, while eukaryotic cells usually undergo a process of nuclear division, called mitosis, followed by division of the cell, called cytokinesis. A diploid cell may also undergo meiosis to produce haploid cells, usually four. Haploid cells serve as gametes in multicellular organisms, fusing to form new diploid cells. DNA replication, or the process of duplicating a cell's genome, always happens when a cell divides through mitosis or binary fission. This occurs during the S phase of the cell cycle. In meiosis, the DNA is replicated only once, while the cell divides twice. DNA replication only occurs before meiosis I. DNA replication does not occur when the cells divide the second time, in meiosis II. Replication, like all cellular activities, requires specialized proteins for carrying out the job. === DNA repair === Cells of all organisms contain enzyme systems that scan their DNA for damage and carry out repair processes when it is detected. Diverse repair processes have evolved in organisms ranging from bacteria to humans. The widespread prevalence of these repair processes indicates the importance of maintaining cellular DNA in an undamaged state in order to avoid cell death or errors of replication due to damage that could lead to
|
{
"page_id": 4230,
"source": null,
"title": "Cell (biology)"
}
|
mutation. E. coli bacteria are a well-studied example of a cellular organism with diverse well-defined DNA repair processes. These include: nucleotide excision repair, DNA mismatch repair, non-homologous end joining of double-strand breaks, recombinational repair and light-dependent repair (photoreactivation). === Growth and metabolism === Between successive cell divisions, cells grow through the functioning of cellular metabolism. Cell metabolism is the process by which individual cells process nutrient molecules. Metabolism has two distinct divisions: catabolism, in which the cell breaks down complex molecules to produce energy and reducing power, and anabolism, in which the cell uses energy and reducing power to construct complex molecules and perform other biological functions. Complex sugars can be broken down into simpler sugar molecules called monosaccharides such as glucose. Once inside the cell, glucose is broken down to make adenosine triphosphate (ATP), a molecule that possesses readily available energy, through two different pathways. In plant cells, chloroplasts create sugars by photosynthesis, using the energy of light to join molecules of water and carbon dioxide. === Protein synthesis === Cells are capable of synthesizing new proteins, which are essential for the modulation and maintenance of cellular activities. This process involves the formation of new protein molecules from amino acid building blocks based on information encoded in DNA/RNA. Protein synthesis generally consists of two major steps: transcription and translation. Transcription is the process where genetic information in DNA is used to produce a complementary RNA strand. This RNA strand is then processed to give messenger RNA (mRNA), which is free to migrate through the cell. mRNA molecules bind to protein-RNA complexes called ribosomes located in the cytosol, where they are translated into polypeptide sequences. The ribosome mediates the formation of a polypeptide sequence based on the mRNA sequence. The mRNA sequence directly relates to the polypeptide sequence by binding
|
{
"page_id": 4230,
"source": null,
"title": "Cell (biology)"
}
|
to transfer RNA (tRNA) adapter molecules in binding pockets within the ribosome. The new polypeptide then folds into a functional three-dimensional protein molecule. === Motility === Unicellular organisms can move in order to find food or escape predators. Common mechanisms of motion include flagella and cilia. In multicellular organisms, cells can move during processes such as wound healing, the immune response and cancer metastasis. For example, in wound healing in animals, white blood cells move to the wound site to kill the microorganisms that cause infection. Cell motility involves many receptors, crosslinking, bundling, binding, adhesion, motor and other proteins. The process is divided into three steps: protrusion of the leading edge of the cell, adhesion of the leading edge and de-adhesion at the cell body and rear, and cytoskeletal contraction to pull the cell forward. Each step is driven by physical forces generated by unique segments of the cytoskeleton. ==== Navigation, control and communication ==== In August 2020, scientists described one way cells—in particular cells of a slime mold and mouse pancreatic cancer-derived cells—are able to navigate efficiently through a body and identify the best routes through complex mazes: generating gradients after breaking down diffused chemoattractants which enable them to sense upcoming maze junctions before reaching them, including around corners. == Multicellularity == === Cell specialization/differentiation === Multicellular organisms are organisms that consist of more than one cell, in contrast to single-celled organisms. In complex multicellular organisms, cells specialize into different cell types that are adapted to particular functions. In mammals, major cell types include skin cells, muscle cells, neurons, blood cells, fibroblasts, stem cells, and others. Cell types differ both in appearance and function, yet are genetically identical. Cells are able to be of the same genotype but of different cell type due to the differential expression of the
|
{
"page_id": 4230,
"source": null,
"title": "Cell (biology)"
}
|
genes they contain. Most distinct cell types arise from a single totipotent cell, called a zygote, that differentiates into hundreds of different cell types during the course of development. Differentiation of cells is driven by different environmental cues (such as cell–cell interaction) and intrinsic differences (such as those caused by the uneven distribution of molecules during division). === Origin of multicellularity === Multicellularity has evolved independently at least 25 times, including in some prokaryotes, like cyanobacteria, myxobacteria, actinomycetes, or Methanosarcina. However, complex multicellular organisms evolved only in six eukaryotic groups: animals, fungi, brown algae, red algae, green algae, and plants. It evolved repeatedly for plants (Chloroplastida), once or twice for animals, once for brown algae, and perhaps several times for fungi, slime molds, and red algae. Multicellularity may have evolved from colonies of interdependent organisms, from cellularization, or from organisms in symbiotic relationships. The first evidence of multicellularity is from cyanobacteria-like organisms that lived between 3 and 3.5 billion years ago. Other early fossils of multicellular organisms include the contested Grypania spiralis and the fossils of the black shales of the Palaeoproterozoic Francevillian Group Fossil B Formation in Gabon. The evolution of multicellularity from unicellular ancestors has been replicated in the laboratory, in evolution experiments using predation as the selective pressure. == Origins == The origin of cells has to do with the origin of life, which began the history of life on Earth. === Origin of life === Small molecules needed for life may have been carried to Earth on meteorites, created at deep-sea vents, or synthesized by lightning in a reducing atmosphere. There is little experimental data defining what the first self-replicating forms were. RNA may have been the earliest self-replicating molecule, as it can both store genetic information and catalyze chemical reactions. Cells emerged around 4 billion
|
{
"page_id": 4230,
"source": null,
"title": "Cell (biology)"
}
|
years ago. The first cells were most likely heterotrophs. The early cell membranes were probably simpler and more permeable than modern ones, with only a single fatty acid chain per lipid. Lipids spontaneously form bilayered vesicles in water, and could have preceded RNA. === First eukaryotic cells === Eukaryotic cells were created some 2.2 billion years ago in a process called eukaryogenesis. This is widely agreed to have involved symbiogenesis, in which archaea and bacteria came together to create the first eukaryotic common ancestor. This cell had a new level of complexity and capability, with a nucleus and facultatively aerobic mitochondria. It evolved some 2 billion years ago into a population of single-celled organisms that included the last eukaryotic common ancestor, gaining capabilities along the way, though the sequence of the steps involved has been disputed, and may not have started with symbiogenesis. It featured at least one centriole and cilium, sex (meiosis and syngamy), peroxisomes, and a dormant cyst with a cell wall of chitin and/or cellulose. In turn, the last eukaryotic common ancestor gave rise to the eukaryotes' crown group, containing the ancestors of animals, fungi, plants, and a diverse range of single-celled organisms. The plants were created around 1.6 billion years ago with a second episode of symbiogenesis that added chloroplasts, derived from cyanobacteria. == History of research == In 1665, Robert Hooke examined a thin slice of cork under his microscope, and saw a structure of small enclosures. He wrote "I could exceeding plainly perceive it to be all perforated and porous, much like a Honey-comb, but that the pores of it were not regular". To further support his theory, Matthias Schleiden and Theodor Schwann both also studied cells of both animal and plants. What they discovered were significant differences between the two types of cells.
|
{
"page_id": 4230,
"source": null,
"title": "Cell (biology)"
}
|
This put forth the idea that cells were not only fundamental to plants, but animals as well. 1632–1723: Antonie van Leeuwenhoek taught himself to make lenses, constructed basic optical microscopes and drew protozoa, such as Vorticella from rain water, and bacteria from his own mouth. 1665: Robert Hooke discovered cells in cork, then in living plant tissue using an early compound microscope. He coined the term cell (from Latin cellula, meaning "small room") in his book Micrographia (1665). 1839: Theodor Schwann and Matthias Jakob Schleiden elucidated the principle that plants and animals are made of cells, concluding that cells are a common unit of structure and development, and thus founding the cell theory. 1855: Rudolf Virchow stated that new cells come from pre-existing cells by cell division (omnis cellula ex cellula). 1931: Ernst Ruska built the first transmission electron microscope (TEM) at the University of Berlin. By 1935, he had built an EM with twice the resolution of a light microscope, revealing previously unresolvable organelles. 1981: Lynn Margulis published Symbiosis in Cell Evolution detailing how eukaryotic cells were created by symbiogenesis. == See also == == References == == Further reading == == External links == "The Inner Life of the Cell". XVIVO website. – 2006 animation of molecular mechanisms inside cells "Inside the Cell". Archived from the original on 2017-07-20. – 2005 science education booklet by National Institutes of Health in PDF and ePub.
|
{
"page_id": 4230,
"source": null,
"title": "Cell (biology)"
}
|
Enzyme potentiated desensitization (EPD), is a treatment for allergies developed in the 1960s by Dr. Leonard M. McEwen in the United Kingdom. EPD uses much lower doses of antigens than conventional desensitization treatment paired with the enzyme β-glucuronidase. EPD is approved in the United Kingdom for the treatment of hay fever, food allergy and intolerance and environmental allergies. EPD was developed for the treatment of autoimmune disease by the United Kingdom company Epidyme which was owned by Dr. McEwen and had been granted a United Kingdom patent. Despite encouraging results in an experimental model of rheumatoid arthritis, the company was placed into liquidation in April 2010. == United States use == EPD was available in the United States until 2001, when the Food and Drug Administration revoked approval for an investigative study which it had previously sanctioned. That study had allowed EPD to be imported into the United States without being licensed. The approval was revoked because the EPD treatments included complex mixtures of allergens that were not allowed under FDA rules. Since 2001, the FDA has banned importation of EPD for the following reasons: EPD is not licensed. the labeling of the medicine does not contain adequate directions for use. (EPD is only supplied to doctors who have been through a one-week training course, and instructions supplied with the medicine would not be adequate) A related treatment, Low Dose Allergens (LDA), was developed in the US by Dr. Shrader, which, being a compounding rather than a drug, is not regulated by the FDA. In addition, LDA uses a different allergen mix for the US environment. However, LDA is considered by many in the field to be a repackaging of EPD that circumvents the FDA guidelines that caused EPD to be revoked. == EPD treatment == The enzyme beta glucuronidase
|
{
"page_id": 6951047,
"source": null,
"title": "Enzyme potentiated desensitization"
}
|
appears to potentiate the desensitizing effect of a small dose of allergen. The quantities of both are smaller than those occurring naturally in the body, but not so small that they can be regarded as homeopathic. Intradermal injections are used. The treatment takes 3–4 weeks before any effect is seen. For food and environmental allergies and intolerances treatments are typically given at two monthly intervals at first, but the interval between treatments is gradually lengthened. Hay fever is treated with two shots of EPD outside the pollen season. == Mechanism for EPD == The treatment uses dilutions of allergen and enzyme to which T-regulatory lymphocytes are believed to respond by favouring desensitization, or down-regulation, rather than sensitization. Once activated these lymphocytes travel to lymph nodes and reproduce or stimulate similar T-lymphocytes. == Evidence for the Effectiveness of EPD == EPD is considered experimental by some doctors and allergists. However, there is evidence for the efficacy of EPD in the treatment of hay fever and other conditions as a result of nine placebo-controlled, double-blind trials involving 271 patients. These trials showed a significant improvement in the symptoms with probabilities of 0.001 to 0.01 (a chance of one in a thousand to one in a hundred that the results of the trial would be seen by chance alone assuming EPD had no effect). However, one trial involving 183 patients published in the British Medical Journal showed no overall effect. Dr Len McEwen, inventor of EPD, speculated that the reason for the failure might have been that the beta glucuronidase enzyme preparation was inadvertently heated or frozen during storage in the hospital pharmacy, as it is sensitive to the storage temperature and enzyme from the same manufactured batch had been used to treat a number of patients successfully. However, there is no evidence
|
{
"page_id": 6951047,
"source": null,
"title": "Enzyme potentiated desensitization"
}
|
available after the event to test this theory as the remaining trial materials were destroyed immediately after the trial ended. == Safety of EPD == While the efficacy of EPD is sometimes the subject of controversy among the medical community, the safety of EPD is demonstrated in one study under the control of an Investigational Review Board and reported by the American EPD Society. 5,400 patients received at least 3 doses of EPD with no severe reactions reported. == Comparison of EPD with conventional escalating-dose immunotherapy (hyposensitization) == By contrast, uncontrolled use of conventional (escalating dose) immunotherapy (hyposensitization not EPD) for general allergic conditions was believed to be responsible for at least 29 deaths in the UK, and is now banned in the United Kingdom except in hospital under close observation. A working party of the British Society for Allergy and Clinical Immunology reviewed the role of conventional high dose specific allergen immunotherapy (not EPD) in the treatment of allergic disease and recommends high dose specific allergen immunotherapy for treating summer hay fever uncontrolled by conventional medication and for wasp and bee venom hypersensitivity. For the recommended indications the risk:benefit ratio was found to be acceptable for conventional immunotherapy provided patients are carefully selected; in particular, patients with asthma should be excluded and injections should be given only by allergists experienced in this form of treatment in a clinic where resuscitative facilities are available and patients remain symptom free for an observation period after injection which is sufficient to detect all serious adverse reactions. Conventional escalating-dose immunotherapy (not EPD) has been used to treat tens of millions of people in the United States with appropriate medical supervision with a death rate of less than one in one million according to the American Academy of Allergy, Asthma, and Immunology. == Restrictions
|
{
"page_id": 6951047,
"source": null,
"title": "Enzyme potentiated desensitization"
}
|
on EPD == EPD has not been developed for treatment of allergy to insect stings (for which convenventional immunotherapy is recommended), nor for contact dermatitis and allergy to drugs. It is not FDA approved. == References ==
|
{
"page_id": 6951047,
"source": null,
"title": "Enzyme potentiated desensitization"
}
|
Molecular Discovery Ltd is a software company working in the area of drug discovery. Founded in 1984 by Peter Goodford, its aim was to provide the GRID software to scientists working in the field of Drug Design, and enabled one of the first examples of rational drug design with the discovery of Zanamivir in 1989. In combination with statistical methods such as GOLPE, GRID's method of modeling molecular interaction (known as a "forcefield") can also be used to perform 3D-QSAR. In the last decade, the GRID forcefield has been applied to other areas of drug discovery, including virtual screening, scaffold-hopping, ADME and pharmacokinetic modelling, optimisation of metabolic stability and metabolite prediction, as well as pKa and tautomer modelling. Molecular Discovery manages a Cytochrome P450 Consortium aimed at generating a large set of homogeneous experimental data for human metabolism, allowing the development of predictive in silico models. == Products == GRID, a program for rational or structure-based design using molecular interaction fields MetaSite, a program for predicting metabolic "hotspots" or "soft spots" and subsequent metabolite formation Mass-MetaSite, a program for identifying metabolites based on experimental LC-MSMS data WebMetaBase, a program for storing, visualising, and data-mining the results from Mass-MetaSite VolSurf+, a program for modelling pharmacokinetic or ADME properties SHOP, a program for scaffold replacement MoKa, a program for modelling pKa and tautomerisation Pentacle, a program for 3D-QSAR (an update of Almond) FLAP, a program for virtual screening, pharmacophore modelling, docking, water prediction, and 3D-QSAR == References == == External links == Molecular Discovery Ltd official homepage
|
{
"page_id": 22220935,
"source": null,
"title": "Molecular Discovery"
}
|
Pitthea famula is a species of moth in the family Geometridae. It was first described by Dru Drury in 1773 from Calabar, in what is now Nigeria. It is found in Angola, Benin, Cameroon, the Republic of the Congo, the Democratic Republic of the Congo, Equatorial Guinea (Bioko), Nigeria, Sierra Leone and Zambia. == Description == Upperside: antennae long and pectinated (comb like). Thorax spiral. Neck orange. Thorax and abdomen dusky grey. Anterior wings about halfway from the tips black, but at the base are of a pellucid (transparent) white; being surrounded along the anterior edge and part of the posterior with black; an oblong white spot is placed near the tips on the black part. Posterior wings black and white; the white entirely surrounded by the black, which on the anterior and abdominal edges is very narrow. Underside: palpi orange, black at the tips. Neck, breast, and sides orange. Feet black. Thighs white. Abdomen white, annulated with dusky grey. Anterior wings as on the upperside, the black parts being of a russet hue. Posterior wings differ a little, the white part running down to the middle of the external edges, with a white spot at the upper corners. Margins of the wings entire. Wingspan 2 inches (50 mm). == References ==
|
{
"page_id": 44437641,
"source": null,
"title": "Pitthea famula"
}
|
A screening information dataset (SIDS) is a study of the hazards associated with a particular chemical substance or group of related substances, prepared under the auspices of the Organisation for Economic Co-operation and Development (OECD). The substances studied are high production volume (HPV) chemicals, which are manufactured or imported in quantities of more than 1000 tonnes per year for any single OECD market. The list of HPV chemicals is prepared by the OECD Secretariat and updated regularly. As of 2004, 4,843 chemicals were on the list. Of these, roughly 1000 have been prioritised for special attention, and SIDS are prepared for these chemicals, usually by an official agency in one of the OECD member countries with the collaboration of the UN International Programme on Chemical Safety (IPCS). The procedures for investigating the risks of an HPV chemical are described in the OECD Manual for Investigation of HPV Chemicals. The initial stage is the collection of existing information (either published or supplied by manufacturers) on the chemical. If the existing information is insufficient to make an assessment of the risks, the chemical may be tested at this stage to collect more data. The initial report of the investigation is discussed at a SIDS initial assessment meeting (SIAM), which includes: representatives of OECD member countries experts nominated by the IPCS, the OECD Business and Industry Advisory Committee, Trade Union Advisory Committee, and environmental organizations representatives of companies which produce the chemical secretariat staff from OECD, IPCS, and UNEP chemicals The SIAM can either accept the draft report or call for revisions (including further testing). Once the comments and discussion of the SIAM have been taken into account, the report is published by the United Nations Environment Programme (UNEP). The possibility of new testing to complete the study is what distinguishes SIDS reports
|
{
"page_id": 24121484,
"source": null,
"title": "Screening information dataset"
}
|
from similar studies such as Concise International Chemical Assessment Documents (CICADs). In this sense, SIDS are similar to European Union Risk Assessment Reports (RARs). The distinction is that the SIDS programme is specifically aimed at HPV chemicals, while the chemicals selected for EU RARs are chosen more on the basis of a hazard profile, so include chemicals with much lower production volumes. == References == == External links == List of Screening Information Datasets (SIDS) Chemical Safety page of the OECD Environment Directorate International Programme on Chemical Safety SIDS available through the Chemicals Branch of UNEP
|
{
"page_id": 24121484,
"source": null,
"title": "Screening information dataset"
}
|
In statistical mechanics, the metastate is a probability measure on the space of all thermodynamic states for a system with quenched randomness. The term metastate, in this context, was first used in by Charles M. Newman and Daniel L. Stein in 1996.. Two different versions have been proposed: 1) The Aizenman-Wehr construction, a canonical ensemble approach, constructs the metastate through an ensemble of states obtained by varying the random parameters in the Hamiltonian outside of the volume being considered. 2) The Newman-Stein metastate, a microcanonical ensemble approach, constructs an empirical average from a deterministic (i.e., chosen independently of the randomness) subsequence of finite-volume Gibbs distributions. It was proved for Euclidean lattices that there always exists a deterministic subsequence along which the Newman-Stein and Aizenman-Wehr constructions result in the same metastate. The metastate is especially useful in systems where deterministic sequences of volumes fail to converge to a thermodynamic state, and/or there are many competing observable thermodynamic states. As an alternative usage, "metastate" can refer to thermodynamic states, where the system is in a metastable state (for example superheated or undercooled liquids, when the actual temperature of the liquid is above or below the boiling or freezing temperature, but the material is still in a liquid state). == References ==
|
{
"page_id": 25694349,
"source": null,
"title": "Metastate"
}
|
Primary and secondary antibodies are two groups of antibodies that are classified based on whether they bind to antigens or proteins directly or target another (primary) antibody that, in turn, is bound to an antigen or protein. == Primary == A primary antibody can be very useful for the detection of biomarkers for diseases such as cancer, diabetes, Parkinson’s and Alzheimer’s disease and they are used for the study of absorption, distribution, metabolism, and excretion (ADME) and multi-drug resistance (MDR) of therapeutic agents. == Secondary == Secondary antibodies provide signal detection and amplification along with extending the utility of an antibody through conjugation to proteins. Secondary antibodies are especially efficient in immunolabeling. Secondary antibodies bind to primary antibodies, which are directly bound to the target antigen(s). In immunolabeling, the primary antibody's Fab domain binds to an antigen and exposes its Fc domain to secondary antibody. Then, the secondary antibody's Fab domain binds to the primary antibody's Fc domain. Since the Fc domain is constant within the same animal class, only one type of secondary antibody is required to bind to many types of primary antibodies. This reduces the cost by labeling only one type of secondary antibody, rather than labeling various types of primary antibodies. Secondary antibodies help increase sensitivity and signal amplification due to multiple secondary antibodies binding to a primary antibody. Whole Immunoglobulin molecule secondary antibodies are the most commonly used format, but these can be enzymatically processed to enable assay refinement. F(ab')2 fragments are generated by pepsin digestion to remove most of the Fc fragment, this avoids recognition by Fc receptors on live cells, or to Protein A or Protein G. Papain digestion generates Fab fragments, which removes the entire Fc fragment including the hinge region, yielding two monovalent Fab moieties. They can be used to block
|
{
"page_id": 27332750,
"source": null,
"title": "Primary and secondary antibodies"
}
|
endogenous immunoglobulins on cells, tissues or other surfaces, and to block the exposed immunoglobulins in multiple labeling experiments using primary antibodies from the same species. === Applications === Secondary antibodies can be conjugated to enzymes such as horseradish peroxidase (HRP) or alkaline phosphatase (AP); or fluorescent dyes such as fluorescein isothiocyanate (FITC), rhodamine derivatives, Alexa Fluor dyes; or other molecules to be used in various applications. Secondary antibodies are used in many biochemical assays including: ELISA, including many HIV tests Western blot Immunostaining Immunohistochemistry Immunocytochemistry == References ==
|
{
"page_id": 27332750,
"source": null,
"title": "Primary and secondary antibodies"
}
|
In physics, a Fano resonance is a type of resonant scattering phenomenon that gives rise to an asymmetric line-shape. Interference between a background and a resonant scattering process produces the asymmetric line-shape. It is named after Italian-American physicist Ugo Fano, who in 1961 gave a theoretical explanation for the scattering line-shape of inelastic scattering of electrons from helium; however, Ettore Majorana was the first to discover this phenomenon. Fano resonance is a weak coupling effect meaning that the decay rate is so high, that no hybridization occurs. The coupling modifies the resonance properties such as spectral position and width and its line-shape takes on the distinctive asymmetric Fano profile. Because it is a general wave phenomenon, examples can be found across many areas of physics and engineering. == History == The explanation of the Fano line-shape first appeared in the context of inelastic electron scattering by helium and autoionization. The incident electron doubly excites the atom to the 2 s 2 p {\displaystyle 2s2p} state, a sort of shape resonance. The doubly excited atom spontaneously decays by ejecting one of the excited electrons. Fano showed that interference between the amplitude to simply scatter the incident electron and the amplitude to scatter via autoionization creates an asymmetric scattering line-shape around the autoionization energy with a line-width very close to the inverse of the autoionization lifetime. == Explanation == The Fano resonance line-shape is due to interference between two scattering amplitudes, one due to scattering within a continuum of states (the background process) and the second due to an excitation of a discrete state (the resonant process). The energy of the resonant state must lie in the energy range of the continuum (background) states for the effect to occur. Near the resonant energy, the background scattering amplitude typically varies slowly with energy
|
{
"page_id": 2166926,
"source": null,
"title": "Fano resonance"
}
|
while the resonant scattering amplitude changes both in magnitude and phase quickly. It is this variation that creates the asymmetric profile. For energies far from the resonant energy E r e s {\displaystyle E_{\mathrm {res} }} the background scattering process dominates. Within 2 Γ r e s {\displaystyle 2\Gamma _{\mathrm {res} }} of the resonant energy, the phase of the resonant scattering amplitude changes by π {\displaystyle \pi } . It is this rapid variation in phase that creates the asymmetric line-shape. Fano showed that the total scattering cross-section σ {\displaystyle \sigma } assumes the following form, σ ≈ ( q Γ r e s / 2 + E − E r e s ) 2 ( Γ r e s / 2 ) 2 + ( E − E r e s ) 2 {\displaystyle \sigma \approx {\frac {\left(q\Gamma _{\mathrm {res} }/2+E-E_{\mathrm {res} }\right)^{2}}{\left(\Gamma _{\mathrm {res} }/2\right)^{2}+\left(E-E_{\mathrm {res} }\right)^{2}}}} where Γ r e s {\displaystyle \Gamma _{\mathrm {res} }} describes the line width of the resonant energy and q, the Fano parameter, measures the ratio of resonant scattering to the direct (background) scattering amplitude. This is consistent with the interpretation within the Feshbach–Fano partitioning theory. In the case the direct scattering amplitude vanishes, the q parameter becomes zero and the Fano formula becomes : σ ( q = 0 ) ≈ ( E − E r e s ) 2 ( Γ r e s / 2 ) 2 + ( E − E r e s ) 2 {\displaystyle \sigma (q=0)\approx {\frac {\left(E-E_{\mathrm {res} }\right)^{2}}{\left(\Gamma _{\mathrm {res} }/2\right)^{2}+\left(E-E_{\mathrm {res} }\right)^{2}}}} Looking at transmission shows that this last expression boils down to the expected Breit–Wigner (Lorentzian) formula, as 1 − σ ( q = 0 ) ≈ ( Γ r e s / 2 ) 2 ( Γ r
|
{
"page_id": 2166926,
"source": null,
"title": "Fano resonance"
}
|
e s / 2 ) 2 + ( E − E r e s ) 2 = f ( E ; E r e s , Γ r e s / 2 , 1 ) {\displaystyle 1-\sigma (q=0)\approx {\frac {\left(\Gamma _{\mathrm {res} }/2\right)^{2}}{\left(\Gamma _{\mathrm {res} }/2\right)^{2}+\left(E-E_{\mathrm {res} }\right)^{2}}}=f(E;E_{\mathrm {res} },\Gamma _{\mathrm {res} }/2,1)} , the three parameters Lorentzian function (note that it is not a density function and does not integrate to 1, as its amplitude I {\displaystyle I} is 1 and not 2 / π Γ r e s {\displaystyle 2/\pi \Gamma _{\mathrm {res} }} ). == Examples == Examples of Fano resonances can be found in atomic physics, nuclear physics, condensed matter physics, electrical circuits, microwave engineering, nonlinear optics, nanophotonics, magnetic metamaterials, and in mechanical waves. Fano can be observed with photoelectron spectroscopy and Raman spectroscopy. The phenomenon can be also observed at visible frequencies using simple glass microspheres, which may allow enhancing the magnetic field of light (which is typically small) by a few orders of magnitude. == See also == Resonance (particle physics) Core-excited shape resonance Antiresonance == References ==
|
{
"page_id": 2166926,
"source": null,
"title": "Fano resonance"
}
|
DNA-encoded chemical libraries (DECL) is a technology for the synthesis and screening on an unprecedented scale of collections of small molecule compounds. DECL is used in medicinal chemistry to bridge the fields of combinatorial chemistry and molecular biology. The aim of DECL technology is to accelerate the drug discovery process and in particular early phase discovery activities such as target validation and hit identification. DECL technology involves the conjugation of chemical compounds or building blocks to short DNA fragments that serve as identification bar codes and in some cases also direct and control the chemical synthesis. The technique enables the mass creation and interrogation of libraries via affinity selection, typically on an immobilized protein target. A homogeneous method for screening DNA-encoded libraries (DELs) has recently been developed which uses water-in-oil emulsion technology to isolate, count and identify individual ligand-target complexes in a single-tube approach. In contrast to conventional screening procedures such as high-throughput screening, biochemical assays are not required for binder identification, in principle allowing the isolation of binders to a wide range of proteins historically difficult to tackle with conventional screening technologies. So, in addition to the general discovery of target specific molecular compounds, the availability of binders to pharmacologically important, but so-far “undruggable” target proteins opens new possibilities to develop novel drugs for diseases that could not be treated so far. In eliminating the requirement to initially assess the activity of hits it is hoped and expected that many of the high affinity binders identified will be shown to be active in independent analysis of selected hits, therefore offering an efficient method to identify high quality hits and pharmaceutical leads. == DNA-encoded chemical libraries and display technologies == Until recently, the application of molecular evolution in the laboratory had been limited to display technologies involving biological molecules, where
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small molecules lead discovery was considered beyond this biological approach. DELs have opened the field of display technology to include non-natural compounds such as small molecules, extending the application of molecular evolution and natural selection to the identification of small molecule compounds of desired activity and function. DNA encoded chemical libraries bear resemblance to biological display technologies such as antibody phage display technology, yeast display, mRNA display and aptamer SELEX. In antibody phage display, antibodies are physically linked to phage particles that bear the gene coding for the attached antibody, which is equivalent to a physical linkage of a “phenotype” (the protein) and a “genotype” (the gene encoding for the protein ). Phage-displayed antibodies can be isolated from large antibody libraries by mimicking molecular evolution: through rounds of selection (on an immobilized protein target), amplification and translation. In DELs the linkage of a small molecule to an identifier DNA code allows the facile identification of binding molecules. DELs are subjected to affinity selection procedures on an immobilized target protein of choice, after which non-binders are removed by washing steps, and binders can subsequently be amplified by polymerase chain reaction (PCR) and identified by virtue of their DNA code (e.g.by DNA sequencing). In evolution-based DEL technologies hits can be further enriched by performing rounds of selection, PCR amplification and translation in analogy to biological display systems such as antibody phage display. This makes it possible to work with much larger libraries. == History == “Synthesize a multi-component mixture of compounds in a single process and screen it also a single process”. This is the principle of combinatorial chemistry invented by Prof. Furka Á. (Eötvös Loránd University Budapest Hungary) in 1982, and described it including the method of synthesis of combinatorial libraries and that of a deconvolution strategy in a document notarized
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"page_id": 22810768,
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in the same year. Motivations that led to the invention had been published in 2002. DNA encoded chemical libraries (DECLs) are synthesized by the combinatorial chemistry principle and it clearly agrees with their application. The concept of DNA-encoding was first described in a theoretical paper by Sydney Brenner and Richard Lerner in 1992 in which was proposed to link each molecule of a chemically synthesized entity to a particular oligonucleotide sequence constructed in parallel and to use this encoding genetic tag to identify and enrich active compounds. In 1993 the first practical implementation of this approach was presented by J Nielsen, S. Brenner and K. Janda and similarly by the group of M.A. Gallop. Brenner and Janda suggested to generate individual encoded library members by an alternating parallel combinatorial synthesis of the heteropolymeric chemical compound and the appropriate oligonucleotide sequence on the same bead in a “split-&-pool”-based fashion (see below). Since unprotected DNA is restricted to a narrow window of conventional reaction conditions, until the end of the 1990s a number of alternative encoding strategies were envisaged (i.e. MS-based compound tagging, peptide encoding, haloaromatic tagging, encoding by secondary amines, semiconductor devices.), mainly to avoid inconvenient solid phase DNA synthesis and to create easily screenable combinatorial libraries in high-throughput fashion. However, the selective amplificability of DNA greatly facilitates library screening and it becomes indispensable for the encoding of organic compounds libraries of this unprecedented size. Consequently, at the beginning of the 2000s DNA-combinatorial chemistry experienced a revival. The beginning of the millennium saw the introduction of several independent developments in DEL technology. These technologies can be classified under two general categories: non-evolution-based and evolution-based DEL technologies capable of molecular evolution. The first category benefits from the ability to use off the shelf reagents and therefore enables rather straightforward library generation. Hits
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"page_id": 22810768,
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can be identified by DNA sequencing, however DNA translation and therefore molecular evolution is not feasible by these methods. The split and pool approaches developed by researchers at Praecis Pharmaceuticals (now owned by GlaxoSmithKline), Nuevolution (Copenhagen, Denmark) and encoded self- assembled chemical (ESAC) technology developed in the laboratory of Prof D. Neri (Institute of Pharmaceutical Science, Zurich, Switzerland) fall under this category. ESAC technology sets itself apart being a combinatorial self-assembling approach which resembles fragment based hit discovery (Fig 1b). Here DNA annealing enables discrete building block combinations to be sampled, but no chemical reaction takes place between them. Examples of evolution-based DEL technologies are DNA-routing developed by Prof. D.R. Halpin and Prof. P.B. Harbury (Stanford University, Stanford, CA), DNA-templated synthesis developed by Prof. D. Liu (Harvard University, Cambridge, MA) and commercialized by Ensemble Therapeutics (Cambridge, MA) and YoctoReactor technology. developed and commercialized by Vipergen (Copenhagen, Denmark). These technologies are described in further detail below. DNA-templated synthesis and YoctoReactor technology require the prior conjugation of chemical building blocks (BB) to a DNA oligonucleotide tag before library assembly, therefore more upfront work is required before library assembly. Furthermore, the DNA tagged BBs enable the generation of a genetic code for synthesized compounds and artificial translation of the genetic code is possible: That is the BB's can be recalled by the PCR-amplified genetic code, and the library compounds can be regenerated. This, in turn, enables the principle of Darwinian natural selection and evolution to be applied to small molecule selection in direct analogy to biological display systems; through rounds of selection, amplification and translation. == Non-evolution based technologies == == Combinatorial libraries == Combinatorial libraries are special multi-component compound mixtures that are synthesized in a single stepwise process. They differ from collection of individual compounds as well as from a series of
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"page_id": 22810768,
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compounds prepared by parallel synthesis. Combinatorial libraries have important features. ″ Mixtures are used in their synthesis. The use of mixtures ensures the very high efficiency of the process. Both reactants could be mixtures but for practical reasons the split-mix procedure is used: one mixture is divided into portions that are coupled with the BBs. The mixtures are so important that there is no combinatorial library without using a mixture in the synthesis, and if a mixture is used in a process inevitably combinatorial library forms. ″ Components of the libraries need to be present in nearly equal molar quantities. In order to achieve this as closely as possible the mixtures are divided into equal portions and after pooling a thorough mixing is needed. ″ Since the structure of components is unknown deconvolution methods need to be used in screening. For this reason, encoding methods had been developed. Coding molecules are attached to the beads of the solid support that record the coupled BBs and their sequence. One of these methods is encoding by DNA oligomers. ″ It is a remarkable feature of combinatorial libraries that the whole compound mixture can be screened in a single process. Since both the synthesis and screening are very efficient procedures the use of combinatorial libraries in pharmaceutical research leads to enormous savings. In solid phase combinatorial synthesis only a single compound forms in each bead. For this reason, the number of components in the library can't exceed the number of beads of the solid support. This means that the number of components in such libraries is limited. This restraint was eliminated by Harbury and Halpin. In their synthesis of DELs, the solid support is omitted and BBs are attached directly to the encoding DNA oligomers. This new approach helps to increase practically unlimitedly
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"page_id": 22810768,
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the number of components of DNA encoded combinatorial libraries (DECLs). === Split-&-Pool DNA Encoding === In order to apply combinatorial chemistry for the synthesis of DNA-encoded chemical libraries, a Split-&-Pool approach was pursued. Initially a set of unique DNA-oligonucleotides (n) each containing a specific coding sequence is chemically conjugated to a corresponding set of small organic molecules. Consequently, the oligonucleotide-conjugate compounds are mixed ("Pool") and divided ("Split") into a number of groups (m). In appropriate conditions a second set of building blocks (m) are coupled to the first one and a further oligonucleotide which is coding for the second modification is enzymatically introduced before mixing again. This “split-&-pool” steps can be iterated a number of times (r) increasing at each round the library size in a combinatorial manner (i.e. (n x m)r). Alternatively, peptide nucleic acids have been used to encode libraries prepared by "split-&-pool" method. A benefit of PNA-encoding is that the chemistry can be performed by standard SPPS. === Stepwise coupling of coding DNA fragments to nascent organic molecules === A promising strategy for the construction of DNA-encoded libraries is represented by the use of multifunctional building blocks covalently conjugated to an oligonucleotide serving as a “core structure” for library synthesis. In a ‘pool-and-split’ fashion a set of multifunctional scaffolds undergo orthogonal reactions with series of suitable reactive partners. Following each reaction step, the identity of the modification is encoded by an enzymatic addition of DNA segment to the original DNA “core structure”. The use of N-protected amino acids covalently attached to a DNA fragment allow, after a suitable deprotection step, a further amide bond formation with a series of carboxylic acids or a reductive amination with aldehydes. Similarly, diene carboxylic acids used as scaffolds for library construction at the 5’-end of amino modified oligonucleotide, could be subjected
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"page_id": 22810768,
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to a Diels-Alder reaction with a variety of maleimide derivatives. After completion of the desired reaction step, the identity of the chemical moiety added to the oligonucleotide is established by the annealing of a partially complementary oligonucleotide and by a subsequent Klenow fill-in DNA-polymerization, yielding a double stranded DNA fragment. The synthetic and encoding strategies described above enable the facile construction of DNA-encoded libraries of a size up to 104 member compounds carrying two sets of “building blocks”. However the stepwise addition of at least three independent sets of chemical moieties to a tri-functional core building block for the construction and encoding of a very large DNA-encoded library (comprising up to 106 compounds) can also be envisaged.(Fig.2) === Combinatorial self-assembling === ==== Encoded self-assembling chemical libraries ==== Encoded Self-Assembling Chemical (ESAC) libraries rely on the principle that two sublibraries of a size of x members (e.g. 103) containing a constant complementary hybridization domain can yield a combinatorial DNA-duplex library after hybridization with a complexity of x2 uniformly represented library members (e.g. 106). Each sub-library member would consist of an oligonucleotide containing a variable, coding region flanked by a constant DNA sequence, carrying a suitable chemical modification at the oligonucleotide extremity. The ESAC sublibraries can be used in at least four different embodiments. A sub-library can be paired with a complementary oligonucleotide and used as a DNA encoded library displaying a single covalently linked compound for affinity-based selection experiments. A sub-library can be paired with an oligonucleotide displaying a known binder to the target, thus enabling affinity maturation strategies. Two individual sublibraries can be assembled combinatorially and used for the de novo identification of bidentate binding molecules. Three different sublibraries can be assembled to form a combinatorial triplex library. Preferential binders isolated from an affinity-based selection can be PCR-amplified and decoded
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"page_id": 22810768,
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on complementary oligonucleotide microarrays or by concatenation of the codes, subcloning and sequencing. The individual building blocks can eventually be conjugated using suitable linkers to yield a drug-like high-affinity compound. The characteristics of the linker (e.g. length, flexibility, geometry, chemical nature and solubility) influence the binding affinity and the chemical properties of the resulting binder.(Fig.3) Bio-panning experiments on HSA of a 600-member ESAC library allowed the isolation of the 4-(p-iodophenyl)butanoic moiety. The compound represents the core structure of a series of portable albumin binding molecules and of Albufluor a recently developed fluorescein angiographic contrast agent currently under clinical evaluation. ESAC technology has been used for the isolation of potent inhibitors of bovine trypsin and for the identification of novel inhibitors of stromelysin-1 (MMP-3), a matrix metalloproteinase involved in both physiological and pathological tissue remodeling processes, as well as in disease processes, such as arthritis and metastasis. == Evolution-based technologies == === DNA-routing === In 2004, D.R. Halpin and P.B. Harbury presented a novel intriguing method for the construction of DNA-encoded libraries. For the first time the DNA-conjugated templates served for both encoding and programming the infrastructure of the “split-&-pool” synthesis of the library components. The design of Halpin and Harbury enabled alternating rounds of selection, PCR amplification and diversification with small organic molecules, in complete analogy to phage display technology. The DNA-routing machinery consists of a series of connected columns bearing resin-bound anticodons, which could sequence-specifically separate a population of DNA-templates into spatially distinct locations by hybridization. According to this split-and-pool protocol a peptide combinatorial library DNA-encoded of 106 members was generated. === DNA-templated synthesis === In 2001 David Liu and co-workers showed that complementary DNA oligonucleotides can be used to assist certain synthetic reactions, which do not efficiently take place in solution at low concentration. A DNA-heteroduplex was used
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"page_id": 22810768,
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to accelerate the reaction between chemical moieties displayed at the extremities of the two DNA strands. Furthermore, the "proximity effect", which accelerates bimolecular reaction, was shown to be distance-independent (at least within a distance of 30 nucleotides). In a sequence-programmed fashion oligonucleotides carrying one chemical reactant group were hybridized to complementary oligonucleotide derivatives carrying a different reactive chemical group. The proximity conferred by the DNA hybridization drastically increases the effective molarity of the reaction reagents attached to the oligonucleotides, enabling the desired reaction to occur even in an aqueous environment at concentrations which are several orders of magnitude lower than those needed for the corresponding conventional organic reaction not DNA-templated. Using a DNA-templated set-up and sequence-programmed synthesis Liu and co-workers generated a 64-member compound DNA encoded library of macrocycles. == 3-Dimensional proximity-based technology (YoctoReactor technology) == The YoctoReactor (yR) is a 3D proximity-driven approach which exploits the self-assembling nature of DNA oligonucleotides into 3, 4 or 5-way junctions to direct small molecule synthesis at the center of the junction. Figure 5 illustrates the basic concept with a 4-way DNA junction. The center of the DNA junction constitutes a volume on the order of a yoctoliter, hence the name YoctoReactor. This volume contains a single molecule reaction yielding reaction concentrations in the high mM range. The effective concentration facilitated by the DNA greatly accelerates chemical reactions that otherwise would not take place at the actual concentration several orders of magnitude lower. === Building a yR library === Figure 6 illustrates the generation of a yR library using a 3-way DNA junction. In summary, chemical building-blocks (BB) are attached via cleavable or non-cleavable linkers to three types of bispecific DNA oligonucleotides (oligo-BBs) representing each arm of the yR. To facilitate synthesis in a combinatorial manner, the oligo-BBs are designed such that the
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DNA contains (a) the code for an attached BB at the distal end of the oligo (colored lines) and (b) areas of constant DNA sequence (black lines) to bring about the self-assembly of the DNA into a 3-way junction (independently of the BB) and the subsequent chemical reaction. Chemical reactions are performed via a stepwise procedure and after each step the DNA is ligated and the product purified by polyacrylamide gel electrophoresis. Cleavable linkers (BB-DNA) are used for all but one position yielding a library of small molecules with a single covalent link to the DNA code. Table 1 outlines how libraries of different sizes can be generated using yR technology. The yR design approach provides an unvarying reaction site with regard to both (a) distance between reactants and (b) sequence environment surrounding the reaction site. Furthermore, the intimate connection between the code and the BB on the oligo-BB moieties which are mixed combinatorially in a single pot confers a high fidelity to the encoding of the library. The code of the synthesized products, furthermore, is not preset, but rather is assembled combinatorially and synthesized in synchronicity with the innate product. === Homogeneous screening of yoctoreactor libraries === A homogeneous method for screening yoctoreactor libraries (yR) has recently been developed which uses water-in-oil emulsion technology to isolate individual ligand-target complexes. Called Binder Trap Enrichment (BTE), ligands to a protein target are identified by trapping binding pairs (DNA-labelled protein target and yR ligand) in emulsion droplets during dissociation dominated kinetics. Once trapped, the target and ligand DNA are joined by ligation, thus preserving the binding information. Hereafter, identification of hits is essentially a counting exercise: information on binding events is deciphered by sequencing and counting the joined DNA - selective binders are counted with a much higher frequency than random binders.
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"page_id": 22810768,
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This is possible because random trapping of target and ligand is "diluted" by the high number of water droplets in the emulsion. The low noise and background signal characteristic of BTE is attributed to the "dilution" of the random signal, the lack of surface artifacts and the high fidelity of the yR library and screening method. Screening is performed in a single tube method. Biologically active hits are identified in a single round of BTE characterized by a low false positive rate. BTE mimics the non-equilibrium nature of in vivo ligand-target interactions and offers the unique possibility to screen for target specific ligands based on ligand-target residence time because the emulsion, which traps the binding complex, is formed during a dynamic dissociation phase. == Decoding of DNA-encoded chemical libraries == Following selection from DNA-encoded chemical libraries, the decoding strategy for the fast and efficient identification of the specific binding compounds is crucial for the further development of the DEL technology. So far, Sanger-sequencing-based decoding, microarray-based methodology and high-throughput sequencing techniques represented the main methodologies for the decoding of DNA-encoded library selections. === Sanger sequencing-based decoding === Although many authors implicitly envisaged a traditional Sanger sequencing-based decoding, the number of codes to sequence simply according to the complexity of the library is definitely an unrealistic task for a traditional Sanger sequencing approach. Nevertheless, the implementation of Sanger sequencing for decoding DNA-encoded chemical libraries in high-throughput fashion was the first to be described. After selection and PCR amplification of the DNA-tags of the library compounds, concatamers containing multiple coding sequences were generated and ligated into a vector. Following Sanger sequencing of a representative number of the resulting colonies revealed the frequencies of the codes present in the DNA-encoded library sample before and after selection. === Microarray-based decoding === A DNA microarray is
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a device for high-throughput investigations widely used in molecular biology and in medicine. It consists of an arrayed series of microscopic spots (‘features’ or ‘locations’) containing few picomoles of oligonucleotides carrying a specific DNA sequence. This can be a short section of a gene or other DNA element that are used as probes to hybridize a DNA or RNA sample under suitable conditions. Probe-target hybridization is usually detected and quantified by fluorescence-based detection of fluorophore-labeled targets to determine relative abundance of the target nucleic acid sequences. Microarray has been used for the successfully decoding of ESAC DNA-encoded libraries and PNA-encoded libraries. The coding oligonucleotides representing the individual chemical compounds in the library, are spotted and chemically linked onto the microarray slides, using a BioChip Arrayer robot. Subsequently, the oligonucleotide tags of the binding compounds isolated from the selection are PCR amplified using a fluorescent primer and hybridized onto the DNA-microarray slide. Afterwards, microarrays are analyzed using a laser scan and spot intensities detected and quantified. The enrichment of the preferential binding compounds is revealed comparing the spots intensity of the DNA-microarray slide before and after selection. === Decoding by high throughput sequencing === According to the complexity of the DNA encoded chemical library (typically between 103 and 106 members), a conventional Sanger sequencing based decoding is unlikely to be usable in practice, due both to the high cost per base for the sequencing and to the tedious procedure involved. High throughput sequencing technologies exploited strategies that parallelize the sequencing process displacing the use of capillary electrophoresis and producing thousands or millions of sequences at once. In 2008 was described the first implementation of a high-throughput sequencing technique originally developed for genome sequencing (i.e. "454 technology") to the fast and efficient decoding of a DNA encoded chemical library comprising 4000 compounds.
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This study led to the identification of novel chemical compounds with submicromolar dissociation constants towards streptavidin and definitely shown the feasibility to construct, perform selections and decode DNA-encoded libraries containing millions of chemical compounds. == See also == Drug discovery High-throughput screening Combinatorial chemistry DNA sequencing Phage display == References ==
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Lysis ( LY-sis; from Greek λῠ́σῐς lýsis 'loosening') is the breaking down of the membrane of a cell, often by viral, enzymic, or osmotic (that is, "lytic" LIT-ik) mechanisms that compromise its integrity. A fluid containing the contents of lysed cells is called a lysate. In molecular biology, biochemistry, and cell biology laboratories, cell cultures may be subjected to lysis in the process of purifying their components, as in protein purification, DNA extraction, RNA extraction, or in purifying organelles. Many species of bacteria are subject to lysis by the enzyme lysozyme, found in animal saliva, egg white, and other secretions. Phage lytic enzymes (lysins) produced during bacteriophage infection are responsible for the ability of these viruses to lyse bacterial cells. Penicillin and related β-lactam antibiotics cause the death of bacteria through enzyme-mediated lysis that occurs after the drug causes the bacterium to form a defective cell wall. If the cell wall is completely lost and the penicillin was used on gram-positive bacteria, then the bacterium is referred to as a protoplast, but if penicillin was used on gram-negative bacteria, then it is called a spheroplast. == Cytolysis == Cytolysis occurs when a cell bursts due to an osmotic imbalance that has caused excess water to move into the cell. Cytolysis can be prevented by several different mechanisms, including the contractile vacuole that exists in some paramecia, which rapidly pump water out of the cell. Cytolysis does not occur under normal conditions in plant cells because plant cells have a strong cell wall that contains the osmotic pressure, or turgor pressure, that would otherwise cause cytolysis to occur. == Oncolysis == Oncolysis is the destruction of neoplastic cells or of a tumour. The term is also used to refer to the reduction of any swelling. == Plasmolysis == Plasmolysis is the
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{
"page_id": 397456,
"source": null,
"title": "Lysis"
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contraction of cells within plants due to the loss of water through osmosis. In a hypertonic environment, the cell membrane peels off the cell wall and the vacuole collapses. These cells will eventually wilt and die unless the flow of water caused by osmosis can stop the contraction of the cell membrane. == Immune response == Erythrocytes' hemoglobin release free radicals in response to pathogens when lysed by them. This can damage the pathogens. == Applications == Cell lysis is used in laboratories to break open cells and purify or further study their contents. Lysis in the laboratory may be affected by enzymes or detergents or other chaotropic agents. Mechanical disruption of cell membranes, as by repeated freezing and thawing, sonication, pressure, or filtration may also be referred to as lysis. Many laboratory experiments are sensitive to the choice of lysis mechanism; often it is desirable to avoid mechanical shear forces that would denature or degrade sensitive macromolecules, such as proteins and DNA, and different types of detergents can yield different results. The unprocessed solution immediately after lysis but before any further extraction steps is often referred to as a crude lysate. For example, lysis is used in western and Southern blotting to analyze the composition of specific proteins, lipids, and nucleic acids individually or as complexes. Depending on the detergent used, either all or some membranes are lysed. For example, if only the cell membrane is lysed then gradient centrifugation can be used to collect certain organelles. Lysis is also used for protein purification, DNA extraction, and RNA extraction. == Methods == Several methods for cell lysis exist, sometimes used in combination. Examples include liquid homogenization, freeze thawing, and physical disruption such as sonication, or the use of hypotonic solutions that cause osmotic swelling and eventual bursting of the
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"page_id": 397456,
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"title": "Lysis"
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cell. === Chemical lysis === This method uses chemical disruption. It is the most popular and simple approach. Chemical lysis chemically deteriorates/solubilizes the proteins and lipids present within the membrane of targeted cells. Common lysis buffers contain sodium hydroxide (NaOH) and sodium dodecyl sulfate (SDS). Cell lysis is best done at a pH range of 11.5–12.5. Although simple, it is a slow process, taking anywhere from 6 to 12 hours. === Acoustic lysis === This method uses ultrasonic waves to generate areas of high and low pressure which causes cavitation and in turn, cell lysis. Though this method usually comes out clean, it fails to be cost effective and consistent. === Mechanical lysis === This method uses physical penetration to pierce or cut a cell membrane. === Enzymatic lysis === This method uses enzymes such as lysozyme or proteases to disintegrate the cell membrane. == See also == Cell disruption Cell unroofing Crenation Hemolysis Lysogenic Pitted keratolysis == References ==
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"page_id": 397456,
"source": null,
"title": "Lysis"
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Karsten Borgwardt (born 1980) is a German computer scientist and biologist specializing in machine learning and computational biology. Since February 2023, he has been a director at the Max Planck Institute of Biochemistry in Martinsried, Germany, where he leads the Department of Machine Learning and Systems Biology. == Education and career == Borgwardt was born in Kaiserslautern. He obtained a Diplom (equivalent to a master’s degree) in computer science from LMU Munich in 2004 and a Master of Science in biology from the University of Oxford in 2003. In 2007, he obtained his PhD from LMU Munich in computer science. Following a postdoctoral position at the University of Cambridge, he became a research group leader for machine learning and computational biology at the Max Planck Institute for Biological Cybernetics and the former Max Planck Institute for Developmental Biology in Tübingen in 2008. In 2011, Borgwardt was appointed professor of data mining in the life sciences at the University of Tübingen. In 2014, he joined ETH Zurich as an associate professor in the Department of Biosystems Science and Engineering (D-BSSE) and was promoted to full professor in 2017. During his tenure at ETH Zurich, he coordinated significant research programs, including two Marie Curie Innovative Training Networks and the Personalized Swiss Sepsis Study, focusing on the prediction of sepsis using machine learning. In 2023, he was appointed as Scientific Member of the Max Planck Society and as Director at the Max Planck Institute of Biochemistry in Martinsried. == Research contributions == Borgwardt’s research integrates big data analysis with biomedical research. He develops novel machine learning algorithms to detect patterns and statistical dependencies in large biological and medical datasets. His work aims to enable the automatic generation of new knowledge from big data and to understand the relationship between the function of biological
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"page_id": 78516370,
"source": null,
"title": "Karsten Borgwardt"
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systems and their molecular properties, which is fundamental for personalized medicine. == Awards and honors == During his studies, he was a scholar of the Stiftung Maximilianeum, and the Bavarian Foundation for the Promotion of the Gifted. Borgwardt received scholarships from the Studienstiftung des deutschen Volkes in 2002 and 2007. His PhD dissertation received the Heinz Schwärtzel Dissertation Award for Foundations of Computer Science in 2007. As a professor in Tübingen, he was awarded the Alfried-Krupp-Förderpreis for Young Professors in 2013. In 2015, he received an SNSF Starting Grant. In 2014, 2015 and 2016, he was listed in “Top 40 under 40” in Germany rankings selected by Capital magazine. In 2018, Borgwardt was named among “25 individuals who have the potential to shape the next 25 years” by Focus magazine. In 2023, Borgwardt received an honorary professorship from Ludwig Maximilian University of Munich by the Faculty of Chemistry and Pharmacy. Publications from Borgwardt's group have received the Outstanding Student Paper Award in NIPS in 2009, the SIB Graduate Paper Award in 2020 and SIB Remarkable Output Awards in 2020 and 2021 from the Swiss Institute of Bioinformatics (SIB). == Selected publications == Weisfeiler-Lehman Graph Kernels (’‘Journal of Machine Learning Research’’, 2011): Introduced an efficient graph kernel based on the Weisfeiler-Lehman algorithm. “Direct antimicrobial resistance prediction from clinical MALDI-TOF mass spectra using machine learning” (’‘Nature Medicine’’, 2022): showcased the feasibility of predicting antimicrobial resistance from readily collected mass spectrometry data in the hospital. The new method is able to identify antibiotic resistance 24 hours earlier than previous methods. == References ==
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"page_id": 78516370,
"source": null,
"title": "Karsten Borgwardt"
}
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In biology, a common name of a taxon or organism (also known as a vernacular name, English name, colloquial name, country name, popular name, or farmer's name) is a name that is based on the normal language of everyday life; and is often contrasted with the scientific name for the same organism, which is often based in Latin. A common name is sometimes frequently used, but that is not always the case. In chemistry, IUPAC defines a common name as one that, although it unambiguously defines a chemical, does not follow the current systematic naming convention, such as acetone, systematically 2-propanone, while a vernacular name describes one used in a lab, trade or industry that does not unambiguously describe a single chemical, such as copper sulfate, which may refer to either copper(I) sulfate or copper(II) sulfate. Sometimes common names are created by authorities on one particular subject, in an attempt to make it possible for members of the general public (including such interested parties as fishermen, farmers, etc.) to be able to refer to one particular species of organism without needing to be able to memorise or pronounce the scientific name. Creating an "official" list of common names can also be an attempt to standardize the use of common names, which can sometimes vary a great deal between one part of a country and another, as well as between one country and another country, even where the same language is spoken in both places. == Use as part of folk taxonomy == A common name intrinsically plays a part in a classification of objects, typically an incomplete and informal classification, in which some names are degenerate examples in that they are unique and lack reference to any other name, as is the case with say, ginkgo, okapi, and ratel. Folk
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{
"page_id": 331921,
"source": null,
"title": "Common name"
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|
taxonomy, which is a classification of objects using common names, has no formal rules and need not be consistent or logical in its assignment of names, so that say, not all flies are called flies (for example Braulidae, the so-called "bee lice") and not every animal called a fly is indeed a fly (such as dragonflies and mayflies). In contrast, scientific or biological nomenclature is a global system that attempts to denote particular organisms or taxa uniquely and definitively, on the assumption that such organisms or taxa are well-defined and generally also have well-defined interrelationships; accordingly the ICZN has formal rules for biological nomenclature and convenes periodic international meetings to further that purpose. == Common names and the binomial system == The form of scientific names for organisms, called binomial nomenclature, is superficially similar to the noun-adjective form of vernacular names or common names which were used by non-modern cultures. A collective name such as owl was made more precise by the addition of an adjective such as screech. Linnaeus himself published a flora of his homeland Sweden, Flora Svecica (1745), and in this, he recorded the Swedish common names, region by region, as well as the scientific names. The Swedish common names were all binomials (e.g. plant no. 84 Råg-losta and plant no. 85 Ren-losta); the vernacular binomial system thus preceded his scientific binomial system. Linnaean authority William T. Stearn said: By the introduction of his binomial system of nomenclature, Linnaeus gave plants and animals an essentially Latin nomenclature like vernacular nomenclature in style but linked to published, and hence relatively stable and verifiable, scientific concepts and thus suitable for international use. == Geographic range of use == The geographic range over which a particularly common name is used varies; some common names have a very local application, while
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{
"page_id": 331921,
"source": null,
"title": "Common name"
}
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others are virtually universal within a particular language. Some such names even apply across ranges of languages; the word for cat, for instance, is easily recognizable in most Germanic and many Romance languages. Many vernacular names, however, are restricted to a single country and colloquial names to local districts. Some languages also have more than one common name for the same animal. For example, in Irish, there are many terms that are considered outdated but still well-known for their somewhat humorous and poetic descriptions of animals. == Constraints and problems == Common names are used in the writings of both professionals and laymen. Lay people sometimes object to the use of scientific names over common names, but the use of scientific names can be defended, as it is in these remarks from a book on marine fish: Because common names often have a very local distribution, the same fish in a single area may have several common names. Because of ignorance of relevant biological facts among the lay public, a single species of fish may be called by several common names, because individuals in the species differ in appearance depending on their maturity, gender, or can vary in appearance as a morphological response to their natural surroundings, i.e. ecophenotypic variation. In contrast to common names, formal taxonomic names imply biological relationships between similarly named creatures. Because of incidental events, contact with other languages, or simple confusion, common names in a given region will sometimes change with time. In a book that lists over 1200 species of fishes more than half have no widely recognised common name; they either are too nondescript or too rarely seen to have earned any widely accepted common name. Conversely, a single common name often applies to multiple species of fishes. The lay public might simply
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not recognise or care about subtle differences in appearance between only very distantly related species. Many species that are rare, or lack economic importance, do not have a common name. == Coining common names == In scientific binomial nomenclature, names commonly are derived from classical or modern Latin or Greek or Latinised forms of vernacular words or coinages; such names generally are difficult for laymen to learn, remember, and pronounce and so, in such books as field guides, biologists commonly publish lists of coined common names. Many examples of such common names simply are attempts to translate the scientific name into English or some other vernacular. Such translation may be confusing in itself, or confusingly inaccurate, for example, gratiosus does not mean "gracile" and gracilis does not mean "graceful". The practice of coining common names has long been discouraged; de Candolle's Laws of Botanical Nomenclature, 1868, the non-binding recommendations that form the basis of the modern (now binding) International Code of Nomenclature for algae, fungi, and plants contains the following:Art. 68. Every friend of science ought to be opposed to the introduction into a modern language of names of plants that are not already there unless they are derived from a Latin botanical name that has undergone but a slight alteration. ... ought the fabrication of names termed vulgar names, totally different from Latin ones, to be proscribed. The public to whom they are addressed derives no advantage from them because they are novelties. Lindley's work, The Vegetable Kingdom, would have been better relished in England had not the author introduced into it so many new English names, that are to be found in no dictionary, and that do not preclude the necessity of learning with what Latin names they are synonymous. A tolerable idea may be given of the
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danger of too great a multiplicity of vulgar names, by imagining what geography would be, or, for instance, the Post-office administration, supposing every town had a totally different name in every language. Various bodies and the authors of many technical and semi-technical books do not simply adapt existing common names for various organisms; they try to coin (and put into common use) comprehensive, useful, authoritative, and standardised lists of new names. The purpose typically is: to create names from scratch where no common names exist to impose a particular choice of name where there is more than one common name to improve existing common names to replace them with names that conform more to the relatedness of the organisms Other attempts to reconcile differences between widely separated regions, traditions, and languages, by arbitrarily imposing nomenclature, often reflect narrow perspectives and have unfortunate outcomes. For example, members of the genus Burhinus occur in Australia, Southern Africa, Eurasia, and South America. A recent trend in field manuals and bird lists is to use the name "thick-knee" for members of the genus. This, in spite of the fact that the majority of the species occur in non-English-speaking regions and have various common names, not always English. For example, "Dikkop" is the centuries-old South African vernacular name for their two local species: Burhinus capensis is the Cape dikkop (or "gewone dikkop", not to mention the presumably much older Zulu name "umBangaqhwa"); Burhinus vermiculatus is the "water dikkop". The thick joints in question are not even, in fact, the birds' knees, but the intertarsal joints—in lay terms the ankles. Furthermore, not all species in the genus have "thick knees", so the thickness of the "knees" of some species is not of clearly descriptive significance. The family Burhinidae has members that have various common names even
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in English, including "stone curlews", so the choice of the name "thick-knees" is not easy to defend but is a clear illustration of the hazards of the facile coinage of terminology. == Lists that include common names == === Lists of general interest === === Collective nouns === For collective nouns for various subjects, see a list of collective nouns (e.g. a flock of sheep, pack of wolves). === Official lists === Some organizations have created official lists of common names, or guidelines for creating common names, hoping to standardize the use of common names. For example, the Australian Fish Names List or AFNS was compiled through a process involving work by taxonomic and seafood industry experts, drafted using the CAAB (Codes for Australian Aquatic Biota) taxon management system of the CSIRO, and including input through public and industry consultations by the Australian Fish Names Committee (AFNC). The AFNS has been an official Australian Standard since July 2007 and has existed in draft form (The Australian Fish Names List) since 2001. Seafood Services Australia (SSA) serve as the Secretariat for the AFNC. SSA is an accredited Standards Australia (Australia's peak non-government standards development organisation) Standards Development The Entomological Society of America maintains a database of official common names of insects, and proposals for new entries must be submitted and reviewed by a formal committee before being added to the listing. Efforts to standardize English names for the amphibians and reptiles of North America (north of Mexico) began in the mid-1950s. The dynamic nature of taxonomy necessitates periodical updates and changes in the nomenclature of both scientific and common names. The Society for the Study of Amphibians and Reptiles (SSAR) published an updated list in 1978, largely following the previous established examples, and subsequently published eight revised editions ending in 2017.
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More recently the SSAR switched to an online version with a searchable database. Standardized names for the amphibians and reptiles of Mexico in Spanish and English were first published in 1994, with a revised and updated list published in 2008. A set of guidelines for the creation of English names for birds was published in The Auk in 1978. It gave rise to Birds of the World: Recommended English Names and its Spanish and French companions. The Academy of the Hebrew Language publish from time to time short dictionaries of common name in Hebrew for species that occur in Israel or surrounding countries e.g. for Reptilia in 1938, Osteichthyes in 2012, and Odonata in 2015. == See also == Folk taxonomy List of historical common names Scientific terminology Category:Plant common names Specific name (zoology) == References == === Citations === === Sources === Stearn, William T. (1959). "The Background of Linnaeus's Contributions to the Nomenclature and Methods of Systematic Biology". Systematic Zoology 8: 4–22. == External links == Plant names Multilingual, Multiscript Plant Name Database The use of common names Chemical Names of Common Substances Plantas medicinales / Medicinal plants (database)
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Megaevolution describes the most dramatic events in evolution. It is no longer suggested that the evolutionary processes involved are necessarily special, although in some cases they might be. Whereas macroevolution can apply to relatively modest changes that produced diversification of species and genera and are readily compared to microevolution, "megaevolution" is used for great changes. Megaevolution has been extensively debated because it has been seen as a possible objection to Charles Darwin's theory of gradual evolution by natural selection. A list was prepared by John Maynard Smith and Eörs Szathmáry which they called The Major Transitions in Evolution. On the 1999 edition of the list they included: Replicating molecules: change to populations of molecules in protocells Independent replicators leading to chromosomes RNA as gene and enzyme change to DNA genes and protein enzymes Bacterial cells (prokaryotes) leading to cells (eukaryotes) with nuclei and organelles Asexual clones leading to sexual populations Single-celled organisms leading to fungi, plants and animals Solitary individuals leading to colonies with non-reproducing castes (termites, ants & bees) Primate societies leading to human societies with language Some of these topics had been discussed before. Numbers one to six on the list are events which are of huge importance, but about which we know relatively little. All occurred before (and mostly very much before) the fossil record started, or at least before the Phanerozoic eon. Numbers seven and eight on the list are of a different kind from the first six, and have generally not been considered by the other authors. Number four is of a type which is not covered by traditional evolutionary theory, The origin of eukaryotic cells is probably due to symbiosis between prokaryotes. This is a kind of evolution which must be a rare event. == The Cambrian radiation example == The Cambrian explosion or
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"page_id": 44241044,
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"title": "Megaevolution"
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Cambrian radiation was the relatively rapid appearance of most major animal phyla around 530 million years ago (mya) in the fossil record, some of which are now extinct. It is the classic example of megaevolution. "The fossil record documents two mutually exclusive macroevolutionary modes separated by the transitional Ediacaran period". Before about 580 mya it seems that most organisms were simple. They were made of individual cells occasionally organized into colonies. Over the following 70 or 80 million years the rate of evolution accelerated by an order of magnitude. Normally rates of evolution are measured by the extinction and origination rate of species, but here we can say that by the end of the Cambrian every phylum, or almost every phylum, existed. The diversity of life began to resemble that of today. The Cambrian explosion has caused much scientific debate. The seemingly rapid appearance of fossils in the 'primordial strata' was noted as early as the mid 19th century, and Charles Darwin saw it as one of the main objections that could be made against his theory of evolution by natural selection. == See also == Saltation (biology) == References ==
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"page_id": 44241044,
"source": null,
"title": "Megaevolution"
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The molecular formula C11H14O2 (molar mass: 178.23 g/mol) may refer to: Actinidiolide 4-tert-Butylbenzaldehyde para-tert-Butylbenzoic acid Methyl eugenol Methyl isoeugenol 2-Phenethyl propionate Wieland–Miescher ketone
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"page_id": 25825429,
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"title": "C11H14O2"
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A designer baby is an embryo or fetus whose genetic makeup has been intentionally selected or altered, often to exclude a particular gene or to remove genes associated with disease, to achieve desired traits. This process usually involves preimplantation genetic diagnosis (PGD), which analyzes multiple human embryos to identify genes associated with specific diseases and characteristics, then selecting embryos that have the desired genetic makeup. While screening for single genes is commonly practiced, advancements in polygenic screening are becoming more prominent, though only a few companies currently offer it. This technique uses an algorithm to aggregate the estimated effects of numerous genetic variants tied to an individual's risk for a particular condition or trait. Other methods of altering a baby's genetic information involve directly editing the genome before birth, using technologies such as CRISPR. A controversial example of this can be seen in the 2018 case involving Chinese twins Lulu and Nana, which had their genomes edited to resist HIV infection, sparking widespread criticism and legal debates. This highlights the implications of germline engineering, which involves introducing the desired genetic material into the embryo or parental germ cells. This process is typically prohibited by law, however, regulations vary globally. Editing embryos in this manner can result in genetic changes that are passed down to future generations, raising significant controversy and ethical concerns. While some scientists advocate for its use in treating genetic diseases, others warn that it could lead to misuse for non-medical purposes, such as cosmetic enhancements and modification of human traits. == Pre-implantation genetic diagnosis == Pre-implantation genetic diagnosis (PGD or PIGD) is a procedure in which embryos are screened prior to implantation. The technique is used alongside in vitro fertilisation (IVF) to obtain embryos for evaluation of the genome – alternatively, oocytes can be screened prior to
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"page_id": 1708182,
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fertilisation. The technique was first used in 1989. PGD is used primarily to select embryos for implantation in the case of possible genetic defects, allowing identification of mutated or disease-related alleles and selection against them. It is especially useful in embryos from parents where one or both carry a heritable disease. PGD can also be used to select for embryos of a certain sex, most commonly when a disease is more strongly associated with one sex than the other (as is the case for X-linked disorders which are more common in males, such as haemophilia). Infants born with traits selected following PGD are sometimes considered to be designer babies. One application of PGD is the selection of 'saviour siblings', children who are born to provide a transplant (of an organ or group of cells) to a sibling with a usually life-threatening disease. Saviour siblings are conceived through IVF and then screened using PGD to analyze genetic similarity to the child needing a transplant, to reduce the risk of rejection. === Process === Embryos for PGD are obtained from IVF procedures in which the oocyte is artificially fertilised by sperm. Oocytes from the woman are harvested following controlled ovarian hyperstimulation (COH), which involves fertility treatments to induce production of multiple oocytes. After harvesting the oocytes, they are fertilised in vitro, either during incubation with multiple sperm cells in culture, or via intracytoplasmic sperm injection (ICSI), where sperm is directly injected into the oocyte. The resulting embryos are usually cultured for 3–6 days, allowing them to reach the blastomere or blastocyst stage. Once embryos reach the desired stage of development, cells are biopsied and genetically screened. The screening procedure varies based on the nature of the disorder being investigated. Polymerase chain reaction (PCR) is a process in which DNA sequences are amplified
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{
"page_id": 1708182,
"source": null,
"title": "Designer baby"
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to produce many more copies of the same segment, allowing screening of large samples and identification of specific genes. The process is often used when screening for monogenic disorders, such as cystic fibrosis. Another screening technique, fluorescent in situ hybridisation (FISH) uses fluorescent probes which specifically bind to highly complementary sequences on chromosomes, which can then be identified using fluorescence microscopy. FISH is often used when screening for chromosomal abnormalities such as aneuploidy, making it a useful tool when screening for disorders such as Down syndrome. Following the screening, embryos with the desired trait (or lacking an undesired trait such as a mutation) are transferred into the mother's uterus, then allowed to develop naturally. === Regulation === PGD regulation is determined by individual countries' governments, with some prohibiting its use entirely, including in Austria, China, and Ireland. In many countries, PGD is permitted under very stringent conditions for medical use only, as is the case in France, Switzerland, Italy and the United Kingdom. Whilst PGD in Italy and Switzerland is only permitted under certain circumstances, there is no clear set of specifications under which PGD can be carried out, and selection of embryos based on sex is not permitted. In France and the UK, regulations are much more detailed, with dedicated agencies setting out framework for PGD. Selection based on sex is permitted under certain circumstances, and genetic disorders for which PGD is permitted are detailed by the countries' respective agencies. In contrast, the United States federal law does not regulate PGD, with no dedicated agencies specifying regulatory framework by which healthcare professionals must abide. Elective sex selection is permitted, accounting for around 9% of all PGD cases in the U.S., as is selection for desired conditions such as deafness or dwarfism. === Polygenic risk score (PRS) screening === In
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the 2020s, companies such as Orchid Bioscience began offering polygenic risk scores (PRS) analysis for embryos during IVF. PRS estimates the likelihood of complex traits, such as height and intelligence, or diseases like diabetes, by summarizing data from thousands of genetic markers. However, many geneticists and bioethicists argue that PRS predictions lack clinical validity and promote eugenic practices that can prioritize socially desirable characteristics. They believe this approach risks reinforcing societal biases that may not be realistic and limits the autonomy and identity of the child as it restricts their life within a framework of genetic predictions. A 2021 study found that PRS explains only 5-10% of variance in educational attainment, highlighting its limited predictive ability. == Pre-implantation Genetic Testing == Based on the specific analysis conducted: PGT-M (Preimplantation Genetic Testing for monogenic diseases) is a technique used during IVF to detect hereditary diseases caused by mutations or alterations of the DNA sequence with a single gene. PGT-A (Preimplantation Genetic Testing for aneuploidy): It is used to diagnose numerical abnormalities (aneuploidies). == Human germline engineering == Human germline engineering is a process in which the human genome is edited within a germ cell, such as a sperm cell or oocyte (causing heritable changes), or in the zygote or embryo following fertilization. Germline engineering results in changes in the genome being incorporated into every cell in the body of the offspring (or of the individual following embryonic germline engineering). This process differs from somatic cell engineering, which does not result in heritable changes. Most human germline editing is performed on individual cells and non-viable embryos, which are destroyed at a very early stage of development. In November 2018, however, a Chinese scientist, He Jiankui, announced that he had created the first human germline genetically edited babies. Genetic engineering relies on a
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"page_id": 1708182,
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knowledge of human genetic information, made possible by research such as the Human Genome Project, which identified the position and function of all the genes in the human genome. As of 2019, high-throughput sequencing methods allow genome sequencing to be conducted very rapidly, making the technology widely available to researchers. Germline modification is typically accomplished through techniques which incorporate a new gene into the genome of the embryo or germ cell in a specific location. This can be achieved by introducing the desired DNA directly to the cell for it to be incorporated, or by replacing a gene with one of interest. These techniques can also be used to remove or disrupt unwanted genes, such as ones containing mutated sequences. Whilst germline engineering has mostly been performed in mammals and other animals, research on human cells in vitro is becoming more common. Most commonly used in human cells are germline gene therapy and the engineered nuclease system CRISPR/Cas9. === Germline gene modification === Gene therapy is the delivery of a nucleic acid (usually DNA or RNA) into a cell as a pharmaceutical agent to treat disease. Most commonly it is carried out using a vector, which transports the nucleic acid (usually DNA encoding a therapeutic gene) into the target cell. A vector can transduce a desired copy of a gene into a specific location to be expressed as required. Alternatively, a transgene can be inserted to deliberately disrupt an unwanted or mutated gene, preventing transcription and translation of the faulty gene products to avoid a disease phenotype. Gene therapy in patients is typically carried out on somatic cells in order to treat conditions such as some leukaemias and vascular diseases. Human germline gene therapy in contrast is restricted to in vitro experiments in some countries, whilst others prohibited it entirely,
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including Australia, Canada, Germany and Switzerland. Whilst the National Institutes of Health in the US does not currently allow in utero germline gene transfer clinical trials, in vitro trials are permitted. The NIH guidelines state that further studies are required regarding the safety of gene transfer protocols before in utero research is considered, requiring current studies to provide demonstrable efficacy of the techniques in the laboratory. Research of this sort is currently using non-viable embryos to investigate the efficacy of germline gene therapy in treatment of disorders such as inherited mitochondrial diseases. Gene transfer to cells is usually by vector delivery. Vectors are typically divided into two classes – viral and non-viral. ==== Viral vectors ==== Viruses infect cells by transducing their genetic material into a host's cell, using the host's cellular machinery to generate viral proteins needed for replication and proliferation. By modifying viruses and loading them with the therapeutic DNA or RNA of interest, it is possible to use these as a vector to provide delivery of the desired gene into the cell. Retroviruses are some of the most commonly used viral vectors, as they not only introduce their genetic material into the host cell, but also copy it into the host's genome. In the context of gene therapy, this allows permanent integration of the gene of interest into the patient's own DNA, providing longer lasting effects. Viral vectors work efficiently and are mostly safe but present with some complications, contributing to the stringency of regulation on gene therapy. Despite partial inactivation of viral vectors in gene therapy research, they can still be immunogenic and elicit an immune response. This can impede viral delivery of the gene of interest, as well as cause complications for the patient themselves when used clinically, especially in those who already have a
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"page_id": 1708182,
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serious genetic illness. Another difficulty is the possibility that some viruses will randomly integrate their nucleic acids into the genome, which can interrupt gene function and generate new mutations. This is a significant concern when considering germline gene therapy, due to the potential to generate new mutations in the embryo or offspring. ==== Non-viral vectors ==== Non-viral methods of nucleic acid transfection involved injecting a naked DNA plasmid into cell for incorporation into the genome. This method used to be relatively ineffective with low frequency of integration, however, efficiency has since greatly improved, using methods to enhance the delivery of the gene of interest into cells. Furthermore, non-viral vectors are simple to produce on a large scale and are not highly immunogenic. Some non-viral methods are detailed below: Electroporation is a technique in which high voltage pulses are used to carry DNA into the target cell across the membrane. The method is believed to function due to the formation of pores across the membrane, but although these are temporary, electroporation results in a high rate of cell death which has limited its use. An improved version of this technology, electron-avalanche transfection, has since been developed, which involves shorter (microsecond) high voltage pulses which result in more effective DNA integration and less cellular damage. The gene gun is a physical method of DNA transfection, where a DNA plasmid is loaded onto a particle of heavy metal (usually gold) and loaded onto the 'gun'. The device generates a force to penetrate the cell membrane, allowing the DNA to enter whilst retaining the metal particle. Oligonucleotides are used as chemical vectors for gene therapy, often used to disrupt mutated DNA sequences to prevent their expression. Disruption in this way can be achieved by introduction of small RNA molecules, called siRNA, which signal cellular
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"page_id": 1708182,
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machinery to cleave the unwanted mRNA sequences to prevent their transcription. Another method utilises double-stranded oligonucleotides, which bind transcription factors required for transcription of the target gene. By competitively binding these transcription factors, the oligonucleotides can prevent the gene's expression. === ZFNs === Zinc-finger nucleases (ZFNs) are enzymes generated by fusing a zinc finger DNA-binding domain to a DNA-cleavage domain. Zinc finger recognizes between 9 and 18 bases of sequence. Thus by mixing those modules, it becomes easier to target any sequence researchers wish to alter ideally within complex genomes. A ZFN is a macromolecular complex formed by monomers in which each subunit contains a zinc domain and a FokI endonuclease domain. The FokI domains must dimerize for activities, thus narrowing target area by ensuring that two close DNA-binding events occurs. The resulting cleavage event enables most genome-editing technologies to work. After a break is created, the cell seeks to repair it. A method is NHEJ, in which the cell polishes the two ends of broken DNA and seals them back together, often producing a frame shift. An alternative method is homology-directed repairs. The cell tries to fix the damage by using a copy of the sequence as a backup. By supplying their own template, researcher can have the system to insert a desired sequence instead. The success of using ZFNs in gene therapy depends on the insertion of genes to the chromosomal target area without causing damage to the cell. Custom ZFNs offer an option in human cells for gene correction. === TALENs === There is a method called TALENs that targets singular nucleotides. TALENs stand for transcription activator-like effector nucleases. TALENs are made by TAL effector DNA-binding domain to a DNA cleavage domain. All these methods work by as the TALENs are arranged. TALENs are "built from arrays
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of 33-35 amino acid modules…by assembling those arrays…researchers can target any sequence they like". This event is referred as Repeat Variable Diresidue (RVD). The relationship between the amino acids enables researchers to engineer a specific DNA domain. The TALEN enzymes are designed to remove specific parts of the DNA strands and replace the section; which enables edits to be made. TALENs can be used to edit genomes using non-homologous end joining (NHEJ) and homology directed repair. === CRISPR/Cas9 === The CRISPR/Cas9 system (CRISPR – Clustered Regularly Interspaced Short Palindromic Repeats, Cas9 – CRISPR-associated protein 9) is a genome editing technology based on the bacterial antiviral CRISPR/Cas system. The bacterial system has evolved to recognize viral nucleic acid sequences and cut these sequences upon recognition, damaging infecting viruses. The gene editing technology uses a simplified version of this process, manipulating the components of the bacterial system to allow location-specific gene editing. The CRISPR/Cas9 system broadly consists of two major components – the Cas9 nuclease and a guide RNA (gRNA). The gRNA contains a Cas-binding sequence and a ~20 nucleotide spacer sequence, which is specific and complementary to the target sequence on the DNA of interest. Editing specificity can therefore be changed by modifying this spacer sequence. Upon system delivery to a cell, Cas9 and the gRNA bind, forming a ribonucleoprotein complex. This causes a conformational change in Cas9, allowing it to cleave DNA if the gRNA spacer sequence binds with sufficient homology to a particular sequence in the host genome. When the gRNA binds to the target sequence, Cas will cleave the locus, causing a double-strand break (DSB). The resulting DSB can be repaired by one of two mechanisms – Non-Homologous End Joining (NHEJ) - an efficient but error-prone mechanism, which often introduces insertions and deletions (indels) at the DSB site.
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This means it is often used in knockout experiments to disrupt genes and introduce loss of function mutations. Homology Directed Repair (HDR) - a less efficient but high-fidelity process which is used to introduce precise modifications into the target sequence. The process requires adding a DNA repair template including a desired sequence, which the cell's machinery uses to repair the DSB, incorporating the sequence of interest into the genome. Since NHEJ is more efficient than HDR, most DSBs will be repaired via NHEJ, introducing gene knockouts. To increase frequency of HDR, inhibiting genes associated with NHEJ and performing the process in particular cell cycle phases (primarily S and G2) appear effective. CRISPR/Cas9 is an effective way of manipulating the genome in vivo in animals as well as in human cells in vitro, but some issues with the efficiency of delivery and editing mean that it is not considered safe for use in viable human embryos or the body's germ cells. As well as the higher efficiency of NHEJ making inadvertent knockouts likely, CRISPR can introduce DSBs to unintended parts of the genome, called off-target effects. These arise due to the spacer sequence of the gRNA conferring sufficient sequence homology to random loci in the genome, which can introduce random mutations throughout. If performed in germline cells, mutations could be introduced to all the cells of a developing embryo. There are developments to prevent unintended consequences otherwise known as off-target effects due to gene editing. There is a race to develop new gene editing technologies that prevent off-target effects from occurring with some of the technologies being known as biased off-target detection, and Anti-CRISPR Proteins. For biased off-target effects detection, there are several tools to predict the locations where off-target effects may take place. Within the technology of biased off-target effects
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detection, there are two main models, Alignment Based Models that involve having the sequences of gRNA being aligned with sequences of genome, after which then the off-target locations are predicted. The second model is known as the Scoring-Based Model where each piece of gRNA is scored for their off-target effects in accordance with their positioning. ==== Regulation on CRISPR use ==== In 2015, the International Summit on Human Gene Editing was held in Washington D.C., hosted by scientists from China, the UK and the U.S. The summit concluded that genome editing of somatic cells using CRISPR and other genome editing tools would be allowed to proceed under FDA regulations, but human germline engineering would not be pursued. In February 2016, scientists at the Francis Crick Institute in London were given a license permitting them to edit human embryos using CRISPR to investigate early development. Regulations were imposed to prevent the researchers from implanting the embryos and to ensure experiments were stopped and embryos destroyed after seven days. In November 2018, Chinese scientist He Jiankui announced that he had performed the first germline engineering on viable human embryos, which have since been brought to term. The research claims received significant criticism, and Chinese authorities suspended He's research activity. Following the event, scientists and government bodies have called for more stringent regulations to be imposed on the use of CRISPR technology in embryos, with some calling for a global moratorium on germline genetic engineering. Chinese authorities have announced stricter controls will be imposed, with Communist Party general secretary Xi Jinping and government premier Li Keqiang calling for new gene-editing legislations to be introduced. As of January 2020, germline genetic alterations are prohibited in 24 countries by law and also in 9 other countries by their guidelines. The Council of Europe's Convention on
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Human Rights and Biomedicine, also known as the Oviedo Convention, has stated in its article 13 "Interventions on the human genome" as follows: "An intervention seeking to modify the human genome may only be undertaken for preventive, diagnostic or therapeutic purposes and only if its aim is not to introduce any modification in the genome of any descendants". Nonetheless, wide public debate has emerged, targeting the fact that the Oviedo Convention Article 13 should be revisited and renewed, especially due to the fact that it was constructed in 1997 and may be out of date, given recent technological advancements in the field of genetic engineering. In 2020, Canada amended its Human Reproduction Act to criminalize heritable genome edits, in which penalties include fines up to CAD$500,000 and 10 years imprisonment. The World Health Organization established a global registry for such practices in 2021 to enhance transparency ==== Recent Advancements ==== Following the 2018 incident of the first CRISPR-edited babies by He Jiankui, efforts to strengthen regulatory oversights have helped to improve the precision of the procedure. These advancements in genome editing now reduce off-target effects, allowing for more controlled and predictable modifications. Techniques such as prime editing and base editing have offered greater accuracy and fewer unintended mutations. Even so, ethical concerns persist as regulatory enforcement remains inconsistent in nations without strict biosafety laws == Lulu and Nana controversy == The Lulu and Nana controversy refers to the two Chinese twin girls born in November 2018, who had been genetically modified as embryos by the Chinese scientist He Jiankui. The twins are believed to be the first genetically modified babies. The girls' parents had participated in a clinical project run by He, which involved IVF, PGD and genome editing procedures in an attempt to edit the gene CCR5. CCR5 encodes
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"page_id": 1708182,
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a protein used by HIV to enter host cells, so by introducing a specific mutation into the gene CCR5 Δ32 He claimed that the process would confer innate resistance to HIV. The project run by He recruited couples wanting children where the man was HIV-positive and the woman uninfected. During the project, He performed IVF with sperm and eggs from the couples and then introduced the CCR5 Δ32 mutation into the genomes of the embryos using CRISPR/Cas9. He then used PGD on the edited embryos during which he sequenced biopsied cells to identify whether the mutation had been successfully introduced. He reported some mosaicism in the embryos, whereby the mutation had integrated into some cells but not all, suggesting the offspring would not be entirely protected against HIV. He claimed that during the PGD and throughout the pregnancy, fetal DNA was sequenced to check for off-target errors introduced by the CRISPR/Cas9 technology, however the NIH released a statement in which they announced "the possibility of damaging off-target effects has not been satisfactorily explored". The girls were born in early November 2018, and were reported by He to be healthy. His research was conducted in secret until November 2018, when documents were posted on the Chinese clinical trials registry and MIT Technology Review published a story about the project. Following this, He was interviewed by the Associated Press and presented his work on 27 November at the Second International Human Genome Editing Summit which was held in Hong Kong. Although the information available about this experiment is relatively limited, it is deemed that the scientist erred against many ethical, social and moral rules but also China's guidelines and regulations, which prohibited germ-line genetic modifications in human embryos, while conducting this trial. From a technological point of view, the CRISPR/Cas9 technique is
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"source": null,
"title": "Designer baby"
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|
one of the most precise and least expensive methods of gene modification to this day, whereas there are still a number of limitations that keep the technique from being labelled as safe and efficient. During the First International Summit on Human Gene Editing in 2015 the participants agreed that a halt must be set on germline genetic alterations in clinical settings unless and until: "(1) the relevant safety and efficacy issues have been resolved, based on appropriate understanding and balancing of risks, potential benefits, and alternatives, and (2) there is broad societal consensus about the appropriateness of the proposed application". However, during the second International Summit in 2018 the topic was once again brought up by stating: "Progress over the last three years and the discussions at the current summit, however, suggest that it is time to define a rigorous, responsible translational pathway toward such trials". Inciting that the ethical and legal aspects should indeed be revisited G. Daley, representative of the summit's management and Dean of Harvard Medical School depicted Dr. He's experiment as "a wrong turn on the right path". The experiment was met with widespread criticism and was very controversial, globally as well as in China. Several bioethicists, researchers and medical professionals have released statements condemning the research, including Nobel laureate David Baltimore who deemed the work "irresponsible" and one pioneer of the CRISPR/Cas9 technology, biochemist Jennifer Doudna at University of California, Berkeley. The director of the NIH, Francis S. Collins stated that the "medical necessity for inactivation of CCR5 in these infants is utterly unconvincing" and condemned He Jiankui and his research team for 'irresponsible work'. Other scientists, including geneticist George Church of Harvard University suggested gene editing for disease resistance was "justifiable" but expressed reservations regarding the conduct of He's work. The Safe Genes program
|
{
"page_id": 1708182,
"source": null,
"title": "Designer baby"
}
|
by DARPA has the goal to protect soldiers against gene editing war tactics. They receive information from ethical experts to better predict and understand future and current potential gene editing issues. The World Health Organization has launched a global registry to track research on human genome editing, after a call to halt all work on genome editing. The Chinese Academy of Medical Sciences responded to the controversy in the journal Lancet, condemning He for violating ethical guidelines documented by the government and emphasizing that germline engineering should not be performed for reproductive purposes. The academy ensured they would "issue further operational, technical and ethical guidelines as soon as possible" to impose tighter regulation on human embryo editing. As of 2023, He has resumed research in genetic medicine after his three year imprisonment by the Chinese government for his "illegal medical practices." He has since shifted his focus to the treatment of genetic diseases, including Duchenne muscular dystrophy (DMD), after his release. Despite backlashes from the Lulu and Nana case, he has been appointed as the inaugural director of the Genetic Medicine Institute at Wuchang University of Technology in Wuhan in September 2023. He's application to work in Hong Kong was initially granted a visa, however, it was later revoked due to ongoing ethical and legal challenges surrounding his career. == Ethical considerations == Editing embryos, germ cells and the generation of designer babies is the subject of ethical debate, as a result of the implications in modifying genomic information in a heritable manner. This includes arguments over unbalanced gender selection and gamete selection. Despite regulations set by individual countries' governing bodies, the absence of a standardized regulatory framework leads to frequent discourse in discussion of germline engineering among scientists, ethicists and the general public. Arthur Caplan, the head of the
|
{
"page_id": 1708182,
"source": null,
"title": "Designer baby"
}
|
Division of Bioethics at New York University suggests that establishing an international group to set guidelines for the topic would greatly benefit global discussion and proposes instating "religious and ethics and legal leaders" to impose well-informed regulations. In many countries, editing embryos and germline modification for reproductive use is illegal. As of 2017, the U.S. restricts the use of germline modification and the procedure is under heavy regulation by the FDA and NIH. The American National Academy of Sciences and National Academy of Medicine indicated they would provide qualified support for human germline editing "for serious conditions under stringent oversight", should safety and efficiency issues be addressed. In 2019, World Health Organization called human germline genome editing as "irresponsible". Since genetic modification poses risk to any organism, researchers and medical professionals must give the prospect of germline engineering careful consideration. The main ethical concern is that these types of treatments will produce a change that can be passed down to future generations and therefore any error, known or unknown, will also be passed down and will affect the offspring. Theologian Ronald Green of Dartmouth College has raised concern that this could result in a decrease in genetic diversity and the accidental introduction of new diseases in the future. When considering support for research into germline engineering, ethicists have often suggested that it can be considered unethical not to consider a technology that could improve the lives of children who would be born with congenital disorders. Geneticist George Church claims that he does not expect germline engineering to increase societal disadvantage, and recommends lowering costs and improving education surrounding the topic to dispel these views. He emphasizes that allowing germline engineering in children who would otherwise be born with congenital defects could save around 5% of babies from living with potentially
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{
"page_id": 1708182,
"source": null,
"title": "Designer baby"
}
|
avoidable diseases. Jackie Leach Scully, professor of social and bioethics at Newcastle University, acknowledges that the prospect of designer babies could leave those living with diseases and unable to afford the technology feeling marginalized and without medical support. However, Professor Leach Scully also suggests that germline editing provides the option for parents "to try and secure what they think is the best start in life" and does not believe it should be ruled out. Similarly, Nick Bostrom, an Oxford philosopher known for his work on the risks of artificial intelligence, proposed that "super-enhanced" individuals could "change the world through their creativity and discoveries, and through innovations that everyone else would use". Many bioethicists emphasize that germline engineering is usually considered in the best interest of a child, therefore associated should be supported. Dr James Hughes, a bioethicist at Trinity College, Connecticut, suggests that the decision may not differ greatly from others made by parents which are well accepted – choosing with whom to have a child and using contraception to denote when a child is conceived. Julian Savulescu, a bioethicist and philosopher at Oxford University believes parents "should allow selection for non‐disease genes even if this maintains or increases social inequality", coining the term procreative beneficence to describe the idea that the children "expected to have the best life" should be selected. The Nuffield Council on Bioethics said in 2017 that there was "no reason to rule out" changing the DNA of a human embryo if performed in the child's interest, but stressed that this was only provided that it did not contribute to societal inequality. Furthermore, Nuffield Council in 2018 detailed applications, which would preserve equality and benefit humanity, such as elimination of hereditary disorders and adjusting to warmer climate. Philosopher and Director of Bioethics at non-profit Invincible Wellbeing
|
{
"page_id": 1708182,
"source": null,
"title": "Designer baby"
}
|
David Pearce argues that "the question [of designer babies] comes down to an analysis of risk-reward ratios - and our basic ethical values, themselves shaped by our evolutionary past." According to Pearce,"it's worth recalling that each act of old-fashioned sexual reproduction is itself an untested genetic experiment", often compromising a child's wellbeing and pro-social capacities even if the child grows in a healthy environment. Pearce thinks that as technology matures, more people may find it unacceptable to rely on "genetic roulette of natural selection". Conversely, several concerns have been raised regarding the possibility of generating designer babies, especially concerning the inefficiencies currently presented by the technologies. Green stated that although the technology was "unavoidably in our future", he foresaw "serious errors and health problems as unknown genetic side effects in 'edited' children" arise. Furthermore, Green warned against the possibility that "the well-to-do" could more easily access the technologies "..that make them even better off". This concern regarding germline editing exacerbating a societal and financial divide is shared amongst other researches, with the chair of the Nuffield Bioethics Council Professor Karen Yeung stressing that if funding of the procedures "were to exacerbate social injustice, in our view that would not be an ethical approach". Since 2020, there have been discussions about American studies that use embryos without embryonic implantation with the CRISPR/Cas9 technique that had been modified with HDR (homology-directed repair), and the conclusions from the results were that gene editing technologies are currently not mature enough for real world use and that there is a need for more studies that generate safe results over a longer period of time. An article in the journal Bioscience Reports discussed how health in terms of genetics is not straightforward and thus there should be extensive deliberation for operations involving gene editing when the
|
{
"page_id": 1708182,
"source": null,
"title": "Designer baby"
}
|
technology gets mature enough for real world use, where all of the potential effects are known on a case-by-case basis to prevent undesired effects on the subject or patient being operated on. Social aspects also raise concern, as highlighted by Josephine Quintavelle, director of Comment on Reproductive Ethics at Queen Mary University of London, who states that selecting children's traits is "turning parenthood into an unhealthy model of self-gratification rather than a relationship". In addition, some disability advocates argue that selecting against traits like deafness reinforces societal stigma. This promotes a narrow definition of normalcy. They also warn of the consequences of increased inequality if genetic enhancements become solely accessible to the wealthy. One major worry among scientists, including Marcy Darnovsky at the Center for Genetics and Society in California, is that permitting germline engineering for correction of disease phenotypes is likely to lead to its use for cosmetic purposes and enhancement. Meanwhile, Henry Greely, a bioethicist at Stanford University in California, states that "almost everything you can accomplish by gene editing, you can accomplish by embryo selection", suggesting the risks undertaken by germline engineering may not be necessary. Alongside this, Greely emphasizes that the beliefs that genetic engineering will lead to enhancement are unfounded, and that claims that we will enhance intelligence and personality are far off – "we just don't know enough and are unlikely to for a long time – or maybe for ever". === Religious Opinions === Religious worries also arise over the possibility of editing human embryos. In a survey conducted by the Pew Research Centre, it was found that only a third of the Americans surveyed who identified as strongly Christian approved of germline editing. Catholic leaders are in the middle ground. This stance is because, according to Catholicism, a baby is a gift
|
{
"page_id": 1708182,
"source": null,
"title": "Designer baby"
}
|
from God, and Catholics believe that people are created to be perfect in God's eyes. Thus, altering the genetic makeup of an infant is unnatural. In 1984, Pope John Paul II addressed that genetic manipulation in aiming to heal diseases is acceptable in the Church. He stated that it "will be considered in principle as desirable provided that it tends to the real promotion of the personal well-being of man, without harming his integrity or worsening his life conditions". However, it is unacceptable if designer babies are used to create a super/superior race including cloning humans. The Catholic Church rejects human cloning even if its purpose is to produce organs for therapeutic usage. The Vatican has stated that "The fundamental values connected with the techniques of artificial human procreation are two: the life of the human being called into existence and the special nature of the transmission of human life in marriage". According to them, it violates the dignity of the individual and is morally illicit. In Islam, a positive view towards genetic engineering is based on the general principle that Islam aims at facilitating human life. However, according to Islamic law, gene editing can only be permitted if several conditions are met, such as definitively proving the safety and efficacy of the procedures in question. Nevertheless, some researchers consider genetic engineering a promising field of research that is capable of meeting the conditions mentioned above in the future. In addition, a negative view comes from the process used to create a designer baby. Oftentimes, it involves the destruction of some embryos, which may be against the teaching of the Qur'an, Hadith, and Shari'ah law, that stress the responsibility to protect human life. However, there is a consensus among Islamic scholars that ensoulment occurs 120 days after conception, well after
|
{
"page_id": 1708182,
"source": null,
"title": "Designer baby"
}
|
the embryonic stage of development. Some scholars see the procedure as "acting like God/Allah" and a violation of the religious prohibition against "changing God's/Allah's creation". Other arguments include the possibility of introducing unforeseen mutations and genetic deficiencies, which would be counter to the principle of protecting human life, and undermining the traditional institutions of lineage, marriage and childbirth. With the idea that parents could choose the gender of their child, some Muslims believe that humans have no decision to choose the gender, and that "gender selection is only up to God". === Public Opinon === Surveys of public attitudes towards designer babies and genetic editing have revealed concerns against the technological advancements, showing fears of eugenics and socioeconomic inequality. A 2018 Pew Research Center study found that 72% of the U.S. adults believed non-medical uses of the technologies would be taking it too far, with many drawing parallels to historical Eugenic practices. Similarly, a 2020 international survey published in Science (journal) reported widespread public concern about the unintended health consequences of genetically modified children and the potential erosion of genetic diversity. Scientists and policymakers have called for a more inclusive and transparent approach in regulation of the technologies, which underscores the need for collaborative governance frameworks and communication between scientists, policymakers, and the people. == See also == == References == == Further reading ==
|
{
"page_id": 1708182,
"source": null,
"title": "Designer baby"
}
|
Biodilution, sometimes referred to as bloom dilution, is the decrease in concentration of an element or pollutant with an increase in trophic level. This effect is primarily observed during algal blooms whereby an increase in algal biomass reduces the concentration of pollutants in organisms higher up in the food chain, like zooplankton or daphnia. The primary elements and pollutants of concern are heavy metals such as mercury, cadmium, and lead. These toxins have been shown to bioaccumulate up a food web. In some cases, metals, such as mercury, can biomagnify. This is a major concern since methylmercury, the most toxic mercury species, can be found in high concentrations in human-consumed fish and other aquatic organisms. Numerous studies have linked lower mercury concentrations in zooplankton found in eutrophic (nutrient-rich and highly productive) as compared to oligotrophic (low nutrient) aquatic environments. Nutrient enrichment (mainly phosphorus and nitrogen) reduce the input of mercury, and other heavy metals, into aquatic food webs through this biodilution effect. Primary producers, such as phytoplankton, uptake these heavy metals and accumulate them into their cells. The higher the population of phytoplankton, the less concentrated these pollutants will be in their cells. Once consumed by primary consumers, such as zooplankton, these phytoplankton-bound pollutants are incorporated into the consumer’s cells. Higher phytoplankton biomass means a lower concentration of pollutants accumulated by the zooplankton, and so on up the food web. This effect causes an overall dilution of the original concentration up the food web. That is, the concentration of a pollutant will be lower in the zooplankton than the phytoplankton in a high bloom condition. Although most biodilution studies have been on freshwater environments, biodilution has been shown to occur in the marine environment as well. The Northwater Polynya, located in Baffin Bay, was found to have a negative correlation
|
{
"page_id": 29102236,
"source": null,
"title": "Biodilution"
}
|
of cadmium, lead, and nickel with an increase in trophic level Cadmium and lead are both non-essential metals that will compete for calcium within an organism, which is detrimental for organism growth. Most studies measure bioaccumulation and biodilution using the δ15N isotope of nitrogen. The δ15N isotopic signature is enriched up the food web. A predator will have a higher δ15N as compared to its prey. This trend allows the trophic position of an organism to be derived. Coupled to the concentration of a specific pollutant, such as mercury, the concentration verses trophic position can be accessed. While most heavy metals bioaccumulate, under certain conditions, heavy metals and organic pollutants have the potential to biodilute, making a higher organism less exposed to the toxin. == References ==
|
{
"page_id": 29102236,
"source": null,
"title": "Biodilution"
}
|
The osmotic stress technique is a method for measuring the effect of water on biological molecules, particularly enzymes. Just as the properties of molecules can depend on the presence of salts, pH, and temperature, they can depend significantly on the amount of water present. In the osmotic stress technique, flexible neutral polymers such as polyethylene glycol and dextran are added to the solution containing the molecule of interest, replacing a significant part of the water. The amount of water replaced is characterized by the chemical activity of water. == See also == Osmotic shock == References == Tables containing osmotic pressure data for use in the osmotic stress technique
|
{
"page_id": 1249440,
"source": null,
"title": "Osmotic stress technique"
}
|
The molecular formula C6H9N3 may refer to: Ampyzine, a central nervous system stimulant IDPN (chemical), a neurotoxin with ototoxic and hepatotoxic effects Cyanomethine, trimer of acetonitrile
|
{
"page_id": 43782305,
"source": null,
"title": "C6H9N3"
}
|
A thermodynamic instrument is any device for the measurement of thermodynamic systems. In order for a thermodynamic parameter or physical quantity to be truly defined, a technique for its measurement must be specified. For example, the ultimate definition of temperature is "what a thermometer reads". The question follows – what is a thermometer? There are two types of thermodynamic instruments: the meter and the reservoir. A thermodynamic meter is any device which measures any parameter of a thermodynamic system. A thermodynamic reservoir is a system which is so large that it does not appreciably alter its state parameters when brought into contact with the test system. == Overview == Two general complementary tools are the meter and the reservoir. It is important that these two types of instruments are distinct. A meter does not perform its task accurately if it behaves like a reservoir of the state variable it is trying to measure. If, for example, a thermometer, were to act as a temperature reservoir it would alter the temperature of the system being measured, and the reading would be incorrect. Ideal meters have no effect on the state variables of the system they are measuring. == Thermodynamic meters == A meter is a thermodynamic system which displays some aspect of its thermodynamic state to the observer. The nature of its contact with the system it is measuring can be controlled, and it is sufficiently small that it does not appreciably affect the state of the system being measured. The theoretical thermometer described below is just such a meter. In some cases, the thermodynamic parameter is actually defined in terms of an idealized measuring instrument. For example, the zeroth law of thermodynamics states that if two bodies are in thermal equilibrium with a third body, they are also in thermal
|
{
"page_id": 3281057,
"source": null,
"title": "Thermodynamic instruments"
}
|
equilibrium with each other. This principle, as noted by James Maxwell in 1872, asserts that it is possible to measure temperature. An idealized thermometer is a sample of an ideal gas at constant pressure. From the ideal gas law, the volume of such a sample can be used as an indicator of temperature; in this manner it defines temperature. Although pressure is defined mechanically, a pressure-measuring device called a barometer may also be constructed from a sample of an ideal gas held at a constant temperature. A calorimeter is a device which is used to measure and define the internal energy of a system. Some common thermodynamic meters are: Thermometer – a device which measures temperature as described above Barometer – a device which measures pressure, most notably atmospheric pressure. An ideal gas barometer may be constructed by mechanically connecting an ideal gas to the system being measured, while thermally insulating it. The volume will then measure pressure, by the ideal gas equation P = NkT/V. Calorimeter – a device which measures the heat energy added to a system. A simple calorimeter is simply a thermometer connected to a thermally isolated system. == Thermodynamic reservoirs == A reservoir is a thermodynamic system which controls the state of a system, usually by "imposing" itself upon the system being controlled. This means that the nature of its contact with the system can be controlled. A reservoir is so large that its thermodynamic state is not appreciably affected by the state of the system being controlled. The term "atmospheric pressure" in the below description of a theoretical thermometer is essentially a "pressure reservoir" which imposes atmospheric pressure upon the thermometer. Some common reservoirs are: Pressure reservoir – by far the most common pressure reservoir is the Earth's atmosphere. Temperature reservoir – A large
|
{
"page_id": 3281057,
"source": null,
"title": "Thermodynamic instruments"
}
|
quantity of water at its triple point forms an effective temperature reservoir. == Theory == Let's assume that we understand mechanics well enough to understand and measure volume, area, mass, and force. These may be combined to understand the concept of pressure, which is force per unit area and density, which is mass per unit volume. It has been experimentally determined that, at low enough pressures and densities, all gases behave as ideal gases. The behavior of an ideal gas is given by the ideal gas law: P V = N k T {\displaystyle PV=NkT\,} where P is pressure, V is volume, N is the number of particles (total mass divided by mass per particle), k is the Boltzmann constant, and T is temperature. In fact, this equation is more than a phenomenological equation, it gives an operational, or experimental, definition of temperature. A thermometer is a tool that measures temperature - a primitive thermometer would simply be a small container of an ideal gas, that was allowed to expand against atmospheric pressure. If we bring it into thermal contact with the system whose temperature we wish to measure, wait until it equilibrates, and then measure the volume of the thermometer, we will be able to calculate the temperature of the system in question via T = PV/Nk. Hopefully, the thermometer will be small enough that it does not appreciably alter the temperature of the system it is measuring, and also that the atmospheric pressure is not affected by the expansion of the thermometer. The ideal gas thermometer can be defined more precisely by saying it is a system containing an ideal gas, which is thermally connected to the system it is measuring, while being dynamically and materially insulated from it. It is simultaneously dynamically connected to an external pressure
|
{
"page_id": 3281057,
"source": null,
"title": "Thermodynamic instruments"
}
|
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