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A lysophosphatidylserine is a lysophospholipid . Various lysophosphatidylserines trigger TLR 2 . [ 1 ] They can also modulate T cell function via suppression of Interleukin_2 (IL-2) production in CD4 T cells. [ 2 ] They can also trigger mast cell degranulation. [ 3 ] They interact with three G protein-coupled receptors (GPCRs), LPS1/ GPR34 , LPS2/ P2Y10 , and LPS3/ GPR174 . [ 2 ]
A recent study showed that lysophosphatidylserines do not stimulate normal leukocytes . [ 4 ] They also enhances glucose transport, lowering blood glucose levels while leaving secretion of insulin unaffected. [ 5 ]
This biochemistry article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Lysophosphatidylserine |
A lysosome ( /ˈlaɪsəˌsoʊm/ ) is a membrane-bound organelle that is found in all mammalian cells, with the exception of red blood cells ( erythrocytes ). [ 1 ] There are normally hundreds of lysosomes in the cytosol, where they function as the cell’s degradation center. Their primary responsibility is catabolic degradation of proteins, polysaccharides and lipids into their respective building-block molecules: amino acids, monosaccharides, and free fatty acids. The breakdown is done by various enzymes, for example proteases, glycosidases and lipases. [ 2 ]
With an acidic lumen limited by a single-bilayer lipid membrane, the lysosome holds an environment isolated from the rest of the cell. The lower pH creates optimal conditions for the over 60 different hydrolases inside. [ 3 ]
Lysosomes receive extracellular particles through endocytosis , and intracellular components through autophagy . [ 2 ] They can also fuse with the plasma membrane and secrete their contents, a process called lysosomal exocytosis. [ 3 ] After degradation lysosomal products are transported out of the lysosome through specific membrane proteins or via vesicular membrane trafficking to be recycled or to be utilized for energy. [ 2 ]
Aside from cellular clearance and secretion, lysosomes mediate biological processes like plasma membrane repair, cell homeostasis , energy metabolism, cell signaling, and the immune response. [ 3 ]
Christian de Duve , a Belgian scientist at the Laboratory of Physiological Chemistry at the Catholic University of Louvain , is credited with discovering lysosomes in the 1950s. De Duve and his team were studying the distribution of hydrolytic enzymes such as acid phosphatase within cells, using cell fractionation methods to isolate subcellular components. De Duve and his team identified an unknown organelle that was rich in acid phosphatase. This led them to propose the existence of lysosomes as membrane bound organelles containing digestive enzymes capable of breaking down a variety of biological molecules.
Using differential centrifugation and enzyme activity assays, the team confirmed the hypothesis and understood that these organelles play a crucial role in intracellular digestion processes, such as phagocytosis and autophagy . The presence of digestive enzymes was further validated using electron microscopy. De Duve’s discovery laid the foundation for new research into lysosomal functions and understanding disorders which could lead to undigested materials accumulating in the cell. De Duve was awarded the Nobel Prize in Physiology or Medicine in 1974. [ 4 ] [ 5 ]
Lysosomes vary in shape and size depending on their state, what they are digesting, and the cell type they are in. [ 6 ] Their shape can differ from spherical and ovoid to occasionally tubular. [ 7 ] The size of lysosomes ranges from 0.1-1.2 μm, [ 6 ] with some tubular ones reaching up to 15 μm in phagocytes. Several hundred lysosomes can be found within a single cell. However, upon nutrient deprivation or induced autophagy, their numbers can drop below 50 in a cell. [ 7 ]
Lysosomes contain a variety of enzymes that enable the cell to break down various biomolecules it engulfs, including peptides , nucleic acids , carbohydrates , and lipids . The enzymes responsible for this hydrolysis require an acidic environment for optimal activity, with a pH ranging from ~4.5–5.0. The interior of the lysosome is acidic compared to the slightly basic cytosol (pH 7.2). [ 8 ]
The lysosomal membrane is a phospholipid bilayer with high carbohydrate content from heavily glycosylated membrane proteins. This forms a glycocalyx that protects the cell from the degradative enzymes held within the lysosome. Lysosomal hydrolases are pH-sensitive and do not function properly in the alkaline environment of the cytosol, ensuring that molecules and organelles in the cytosol are not degraded if there is leakage of hydrolytic enzymes from the lysosome.
In addition to breaking down polymers, lysosomes are capable of killing and digesting microbes, cells, or cellular debris. Through cooperation with phagosomes , lysosomes conduct autophagy , clearing out damaged structures and forming simple compounds, which are then used as new building materials. Similarly, lysosomes break down virus particles or bacteria during phagocytosis in macrophages. [ 9 ]
Lysosomes also help detect pathogens through toll-like receptors (TLRs), like TLR7 and TLR9. Microbes can be degraded into antigens, which are then loaded onto MHC molecules and presented to T-cells, a critical part of immune defense. Additionally, lysosomal enzymes can trigger lysosomal-mediated programmed cell death (LM-PCD) if released into the cytoplasm.
To maintain their acidic environment, lysosomes pump protons (H⁺ ions) from the cytosol into the lysosomal lumen via a proton pump in the lysosomal membrane. Vacuolar-ATPases are responsible for the transport of protons, while the counter transport of chloride ions is performed by ClC-7 Cl⁻/H⁺ antiporter. [ 10 ] This mechanism helps maintain a steady acidic environment, as well as ionic homeostasis, within the lysosome. [ 11 ] [ 12 ]
Lysosomes also help balance cellular metabolism by sensing nutrient availability. When nutrients are plentiful, they activate mTOR signaling to support anabolic (biosynthetic) processes. During starvation, lysosomes degrade autophagic material, recycling components to maintain cell survival.
The lysosome is delivered material for degradation via transient interactions or complete fusion, forming endolysosomes and autolysosomes respectively. This way, the lysosomes act as reservoirs for acidic hydrolases, cycling through fusion and fission events with late endosomes and autophagosomes. The actual breakdown of endocytic and autophagic cargo primarily happens within these transient structures—endolysosomes and autolysosomes—under normal physiological conditions. [ 13 ]
Endocytosed materials – such as complex lipids, membrane proteins, and polysaccharides – enter the endocytic pathway; moving first in early endosomes, then in late endosomes containing intraluminal vesicles (also referred to as multivesicular bodies, MVBs). Then they interact with lysosomes, either via full fusion, or via "kiss-and-run" events where brief membrane contact allows content exchange before the organelles separate. The resulting hybrid structure is called an endolysosome. [ 14 ] [ 13 ]
Intracellular materials – like damaged organelles or misfolded proteins – are processed through the autophagic pathway. [ 14 ] Autophagy, or “self-eating,” is a continuous cellular process that delivers cytosolic components to lysosomes for degradation. There are three main types of autophagy: macroautophagy, microautophagy, and chaperone-mediated autophagy (CMA)—each differing in how cargo is delivered to the lysosome. [ 13 ] After merging with lysosomes they create hybrid organelles called autolysosomes. [ 14 ]
The resulting catabolites serve as building-block molecules for synthesizing complex macromolecules. These are exported from lysosomes via specific transporters or through vesicle trafficking. Once released into the cytosol or delivered to the Golgi apparatus, these catabolites are either further metabolized to generate energy or reused in biosynthetic pathways to form new complex molecules. Alternatively, some degradation products can be secreted out of the lysosomes through exocytosis. [ 14 ]
Because catabolic (degradative) and anabolic (biosynthetic) pathways are interconnected and tightly regulated, the flow of cargo through the endocytic and autophagic systems is modulated by cellular signaling and nutrient availability. Nutrient deprivation, for example, activates autophagy, which is then halted once lysosomal degradation is complete. Lysosomes themselves play a direct role in sensing nutrient levels through the lysosomal nutrient-sensing (LYNUS) system, which includes components such as V-ATPase, Rag GTPases, and the mTOR complex. [ 14 ]
The formation of lysosomes begins in the endoplasmic reticulum, where hydrolytic enzymes are synthesized. These enzymes are then transported to the Golgi apparatus (Golgi body), where they undergo modifications to ensure proper targeting and function. The enzymes are tagged with mannose-6-phosphate, [ 15 ] allowing them to be sorted into vesicles. These vesicles then bud off from the trans-Golgi network and fuse with early endosomes. [ 15 ] [ 16 ]
Early endosomes degrade cargo from the extracellular environment, and as they mature into late endosomes, proton pumps are activated, causing the internal environment to become acidic. This acidic environment activates the hydrolytic enzymes, which further mature the endosome into a lysosome. [ 17 ] The lysosome then breaks down and recycles cellular waste. [ 18 ]
Disruptions in lysosomal formation can lead to dysfunctional lysosomes and the accumulation of undigested molecules, contributing to various lysosomal storage disorders. [ 18 ]
Lysosomes play a crucial role in defending the cell against pathogens such as viruses or bacteria. When a pathogen enters the cell, it is often enclosed in a phagosome which then fuses with a lysosome to form a phagolysosome where the hydrolytic enzymes break down the pathogen. [ 19 ] [ 4 ] Lysosomes are a crucial part of innate immune system. [ 19 ] Lysosomes also play a big role in adaptive immune system where fragments of pathogens that are broken down by phagolysosomes are sent to the major histocompatibility complex class II (MHC II) and presented on the surface of antigen presenting cells (APCs). Which then activates helper T cells and then causes an adaptive immune response. [ 20 ]
When viruses enter the cell via endocytosis, they get degraded in lysosomes but then some viruses have evolved strategies to escape lysosomes. During degradation of viruses in the lysosome, the virus can escape the lysosome before complete degradation and spreading viral material into the cytoplasm which then spreads viral infection in the cell. So, lysosomes need to effectively degrade all the biomolecules, in other words, poor lysosomal activity results in higher viral infections by viruses such as HIV. [ 4 ] [ 21 ]
Lysosomal storage disorders are a group of metabolic disorders that stem from inherited genetic mutations that disrupt normal lysosomal function and homeostasis. [ 14 ] [ 13 ] Most frequently, the mutations are located in the acidic hydrolases but can also be found in non-enzymatic lysosomal proteins (soluble and membrane-bound) and non-lysosomal factors controlling lysosomal function. [ 22 ] This leads to defective degradation, and therefore induces abnormal accumulations of un- or partially digested macromolecules within lysosomes. Lysosomal dysfunction also affect transport across the lysosomal membrane, vesicle trafficking, lysosome reformation and autophagy. [ 23 ] [ 14 ]
The stress of accumulated lysosomal substrates can lead to lysosomal membrane permeabilization, allowing hydrolytic enzymes to leak into the cytosol and initiate cell death. This cell loss particularly affects post-mitotic tissues such as the brain, liver, eyes, muscles, and spleen—resulting in the hallmark symptoms of lysosomal storage disorders, including neurodegeneration, cognitive impairment, and motor dysfunction. [ 13 ] [ 24 ]
The age of onset and the specific symptoms in lysosomal storage disorders differ depending on the severity of the mutations, the cell types affected and what substrates accumulate. However, the clinical presentation is typically a neurodegenerative disease at childhood, with more variations presenting themselves in adulthood. In most cases, the central nervous system (CNS) is affected, causing the brain to experience global neurodegeneration, inflammation, activation of the innate immune system and astrogliosis. [ 13 ]
Several therapeutic strategies have been developed to address lysosomal storage disorders. These include substrate reduction therapy, bone marrow transplantation, gene therapy, and enzyme replacement therapy. Currently, enzyme replacement therapy and substrate reduction are the most widely used. However, despite these advancements most lysosomal storage disorders still lack effective treatments as the existing ones often are limited by poor efficacy and are typically disease specific. [ 13 ]
Lysosomotropism refers to the tendency of lipophilic weak bases to accumulate in acidic organelles like lysosomes. While neutral forms of these compounds cross membranes easily, their protonated (charged) forms become trapped inside lysosomes, leading to concentrations up to 1000 times higher than outside the cell. [ 25 ] [ 26 ] This “acid trapping” or “proton pump” effect can be predicted using mathematical models. [ 27 ]
Many approved drugs, including haloperidol, [ 28 ] levomepromazine, [ 29 ] and amantadine, [ 30 ] exhibit lysosomotropic behavior. This helps explain their high tissue-to-blood concentration ratios and prolonged tissue retention, though fat solubility also contributes.
Some lysosomotropic drugs can interfere with lysosomal enzymes like acid sphingomyelinase. [ 31 ] [ 32 ] Ambroxol, a mucolytic, promotes lysosomal exocytosis by neutralizing lysosomal pH and releasing stored calcium. [ 33 ] This action may underlie its observed benefits in diseases linked to lysosomal dysfunction, including Parkinson's disease and lysosomal storage disorders. [ 34 ] [ 35 ]
Systemic lupus erythematosus (SLE) otherwise known as Lupus is an autoimmune disease where the immune system attacks healthy cells. [ 36 ] Lupus is prominent in systemic lupus erythematosus preventing macrophages and monocytes from degrading neutrophil extracellular traps [ 37 ] and immune complexes. [ 38 ] [ 39 ] [ 40 ] The failure to degrade internalized immune complexes rises from irregularly extended activity of mTORC2, which impairs lysosome acidification. [ 41 ] As a result, immune complexes in the lysosome recycle to the surface of macrophages causing an accumulation of DNA fragments and nuclear complexes which triggers an immune response from the body which is leads to the multiple lupus-associated pathologies. [ 38 ] [ 42 ] [ 43 ]
There are over 50 different types of hydrolytic enzymes in lysosomes, the table below shows a few of the main types and their substrates. It is important to keep in mind that each category below has multiple different types of enzymes. | https://en.wikipedia.org/wiki/Lysosome |
Lysozyme ( EC 3.2.1.17 , muramidase, N -acetylmuramide glycanhydrolase ; systematic name peptidoglycan N -acetylmuramoylhydrolase ) is an antimicrobial enzyme produced by animals that forms part of the innate immune system . It is a glycoside hydrolase that catalyzes the following process:
Peptidoglycan is the major component of gram-positive bacterial cell wall. [ 1 ] This hydrolysis in turn compromises the integrity of bacterial cell walls causing lysis of the bacteria.
Lysozyme is abundant in secretions including tears , saliva , human milk , and mucus . It is also present in cytoplasmic granules of the macrophages and the polymorphonuclear neutrophils (PMNs). Large amounts of lysozyme can be found in egg white . C-type lysozymes are closely related to α-lactalbumin in sequence and structure, making them part of the same glycoside hydrolase family 22 . [ 2 ] In humans, the C-type lysozyme enzyme is encoded by the LYZ gene. [ 3 ] [ 4 ]
Hen egg white lysozyme is thermally stable, with a melting point reaching up to 72 °C at pH 5.0. [ 5 ] However, lysozyme in human milk loses activity very quickly at that temperature. [ 6 ] Hen egg white lysozyme maintains its activity in a large range of pH (6–9). [ 7 ] Its isoelectric point is 11.35. [ 8 ] The isoelectric point of human milk lysozyme is 10.5–11. [ 9 ]
The enzyme functions by hydrolyzing glycosidic bonds in peptidoglycans . The enzyme can also break glycosidic bonds in chitin , although not as effectively as true chitinases . [ 10 ]
Lysozyme's active site binds the peptidoglycan molecule in the prominent cleft between its two domains. It attacks peptidoglycans (found in the cell walls of bacteria, especially Gram-positive bacteria ), its natural substrate , between N -acetylmuramic acid (NAM) and the fourth carbon atom of N-acetylglucosamine (NAG). [ citation needed ]
Shorter saccharides like tetrasaccharide have also shown to be viable substrates but via an intermediate with a longer chain. [ 11 ] Chitin has also been shown to be a viable lysozyme substrate. Artificial substrates have also been developed and used in lysozyme. [ 12 ]
The Phillips mechanism proposed that the enzyme's catalytic power came from both steric strain on the bound substrate and electrostatic stabilization of an oxo-carbenium intermediate. From X-ray crystallographic data, Phillips proposed the active site of the enzyme, where a hexasaccharide binds. The lysozyme distorts the fourth sugar (in the D or -1 subsite) in the hexasaccharide into a half-chair conformation. In this stressed state, the glycosidic bond is more easily broken. [ 13 ] An ionic intermediate containing an oxo-carbenium is created as a result of the glycosidic bond breaking. [ 14 ] Thus distortion causing the substrate molecule to adopt a strained conformation similar to that of the transition state will lower the energy barrier of the reaction. [ 15 ]
The proposed oxo-carbonium intermediate was speculated to be electrostatically stabilized by aspartate and glutamate residues in the active site by Arieh Warshel in 1978. The electrostatic stabilization argument was based on comparison to bulk water, the reorientation of water dipoles can cancel out the stabilizing energy of charge interaction. In Warshel's model, the enzyme acts as a super-solvent, which fixes the orientation of ion pairs and provides super- solvation (very good stabilization of ion pairs), and especially lower the energy when two ions are close to each other. [ 16 ]
The rate-determining step (RDS) in this mechanism is related to formation of the oxo-carbenium intermediate. There were some contradictory results to indicate the exact RDS. By tracing the formation of product ( p-nitrophenol ), it was discovered that the RDS can change over different temperatures, which was a reason for those contradictory results. At a higher temperature the RDS is formation of glycosyl enzyme intermediate and at a lower temperature the breakdown of that intermediate. [ 17 ]
In an early debate in 1969, Dahlquist proposed a covalent mechanism for lysozyme based on kinetic isotope effect , [ 14 ] but for a long time the ionic mechanism was more accepted. In 2001, a revised mechanism was proposed by Vocadlo via a covalent but not ionic intermediate. Evidence from ESI - MS analysis indicated a covalent intermediate. A 2-fluoro substituted substrate was used to lower the reaction rate and accumulate an intermediate for characterization. [ 19 ] The amino acid side-chains glutamic acid 35 (Glu35) and aspartate 52 (Asp52) have been found to be critical to the activity of this enzyme. Glu35 acts as a proton donor to the glycosidic bond, cleaving the C-O bond in the substrate, whereas Asp52 acts as a nucleophile to generate a glycosyl enzyme intermediate. The Glu35 reacts with water to form hydroxyl ion, a stronger nucleophile than water, which then attacks the glycosyl enzyme intermediate, to give the product of hydrolysis and leaving the enzyme unchanged. [ 20 ] This type of covalent mechanism for enzyme catalysis was first proposed by Koshland . [ 21 ]
More recently, quantum mechanics/ molecular mechanics (QM/MM) molecular dynamics simulations have been using the crystal of HEWL and predict the existence of a covalent intermediate. [ 22 ] Evidence for the ESI-MS and X-ray structures indicate the existence of covalent intermediate, but primarily rely on using a less active mutant or non-native substrate. Thus, QM/MM molecular dynamics provides the unique ability to directly investigate the mechanism of wild-type HEWL and native substrate. The calculations revealed that the covalent intermediate from the covalent mechanism is ~30 kcal/mol more stable than the ionic intermediate from the Phillips mechanism. [ 22 ] These calculations demonstrate that the ionic intermediate is extremely energetically unfavorable and the covalent intermediates observed from experiments using less active mutant or non-native substrates provide useful insight into the mechanism of wild-type HEWL. [ citation needed ]
Imidazole derivatives can form a charge-transfer complex with some residues (in or outside active center) to achieve a competitive inhibition of lysozyme. [ 23 ] In Gram-negative bacteria , the lipopolysaccharide acts as a non-competitive inhibitor by highly favored binding with lysozyme. [ 24 ]
Despite that the muramidase activity of lysozyme has been supposed to play the key role for its antibacterial properties, evidence of its non-enzymatic action was also reported. For example, blocking the catalytic activity of lysozyme by mutation of critical amino acid in the active site (52- Asp -> 52- Ser ) does not eliminate its antimicrobial activity. [ 25 ] The lectin-like ability of lysozyme to recognize bacterial carbohydrate antigen without lytic activity was reported for tetrasaccharide related to lipopolysaccharide of Klebsiella pneumoniae . [ 26 ] Also, lysozyme interacts with antibodies and T-cell receptors . [ 27 ]
Lysozyme exhibits two conformations: an open active state and a closed inactive state. The catalytic relevance was examined with single walled carbon nanotubes (SWCN) field effect transistors (FETs), where a singular lysozyme was bound to the SWCN FET. [ 28 ] Electronically monitoring the lysozyme showed two conformations, an open active site and a closed inactive site. In its active state lysozyme is able to processively hydrolyze its substrate, breaking on average 100 bonds at a rate of 15 per second. In order to bind a new substrate and move from the closed inactive state to the open active state requires two conformation step changes, while inactivation requires one step. [ citation needed ]
The conventional C-type lysozyme is part of a larger group of structurally and mechanistically related enzymes termed the lysozyme superfamily . This family unites GH22 C-type ("chicken") lysozymes with plant chitinase GH19 , G-type ("goose") lysozyme GH23 , V-type ("viral") lysozyme GH24 and the chitosanase GH46 families. The lysozyme-type nomenclature only reflects the source a type is originally isolated from and does not fully reflect the taxonomic distribution. [ 29 ] For example, humans and many other mammals have two G-type lysozyme genes, LYG1 and LYG2 . [ 30 ]
133L , 134L , 1B5U , 1B5V , 1B5W , 1B5X , 1B5Y , 1B5Z , 1B7L , 1B7M , 1B7N , 1B7O , 1B7P , 1B7Q , 1B7R , 1B7S , 1BB3 , 1BB4 , 1BB5 , 1C43 , 1C45 , 1C46 , 1C7P , 1CJ6 , 1CJ7 , 1CJ8 , 1CJ9 , 1CKC , 1CKD , 1CKF , 1CKG , 1CKH , 1D6P , 1D6Q , 1DI3 , 1DI4 , 1DI5 , 1EQ4 , 1EQ5 , 1EQE , 1GAY , 1GAZ , 1GB0 , 1GB2 , 1GB3 , 1GB5 , 1GB6 , 1GB7 , 1GB8 , 1GB9 , 1GBO , 1GBW , 1GBX , 1GBY , 1GBZ , 1GDW , 1GDX , 1GE0 , 1GE1 , 1GE2 , 1GE3 , 1GE4 , 1GEV , 1GEZ , 1GF0 , 1GF3 , 1GF4 , 1GF5 , 1GF6 , 1GF7 , 1GF8 , 1GF9 , 1GFA , 1GFE , 1GFG , 1GFH , 1GFJ , 1GFK , 1GFR , 1GFT , 1GFU , 1GFV , 1HNL , 1I1Z , 1I20 , 1I22 , 1INU , 1IOC , 1IP1 , 1IP2 , 1IP3 , 1IP4 , 1IP5 , 1IP6 , 1IP7 , 1IWT , 1IWU , 1IWV , 1IWW , 1IWX , 1IWY , 1IWZ , 1IX0 , 1IY3 , 1IY4 , 1JKA , 1JKB , 1JKC , 1JKD , 1JSF , 1JWR , 1LAA , 1LHH , 1LHI , 1LHJ , 1LHK , 1LHL , 1LHM , 1LMT , 1LOZ , 1LYY , 1LZ1 , 1LZ4 , 1LZ5 , 1LZ6 , 1LZR , 1LZS , 1OP9 , 1OUA , 1OUB , 1OUC , 1OUD , 1OUE , 1OUF , 1OUG , 1OUH , 1OUI , 1OUJ , 1QSW , 1RE2 , 1REM , 1REX , 1REY , 1REZ , 1TAY , 1TBY , 1TCY , 1TDY , 1UBZ , 1W08 , 1WQM , 1WQN , 1WQO , 1WQP , 1WQQ , 1WQR , 1YAM , 1YAN , 1YAO , 1YAP , 1YAQ , 207L , 208L , 2BQA , 2BQB , 2BQC , 2BQD , 2BQE , 2BQF , 2BQG , 2BQH , 2BQI , 2BQJ , 2BQK , 2BQL , 2BQM , 2BQN , 2BQO , 2HEA , 2HEB , 2HEC , 2HED , 2HEE , 2HEF , 2LHM , 2MEA , 2MEB , 2MEC , 2MED , 2MEE , 2MEF , 2MEG , 2MEH , 2MEI , 2NWD , 2ZIJ , 2ZIK , 2ZIL , 2ZWB , 3EBA , 3FE0 , 3LHM , 3LN2 , 4I0C , 4ML7 , 4R0P
4069
17110
ENSG00000090382
ENSMUSG00000069515
P61626
P17897
NM_000239
NM_013590
NP_000230
NP_038618
Lysozyme is part of the innate immune system. Reduced lysozyme levels have been associated with bronchopulmonary dysplasia in newborns. [ 35 ] Piglets fed with human lysozyme milk can recover from diarrheal disease caused by E. coli faster. The concentration of lysozyme in human milk is 1,600 to 3,000 times greater than the concentration in livestock milk. Human lysozyme is more active than hen egg white lysozyme. A transgenic line of goats (with a founder named "Artemis") were developed to produce milk with human lysozyme to protect children from diarrhea if they can't get the benefits of human breastfeeding. [ 36 ] [ 37 ]
Since lysozyme is a natural form of protection from Gram-positive pathogens like Bacillus and Streptococcus , [ 38 ] it plays an important role in immunology of infants in human milk feeding. [ 39 ] Whereas the skin is a protective barrier due to its dryness and acidity, the conjunctiva (membrane covering the eye) is, instead, protected by secreted enzymes, mainly lysozyme and defensin . However, when these protective barriers fail, conjunctivitis results. [ citation needed ]
In certain cancers (especially myelomonocytic leukemia) excessive production of lysozyme by cancer cells can lead to toxic levels of lysozyme in the blood. High lysozyme blood levels can lead to kidney failure and low blood potassium, conditions that may improve or resolve with treatment of the primary malignancy. [ citation needed ]
Serum lysozyme is much less specific for diagnosis of sarcoidosis than serum angiotensin converting enzyme; however, since it is more sensitive, it is used as a marker of sarcoidosis disease activity and is suitable for disease monitoring in proven cases. [ 40 ]
The first chemical synthesis of a lysozyme protein was attempted by Prof. George W. Kenner and his group at the University of Liverpool in England. [ 41 ] This was finally achieved in 2007 by Thomas Durek in Steve Kent's lab at the University of Chicago who made a synthetic functional lysozyme molecule. [ 42 ]
Lysozyme crystals have been used to grow other functional materials for catalysis and biomedical applications. [ 43 ] [ 44 ] [ 45 ] Lysozyme is a commonly used enzyme for lysing gram positive bacteria. [ 46 ] Due to the unique function of lysozyme in which it can digest the cell wall and causes osmotic shock (burst the cell by suddenly changing solute concentration around the cell and thus the osmotic pressure ), lysozyme is commonly used in lab setting to release proteins from bacterium periplasm while the inner membrane remains sealed as vesicles called the spheroplast . [ 47 ] [ 48 ]
For example, E. coli can be lysed using lysozyme to free the contents of the periplasmic space. It is especially useful in lab setting for trying to collect the contents of the periplasm. [ 1 ] Lysozyme treatment is optimal at particular temperatures, pH ranges, and salt concentrations. Lysozyme activity increases with increasing temperatures, up to 60 degrees Celsius, with a pH range of 6.0-7.0. The salts present also affect lysozyme treatment, where some assert inhibitory effects, and others promote lysis via lysozyme treatment. Sodium chloride induces lysis, but at high concentrations, it is an active inhibitor of lysis. Similar observations have been seen with the use of potassium salts. Slight variations are present due to differences in bacterial strains. [ 49 ] A consequence of the use of lysozyme in extracting recombinant proteins for protein crystallization is that the crystal may be contaminated with units of lysozyme, producing a physiologically irrelevant combination. In fact, some proteins simply cannot crystalize without such contamination. [ 50 ] [ 51 ]
Furthermore, lysozyme can serve as a tool in the expression of toxic recombinant proteins. Expressing recombinant proteins in BL21(DE3) strains is typically accomplished by the T7-RNA-polymerase. Via IPTG induction, the UV-5 repressor is inhibited, leading to the transcription of the T7-RNA-polymerase and thereby of the protein of interest. Nonetheless, a basal level of the T7-RNA-polymerase is observable even without induction. T7 lysozyme acts as an inhibitor of the T7-RNA-polymerase. Newly invented strains, containing a helper plasmid (pLysS), constitutively co-express low levels of T7 lysozyme, providing high stringency and consistent expression of the toxic recombinant protein. [ 52 ]
The antibacterial property of hen egg white, due to the lysozyme it contains, was first observed by Laschtschenko in 1909. [ 53 ] The bacteria-killing activity of nasal mucus was demonstrated in 1922 by Alexander Fleming , the discoverer of penicillin , who coined the term "lysozyme". [ 54 ] He is reported as saying: "As this substance has properties akin to those of ferments I have called it a 'Lysozyme'." [ 55 ] Fleming went on to show that an enzymic substance was present in a wide variety of secretions and was capable of rapidly lysing (i.e. dissolving) different bacteria, particularly a yellow "coccus" that he studied". [ 56 ]
Lysozyme was first crystallised by Edward Abraham in 1937, enabling the three-dimensional structure of hen egg white lysozyme to be described by David Chilton Phillips in 1965, when he obtained the first 2- ångström (200 pm ) resolution model via X-ray crystallography . [ 57 ] [ 58 ] The structure was publicly presented at a Royal Institution lecture in 1965. [ 59 ] Lysozyme was the second protein structure and the first enzyme structure to be solved via X-ray diffraction methods, and the first enzyme to be fully sequenced that contains all twenty common amino acids. [ 60 ] As a result of Phillips' elucidation of the structure of lysozyme, it was also the first enzyme to have a detailed, specific mechanism suggested for its method of catalytic action. [ 61 ] [ 62 ] [ 63 ] This work led Phillips to provide an explanation for how enzymes speed up a chemical reaction in terms of its physical structures. The original mechanism proposed by Phillips was more recently revised. [ 19 ] | https://en.wikipedia.org/wiki/Lysozyme |
Lysozyme PEGylation is the covalent attachment of Polyethylene glycol (PEG) to Lysozyme, which is one of the most widely investigated PEGylated proteins.
The PEGylation of proteins has become a common practice of modern therapeutic drugs, as the process is capable of enhancing solubility, thermal stability, enzymatic degradation resistance, and serum half-life of the proteins of interest. [ 1 ] [ 2 ] Lysozyme , as a natural bactericidal enzyme, lyses the cell wall of various gram-positive bacteria and offers protection against microbial infections. [ 2 ] Lysozyme has six lysine residues which are accessible for PEGylation reactions. [ 3 ] Thus, the PEGylation of lysozyme , or lysozyme PEGylation, can be a good model system for the PEGylation of other proteins with enzymatic activities by showing the enhancement of its physical and thermal stability while retaining its activity. [ 2 ]
Previous works on lysozyme PEGylation showed various chromatographic schemes in order to purify PEGylated lysozyme, which included ion exchange chromatography , hydrophobic interaction chromatography , and size-exclusion chromatography ( fast protein liquid chromatography ), and proved its stable conformation via circular dichroism and improved thermal stability by enzymatic activity assays, SDS-PAGE , and size-exclusion chromatography ( high-performance liquid chromatography ). [ 1 ] [ 4 ] [ 5 ]
The chemical modification of lysozyme by PEGylation involves the addition of methoxy-PEG-aldehyde (mPEG-aldehyde) with varying molecular sizes, ranging from 2 kDa to 40 kDa, to the protein. [ 6 ] [ 7 ] The protein and mPEG-aldehyde are dissolved using a sodium phosphate buffer with sodium cyanoborohydride , which acts as a reducing agent and conditions the aldehyde group of mPEG-aldehyde to have a strong affinity towards the lysine residue on the N-terminal of lysozyme. [ 7 ] The commonly used molar ratio of lysozyme and mPEG-aldehyde is 1:6 or 1:6.67. [ 6 ] [ 5 ] When sufficient PEGylation is reached, the reaction can be terminated by addition of lysine to the solution or boiling of the solution. [ 2 ] [ 8 ] Various profiles can result in the PEGylation of the protein, which includes intact mono-PEGylated, di-PEGylated, tri-PEGylated, and also possibly their isoforms . [ 5 ]
Ion exchange chromatography is often employed in the first step, or capturing step, for the separation of PEGylated proteins as PEGylation may affect the charges of target proteins by neutralizing electrostatic interaction , changing the isoelectric point (pI), and increasing the pKa value. [ 2 ] Due to the high pI of lysozyme (pI = 10.7), cation exchange chromatography is used. [ 2 ] [ 9 ] As the increased degree of PEGylation decreases the ion strength of the protein, the poly-PEGylated proteins tend to bind to the cation resin weaker than the mono-PEGylated protein or the intact form does. Thus, the poly-PEGylated proteins elute faster and the intact protein eludes last in the cation exchange chromatography. [ 10 ] As mono-PEGylated is widely investigated and described as a protection of target proteins, the target eluate in the cation exchange chromatography is usually the mono-PEGylated proteins. [ 7 ]
Despite the capability of the cation exchange chromatography in purification process, hydrophobic interaction chromatography is also employed, usually at the second step as a polishing step. By using relatively small bead-sized cation resin, the cation exchange chromatography can identify and separate between isoforms by the apparent charges in the condition, but hydrophobic interaction chromatography is capable of identification and separation of the isoforms by their hydrophobicity. [ 11 ]
Due to the apparent size differences by the degree of PEGylation of the protein, size-exclusion chromatography ( fast protein liquid chromatography or FPLC) can be used. [ 4 ] [ 5 ] There is a negative correlation between molecular weight and the retention time of the PEGylated protein in the chromatogram; larger protein, or more PEGylated protein elutes first, and smaller protein, or intact protein the latest. [ 2 ]
The most common analyses for identifying intact and PEGylated lysozyme can be achieved via size-exclusion chromatography ( high-performance liquid chromatography or HPLC), SDS-PAGE and Matrix-assisted laser desorption/ionization (MALDI) . [ 2 ]
The secondary structure of intact and PEGylated lysozyme can be characterized by circular dichroism (CD) spectroscopy. [ 4 ] [ 7 ] The CD spectra range from 189 - 260 nm with a pitch of 0.1 nm showed no significant change in the secondary structure of the intact and PEGylated lysozyme. [ 4 ] [ 7 ]
Enzymatic activity of intact and PEGylated lysozyme can be evaluated using glycol chitosan by reacting 1 mL of 0.05% (w/v) glycol chitosan in 100 mM of pH 5.5 acetate buffer and 100 μL of the intact or PEGylated protein at 40 °C for 30 min and subsequently adding 2 mL of 0.5 M sodium carbonate with 1 μg of potassium ferricyanide . [ 12 ] The mixture is immediately heated, boiled for 15 minutes, and cooled for spectral analysis at 420 nm. [ 12 ] As the enzymatic activity to hydrolyze β-1,4- N-acetylglucosamine linkage was retained after PEGylation, there was no decay in the enzymatic activity by increasing the degree of PEGylation. [ 4 ]
By the measurement of decrease in turbidity of M. lysodeikticus by incubating it with lysozyme, enzymatic activity can be evaluated. [ 13 ] 7.5 μL of 0.1 - 1 mg/mL proteins is added to 200 μL of M. lysodeikticus at its optical density (OD) of 1.7 AU, and the mixture is measured at 450 nm periodically for reaction rate calculation. [ 5 ] [ 13 ] On the contrary to the result from glycol chitosan enzymatic activity, the increasing degree of PEGylation decreased the enzymatic activity. [ 4 ] [ 5 ] This difference in the trend of the enzymatic activity can be due to PEGylation to free lysine causing steric hindrance and subsequently preventing from forming enzyme-substrate complex in the case of reacting with macromolecule, such as M. lysodeikticus. [ 4 ] [ 5 ] [ 14 ] | https://en.wikipedia.org/wiki/Lysozyme_PEGylation |
László Fejes Tóth ( Hungarian : Fejes Tóth László , pronounced [ˈfɛjɛʃ ˈtoːt ˈlaːsloː] ; 12 March 1915 – 17 March 2005) was a Hungarian mathematician who specialized in geometry. He proved that a lattice pattern is the most efficient way to pack centrally symmetric convex sets on the Euclidean plane (a generalization of Thue's theorem , a 2-dimensional analog of the Kepler conjecture ). [ 1 ] He also investigated the sphere packing problem. He was the first to show, in 1953, that proof of the Kepler conjecture can be reduced to a finite case analysis and, later, that the problem might be solved using a computer.
He was a member of the Hungarian Academy of Sciences (from 1962) and a director of the Alfréd Rényi Institute of Mathematics (1970-1983). He received both the Kossuth Prize (1957) and State Award (1973). [ 2 ] [ 3 ]
Together with H.S.M. Coxeter and Paul Erdős , he laid the foundations of discrete geometry . [ 4 ] [ 5 ] [ 6 ]
As described in a 1999 interview with István Hargittai , Fejes Tóth's father was a railway worker, who advanced in his career within the railway organization ultimately to earn a doctorate in law. Fejes Tóth's mother taught Hungarian and German literature in a high school. The family moved to Budapest, when Fejes Tóth was five; there he attended elementary school and high school—the Széchenyi István Reálgimnázium—where his interest in mathematics began. [ 3 ]
Fejes Tóth attended Pázmány Péter University , now the Eötvös Loránd University. As a freshman, he developed a generalized solution regarding Cauchy exponential series, which he published in the proceedings of the French Academy of Sciences —1935. [ 3 ] [ 7 ] He then received his doctorate at Pázmány Péter University, under the direction of Lipót Fejér . [ 8 ]
After university, he served as a soldier for two years, but received a medical exemption. In 1941 he joined the University of Kolozsvár ( Cluj ). [ 8 ] It was here that he became interested in packing problems. [ 9 ] In 1944, he returned to Budapest to teach mathematics at Árpád High School. Between 1946 and 1949 he lectured at Pázmány Péter University and starting in 1949 became a professor at the University of Veszprém (now University of Pannonia ) for 15 years, [ 3 ] where he was the primary developer of the "geometric patterns" theory "of the plane, the sphere and the surface space" and where he "had studied non grid-like structures and quasicrystals" which later became an independent discipline, as reported by János Pach . [ 8 ]
The editors of a book dedicated to Fejes Tóth described some highlights of his early work; e.g. having shown that the maximum density of a packing of repeated symmetric convex bodies occurs with a lattice pattern of packing. He also showed that, of all convex polytopes of given surface area that are equivalent to a given Platonic solid (e.g. a tetrahedron or an octahedron ), a regular polytope always has the largest possible volume. He developed a technique that proved Steiner's conjecture for the cube and for the dodecahedron . [ 9 ] By 1953, Fejes Tóth had written dozens of papers devoted to these types of fundamental issues. [ 8 ] His distinguished academic career allowed him to travel abroad beyond the Iron Curtain to attend international conferences and teach at various universities, including those at Freiburg ; Madison, Wisconsin ; Ohio ; and Salzburg . [ 3 ]
Fejes Tóth met his wife in university. She was a chemist. They were parents of three children, two sons—one a professor of mathematics at the Alfréd Rényi Institute of Mathematics , the other a professor of physiology at Dartmouth College —and one daughter, a psychologist. [ 3 ] He enjoyed sports, being skilled at table tennis, tennis, and gymnastics. A family photograph shows him swinging by his arms over the top of a high bar when he was around fifty. [ 8 ]
Fejes Tóth held the following positions over his career: [ 2 ]
In addition to his positions in residence, he was a corresponding member of the Saxonian Academy of Sciences and Humanities , Akademie der Wissenschaften der DDR , [ 10 ] and of the Braunschweigische Wissenschaftlische Gesellschaft .
According to J. A. Todd , [ 11 ] a reviewer of Fejes Tóth's book Regular Figures , [ 12 ] Fejes Tóth divided the topic into two sections. One, entitled "Systematology of the Regular Figures", develops a theory of "regular and Archimedean polyhedra and of regular polytopes ". Todd explains that the treatment includes:
The other section, entitled "Genetics of the Regular Figures", covers a number of special problems, according to Todd. These problems include "packings and coverings of circles in a plane, and ... with tessellations on a sphere" and also problems "in the hyperbolic plane, and in Euclidean space of three or more dimensions." At the time, Todd opined that those problems were "a subject in which there is still much scope for research, and one which calls for considerable ingenuity in approaching its problems". [ 11 ]
Imre Bárány credited Fejes Tóth with several influential proofs in the field of discrete and convex geometry, pertaining to packings and coverings by circles, to convex sets in a plane and to packings and coverings in higher dimensions, including the first correct proof of Thue's theorem . He credits Fejes Tóth, along with Paul Erdős , as having helped to "create the school of Hungarian discrete geometry." [ 6 ]
Fejes Tóth's monograph, Lagerungen in der Ebene, auf der Kugel und im Raum , [ 17 ] [ 18 ] which was translated into Russian and Japanese, won him the Kossuth Prize in 1957 and the Hungarian Academy of Sciences membership in 1962. [ 2 ] [ 8 ]
William Edge , [ 19 ] another reviewer of Regular Figures , [ 12 ] cites Fejes Tóth's earlier work, Lagerungen in der Ebene, auf der Kugel und im Raum , [ 17 ] as the foundation of his second chapter in Regular Figures . He emphasized that, at the time of this work, the problem of the upper bound for the density of a packing of equal spheres was still unsolved.
The approach that Fejes Tóth suggested in that work, which translates as "packing [of objects] in a plane, on a sphere and in a space", provided Thomas Hales a basis for a proof of the Kepler conjecture in 1998. The Kepler conjecture, named after the 17th-century German mathematician and astronomer Johannes Kepler , says that no arrangement of equally sized spheres filling space has a greater average density than that of the cubic close packing ( face-centered cubic ) and hexagonal close packing arrangements. Hales used a proof by exhaustion involving the checking of many individual cases, using complex computer calculations. [ 20 ] [ 21 ] [ 22 ] [ 23 ] [ 24 ]
Fejes Tóth received the following prizes: [ 2 ]
He received honorary degrees from the University of Salzburg (1991) and the University of Veszprém (1997).
In 2008, a conference was convened in Fejes Tóth's memory in Budapest from June 30 – July 6; [ 4 ] it celebrated the term, "Intuitive Geometry", coined by Fejes Tóth to refer to the kind of geometry, which is accessible to the "man in the street". According to the conference organizers, the term encompasses combinatorial geometry, the theory of packing , covering and tiling , convexity , computational geometry , rigidity theory , the geometry of numbers , crystallography and classical differential geometry .
The University of Pannonia administers the László Fejes Tóth Prize (Hungarian: Fejes Tóth László-díj) to recognize "outstanding contributions and development in the field of mathematical sciences". [ 25 ] In 2015, the year of Fejes Tóth's centennial birth anniversary, the prize was awarded to Károly Bezdek of the University of Calgary in a ceremony held on 19 June 2015 in Veszprém, Hungary. [ 26 ] | https://en.wikipedia.org/wiki/László_Fejes_Tóth |
László Fuchs (born June 24, 1924) is a Hungarian -born American mathematician, the Evelyn and John G. Phillips Distinguished Professor Emeritus in Mathematics at Tulane University . [ 1 ] He is known for his research and textbooks in group theory and abstract algebra . [ 2 ] [ 3 ]
Fuchs was born on June 24, 1924, in Budapest , [ 4 ] into an academic family: his father was a linguist and a member of the Hungarian Academy of Sciences . [ 4 ] He earned a bachelor's degree in 1946 and a doctorate in 1947 from Eötvös Loránd University . [ 4 ] [ 5 ] After teaching high school mathematics for two years, and then holding positions at Eötvös Loránd, the Mathematical Research Institute of the Hungarian Academy of Sciences , and the University of Miami , he joined the Tulane faculty in 1968. [ 4 ] [ 1 ] At Tulane, Fuchs chaired the mathematics department from 1977 to 1979. [ 4 ] He retired in 2004. [ 6 ]
In 2004, Fuchs was honored at the Hungarian Academy of Sciences 80th anniversary as one of the "big five" most distinguished Hungarian mathematicians. The other honorees included John Horvath , János Aczél , Ákos Császár and Steven Gaal . [ 7 ] Fuchs has nearly 100 academic descendants , many of them through his student at Eötvös Loránd, George Grätzer . [ 5 ] He was treasurer of the János Bolyai Mathematical Society from 1949 until 1963, and secretary-general of the society from 1963 to 1966. [ 4 ]
Fuchs turned 100 on June 24, 2024. [ 8 ]
Fuchs won the Kossuth Prize in 1953. [ 4 ] He is a foreign member of the Hungarian Academy of Sciences . [ 4 ] Two conferences were dedicated to him on the occasion of his 70th birthday, and another on his 75th. [ 4 ] [ 2 ] [ 3 ]
At Tulane University, Fuchs held the W. R. Irby Professorship from 1979 to 1992, and the Evelyn and John G. Phillips Distinguished Professorship from then until his retirement. [ 4 ]
In 2012 he became a fellow of the American Mathematical Society . [ 10 ] | https://en.wikipedia.org/wiki/László_Fuchs |
László Rédei (15 November 1900 – 21 November 1980) was a Hungarian mathematician .
Rédei graduated from the University of Budapest and initially worked as a schoolteacher. In 1940 he was appointed professor in the University of Szeged and in 1967 moved to the Mathematical Institute of the Hungarian Academy of Sciences in Budapest .
His mathematical work was in algebraic number theory and abstract algebra , especially group theory . He proved that every finite tournament contains an odd number of Hamiltonian paths . He gave several proofs of the theorem on quadratic reciprocity . He proved important results concerning the invariants of the class groups of quadratic number fields . [ 1 ] In several cases, he determined if the ring of integers of the real quadratic field Q ( √ d ) is Euclidean or not. He successfully generalized Hajós's theorem . This led him to the investigations of lacunary polynomials over finite fields , which he eventually published in a book. This work on lacunary polynomials has had a big influence in the field of finite geometry where it plays an important role in the theory of blocking sets . He introduced a very general notion of skew product of groups, of which both the Schreier-extension and the Zappa–Szép product are special case. He explicitly determined those finite noncommutative groups whose all proper subgroups were commutative (1947). This is one of the very early results which eventually led to the classification of all finite simple groups .
Rédei was the president of the János Bolyai Mathematical Society (1947–1949). He was awarded the Kossuth Prize twice. He was elected corresponding member (1949), full member (1955) of the Hungarian Academy of Sciences . | https://en.wikipedia.org/wiki/László_Rédei |
László Tisza (July 7, 1907 – April 15, 2009) was a Hungarian-born American physicist who was Professor of Physics Emeritus at MIT . He was a colleague of famed physicists Edward Teller , Lev Landau and Fritz London , and initiated the two-fluid model of liquid helium . [ 1 ]
In 1941, Tisza immigrated to the United States and joined the faculty at the Massachusetts Institute of Technology . His research areas included theoretical physics and the history and philosophy of science , specifically on the foundation of thermodynamics [ 2 ] and quantum mechanics . He taught at MIT until 1973.
Tisza was the author of the 1966 book, Generalized Thermodynamics . The 1982 publication, Physics as Natural Philosophy: Essays in Honor of László Tisza , was written by Tisza's colleagues and former students in honor of his 75th birthday.
He was a Fellow of The American Physical Society and American Academy of Arts and Sciences , a John Simon Guggenheim Fellow and had been a visiting professor at the University of Paris in Sorbonne .
This article about a Hungarian scientist is a stub . You can help Wikipedia by expanding it .
This article about an American physicist is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/László_Tisza |
A Lénárt sphere is an educational manipulative and writing surface for exploring spherical geometry , invented by Hungarian István Lénárt as a modern replacement for a spherical blackboard . [ 1 ] [ 2 ] It can be used for visualizing the geometry of points , great and small circles , triangles , polygons , conics , and other objects on a sphere , and comparing spherical geometry to Euclidean geometry as drawn on a flat piece of paper or blackboard. The included spherical ruler and compass support synthetic straightedge and compass construction on the sphere.
The Lénárt sphere and accessories are produced by the company Lénárt Educational Research and Technology.
The basic set includes: [ 3 ]
The company also sells replacement parts, extra transparency sheets, wet-wipe markers , and Lénárt's book Non-Euclidean Adventures on the Lenart Sphere , which describes more activities for students.
Spherical Easel is an interactive geometry software tool for exploring spherical geometry (see § External links ). Other interactive geometry software is typically limited to the flat plane.
Spherical trigonometry is fundamental to ancient astronomy and astrology , celestial navigation , and geodesy and cartography , and it used to be a standard part of undergraduate mathematics education . In recent decades hand computations have been replaced by electronic computers and spherical trigonometry has been pushed out of the typical mathematics curriculum by other topics. [ 1 ]
The Lénárt sphere was invented by István Lénárt in Hungary in the early 1990s and its use is described in his 2003 book comparing planar and spherical geometry. [ 4 ]
The Lénárt sphere is widely used throughout Europe in university courses on non-Euclidean geometry and geographic information systems (GIS). | https://en.wikipedia.org/wiki/Lénárt_sphere |
In mathematics Lévy's constant (sometimes known as the Khinchin–Lévy constant ) occurs in an expression for the asymptotic behaviour of the denominators of the convergents of simple continued fractions . [ 1 ] In 1935, the Soviet mathematician Aleksandr Khinchin showed [ 2 ] that the denominators q n of the convergents of the continued fraction expansions of almost all real numbers satisfy
Soon afterward, in 1936, the French mathematician Paul Lévy found [ 3 ] the explicit expression for the constant, namely
The term "Lévy's constant" is sometimes used to refer to π 2 / ( 12 ln 2 ) {\displaystyle \pi ^{2}/(12\ln 2)} (the logarithm of the above expression), which is approximately equal to 1.1865691104… The value derives from the asymptotic expectation of the logarithm of the ratio of successive denominators, using the Gauss-Kuzmin distribution . In particular, the ratio has the asymptotic density function [ citation needed ]
f ( z ) = 1 z ( z + 1 ) ln ( 2 ) {\displaystyle f(z)={\frac {1}{z(z+1)\ln(2)}}}
for z ≥ 1 {\displaystyle z\geq 1} and zero otherwise. This gives Lévy's constant as
β = ∫ 1 ∞ ln z z ( z + 1 ) ln 2 d z = ∫ 0 1 ln z − 1 ( z + 1 ) ln 2 d z = π 2 12 ln 2 {\displaystyle \beta =\int _{1}^{\infty }{\frac {\ln z}{z(z+1)\ln 2}}dz=\int _{0}^{1}{\frac {\ln z^{-1}}{(z+1)\ln 2}}dz={\frac {\pi ^{2}}{12\ln 2}}} .
The base-10 logarithm of Lévy's constant, which is approximately 0.51532041…, is half of the reciprocal of the limit in Lochs' theorem .
[ 4 ]
The proof assumes basic properties of continued fractions .
Let T : x ↦ 1 / x mod 1 {\displaystyle T:x\mapsto 1/x\mod 1} be the Gauss map .
| ln x − ln p n ( x ) / q n ( x ) | ≤ 1 / q n ( x ) ≤ 1 / F n {\displaystyle |\ln x-\ln p_{n}(x)/q_{n}(x)|\leq 1/q_{n}(x)\leq 1/F_{n}} where F n {\textstyle F_{n}} is the Fibonacci number.
Proof. Define the function f ( t ) = ln p n + p n − 1 t q n + q n − 1 t {\textstyle f(t)=\ln {\frac {p_{n}+p_{n-1}t}{q_{n}+q_{n-1}t}}} . The quantity to estimate is then | f ( T n x ) − f ( 0 ) | {\displaystyle |f(T^{n}x)-f(0)|} .
By the mean value theorem , for any t ∈ [ 0 , 1 ] {\textstyle t\in [0,1]} , | f ( t ) − f ( 0 ) | ≤ max t ∈ [ 0 , 1 ] | f ′ ( t ) | = max t ∈ [ 0 , 1 ] 1 ( p n + t p n − 1 ) ( q n + t q n − 1 ) = 1 p n q n ≤ 1 q n {\displaystyle |f(t)-f(0)|\leq \max _{t\in [0,1]}|f'(t)|=\max _{t\in [0,1]}{\frac {1}{(p_{n}+tp_{n-1})(q_{n}+tq_{n-1})}}={\frac {1}{p_{n}q_{n}}}\leq {\frac {1}{q_{n}}}} The denominator sequence q 0 , q 1 , q 2 , … {\displaystyle q_{0},q_{1},q_{2},\dots } satisfies a recurrence relation , and so it is at least as large as the Fibonacci sequence 1 , 1 , 2 , … {\displaystyle 1,1,2,\dots } .
Since p n ( x ) = q n − 1 ( T x ) {\textstyle p_{n}(x)=q_{n-1}(Tx)} , and p 1 = 1 {\textstyle p_{1}=1} , we have − ln q n = ln p n ( x ) q n ( x ) + ln p n − 1 ( T x ) q n − 1 ( T x ) + ⋯ + ln p 1 ( T n − 1 x ) q 1 ( T n − 1 x ) {\displaystyle -\ln q_{n}=\ln {\frac {p_{n}(x)}{q_{n}(x)}}+\ln {\frac {p_{n-1}(Tx)}{q_{n-1}(Tx)}}+\dots +\ln {\frac {p_{1}(T^{n-1}x)}{q_{1}(T^{n-1}x)}}} By the lemma, − ln q n = ln x + ln T x + ⋯ + ln T n − 1 x + δ {\displaystyle -\ln q_{n}=\ln x+\ln Tx+\dots +\ln T^{n-1}x+\delta }
where | δ | ≤ ∑ k = 1 ∞ 1 / F n {\textstyle |\delta |\leq \sum _{k=1}^{\infty }1/F_{n}} is finite, and is called the reciprocal Fibonacci constant .
By Birkhoff's ergodic theorem, the limit lim n → ∞ ln q n n {\textstyle \lim _{n\to \infty }{\frac {\ln q_{n}}{n}}} converges to ∫ 0 1 ( − ln t ) ρ ( t ) d t = π 2 12 ln 2 {\displaystyle \int _{0}^{1}(-\ln t)\rho (t)dt={\frac {\pi ^{2}}{12\ln 2}}} almost surely, where ρ ( t ) = 1 ( 1 + t ) ln 2 {\displaystyle \rho (t)={\frac {1}{(1+t)\ln 2}}} is the Gauss distribution.
This number theory -related article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Lévy's_constant |
In probability theory , Lévy’s continuity theorem , or Lévy's convergence theorem , [ 1 ] named after the French mathematician Paul Lévy , connects convergence in distribution of the sequence of random variables with pointwise convergence of their characteristic functions .
This theorem is the basis for one approach to prove the central limit theorem and is one of the major theorems concerning characteristic functions.
Suppose we have
If the sequence of characteristic functions converges pointwise to some function φ {\displaystyle \varphi }
then the following statements become equivalent:
Rigorous proofs of this theorem are available. [ 1 ] [ 2 ] | https://en.wikipedia.org/wiki/Lévy's_continuity_theorem |
Lévy's modulus of continuity theorem is a theorem that gives a result about an almost sure behaviour of an estimate of the modulus of continuity for Wiener process , that is used to model what's known as Brownian motion .
Lévy's modulus of continuity theorem is named after the French mathematician Paul Lévy .
Let B : [ 0 , 1 ] × Ω → R {\displaystyle B:[0,1]\times \Omega \to \mathbb {R} } be a standard Wiener process. Then, almost surely ,
In other words, the sample paths of Brownian motion have modulus of continuity
with probability one, for c > 1 {\displaystyle c>1} and sufficiently small δ > 0 {\displaystyle \delta >0} . [ 1 ] | https://en.wikipedia.org/wiki/Lévy's_modulus_of_continuity_theorem |
In quantum mechanics , the Lévy-Leblond equation describes the dynamics of a spin-1/2 particle. It is a linearized version of the Schrödinger equation and of the Pauli equation . It was derived by French physicist Jean-Marc Lévy-Leblond in 1967. [ 1 ]
Lévy-Leblond equation was obtained under similar heuristic derivations as the Dirac equation , but contrary to the latter, Lévy-Leblond equation is not relativistic . As both equations recover the electron gyromagnetic ratio , it is suggested that spin is not necessarily a relativistic phenomenon.
For a nonrelativistic spin-1/2 particle of mass m, a representation of the time-independent Lévy-Leblond equation reads: [ 1 ]
where c is the speed of light , E is the nonrelativistic particle energy, p = − i ℏ ∇ {\displaystyle \mathbf {p} =-i\hbar \nabla } is the momentum operator , and σ = ( σ x , σ y , σ z ) {\displaystyle {\boldsymbol {\sigma }}=(\sigma _{x},\sigma _{y},\sigma _{z})} is the vector of Pauli matrices , which is proportional to the spin operator S = 1 2 ℏ σ {\displaystyle \mathbf {S} ={\tfrac {1}{2}}\hbar {\boldsymbol {\sigma }}} . Here ψ , χ {\displaystyle \psi ,\chi } are two components functions ( spinors ) describing the wave function of the particle.
By minimal coupling , the equation can be modified to account for the presence of an electromagnetic field , [ 1 ]
where q is the electric charge of the particle. V is the electric potential , and A is the magnetic vector potential . This equation is linear in its spatial derivatives.
In 1928, Paul Dirac linearized the relativistic dispersion relation and obtained Dirac equation, described by a bispinor . This equation can be decoupled into two spinors in the non-relativistic limit, leading to predict the electron magnetic moment with a gyromagnetic ratio g = 2 {\textstyle g=2} . [ 2 ] The success of Dirac theory has led to some textbooks to erroneously claim that spin is necessarily a relativistic phenomena. [ 3 ] [ 4 ]
Jean-Marc Lévy-Leblond applied the same technique to the non-relativistic energy relation showing that the same prediction of g = 2 {\textstyle g=2} can be obtained. [ 2 ] Actually to derive the Pauli equation from Dirac equation one has to pass by Lévy-Leblond equation. [ 2 ] Spin is then a result of quantum mechanics and linearization of the equations but not necessarily a relativistic effect. [ 3 ] [ 5 ]
Lévy-Leblond equation is Galilean invariant . This equation demonstrates that one does not need the full Poincaré group to explain the spin 1/2. [ 4 ] In the classical limit where c → ∞ {\textstyle c\to \infty } , quantum mechanics under the Galilean transformation group are enough. [ 1 ] Similarly, one can construct a non-relativistic linear equation for any arbitrary spin. [ 1 ] [ 6 ] Under the same idea one can construct equations for Galilean electromagnetism . [ 1 ]
Taking the second line of Lévy-Leblond equation and inserting it back into the first line, one obtains through the algebra of the Pauli matrices, that [ 3 ]
which is the Schrödinger equation for a two-valued spinor . Note that solving for χ {\displaystyle \chi } also returns another Schrödinger's equation. Pauli's expression for spin- 1 ⁄ 2 particle in an electromagnetic field can be recovered by minimal coupling: [ 3 ]
While Lévy-Leblond is linear in its derivatives, Pauli's and Schrödinger's equations are quadratic in the spatial derivatives.
Dirac equation can be written as: [ 1 ]
where E {\textstyle {\mathcal {E}}} is the total relativistic energy. In the non-relativistic limit, E ≪ m c 2 {\textstyle E\ll mc^{2}} and E ≈ m c 2 + E + ⋯ {\textstyle {\mathcal {E}}\approx mc^{2}+E+\cdots } one recovers, Lévy-Leblond equations.
Similar to the historical derivation of Dirac equation by Paul Dirac , one can try to linearize the non-relativistic dispersion relation E = p 2 2 m {\textstyle E={\frac {\mathbf {p} ^{2}}{2m}}} . We want two operators Θ and Θ' linear in p {\textstyle \mathbf {p} } (spatial derivatives) and E , like [ 3 ]
for some A , A ′ , B = ( B x , B y , B z ) , B ′ = ( B x ′ , B y ′ , B z ′ ) , C , C ′ {\textstyle A,A',\mathbf {B} =(B_{x},B_{y},B_{z}),\mathbf {B} '=(B_{x}',B_{y}',B_{z}'),C,C'} , such that their product recovers the classical dispersion relation, that is
where the factor 2 mc 2 is arbitrary an it is just there for normalization. By carrying out the product, one find that there is no solution if A , A ′ , B i , B i ′ , C , C ′ {\textstyle A,A',B_{i},B_{i}',C,C'} are one dimensional constants. The lowest dimension where there is a solution is 4. Then A , A ′ , B , B ′ , C , C ′ {\textstyle A,A',\mathbf {B} ,\mathbf {B} ',C,C'} are matrices that must satisfy the following relations:
these relations can be rearranged to involve the gamma matrices from Clifford algebra . [ 3 ] [ 2 ] I N {\textstyle I_{N}} is the Identity matrix of dimension N . One possible representation is
such that Θ Ψ = 0 {\textstyle \Theta \Psi =0} , with Ψ = ( ψ , χ ) {\textstyle \Psi =(\psi ,\chi )} , returns Lévy-Leblond equation. Other representations can be chosen leading to equivalent equations with different signs or phases. [ 2 ] [ 3 ] | https://en.wikipedia.org/wiki/Lévy-Leblond_equation |
The Lévy flight foraging hypothesis is a hypothesis in the field of biology that may be stated as follows:
Since Lévy flights and walks can optimize search efficiencies, therefore natural selection should have led to adaptations for Lévy flight foraging. [ 1 ]
The movement of animals closely resembles in many ways the random walks of dust particles in a fluid . [ 2 ] This similarity led to interest in trying to understand how animals move via the analogy to Brownian motion. This conventional wisdom held until the early 1990s. However, starting in the late 1980s, evidence began to accumulate that did not fit the theoretical predictions. [ 2 ]
In 1999, a theoretical investigation of the properties of Lévy flights showed that an inverse square distribution of flight times or distances could optimize the search efficiency under certain circumstances. [ 3 ] Specifically, a search based on an inverse-square Lévy walk, consisting of a constant velocity search following a path whose length is distributed over an inverse square Levy stable distribution, is optimal for searching sparsely and randomly distributed revisitable targets in the absence of memory. These results have been published in 1999 in the journal Nature . [ 3 ]
There has been some controversy about the reality of Lévy flight foraging. Early studies were limited to a small range of movement, and thus the type of motion could not be unequivocally determined; and in 2007 flaws were found in a study of wandering albatrosses which was the first empirical example of such a strategy. [ 4 ] There are however many new studies backing the Lévy flight foraging hypothesis. [ 5 ] [ 6 ] [ 7 ] [ 8 ]
Recent studies use newer statistical methods [ 9 ] and larger data sets showing longer movement paths. [ 10 ] Studies published in 2012 and 2013 re-analysed wandering albatross foraging paths and concluded strong support for truncated Lévy flights and Brownian walks consistently with predictions of the Lévy flight foraging hypothesis. [ 11 ] [ 12 ]
From the theoretical point of view, a recent study [ 13 ] disputes the validity of the optimality result published in 1999, by concluding that for bi- or tri-dimensional random walks, this result is only valid for very specific conditions: (i) once a target has been foraged, it has to reappear infinitely fast, (ii) the typical scale of the animal displacement has to be very small compared to the typical size of the targets, (iii) after a target is found, the animal has to start a new random walk infinitely close to the border of this target. If any of these conditions is not valid, the optimality result does not hold: inverse-square Levy walks are not optimal, and the gain of any optimal Levy walk over others is necessarily marginal (in the sense that it does not diverge when the density of targets is low).
In contrast, assuming that the search is intermittent [ 14 ] (i.e., detection is possible only at the short pauses between jumps), a different argument for the optimality of the inverse-square Lévy walk has been given. [ 15 ] Mathematical arguments show that in finite two-dimensional domains the intermittent inverse-square Lévy walk is optimal when the goal is to minimize the search time until finding a target of unpredictable size. In contrast, any intermittent Lévy walks other than the inverse-square walk fail to efficiently find either small or large targets. In other words, the inverse-square Lévy walk stands out as the only intermittent Lévy process that is highly efficient with respect to all target scales without the need for any adaptation. This result highlights the relationships between the detection ability of the searcher and the robustness and speed of the search. [ 15 ]
Another mathematical argument which shows that inverse-square Lévy walks are not generally optimal has been subsequently provided by studying the search efficiency of a group of individuals that have to find a single target in the infinite two-dimensional grid Z 2 {\displaystyle \mathbb {Z} ^{2}} . [ 16 ] In particular, it has been considered a setting with k {\displaystyle k} individuals that start performing a Lévy walk at the origin of the grid (a nest-site), and where there is a target at some fixed ( Manhattan ) distance D {\displaystyle D} from the origin; D {\displaystyle D} must be at most some exponential function in k {\displaystyle k} , which is a reasonable assumption since otherwise the target might not be found with non-negligible probability. It can then be proven that the target is found in almost-optimal time with high probability if the exponent of the power-law density distribution is α ⋆ ∼ 3 − log k / log D {\displaystyle \alpha ^{\star }\sim 3-\log k/\log D} . Any constant deviation from α ⋆ {\displaystyle \alpha ^{\star }} results in sub-optimal hitting time. However, such a choice for the power-law exponent requires the knowledge, by the individuals, of both the number of individuals k {\displaystyle k} and the target distance D {\displaystyle D} , which may be a very strong assumption in living societies. For this reason, it has been provided a simple almost-optimal search strategy without such requirements: if each individual samples uniformly at random the power-law exponent from the interval ( 2 , 3 ) {\displaystyle (2,3)} and then performs the corresponding Lévy walk, the target is still found in almost-optimal time with high probability. This strategy surprisingly achieves near-optimal search efficiency for all distance scales, and implies that different members of the same group follow different search patterns.
The existence of such variation in the search patterns among individuals of the same species requires empirical validation. [ 16 ] These results highlight that Lévy walks are indeed optimal search strategies, but there isn't any power-law exponent playing a universal role; instead, in the latter setting, any exponent between 2 {\displaystyle 2} and 3 {\displaystyle 3} might be employed depending on the number of individuals k {\displaystyle k} and the target distance D {\displaystyle D} . | https://en.wikipedia.org/wiki/Lévy_flight_foraging_hypothesis |
In set theory and mathematical logic , the Lévy hierarchy , introduced by Azriel Lévy in 1965, is a hierarchy of formulas in the formal language of the Zermelo–Fraenkel set theory , which is typically called just the language of set theory. This is analogous to the arithmetical hierarchy , which provides a similar classification for sentences of the language of arithmetic .
In the language of set theory, atomic formulas are of the form x = y or x ∈ y, standing for equality and set membership predicates, respectively.
The first level of the Lévy hierarchy is defined as containing only formulas with no unbounded quantifiers and is denoted by Δ 0 = Σ 0 = Π 0 {\displaystyle \Delta _{0}=\Sigma _{0}=\Pi _{0}} . [ 1 ] The next levels are given by finding a formula in prenex normal form which is provably equivalent over ZFC, and counting the number of changes of quantifiers : [ 2 ] p. 184
A formula A {\displaystyle A} is called: [ 1 ] [ 3 ]
As a formula might have several different equivalent formulas in prenex normal form, it might belong to several different levels of the hierarchy. In this case, the lowest possible level is the level of the formula. [ citation needed ]
Lévy's original notation was Σ i Z F C {\displaystyle \Sigma _{i}^{\mathsf {ZFC}}} (resp. Π i Z F C {\displaystyle \Pi _{i}^{\mathsf {ZFC}}} ) due to the provable logical equivalence, [ 4 ] strictly speaking the above levels should be referred to as Σ i Z F C {\displaystyle \Sigma _{i}^{\mathsf {ZFC}}} (resp. Π i Z F C {\displaystyle \Pi _{i}^{\mathsf {ZFC}}} ) to specify the theory in which the equivalence is carried out, however it is usually clear from context. [ 5 ] pp. 441–442 Pohlers has defined Δ 1 {\displaystyle \Delta _{1}} in particular semantically, in which a formula is " Δ 1 {\displaystyle \Delta _{1}} in a structure M {\displaystyle M} ". [ 6 ]
The Lévy hierarchy is sometimes defined for other theories S . In this case Σ i {\displaystyle \Sigma _{i}} and Π i {\displaystyle \Pi _{i}} by themselves refer only to formulas that start with a sequence of quantifiers with at most i −1 alternations, [ citation needed ] and Σ i S {\displaystyle \Sigma _{i}^{S}} and Π i S {\displaystyle \Pi _{i}^{S}} refer to formulas equivalent to Σ i {\displaystyle \Sigma _{i}} and Π i {\displaystyle \Pi _{i}} formulas in the language of the theory S . So strictly speaking the levels Σ i {\displaystyle \Sigma _{i}} and Π i {\displaystyle \Pi _{i}} of the Lévy hierarchy for ZFC defined above should be denoted by Σ i Z F C {\displaystyle \Sigma _{i}^{ZFC}} and Π i Z F C {\displaystyle \Pi _{i}^{ZFC}} .
Let n ≥ 1 {\displaystyle n\geq 1} . The Lévy hierarchy has the following properties: [ 2 ] p. 184
Devlin p. 29 | https://en.wikipedia.org/wiki/Lévy_hierarchy |
In mathematics, the Lévy–Steinitz theorem identifies the set of values to which sums of rearrangements of an infinite series of vectors in R n can converge. It was proved by Paul Lévy in his first published paper when he was 19 years old. [ 1 ] In 1913 Ernst Steinitz filled in a gap in Lévy's proof and also proved the result by a different method. [ 2 ]
In an expository article, Peter Rosenthal stated the theorem in the following way. [ 3 ] | https://en.wikipedia.org/wiki/Lévy–Steinitz_theorem |
In mathematical logic , Löb's theorem states that in Peano arithmetic (PA) (or any formal system including PA), for any formula P , if it is provable in PA that "if P is provable in PA then P is true", then P is provable in PA. If Prov( P ) is the assertion that the formula P is provable in PA, we may express this more formally as
An immediate corollary (the contrapositive ) of Löb's theorem is that, if P is not provable in PA, then "if P is provable in PA, then P is true" is not provable in PA. For example, "If 1 + 1 = 3 {\displaystyle 1+1=3} is provable in PA, then 1 + 1 = 3 {\displaystyle 1+1=3} " is not provable in PA. [ 1 ]
Löb's theorem is named for Martin Hugo Löb , who formulated it in 1955. [ 2 ] It is related to Curry's paradox . [ 3 ]
Provability logic abstracts away from the details of encodings used in Gödel's incompleteness theorems by expressing the provability of ϕ {\displaystyle \phi } in the given system in the language of modal logic , by means of the modality ◻ ϕ {\displaystyle \Box \phi } . That is, when ϕ {\displaystyle \phi } is a logical formula, another formula can be formed by placing a box in front of ϕ {\displaystyle \phi } , and is intended to mean that ϕ {\displaystyle \phi } is provable.
Then we can formalize Löb's theorem by the axiom
known as axiom GL, for Gödel–Löb. This is sometimes formalized by means of the inference rule:
The provability logic GL that results from taking the modal logic K4 (or K , since the axiom schema 4, ◻ A → ◻ ◻ A {\displaystyle \Box A\rightarrow \Box \Box A} , then becomes redundant) and adding the above axiom GL is the most intensely investigated system in provability logic.
Löb's theorem can be proved within normal modal logic using only some basic rules about the provability operator (the K4 system) plus the existence of modal fixed points .
We will assume the following grammar for formulas:
A modal sentence is a formula in this syntax that contains no propositional variables. The notation ⊢ A {\displaystyle \vdash A} is used to mean that A {\displaystyle A} is a theorem.
If F ( X ) {\displaystyle F(X)} is a modal formula with only one propositional variable X {\displaystyle X} , then a modal fixed point of F ( X ) {\displaystyle F(X)} is a sentence Ψ {\displaystyle \Psi } such that
We will assume the existence of such fixed points for every modal formula with one free variable. This is of course not an obvious thing to assume, but if we interpret ◻ {\displaystyle \Box } as provability in Peano Arithmetic, then the existence of modal fixed points follows from the diagonal lemma .
In addition to the existence of modal fixed points, we assume the following rules of inference for the provability operator ◻ {\displaystyle \Box } , known as Hilbert–Bernays provability conditions :
Much of the proof does not make use of the assumption ◻ P → P {\displaystyle \Box P\to P} , so for ease of understanding, the proof below is subdivided to leave the parts depending on ◻ P → P {\displaystyle \Box P\to P} until the end.
Let P {\displaystyle P} be any modal sentence.
More informally, we can sketch out the proof as follows.
An immediate corollary of Löb's theorem is that, if P is not provable in PA, then "if P is provable in PA, then P is true" is not provable in PA. Given we know PA is consistent (but PA does not know PA is consistent), here are some simple examples:
In doxastic logic , Löb's theorem shows that any system classified as a reflexive " type 4 " reasoner must also be " modest ": such a reasoner can never believe "my belief in P would imply that P is true", without also believing that P is true. [ 4 ]
Gödel's second incompleteness theorem follows from Löb's theorem by substituting the false statement ⊥ {\displaystyle \bot } for P .
Not only does the existence of modal fixed points imply Löb's theorem, but the converse is valid, too. When Löb's theorem is given as an axiom (schema), the existence of a fixed point (up to provable equivalence) p ↔ A ( p ) {\displaystyle p\leftrightarrow A(p)} for any formula A ( p ) modalized in p can be derived. [ 5 ] Thus in normal modal logic , Löb's axiom is equivalent to the conjunction of the axiom schema 4 , ( ◻ A → ◻ ◻ A ) {\displaystyle (\Box A\rightarrow \Box \Box A)} , and the existence of modal fixed points. | https://en.wikipedia.org/wiki/Löb's_theorem |
Löffler's medium is a special substance used to grow diphtheria bacilli to confirm the diagnosis.
In 1887, Friedrich Loeffler devised a culture medium containing horse serum, meat infusion, and dextrose for use in the cultivation of corynebacteria and for differentiating them from other organisms. [ 1 ] Perry and Petran suggested modification of the original
formulation. [ 2 ] Buck, in 1949, described a modified Loeffler's medium for cultivating Corynebacterium diphtheriae . [ 3 ]
This medium has a variety of uses in microbiological investigations. The current formulation incorporated these later modifications:
Heart muscle and animal tissue peptone provide the amino acids and other complex nitrogenous substances necessary to support
growth of corynebacteria. Sodium chloride supplies essential ions.
Dextrose is a source of fermentable carbohydrate . The eggs and beef serum cause the medium to coagulate during the
sterilization process and are sources of protein which are used for metabolism of the corynebacteria and other organisms. | https://en.wikipedia.org/wiki/Löffler's_medium |
In mathematical logic the Löwenheim number of an abstract logic is the smallest cardinal number for which a weak downward Löwenheim–Skolem theorem holds. [ 1 ] They are named after Leopold Löwenheim , who proved that these exist for a very broad class of logics.
An abstract logic, for the purpose of Löwenheim numbers, consists of:
The theorem does not require any particular properties of the sentences or models, or of the satisfaction relation, and they may not be the same as in ordinary first-order logic . It thus applies to a very broad collection of logics, including first-order logic , higher-order logics , and infinitary logics .
The Löwenheim number of a logic L is the smallest cardinal κ such that if an arbitrary sentence of L has any model, the sentence has a model of cardinality no larger than κ .
Löwenheim proved the existence of this cardinal for any logic in which the collection of sentences forms a set , using the following argument. Given such a logic, for each sentence φ , let κ φ be the smallest cardinality of a model of φ , if φ has any model, and let κ φ be 0 otherwise. Then the set of cardinals
exists by the axiom of replacement . The supremum of this set, by construction, is the Löwenheim number of L . This argument is non-constructive: it proves the existence of the Löwenheim number, but does not provide an immediate way to calculate it.
Two extensions of the definition have been considered: [ 2 ]
For any logic for which the numbers exist, the Löwenheim–Skolem–Tarski number will be no less than the Löwenheim–Skolem number, which in turn will be no less than the Löwenheim number.
Note that versions of these definitions replacing "has a model of size no larger than" with "has a model smaller than" are sometimes used, as this yields a more fine-grained classification. [ 2 ] | https://en.wikipedia.org/wiki/Löwenheim_number |
In mathematical logic , the Löwenheim–Skolem theorem is a theorem on the existence and cardinality of models , named after Leopold Löwenheim and Thoralf Skolem .
The precise formulation is given below. It implies that if a countable first-order theory has an infinite model , then for every infinite cardinal number κ it has a model of size κ , and that no first-order theory with an infinite model can have a unique model up to isomorphism .
As a consequence, first-order theories are unable to control the cardinality of their infinite models.
The (downward) Löwenheim–Skolem theorem is one of the two key properties, along with the compactness theorem , that are used in Lindström's theorem to characterize first-order logic .
In general, the Löwenheim–Skolem theorem does not hold in stronger logics such as second-order logic .
In its general form, the Löwenheim–Skolem Theorem states that for every signature σ , every infinite σ - structure M and every infinite cardinal number κ ≥ | σ | , there is a σ -structure N such that | N | = κ and such that
The theorem is often divided into two parts corresponding to the two cases above. The part of the theorem asserting that a structure has elementary substructures of all smaller infinite cardinalities is known as the downward Löwenheim–Skolem Theorem . [ 1 ] : 160–162 The part of the theorem asserting that a structure has elementary extensions of all larger cardinalities is known as the upward Löwenheim–Skolem Theorem . [ 2 ]
Below we elaborate on the general concept of signatures and structures.
A signature consists of a set of function symbols S func , a set of relation symbols S rel , and a function ar : S func ∪ S rel → N 0 {\displaystyle \operatorname {ar} :S_{\operatorname {func} }\cup S_{\operatorname {rel} }\rightarrow \mathbb {N} _{0}} representing the arity of function and relation symbols. (A nullary function symbol is called a constant symbol.) In the context of first-order logic, a signature is sometimes called a language. It is called countable if the set of function and relation symbols in it is countable, and in general the cardinality of a signature is the cardinality of the set of all the symbols it contains.
A first-order theory consists of a fixed signature and a fixed set of sentences (formulas with no free variables) in that signature. [ 3 ] : 40 Theories are often specified by giving a list of axioms that generate the theory, or by giving a structure and taking the theory to consist of the sentences satisfied by the structure.
Given a signature σ , a σ - structure M is a concrete interpretation of the symbols in σ . It consists of an underlying set (often also denoted by " M ") together with an interpretation of the function and relation symbols of σ . An interpretation of a constant symbol of σ in M is simply an element of M . More generally, an interpretation of an n -ary function symbol f is a function from M n to M . Similarly, an interpretation of a relation symbol R is an n -ary relation on M , i.e. a subset of M n .
A substructure of a σ -structure M is obtained by taking a subset N of M which is closed under the interpretations of all the function symbols in σ (hence includes the interpretations of all constant symbols in σ ), and then restricting the interpretations of the relation symbols to N . An elementary substructure is a very special case of this; in particular an elementary substructure satisfies exactly the same first-order sentences as the original structure (its elementary extension).
The statement given in the introduction follows immediately by taking M to be an infinite model of the theory. The proof of the upward part of the theorem also shows that a theory with arbitrarily large finite models must have an infinite model; sometimes this is considered to be part of the theorem. [ 1 ]
A theory is called categorical if it has only one model, up to isomorphism. This term was introduced by Veblen (1904) , and for some time thereafter mathematicians hoped they could put mathematics on a solid foundation by describing a categorical first-order theory of some version of set theory. The Löwenheim–Skolem theorem dealt a first blow to this hope, as it implies that a first-order theory which has an infinite model cannot be categorical. Later, in 1931, the hope was shattered completely by Gödel's incompleteness theorem . [ 1 ]
Many consequences of the Löwenheim–Skolem theorem seemed counterintuitive to logicians in the early 20th century, as the distinction between first-order and non-first-order properties was not yet understood. One such consequence is the existence of uncountable models of true arithmetic , which satisfy every first-order induction axiom but have non-inductive subsets.
Let N denote the natural numbers and R the reals. It follows from the theorem that the theory of ( N , +, ×, 0, 1) (the theory of true first-order arithmetic) has uncountable models, and that the theory of ( R , +, ×, 0, 1) (the theory of real closed fields ) has a countable model. There are, of course, axiomatizations characterizing ( N , +, ×, 0, 1) and ( R , +, ×, 0, 1) up to isomorphism.
The Löwenheim–Skolem theorem shows that these axiomatizations cannot be first-order.
For example, in the theory of the real numbers, the completeness of a linear order used to characterize R as a complete ordered field, is a non-first-order property. [ 1 ] : 161
Another consequence that was considered particularly troubling is the existence of a countable model of set theory, which nevertheless must satisfy the sentence saying the real numbers are uncountable. Cantor's theorem states that some sets are uncountable. This counterintuitive situation came to be known as Skolem's paradox ; it shows that the notion of countability is not absolute . [ 4 ]
For each first-order σ {\displaystyle \sigma } -formula φ ( y , x 1 , … , x n ) {\displaystyle \varphi (y,x_{1},\ldots ,x_{n})} , the axiom of choice implies the existence of a function
such that, for all a 1 , … , a n ∈ M {\displaystyle a_{1},\ldots ,a_{n}\in M} , either
or
Applying the axiom of choice again we get a function from the first-order formulas φ {\displaystyle \varphi } to such functions f φ {\displaystyle f_{\varphi }} .
The family of functions f φ {\displaystyle f_{\varphi }} gives rise to a preclosure operator F {\displaystyle F} on the power set of M {\displaystyle M}
for A ⊆ M {\displaystyle A\subseteq M} .
Iterating F {\displaystyle F} countably many times results in a closure operator F ω {\displaystyle F^{\omega }} . Taking an arbitrary subset A ⊆ M {\displaystyle A\subseteq M} such that | A | = κ {\displaystyle \left\vert A\right\vert =\kappa } , and having defined N = F ω ( A ) {\displaystyle N=F^{\omega }(A)} , one can see that also | N | = κ {\displaystyle \left\vert N\right\vert =\kappa } . Then N {\displaystyle N} is an elementary substructure of M {\displaystyle M} by the Tarski–Vaught test .
The trick used in this proof is essentially due to Skolem, who introduced function symbols for the Skolem functions f φ {\displaystyle f_{\varphi }} into the language. One could also define the f φ {\displaystyle f_{\varphi }} as partial functions such that f φ {\displaystyle f_{\varphi }} is defined if and only if M ⊨ ∃ y φ ( y , a 1 , … , a n ) {\displaystyle M\models \exists y\,\varphi (y,a_{1},\ldots ,a_{n})} . The only important point is that F {\displaystyle F} is a preclosure operator such that F ( A ) {\displaystyle F(A)} contains a solution for every formula with parameters in A {\displaystyle A} which has a solution in M {\displaystyle M} and that
First, one extends the signature by adding a new constant symbol for every element of M {\displaystyle M} . The complete theory of M {\displaystyle M} for the extended signature σ ′ {\displaystyle \sigma '} is called the elementary diagram of M {\displaystyle M} . In the next step one adds κ {\displaystyle \kappa } many new constant symbols to the signature and adds to the elementary diagram of M {\displaystyle M} the sentences c ≠ c ′ {\displaystyle c\neq c'} for any two distinct new constant symbols c {\displaystyle c} and c ′ {\displaystyle c'} . Using the compactness theorem , the resulting theory is easily seen to be consistent. Since its models must have cardinality at least κ {\displaystyle \kappa } , the downward part of this theorem guarantees the existence of a model N {\displaystyle N} which has cardinality exactly κ {\displaystyle \kappa } . It contains an isomorphic copy of M {\displaystyle M} as an elementary substructure. [ 5 ] [ 6 ] : 100–102
Although the (classical) Löwenheim–Skolem theorem is tied very closely to first-order logic, variants hold for other logics. For example, every consistent theory in second-order logic has a model smaller than the first supercompact cardinal (assuming one exists). The minimum size at which a (downward) Löwenheim–Skolem–type theorem applies in a logic is known as the Löwenheim number, and can be used to characterize that logic's strength. Moreover, if we go beyond first-order logic, we must give up one of three things: countable compactness, the downward Löwenheim–Skolem Theorem, or the properties of an abstract logic . [ 7 ] : 134
This account is based mainly on Dawson (1993) . To understand the early history of model theory one must distinguish between syntactical consistency (no contradiction can be derived using the deduction rules for first-order logic) and satisfiability (there is a model). Somewhat surprisingly, even before the completeness theorem made the distinction unnecessary, the term consistent was used sometimes in one sense and sometimes in the other.
The first significant result in what later became model theory was Löwenheim's theorem in Leopold Löwenheim 's publication "Über Möglichkeiten im Relativkalkül" (1915):
Löwenheim's paper was actually concerned with the more general Peirce –Schröder calculus of relatives ( relation algebra with quantifiers). [ 1 ] He also used the now antiquated notations of Ernst Schröder . For a summary of the paper in English and using modern notations see Brady (2000 , chapter 8).
According to the received historical view, Löwenheim's proof was faulty because it implicitly used Kőnig's lemma without proving it, although the lemma was not yet a published result at the time. In a revisionist account, Badesa (2004) considers that Löwenheim's proof was complete.
Skolem (1920) gave a (correct) proof using formulas in what would later be called Skolem normal form and relying on the axiom of choice:
Skolem (1922) also proved the following weaker version without the axiom of choice:
Skolem (1929) simplified Skolem (1920) . Finally, Anatoly Ivanovich Maltsev (Анато́лий Ива́нович Ма́льцев, 1936) proved the Löwenheim–Skolem theorem in its full generality ( Maltsev 1936 ). He cited a note by Skolem, according to which the theorem had been proved by Alfred Tarski in a seminar in 1928. Therefore, the general theorem is sometimes known as the Löwenheim–Skolem–Tarski theorem . But Tarski did not remember his proof, and it remains a mystery how he could do it without the compactness theorem .
It is somewhat ironic that Skolem's name is connected with the upward direction of the theorem as well as with the downward direction:
The Löwenheim–Skolem theorem is treated in all introductory texts on model theory or mathematical logic . | https://en.wikipedia.org/wiki/Löwenheim–Skolem_theorem |
Lüders bands are a type of plastic bands, slip band or stretcher-strain mark which are formed due to localized bands of plastic deformation in metals experiencing tensile stresses, common to low-carbon steels and certain Al-Mg alloys. [ 1 ] First reported by Guillaume Piobert , and later by W. Lüders , [ 2 ] the mechanism that stimulates their appearance is known as dynamic strain aging , or the inhibition of dislocation motion by interstitial atoms (in steels, typically carbon and nitrogen ), around which " atmospheres " or "zones" naturally congregate.
As internal stresses tend to be highest at the shoulders of tensile test specimens, band formation is favored in those areas. However, the formation of Lüders bands depends primarily on the microscopic (i.e. average grain size and crystal structure , if applicable) and macroscopic geometries of the material. For example, a tensile-tested steel bar with a square cross-section tends to develop comparatively more bands than would a bar of identical composition having a circular cross-section. [ 3 ]
The formation of a Lüders band is preceded by a yield point and a drop in the flow stress. Then the band appears as a localized event of a single band between plastically deformed and undeformed material that moves with the constant cross head velocity. The Lüders Band usually starts at one end of the specimen and propagates toward the other end. [ 4 ] The visible front on the material usually makes a well-defined angle typically 50–55° from the specimen axis as it moves down the sample. [ 5 ] During the propagation of the band the nominal stress–strain curve is flat. [ 4 ] After the band has passed through the material the deformation proceeds uniformly with positive strain hardening . Sometimes Lüders band transition into the Portevin–Le Chatelier effect while changing the temperature or strain rate , this implies these are related phenomena [ 4 ] Lüders bands are known as a strain softening instability. [ 5 ]
If a sample is stretched beyond the range of the Lüder strain once, no Lüder strain occurs any more when the sample is deformed again, since the dislocations have already torn themselves away from the interstitial atoms. For this reason, deep drawing sheets are often cold rolled in advance to prevent the formation of stretcher-strain marks during the actual deep drawing process. [ 6 ] The formation of Lüder bands can occur again with a deformation over time, since the interstitial atoms accumulate by diffusing processes called precipitation hardening (or aging ). | https://en.wikipedia.org/wiki/Lüders_band |
M-PHY is a high speed data communications physical layer protocol standard developed by the MIPI Alliance , PHY Working group, and targeted at the needs of mobile multimedia devices. [ 1 ] The specification's details are proprietary to MIPI member organizations, but a substantial body of knowledge can be assembled from open sources. A number of industry standard settings bodies have incorporated M-PHY into their specifications including Mobile PCI Express , [ 2 ] [ 3 ] [ 4 ] [ 5 ] [ 6 ] [ 7 ] [ 8 ] Universal Flash Storage , [ 9 ] [ 10 ] [ 11 ] and as the physical layer for SuperSpeed InterChip USB . [ 12 ] [ 13 ] [ 14 ] [ 15 ] [ 16 ] [ 17 ]
To support high speed, M-PHY is generally transmitted using differential signaling over impedance controlled traces between components. When use on a single circuit card , the use of electrical termination may be optional. Options to extend its range could include operation over a short flexible flat cable , and M-PHY was designed to support optical media converters allowing extended distance between transmitters and receivers, and reducing concerns with electromagnetic interference. [ 15 ]
M-PHY (like its predecessor [ dubious – discuss ] D-PHY ) is intended to be used in high-speed point-to-point communications, for example video Camera Serial Interfaces . The CSI-2 interface was based on D-PHY (or C-PHY ), while the newer CSI-3 interface is based on M-PHY. M-PHY was designed to supplant D-PHY in many applications, but this is expected to take a number of years.
The M-PHY the physical layer is also used in a number of different high-speed emergent industry standards , DigRF (High speed radio interface), MIPI LLI (Low latency memory interconnect for multi-processors systems), and one possible physical layer for the UniPro protocol stack .
M-PHY supports a scalable variety of signaling speeds, ranging from 10 kbit/s to over 11.6 Gbit/s per lane. This is accomplished using two different major signaling/speed modes, a simple low-speed (using PWM ) mode and high speed (using 8b10b ). [ 18 ] Communications goes on in bursts, and the design of both high-speed and low-speed forms allows for extended periods of idle communications at low-power, making the design particularly suitable for mobile devices.
Within each signaling method, a number of standard speeds, known as "gears", is defined, with the expectation that additional gears will be defined in future versions of the standard. [ 19 ]
This computer networking article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/M-PHY |
In M-SG an alkali metal is absorbed into silica gel at elevated temperatures. The resulting black powder material is an effective reducing agent and safe to handle as opposed to the pure metal. The material can also be used as a desiccant and as a hydrogen source. [ 1 ]
The metal is either sodium or a sodium - potassium alloy ( Na 2 K ). The molten metal is mixed with silica gel under constant agitation at room temperature . This phase 0 material must be handled in an inert atmosphere. Heating phase 0 at 150 °C (302 °F) takes it to phase I . When this material is exposed to dry oxygen the reducing power is not affected. At further heating to 400 °C (752 °F) phase II can be handled safely in an ambient environment.
The metal reacts with the silica gel in an exothermic reaction in which Na 4 Si 4 nanoparticles are formed. The powder reacts with water to form hydrogen .
Compounds such as biphenyl and naphthalene are reduced by the powder and form highly coloured radical anions . The powder can also be introduced in a column chromatography setup and eluted with organic reactants in order to probe the reducing power. The powder is mixed with additional (wet) silica gel which provides additional hydrogen. A Birch reduction of naphthalene takes 5 minutes elution time . The column converts benzyl chloride to bibenzyl in a Wurtz coupling and in a similar fashion dibenzothiophene is reduced to biphenyl . | https://en.wikipedia.org/wiki/M-SG_reducing_agent |
This page provides supplementary chemical data on m -Xylene .
The handling of this chemical may incur notable safety precautions. It is highly recommend that you seek the Material Safety Datasheet ( MSDS ) for this chemical from a reliable source such as SIRI, and follow its directions.
Table data obtained from CRC Handbook of Chemistry and Physics 44th ed.
See also:
Linstrom, Peter (1997). "NIST Standard Reference Database" . National Institute of Standards and Technology. doi : 10.18434/T4D303 . {{ cite journal }} : Cite journal requires |journal= ( help ) | https://en.wikipedia.org/wiki/M-Xylene_(data_page) |
An M -ary transmission is a type of digital modulation where instead of transmitting one bit at a time, two or more bits are transmitted simultaneously. This type of transmission results in reduced channel bandwidth . However, sometimes, two or more quadrature carriers are used for modulation. This process is known as quadrature modulation .
This computing article is a stub . You can help Wikipedia by expanding it .
This article related to radio communications is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/M-ary_transmission |
M-learning , or mobile learning , is a form of distance education or technology enhanced active learning where learners use portable devices such as mobile phones to learn anywhere and anytime. The portability that mobile devices provide allows for learning anywhere, hence the term "mobile" in "mobile learning." [ 1 ] M-learning devices include computers , MP3 players , mobile phones, and tablets . M-learning can be an important part of informal learning . [ 2 ]
M-learning is convenient in that it is accessible virtually anywhere. It allows for the instant sharing of feedback and tips since mobile devices are often connected to the internet. M-learning also offers strong portability by replacing books and notes with small devices filled with tailored learning content. Moreover, it has the added benefit of being cost-effective, as the price of digital content on tablets is falling sharply compared to traditional media such as books, CDs, DVDs, etc. For example, a digital textbook costs one-third to half the price of a paper textbook, with zero marginal cost. [ 3 ]
According to Fombona, Pascual-Sevillana, and González-Videgaray, this methodology offers various possibilities, including greater and different access to information. It also introduces significant innovations, such as the increase in informal and playful activities, iconic virtual membership, and networks of friendly interaction within new scales of values. [ 4 ]
Mobile learning is seen as either the “delivery” of education, or the “provision” of support on mobile phones, PDAs, or tablets. New mobile technology, such as hand-held-based devices, is playing a large role in redefining how people receive and process information. [ 5 ]
Concepts of m-learning were introduced by Alan Kay in the 1970s when he joined Xerox Corporation 's Palo Alto Research Center and formed a group to develop the "Dynabook," a portable and hands-on personal computer. The aim was to provide children with access to the digital world. [ 6 ] However, this project eventually failed due to a lack of technological support at that time. In 1994, Mitsubishi Electric Corp. created the first smartphone called IBM Simon , which was defined as a handheld personal communicator. [ 7 ] Following this, various technological companies began designing what we now know as " smartphones ." The creation of smartphones laid the foundation for mobile learning, and subsequent innovations in mobile devices propelled mobile learning into the realm of projects and research.
Chronologically, m-learning research has been characterized into three phases: the first phase is the focus on devices; the second is the focus on learning outside the classroom; the third phase is the focus on the mobility of the learner. [ 8 ] In its second phase, around 2005, a tremendous number of projects have been completed, four major projects are "The Leonardo da Vinci project From e-learning to m-learning led by Ericsson Education Dublin", "The Leonardo da Vinci project Mobile learning: the next generation of learning led by Ericsson Education Dublin", "The IST project M-Learning led by the United Kingdom government Learning and Skills Development Agency (LSDA)" and "The IST project MOBILearn led by Giunti Ricerca of Genoa, Italy". These projects are mainly targeted on the effects of m-learning, like motivation to learn, engagement in learning activities, and focus on special needs people; [ 9 ] they set the tone for mobile learning, and m-learning is prepared to transfer from project status to mainstream education and training. [ 10 ]
Chronologically, m-learning research can be divided into three phases: the first phase focused on devices, the second phase emphasised learning outside the classroom, and the third phase emphasised the mobility of learners. [ 8 ] During the second phase, around 2005, a significant number of projects were completed. Four notable projects were "The Leonardo da Vinci project: From e-learning to m-learning," led by Ericsson Education Dublin; "The Leonardo da Vinci project: Mobile learning - the next generation of learning," also led by Ericsson Education Dublin; "The IST project: M-Learning," led by the United Kingdom government Learning and Skills Development Agency (LSDA); and "The IST project: MOBILearn," led by Giunti Ricerca of Genoa , Italy . These projects primarily focused on the effects of m-learning, such as motivation to learn, engagement in learning activities, and catering to the needs of special needs individuals. [ 11 ] They set the stage for mobile learning, preparing it to transition from project status to mainstream education and training. [ 12 ]
Currently, m-learning research has become globalised, with Africa, Asia, North America, Europe, Scandinavia, Australia, and New Zealand all making remarkable achievements in this field. [ 8 ]
Applications in classrooms and other learning spaces combine the use of handheld computers , PDAs , smartphones , or handheld voting systems (such as clickers ) with traditional resources. [ 13 ]
Mobile devices in brick-and-mortar classrooms can be used to enhance student-centered learning and group collaboration among students through communication applications, interactive displays, quick response codes, [ 14 ] and video features. [ 15 ]
In a literature review conducted by FutureLab, researchers found that increased communication, collaboration, and understanding of concepts were a result of mobile technology applications. [ 17 ]
Mobile devices can be used in online settings to enhance learning experiences. [ 18 ]
Podcasting consists of listening to audio recordings of lectures. It can be used to review live lectures [ 20 ] and to provide opportunities for students to rehearse oral presentations.
Podcasts may also provide supplemental information to enhance traditional lectures. [ 21 ]
Psychological research suggests that university students who download podcast lectures achieve substantially higher exam results than those who attend the lecture in person (only in cases in which students take notes ). [ 22 ]
Podcasts may be delivered using syndication , although this method of delivery is not always easily adopted. [ 23 ]
M-learning in the context of work can encompass various forms of learning. It has been defined as the "processes of coming to know, and of being able to operate successfully in, and across, new and ever-changing contexts, including learning for, at and through work, by utilising mobile devices". [ 24 ]
Learning for work , also known as 'just-in-case' learning, involves traditional and formal educational activities, such as training courses, that prepare learners for future work-related tasks. A typical corporate application is the delivery of mobile compliance training, which can effectively reach geographically mobile employees like consultants [ 25 ] or staff in logistics and transport systems. [ 26 ] Another application is mobile simulations that prepare learners for future situations, such as real-time SMS-based simulations for disaster response training. [ 27 ]
Learning at and through work , labeled as "just-in-time" mobile learning, [ 28 ] occurs in informal educational settings within the workplace. Employees can use mobile phones and handheld devices to solve problems on the spot, for example, by accessing informational resources like checklists and reference guides before customer visits [ 29 ] or mobile decision support systems. The latter is particularly popular in clinical settings, where they assist highly mobile medical staff in making decisions regarding complex patient cases using rule-based algorithms. Their application has been associated with learning and, specifically, with improving the practice of medical staff. [ 30 ] Learning through work also occurs through interaction with distant peers via phone. "People tagging" is an approach where individuals assign topics to their co-workers. The aggregation of interests and experiences serves as a means to raise awareness and locate competent experts when needed, particularly with context-sensitive expert location systems. [ 31 ]
Cross-contextual learning , which bridges the gap between work settings and formal education formats, holds significant potential for work-based mobile learning, [ 24 ] especially within tertiary education systems. This involves approaches where learning in the workplace is facilitated and supported (e.g., through formative assessments, [ 32 ] reflective questions, [ 33 ] or the documentation of personal achievements in multimedia learning diaries or portfolios [ 34 ] ) The materials created in this process are later utilised in more formal educational formats, such as classrooms or discussions with tutors. The value of these mobile phone-mediated learning practices lies in the integration and harmonisation of work-based learning and formal education experiences, which otherwise tend to remain separate.
Mobile technologies and approaches, i.e. mobile-assisted language learning (MALL), are also used to assist in language learning . For instance handheld computers, cell phones, and podcasting [ 35 ] have been used to help people acquire and develop language skills.
Refugees are confronted several individual challenges that can negatively impact their learning and teaching opportunities, as well as their lives beyond the learning environment. Mobile solutions play a key role in enhancing refugees' informal learning. Technology provides support for refugees' informal learning in the following challenges: [ 37 ]
The Finnish National Core Curriculum for Basic Education was renewed in 2014. Considering the increasing significance of technology as both an objective and a means of learning, ICT and mobile learning were integrated into the new National Core Curriculum as a transversal competence that is present in all learning and teaching.
PaikkaOppi (which roughly means ’learning of places’) is a Finnish educational innovation supporting open science and the information society. It is an open web-based learning environment for Geographic Information System (GIS) usage in schools. Moreover, it is a potential spearhead in national policy for the development of skills and education by integrating disciplines and promoting the use of mobile learning. Students are able to view, analyze and share their data collaboratively or individually with browser-based map applications. Mobile applications for Android and iOS devices are for saving personal data in the field trips or at home. Being accessible to all users free of charge, PaikkaOppi is very widely used at schools, home and on free time as well. The service supports teaching the core curricula: competences for spatial citizenship, multi-literacy skills, logical thinking, and problem solving skills. The service is being used all over the country as a project platform for several school subjects and multidisciplinary learning modules from primary schools to upper secondary. [ 38 ]
In Pakistan, the Rehan School was one of the first initiatives to offer remote courses that could be accessed from a basic mobile phone. The application offers short educational sequences, showing how to write common names and words and conveying mathematical and scientific concepts. Sometimes featuring television personalities, the teaching sketches are intended for viewing on small telephone screens. The films are sold for a few cents in the telecoms boutiques and can then be exchanged by Bluetooth. The Rehan School estimates that over 40,000 individuals follow its lessons, but the real number is certainly higher. [ 3 ]
In Papua New Guinea, the SMS Story project has improved teachers' classroom practices in teaching children to read by using short messages and sent by SMS. [ 3 ]
Since the 1960s, various information and communication technologies have aroused strong interest in Sub-Saharan Africa as a way of increasing access to education, and enhancing its quality and fairness. In Sub-Saharan Africa, teachers and students are faced with an extreme shortage of teaching materials. The number of textbooks available are limited, so few students have individual access to textbooks in class or at home. Given the shortage of textbooks in many African schools, tablets and mobile phones are being viewed by governments and international organizations as a solution to provide access to learning materials. In one example, the Tangerine mobile assessment and coaching system, deployed in Kenya, aims to help teachers in their assessment activities. With Tangerine, a student's reading level can be evaluated by recording the student's answers on a mobile phone or a tablet. The data gathered by the application also allows comparisons of the learning levels of students according to their age, geographical area and gender. [ 3 ]
A recent study on health professions education combined evidence from 29 studies, which included 3175 learners, and concluded that mLearning is as effective as traditional learning in terms of improving learners' knowledge and skill. The study highlights that mLearning is a novel educational strategy that is rapidly developing in the field of health professions education, "21 of the 29 included studies (72%) published between 2014 and 2017, it’s clear that mLearning is an emerging educational strategy. The remaining 8 studies were published between 2006 and 2013, with no studies published before 2006, further highlighting the modern nature of this approach to health professions education and its relevance" [ 39 ]
Tutors who have used m-learning programs and techniques have made the following value statements in favor of m-learning.
Characterization of M-learning
Aspects of M-learning
Along with the development of m-learning, many theories about mobile educations are raised by researchers, major aspects are listed.
Technical challenges
Social and educational challenges [ 49 ]
Mobile learning is widely used in schools, workplaces, museums , cities and rural areas around the world. [ 56 ] In comparison to traditional classroom pedagogical approaches, mobile learning allows widened opportunities for timing, location, accessibility and context of learning. [ 5 ] [ 57 ]
Current areas of growth include: | https://en.wikipedia.org/wiki/M-learning |
In no-limit or pot-limit poker , a player's M-ratio (also called "M number", "M factor" [ 1 ] or just "M") is a measure of the health of a player's chip stack as a function of the cost to play each round. In simple terms, a player can sit passively in the game, making only compulsory bets, for M laps of the dealer button before running out of chips. A high M means the player can afford to wait a high number of rounds before making a move. The concept applies primarily in tournament poker; in a cash game, a player can in principle manipulate their M at will, simply by purchasing more chips.
A player with a low M must act soon or be weakened by the inability to force other players to fold with aggressive raises.
The term was named after Paul Magriel .
The M-ratio is calculated by the formula:
For example, a player in an eight-player game with blinds of $50/$100, an ante of $10, and a stack of $2,300 has an M-ratio of 10:
That is, if the player only makes the compulsory bets, they will be "blinded out" of the game in 10 rounds, or 80 hands.
Dan Harrington studied the concept in great detail in Harrington on Holdem : Volume II The Endgame , [ 2 ] defining several "zones" in which the M-ratio may fall: [ 3 ]
Harrington further develops the concept to account for shortening tables, as is seen at the closing stages of multi-table tournaments. The M-ratio is simply multiplied by the percentage of players remaining at the table, assuming a ten-player table to be "full". [ 5 ]
Therefore, for a player with a "simple M ratio" of 9 at a five player table, the effective M is 4.5:
This means that although the player's simple M value places him in the orange zone, their effective M dictates a shift in playing style appropriate for the red zone. In essence, ten times the effective M denotes the expected number of hands a player can let pass before running out of chips. | https://en.wikipedia.org/wiki/M-ratio |
M Anwar Hossain (born 20 August 1949) is a Bangladeshi scientist , writer, and politician. He is a professor at the Department of Biochemistry and Molecular Biology of University of Dhaka and a member of the Standing Committee of the Jatiya Samajtantrik Dal . [ 1 ] [ 2 ] [ 3 ] [ 4 ] He was the 14th vice chancellor of Jahangirnagar University and the former president of the Dhaka University Teachers' Association (DUTA) and Bangladesh Society of Biochemistry and Molecular Biology. [ 5 ] [ 6 ] Hossain was a freedom fighter of the Bangladesh Liberation War of 1971 during which he served as a staff officer of sector 11. Hossain has been detained and imprisoned twice by military rulers of Bangladesh and has been described by Senator Edward Kennedy as a 'prisoner of conscience'. [ 7 ] [ 8 ]
Hossain was born in the Juri Station of Sylhet on 20 August 1949 to his parents Mohiuddin Ahmed and Begum Ashrafunnessa. Mohiuddin who began his career as an apprentice of the British Railway was serving as station master of Juri when Anwar was born. Anwar had three sisters and eight brothers. Eight of the eleven brothers and sisters actively participated in the Liberation War of Bangladesh in 1971. Four of Anwar's brothers, Lt. Colonel Abu Taher , Abu Yusuf Khan, Shakhawat Hossain Bahar and Waresat Hussain Belal , were awarded the Bir Uttam, Bir Bikram, Bir Protik and Bir Protik respectively.
Anwar obtained his bachelor's and master's from the Department of Biochemistry and Molecular Biology at the University of Dhaka in 1971 and 1972 respectively. He did his MSc thesis under the supervision of Kamaluddin Ahmad. [ 9 ] Anwar joined Department of Biochemistry and Molecular Biology at the University of Dhaka as a lecturer on 1 January 1975. In 1982 Anwar was awarded a Monbukagakusho Scholarship with which he pursued doctoral studies at Kyoto University , Japan under the supervision of Kozi Asada. His Ph.D. thesis was titled "Photosynthesis: Plant's Defence Mechanism Against Photo-Oxidative Damage” and was awarded the degree in 1985. He became an assistant professor at 1985 and associate professor at 1990. From 1994 to till date he is working as a selection grade professor in the Department of Biochemistry and Molecular Biology, University of Dhaka. He was Chairman of the Department from 2001 to 2003. Hossain was elected as Dean of the Biological Sciences and the Founding Project Director of Dhaka University's Department of Biotechnology and Genetic Engineering. [ 10 ] Currently he is also teaching in Biochemistry and Microbiology Department in North South University. He has, in the past, served as the elected General Secretary and President of the Dhaka University Teachers' Association (DUTA) for multiple terms. [ 11 ] [ 12 ] Hossain was elected as the vice-chancellor of Jahangirnagar University (JU) on 17 July 2012, a position which he served till January 2014. [ 13 ]
Hossain has conducted research with world renowned plant scientists, among whom are Joseph C. Arthur Distinguished Professor of Plant Physiology and Emeritus Professor of Botany and Plant Pathology of Purdue University Thomas K Hodges, Japanese plant physiologist and Professor Emeritus of Kyoto University Kozi Asada, former president of the Australian Academy of Science Jim Peacock and Professor Kamaluddin Ahmad. With over 1400 citations, Hossain is one of the most cited plant scientists in Bangladesh. [ 14 ] His works have appeared in premier scientific journals including the Journal of Biological Chemistry , Plant Physiology , Plant Molecular Biology and Plant and Cell Physiology. [ 15 ] [ 16 ] [ 17 ] [ 18 ] [ 19 ] [ 20 ] [ 21 ] Hossain serves in the Editorial Board of Bioresearch Communications . [ 22 ] After his PhD he returned to Bangladesh for 2–3 years, and then again went to Kyoto Prefectural University as a part of a Biotechnology Career Fellowship Program (1987–1990). This time he studied plant genetic engineering.
From 1991 to 1994 and 1995–1996 he worked at Purdue University, USA and Kyoto University, Japan respectively as visiting scientist (full-time professor) during which he worked for developing submergence (flood) tolerant rice.
After the fall of the Sheikh Hasina led Awami League government, Hossain was assaulted outside Shahjalal International Airport on 9 August 2024. [ 23 ] The attackers allegedly said, “You spoke against Jamaat. We’re going to slit your throat.”. [ 23 ] In May 2025, an attempted murder case was filed against him over a student of Alia Madrasa getting injured in Old Dhaka during protests against former Prime Minister Sheikh Hasina in August 2024. [ 24 ]
Hossain's columns have appeared in leading national dailies such as bdnews24 , Janakantha , Kaler Kantho , and Samakal . [ 25 ] He has written four books. | https://en.wikipedia.org/wiki/M._Anwar_Hossain |
M. C. Escher: Visions of Symmetry is a book by mathematician Doris Schattschneider published by W. H. Freeman in 1990. The book analyzes the symmetry of M. C. Escher's colored periodic drawings and explains the methods he used to construct his artworks. Escher made extensive use of two-color and multi-color symmetry in his periodic drawings. The book contains more than 350 illustrations, half of which were never previously published.
The book is divided into five chapters. Before the main text there is a foreword and a preface, and the book is concluded with a concordance, afterword (in the second edition only), bibliography and four indexes.
The first chapter, 'The Route to Regular Division', describes Escher's early artistic development, and how Escher first became intrigued by the problem of filling the plane with interlocking shapes ( tessellation ). This work came to dominate his art from 1937. He was also encouraged, by a half-brother who was a professor of geology, to study papers on symmetry by Pólya and other mathematicians in the Zeitschrift für Kristallographie . These helped launch Escher into his own detailed investigations of the rules for generating the allowable patterns for tiling the plane.
The second chapter 'The 1941–1942 Notebooks' presents, for the first time, the complete set of numbered drawings from the two 1941–1942 notebooks which summarize Escher's theory of the regular divisions of the plane, and details the classification system Escher used to organize his drawings.
The third chapter 'The Regular Division Drawings' is the longest in the book at 118 pages. It reproduces all of the known drawings (numbers 1 to 137) and the known periodic designs (A1 to A14) from Escher's 1938–1941 notebooks together with his notes on their symmetry type.
The fourth chapter 'The Use of Regular Division' explains that Escher regarded his periodic drawings as a means to an end rather than as finished works of art in their own right. The periodic drawings were the solutions to the question of what was possible when tiling the plane using the rules that Escher had established. Escher used the periodic drawings as a basis for developing his completed artworks.
The fifth chapter 'Notes on the drawings' provides additional information of each of the drawings in chapter 3. For each drawing the following information is given: number, title, place drawn, medium, dimensions, Escher system type, symmetry group, previous publication, and notes.
The book concludes with a concordance which gives a complete tabulation of the symmetry groups represented by Escher's periodic drawings and an afterword, in the second edition only, which outlines the developments in the subject between 1990 and 2004. [ 1 ] [ 2 ]
In her preface, the author's stated objective for the book is to answer the question "How did he do it?". The audience for the book is any person who admires, or is interested in, M. C. Escher's periodic drawings and would like to understand his methods for designing and executing his artworks. As no prior mathematical knowledge is assumed by the author to understand the material presented in the book, it is appropriate for a general audience. As Michele Emmer comments in his review: "It is important that, with this beautiful volume, artists and scientists can look at Escher's original notebooks." [ 1 ]
The book was widely reviewed and its reception was very positive. [ 3 ] Alan L. Mackay in a full-page review for Nature wrote: "This book contains very many colour reproductions of the periodic drawings and analyses the 1941–42 notebooks which show Escher's development [...] Taking Doris Schattschneider's beautiful volume with earlier books, especially that by Bruno Ernst, documentation of Escher's life, intellectual development and corpus must now be almost complete." [ 4 ] Roger Goodwin writing in The British Journal of Aesthetics said "This book, the product of more than fifteen years of research by its mathematician author, provides the definitive account of how Escher produced his renowned interlocking drawings, based on the regular division of the plane." [ 5 ] Michele Emmer reviewing the book in Leonardo wrote: "Escher's theory, recorded in the notebooks of 1941–1942, has never been completely published before. All the 150 color drawings of interlocking patterns that he produced from 1937 to 1941 are reproduced in the book. It is, of course, the most essential part of the volume." [ 1 ] Marjorie Senechal wrote the entry for Mathematical Reviews : "The development of Escher's ideas is carefully traced, the influence of his work on others, and vice versa, is discussed, and all of the notebook drawings are presented in full color. Doris Schattschneider has written the Escher book for mathematicians." [ 6 ]
John Galloway reviewing the book for New Scientist said: "Many books have been written about Escher's art. None has approached Visions of Symmetry for its scope, scale and sumptuousness. The sheer beauty and ingenuity of the pictures keep you turning the pages as though the book were a collection of detective stories whose plots are brilliantly organised patterns." [ 7 ] In an extensive review in The American Mathematical Monthly Douglas Dunham said: "For the Escher fan, Visions of Symmetry fills a gap in the literature by showing all of his notebook patterns, answering the question "how did he do it?", and relating the patterns to his prints. For the person interested in tilings and patterns, Visions of Symmetry provides many beautiful examples (which illustrate the theory expounded in Grünbaum and Shepard's Tilings and patterns [1987])." [ 8 ] J. Kevin Colligan reviewing the book for The Mathematics Teacher wrote: "This book sits on the boundary between mathematics and art, as did Escher. In fact, this book supports the argument that no such boundary exists; rather, the two disciplines coexist and intermingle, enriching both." [ 9 ] Paul Garcia writing in The Mathematical Gazette writes: "I recommend the book highly to anyone - the price is small compared to the scope and interest of the work. Doris Schattschneider has done us all a tremendous favour by compiling this book." [ 2 ]
David Topper writing of the second edition in Choice said "This beautiful book remains one of the essential studies of this most popular artist." [ 10 ] Gerald L. Alexanderson writing in MAA Reviews said "It's an impressive piece of scholarship that is extraordinarily beautiful as well. This book is an old friend and it's good to welcome it back in such an elegant and sumptuous form." [ 11 ] Laurence Goldstein reviewing the second edition in Print Quarterly said: "... the reader is enabled to glimpse the process through which the artist struggled towards the finished works of art that Hofstadter (and, of course, many others) find so sensuously gratifying. There is also a wealth of biographical information concerning the mathematical and artistic influences on Escher's work, and on the creative process as witnessed by people close to him and as perceived by the artist himself." [ 12 ] A brief, unsigned review in Science said: "Escher's periodic tilings have made the artist a favorite of mathematicians and scientists. In her classic 1990 book, Schattschneider analyzed his art and notebooks to explain how Escher created his colorful, puzzle-like regular divisions of the plane [...] This new edition adds a short survey of reflections of his work in mathematics, computer graphics, the Internet, and contemporary art." [ 13 ] An unsigned review in the Epsilon Pi Tau Journal of Technology Studies said: "A revision of a classic book that appeared in 1990, this is the most penetrating study of Escher's work in existence and the one most admired by scientists and mathematicians. It deals with one powerful obsession that preoccupied Escher: what he called the 'regular division of the plane', the puzzle-like interlocking of birds, fish, lizards, and other natural forms in continuous patterns. Schattschneider explores how he succeeded at this task by meticulously analyzing his notebooks." [ 14 ] | https://en.wikipedia.org/wiki/M._C._Escher:_Visions_of_Symmetry |
Mary Grace Burke is an American materials scientist who is an emeritus professor at the University of Manchester . She was awarded the 2020 International Metallographic Society Henry Clifton Sorby Award and was the 2019-2023 President of the Royal Microscopical Society .
Burke was raised in Pittsburgh . [ 1 ] She remained in Pittsburgh for undergraduate studies, during which she specialized in metallurgical engineering at the University of Pittsburgh . Burke attended Imperial College London , where she did her PhD research on stress corrosion cracking (SCC). Working under the supervision of P. R. Swann and F. J. Humphreys, Burke studied the mechanism of SCC of austenitic stainless steel. Burke was interested in the relationship between materials behavior and microstructure. [ 1 ]
After earning her doctorate, Burke returned to the United States , where she worked at the U.S. Steel Research Laboratory in Monroeville , Pennsylvania. [ 1 ] She studied thermomechanical processing effects on microstructural evolution in steels, using analytical transmission electron microscopy . She also performed correlative TEM analyses in combination with atom probe field ion microscopy (APFIM).
Burke also studies irradiation embrittlement of the steels and alloys used in light water reactor systems. She joined the Westinghouse Science and Technology Center, where she studied a broad range materials and alloys for nuclear power systems. [ 2 ] She transferred to the Bettis Atomic Power Laboratory , where she studied how microstructure impacted the performance of materials. [ 1 ]
Burke joined the University of Manchester in England as a Professor of Materials Performance and Director of the Materials Performance Centre in 2011. [ 3 ] | https://en.wikipedia.org/wiki/M._Grace_Burke |
M. Lothaire is the pseudonym of a group of mathematicians, many of whom were students of Marcel-Paul Schützenberger . The name is used as the author of several of their joint books about combinatorics on words . The group is named for Lothair I . [ 1 ]
Mathematicians in the group have included
Jean-Paul Allouche, [ 2 ] Jean Berstel , [ 3 ] [ 4 ] Valérie Berthé , [ 2 ] Véronique Bruyère , [ 3 ] Julien Cassaigne, [ 3 ] Christian Choffrut, [ 4 ] Robert Cori, [ 4 ] Maxime Crochemore [ 2 ] Jacques Desarmenien, [ 3 ] Volker Diekert, [ 3 ] Dominique Foata , [ 3 ] [ 4 ] Christiane Frougny, [ 3 ] Guo-Niu Han, [ 3 ] Tero Harju, [ 3 ] Philippe Jacquet, [ 2 ] Juhani Karhumäki , [ 3 ] Roman Kolpakov, [ 2 ] Gregory Koucherov, [ 2 ] Eric Laporte, [ 2 ] Alain Lascoux , [ 3 ] Bernard Leclerc, [ 3 ] Aldo De Luca, [ 3 ] Filippo Mignosi, [ 3 ] Mehryar Mohri , [ 2 ] Dominique Perrin , [ 3 ] [ 4 ] Jean-Éric Pin , [ 4 ] Giuseppe Pirillo, [ 4 ] Nadia Pisanti, [ 2 ] Wojciech Plandowski, [ 3 ] Dominique Poulalhon, [ 2 ] Gesine Reinert , [ 2 ] Antonio Restivo, [ 3 ] Christophe Reutenauer, [ 3 ] [ 4 ] Marie-France Sagot , [ 2 ] Jacques Sakarovitch, [ 4 ] Gilles Schaeffer, [ 2 ] Sophie Schbath , [ 2 ] Marcel-Paul Schützenberger , [ 4 ] Patrice Séébold, [ 3 ] Imre Simon , [ 4 ] Wojciech Szpankowski , [ 2 ] Jean-Yves Thibon, [ 3 ] Stefano Varricchio, [ 3 ] and Michael Waterman . [ 2 ] | https://en.wikipedia.org/wiki/M._Lothaire |
Sir Michael Stanley Whittingham (born 22 December 1941) is a British-American chemist . He is a professor of chemistry and director of both the Institute for Materials Research and the Materials Science and Engineering program at Binghamton University , State University of New York . He also serves as director of the Northeastern Center for Chemical Energy Storage (NECCES) of the U.S. Department of Energy at Binghamton. He was awarded the Nobel Prize in Chemistry in 2019 alongside Akira Yoshino and John B. Goodenough . [ 1 ] [ 2 ]
Whittingham is a key figure in the history of lithium-ion batteries , which are used in everything from mobile phones to electric vehicles. He discovered intercalation electrodes and thoroughly described intercalation reactions in rechargeable batteries in the 1970s. He holds the patents on the concept of using intercalation chemistry in high power-density, highly reversible lithium-ion batteries. He also invented the first rechargeable lithium metal battery (LMB), patented in 1977 and assigned to Exxon for commercialization in small devices and electric vehicles. Whittingham's rechargeable lithium metal battery is based on a LiAl anode and an intercalation-type TiS 2 cathode. His work on lithium batteries laid the foundation for others' developments, so he is called the founding father of lithium-ion batteries. [ 3 ]
Whittingham was born in the Carlton suburb of Nottingham , England , on 22 December 1941. [ 4 ] [ 5 ] His father was a civil engineer, the first in the family to go to college. [ 6 ] His mother Dorothy Mary (née Findley) was a chemist before marriage. [ 7 ] He was educated at Stamford School from 1951 to 1960, before going up to New College, Oxford to read chemistry. At the University of Oxford , he took his BA (1964), MA (1967), and DPhil (1968). [ 8 ] After completing his graduate studies, Whittingham became a postdoctoral fellow at Stanford University . [ 9 ] He worked 16 years for Exxon Research & Engineering Company [ 9 ] and four years working for Schlumberger prior to becoming a professor at Binghamton University . [ 8 ]
From 1994 to 2000, he served as the university's vice provost for research. [ 4 ] He also served as vice-chair of the Research Foundation of the State University of New York for six years. He is a Distinguished Professor of Chemistry and Materials Science and Engineering at Binghamton University. [ 9 ] Whittingham was named Chief Scientific Officer of NAATBatt International in 2017. [ 4 ]
Whittingham co-chaired the DOE study of Chemical Energy Storage in 2007, [ 10 ] and is a director of the Northeastern Center for Chemical Energy Storage (NECCES), a U.S. Department of Energy Energy Frontier Research Center (EFRC) at Binghamton. In 2014, NECCES was awarded $12.8 million, from the U.S. Department of Energy to help accelerate scientific breakthroughs needed to build the 21st-century economy. In 2018, NECCES was granted another $3 million by the Department of Energy to continue its research on batteries. The NECCES team is using the funding to improve energy-storage materials and to develop new materials that are "cheaper, environmentally friendly, and able to store more energy than current materials can". [ 11 ]
Whittingham conceived the intercalation electrode. Exxon manufactured Whittingham's lithium-ion battery in the 1970s, based on a titanium disulfide cathode and a lithium-aluminum anode. [ 12 ] The battery had high energy density and the diffusion of lithium ions into the titanium disulfide cathode was reversible, making the battery rechargeable. In addition, titanium disulfide has a particularly fast rate of lithium ion diffusion into the crystal lattice. Exxon threw its resources behind the commercialization of a Li/LiClO 4 / TiS 2 battery. However, safety concerns led Exxon to end the project. Whittingham and his team continued to publish their work in academic journals of electrochemistry and solid-state physics. He left Exxon in 1984 and spent four years at Schlumberger as a manager. In 1988, he became Professor at the Chemistry Department, Binghamton University, U.S. to pursue his academic interests.
"All these batteries are called intercalation batteries. It’s like putting jam in a sandwich. In the chemical terms, it means you have a crystal structure, and we can put lithium ions in, take them out, and the structure’s exactly the same afterwards," Whittingham said. "We retain the crystal structure. That’s what makes these lithium batteries so good, allows them to cycle for so long." [ 12 ]
Lithium batteries have limited capacity because less than one lithium-ion/electron is reversibly intercalated per transition metal redox center. To achieve higher energy densities, one approach is to go beyond the one-electron redox intercalation reactions. Whittingham's research has advanced to multi-electron intercalation reactions, which can increase the storage capacity by intercalating multiple lithium ions. A few multi-electron intercalation materials have been successfully developed by Whittingham, like LiVOPO 4 /VOPO 4 . The multivalent vanadium cation (V 3+ <->V 5+ ) plays an important role to accomplish the multi-electron reactions. These promising materials shine lights on the battery industry to increase energy density rapidly.
Whittingham received the Young Author Award from The Electrochemical Society in 1971, [ 13 ] the Battery Research Award in 2003, [ 14 ] and was elected a Fellow in 2004. [ 15 ] In 2010, he was listed as one of the Top 40 innovators for contributions to advancing green technology by Greentech Media . [ 16 ] In 2012, Whittingham received the IBA Yeager Award for Lifetime Contribution to Lithium Battery Materials Research, [ 17 ] and he was elected a Fellow of Materials Research Society in 2013. [ 18 ] He was listed along with John B. Goodenough , for pioneering research leading to the development of the lithium-ion battery on a list of Clarivate Citation Laureates for the Nobel Prize in Chemistry by Thomson Reuters in 2015. [ 12 ] [ 19 ] In 2018, Whittingham was elected to the National Academy of Engineering , "for pioneering the application of intercalation chemistry for energy storage materials." [ 20 ]
In 2019, Whittingham, along with John B. Goodenough and Akira Yoshino , was awarded the 2019 Nobel Prize in Chemistry "for the development of lithium-ion batteries." [ 1 ] [ 2 ]
Stanley is married to Dr. Georgina Whittingham, a professor of Spanish at the State University of New York at Oswego . He has two children, Michael Whittingham and Jenniffer Whittingham-Bras.
[ 21 ] [ 22 ]
(As of 2019 [update] : [ 30 ] ) | https://en.wikipedia.org/wiki/M._Stanley_Whittingham |
Mandyam Tondanur Naraniengar (1871–1940) [ 1 ] was an Indian mathematician. He first proved in 1909 the Morley's trisector theorem after it was posed in 1899 by Frank Morley . [ 2 ]
He was the president of Indian Mathematical Society from 1930 to 1932 [ 3 ] and the editor of the Journal of the Indian Mathematical Society from its founding in 1909 until 1927. [ 1 ] | https://en.wikipedia.org/wiki/M._T._Naraniengar |
Manapurathu Verghese George (3 October 1928 - 9 December 2019) was an Indian photochemist and an emeritus professor of the National Institute for Interdisciplinary Science and Technology (NIIST). [ 2 ] He was known for establishing the Photochemistry Research Unit at NIIST and his studies on the mechanism of organic reactions . [ 3 ] He is a recipient of the 1992 TWAS Award [ 4 ] and an elected fellow of The World Academy of Sciences , [ 5 ] the Indian National Science Academy [ 6 ] and the Indian Academy of Sciences . [ 7 ] The Council of Scientific and Industrial Research , the apex agency of the Government of India for scientific research, awarded him the Shanti Swarup Bhatnagar Prize for Science and Technology , one of the highest Indian science awards, in 1973, for his contributions to chemical sciences. [ 8 ]
M. V. George, born on 3 October 1928 in the south Indian state of Kerala , graduated in chemistry from Madras University in 1948 and moved to the Dr. Bhimrao Ambedkar University (then known as Agra University) from where he secured his master's degree in 1951. [ 6 ] He did his doctoral studies at St. John's College, Agra of Agra University under the guidance of P. I. Ittyerah, a former principal of the college, and after securing PhD in 1954, he did his post-doctoral studies at various colleges in the US, UK, Germany and Canada. [ citation needed ]
He returned to India in 1963 and started his career as a member of faculty at the Indian Institute of Technology, Kanpur . [ citation needed ] He stayed at the institution for quarter of a century until 1988 during which period he headed the Department of Chemistry from 1966 to 1969, succeeding C. N. R. Rao . [ 9 ] Returning to his home state of Kerala in 1988, he joined the Regional Research Laboratory of the Council of Scientific and Industrial Research (present-day National Institute for Interdisciplinary Science and Technology ) as an emeritus professor and served the institution until his superannuation from service. In between, he had various stints at the University of Notre Dame as a visiting professor during 1978–2001. [ 6 ]
The main focus of George's research was centered on the mechanical implications of the thermal and photochemical organic reactions. [ 10 ] His studies covered different areas of organometallic chemistry and he worked on electron transfer processes, organic reactions and functional group transformations. Thus he studied the organic reactions and functional group transformations, heterohexa-1, 3, 5-triene systems with regard to its electrocyclic reactions and the synthetic utility and phototransformations of dibenzobarrelenes. He also studied the picosecond laser flash photolysis techniques and the transient intermediates involved in photoreactions. [ 6 ] He was noted for the original approach in his studies of hetero-aromatic systems. [ 10 ]
George published his research through over 200 articles in peer-reviewed journals [ 11 ] [ note 1 ] and guided a number of doctoral and post-doctoral scholars in their researches. He has contributed chapters to the Handbook of Chemistry and Physics , [ 12 ] edited by C. N. R. Rao [ 13 ] and his works have been cited by various authors in their publications. [ 14 ] [ 15 ] He pioneered photochemistry research at the National Institute for Interdisciplinary Science and Technology and established the Photochemistry Research Unit at the institution. [ 2 ] He was a collaborator of C. N. R. Rao in popularizing science education at academic levels and is associated, as the executive director, with the Foundation for Capacity Building in Science (FCBS) initiative which promotes science education among Indian students through seminars and workshops. [ 16 ] He also served as a member of the council of the Indian National Science Academy from 1989 to 1991. [ 6 ]
The Indian Academy of Sciences elected George as a fellow in 1973 before he became an elected fellow of the Indian National Science Academy in 1975. [ 7 ] The Council of Scientific and Industrial Research awarded him the Shanti Swarup Bhatnagar Prize , one of the highest Indian science awards, in 1973. [ 17 ] He received the C. V. Raman Award in 1985 and the Professor T. R. Seshadri 70th Birthday Commemoration Medal of the Indian National Science Academy in 1990. [ 18 ] The World Academy of Sciences awarded him the TWAS Prize in 1992 [ 4 ] and two years later, elected him as their fellow. [ 5 ] He is also a recipient of the Lifetime Achievement Award of the Chemical Research Society of India and a life member of the society. [ 19 ] | https://en.wikipedia.org/wiki/M._V._George |
M 1 G ( pyrimido[1,2- a ]purin-10( 3H )-one ) is a heterocyclic compound which is a by-product of base excision repair (BER) of a specific type of DNA adduct called M 1 dG. The M 1 dG adduct in turn is formed by a condensation reaction between guanosine nucleotides in DNA and either malondialdehyde (propanedial) [ 1 ] or acrolein . [ 2 ] If not repaired, these adducts are mutagenic and carcinogenic .
Malondialdehyde is an end product of lipid peroxidation [ 2 ] while acrolein is a result of DNA peroxidation. [ 3 ]
M 1 dG is the major endogenous DNA adduct in humans. M 1 dG adducts have been detected in cell DNA in liver , leucocytes , pancreas and breast in concentrations of 1-120 per 10 8 nucleotides . [ 1 ] Detection and quantification of M 1 dG adducts in the body as measured by free M 1 G is a tool for detecting DNA damage that may lead to cancer. Free M 1 G is also biomarker for oxidative stress . [ 1 ] | https://en.wikipedia.org/wiki/M1G |
The M-1 (or M-59 ) was a standard issue gas mask for troops in Yugoslavia , as well as for SFRY successor states ( Bosnia , Croatia , Macedonia , Montenegro , Slovenia , Serbia ). This respirator was only available until 2005, therefore, the filters are said to have had a limited working lifetime assigned. [ 1 ] It is a copy of the U.S. M-9 gas mask. It was also used by the Iraqi army in the Gulf War , where it was designated M-59 . It is OD green in color, and has a side-loading canister which uses a 60mm opening. The M-1 is not very common in the United States, as few were imported as surplus. There are different versions of the mask, MC-1 (civilian version), M-1 (civilian version but with oral nasal cup, and some things in the bag are different) and the M-59 (the military version). The filter doesn't have asbestos, but contains chromium.
This Yugoslavia -related article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/M1_gas_mask |
The M2 gas mask was a French -made gas mask used by French, British and American forces from April 1916 to August 1918 during World War I . [ 1 ] The M2 was fabricated in large quantities, with about 29,300,000 being made during the war. [ 2 ] It was intended to protect the wearer from at least five hours' exposure to phosgene gas, a common chemical weapon of the time. [ 3 ]
The M2 mask was based on a design proposed in 1915 by René Louis Gravereaux of Paris . An order of 600,000 masks was produced in February 1916 and introduced for British forces the following month. The first M2 model was produced in only one size and often incurred damage when it was folded for placement in a metal container. A second model introduced in April 1916 was produced in three different sizes and included two separate eyepieces, so folding it would not cause damage. British forces were issued 6.2 million units of the second model between May and November 1916 and used it as late as August 1918. [ 4 ]
When the United States entered World War I in 1917, it was unprepared for chemical warfare . The US Army issued its soldiers the British-made Small Box Respirator to protect against chemical attack, and the French-made M2 gas mask in case a mask had to be worn for an extended period of time. The untrained soldiers tended to put on the Small Box Respirator when first confronted with a gas attack and then switch to the M2 when they realized they would have to wear it for a long time. While switching gear, some soldiers inhaled the poison gas and became casualties. [ 5 ] [ 6 ]
In contrast with gas masks made later in the war, the M2 did not have a special filter that fit onto the mask. Instead, it was made of one piece of material which covered the face completely. During 1917, an additional mask strap was produced, intended to be worn around the head of the wearer. [ 4 ]
The first model of the M2 mask was introduced during March 1916 and had a rectangular piece of cellophane glass for viewing, protected by a piece of glass in front of it. In April, the rectangle was replaced by two round pieces of cellophane glass due to problems on the earlier model, which could not be cleaned without removing the glass. These two glasses were held in place by a metal ring on each eyehole, with 12 dents in each so as to better hold the glass on the mask. [ 4 ]
The M2 protected the wearer for at least five hours against the common World War I chemical weapon phosgene. [ 3 ] After a while, condensation in the mask built up, which severely encumbered the wearer, requiring the mask to be taken off. [ 2 ] | https://en.wikipedia.org/wiki/M2_gas_mask |
M30 Apoptosense® ELISA is an enzyme -linked immunosorbent assay developed for the detection of soluble caspase - cleaved keratin 18 (ccK18, K18-Asp396, formerly cytokeratin 18, ccCK18 or CK18-Asp396).
The M30 Apoptosense® ELISA is a PEVIVA product owned by VLVbio (Nacka, Sweden) and was developed in collaboration with the Karolinska Institute in 2000.
Distributors:
The M30 Apoptosense® ELISA is a non-invasive test for the detection of apoptosis of epithelially derived cells. Caspases are activated in apoptotic cells and cleave intracellular protein substrates . Keratin 18 (K18) is one such substrate, expressed by many epithelial cells (e.g. hepatocytes, intestinal cells, breast cells, prostate cells). Cleaved K18 is released into the circulation after cell death. The main uses of M30 Apoptosense® ELISA are to:
Caspases cleave keratin 18 at two sites during apoptosis. Cleavage at Asp396 generates a neo-epitope recognized by the monoclonal antibody M30®. [ 6 ] This antibody does not recognize uncleaved K18 and is therefore specific for apoptotic epithelial cells. M30 Apoptosense® ELISA utilizes a second monoclonal antibody (M5) which recognizes an epitope N-terminal from the M30® epitope.
M30 Apoptosense® ELISA can be combined with the M65® ELISA (uncleaved K18) (PEVIVA®, VLVbio) to determine cell death mode (apoptosis versus necrosis). [ 7 ]
There has been some confusion in the literature on the use of the term “M30”. Although it should be very clear that “M30” is a monoclonal antibody (“M”) that detects the antigen “ccK18”/“K18-Asp396” people sometimes refer to the antigen as “M30”. This is incorrect.
It is clear that the use of the term “M30” in connection with “keratin” means the monoclonal antibody M30® or (possibly, but erroneously) the neo-epitope DALD396 on K18 recognized by the M30® monoclonal. “M30” is not a biological entity expressed in cells but a (patent protected) monoclonal antibody.
Caspase-cleaved fragment of keratin 18 = ccK18
Keratin 18 = K18 (or CK18)
M30® = the antibody that recognizes a neoepitope on ccK18
M65® ELISA = an ELISA composed of two antibodies (M5 and M6) for conventional epitopes of K18
M30®, Apoptosense®, M65®, EpiDeath®, and PEVIVA® are registered trademarks, including U.S. Trademarks 4,577,969, 2,749,204, 1,009,048, and 896,269. Additionally, VLVBio™ holds additional Trademarks in most countries worldwide. | https://en.wikipedia.org/wiki/M30-Apoptosense_ELISA |
M82 X-2 is an X-ray pulsar located in the galaxy Messier 82 , approximately 12 million light-years from Earth. [ 2 ] It is exceptionally luminous, radiating energy equivalent to approximately ten million Suns . This object is part of a binary system : If the pulsar is of an average size, 1.4 M ☉ , then its companion is at least 5.2 M ☉ . [ 3 ] On average, the pulsar rotates every 1.37 seconds, and revolves around its more massive companion every 2.5 days. [ 4 ]
M82 X-2 is an ultraluminous X-ray source (ULX), shining about 100 times brighter than theory suggests something of its mass should be able to. Its brightness is many times higher than the Eddington limit , a basic physics guideline that sets an upper limit on the brightness that an object of a given mass should be able to achieve. Possible explanations for violations of the Eddington limit include geometrical effects arising from the funneling of in-falling material along magnetic field lines.
While M82 X-2 was previously known as an X-ray source, it was not until an observation campaign to study the newly discovered supernova SN 2014J in January 2014 that X-2's true nature was uncovered. [ 5 ] [ 6 ] Scientists looking at data from the NuSTAR spacecraft noticed a pulsing in the X-ray spectrum coming from near the supernova in Messier 82. [ 2 ] [ 7 ] Data from the Chandra and Swift spacecraft was used to verify the NuSTAR findings and provide the necessary spatial resolution to determine the exact source. [ 3 ] [ 4 ] After combining the NuSTAR and Chandra data, scientists were able to discern that M82 X-2 emitted both an X-ray beam and continuous broad X-ray radiation. [ 1 ] LXs). In 2023 new NuSTAR data confirmed that it exceeded the Eddington limit. [ 8 ] [ 9 ] | https://en.wikipedia.org/wiki/M82_X-2 |
MA-FRA is an Italian chemical company specializing in automotive, motorcycle, boat, and industry care and cleaning products and is one of oldest in the industry. [ 1 ] [ 2 ]
MA-FRA was founded in 1965 by Gianfranco Mattioli [ 3 ] during the Economic Boom of the 1960s in Bresso , Italy. [ 4 ]
The company collaborated with Nelson Piquet in F1 during the 1980s and with Peugeot Rally in the 1990s. Later, MA-FRA became involved in Ferrari Challenge and collaborated closely with the Mille Miglia . [ 5 ]
In 2001, MA-FRA's headquarters moved to the plant in Baranzate, which is still the company's headquarters on the outskirts of Milan. [ 6 ]
In the 2010-2020 decade, MAFRA produced the "Ecolabel" line with totally "green" formulations made with natural and biodegradable surfactants. [ 7 ]
MA-FRA established the "Detailing School" in 2016 to technically train new professionals dedicated to car detailing. [ 8 ] [ 9 ] [ 10 ] The #Labocosmetica brand was launched in the same year, a line of products specifically for car detailing professionals. [ 11 ] [ 4 ]
During COVID-19, MA-FRA launched a series of products for car and room sanitization to counter the spread of the pandemic. [ 12 ] [ 13 ]
In 2022, MA-FRA was represented as a sponsor at numerous automotive events: Autopromotec 2022, the international aftermarket exhibition in Bologna. [ 14 ] [ 15 ]
The company was announced to participate in the Car Wash Show Europe 2023, the industry's largest event. [ 16 ] | https://en.wikipedia.org/wiki/MA-FRA |
MACD operations are basic actions (Move, Add, Change, Delete) taken by computer network or telecom service agents in the support of hardware and services. It can also refer to the "hours" spent and billed doing those kinds of support tasks. [ 1 ]
This computing article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/MACD_operations |
4DZO , 1GO4
8379
17120
ENSG00000002822
ENSMUSG00000029554
Q9Y6D9
Q9WTX8
NM_003550
NM_010752 NM_001359025 NM_001359027
NP_003541
NP_034882 NP_001345954 NP_001345956
Mitotic spindle assembly checkpoint protein MAD1 is a protein that in humans is encoded by the MAD1L1 gene . [ 5 ] [ 6 ] [ 7 ]
MAD1L1 is also known as Human Accelerated Region 3. It may have played a key role in the evolution of humans from apes. [ 8 ]
MAD1L1 is a component of the mitotic spindle-assembly checkpoint that prevents the onset of anaphase until all chromosome are properly aligned at the metaphase plate. MAD1L1 functions as a homodimer and interacts with MAD2L1 . MAD1L1 may play a role in cell cycle control and tumor suppression. Some studies indicate associations of MAD1L1 with psychiatric disorders, including schizophrenia, bipolar disorder, and depression. [ 9 ] [ 10 ] [ 11 ] Three transcript variants encoding the same protein have been found for this gene. [ 7 ]
MAD1L1 has been shown to interact with:
This biochemistry article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/MAD1L1 |
Multichannel Audio Digital Interface ( MADI ) standardized as AES10 by the Audio Engineering Society (AES) defines the data format and electrical characteristics of an interface that carries multiple channels of digital audio . The AES first documented the MADI standard in AES10-1991 and updated it in AES10-2003 and AES10-2008. The MADI standard includes a bit-level description and has features in common with the two-channel AES3 interface.
MADI supports serial digital transmission over coaxial cable or fibre-optic lines of 28, 56, 32, or 64 channels; and sampling rates to 96 kHz and beyond [ 1 ] : 5.1 with an audio bit depth of up to 24 bits per channel. Like AES3 and ADAT Lightpipe , it is a unidirectional interface from one sender to one receiver.
MADI was developed by AMS Neve , Solid State Logic , Sony and Mitsubishi [ 2 ] [ 3 ] and is widely used in the audio industry, especially in the professional audio sector. It provides advantages over other audio digital interface protocols and standards such as AES3 , ADAT Lightpipe , TDIF ( Tascam Digital Interface), and S/PDIF (Sony/Philips Digital Interface). These advantages include:
The original specification (AES10-1991) defined the MADI link as a 56-channel transport for linking large-format mixing consoles to digital multitrack recording devices. Large broadcast studios also adopted it for routing multi-channel audio throughout their facilities. The 2003 revision (AES10-2003) adds a 64-channel capability by removing varispeed operation and supports 96 kHz sampling frequency with reduced channel capacity. [ a ] The latest AES10-2008 standard includes minor clarifications and updates to correspond to the current AES3 standard.
Audio over Ethernet of various types is the primary alternative to MADI for transport of many channels of professional digital audio.
MADI links use a transmission format similar to Fiber Distributed Data Interface (FDDI) networking. Since MADI is most often transmitted on copper links via 75-ohm coaxial cables, it more closely compares to the FDDI specification for copper-based links, called CDDI. AES10-2003 recommends using BNC connectors with coaxial cables [ 1 ] : 7.1.4 and SC connectors [ b ] with optic fibers. [ 1 ] : 7.2.1 MADI over fibre can support a range of up to 2 km.
The basic data rate is 100 Mbit/s of data using 4B5B encoding to produce a 125 MHz physical baud rate . Unlike AES3, this clock is not synchronized to the audio sample rate , and the audio data payload is padded using JK sync symbols. Sync symbols may be inserted at any subframe boundary, and must occur at least once per frame. [ c ] Though the standard disassociates the transmission clock from the audio sample rate, and thus requires a separate word clock connection to maintain synchronization, some vendors do give the option of locking to parts of the transmission timing information for purposes of deriving a word clock.
The audio data is almost identical to the AES3 payload, though with more channels. Rather than letters, MADI assigns channel numbers from 0–63. Frame synchronization is provided by sync symbols outside the data itself, rather than an embedded preamble sequence, and the first four time slots of each sub-channel are encoded as normal data, used for sub-channel identification: [ 6 ]
The original AES10-1991 specification allowed 56 channels at sample rates from 32 to 48 kHz with an additional vari-speed range of ± 12.5%. [ 7 ] [ 8 ] This leads to a total range of 28 to 54 kHz. At the highest frequency, this produces a total of 56 × 32 × 54 = 96768 kbit/s, leaving 3.232% of the channel for synchronization marks and transmit clock error.
The 2003 revision specifies different relations between sampling frequency and number of channels. [ 9 ]
With a 48 kHz sampling frequency, 64 channels take 64 × 32 × 48000 = 98.304 Mbit/s. Adding the minimum 8 × 58 kbit/s of framing produces 98688 bit/s, leaving 1.312% free for timing variation and other overhead.
Both versions of the standard accommodate higher sampling frequencies (for example, 96 kHz or 192 kHz) by using two or more channels per audio sample on the link. | https://en.wikipedia.org/wiki/MADI |
MADNESS ( Multiresolution Adaptive Numerical Environment for Scientific Simulation )
is a high-level software environment for the solution of integral and differential equations in many dimensions using adaptive and fast harmonic analysis methods with guaranteed precision based on multiresolution analysis [ 2 ] [ 3 ] and separated representations
. [ 4 ]
There are three main components to MADNESS. At the lowest level is a petascale parallel programming environment [ 5 ] that aims to increases programmer productivity and code performance/scalability while maintaining backward compatibility with current programming tools such as the message-passing interface and Global Arrays . The numerical capabilities built upon the parallel tools provide a high-level environment for composing and solving numerical problems in many (1-6+) dimensions. Finally, built upon the numerical tools are new applications with initial focus upon chemistry, [ 6 ] [ 7 ] , atomic and molecular physics, [ 8 ] material science, and nuclear structure. It is open-source , has an object-oriented design, and is designed to be a parallel processing program for computers with up to millions of cores running already on the Cray XT5 at Oak Ridge National Laboratory and the IBM Blue Gene at Argonne National Laboratory . The small matrix multiplication (relative to large, BLAS -optimized matrices) is the primary computational kernel in MADNESS; thus, an efficient implement on modern CPUs is an ongoing research effort. [ 9 ] . [ 10 ] Adapting the irregular computation in MADNESS to heterogeneous platforms is nontrivial due to the size of the kernel, which is too small to be offloaded via compiler directives (e.g. OpenACC ), but has been demonstrated for CPU – GPU systems
. [ 11 ] Intel has publicly stated that MADNESS is one of the codes running on the Intel MIC architecture [ 12 ] [ 13 ] but no performance data has been published yet.
MADNESS' chemistry capability includes Hartree–Fock and density functional theory in chemistry [ 14 ] [ 15 ] (including analytic derivatives, [ 16 ] response properties [ 17 ] and time-dependent density functional theory with asymptotically corrected potentials [ 18 ] )
as well as nuclear density functional theory [ 19 ] and Hartree–Fock – Bogoliubov theory. [ 20 ] [ 21 ] MADNESS and BigDFT are the two most widely known codes that perform DFT and TDDFT using wavelets
. [ 22 ] Many-body wavefunctions requiring six-dimensional spatial representations are also implemented
(e.g. MP2 [ 23 ] ).
The parallel runtime inside of MADNESS has been used to implement a wide variety of features, including graph optimization
. [ 24 ] From a mathematical perspective, MADNESS emphasizes rigorous numerical precision without loss of computational performance
. [ 25 ] This is useful not only in quantum chemistry and nuclear physics, but also the modeling of partial differential equations . [ 26 ]
MADNESS was recognized by the R&D 100 Awards in 2011. [ 27 ] [ 28 ] It is an important code to Department of Energy supercomputing sites and is being used by both the leadership computing facilities at Argonne National Laboratory [ 29 ] and Oak Ridge National Laboratory [ 30 ] to evaluate the stability and performance of their latest supercomputers. It has users around the world, including the United States and Japan
. [ 31 ] MADNESS has been a workhorse code for computational chemistry in the DOE INCITE program [ 32 ] at the Oak Ridge Leadership Computing Facility [ 33 ] and is noted as one of the important codes to run on the Cray Cascade architecture. [ 34 ] | https://en.wikipedia.org/wiki/MADNESS |
The MADS box is a conserved sequence motif . The genes which contain this motif are called the MADS-box gene family. [ 1 ] The MADS box encodes the DNA-binding MADS domain. The MADS domain binds to DNA sequences of high similarity to the motif CC[A/T] 6 GG termed the CArG-box. [ 2 ] MADS-domain proteins are generally transcription factors . [ 2 ] [ 3 ] The length of the MADS-box reported by various researchers varies somewhat, but typical lengths are in the range of 168 to 180 base pairs, i.e. the encoded MADS domain has a length of 56 to 60 amino acids. [ 4 ] [ 5 ] [ 6 ] [ 7 ] There is evidence that the MADS domain evolved from a sequence stretch of a type II topoisomerase in a common ancestor of all extant eukaryotes. [ 8 ]
The first MADS-box gene to be identified was ARG80 from budding yeast, Saccharomyces cerevisiae , [ 9 ] but was at that time not recognized as a member of a large gene family. The MADS-box gene family got its name later as an acronym referring to the four founding members, [ 1 ] ignoring ARG80 :
In A. thaliana , A. majus , and Zea mays this motif is involved in floral development. Early study in these model angiosperms was the beginning of research into the molecular evolution of floral structure in general, as well as their role in nonflowering plants. [ 11 ]
MADS-box genes have been detected in nearly all eukaryotes studied. [ 8 ] While the genomes of animals and fungi generally possess only around one to five MADS-box genes, genomes of flowering plants have around 100 MADS-box genes. [ 12 ] [ 13 ] Two types of MADS-domain proteins are distinguished; the SRF-like or Type I MADS-domain proteins and the MEF2-like (after MYOCYTE-ENHANCER-FACTOR2 ) or Type II MADS-domain proteins. [ 8 ] [ 13 ] SRF-like MADS-domain proteins in animals and fungi have a second conserved domain, the SAM (SRF, ARG80, MCM1) domain. [ 14 ] MEF2-like MADS-domain proteins in animals and fungi have the MEF2 domain as a second conserved domain. [ 14 ] In plants, the MEF2-like MADS-domain proteins are also termed MIKC-type proteins referring to their conserved domain structure, where the MADS (M) domain is followed by an Intervening (I), a Keratin-like (K) and a C-terminal domain . [ 12 ] In plants, MADS-domain protein form tetramers and this is thought to be central for their function. [ 15 ] [ 16 ] The structure of the tetramerisation domain of the MADS-domain protein SEPALLATA3 was solved illustrating the structural basis for tetramer formation [ 17 ]
A geneticist intensely investigating MADS-box genes is Günter Theißen at the University of Jena . For example, he and his coworkers have used these genes to show that the order Gnetales is more closely related to the conifers than to the flowering plants . [ 18 ]
MADS-box is under-studied in wheat as of 2021 [update] . [ 19 ]
In Zea mays the mutant Tunicate1 produces pod corn . Tunicate1 is a mutant of Z. mays MADS19 ( ZMM19 ), in the SHORT VEGETATIVE PHASE gene family. ZMM19 can be ectopically expressed . [ 19 ]
Such ectopic expression of ZMM19 in A. thaliana enlarges sepals , suggesting conservation . [ 19 ]
MADS-box genes have a variety of functions. In animals, MADS-box genes are involved in muscle development and cell proliferation and differentiation. [ 14 ] Functions in fungi range from pheromone response to arginine metabolism. [ 14 ]
In plants, MADS-box genes are involved in controlling all major aspects of development, including male and female gametophyte development, embryo and seed development, as well as root, flower and fruit development. [ 12 ] [ 13 ]
Some MADS-box genes of flowering plants have homeotic functions like the HOX genes of animals. [ 1 ] The floral homeotic MADS-box genes (such as AGAMOUS and DEFICIENS ) participate in the determination of floral organ identity according to the ABC model of flower development . [ 20 ]
Another function of MADS-box genes is flowering time determination. In Arabidopsis thaliana the MADS box genes SOC1 [ 21 ] and Flowering Locus C [ 22 ] ( FLC ) have been shown to have an important role in the integration of molecular flowering time pathways. These genes are essential for the correct timing of flowering , and help to ensure that fertilization occurs at the time of maximal reproductive potential.
The MADS box protein structure is characterized by four domains. At the N terminal end is the highly conserved MADS DNA binding domain . [ 23 ] Next to the MADS domain is the moderately conserved Intervening (I) and Keratin -like (K) domains, which are involved in specific protein-protein interactions . [ 23 ] The carboxyl terminal (C) domain is highly variable and is involved in transcriptional activation and assemblage of heterodimers and multimeric protein complexes. [ 24 ] | https://en.wikipedia.org/wiki/MADS-box |
MAFA (Mast cell function-associated antigen) is a type II membrane glycoprotein , first identified on the surface of rat mucosal-type mast cells of the RBL-2H3 line . More recently, human and mouse homologues of MAFA have been discovered yet also (or only) expressed by NK and T-cells . [ 1 ] MAFA is closely linked with the type 1 Fcɛ receptors in not only mucosal mast cells of humans and mice but also in the serosal mast cells of these same organisms. [ 2 ]
It has the ability to function as both a channel for calcium ions along with interact with other receptors to inhibit certain cell processes. It function is based on its specialized structure, which contains many specialized motifs and sequences that allow its functions to take place. [ 3 ]
MAFA was initially discovered by Enrique Ortega and Israel Pecht in 1988 while studying the type 1 Fcɛ receptors (FcɛRI) and the unknown Ca 2+ channels that allowed these receptors to work in the cellular membrane. Ortega and Pecht experimented through using a series of monoclonal antibodies on the RBL -2H3 line of rat mast cells. While experimenting and trying to find a specific antibody that would raise a response, the G63 monoclonal antibody was shown to raise a response by inhibiting the cellular secretions linked to the FcɛRI receptors in these rat mucosal mast cells. The G63 antibody attached to a specific membrane receptor protein that caused the inhibition process to occur. Specifically, the inhibition occurred by the G63 antibody and glycoprotein cross-linking so that the processes of inflammation mediator formation, Ca2+ intake into the cell, and the hydrolysis of phosphatidylinositides were all stopped. This caused biochemical inhibition of the normal FcɛRI response. The identified receptor protein was then isolated and studied where it was found that when cross-linked, the protein actually had a conformational change that localized the FcɛRI receptors. Based on these results, both Ortega and Pecht named this newly discovered protein Mast cell function-associated antigen or MAFA for short. [ 2 ]
MAFA is said to be a type II membrane glycoprotein, which means that its N-terminus will face the cytosol while its C-terminus will face the extracellular environment. The protein is 188 amino acids in length and has both hydrophobic and hydrophilic regions within these amino acids. The MAFA protein weighs between 28 and 40 kilodaltons and can exist as both a monomer or a homodimer in various species as seen by the SDS-PAGE results that show two broad bands based on these two forms. [ 2 ] The MAFA core polypeptide sequence weights about 19 kilodaltons, however, a large amount of the weight comes from the N-linked oligosaccharides that are attached onto the protein. This heavy glycosylation is a common occurrence among type II membrane glycoproteins and is a key part of both their structure and function. The variation among glycosylation levels helps play an important role in the properties of MAFA proteins, so the protein must be properly made and modified in order to have full functionality. [ 4 ]
The C-terminus of MAFA contains 114 amino acids and has a distinct region called the carbohydrate recognition domain , or CRD for short. This region, as implied in the name, is where various carbohydrates and signaling molecules are recognized and attach to the protein. This CRD is present in many other glycoproteins present in higher level eukaryotes. The CRD is distinguished by a conserved 15 amino acid sequence that includes the following number of amino acids: two glycine residues, two leucine residues, five tryptophan residues, and six cysteine residues. These residues help to form various motifs through their interactions including both WIGL and CYYF motifs. [ 4 ]
Along with specialized sequences on both the N terminus and C terminus, the intracellular domain of this protein contains a specialized sequence called the SIYSTL sequence, where the name is the one letter amino acid abbreviations of its residues. [ 5 ] All of the amino acids in this sequence are polar in nature and are considered to be a part of the Immunoreceptor Tyrosine-based Inhibitory Motif (ITM) . This ITIM allows the MAFA receptor protein to not only be considered a type II glycoprotein, but is also classified as an inhibitory receptor. [ 5 ]
As with other proteins, the MAFA undergoes both transcription followed by translation and post-translational modifications in the ER and Golgi. The genomic coding region of this protein consists of 13 kilobytes of genetic information with five exons that are split by four introns in the gene. Of these five exons, three are used to help code the CRD region that was previously mentioned. This gene is also regulated through an upstream promoter region that is 664 basepairs up from the first nucleotide of the protein. Like other proteins, the gene is copied in multiple starting points and put together into an mRNA transcript . [ 6 ]
After the code was transcribed into mRNA, the MAFA strand was also found to undergo alternative splicing which has allowed various forms of the MAFA protein to be translated and lead to many of the variations previously discussed. One form of this code deletes the transmembrane portion of the MAFA protein and causes a soluble version to be made, being unique to this protein and has allowed scientists to apply this alternative splicing idea to other Mast cell transmembrane proteins as well. [ 4 ] Once translated, the protein enters the proper cellular pathways from the ER to the Golgi and eventually the cellular membrane, where it is integrated and begins its functionality.
As discovered by Ortega and Pecht, one of the main functions of MAFA is to function as a Ca 2+ channel as seen in their experiment with inhibition of Ca 2+ when the G63 antibody was bound to the MAFA receptor region. Additionally, as seen by the fact that it is a type II membrane glycoprotein and by its ability to change conformation to allow varying amount of calcium to enter the cell, MAFA also functions as a receptor molecule and can be inhibit various processes in the mast cells. Specifically, this inhibition is in part due to the SIYSTL motif at the C-terminus of the protein, which is in the extracellular matrix. This motif is dense with Tyrosine residues, some of which are phosphorylated. The phosphorylation on these residues play the primary role in allowing MAFA to inhibit different biochemical processes. [ 4 ]
MAFA protein also interact greatly with FcɛRI receptors through the formation of aggregates and lipid rafts within the cellular membrane. By forming these aggregate structures, the conformation of MAFA is changed so that it can fully interact with the FcɛRI receptors and therefore cannot bind with the G63 monoclonal antibodies and is inhibited from allowing diffusion across its membrane. Along with inhibition of MAFA function, the FcɛRI receptor is also inhibited, meaning that even if a stimulus was bound to its receptor, the FcɛRI would not cause the hydrolysis of phosphatidylinositides as it normally does. [ 3 ] Therefore, by forming these large clusters, both the function of MAFA and FcɛRI receptors are inhibited and can lead to further inhibitions of cell signaling processes within the cell. Even when the MAFA is not induced to interact heavily with FcɛRI, the mast cell membrane has natural interactions between these two receptors that cause small amounts of MAFA-FcɛRI complexes to be found without large changes to either of their functions. [ 6 ] The specific mechanism by which the MAFA and FcɛRI interact and aggregate is still yet to be discovered. [ 4 ]
Along with interacting with other proteins, MAFA can form aggregates consisting only of itself, which are induced by either the monoclonal antibody G63, which was involved in its discovery, or by parts of the F(ab')2 antibody binding to its extracellular complex. By forming these MAFA groups, it was found to cause inhibition of cell cycle processes and prevent mitosis or DNA Replication from occurring. [ 5 ] Specifically, this formation causes an increase in the tyrosine phosphorylation of various cyclins and proteins involved in the cell cycle. The main two proteins that are phosphorylated are p62 DOK and inositol phosphatase SHIP and this causes further change of downstream processes that these proteins are involved in. For p62 DOK , the phosphorylation process causes it to have increased binding to RasGAP , which functions to inhibit the Ras protein function by taking causing GTPase activity to take place and GDP to be bound, which inhibits Ras functionality. By having inhibition of Ras, further downstream promotion of DNA transcription is also halted, which includes some cell cycle proteins. [ 5 ] For inositol phosphatase SHIP, the phosphorylation caused an increased amount of binding to Shc , which is normally found to be bound to Sos1 during cell cycling. Sos1 and SHIP both bind to Shc competitively and by having an increased affinity for Shc during phosphorylation, Sos1 binding decreases greatly. This relationship suggests that decreased Sos1 binding is also associated with halting the cell cycle, although the mechanism by which this inhibition occurs has not been discovered. [ 5 ]
MAFA can also exist in multiple forms due to alternative splicing and one of these forms in a soluble version of the protein where its transmembrane portion was not translated and modified. This form of MAFA can diffuse out of the cellular membrane and into the extracellular matrix without being degraded or broken down by lysosomes, meaning that it does serve a function within human cells. The degree of glycosylation along with the specific function of these proteins is still yet to be discovered, but it is hypothesized that they play an important role in helping maintain calcium levels along with limiting the formation of inflammation mediators within these mast cells. [ 1 ] Much about these alternative forms is yet to be discovered. | https://en.wikipedia.org/wiki/MAFA |
Multiplexed Accurate Genome Editing with Short, Trackable, Integrated Cellular barcodes ( MAGESTIC ) is a platform that builds on the CRISPR /Cas technique. It further improves CRISPR/Cas by making the gene-editing process more precise. It also increases cell survival during the editing process up to sevenfold. [ 1 ] [ 2 ]
This technology was invented at the Stanford Genome Technology Center in collaboration with the Joint Initiative for Metrology in Biology (JIMB) [ 3 ] which is a coalition of Stanford University and the National Institute of Standards and Technology .
Gene editing is used for a variety of tasks including the modifying of crops, the modifying of bacteria, and the modifying of disease-causing genetic mutations in patients . When only a single edited cell line is required, CRISPR/Cas combined with the endogenous DNA repair efficiency is sufficient to obtain an edited cell line. However, when trying to introduce many edits in multiplex, a higher efficiency of Homology directed repair is required. The MAGESTIC technology has multiple components. One component, the LexA-Fkh1 protein is involved in the process of Donor Recruitment that increases the efficiency of homology directed repair. The second component is a library of CRISPR Guide RNAs paired with donor DNA which encodes for specified edited to be integrated through homology directed repair. This in turn is linked to a DNA barcodes that allows for specific variants to be tracked in pools, similar to how Genome-wide CRISPR-Cas9 knockout screens work, only MAGESTIC is more versatile as it allows for not only loss of function edits, but also DNA Codon changes, Single-nucleotide polymorphism , Indels , and other types of genetic changes to be introduced and tracked. By improving DNA repair efficiency, using array-synthesized guide–donor oligos for the plasmid-based high-throughput editing, and integrating a genomic barcode to prevent plasmid barcode loss, MAGESTIC leads to more uniform pools with genome integrated stable single copy barcodes and enables robust phenotyping.
Because editing multiple sites in pools can be impacted by a number of factors including ineffective CRISPR Guide RNA , DNA synthesis errors, competition with Non-homologous end joining and other challenges that occur when building multiplex libraries, MAGESTIC screens required improved DNA repair. This is where the donor recruitment aspect of MAGESTIC comes in. MAGESTIC achieves greater editing efficiency by localizing donor DNA to the site of DNA breaks introduced by a CRISPR cut.
A CRISPR machinery cuts at desired locations in the genome, and then MAGESTIC direct the donor DNA to the site of this cut to direct cells to introduce designed edits at the DNA cut sites. This technology is called donor recruitment and relies on a fusion protein that contains one domain recruited to DNA breaks and another domain that binds to the donor DNA. This allows for the production of high quality precision edit pools in yeast, where each cells contains a single edit and a DNA barcode. The donor recruitment aspect of the technology also holds the potential to improve editing efficiency in additional cell types, such as mammalian cells. This may one day prove beneficial to gene therapies or other therapeutic editing. | https://en.wikipedia.org/wiki/MAGESTIC |
MAGIChips , also known as " microarrays of gel-immobilized compounds on a chip " or " three-dimensional DNA microarrays ", are devices for molecular hybridization produced by immobilizing oligonucleotides , DNA , enzymes , antibodies , and other compounds on a photopolymerized micromatrix of polyacrylamide gel pads of 100x100x20 μm or smaller size. This technology is used for analysis of nucleic acid hybridization , specific binding of DNA, and low-molecular weight compounds with proteins, and protein-protein interactions.
The gel pads increase the surface for hybridization to 50 times, compared to typical microarrays which are printed on flat surface of a glass slide that is usually treated by chemical compounds on which the probes adhere. A probe density of more than 1012 molecules per gel pad can be achieved due to 3D nature of the gel pads. The array is based on a glass surface that has small polyacrylamide gel units affixed to it. Each gel unit functions as an individual reaction cell as it is surrounded by a hydrophobic glass surface that prevents mixing of the solution in the gel units. This lays a foundation for performing ligation , single base extension, PCR amplification of DNA, on-chip MALDI-TOF mass spectrometry and other reactions.
MAGIChip technology was developed as a result of collaboration between Dr. David Stahl at University of Washington and Dr Andrei Mirzabekov, formerly of Argonne National laboratory. Andrei Mirzabekov initiated the development of the DNA sequencing by hybridization with oligonucleotides: a novel method in 1988. This method was a foundation for the biotechnology that uses biological microchips to identify DNA structures rapidly, which is of great importance in the fight against a variety of diseases.
A joint research project was announced in 1998 among Motorola Inc, Packard Instrument Company and the U.S. Department of Energy's Argonne National Laboratory. In 1999, the researchers at Argonne National Lab pushed the development of microarray-type biochip technology they co-designed with the Engelhardt Institute to ward off a worldwide outbreak of tuberculosis.
Motorola developed manufacturing processes to mass-produce biochips, and Packard developed and manufactured the analytical instruments to process and analyze the biochips. Argonne's contribution, in conjunction with Engelhardt Institute of Molecular Biology (EIMB) , was intellectual property in the form of 19 inventions related to biological microchips.
But this collaboration between EIMB in Moscow and Argonne National Laboratory at Illinois and two other US-based commercial partners collapsed as result of argument on contractual arrangement between the parties in 2001. As a result of this dispute, Dr Andrei Mirzabekov resigned as a director of Argonne's Biochip Technology Centre. [ citation needed ]
Arrays of gel elements (pads) are created on the glass surface (micromatrix) which is followed by application and chemical immobilization of different compounds (probes) onto these gel pads. Test sample is then added to this micromatrix containing immobilized probes in gel pads and molecular recognition reactions are allowed to take place under specified conditions. The test sample is fluorescent labelled to monitor the molecular interactions. The analysis of molecular interaction patterns is done by using specialized software.
The array of gel elements on a glass slide is prepared by ‘’’photopolymerization‘’’. The acrylamide solution to be polymerized is applied to the polymerization chamber. Polymerization chamber consists of a quartz mask, two Teflon spacers, and a microscopic glass slide, clamped together by two metal clamps. The inner side of quartz mask has ultraviolet (UV)-transparent windows arranged in a specified spatial manner in a non-transparent chromium film. Assembled chamber containing the acrylamide gel is exposed to UV light to allow polymerization in only those positions of the chamber that are situated directly under the transparent windows.
Oligonucleotides or DNA fragments need to be activated to contain chemically reactive groups to facilitate coupling with the activated gel elements. Probe activation depends on the chemistry of activation of the polyacrylamide gels. Thus to immobilize in the aldehyde-containing gel the probe should have reactive amino group and if the gels are activated by introduction of amino groups, the probes should contain free aldehyde group. Probes are usually prepared by introduction of chemically active groups in terminal position of the oligonucleotides during their synthesis.
Probes for immobilization are transferred into gel elements of micromatrix by using dispensing robots. The fibre-optic pin of the robots has a hydrophobic side surface and a hydrophilic tip, and operates at a dew temperature to prevent evaporation of the sample during transfer. The activated probes are chemically immobilized by coupling oligonucleotides bearing amino or aldehyde groups with gel supports containing aldehyde or amino groups respectively.
The target molecules are labelled with fluorescent dyes . The fluorescent detection enables monitoring the process in real time with high spatial resolution. The criteria for labelling procedure includes –
On-chip amplification of the hybridization reaction serves as a very useful tool when the DNA or protein under study are present in relatively small proportion in the molecular population applied to the chip, e.g., when one is dealing with a single copy gene or mRNA of low abundance.
In a single base extension method, [ 1 ] a primer is hybridized to DNA and extended by a dideoxyribonucleoside triphosphate that matches the nucleotide at a polymorphic site. By performing this reaction at a temperature above the melting temperature of the duplex between the DNA and immobilized probe allows rapid association/dissociation of the target DNA. Thus the same DNA molecule reacts with many individual primers, leading to amplification of the primers in each individual gel pads. This procedure was applied to the identification of beta-globin gene mutation in the patients of beta thalassemia patients and to detection of anthrax toxin gene.
The chips also provides a good platform for performing PCR directly on the chip (in individual gel pads) as it is easy to isolate each gel pad from its neighbour unlike typical microarray chips which face serious problems in doing the same task
For the analysis of hybridization results obtained with fluorescently labelled target molecules fluorescence microscopes are employed. The instrument is equipped with controlled-temperature sample table to vary the temperature in the chip-containing reaction chamber during the course of the experiment. A cooled charge-coupled device (CCD) camera is used to record the light signals from the chip, which are then sent to the computer program for quantitative evaluation of the hybridization signals over the entire chip. Data generated by these experiments is stored in a database and analyzed by software that help provide evaluation, in silico experimentation, and hardware and software quality control.
Customized oligonucleotide biochips are designed to interrogate test samples of known nucleotide sequences. For example, known genes in cases when one is interested in their expression levels under certain conditions, genes that are known to contain point mutations, or to be polymorphic in a given population. The success of the microarray depends on the proper choice of probes in these cases.
A set of potential hybridization probes are created for each DNA sequence that form perfect duplexes with that sequence. The potential probes that may create ambiguities in the interpretation of the hybridization pattern are excluded on the basis of AT vs GC content, and the propensity to form hairpins and other types of stable secondary structures that may drastically affect the intensity of hybridization.
One of the cases of successful applications of customized oligonucleotide chips include detection of beta-thalassemia mutation in patients. For the diagnostics of beta-thalassemia mutations, a simple chip was designed that contained six probes corresponding to different beta-thalassemia genotypes and hybridized with PCR-amplified DNA from healthy humans and patients. [ 2 ] The hybridization results showed the expected significant differences in signal intensity between matched and mismatched duplexes, thus allowing reliable identification of both homozygous and heterozygous mutations.
These chips haves been developed for ribosomal RNA (rRNA) targets, commonly used for detecting bacteria. rRNA are very abundant in the cell comprising about 80% of the RNA content of the typical eukaryotic cell. [ 3 ] The rRNA is pre-amplified by bacteria and there are present in several thousand copies per cell, making a good target for microassays. Single nucleotide polymorphisms present in the bacterial rRNA sequence are used to differentiate bacteria at the genus, species and strain level. This is a unique feature of this microchip that does not require PCR based amplification. The process for detecting bacterial is relatively simple. The bacteria are cultured, washed and pelleted. Lysosome is used to lyse the pellets - to destroy the cell walls and release the nucleic acid. Lysed bacteria are passed through a colourmn [ check spelling ] preparation where nucleic acid from the cell is immobilized and other debris is washed out. All the processes after lysis - isolation, purification, fragmentation and labelling of target rRNA's - are stable chemical reactions Fragments <500 bp easily hybridize to the gel matrix. The total number of eluted off the chip is determined by UV spectrophotometer. The process from sample preparation to identification of organisms based on automated algorithms take place in 2 hours.
cDNAs obtained from reverse transcription of mRNA population extracted from the cells in varying physiological and experimental conditions are used as immobilized probes. These arrays are widely used to study gene expression. The potential obstacle in using cDNAs is due to the difficulty of injecting and evenly distributing long molecules into the gel pads. This problem is resolved by developing polyacrylamide gels that contain larger average pore size. Another way to approach this problem is to randomly fragment the cDNA into relatively small pieces before immobilization
Protein chips can be prepared that contain different proteins immobilized as probes in a way that preserves their biological activity. [ 4 ] A large pore gel is used to prevent the diffusion of protein into the gel. There are two ways to immobilize proteins to the gel pads. The first is based on activation of the gel with glutyraldehyde . In the second procedure the gel is activated by partial substitution of amino groups with hydrazide groups. The reaction between hydrazide and aldehyde groups efficiently cross-links the protein to the cell. Protein microchips show the high specificity in molecular recognition reactions as seen in solution. Interaction between antigen and their specific antibodies can be studied on-chip in variety of experimental conditions. Either the antigen or antibody can be immobilized and monitored by both direct and indirect methods. In direct method, one uses target molecules labelled with fluorescent dye and in the indirect method the reaction is detected using the labelled molecule that specifically recognizes the target.
These chips can be used to study enzymatic activity of immobilized enzymes by coating the chip with solution containing specific substrates. The reaction is monitored by detecting the formation of coloured or fluorescent precipitates | https://en.wikipedia.org/wiki/MAGIChip |
MAGSTEC was a one-of-a-kind computer built by ERA for the US Navy . The machine was an experiment in using magnetic amplifiers for computer use. The US Air Force later contracted Univac , who had purchased ERA, to build the same basic architecture using transistors in place of the mag amps, creating TRANSTEC . [ 1 ]
This computing article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/MAGSTEC |
Multiple Annealing and Looping Based Amplification Cycles ( MALBAC ) is a quasilinear whole genome amplification method. Unlike conventional DNA amplification methods that are non-linear or exponential (in each cycle, DNA copied can serve as template for subsequent cycles), MALBAC utilizes special primers that allow amplicons to have complementary ends and therefore to loop, preventing DNA from being copied exponentially. This results in amplification of only the original genomic DNA and therefore reduces amplification bias. MALBAC is “used to create overlapped shotgun amplicons covering most of the genome”. [ 1 ] For next generation sequencing, MALBAC is followed by regular PCR which is used to further amplify amplicons.
Prior to MALBAC, a single cell is isolated by various methods including laser capture microdissection , microfluidic devices, flow cytometry , or micro pipetting, then lysed. MALBAC single-cell whole-genome amplification involves 5 cycles of quenching, extending, melting, and looping.
The major advantage of MALBAC is that DNA is amplified almost linearly. The utilization of specialized primers enables looping of amplicons which then prevents them from being further amplified in subsequent cycles of MALBAC. These primers are 35 nucleotides long, with 8 variable nucleotides that hybridize to the templates and 27 common nucleotides. [ 1 ] The common nucleotide sequence is GTG AGT GAT GGT TGA GGT AGT GTG GAG. The 8 variable nucleotides anneal randomly to the single stranded genomic DNA molecule. After one extension, semi-amplicon, an amplicon containing the common nucleotide sequence on only the 5’ end, is made. This semi-amplicon is used as a template for another round of extension, which then results in a full-amplicon, an amplicon where the 3’ end is complementary to the sequence on the 5’ end.
MALBAC primers have variable components which allow them to randomly bind to the template DNA. This means that on a single fragment at any cycle, there could be multiple primers annealed to the fragment. A DNA polymerase such as one derived from Bacillus stearothermophilus ( Bst polymerase) is able to displace the 5’ end of another upstream strand growing in the same direction. [ 2 ]
Bst DNA polymerase has an error rate of 1/10000 bases. [ 3 ]
At the end of PCR, picograms of genetic material is amplified to microgram of DNA, yielding enough DNA to be sequenced.
MALBAC offers an unbiased approach to the amplification of DNA from a single cell. This method of single cell sequencing has a vast number of applications, many of which have yet to be exploited. MALBAC may aid in the analysis of forensic specimens, in pre-natal screening for genetic diseases, in understanding the development of reproductive cells, or in elucidating the complexity of a tumour. [ 1 ] [ 4 ] At its foundation, this technology allows researchers to observe the frequency with which mutations accumulate in single cells. [ 1 ] Moreover, it permits the detection of chromosomal abnormalities and gene copy number variations (CNVs) within and between cells, and further facilitates the detection of uncommon mutations that result in single nucleotide polymorphisms (SNPs). [ 1 ]
In the field of cancer research , MALBAC has many applications. It may be used to examine intratumor heterogeneity, to identify genes which may confer an aggressive or metastatic phenotype, or to evaluate the potential for a tumour to develop drug resistance . [ 4 ] [ 5 ] A pioneering application of MALBAC was published in a December 2012 issue of Science and described the use of this technology to measure the mutation rate of the colon cancer cell line SW4802. [ 1 ] By sequencing the amplified DNA of three kindred colon cancer cells in parallel with unrelated colon cancer cells from a different lineage, SNPs were identified with no false positives detected. [ 1 ] It was also observed that purine-pyrimidine transversions occurred at a high frequency among the SNPs. [ 1 ] The characterization of copy number and single nucleotide variations of single colon cancer cells highlighted the heterogeneity present within a tumour. [ 1 ]
MALBAC has been applied as a method to examine the genetic diversity amongst reproductive cells. By sequencing the genomes of 99 individual human sperm cells from an anonymous donor, MALBAC was used to examine genetic recombination events involving single gametes and ultimately provide insight into the dynamics of genetic recombination and its contribution to male infertility. [ 6 ] Additionally, within an individual sperm, MALBAC identified duplicated or missing chromosomes, as well as SNPs or CNVs which could negatively affect fertility. [ 6 ]
MALBAC has resulted in many significant advances over other single cell sequencing techniques, foremost that it can report 93% of the genome of a single human cell. [ 1 ] Some advantages of this technology include reduced amplification bias and increased genome coverage , the requirement for very little template DNA, and low rates of false positive and false negative mutations. [ 4 ] [ 6 ]
MALBAC is a form of whole genome sequencing which reduces the bias associated with exponential PCR amplification by using a quasilinear phase of pre-amplification. [ 1 ] MALBAC utilizes five cycles of pre-amplification and primers containing a 27 nucleotide common sequence and an 8 nucleotide variable sequence to produce fragments of amplified DNA (amplicons) which loop back on themselves to prevent additional copying and cross-hybridization. [ 1 ] [ 7 ] These loops cannot be used as a template for amplification during MALBAC and therefore reduce the amplification bias commonly associated with the uneven exponential amplification of DNA fragments by polymerase chain reaction. [ 1 ] MALBAC has been described to have better amplification uniformity than other methods of single sequencing, such as multiple displacement amplification (MDA). [ 1 ] [ 5 ] MDA does not utilize DNA looping and amplifies DNA in an exponential fashion, resulting in bias. [ 1 ] Accordingly, the amplification bias associated with other single cell sequencing methods results in low coverage of the genome. [ 1 ] [ 5 ] The reduced bias associated with MALBAC has generated better genome sequence coverage than other single cell sequencing methods.
MALBAC can be used to amplify and subsequently sequence DNA when only one or a few cells are available, such as in the analysis of circulating tumour cells, pre-natal screens or forensic samples. [ 4 ] [ 7 ] Only a small amount of starting template (picograms of DNA) is required to initiate the process, and therefore it is an ideal method for the sequencing of a single human cell. [ 1 ]
Single cell sequencing often has a high rate of false negative mutations. [ 1 ] A false negative mutation rate is defined as the probability of not detecting a real mutation, and this may occur due to amplification bias resulting from the loss, or drop-out, of an allele. [ 8 ] The sequence coverage uniformity of MALBAC in comparison to other single cell sequencing techniques has enhanced the detection of SNPs and reduced allele dropout rate. [ 1 ] Allelic dropout rate increases when an allele of a heterozygote fails to amplify resulting in identification of a ‘false homozygote.’ This may occur due to low concentration of DNA template, or the uneven amplification of template resulting in one allele of a heterozygote being copied more than the other. [ 8 ] The allele dropout rate of MALBAC has been shown to be much lower (approximately 1%) compared to MDA which is approximately 65%. In contrast to MDA which has been shown to have a 41% SNP detection efficiency in comparison with bulk sequencing, MALBAC has been reported to have SNP detection efficiency of 76%. [ 1 ] MALBAC has also been reported to have a low false positive rate . False positive mutations generated by MALBAC largely result from errors introduced by DNA polymerase during the first cycle of amplification that are further propagated during subsequent cycles. This false positive rate can be eliminated by sequencing 2-3 cells within a lineage derived from a single cell to verify the presence of a SNP, and by eliminating sequencing and amplification errors by sequencing unrelated cells from a separate lineage. [ 1 ] | https://en.wikipedia.org/wiki/MALBAC |
The Molecular Ancestry Network (MANET) database is a bioinformatics database that maps evolutionary relationships of protein architectures directly onto biological networks. [ 1 ] It was originally developed by Hee Shin Kim, Jay E. Mittenthal and Gustavo Caetano-Anolles in the Department of Crop Sciences of the University of Illinois at Urbana-Champaign . [ 2 ]
MANET traces for example the ancestry of individual metabolic enzymes in metabolism with bioinformatic, phylogenetic, and statistical methods. MANET currently links information in the Structural Classification of Proteins ( SCOP ) database, the metabolic pathways database of the Kyoto Encyclopedia of Genes and Genomes ( KEGG ), and phylogenetic reconstructions describing the evolution of protein fold architecture at a universal level. [ 3 ] The database has been updated to reflect evolution of metabolism at the level of protein fold families. [ 4 ] MANET literally "paints" the ancestries of enzymes derived from rooted phylogenetic trees directly onto over one hundred metabolic pathways representations, paying homage to one of the fathers of impressionism . It also provides numerous functionalities that enable searching specific protein folds with defined ancestry values, displaying the distribution of enzymes that are painted, and exploring quantitative details describing individual protein folds. This permits the study of global and local metabolic network architectures, and the extraction of evolutionary patterns at global and local levels.
A statistical analysis of the data in MANET showed for example a patchy distribution of ancestry values assigned to protein folds in each subnetwork, indicating that evolution of metabolism occurred globally by widespread recruitment of enzymes. [ 2 ] MANET was used recently to sort out enzymatic recruitment processes in metabolic networks and propose that modern metabolism originated in the purine nucleotide metabolic subnetwork. [ 5 ] The database is useful for the study of metabolic evolution . | https://en.wikipedia.org/wiki/MANET_database |
MANTIS ( Monitoring Activity from Nearby Stars with UV Imaging and Spectroscopy ) is a planned NASA space telescope . MANTIS will study the emission of ultraviolet (UV) radiation of stars, especially in the extreme UV range, to judge the habitability of planets orbiting them. The telescope will be built by the University of Colorado Boulder as a cubesat at a cost of $8.5 million. [ 1 ]
Ultraviolet radiation and stellar flares can impact the habitability of planets. For many stars, MANTIS will perform the first measurements of extreme UV emissions. [ 2 ]
This article about one or more spacecraft of the United States is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/MANTIS_(space_telescope) |
MAP-Seq or M ultiplexed A nalysis of P rojections by Seq uencing is a RNA-Seq based method for high-throughput mapping of neuronal projections . It was developed by Anthony M. Zador and his team at Cold Spring Harbor Laboratory and published in Neuron, a Cell Press magazine. [ 1 ] It has been cited over 300 times. [ 1 ]
The method works by uniquely labeling neurons in a source region by injecting a viral library encoding a diverse collection of RNA sequences ("barcodes"). The barcode mRNA is expressed at high levels and transported into the axon terminals at distal target projection regions. Following this, the cells from source and putative target regions of interest are harvested, and their RNA is extracted and sequenced. By matching the presence of the unique "barcode" in the source and target tissue, one can map the projections of neuron in a one-to-many fashion. [ 2 ]
This neuroscience article is a stub . You can help Wikipedia by expanding it .
This molecular biology article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/MAP-Seq |
4214
26401
ENSG00000095015
ENSMUSG00000021754
Q13233
P53349
NM_005921
NM_011945
NP_005912
n/a
Mitogen -activated protein kinase kinase kinase 1 (MAP3K1) is a signal transduction enzyme that in humans is encoded by the autosomal MAP3K1 gene . [ 5 ] [ 6 ]
MAP3K1 (or MEKK1) is a serine/threonine kinase and ubiquitin ligase that performs a pivotal role in a network of enzymes integrating cellular receptor responses to a number of mitogenic and metabolic stimuli, including: TNF receptor superfamily (TNFRs), T-cell receptor (TCR), Epidermal growth factor receptor (EGFR), and TGF beta receptor (TGFβR). [ 7 ] [ 8 ] Mitogen-activated protein kinase kinases (MAP2Ks) are substrates for direct phosphorylation by the MAP3K1 protein kinase . [ 9 ] [ 10 ] The MAP3K1 kinase domain may also be a modest activator of IκB kinase activation. [ 11 ] The MAP3K1 E3 ubiquitin ligase recruits a ubiquitin-conjugating enzyme (including UBE2D2 , UBE2D3 , and UBE2N : UBE2V1 ) that has been loaded with ubiquitin , interacts with its substrates, and facilitates the transfer of ubiquitin from the ubiquitin-conjugating enzyme onto its substrates. [ 12 ] Genetics has revealed that MAP3K1 is important in: embryonic development , tumorigenesis , cell growth , cell migration , cytokine production, and humoral immunity . [ 8 ] MAP3K1 mutants were identified in breast cancer by GWAS . [ 13 ] [ 14 ]
MAP3K1 contains a protein kinase domain , PHD finger (which has a RING finger domain -like structure) that serves as an E3 ubiquitin ligase , and scaffold protein regions that mediate protein–protein interactions . [ 15 ] [ 16 ] [ 17 ] [ 18 ]
MAP3K1 is highly conserved in Euteleostomi . [ 19 ] The spontaneous recessive lidgap-Gates mutation (deletion of Map3k1 exons 2–9, initially described in the 1960s) identified on the SELH/Bc mouse strain causes the same open-eyelids-at-birth mutational phenotype as the gene knockout mutations of the mouse (but not human) MAP3K1 homolog ( Map3k1 ) and also co-maps to distal Chromosome 13. [ 20 ] MAP3K1 was analysed genetically by targeted mutagenesis using transgenic mice ( C57BL/6 and C57BL/6 × 129 backgrounds), embryonic stem cells , and the DT40 cell line to identify genetic traits .
MAP3K1 contains multiple amino acid sites that are phosphorylated and ubiquitinated . [ 33 ] Early biochemical analysis demonstrated that triple co-expression of MAP3K1, MAP2K and MAPK in bacterial cells was sufficient for the activation of MAPK. [ 34 ] Later analysis of syngenic mice that harbour mutations in TRAF2 , UBE2N , Map3k1 and Map3k7 identified critical regulators of cytokine-induced MAPK signal transduction in B cells. [ 35 ] [ 36 ] [ 37 ] [ 38 ] Cytokine signaling through MAP3K1 utilises two-stage cell signaling to recruit the signal transduction mechanism to cytokine receptors and then release the signal transduction components, altered by post-translational modification , from the cellular membrane to activate MAPKs. [ 39 ] [ 40 ] Genetic analysis has demonstrated that the E3 Ub ligase and the kinase domains of MAP3K1 are required for MAPK activation. [ 32 ] [ 41 ] [ 42 ]
MAP3K1 is a biomarker mutated in 3.24% of all human cancers. [ 43 ] MAP3K1 has been associated with several diseases in non-syngeneic human populations, [ 44 ] including: breast cancer , [ 45 ] adenocarcinoma of the prostate , [ 46 ] sarcomatoid hepatocellular carcinoma , [ 47 ] acute respiratory distress syndrome , [ 48 ] Langerhans cell histiocytosis , [ 49 ] and 46,XY disorders of sex development . [ 50 ] E6201 is an enzyme inhibitor of MAP3K1 that shows cross-specificity with MAP2K1 . [ 51 ]
MAP3K1 has been shown to interact with a number of proteins, [ 44 ] including: | https://en.wikipedia.org/wiki/MAP3K1 |
The MAPK/ERK pathway (also known as the Ras-Raf-MEK-ERK pathway ) is a chain of proteins in the cell that communicates a signal from a receptor on the surface of the cell to the DNA in the nucleus of the cell.
The signal starts when a signaling molecule binds to the receptor on the cell surface and ends when the DNA in the nucleus expresses a protein and produces some change in the cell, such as cell division . The pathway includes many proteins, such as mitogen-activated protein kinases (MAPKs), originally called extracellular signal-regulated kinases (ERKs), which communicate by adding phosphate groups to a neighboring protein ( phosphorylating it), thereby acting as an "on" or "off" switch.
When one of the proteins in the pathway is mutated, it can become stuck in the "on" or "off" position, a necessary step in the development of many cancers. In fact, components of the MAPK/ERK pathway were first discovered in cancer cells, and drugs that reverse the "on" or "off" switch are being investigated as cancer treatments. [ 1 ]
The signal that starts the MAPK/ERK pathway is the binding of extracellular mitogen to a cell surface receptor . This allows a Ras protein (a Small GTPase ) to swap a GDP molecule for a GTP molecule, flipping the "on/off switch" of the pathway. The Ras protein can then activate MAP3K (e.g., Raf ), which activates MAP2K , which activates MAPK . Finally, MAPK can activate a transcription factor , such as Myc . This process is described in more detail below.
Receptor-linked tyrosine kinases , such as the epidermal growth factor receptor (EGFR), are activated by extracellular ligands , such as the epidermal growth factor (EGF). Binding of EGF to the EGFR activates the tyrosine kinase activity of the cytoplasmic domain of the receptor. The EGFR becomes phosphorylated on tyrosine residues. Docking proteins such as GRB2 contain an SH2 domain that binds to the phosphotyrosine residues of the activated receptor. [ 2 ] GRB2 binds to the guanine nucleotide exchange factor SOS by way of the two SH3 domains of GRB2. When the GRB2-SOS complex docks to phosphorylated EGFR, SOS becomes activated. [ 3 ] Activated SOS then promotes the removal of GDP from a member of the Ras subfamily (most notably H-Ras or K-Ras ). The Ras protein can then bind GTP and become active.
Apart from EGFR, other cell surface receptors that can activate this pathway via GRB2 include Trk A/B , Fibroblast growth factor receptor (FGFR) and PDGFR .
Activated Ras then activates the protein kinase activity of a RAF kinase . [ 4 ] The RAF kinase phosphorylates and activates a MAPK/ERK Kinase ( MEK1 or MEK2 ). The MEK phosphorylates and activates a mitogen-activated protein kinase (MAPK).
RAF and MAPK/ERK are both serine/threonine-specific protein kinases . MEK is a serine/tyrosine/threonine kinase.
In a technical sense, RAF, MEK, and MAPK are all mitogen -activated kinases, as is MNK (see below). MAPKs were originally called " extracellular signal-regulated kinases " (ERKs) and "microtubule associated protein kinases" (MAPKs). One of the first proteins known to be phosphorylated by ERK was a microtubule-associated protein (MAP). As discussed below, many additional targets for phosphorylation by MAPK were later found, and the protein was renamed "mitogen-activated protein kinase" (MAPK). The series of kinases from RAF to MEK to MAPK is an example of a protein kinase cascade . Such series of kinases provide opportunities for feedback regulation and signal amplification.
Three of the many proteins that are phosphorylated by MAPK are shown in the figure to the right. One effect of MAPK activation is to alter the translation of mRNA to proteins. MAPK phosphorylates the 40S ribosomal protein S6 kinase (RSK) . This activates RSK, which, in turn, phosphorylates ribosomal protein S6 . [ 5 ] Mitogen-activated protein kinases that phosphorylate ribosomal protein S6 were the first to be isolated. [ 4 ]
MAPK regulates the activities of several transcription factors . MAPK can phosphorylate C-myc . MAPK phosphorylates and activates MNK, which, in turn, phosphorylates CREB . MAPK also regulates the transcription of the C-Fos gene. By altering the levels and activities of transcription factors, MAPK leads to altered transcription of genes that are important for the cell cycle .
The 22q11, 1q42, and 19p13 genes, by affecting the ERK pathway, are associated with schizophrenia , schizoaffective disorder , bipolar disorder , and migraines .
The ERK pathway plays an important role of integrating external signals from the presence of mitogens such as epidermal growth factor (EGF) into signaling events promoting cell growth and proliferation in many mammalian cell types. In a simplified model, the presence of mitogens and growth factors trigger the activation of canonical receptor tyrosine kinases such as EGFR leading to their dimerization and subsequent activation of the small GTPase Ras. [ 6 ] This then leads to a series of phosphorylation events downstream in the MAPK cascade (Raf-MEK-ERK) ultimately resulting in the phosphorylation and activation of ERK. The phosphorylation of ERK results in an activation of its kinase activity and leads to phosphorylation of its many downstream targets involved in regulation of cell proliferation. In most cells, some form of sustained ERK activity is required for cells to activate genes that induce cell cycle entry and suppress negative regulators of the cell cycle. Two such important targets include Cyclin D complexes with Cdk4 and Cdk6 (Cdk4/6) which are both phosphorylated by ERK. [ 7 ] The transition from G1 to S phase is coordinated by the activity of Cyclin D-Cdk4/6, which increases during late G1 phase as cells prepare to enter S-phase in response to mitogens. Cdk4/6 activation contributes to hyper-phosphorylation and the subsequent destabilization of retinoblastoma protein (Rb). [ 7 ] Hypo-phosphorylated Rb, is normally bound to transcription factor E2F in early G1 and inhibits its transcriptional activity, preventing expression of S-phase entry genes including Cyclin E, Cyclin A2 and Emi1. [ 6 ] ERK1/2 activation downstream of mitogen induced Ras signaling is necessary and sufficient to remove this cell cycle block and allow cells to progress to S-phase in most mammalian cells.
The restriction point (R-point) marks the critical event when a mammalian cell commits to proliferation and becomes independent of growth stimulation. It is fundamental for normal differentiation and tissue homeostasis, and seems to be dysregulated in virtually all cancers. Although the R-point has been linked to various activities involved in the regulation of G1–S transition of the mammalian cell cycle, the underlying mechanism remains unclear. Using single-cell measurements, Yao et al., shows that the Rb–E2F pathway functions as a bistable switch to convert graded serum inputs into all-or-none E2F responses. [ 8 ]
Growth and mitogen signals are transmitted downstream of the ERK pathway are incorporated into multiple positive feedback loops to generate a bistable switch at the level of E2F activation. [ 8 ] This occurs due to three main interactions during late G1 phase. The first is a result of mitogen stimulation though the ERK leading to the expression of the transcription factor Myc, which is a direct activator of E2F. [ 7 ] The second pathway is a result of ERK activation leading to the accumulation of active complexes of Cyclin D and Cdk4/6 which destabilize Rb via phosphorylation and further serve to activate E2F and promote expression of its targets. Finally, these interactions are all reinforced by an additional positive feedback loop by E2F on itself, as its own expression leads to production of the active complex of Cyclin E and CDK2, which further serves to lock in a cell's decision to enter S-phase. As a result, when serum concentration is increased in a gradual manner, most mammalian cells respond in a switch-like manner in entering S-phase. This mitogen stimulated, bistable E2F switch is exhibits hysteresis, as cells are inhibited from returning to G1 even after mitogen withdrawal post E2F activation. [ 8 ]
The EGFR-ERK/MAPK (epidermal growth factor receptor extracellular-regulated kinase/mitogen-activated protein kinase) pathway stimulated by EGF is critical for cellular proliferation, but the temporal separation between signal and response obscures the signal-response relationship in previous research.In 2013, Albeck et al. [ 9 ] provided key experimental evidence to fill this gap of knowledge. They measured signal strength and dynamics with steady-state EGF stimulation, in which the signaling and output can be easily related. They further mapped the signal-response relationship across the pathway’s full dynamic range. Using high-content immunofluorescence (HCIF) detection of phosphorylated ERK (pERK) and live cell FRET biosensors, they monitored downstream output of the ERK pathway in both live cells and fixed cells. To further link the quantitative characteristics of ERK signaling to proliferation rates, they established a series of steady-state conditions using a range of EGF concentrations by applying EGF with different concentrations.
Single cell imaging experiments have shown ERK to be activated in stochastic bursts in the presence of EGF. Furthermore, the pathway has been shown to encode the strength of signaling inputs though frequency modulated pulses of its activity. Using live cell FRET biosensors, cells induced with different concentrations of EGF illicit activity bursts of different frequency, where higher levels of EGF resulted in more frequent bursts of ERK activity. To figure out how S phase entry can be affected by sporadic pulses of ERK activity at low EGF concentrations, they used MCF-10A cells co-expressing EKAR-EV and RFP-geminin and identified the pulses of ERK activity with the scoring and then align this ERK activity profiles with time of GFP-geminin induction. They found that longer periods of ERK activity stimulate S phase entry, as suggested by increased pulse length. To understand the dynamics of EGFR-ERK pathway, specifically how is the frequency and amplitude modulated, they applied the EGFR inhibitor gefitinib or the highly selective MAPK/ERK kinase (MEK) inhibitor PD0325901 (PD). Two inhibitors yield actually a little bit different result: gefitinib, at intermediate concentration, would induce pulsatory behavior and also bimodal shift, which is not observed with PD. They further combine EGF and PD together and draw the conclusion that the frequency of ERK activities is modulated by quantitative variation while the amplitude is modulated by MEK activity’s change. Lastly they turned to Fra-1, one of downstream effectors of ERK pathway, as it’s technically challenging to estimate ERK activities directly. To understand how the integrated ERK pathway output (which should be independent of either frequency or amplitude) affect the proliferation rate, they used the combination of a wide range of EGF and PD concentrations and find that there’s actually an inverted “L” shape single curvilinear relationship, which suggests that at low levels of ERK pathway output, small changes in signal intensity correspond to large changes in proliferative rate, while large changes in signal intensity near the high end of the dynamic range have little impact on proliferation. The fluctuation of ERK signaling highlights potential issues with current therapeutic approaches, providing new perspective in terms of thinking about drug targeting in the ERK pathway in cancer.
Recent live cell imaging experiments in MCF10A and MCF7 cells have shown that a combination of mitogen signaling though ERK and stress signals through activation of p53 in mother cells contributes to the likelihood of whether newly formed daughter cells will immediately re-enter the cell cycle or enter quiescence (G0) preceding mitosis. [ 10 ] Rather than daughter cells starting with no key signaling proteins after division, mitogen/ERK induced Cyclin D1 mRNA and DNA damage induced p53 protein, both long lived factors in cells, can be stably inherited from mother cells after cell division. The levels of these regulators vary from cell to cell after mitosis and stoichiometry between them strongly influences cell cycle commitment though activation of Cdk2. Chemical perturbations using inhibitors of ERK signaling or inducers p53 signaling in mother cells suggest daughter cells with high levels of p53 protein and low levels of Cyclin D1 transcripts were shown to primarily enter G0 whereas cells with high Cyclin D1 and low levels of p53 are most likely to reenter the cell cycle. These results illustrate a form of encoded molecular memory though the history of mitogen signaling through ERK and stress response though p53. [ 11 ] [ 12 ]
Uncontrolled growth is a necessary step for the development of all cancers. [ 13 ] In many cancers (e.g. melanoma ), a defect in the MAP/ERK pathway leads to that uncontrolled growth. Many compounds can inhibit steps in the MAP/ERK pathway, and therefore are potential drugs for treating cancer, [ 14 ] [ 15 ] [ 16 ] [ 17 ] [ 18 ] such as Hodgkin disease . [ 19 ]
The first drug licensed to act on this pathway is sorafenib — a Raf kinase inhibitor. Other Raf inhibitors include SB590885, PLX4720, XL281, RAF265, encorafenib , dabrafenib , and vemurafenib . [ 18 ]
Some MEK inhibitors include cobimetinib , CI-1040, PD0325901, binimetinib (MEK162), selumetinib , [ 18 ] and trametinib (GSK1120212) [ 20 ]
It has been found that acupoint-moxibustion has a role in relieving alcohol-induced gastric mucosal injury in a mouse model, which may be closely associated with its effects in up-regulating activities of the epidermal growth factor/ERK signal transduction pathway. [ 21 ]
RAF-ERK pathway is also involved in the pathophysiology of Noonan syndrome , a polymalformative disease.
Protein microarray analysis can be used to detect subtle changes in protein activity in signaling pathways. [ 22 ] The developmental syndromes caused by germline mutations in genes that alter the RAS components of the MAP/ERK signal transduction pathway are called RASopathies . | https://en.wikipedia.org/wiki/MAPK/ERK_pathway |
Mitogen-activated protein kinase (MAPK) networks are the pathways and signaling of MAPK , which is a protein kinase that consists of amino acids serine and threonine . [ 1 ] MAPK pathways have both a positive and negative regulation in plants. A positive regulation of MAPK networks is to help in assisting with stresses from the environment. A negative regulation of MAPK networks is pertaining to a high quantity of reactive oxygen species (ROS) in the plant. [ 1 ] [ 2 ] [ 3 ]
Mitogen-activated protein kinase (MAPK) networks can be found in eukaryotic cells. MAPK pathways in plants are known to regulate cell growth , cell development , cell death , and cell responses to environmental stimuli. Only a few of the MAPK mechanism components are known and have been studied. The components such as Arabidopsis MAPKKKs YODA , ANP2 / ANP3 , and MP3K6 / MP3K7 functions in the development of the cell. MEKK1 and ANP1 function in the response to environmental stress. Unfortunately, only eight out of the twenty mitogen-activated protein kinases have been studied. The most commonly studied MAPKs are MPK3 , MPK4 , and MPK6 , which are activated by a diversity of stimuli including abiotic stresses, pathogens, and oxidative stressors . MPK4 negatively regulates biotic stress signaling, while MPK3 and MPK6 function as positive mediators of defense responses. The plant has these positive and negative mediators allowing for normal plant growth and development, which has been proven true by the severely dwarfed phenotype of mpk4 and the embryo lethal phenotype of mpk3 and mpk6 mutants. [ 2 ]
Plants have many protection mechanisms to cope with stresses from the environment, which include ultraviolet light , cold or hot weather, windy days, and mechanical wounding. [ 3 ] There are multiple pathways, but one pathway that plants have been able to develop is a self-defense mechanism by recognize pathogens through pathogen-associated molecular patterns (PAMPs) via cell surface-located pathogen-recognition receptors. These receptors induce intracellular signal pathways within the plant cells, while also resulting in PAMP-triggered immunity. Responses to PAMPs target broadly instead of specifically. This immunity requires downstream components via the MAPK cascade to activate the MAP kinases. The flagellin, a peptide of flg22, triggers a rapid and strong activation of MPK3, MPK4, and MPK6. MPK4 and MPK6 can be activated by harpin proteins . MPK3 and MPK6 are very similar proteins and have a function as regulators in abscission, stomatal development, signaling various abiotic stresses, and defense responses to certain pathogens. Experimentation has proposed that the MAPK module MEKK1-MKK4/MKK5-MPK3/MPK6 may be responsible for flg22 signal transmission. All of the proposed modules appear to be correct expect for MEKK1 because plants with mekk1 mutated have a compromised flg22-triggered activation of MPK4, yet they have normal activation of MPK3 and MPK6. Data has shown that MAPK cascade is composed of MKK4/MKK5 and MPK3/MPK6 in response to fungal pathogens. The observation shows that the activation of MPK3/MPK6 in conditional gain-of-function plants for MKK4/MKK5 or MEKK1/MKKKa is sufficient to induce camalexin , which is a major phytoalexin in Arabidopsis. The stomata are considered to be the entry point for pathogenic invaders because microbial invaders enter the plant at the stomata. A recent study has shown that MAPK cascades play a role in abiotic and biotic stress responses. The main pathways in stomatal development and dynamics are MPK3 and MPK6. During a drought , the stomata closes and is believed to be mediated by the phytohormone , abscisic acid , and involves MKK1 , MPK3, and MPK6. Another way of closing the stomata is through a closing process that is called pathogen-induced, which is an innate response from the plant. Campestris (Xcc) excretes a chemical that reverts stomatal closure that was caused by bacteria and abscisic acid (ABA). Most stomata close in the presence of ABA, but some are unresponsive to bacteria. In Arabidopsis Xcc does not revert bacteria-induced or ABA-induced stomatal closure. Scientists are not certain if MAPK cascades are responsible for the signaling, so further investigation is needed for this. [ 2 ]
The identification of MEKK1-MKK1/2-MPK4 in pathogen signaling has been a tremendous finding. Mekk1, mkk1/mkk2 double and mpk4 mutations are dwarfed and acquire too much of reactive oxygen species. The mutations are considered to be from the enhancement of SA levels, which is partially reversed by bacterial SA hydrolase . Mekk1, mkk1/mkk2 double and mpk4 mutations have cell death occur spontaneously, pathogenesis-related genes and increased resistance to pathogens. MEKK1 appears to have deregulation pathways that are unknown and do not involve MKK1/MKK2 nor MPK4. MEKK1 interact with WRKY53, which is responsible for mekk1 genes set, and alter the activity of WRKY53 that is a short portion of MAPK signaling. Substrates of MPK4 are three proteins: WRKY33 , WRKY25 , and MKS1. Ternary MKS1-MPK4-WRKY33 complexes have been recognized by nuclear extracts. Recruitment of WRKY33 depends on the phosphorylation of MPK4. Once activated, MPK3 phosphorylates MKS1, which releases WRKY33 from the ternary complex. The free WRKY33 is believed to induce transcription on target genes., allowing for a negative regulation by MPK4. Pathogens have developed mechanisms that inactivate PAMP-induced signaling pathways through the MAPK networks. Andrea Pitzschke and her colleges claim “AvrPto and AvrPtoB interact with the FLS2 receptor and its co-receptor BAK1. AvrPtoB catalyzes the polyubiquitination and subsequent proteasome -dependent degradation of FLS2 ” (Pitzschke 3). AvrPto interacts with BAK1 and interrupts the binding of FLS2. Pseudomonas syringae have HopAI1, which is a phosphothreonin lyase , and dephosphorylates the threonine residue at the upstream MAPKKs. HopAI1 interacts with MPK3 and MPK6 allowing for flg22 activation to occur. In certain soil-borne pathogens that carry flagellin variants cannot be detected by FLS2, but there is still a triggered innate immune response. The immune response has been shown to be from the EF-Tu protein . Flg22 , elf18 , FLS2 and EFR have receptors that are in the same subfamily of LRR-RLKs, LRRXII. This means that elf18 and flg22 induce extracellular alkalization, rapid activation of MAPKs, and gene responses that are similar to each other. Although there appears to be an important relationship between MAPKs with EF-Tu-triggered defense, the evidence remains to be unclear. The reason for this unclear relationship is because of Agrobacterium tumefaciens , which infects into segments of plant DNA. EFR1 mutants do not recognize EF-Tu, but there is no research on MAPK activities and efr1. Initiation of defense signaling can be a positive effect to the plant pathogens because activating MPK3 in response to flg22 causes phosphorylation and translocation of virE2 interacting protein 1 (VIP1). VIP1 serves as a shuttle for the pathogenic T-DNA, but the induction of defense genes can occur as well. This allows for the spreading and cessation of the pathogen in the plant, but the pathogen can overcome the problem by attacking VIP1 for proteasome degradation by VirF, which is a virulence factor that encodes an F-box protein. [ 2 ] | https://en.wikipedia.org/wiki/MAPK_networks |
Mitogen-activated protein kinase kinase kinase kinase ( MAP4K ) is a family of proteins involved in cellular signal transduction .
This biochemistry article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/MAP_kinase_kinase_kinase_kinase |
Mosaic analysis with a repressible cell marker , or MARCM , is a genetics technique for creating individually labeled homozygous cells in an otherwise heterozygous Drosophila melanogaster . [ 1 ] It has been a crucial tool in studying the development of the Drosophila nervous system. This technique relies on recombination during mitosis mediated by FLP-FRT recombination . As one copy of a gene, provided by the balancer chromosome , is often enough to rescue a mutant phenotype , MARCM clones can be used to study a mutant phenotype in an otherwise wildtype animal.
In order to label small populations of cells from a common progenitor , MARCM uses the GAL4-UAS system . A marker gene such as GFP is placed under control of a UAS promoter . GAL4 is ubiquitously expressed in these flies, thus driving marker expression. In addition, GAL80 is driven by a strong promoter such as tubP. Gal80 is an inhibitor of GAL4 , and will suppress GFP expression under normal conditions. This tubP-GAL80 element is placed distal to an FRT site. A second FRT site is placed in trans to the GAL80 site, usually with a gene or mutation of interest distal to it. Finally, FLP recombinase is driven by an inducible promoter such as heat shock.
When FLP transcription is induced, it will recombine the chromosomes at the two FRT sites in cells undergoing mitosis. These cells will divide into two homozygous daughter cells—one carrying both GAL80 elements, and one carrying none. The daughter cell lacking GAL80 will be labeled due to expression of the marker via the GAL4-UAS system. All subsequent daughter cells from this progenitor will also express the marker.
Labs will often have MARCM-ready lines which have the inducible FLP, GAL80 distal to a FRT site, GAL4, and UAS-Marker. These can be readily crossed with flies that have a mutation of interest distal to a FRT site. [ 2 ]
By taking advantage of MARCM, one can easily trace all the cells that have been generated from a single progenitor. This is a useful tool in tracking development and specific cell lineages in various environmental conditions. Applications for MARCM include studying neuronal circuits , [ 3 ] clonal analysis, [ 4 ] genetic screens , [ 5 ] spermatogenesis , [ 6 ] growth cone development, [ 7 ] neurogenesis , [ 8 ] and tumor metastasis . [ 9 ]
Many advances in the understanding of Drosophila development have been achieved through MARCM. The development, lineages, and characterizations of secondary axon tracts, [ 10 ] anatomical maps of cholinergic neurons in the visual systems, [ 11 ] lineages giving rise to a thoracic hemineuromere scaffold and the developmental framework for CNS architecture, [ 12 ] the role of Delta in developmental programming in the ventral nerve cord, [ 13 ] the wake-promoting octopaminergic cells in the medial protocerebrum , [ 14 ] genes involved in neuronal morphogenesis of the mushroom bodies , [ 15 ] and the regulation of commissural axon guidance [ 16 ] have all been identified through MARCM techniques.
There are many variations of MARCM. Twin-spot MARCM allows for the labeling of sister clones with two separate markers, thus allowing for a higher resolution of lineage tracing. [ 17 ] In reverse MARCM, the mutation of interest is placed on the same chromosome as GAL80, so that the wild-type homozygous clones will be labeled. [ 18 ] Flip-Out MARCM highlights individual cells inside of mutant clones (ref "Drosophila Dscam is required for divergent segregation of sister branches and suppresses ectopic bifurcation of axons," Neuron, 2002). The Q system allows for GAL4 independent MARCM by using the QF/QS system. [ 19 ] Lethal MARCM allows for the generation of large marked homozygous populations by including a lethal mutation near the GAL80 site. [ 20 ] Dual-expression control MARCM uses the LexA-VP16 transcriptional system in concordance with GAL4-UAS. [ 21 ] MARCM is also often used as a genetic screen. [ 15 ] | https://en.wikipedia.org/wiki/MARCM |
The International Convention for the Prevention of Pollution from Ships, 1973 as modified by the Protocol of 1978 , or " MARPOL 73/78 " (short for "marine pollution") is one of the most important international marine environmental conventions . [ 2 ] It was developed by the International Maritime Organization with an objective to minimize pollution of the oceans and seas, including dumping , oil and air pollution .
The original MARPOL was signed on 17 February 1973, but did not come into force at the signing date. The current convention is a combination of 1973 Convention and the 1978 Protocol, [ 3 ] which entered into force on 2 October 1983. As of January 2018, 156 states are parties to the convention, being flag states of 99.42% of the world's shipping tonnage. [ 1 ]
All ships flagged under countries that are signatories to MARPOL are subject to its requirements, regardless of where they sail, and member nations are responsible for vessels registered on their national ship registry. [ 4 ]
MARPOL is divided into Annexes according to various categories of pollutants, each of which deals with the regulation of a particular group of ship emissions.
Notes
MARPOL Annex I came into force on 2 October 1983 and deals with the discharge of oil into the ocean environment. [ 6 ] It incorporates the oil discharge criteria prescribed in the 1969 amendments to the 1954 International Convention for the Prevention of Pollution of the Sea by Oil (OILPOL). It specifies tanker design features that are intended to minimize oil discharge into the ocean during ship operations and in case of accidents. It provides regulations with regard to the treatment of engine room bilge water ( OWS ) for all large commercial vessels and ballast and tank cleaning waste ( ODME ). It also introduces the concept of "special sea areas (PPSE)", which are considered to be at risk to pollution by oil. Discharge of oil within them has been completely outlawed, with a few minimal exceptions. [ 5 ]
The first half of MARPOL Annex I deals with engine room waste. There are various generations of technologies and equipment that have been developed to prevent waste such as oily water separators (OWS), oil content meters (OCM), and port reception facilities . [ 7 ]
The second part of the MARPOL Annex I has more to do with cleaning the cargo areas and tanks. Oil discharge monitoring equipment (ODME) is a very important technology mentioned in MARPOL Annex I that has greatly helped improve sanitation in these areas. [ 7 ]
The oil record book is another integral part of MARPOL Annex I , helping crew members log and keep track of oily wastewater discharges, among other things.
MARPOL Annex II came into force on 2 October 1983. It details the discharge criteria for the elimination of pollution by noxious liquid substances carried in large quantities. It divides substances into [ clarification needed ] and introduces detailed operational standards and measures. The discharge of pollutants is allowed only to reception facilities with certain concentrations and tions. No matter what, no discharge of residues containing pollutants is permitted within 12 nautical miles (22 kilometres) of the nearest land. Stricter restrictions apply to "special areas". [ 5 ]
Annex II covers the International Bulk Chemical Code (IBC Code) in conjunction with Chapter 7 of the SOLAS Convention . Previously, chemical tankers constructed before 1 July 1986 must comply with the requirements of the Code for the Construction and Equipment of Ships Carrying Dangerous Chemicals in Bulk (BCH Code). [ 8 ]
MARPOL Annex III came into force on 1 July 1992. It contains general requirements for the standards on packing, marking, labeling, documentation, stowage, quantity subtraction, division and notifications for preventing pollution by harmful substances. The Annex is in line with the procedures detailed in the International Maritime Dangerous Goods (IMDG) Code, which has been expanded to include marine pollutants. [ 9 ] The amendments entered into force on 1 January 1991. [ 5 ]
Marpol Annex IV came into force on 27 September 2003. It introduces requirements to control pollution of the sea by sewage from ships.
MARPOL Annex V ( Regulations for the Prevention of Pollution by Garbage from Ships ) came into force on 31 December 1988. It specifies the distances from land in which materials may be disposed of and subdivides different types of garbage and marine debris. The requirements are much stricter in a number of "special areas" but perhaps the most prominent part of the Annex is the complete ban of dumping plastic into the ocean. [ 10 ]
MARPOL Annex VI came into force on 19 May 2005. It introduces requirements to regulate the air pollution being emitted by ships, including the emission of ozone-depleting substances, Nitrogen Oxides (NOx) , Sulfur Oxides (SOx) , Volatile Organic Compounds (VOCs) and shipboard incineration. It also establishes requirements for reception facilities for wastes from exhaust gas cleaning systems, incinerators, fuel oil quality, off-shore platforms and drilling rigs, and the establishment of Sulfur Emission Control Areas (SECAs) . [ 5 ]
As of 1 January 2020, new emission standards are enforced for fuel oil used by ships, in a regulation known as IMO 2020 . The global sulphur limit (outside SECA's) dropped from an allowed 3.5% sulphur in marine fuels to 0.5%. [ 11 ] This will significantly improve the air quality in many populated coastal and port areas, which will prevent over 100,000 early deaths each year, and many more cases of asthma in these regions and cities. [ 12 ] [ 13 ] Over 170 countries have signed on to the changes, including the United States. [ 14 ] This is expected to create massive changes for the shipping and oil industries, with major updates required to ships and the increased production of lower sulfur fuel. [ 15 ]
Bunker fuels used within an emission control zone (i.e. North Sea) must have a sulphur content level of less than 0.1% (1000ppm).
The IMO has worked on ensuring consistent implementation of the 0.5% sulphur limit in its Marine Environmental Protection Committee (MEPC) and its subcommittee on Pollution Prevention and Response (PPR). This has led to the development on several regulatory and practical measures (FONAR's, Carriage Ban, Ship Implementation Plan etc.) to enable any non-compliance to be detected, for example during port state controls (PSC's). [ 16 ]
MARPOL Annex VI amendments according with MEPC 176(58) came into force 1 July 2010. [ 17 ]
Amended Regulations 12 concerns control and record keeping of Ozone Depleting Substances. [ 18 ]
Amended Regulation 14 [ 19 ] concerns mandatory fuel oil change over procedures for vessels entering or leaving SECA areas and FO sulphur limits.
MARPOL Annex V has been amended multiple times, changing different aspects of the original text.
MEPC.219(63) came into force on 2 March 2012 to generally prohibit the discharge of any garbage into the ocean, with the exception of food wastes, cargo residues, wash-water, and animal carcasses. [ 20 ] There are further provisions describing when and how to dispose of the acceptable wastes.
MEPC.220(63) came into force on 2 March 2012 to encourage the creation of a waste management plan on-board vessels. [ 21 ]
In order for IMO standards to be binding, they must first be ratified by a total number of member countries whose combined gross tonnage represents at least 50% of the world's gross tonnage, a process that can be lengthy. A system of tacit acceptance has therefore been put into place, whereby, if no objections are heard from a member state after a certain period has elapsed, it is assumed they have assented to the treaty.
All six Annexes have been ratified by the requisite number of nations; the most recent is Annex VI, which took effect in May 2005. The country where a ship is registered ( Flag State ) is responsible for certifying the ship's compliance with MARPOL's pollution prevention standards. Each signatory nation is responsible for enacting domestic laws to implement the convention and effectively pledges to comply with the convention, annexes, and related laws of other nations. In the United States, for example, the relevant implementation legislation is the Act to Prevent Pollution from Ships .
One of the difficulties in implementing MARPOL arises from the very international nature of maritime shipping. The country that the ship visits can conduct its own examination to verify a ship's compliance with international standards and can detain the ship if it finds significant noncompliance . When incidents occur outside such country's jurisdiction or jurisdiction cannot be determined, the country refers cases to flag states, in accordance with MARPOL. A 2000 US GAO report documented that even when referrals have been made, the response rate from flag states has been poor. [ 22 ]
On 1 January 2015, maritime shipping levels became legally subject to new MARPOL directives because the SECA (Sulphur Emission Controlled Areas) zone increased in size. This larger SECA zone will include the North Sea , Scandinavia , and parts of the English Channel . This area is set to include all of the Republic of Ireland's international waters in 2020 culminating in all of Western Europe's subjection to the MARPOL directive. This has proven controversial for shipping and ferry operators across Europe.
Concerns have been raised about the environmental damage moving back to the roads by some of the larger ferry operators that ship substantial amounts of freight and passenger traffic via these routes affected by IMO standards. They claim that MARPOL will drive up ferry costs for the consumer and freight forwarding companies pushing them back onto the European roadways as a financially more cost effective measure compared to increased ferry costs, thereby defeating the object of reducing water pollution. [ 23 ]
Concerns have also been raised whether the emission regulation in MARPOL Annex VI, such as the 0.5% global sulphur limit, can be enforced on international waters by non-flag States, as some ships sail under a flag of convenience . It is believed that the United Nations Convention on the Law of the Sea ( UNCLOS ) allows port States to assert jurisdiction over such violations of emission regulation (also of future regulations of GHG) when they occur on the high seas. Coastal States can assert jurisdiction over violations occurring within their waters, with certain exceptions pertaining to innocent passage and the right of transit passage. The special obligations for flag States and the broadened jurisdictions for coastal and port States, to enforce MARPOL (including Annex VI) are found within the special provisions of part XII of UNCLOS. [ 24 ] | https://en.wikipedia.org/wiki/MARPOL_73/78 |
MASS syndrome is a medical disorder of the connective tissue similar to Marfan syndrome .
MASS stands for m itral valve prolapse , a ortic root diameter at upper limits of normal for body size, s tretch marks of the skin, and s keletal conditions similar to Marfan syndrome. It is caused by a mutation in the FBN1 gene, which encodes fibrillin-1 . [ 2 ] Fibrillin-1 is an extracellular matrix protein that is found in microfibrils ; [ 3 ] defects in the fibrillin-1 protein cause the malfunctioning of microfibrils, [ 4 ] which results in improper stretching [ 4 ] of ligaments, blood vessels, and skin.
Treatment options for MASS syndrome are largely determined on a case-by-case basis and generally address the symptoms as opposed to the cause of the disorder. [ 5 ] Due to the similarities between MASS syndrome and Marfan syndrome, the treatment plans are also similar. [ 6 ]
Other possible symptoms are mitral valve prolapse , a large aortic root diameter, and myopia . [ 2 ] The skeletal features found in MASS syndrome include curvature of the spine ( scoliosis ), chest wall deformities, and joint hypermobility . [ 2 ]
MASS syndrome and Marfan syndrome are overlapping connective tissue disorders . Both can be caused by mutations in the gene encoding a protein called fibrillin. These conditions share many of the same signs and symptoms including long limbs and fingers, chest wall abnormalities (indented chest bone or protruding chest bone), flat feet, scoliosis, mitral valve prolapse, loose or hypextensible joints, highly arched roof of the mouth, and mild dilatation of the aortic root. Unlike in Marfan syndrome, aneurysm does not develop. [ 2 ]
Individuals with MASS syndrome do not have progressive aortic enlargement or lens dislocation , while people with Marfan syndrome do. Skin involvement in MASS syndrome is typically limited to stretch marks ( striae distensae ). Also, the skeletal manifestations of MASS syndrome are generally mild. [ citation needed ]
Ankyrin : Long QT syndrome 4 | https://en.wikipedia.org/wiki/MASS_syndrome |
MATLAB (an abbreviation of "MATrix LABoratory" [ 18 ] ) is a proprietary multi-paradigm programming language and numeric computing environment developed by MathWorks . MATLAB allows matrix manipulations, plotting of functions and data, implementation of algorithms , creation of user interfaces , and interfacing with programs written in other languages.
Although MATLAB is intended primarily for numeric computing, an optional toolbox uses the MuPAD symbolic engine allowing access to symbolic computing abilities. An additional package, Simulink , adds graphical multi-domain simulation and model-based design for dynamic and embedded systems .
As of 2020 [update] , MATLAB has more than four million users worldwide. [ 19 ] They come from various backgrounds of engineering , science , and economics . As of 2017 [update] , more than 5000 global colleges and universities use MATLAB to support instruction and research. [ 20 ]
MATLAB was invented by mathematician and computer programmer Cleve Moler . [ 21 ] The idea for MATLAB was based on his 1960s PhD thesis . [ 21 ] Moler became a math professor at the University of New Mexico and started developing MATLAB for his students [ 21 ] as a hobby. [ 22 ] He developed MATLAB's initial linear algebra programming in 1967 with his one-time thesis advisor, George Forsythe . [ 21 ] This was followed by Fortran code for linear equations in 1971. [ 21 ]
Before version 1.0, MATLAB "was not a programming language; it was a simple interactive matrix calculator. There were no programs, no toolboxes, no graphics. And no ODEs or FFTs ." [ 23 ]
The first early version of MATLAB was completed in the late 1970s. [ 21 ] The software was disclosed to the public for the first time in February 1979 at the Naval Postgraduate School in California. [ 22 ] Early versions of MATLAB were simple matrix calculators with 71 pre-built functions. [ 24 ] At the time, MATLAB was distributed for free [ 25 ] [ 26 ] to universities. [ 27 ] Moler would leave copies at universities he visited and the software developed a strong following in the math departments of university campuses. [ 28 ] : 5
In the 1980s, Cleve Moler met John N. Little . They decided to reprogram MATLAB in C and market it for the IBM desktops that were replacing mainframe computers at the time. [ 21 ] John Little and programmer Steve Bangert re-programmed MATLAB in C, created the MATLAB programming language, and developed features for toolboxes. [ 22 ]
MATLAB was first released as a commercial product in 1984 at the Automatic Control Conference in Las Vegas . [ 21 ] [ 22 ] MathWorks , Inc. was founded to develop the software [ 26 ] and the MATLAB programming language was released. [ 24 ] The first MATLAB sale was the following year, when Nick Trefethen from the Massachusetts Institute of Technology bought ten copies. [ 22 ] [ 29 ]
By the end of the 1980s, several hundred copies of MATLAB had been sold to universities for student use. [ 22 ] The software was popularized largely thanks to toolboxes created by experts in various fields for performing specialized mathematical tasks. [ 25 ] Many of the toolboxes were developed as a result of Stanford students that used MATLAB in academia, then brought the software with them to the private sector. [ 22 ]
Over time, MATLAB was re-written for early operating systems created by Digital Equipment Corporation , VAX , Sun Microsystems , and for Unix PCs. [ 22 ] [ 24 ] Version 3 was released in 1987. [ 30 ] The first MATLAB compiler was developed by Stephen C. Johnson in the 1990s. [ 24 ]
In 2000, MathWorks added a Fortran-based library for linear algebra in MATLAB 6, replacing the software's original LINPACK and EISPACK subroutines that were in C. [ 24 ] MATLAB's Parallel Computing Toolbox was released at the 2004 Supercomputing Conference and support for graphics processing units (GPUs) was added to it in 2010. [ 24 ]
Some especially large changes to the software were made with version 8 in 2012. [ 31 ] The user interface was reworked [ citation needed ] and Simulink 's functionality was expanded. [ 32 ]
By 2016, MATLAB had introduced several technical and user interface improvements, including the MATLAB Live Editor notebook, and other features. [ 24 ]
For a complete list of changes of both MATLAB an official toolboxes, check MATLAB previous releases. [ 33 ]
The MATLAB application is built around the MATLAB programming language.
Common usage of the MATLAB application involves using the " Command Window " as an interactive mathematical shell or executing text files containing MATLAB code. [ 34 ]
An example of a "Hello, world!" program exists in MATLAB.
It displays like so:
Variables are defined using the assignment operator, = .
MATLAB is a weakly typed programming language because types are implicitly converted. [ 35 ] It is an inferred typed language because variables can be assigned without declaring their type, except if they are to be treated as symbolic objects, [ 36 ] and that their type can change.
Values can come from constants , from computation involving values of other variables, or from the output of a function .
For example:
A simple array is defined using the colon syntax: initial : increment : terminator . For instance:
defines a variable named array (or assigns a new value to an existing variable with the name array ) which is an array consisting of the values 1, 3, 5, 7, and 9. That is, the array starts at 1 (the initial value), increments with each step from the previous value by 2 (the increment value), and stops once it reaches (or is about to exceed) 9 (the terminator value).
The increment value can actually be left out of this syntax (along with one of the colons), to use a default value of 1.
assigns to the variable named ari an array with the values 1, 2, 3, 4, and 5, since the default value of 1 is used as the increment.
Indexing is one-based, [ 37 ] which is the usual convention for matrices in mathematics, unlike zero-based indexing commonly used in other programming languages such as C, C++ , and Java .
Matrices can be defined by separating the elements of a row with blank space or comma and using a semicolon to separate the rows. The list of elements should be surrounded by square brackets [] . Parentheses () are used to access elements and subarrays (they are also used to denote a function argument list).
Sets of indices can be specified by expressions such as 2:4 , which evaluates to [2, 3, 4] . For example, a submatrix taken from rows 2 through 4 and columns 3 through 4 can be written as:
A square identity matrix of size n can be generated using the function eye , and matrices of any size with zeros or ones can be generated with the functions zeros and ones , respectively.
Transposing a vector or a matrix is done either by the function transpose or by adding dot-prime after the matrix (without the dot, prime will perform conjugate transpose for complex arrays):
Most functions accept arrays as input and operate element-wise on each element. For example, mod(2*J,n) will multiply every element in J by 2, and then reduce each element modulo n . MATLAB does include standard for and while loops, but (as in other similar applications such as APL and R ), using the vectorized notation is encouraged and is often faster to execute. The following code, excerpted from the function magic.m , creates a magic square M for odd values of n (MATLAB function meshgrid is used here to generate square matrices I and J containing 1 : n {\displaystyle 1:n} ):
MATLAB supports structure data types. [ 38 ] Since all variables in MATLAB are arrays, a more adequate name is "structure array", where each element of the array has the same field names. In addition, MATLAB supports dynamic field names [ 39 ] (field look-ups by name, field manipulations, etc.).
When creating a MATLAB function, the name of the file should match the name of the first function in the file. Valid function names begin with an alphabetic character, and can contain letters, numbers, or underscores. Variables and functions are case sensitive. [ 40 ]
MATLAB supports elements of lambda calculus by introducing function handles, [ 41 ] or function references, which are implemented either in .m files or anonymous [ 42 ] /nested functions. [ 43 ]
MATLAB supports object-oriented programming including classes, inheritance , virtual dispatch, packages, pass-by-value semantics, and pass-by-reference semantics. [ 44 ] However, the syntax and calling conventions are significantly different from other languages. MATLAB has value classes and reference classes, depending on whether the class has handle as a super-class (for reference classes) or not (for value classes). [ 45 ]
Method call behavior is different between value and reference classes. For example, a call to a method:
can alter any member of object only if object is an instance of a reference class, otherwise value class methods must return a new instance if it needs to modify the object.
An example of a simple class is provided below:
When put into a file named hello.m , this can be executed with the following commands:
MATLAB has tightly integrated graph-plotting features. For example, the function plot can be used to produce a graph from two vectors x and y . The code:
produces the following figure of the sine function :
MATLAB supports three-dimensional graphics as well:
MATLAB supports developing graphical user interface (GUI) applications. [ 46 ] UIs can be generated either programmatically or using visual design environments such as GUIDE and App Designer . [ 47 ] [ 48 ]
MATLAB can call functions and subroutines written in the programming languages C or Fortran . [ 49 ] A wrapper function is created allowing MATLAB data types to be passed and returned. MEX files (MATLAB executables) are the dynamically loadable object files created by compiling such functions. [ 50 ] [ 51 ] Since 2014 increasing two-way interfacing with Python was being added. [ 52 ] [ 53 ]
Libraries written in Perl , Java , ActiveX or .NET can be directly called from MATLAB, [ 54 ] [ 55 ] and many MATLAB libraries (for example XML or SQL support) are implemented as wrappers around Java or ActiveX libraries. Calling MATLAB from Java is more complicated, but can be done with a MATLAB toolbox [ 56 ] which is sold separately by MathWorks , or using an undocumented mechanism called JMI (Java-to-MATLAB Interface), [ 57 ] [ 58 ] (which should not be confused with the unrelated Java Metadata Interface that is also called JMI). Official MATLAB API for Java was added in 2016. [ 59 ]
As alternatives to the MuPAD based Symbolic Math Toolbox available from MathWorks, MATLAB can be connected to Maple or Mathematica . [ 60 ] [ 61 ]
Libraries also exist to import and export MathML . [ 62 ]
In 2020, MATLAB withdrew services from two Chinese universities as a result of US sanctions. The universities said this will be responded to by increased use of open-source alternatives and by developing domestic alternatives. [ 63 ] | https://en.wikipedia.org/wiki/MATLAB |
MAVLink or Micro Air Vehicle Link is a protocol for communicating with small unmanned vehicle . It is designed as a header-only message marshalling library. MAVLink was first released early 2009 [ 1 ] by Lorenz Meier under the LGPL license. [ 2 ]
It is used mostly for communication between a Ground Control Station (GCS) and Unmanned vehicles , and in the inter-communication of the subsystem of the vehicle. It can be used to transmit the orientation of the vehicle, its GPS location and speed.
In version 1.0 the packet structure is the following:
After Version 2, the packet structure was expanded into the following: [ 3 ]
To ensure message integrity a cyclic redundancy check (CRC) is calculated to every message into the last two bytes. Another function of the CRC field is to ensure the sender and receiver both agree in the message that is being transferred. It is computed using an ITU X.25/SAE AS-4 hash of the bytes in the packet, excluding the Start-of-Frame indicator (so 6+n+1 bytes are evaluated, the extra +1 is the seed value).
Additionally a seed value is appended to the end of the data when computing the CRC. The seed is generated with every new message set of the protocol, and it is hashed in a similar way as the packets from each message specifications. Systems using the MAVLink protocol can use a precomputed array to this purpose. [ 4 ]
The CRC algorithm of MAVLink has been implemented in many languages, like Python [ 5 ] and Java. [ 6 ] [ 7 ] [ 8 ]
The payload from the packets described above are MAVLink messages. Every message is identifiable by the ID field on the packet, and the payload contains the data from the message. An XML document in the MAVlink source [ 9 ] has the definition of the data stored in this payload.
Below is the message with ID 24 extracted from the XML document.
Note: The XML document describes the logical ordering of the fields for the protocol. The actual wire format (and typical in-memory representation) has the fields reordered [ 10 ] to reduce Data structure alignment issues. This can be a source of confusion when reading the code generated from the message definitions.
MAVLink is used as the communication protocol in many projects, which may mean there is some compatibility between them. A tutorial explaining basics of MAVLink has been written. [ 11 ] | https://en.wikipedia.org/wiki/MAVLink |
Within computational biology , an MA plot is an application of a Bland–Altman plot for visual representation of genomic data. The plot visualizes the differences between measurements taken in two samples, by transforming the data onto M (log ratio) and A ( mean average ) scales, then plotting these values. Though originally applied in the context of two channel DNA microarray gene expression data, MA plots are also used to visualise high-throughput sequencing analysis. [ 1 ] [ 2 ]
Microarray data is often normalized within arrays to control for systematic biases in dye coupling and hybridization efficiencies, as well as other technical biases in the DNA probes and the print tip used to spot the array. [ 3 ] By minimizing these systematic variations, true biological differences can be found. To determine whether normalization is needed, one can plot Cy5 (R) intensities against Cy3 (G) intensities and see whether the slope of the line is around 1. An improved method, which is basically a scaled, 45 degree rotation of the R vs. G plot is an MA-plot. [ 4 ] The MA-plot is a plot of the distribution of the red/green intensity ratio ('M'), that is plotted against the average intensity ('A'). M and A are defined by the following equations.
M is, therefore, the binary logarithm of the intensity ratio (or difference between log intensities) and A is the average log intensity for a dot in the plot. MA plots are then used to visualize intensity-dependent ratio of raw microarray data (microarrays typically show a bias here, with higher A resulting in higher |M|, i.e. the brighter the spot the more likely an observed difference between sample and control). The MA plot puts the variable M on the y -axis and A on the x -axis and gives a quick overview of the distribution of the data.
In many microarray gene expression experiments, an underlying assumption is that most of the genes would not see any change in their expression; therefore, the majority of the points on the y -axis ( M ) would be located at 0, since log(1) is 0. If this is not the case, then a normalization method such as LOESS should be applied to the data before statistical analysis. (On the diagram below see the red line running below the zero mark before normalization, it should be straight. Since it is not straight, the data should be normalized. After being normalized, the red line is straight on the zero line and shows as pink/black.)
Several Bioconductor packages, for the R software , provide the facility for creating MA plots. These include affy (ma.plot, mva.pairs), limma (plotMA), marray (maPlot), and edgeR(maPlot)
Similar "RA" plots can be generated using the raPlot function in the caroline CRAN R package.
An interactive MA plot to filter genes by M, A and p-values, search by names or with a lasso, and save selected genes, is available as an R-Shiny code Enhanced-MA-Plot . | https://en.wikipedia.org/wiki/MA_plot |
The Maťo ( Matthew ) was an 8-bit personal computer produced in the former Czechoslovakia by Štátny majetok Závadka š.p., Závadka nad Hronom, from 1989 to 1992. [ 1 ] [ 2 ] [ 3 ] Their primary goal was to produce a personal computer as cheaply as possible, and therefore it was also sold as a self-assembly kit . It was basically a modified PMD 85 , but without backward compatibility . This, combined with its late arrival to the market, made the MAŤO a commercial failure.
This computing article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/MAŤO |
A methylene blue active substances assay , or MBAS assay , is a colorimetric analysis test method that uses methylene blue to detect the presence of anionic surfactants (such as a detergent or foaming agent ) in a sample of water . An anionic surfactant detected by the color reaction is called a methylene blue active substance (MBAS). [ 1 ]
After first acidifying a water sample (with boric acid , for example), one adds to it chloroform and a solution of methylene blue et al. [ 2 ] Methylene blue is a cationic dye . The biphasic solution is then agitated to distribute these reagents throughout the aqueous and organic phases. [ 2 ] If an anionic surfactant is present, then the cationic methylene blue and the anionic surfactant forms an ion pair, which is extracted into the organic phase. The color saturation of the chloroform increases with the concentration of anionic surfactants.
MBAS assay is an ASTM International standard technique for detecting anionic surfactants. [ 3 ] These include carboxylates , phosphates , sulfates , and sulfonates . An MBAS assay alone does not, however, identify specific surfactants. ASTM withdrew the standard (ASTM D2330-02) in 2011 pending a review and update of the method, which was last approved in 2003. [ 3 ]
The publication Standard Methods for the Examination of Water and Wastewater lists the following methods used by certified laboratories testing wastewater in the United States. | https://en.wikipedia.org/wiki/MBAS_assay |
MBN Explorer ( MesoBioNano Explorer ) is a software package for molecular dynamics simulations, structure optimization and kinetic Monte Carlo simulations. It is designed for multiscale computational analysis of structure and dynamics of atomic clusters and nanoparticles , biomolecules and nanosystems, nanostructured materials, different states of matter and various interfaces. [ 1 ] The software has been developed by MBN Research Center.
MBN Explorer inherited the experience obtained on the development of the software package Cluster Searcher. It started around 2000 as a classical molecular dynamics code for simulating many-body systems interacting via the Morse and the Lennard-Jones potentials. [ 2 ] A variety of interatomic potentials and the possibility to combine a group of atoms into rigid blocks were introduced in 2005–2007. The first version of MBN Explorer was released in 2012 as a multipurpose computer code allowing to model different molecular systems of varied level of complexity. [ 3 ]
MBN Explorer allows for the multiscale description of molecular systems by means of kinetic Monte Carlo approach [ 4 ] and the irradiation-driven molecular dynamics. [ 5 ] By means of the Monte Carlo approach, the software allows to simulate diffusion-drive processes involving molecular systems on much larger time scales that can be reached in conventional molecular dynamics simulations. [ 6 ] The software allows to combine different types of interatomic potentials to specify more than one interaction to a particular atom or a group of atoms.
MBN Explorer supports several standard atomic trajectory formats, such as XYZ (text format), DCD [ 7 ] (binary format) and DCD+XYZ (hybrid format). It also supports the Protein Data Bank [ 8 ] (pdb) file format for describing the three-dimensional structures of biomolecules.
Advanced features of the program include:
MBN Explorer is complemented with MBN Studio [ 6 ] [ 10 ] - a multi-task program for molecular modeling and design, as well as for visualization and analysis of results of the simulations performed with MBN Explorer. The built-in molecular modeler can be used to construct isolated and solvated biomolecules, condensed molecular materials, carbon nanotubes and graphene sheets, nanoparticles and crystalline samples.
MBN Explorer has been utilized in different research projects in the fields of materials science, nanotechnology and radiation damage: | https://en.wikipedia.org/wiki/MBN_Explorer |
MCEF or Major Cdk9 -interacting elongation factor is a transcription factor related to Af4. It is the fourth member of the Af4 family (AFF) of transcription factors, involved in numerous pathologies, including Acute Lymphoblastic Leukemia (ALL), abnormal CNS development, breast cancer and azoospermia .
Because it apparently interacts with the species-specific human co-factor ( P-TEFb ) for HIV-1 transcription, and because it can repress HIV-1 replication, MCEF (also known as AFF4 or AF5q31) may have future therapeutic uses. [ 1 ]
MCEF was originally cloned and named by Mario Clemente Estable of Ryerson University , while he was a post-doctoral fellow in the laboratory of Robert G. Roeder , at the Rockefeller University .
Transcription factors
This biochemistry article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/MCEF |
MCF Employees' Union , a trade union at the Mangalore Chemicals and Fertilisers , in Karnataka, India. MCFEU is affiliated to Hind Mazdoor Sabha .
This article related to an Indian trade union is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/MCF_Employees'_Union |
MCF Mazdoor Sangh , a trade union at the Mangalore Chemicals and Fertilisers , in Karnataka, India. MCFMS is affiliated to Bharatiya Mazdoor Sangh .
This article related to an Indian trade union is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/MCF_Mazdoor_Sangh |
MDGRAPE-4 is a supercomputer under development at the RIKEN Quantitative Biology Center (QBiC) in Suita , Osaka, Japan. [ 1 ]
This article about a computer book or series of books is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/MDGRAPE-4 |
MDL Chime was a free plugin used by web browsers to display the three-dimensional structures of molecules . [ 2 ] and was based on the RasMol code. [ 3 ]
Chime was used by a wide range of biochemistry web sites for the visualization of macromolecules , many of which were linked to the World Index of Molecular Visualization Resources MolVisIndex.Org. Chime was also used until 2006 at the Protein Data Bank (PDB) to examine structures stored there.
Although available in 1996 in both Windows 95 and classic Mac OS versions for both Netscape and Internet Explorer browsers, development of Chime did not follow the move to Mac OS X for the Mac and support for Windows-based browsers other than Internet Explorer was limited (although it works well in Mozilla Firefox ). One significant feature added in 1997 was the ability to display spectroscopic data in the form of the IUPAC JCAMP-DX protocols. Apart from this, most subsequent updates were for the installation package to follow the development of Windows and Internet Explorer. Accelrys announced in 2012 that Chime was no longer supported and would remain available for download until the end of 2012. [ 4 ] Chime was part of the ISIS product line acquired by Symyx Technologies from scientific publisher Elsevier in October 2007. Now Chime is owned by Dassault Systemes BIOVIA (formerly Accelrys), and has been merged into Discovery Studio , but no longer exists as a free browser plugin.
Chime largely has been superseded by Jmol , [ 5 ] a non-proprietary open-source Java molecular visualization application and JavaScript applet that has maintained most Chime command compatibility while adding numerous features. | https://en.wikipedia.org/wiki/MDL_Chime |
MDN Web Docs , previously Mozilla Developer Network and formerly Mozilla Developer Center , is a documentation repository and learning resource for web developers . It was started by Mozilla in 2005 [ 2 ] as a unified place for documentation about open web standards, Mozilla's own projects, and developer guides. [ 3 ]
MDN Web Docs content is maintained by Mozilla, Google employees, and volunteers (community of developers and technical writers). It also contains content contributed by Microsoft , Google , and Samsung who, in 2017, announced they would shut down their own web documentation projects and move all their documentation to MDN Web Docs. [ 4 ] Topics include HTML5 , JavaScript , CSS , Web APIs , Django , Node.js , WebExtensions , MathML , and others. [ 5 ]
In 2005, Mozilla Corporation started the project under the name Mozilla Developer Center, [ 2 ] and still funds the servers and staff of its projects.
The initial content for the website was provided by DevEdge , for which the Mozilla Foundation was granted a license by AOL . [ 6 ] [ 2 ] The site now contains a mix of content migrated from DevEdge and mozilla.org, as well as original and more up-to-date content. [ 7 ] [ 8 ] Documentation was also migrated from XULPlanet.com.
On Oct 3, 2016, Brave browser added Mozilla Developer Network as one of its default search engines options. [ 9 ]
In 2017, MDN Web Docs became the unified documentation of web technology for Google, Samsung, Microsoft, and Mozilla. [ 4 ] [ 10 ] Microsoft started redirecting pages from Microsoft Developer Network to MDN. [ 11 ]
In 2019, Mozilla started Beta testing a new reader site for MDN Web Docs written in React (instead of jQuery ; some jQuery functionality was replaced with Cheerio library). [ 12 ] The new site was launched on December 14, 2020. [ 13 ] Since December 14, 2020, all editable content is stored in a Git repository hosted on GitHub , where contributors open pull requests and discuss changes. [ 14 ]
On January 25 2021, [ 15 ] the Open Web Docs (OWD) organization was launched as a non-profit fiscal entity to collect funds for MDN development. [ 16 ] As of March 2023 [update] , the top financial contributors of OWD are Google , Microsoft , Igalia , Canva , and JetBrains . [ 17 ]
In March 2022, MDN launched a redesign with a new logo [ 18 ] and a paid subscription called MDN Plus. [ 19 ] | https://en.wikipedia.org/wiki/MDN_Web_Docs |
MECHATROLINK is an open protocol used for industrial automation , originally developed by Yaskawa and presently maintained by Mechatrolink Members Association (MMA). [ 1 ]
Mechatrolink protocol has two major variants: | https://en.wikipedia.org/wiki/MECHATROLINK |
MECP2 duplication syndrome ( M2DS ) is a rare disease that is characterized by severe intellectual disability and impaired motor function. It is an X-linked genetic disorder caused by the overexpression of MeCP2 protein.
Symptoms of M2DS include infantile hypotonia and failure to thrive, delayed psychomotor development , impaired speech, abnormal or absent gait , epilepsy , spasticity , gastrointestinal motility problems, recurrent infections, and genitourinary abnormalities. [ 1 ] [ 2 ] [ 3 ] Many of those affected by M2DS also fit diagnostic criteria for autism . [ 4 ] M2DS can be associated with syndromic facies , namely an abnormally flat back of the head, underdevelopment of the midface, ear anomalies, deep-set eyes, prominent chin, pointed nose, and a flat nasal bridge. [ 4 ]
M2DS is one of the several types of X-linked intellectual disability . The cause of M2DS is a duplication of the MECP2 or Methyl CpG binding protein 2 gene located on the X chromosome (Xq28). [ 5 ] The MeCP2 protein plays a pivotal role in regulating brain function. Increased levels of MECP2 protein results in abnormal neural function and impaired immune system. [ 4 ] Mutations in the MECP2 gene are also commonly associated with Rett syndrome in females. Advances in genetic testing and more widespread use of Array Comparative Genomic Hybridization has led to increased diagnosis of MECP2 duplication syndrome. [ 6 ] It is thought to represent ~1% of X-linked male mental disability cases. [ 7 ] Females affected by this condition often do not show symptoms. [ 4 ]
Diagnosis is made based on genetic testing. [ 4 ]
Treatment is supportive and based on symptoms. [ 4 ]
The syndrome primarily affects young males. [ 7 ] Preliminary studies suggest that prevalence may be 1.8 per 10,000 live male births. 50% of those affected do not live beyond 25 years of age, with deaths attributed to the impaired immune function. [ 8 ]
M2DS was first described in 1999. [ 4 ]
In a Nature article published on November 25, 2015, it was revealed that researchers at the Baylor College of Medicine , led by Dr. Huda Y. Zoghbi , have reversed MECP2 Duplication Syndrome in adult symptomatic mice using antisense therapy . [ 9 ] Mice treated with an experimental ASO administered through the central nervous system had a reduction of MECP2 protein to normal levels and symptoms of hypoactivity, anxiety, and abnormal social behavior were resolved. Additionally, the seizure activity of the mice and abnormal EEG discharges were abolished. Initial studies demonstrated that reducing the MECP2 protein levels to the correct amount also normalized the expression of the other genes controlled by the MECP2 protein. [ citation needed ] | https://en.wikipedia.org/wiki/MECP2_duplication_syndrome |
MEDUSA ( Mob Excess Deterrent Using Silent Audio ) is a directed-energy non-lethal weapon designed by WaveBand Corporation in 2003-2004 for temporary personnel incapacitation. [ 1 ] The weapon is based on the microwave auditory effect resulting in a strong sound sensation in the human head when it is subject to certain kinds of pulsed/modulated microwave radiation. The developers claimed that through the combination of pulse parameters and pulse power, it is possible to raise the auditory sensation to a “discomfort” level, deterring personnel from entering a protected perimeter or, if necessary, temporarily incapacitating particular individuals. [ 1 ] In 2005, Sierra Nevada Corporation acquired WaveBand Corporation. [ 2 ]
According to the U.S. Navy in 2004, the system would be "portable, low power, have a controllable radius of coverage, be able to switch from crowd to individual coverage, cause a temporarily incapacitating effect, have a low probability of fatality or permanent injury, cause no damage to property, and have a low probability of affecting friendly personnel". [ 3 ] In addition to perimeter protection and crowd control , a proposed application of MEDUSA was "for use in systems to assist communication with hearing impaired persons". [ 3 ]
The project received a positive initial evaluation from the Navy. However, Sierra Nevada Corporation had discontinued the project as of 2008, "possibly because it may have [been] shown to permanently damage human brain tissue". [ 4 ] | https://en.wikipedia.org/wiki/MEDUSA_(weapon) |
MEGAN ("MEtaGenome ANalyzer") is a computer program that allows optimized analysis of large metagenomic datasets. [ 1 ] [ 2 ]
Metagenomics is the analysis of the genomic sequences from a usually uncultured environmental sample. A large term goal of most metagenomics is to inventory and measure the extent and the role of microbial biodiversity in the ecosystem due to discoveries that the diversity of microbial organisms and viral agents in the environment is far greater than previously estimated. [ 3 ] Tools that allow the investigation of very large data sets from environmental samples using shotgun sequencing techniques in particular, such as MEGAN, are designed to sample and investigate the unknown biodiversity of environmental samples where more precise techniques with smaller, better known samples, cannot be used.
Fragments of DNA from an metagenomics sample, such as ocean waters or soil, are compared against databases of known DNA sequences using BLAST or another sequence comparison tool to assemble the segments into discrete comparable sequences. MEGAN is then used to compare the resulting sequences with gene sequences from GenBank in NCBI . [ 4 ] The program was used to investigate the DNA of a woolly mammoth recovered from the Siberian permafrost [ 5 ] and Sargasso Sea data set. [ 6 ]
Metagenomics is the study of genomic content of samples from same habitat, which is designed to determine the role and the extent of species diversity. Targeted or random sequencing are widely used with comparisons against sequence databases. [ 1 ] Recent developments in sequencing technology increased the number of metagenomics samples. MEGAN is an easy to use tool for analysing such metagenomics data. First version of MEGAN was released in 2007 [ 1 ] and the most recent version is MEGAN6 . [ 7 ] First version is capable of analysing taxonomic content of a single dataset while the latest version can analyse multiple datasets including new features (query different databases, new algorithm etc.).
MEGAN analysis starts with collecting reads from any shotgun platform. Then, the reads are compared with sequence databases using BLAST or similar. Third, MEGAN assigns a taxon ID to processed read results based on NCBI taxonomy which creates a MEGAN file that contains required information for statistical and graphical analysis. Lastly, lowest common ancestor ( LCA ) algorithm can be run to inspect assignments, to analyze data and to create summaries of data based on different NCBI taxonomy levels. LCA algorithm simply finds the lowest common ancestor of different species. [ 1 ] [ 2 ] | https://en.wikipedia.org/wiki/MEGAN |
MELISA ( Memory Lymphocyte Immunostimulation Assay ) is a blood test that detects type IV hypersensitivity to metals, chemicals, environmental toxins and molds. Type IV hypersensitivity reactions, particularly to nickel, are well established and may affect 20% of the population. [ 1 ]
The MELISA test measures type-IV delayed hypersensitivity reaction. Type-IV reactions are mediated by T-lymphocytes (or memory lymphocytes) that have had prior contact with a given allergen. [ 2 ] This is in contrast to a type-I allergy, which is mediated by IgE antibodies and is often tested using an ELISA test. In genetically predisposed individuals, an ongoing exposure to allergens can induce type-IV hypersensitivity. [ citation needed ]
The MELISA assay is a cell culture and requires live memory lymphocytes. Lymphocytes are isolated from a blood sample and cultured in an incubator for five days. A portion of the blood is kept intact (unexposed to allergens) to serve as a negative control. A second portion is exposed to a universal allergen, Pokeweed , to serve as a positive control. Finally, the blood is exposed to the suspected allergen/s in several different concentrations, to ensure that the conditions in vitro are as similar as possible to those in vivo. The lymphocyte reaction to each allergen is measured by two separate technologies: one based on the uptake of a radioactive isotope , 3 H-thymidine, by dividing lymphocytes (proliferation); the other by cell staining and microscopy evaluation. The level of reactivity is measured as a Stimulation Index (SI), against the naïve lymphocytes from the unexposed sample (negative control). Viability and reactivity are determined by cell count as well as reaction to the positive control. [ 3 ]
MELISA is an optimised, standardised version of the lymphocyte transformation test (LTT) which was developed in the early 1960s to help identify allergies to drugs, metabolites and metals. The LTT for beryllium is now accepted as the gold standard for diagnosing berylliosis . [ 4 ]
MELISA differs from standard LTTs in several ways:
MELISA was further developed to help to assess the impact of hypersensitivity to metals used in dentistry. Hypersensitivity to dental metals may be associated with local oral reactions including oral lichen planus, stomatitis and ulceration. [ 6 ] [ 7 ] [ 8 ] [ 9 ]
The frequency of metal-induced lymphocyte responses was examined in 3,162 dental patients in three European laboratories using the MELISA test. [ 10 ] The patients suffered from local and systemic symptoms attributed to their dental restorations. The effect of dental metal removal was studied in 111 patients with metal hypersensitivity and symptoms resembling chronic fatigue syndrome ( CFS ). After consultation with a dentist, a subgroup of 111 patients who showed allergy to their dental metals replaced their restorations with non-metallic materials. Nickel was the most common sensitizer, followed by inorganic mercury, gold, phenylmercury, cadmium and palladium. As compared to lymphocyte responses in healthy subjects, the CFS group had significantly increased responses to several metals, especially to inorganic mercury, phenylmercury and gold. [ citation needed ]
Following dental metal removal:
Type IV hypersensitivity to metals is common, particularly to nickel, however hypersensitivity related complications associated with metal implants are less frequently reported. Potential hypersensitivity complications include skin rashes, chronic joint pain, swelling, aseptic loosening, and joint failure. [ 11 ] [ 12 ]
Many authors conclude that LTT-based blood tests like MELISA may be a better option for detecting systemic allergies from implants, while patch testing is better suited to detecting dermal hypersensitivity. They add that LTT based testing may also be a good option in cases of indeterminate hypersensitivity or in patients with joint failure of an unknown cause since it has higher sensitivity than patch testing [ 13 ] [ 14 ]
Some surgeons and researchers suggest LTT testing prior to surgery in patients with suspected/self-reported metal allergy [ 15 ] [ 16 ] [ 17 ] [ 18 ]
Titanium and its main alloy (Ti6Al4V) are generally seen as hypoallergenic options for arthroplasty and for dental implants. Although uncommon, with a prevalence estimated at between 0.6-6.3%, [ 19 ] [ 20 ] titanium hypersensitivity has been reported post-implantation with symptoms including impaired fracture healing, local eczema, pain, swelling, systemic dermatitis, implant loosening, and failure, all of which have been reported to resolve with implant removal and replacement with a non-titanium implant [ 21 ] [ 22 ] [ 23 ] [ 24 ]
In spinal surgery, microscopic titanium particles are present in the tissues surrounding the implant. [ 25 ] These particles activate macrophages that increase bone absorption and inflammatory reactions. [ 26 ] Released nanoparticles will circulate in the body fluids, eventually accumulating in remote organs. [ 27 ]
Titanium has been shown to induce clinically relevant hypersensitivity which can be detected with MELISA testing. [ 28 ] The accuracy of patch testing for titanium allergy, in particular, seems to be variable; the Mayo clinic failed to find any positive reactions to titanium in over a decade, [ 29 ] despite several published cases of titanium allergy. [ 22 ] [ 30 ]
The test is also used to determine whether metal allergy is a contributing factor in the development of chronic diseases such as CFS (Sterzl, et al., 1999) and multiple sclerosis . The authors hypothesize that if the immune system is constantly displaying an allergic reaction to a metal present in the body, this will alert the HPA axis inducing fatigue-like symptoms. A study (Stejskal, et al., 1999) of 930 patients with CFS-like symptoms showed 62% testing MELISA-positive to metal allergy. Of those who removed the offending metals, 76% improved, but there was no placebo control. Metal hypersensitivity is not widely recognized by researchers as an accepted cause of CFS or multiple sclerosis . [ citation needed ]
The MELISA test is used in occupational medicine and environmental health. It has been used to screen workers exposed to metals, chemicals or other allergens in their workplace. This is what the test was developed for originally, at Astra’s (now Astra-Zeneca) laboratories in Södertälje, Sweden. In the U.S., a similar technique (BeLT) is routinely used to screen for beryllium allergy in asymptomatic workers exposed to beryllium dust (Mroz, et al., 1991) (Newman LS, 1996).
Whilst two articles have concluded that the MELISA test may give false positive (Cederbrant, et al., 1999) (Cederbrant, et al., 1997) reactions, a subsequent study concluded the MELISA test is "reproducible, sensitive, specific, and reliable for detecting metal sensitivity in metal-sensitive patients." (Valentine-Thon & Schiawara, 2003)
The developers of the MELISA test argue that the critical articles calculated the sensitivity and specificity of in vitro lymphocyte proliferation tests using patch testing as its reference. It is well-known that patch testing can cause irritative local reactions.
It is generally agreed that LTT based tests like MELISA are better suited for diagnosing implant-related metals sensitivity than patch testing as the relationship between skin hypersensitivity and systemic hypersensitivity (Ständer, et al., 2017) is ill-defined. Performing the LTT under optimised stimulating conditions might be a useful additional tool for the diagnosis of hypersensitivity (Ständer, et al., 2017) (FDA, 2019).
To test whether patients with symptoms attributed to dental amalgam differed from healthy controls, a study compared 23 amalgam patients, 30 subjects who considered themselves healthy with amalgams and 10 subjects without amalgam using MELISA and other tests. The researchers found that a high frequency of positive results was obtained among healthy subjects with or without dental amalgam, and concluded that the test cannot be used as an objective test for mercury allergy (Cederbrant, et al., 1999).
Another study by the same critical author used 34 patients to test the sensitivity and specificity if the MELISA test, and concluded that it is not useful for diagnosis of contact allergy to the metals gold, palladium and nickel, since many false-positive results will be obtained (Cederbrant, et al., 1997).
The clinical relevance of the test has been shown by the decrease of patient-reported metal-specific responses following the removal of the allergy-causing metals (however the trial did not have a placebo control). (Stejskal, et al., 2006) (Valentine-Thon, et al., 2006) | https://en.wikipedia.org/wiki/MELISA |
The MEMO model (version 6.2) is a Eulerian non-hydrostatic prognostic mesoscale model for wind-flow simulation. It was developed by the Aristotle University of Thessaloniki in collaboration with the Universität Karlsruhe . The MEMO Model together with the photochemical dispersion model MARS are the two core models of the European zooming model (EZM). This model belongs to the family of models designed for describing atmospheric transport phenomena in the local-to-regional scale, frequently referred to as mesoscale air pollution models.
Initially, EZM was developed for modelling the transport and chemical transformation of pollutants in selected European regions in the frame of the EUROTRAC sub-project EUMAC and therefore it was formerly called the EUMAC Zooming Model (EUROTRAC, 1992). EZM has evolved to be one of the most frequently applied mesoscale air pollution model systems in Europe. It has already been successfully applied for various European airsheds including the Upper Rhine valley and the areas of Basel , Graz , Barcelona , Lisbon , Madrid , Milano , London , Cologne , Lyon , The Hague , Athens ( Moussiopoulos , 1994; Moussiopoulos, 1995) and Thessaloniki . More details are to be found elsewhere (Moussiopoulos 1989), (Flassak 1990), (Moussiopoulos et al. 1993).
The prognostic mesoscale model MEMO describes the dynamics of the atmospheric boundary layer . In the present model version, air is assumed to be unsaturated. The model solves the continuity equation , the momentum equations and several transport equations for scalars (including the thermal energy equation and, as options, transport equations for water vapour, the turbulent kinetic energy and pollutant concentrations).
The lower boundary of the model domain coincides with the ground. Because of the inhomogeneity of the terrain, it is not possible to impose boundary conditions at that boundary with respect to Cartesian coordinates . Therefore, a transformation of the vertical coordinate to a terrain-following one is performed. Hence, the originally irregularly bounded physical domain is mapped onto one consisting of unit cubes.
The discretized equations are solved numerically on a staggered grid, i.e. the scalar quantities ρ {\displaystyle \rho } , p {\displaystyle p} and θ {\displaystyle \theta } are defined at the cell centre while the velocity components u {\displaystyle u} , v {\displaystyle v} and w {\displaystyle w} are defined at the centre of the appropriate interfaces.
Temporal discretization of the prognostic equations is based on the explicit second order Adams-Bashforth scheme . There are two deviations from the Adams-Bashforth scheme: The first refers to the implicit treatment of the nonhydrostatic part of the mesoscale pressure perturbation p n h {\displaystyle p_{nh}} . To ensure non-divergence of the flow field, an elliptic equation is solved. The elliptic equation is derived from the continuity equation wherein velocity components are expressed in terms of p n h {\displaystyle p_{nh}} . Since the elliptic equation is derived from the discrete form of the continuity equation and the discrete form of the pressure gradient, conservativity is guaranteed (Flassak and Moussiopoulos, 1988). The discrete pressure equation is solved numerically with a fast elliptic solver in conjunction with a generalized conjugate gradient method. The fast elliptic solver is based on fast Fourier analysis in both horizontal directions and Gaussian elimination in the vertical direction (Moussiopoulos and Flassak, 1989).
The second deviation from the explicit treatment is related to the turbulent diffusion in vertical direction. In case of an explicit treatment of this term, the stability requirement may necessitate an unacceptable abridgement of the time increment. To avoid this, vertical turbulent diffusion is treated using the second order Crank–Nicolson method .
On principle, advective terms can be computed using any suitable advection scheme. In the present version of MEMO, a 3D second-order total-variation-diminishing (TVD) scheme is implemented which is based on the 1D scheme proposed by Harten (1986). It achieves a fair (but not any) reduction of numerical diffusion, the solution being independent of the magnitude of the scalar (preserving transportivity).
Turbulence and radiative transfer are the most important physical processes that have to be parameterized in a prognostic mesoscale model. In the MEMO model, radiative transfer is calculated with an efficient scheme based on the emissivity method for longwave radiation and an implicit multilayer method for shortwave radiation (Moussiopoulos 1987).
The diffusion terms may be represented as the divergence of the corresponding fluxes. For turbulence parameterizations, K-theory is applied. In case of MEMO turbulence can be treated either with a zero-, one- or two-equation turbulence model. For most applications a one-equation model is used, where a conservation equation for the turbulent kinetic energy is solved.
In MEMO, initialization is performed with suitable diagnostic methods: a mass-consistent initial wind field is formulated using an objective analysis model and scalar fields are initialized using appropriate interpolating techniques (Kunz, R., 1991). Data needed to apply the diagnostic methods may be derived either from observations or from larger scale simulations.
Suitable boundary conditions have to be imposed for the wind velocity components u {\displaystyle u} , v {\displaystyle v} and w {\displaystyle w} , the potential temperature θ {\displaystyle \theta } and pressure p {\displaystyle p} at all boundaries. At open boundaries, wave reflection and deformation may be minimized by the use of so-called radiation conditions ( Orlanski 1976).
According to the experience gained so far with the model MEMO, neglecting large scale environmental information might result in instabilities in case of simulations over longer time periods.
For the nonhydrostatic part of the mesoscale pressure perturbation, homogeneous Neumann boundary conditions are used at lateral boundaries. With these conditions, the wind velocity component perpendicular to the boundary remains unaffected by the pressure change.
At the upper boundary, Neumann boundary conditions are imposed for the horizontal velocity components and the potential temperature. To ensure non-reflectivity, a radiative condition is used for the hydrostatic part of the mesoscale pressure perturbation p h {\displaystyle p_{h}} at that boundary. Hence, vertically propagating internal gravity waves are allowed to leave the computational domain (Klemp and Durran 1983). For the nonhydrostatic part of the mesoscale pressure perturbation, homogeneous staggered Dirichlet conditions are imposed. Being justified by the fact that nonhydrostatic effects are negligible at large heights, this condition is necessary, if singularity of the elliptic pressure equation is to be avoided in view of the Neumann boundary conditions at all other boundaries.
The lower boundary coincides with the ground (or, more precisely, a height above ground corresponding to its aerodynamic roughness). For the non-hydrostatic part of the mesoscale pressure perturbation, inhomogeneous Neumann conditions are imposed at that boundary. All other conditions at the lower boundary follow from the assumption that the –Obukhov similarity theory is valid.
The one way interactive nesting facility is possible within MEMO. Thus, successive simulations on grids of increasing resolution are possible. During these simulations, the results of the application to a coarse grid are used as boundary conditions for the application to the finer grid (Kunz and Moussiopoulos, 1995).
The governing equations are solved numerically on a staggered grid. Scalar quantities as the temperature, pressure, density and also the cell volume are defined at the centre of a grid cell and the velocity components u {\displaystyle u} , v {\displaystyle v} and w {\displaystyle w} at the centre of the appropriate interface. Turbulent fluxes are defined at different locations: Shear fluxes are defined at the centre of the appropriate edges of a grid cell and normal stress fluxes at scalar points. With this definition, the outgoing fluxes of momentum, mass, heat and also turbulent fluxes of a grid cell are identical to incoming flux of the adjacent grid cell. So the numerical method is conservative.
For calculations with MEMO, a file must be provided which contains orography height and surface type for each grid location The following surface types are distinguished and must be stored as percentage:
Only surface types 1–6 have to be stored. Type 7 is the difference between 100% and the sum of types 1–6. If the percentage of a surface type is 100%, then write the number 10 and for all other surface types the number 99.
The orography height is the mean height for each grid location above sea level in meter.
The prognostic model MEMO is a set of partial differential equations in three spatial directions and in time. To solve these equations, information about the initial state in the whole domain and about the development of all relevant quantities at the lateral boundaries is required.
To generate an initial state for the prognostic model, a diagnostic model (Kunz, R., 1991) is applied using measured temperature and wind data. Both data can be provided as:
Information about quantities at the lateral boundaries can be taken into account as surface measurements and upper air soundings. Therefore, a key word and the time when boundary data is given must occur in front of a set of boundary information.
In MEMO, a one-way interactive nesting scheme is implemented. With this nesting scheme a coarse grid and a fine grid simulation can be nested. During the coarse grid simulation, data is interpolated and written to a file. A consecutive fine grid simulation uses this data as lateral boundary values. | https://en.wikipedia.org/wiki/MEMO_model_(wind-flow_simulation) |
MEMS ( micro-electromechanical systems ) is the technology of microscopic devices incorporating both electronic and moving parts. MEMS are made up of components between 1 and 100 micrometres in size (i.e., 0.001 to 0.1 mm), and MEMS devices generally range in size from 20 micrometres to a millimetre (i.e., 0.02 to 1.0 mm), although components arranged in arrays (e.g., digital micromirror devices ) can be more than 1000 mm 2 . [ 1 ] They usually consist of a central unit that processes data (an integrated circuit chip such as microprocessor ) and several components that interact with the surroundings (such as microsensors ). [ 2 ]
Because of the large surface area to volume ratio of MEMS, forces produced by ambient electromagnetism (e.g., electrostatic charges and magnetic moments ), and fluid dynamics (e.g., surface tension and viscosity ) are more important design considerations than with larger scale mechanical devices. MEMS technology is distinguished from molecular nanotechnology or molecular electronics in that the latter two must also consider surface chemistry .
The potential of very small machines was appreciated before the technology existed that could make them (see, for example, Richard Feynman 's famous 1959 lecture There's Plenty of Room at the Bottom ). MEMS became practical once they could be fabricated using modified semiconductor device fabrication technologies, normally used to make electronics . [ 3 ] These include molding and plating, wet etching ( KOH , TMAH ) and dry etching ( RIE and DRIE), electrical discharge machining (EDM), and other technologies capable of manufacturing small devices.
They merge at the nanoscale into nanoelectromechanical systems (NEMS) and nanotechnology .
An early example of a MEMS device is the resonant-gate transistor, an adaptation of the MOSFET , developed by Robert A. Wickstrom for Harvey C. Nathanson in 1965. [ 4 ] Another early example is the resonistor, an electromechanical monolithic resonator patented by Raymond J. Wilfinger between 1966 and 1971. [ 5 ] [ 6 ] During the 1970s to early 1980s, a number of MOSFET microsensors were developed for measuring physical, chemical, biological and environmental parameters. [ 7 ]
The term "MEMS" was introduced in 1986. S.C. Jacobsen (PI) and J.E. Wood (Co-PI) introduced the term "MEMS" by way of a proposal to DARPA (15 July 1986), titled "Micro Electro-Mechanical Systems (MEMS)", granted to the University of Utah. The term "MEMS" was presented by way of an invited talk by S.C. Jacobsen, titled "Micro Electro-Mechanical Systems (MEMS)", at the IEEE Micro Robots and Teleoperators Workshop, Hyannis, MA Nov. 9–11, 1987. The term "MEMS" was published by way of a submitted paper by J.E. Wood, S.C. Jacobsen, and K.W. Grace, titled "SCOFSS: A Small Cantilevered Optical Fiber Servo System", in the IEEE Proceedings Micro Robots and Teleoperators Workshop, Hyannis, MA Nov. 9–11, 1987. [ 8 ] CMOS transistors have been manufactured on top of MEMS structures. [ 9 ]
There are two basic types of MEMS switch technology: capacitive and ohmic . A capacitive MEMS switch is developed using a moving plate or sensing element, which changes the capacitance. [ 10 ] Ohmic switches are controlled by electrostatically controlled cantilevers. [ 11 ] Ohmic MEMS switches can fail from metal fatigue of the MEMS actuator (cantilever) and contact wear, since cantilevers can deform over time. [ 12 ]
The fabrication of MEMS evolved from the process technology in semiconductor device fabrication , i.e. the basic techniques are deposition of material layers, patterning by photolithography and etching to produce the required shapes. [ 14 ]
One of the basic building blocks in MEMS processing is the ability to deposit thin films of material with a thickness anywhere from one micrometre to about 100 micrometres. The NEMS process is the same, although the measurement of film deposition ranges from a few nanometres to one micrometre. There are two types of deposition processes, as follows.
Physical vapor deposition ("PVD") consists of a process in which a material is removed from a target, and deposited on a surface. Techniques to do this include the process of sputtering , in which an ion beam liberates atoms from a target, allowing them to move through the intervening space and deposit on the desired substrate, and evaporation , in which a material is evaporated from a target using either heat (thermal evaporation) or an electron beam (e-beam evaporation) in a vacuum system.
Chemical deposition techniques include chemical vapor deposition (CVD), in which a stream of source gas reacts on the substrate to grow the material desired. This can be further divided into categories depending on the details of the technique, for example LPCVD (low-pressure chemical vapor deposition) and PECVD ( plasma-enhanced chemical vapor deposition ). Oxide films can also be grown by the technique of thermal oxidation , in which the (typically silicon) wafer is exposed to oxygen and/or steam, to grow a thin surface layer of silicon dioxide .
Patterning is the transfer of a pattern into a material.
Lithography in a MEMS context is typically the transfer of a pattern into a photosensitive material by selective exposure to a radiation source such as light. A photosensitive material is a material that experiences a change in its physical properties when exposed to a radiation source. If a photosensitive material is selectively exposed to radiation (e.g. by masking some of the radiation) the pattern of the radiation on the material is transferred to the material exposed, as the properties of the exposed and unexposed regions differs.
This exposed region can then be removed or treated providing a mask for the underlying substrate. Photolithography is typically used with metal or other thin film deposition, wet and dry etching. Sometimes, photolithography is used to create structure without any kind of post etching. One example is SU8 based lens where SU8 based square blocks are generated. Then the photoresist is melted to form a semi-sphere which acts as a lens.
Electron beam lithography (often abbreviated as e-beam lithography) is the practice of scanning a beam of electrons in a patterned fashion across a surface covered with a film (called the resist ), [ 16 ] ("exposing" the resist) and of selectively removing either exposed or non-exposed regions of the resist ("developing"). The purpose, as with photolithography , is to create very small structures in the resist that can subsequently be transferred to the substrate material, often by etching. It was developed for manufacturing integrated circuits , and is also used for creating nanotechnology architectures. The primary advantage of electron beam lithography is that it is one of the ways to beat the diffraction limit of light and make features in the nanometer range. This form of maskless lithography has found wide usage in photomask -making used in photolithography , low-volume production of semiconductor components, and research & development. The key limitation of electron beam lithography is throughput, i.e., the very long time it takes to expose an entire silicon wafer or glass substrate. A long exposure time leaves the user vulnerable to beam drift or instability which may occur during the exposure. Also, the turn-around time for reworking or re-design is lengthened unnecessarily if the pattern is not being changed the second time.
It is known that focused- ion beam lithography has the capability of writing extremely fine lines (less than 50 nm line and space has been achieved) without proximity effect. [ 17 ] However, because the writing field in ion-beam lithography is quite small, large area patterns must be created by stitching together the small fields.
Ion track technology is a deep cutting tool with a resolution limit around 8 nm applicable to radiation resistant minerals, glasses and polymers. It is capable of generating holes in thin films without any development process. Structural depth can be defined either by ion range or by material thickness. Aspect ratios up to several 10 4 can be reached. The technique can shape and texture materials at a defined inclination angle. Random pattern, single-ion track structures and an aimed pattern consisting of individual single tracks can be generated.
X-ray lithography is a process used in the electronic industry to selectively remove parts of a thin film. It uses X-rays to transfer a geometric pattern from a mask to a light-sensitive chemical photoresist, or simply "resist", on the substrate. A series of chemical treatments then engraves the produced pattern into the material underneath the photoresist.
Diamond patterning is a method of forming diamond MEMS. It is achieved by the lithographic application of diamond films to a substrate such as silicon. The patterns can be formed by selective deposition through a silicon dioxide mask, or by deposition followed by micromachining or focused ion beam milling . [ 18 ]
There are two basic categories of etching processes: wet etching and dry etching . In the former, the material is dissolved when immersed in a chemical solution. In the latter, the material is sputtered or dissolved using reactive ions or a vapor phase etchant. [ 19 ] [ 20 ]
Wet chemical etching consists of the selective removal of material by dipping a substrate into a solution that dissolves it. The chemical nature of this etching process provides good selectivity, which means the etching rate of the target material is considerably higher than the mask material if selected carefully. Wet etching can be performed using either isotropic wet etchants or anisotropic wet etchants. Isotropic wet etchant etch in all directions of the crystalline silicon at approximately equal rates. Anisotropic wet etchants preferably etch along certain crystal planes at faster rates than other planes, thereby allowing more complicated 3-D microstructures to be implemented. Wet anisotropic etchants are often used in conjunction with boron etch stops wherein the surface of the silicon is heavily doped with boron resulting in a silicon material layer that is resistant to the wet etchants. This has been used in MEWS pressure sensor manufacturing for example.
Etching progresses at the same speed in all directions. Long and narrow holes in a mask will produce v-shaped grooves in the silicon. The surface of these grooves can be atomically smooth if the etch is carried out correctly, with dimensions and angles being extremely accurate.
Some single crystal materials, such as silicon, will have different etching rates depending on the crystallographic orientation of the substrate. This is known as anisotropic etching and one of the most common examples is the etching of silicon in KOH (potassium hydroxide), where Si <111> planes etch approximately 100 times slower than other planes ( crystallographic orientations ). Therefore, etching a rectangular hole in a (100)-Si wafer results in a pyramid shaped etch pit with 54.7° walls, instead of a hole with curved sidewalls as with isotropic etching.
Hydrofluoric acid is commonly used as an aqueous etchant for silicon dioxide ( SiO 2 , also known as BOX for SOI), usually in 49% concentrated form, 5:1, 10:1 or 20:1 BOE ( buffered oxide etchant ) or BHF (Buffered HF). They were first used in medieval times for glass etching. It was used in IC fabrication for patterning the gate oxide until the process step was replaced by RIE. Hydrofluoric acid is considered one of the more dangerous acids in the cleanroom .
Electrochemical etching (ECE) for dopant-selective removal of silicon is a common method to automate and to selectively control etching. An active p–n diode junction is required, and either type of dopant can be the etch-resistant ("etch-stop") material. Boron is the most common etch-stop dopant. In combination with wet anisotropic etching as described above, ECE has been used successfully for controlling silicon diaphragm thickness in commercial piezoresistive silicon pressure sensors. Selectively doped regions can be created either by implantation, diffusion, or epitaxial deposition of silicon.
Xenon difluoride ( XeF 2 ) is a dry vapor phase isotropic etch for silicon originally applied for MEMS in 1995 at University of California, Los Angeles. [ 21 ] [ 22 ] Primarily used for releasing metal and dielectric structures by undercutting silicon, XeF 2 has the advantage of a stiction -free release unlike wet etchants. Its etch selectivity to silicon is very high, allowing it to work with photoresist, SiO 2 , silicon nitride, and various metals for masking. Its reaction to silicon is "plasmaless", is purely chemical and spontaneous and is often operated in pulsed mode. Models of the etching action are available, [ 23 ] and university laboratories and various commercial tools offer solutions using this approach.
Modern VLSI processes avoid wet etching, and use plasma etching instead. Plasma etchers can operate in several modes by adjusting the parameters of the plasma. Ordinary plasma etching operates between 0.1 and 5 Torr. (This unit of pressure, commonly used in vacuum engineering, equals approximately 133.3 pascals.) The plasma produces energetic free radicals, neutrally charged, that react at the surface of the wafer. Since neutral particles attack the wafer from all angles, this process is isotropic. Plasma etching can be isotropic, i.e., exhibiting a lateral undercut rate on a patterned surface approximately the same as its downward etch rate, or can be anisotropic, i.e., exhibiting a smaller lateral undercut rate than its downward etch rate. Such anisotropy is maximized in deep reactive ion etching. The use of the term anisotropy for plasma etching should not be conflated with the use of the same term when referring to orientation-dependent etching. The source gas for the plasma usually contains small molecules rich in chlorine or fluorine. For instance, carbon tetrachloride ( CCl 4 ) etches silicon and aluminium, and trifluoromethane etches silicon dioxide and silicon nitride. A plasma containing oxygen is used to oxidize ("ash") photoresist and facilitate its removal.
Ion milling, or sputter etching , uses lower pressures, often as low as 10 −4 Torr (10 mPa). It bombards the wafer with energetic ions of noble gases, often Ar+, which knock atoms from the substrate by transferring momentum. Because the etching is performed by ions, which approach the wafer approximately from one direction, this process is highly anisotropic. On the other hand, it tends to display poor selectivity. Reactive-ion etching (RIE) operates under conditions intermediate between sputter and plasma etching (between 10 −3 and 10 −1 Torr). Deep reactive-ion etching (DRIE) modifies the RIE technique to produce deep, narrow features. [ citation needed ]
In reactive-ion etching (RIE), the substrate is placed inside a reactor, and several gases are introduced. A plasma is struck in the gas mixture using an RF power source, which breaks the gas molecules into ions. The ions accelerate towards, and react with, the surface of the material being etched, forming another gaseous material. This is known as the chemical part of reactive ion etching. There is also a physical part, which is similar to the sputtering deposition process. If the ions have high enough energy, they can knock atoms out of the material to be etched without a chemical reaction. It is a very complex task to develop dry etch processes that balance chemical and physical etching, since there are many parameters to adjust. By changing the balance it is possible to influence the anisotropy of the etching, since the chemical part is isotropic and the physical part highly anisotropic the combination can form sidewalls that have shapes from rounded to vertical.
Deep reactive ion etching (DRIE) is a special subclass of RIE that is growing in popularity. In this process, etch depths of hundreds of micrometers are achieved with almost vertical sidewalls. The primary technology is based on the so-called "Bosch process", [ 24 ] named after the German company Robert Bosch, which filed the original patent, where two different gas compositions alternate in the reactor. Currently, there are two variations of the DRIE. The first variation consists of three distinct steps (the original Bosch process) while the second variation only consists of two steps.
In the first variation, the etch cycle is as follows:
In the 2nd variation, steps (i) and (iii) are combined.
Both variations operate similarly. The C 4 F 8 creates a polymer on the surface of the substrate, and the second gas composition ( SF 6 and O 2 ) etches the substrate. The polymer is immediately sputtered away by the physical part of the etching, but only on the horizontal surfaces and not the sidewalls. Since the polymer only dissolves very slowly in the chemical part of the etching, it builds up on the sidewalls and protects them from etching. As a result, etching aspect ratios of 50 to 1 can be achieved. The process can easily be used to etch completely through a silicon substrate, and etch rates are 3–6 times higher than wet etching.
After preparing a large number of MEMS devices on a silicon wafer , individual dies have to be separated, which is called die preparation in semiconductor technology. For some applications, the separation is preceded by wafer backgrinding in order to reduce the wafer thickness. Wafer dicing may then be performed either by sawing using a cooling liquid or a dry laser process called stealth dicing .
Bulk micromachining is the oldest paradigm of silicon-based MEMS. The whole thickness of a silicon wafer is used for building the micro-mechanical structures. [ 20 ] Silicon is machined using various etching processes . Bulk micromachining has been essential in enabling high performance pressure sensors and accelerometers that changed the sensor industry in the 1980s and 1990s.
Surface micromachining uses layers deposited on the surface of a substrate as the structural materials, rather than using the substrate itself. [ 25 ] Surface micromachining was created in the late 1980s to render micromachining of silicon more compatible with planar integrated circuit technology, with the goal of combining MEMS and integrated circuits on the same silicon wafer. The original surface micromachining concept was based on thin polycrystalline silicon layers patterned as movable mechanical structures and released by sacrificial etching of the underlying oxide layer. Interdigital comb electrodes were used to produce in-plane forces and to detect in-plane movement capacitively. This MEMS paradigm has enabled the manufacturing of low cost accelerometers for e.g. automotive air-bag systems and other applications where low performance and/or high g-ranges are sufficient. Analog Devices has pioneered the industrialization of surface micromachining and has realized the co-integration of MEMS and integrated circuits.
Wafer bonding involves joining two or more substrates (usually having the same diameter) to one another to form a composite structure. There are several types of wafer bonding processes that are used in microsystems fabrication including: direct or fusion wafer bonding, wherein two or more wafers are bonded together that are usually made of silicon or some other semiconductor material; anodic bonding wherein a boron-doped glass wafer is bonded to a semiconductor wafer, usually silicon; thermocompression bonding, wherein an intermediary thin-film material layer is used to facilitate wafer bonding; and eutectic bonding, wherein a thin-film layer of gold is used to bond two silicon wafers. Each of these methods have specific uses depending on the circumstances. Most wafer bonding processes rely on three basic criteria for successfully bonding: the wafers to be bonded are sufficiently flat; the wafer surfaces are sufficiently smooth; and the wafer surfaces are sufficiently clean. The most stringent criteria for wafer bonding is usually the direct fusion wafer bonding since even one or more small particulates can render the bonding unsuccessful. In comparison, wafer bonding methods that use intermediary layers are often far more forgiving.
Both bulk and surface silicon micromachining are used in the industrial production of sensors, ink-jet nozzles, and other devices. But in many cases the distinction between these two has diminished. A new etching technology, deep reactive-ion etching , has made it possible to combine good performance typical of bulk micromachining with comb structures and in-plane operation typical of surface micromachining . While it is common in surface micromachining to have structural layer thickness in the range of 2 μm, in HAR silicon micromachining the thickness can be from 10 to 100 μm. The materials commonly used in HAR silicon micromachining are thick polycrystalline silicon, known as epi-poly, and bonded silicon-on-insulator (SOI) wafers although processes for bulk silicon wafer also have been created (SCREAM). Bonding a second wafer by glass frit bonding, anodic bonding or alloy bonding is used to protect the MEMS structures. Integrated circuits are typically not combined with HAR silicon micromachining.
Some common commercial applications of MEMS include:
The global market for micro-electromechanical systems, which includes products such as automobile airbag systems, display systems and inkjet cartridges totaled $40 billion in 2006 according to Global MEMS/Microsystems Markets and Opportunities, a research report from SEMI and Yole Development and is forecasted to reach $72 billion by 2011. [ 39 ]
Companies with strong MEMS programs come in many sizes. Larger firms specialize in manufacturing high volume inexpensive components or packaged solutions for end markets such as automobiles, biomedical, and electronics. Smaller firms provide value in innovative solutions and absorb the expense of custom fabrication with high sales margins. Both large and small companies typically invest in R&D to explore new MEMS technology.
The market for materials and equipment used to manufacture MEMS devices topped $1 billion worldwide in 2006. Materials demand is driven by substrates, making up over 70 percent of the market, packaging coatings and increasing use of chemical mechanical planarization (CMP). While MEMS manufacturing continues to be dominated by used semiconductor equipment, there is a migration to 200mm lines and select new tools, including etch and bonding for certain MEMS applications. | https://en.wikipedia.org/wiki/MEMS |
A MEMS electrothermal actuator is a microelectromechanical device that typically generates motion by thermal expansion . It relies on the equilibrium between the thermal energy produced by an applied electric current and the heat dissipated into the environment or the substrate . Its working principle is based on resistive heating . [ 2 ] [ 3 ] Fabrication processes for electrothermal actuators include deep X-ray lithography , LIGA (lithography, electroplating, and molding) , and deep reactive ion etching (DRIE) . These techniques allow for the creation of devices with high aspect ratios . [ 4 ] [ 5 ] Additionally, these actuators are relatively easy to fabricate and are compatible with standard Integrated Circuits (IC) and MEMS fabrication methods. These electrothermal actuators can be utilized in different kind of MEMS devices like microgrippers, micromirrors , tunable inductors and resonators . [ 6 ] [ 7 ]
Generally, there are three types of MEMS electrothermal actuators. One is asymmetric thermal actuator, also known as hot-and-cold-arm or U-shaped actuator. Its working principle is based on the unequal thermal expansion of its components. The second type of electrothermal actuators is the symmetric thermal actuator, also known as chevron or bent beam actuator. Its operation is based on the total thermal expansion and its output motion is limited to one direction. The third type of MEMS electrothermal actuator is the bimorph actuator. Its motion relies on the varying coefficients of thermal expansion of the materials used in their fabrication. [ 8 ]
An asymmetric MEMS electrothermal actuator, often referred to as a bimorph or U-shaped thermal actuator, consists of a narrow "hot" arm and a wider "cold" arm connected in series to an electrical circuit. When current flows through the actuator, Joule heating occurs, producing more heat in the narrow arm due to its higher electrical resistance , resulting in greater thermal expansion compared to the wide arm. This differential thermal expansion creates a bending moment , causing the actuator to bend towards the cold arm. This design allows for precise actuation and is suitable for various MEMS applications, including micro and nano manipulation tools like microgrippers and micro positioners. [ 10 ] [ 11 ] These tools are essential for tasks such as micro assembly, biological cell manipulation, and material characterization , offering advantages such as low driving voltages and easy control. [ 12 ] [ 13 ] Various microgripper designs have been developed to enhance performance, including different arm widths and lengths, [ 14 ] electro-thermo-compliant actuators, [ 15 ] three-beam actuators, [ 16 ] folded and meander heaters, [ 17 ] sandwiched structures, [ 18 ] inclined arms, [ 19 ] and curved hot arms. [ 20 ] These actuators are used in applications requiring precise control of temperature and force , such as handling fragile micro-particles and single-cell manipulation. Additionally, they are employed in switching mechanisms, optical devices , and bi-directional actuators for applications like RF MEMS switches and micro-positioning platforms, providing larger displacement ranges and improved functionality. [ 21 ] [ 22 ] [ 23 ]
The symmetric or Chevron actuator, also known as the V-shape or bent-beam actuator, is a widely used in-plane electrothermal actuator. It features a V-shaped design but can also be found in other shapes. Unlike the differential expansion in hot-and-cold-arm actuators, the Chevron actuator relies on the total thermal expansion for actuation. It consists of two equal slanted beams connected at an apex and anchored to the substrate, forming a single conduction path. When current passes through the beams, resistive heating causes thermal expansion, pushing the apex forward. A comprehensive deflection model for this actuator involves solving a transcendental function numerically to determine the tip displacement, influenced by factors like beam length, pre-bending angle, and temperature increase. [ 25 ] The critical parameters include the beam length, pre-bending angle, and thickness. Smaller inclination angles yield larger displacements but risk out-of-plane buckling and fabrication issues. The stiffness and output force can be increased by stacking multiple beams. [ 26 ] Chevron actuators are versatile, being used in MEMS applications like micro-switches, microgrippers, and material characterization tools. They can produce substantial gripping force but with limited lateral displacement. [ 27 ] To amplify displacement, mechanical amplifiers are often used. Applications include pick-and-place operations for nanomaterials, [ 28 ] biological cell manipulation, [ 29 ] and RF MEMS switches, [ 30 ] where the actuator's stability and high force are advantageous. Variants like Z-shape [ 31 ] and kink [ 32 ] actuators offer alternative designs for specific needs, such as larger displacement or easier fabrication. Cascaded Chevron actuators enhance displacement further by connecting multiple stages, albeit with increased buckling risk. Applications include micro-engines and advanced microgrippers. [ 33 ] These actuators provide significant advantages over other types due to their rectilinear motion, high output force, and low driving voltage, making them suitable for a wide range of precise, small-scale tasks. [ 34 ] [ 35 ]
The bimorph design is a prominent type of electrothermal actuator consisting of two or more layers of different materials with varied coefficients of thermal expansion (CTE). [ 37 ] When subjected to thermal stimuli, the differential expansion causes the actuator to bend, producing out-of-plane displacement. This makes bimorph actuators ideal for applications where in-plane actuators are unsuitable, offering a broad range of applications. [ 38 ] The deflection mechanism relies on material properties, such as Young’s modulus and CTE mismatch, as well as the thickness ratio of the layers and the beam's geometrical parameters. A basic bimorph cantilever consists of two layers: one with a high CTE and another with a low CTE. Joule heating induces more expansion in the high-CTE layer, causing the structure to bend towards the low-CTE layer. The theoretical models for the behavior of bimorph actuators, such as tip deflection and output force, are well-established. For a simple two-layer cantilever, the curvature due to thermal expansion mismatch can be calculated using specific formulas involving temperature change, CTE, width, thickness, and Young’s modulus of each layer. The choice of materials for bimorph actuators is diverse, with metals and polymers commonly used for high-CTE layers, and dielectrics or semiconductors for low-CTE layers. Recent advancements include the use of carbon materials like graphene , which has a negative CTE, and graphene/ polymer composites. [ 39 ]
Bimorph actuators are typically designed for out-of-plane actuation due to the planar deposition of layers, innovative designs such as the "vertical bimorph" and lateral actuators have been developed to achieve in-plane actuation using techniques like angled electron-beam evaporation and post- CMOS micromachining . [ 40 ] Bimorph actuators find applications in various fields. In micromanipulation, conventional bimorph actuators are less feasible for in-plane microgrippers, [ 41 ] but novel designs like a four-finger microgripper provide stable and reliable gripping by curling upwards when open. In micromirrors, [ 42 ] bimorph actuators enable large displacement with low power consumption , [ 43 ] ideal for tilting and piston motion in applications like projection displays , optical switches , barcode readers , biomedical imaging , tunable lasers , spectroscopy , and adaptive optics . [ 44 ] They are also used in atomic force microscopy (AFM) [ 45 ] and scanning probe nanolithography (SPN), [ 46 ] offering nanometer-scale resolution imaging and efficient patterning. Additionally, bimorph actuators are utilized in tunable RF devices due to their precise control and actuation capabilities. However, challenges such as shear stress at layer interfaces must be managed to ensure the longevity of bimorph devices. [ 47 ] [ 48 ]
Electrothermal actuators offer several advantages over other types of actuators, making them valuable components for MEMS. They operate with relatively low driving voltages yet can generate large forces and displacements, either parallel or perpendicular to the substrate. [ 49 ] Unlike actuators that rely on electrostatic or magnetic fields , electrothermal actuators are suitable for manipulating biological samples [ 50 ] and electronic chips . [ 51 ] These actuators are also easy to control, as they do not exhibit significant hysteresis like piezoresistive and shape memory alloy (SMA) actuators. Electrothermal actuators are scalable in size and typically have a more compact structure compared to electrostatic actuators, which use large arrays of comb drives , or electromagnetic and SMA actuators, which are challenging to implement on a small scale. They are versatile in their operating environments, functioning well in air, vacuum , dusty conditions, liquid media , and under the electron beam in scanning electron microscopy (SEM). However, electrothermal actuators generally have low switching speeds due to the large time constants of thermal processes. Despite this, high-frequency thermal actuation has been demonstrated. [ 52 ] The method of electrothermal excitation is also attractive for actuation in resonance mode, particularly for microcantilever -based sensing and probing applications. MEMS resonators using this method have shown high- quality factors and wide frequency tuning ranges. [ 53 ] | https://en.wikipedia.org/wiki/MEMS_electrothermal_actuator |
MEMS for in situ mechanical characterization refers to microelectromechanical systems (MEMS) used to measure the mechanical properties (such as the Young’s modulus and fracture strength ) of nanoscale specimens such as nanowires , nanorods , whiskers, nanotubes and thin films . They distinguish themselves from other methods of nanomechanical testing because the sensing and actuation mechanisms are embedded and/or co-fabricated in the microsystem , providing—in the majority of cases—greater sensitivity and precision.
This level of integration and miniaturization allows carrying out the mechanical characterization in situ , i.e., testing while observing the evolution of the sample in high magnification instruments such as optical microscopes , scanning electron microscopes (SEM), transmission electron microscopes (TEM) and X-ray setups. Furthermore, analytical capabilities of these instruments such as spectroscopy and diffraction can be used to further characterize the sample, providing a complete picture of the evolution of the specimen as it is loaded and fails. Owing to the development of mature MEMS microfabrication technologies, the use of these microsystems for research purposes has been increasing in recent years.
Most of the current developments aim to implement in situ mechanical testing coupled with other type of measurements, such as electrical or thermal, and to extend the range of samples tested to the biological domain, testing specimens such as cells and collagen fibrils.
Typical macroscale mechanical characterization is mostly performed under uniaxial tensile conditions. Despite the existence of other methods of mechanical characterization such as three-point bending, hardness testing, etc., uniaxial tensile testing allows for the measurement of the most fundamental mechanical measurement of the specimen, namely its stress-strain curve. From this curve, important properties like the Young’s modulus, Yield strength, Fracture Strength can be computed. Other properties such as toughness and ductility can be computed as well.
At the nanoscale, owing to the reduced size of the specimen and the forces and displacements to be measured, uniaxial testing or any mechanical testing for that matter, are challenging. As a result, most tests are carried in configurations other than uniaxial-tensile, using available nanoscale science tools like the atomic force microscope (AFM) to perform a three-point bending test, SEM and TEM to perform bending resonance tests and nanoindenters to perform compression tests. In recent years, it has been found that results are not completely unambiguous. This was exemplified by the fact that different researchers obtained different values of the same property for the same material. [ 1 ] This spurred the development of MEMS with the capability of carrying out tensile tests on individual nanoscale elements.
The interest in nanomechanical testing was initially spurred by a need to characterize the materials that were used in the fabrication of MEMS. William N. Sharpe at Johns Hopkins University conducted pioneering work in the testing of microscale specimen of polycrystalline silicon. [ 2 ] Some of the initial developments consisted mostly of miniaturized versions of universal testing machines , which were fabricated by standard machining techniques. However, important contributions and insights were provided into specimen gripping mechanisms and the mechanics of materials at the micron scale. Likewise, Horacio D. Espinosa at Northwestern University developed a membrane deflection experiment, [ 3 ] which was employed at the MEMS level [ 4 ] as well as in thin film specimens. The latest revealed the first experimental evidence of size scale plasticity in thin metallic freestanding films. [ 5 ] Later, size effect studies were performed on single crystal pillars using nanoindentation of microfabricated samples by means of focused ion beam. [ 1 ]
Later on, Taher Saif at University of Illinois- Urbana Champaign can be credited on developing microfabricated stages. [ 6 ] Several results in situ SEM and TEM were demonstrated for thin films by his group [ 7 ] including a stage for simultaneous electrical and mechanical testing, although this set-up used external actuation and sensing. [ 8 ] A major breakthrough in MEMS-electronic integration was made by Horacio D. Espinosa and his group at Northwestern University. They designed and developed a true MEM system that incorporated capacitive sensing for electronic measurement of load and thermal actuation for specimen straining in one single chip. [ 9 ] The system could be operated inside a transmission electron microscope. The MEMS based platform was applied to the study of poly-Silicon samples, [ 10 ] multi-walled CNTs [ 11 ] and more recently metallic [ 10 ] and semiconducting nanowires. [ 12 ] [ 13 ] In particular, the theoretical strength of carbon nanotubes was experimentally measured for the first time using this device. [ 11 ]
Following these pioneering works, other research groups have followed on developing their own MEMS for mechanical testing. Important examples include the deBoer group at Sandia National Labs who specializes in the testing of polysilicon samples. [ 14 ] At the Ecole Polythecnique Federale de Lausanne (EPFL), an electrostatically actuated device, similar to Espinosa’s original design, was developed in Silicon-On-Insulator technology by the Michler’s group. [ 15 ] These devices have the advantage of a higher aspect ratio and therefore a higher sensitivity in the sensing structures. Some other researchers have developed other devices following the models outlines by Espinosa, Saif and Haque; for example Victor Bright at University of Colorado – Boulder. [ 16 ] The technology has reached a level of maturity such that standard devices are now offered by the Center for Integrated Nanotechnologies (CINT) at Sandia National Labs to researchers interested in mechanical testing of nanoscale samples. [ 17 ]
Several nanomechanical characterization methods have yielded many results for properties of matter at the nanoscale. What has been found consistently is that mechanical properties of materials change as a function of size. In metals, elastic modulus, yield strength and fracture strength all increase, while in semiconducting brittle materials, either increments or reductions are observed depending on the material. [ 1 ]
The discovery that mechanical properties are intrinsically size-dependent has spurred theoretical and experimental interest in the size-dependence of other material properties, such as thermal and electrical; and also coupled effects like electromechanical or thermomechanical behavior. Particular interest has been focused on characterizing electromechanical properties such as piezoresistivity and piezoelectricity. Most of the current focus in the developing of MEMS for in situ testing lies in this area with examples from Haque, Espinosa and Zhang. [ 18 ]
On the other hand, given that MEMS has demonstrated to be a feasible technology for characterizing mechanical properties at the nanoscale, application of the technology to other types of problems has been sought. In particular, biological systems spur an interest because understanding mechanics in biological systems finds application in disease diagnosis and treatment, and in the engineering of new materials. The size scales in biological testing are in the micron range, with structures that are typically very compliant. This requires the development of devices with high displacement capabilities and very high force resolution. Recent examples are the tensile characterization of collagen fibrils [ 19 ] [ 20 ] and DNA bundles. [ 21 ] | https://en.wikipedia.org/wiki/MEMS_for_in_situ_mechanical_characterization |
MEMS sensor generations represent the progress made in micro sensor technology and can be categorized as follows: | https://en.wikipedia.org/wiki/MEMS_sensor_generations |
MEMS testing is one of the processes in the development of a MEMS device. It is a collection of testing methods such as electrical, mechanical and environment tests. [ 1 ]
When looking at the electronic market it becomes obvious, as there is a need for production output, high system performance, product reliability and long lifecycle, for MEMS to create trust in the eyes of customers. If those conditions would not be met customers would not invest into technologies using MEMS, which justifies the need for testing as a part of a high quality standard. [ 2 ]
Testing is also fairly important from an economical point of view. As it is said that the failure cost increase by a factor of ten for each stage before it gets discovered.
Most MEMS producers check their products at two distinct stages(at the wafer level, and the packaging), as well as random sampling on every stage.
If one includes this into cost calculation for a MEMS device the costs for testing amounts to 20-50% of the overall unit costs.
Even when looking at producers that manufacture MEMS, and CMOS devices it is not really possible to reduce the costs by including the economy of scopes effect for testing, as both types of device. This is because even though about 80% of the processing is shared, only 20% of the tests are.
To decrease these costs for U.S. manufactures the National Institute of Standards and Technologies( NIST ) conducted several workshops and questionnaires to tackle this issue and increase competitiveness of US companies. [ 3 ]
Due to the wide variety of MEMS it is hard to be very specific as of what is tested the table below shows what is tested in general:
To test MEMS researchers came up with a wide variety of techniques that can display certain values. However, there is no single technology that can cover all; each has strengths as well as weaknesses.
Below is a list with all major and some minor technologies employed in MEMS testing:
Following technologies were experimented with but are no longer considered for MEMS testing:
All these technologies have strengths and weaknesses, so in order to maximize the effectiveness of test equipment researchers combined technologies. For instance Christian Rembe, former researcher at UC Berkeley, combined laser doppler vibrometry, white light interferometry and strobe video microscopy into one tool to eliminate each technologies weakness. [ 2 ] | https://en.wikipedia.org/wiki/MEMS_testing |
Mercon represents a series of technical standards for automatic transmission fluid , developed and trademarked by Ford Motor Company . This designation serves as a mark of quality that Ford has established for fluids used in automatic transmissions. The Mercon name, which has evolved into a brand, is licensed by Ford to various manufacturers. These companies are authorized to produce the fluid according to Ford's specifications and market it under their own brand names.
The specifications outlined under the Mercon label cover various aspects such as viscosity, friction characteristics, and thermal stability, which are essential for the transmission fluid to perform under a wide range of operating conditions. This careful regulation ensures that all licensed Mercon fluids provide consistent quality and performance, giving consumers confidence in their use of aftermarket products.
The original Mercon (M2C185-A) Transmission Fluid was introduced in January 1987. Over the years, the original Mercon was supplanted by Mercon "V", Mercon "SP", Mercon LV, and Mercon ULV, which is the latest automatic transmission fluid. Ford has upgraded the Mercon specifications over the years; the newer fluids are not always backward compatible with previous fluids. Newer 6 and 10-speed transmissions as well as Plug-In Hybrid (PHEV), and Electric Vehicle (EV) transmission technologies require specialized fluids to operate properly. There remains a market for older fluids that claim to meet the earlier fluid specifications. See the details below for the backward compatibility of each fluid.
Originally the name MERCON was associated exclusively with automatic transmission fluids, later Ford released MERCON Gear oils and other lubricants under the MERCON brand. Not all Mercon fluids are licensed for reselling under another brand name. All licensed Mercon fluids must have a license number on the container. If no license number is found, the fluid may not be Ford-approved and the automatic transmission fluid cannot be guaranteed to meet Ford specifications. Ford, like many automobile manufacturers, uses transmissions sourced from other suppliers or transmission manufacturers around the world; these transmissions are not manufactured by Ford. Many of these automatic transmissions use unique fluids that might not be shown on this page.
In 1942, The Mercury 8 and Lincoln offered cars with an optional "Liquamatic Drive" using a fluid coupling , conventional clutch, and semi-automatic three-speed transmission. The transmission had an overrunning clutch on the transmission countershaft. The flywheel's fluid coupling used S.A.E 10 motor oil for lubrication. The transmission gearbox used traditional gear oil. This transmission was only produced for a few months before the U.S.A. entered World War II , production of this transmission was not resumed after the war. [ 1 ]
In April 1949, Lincoln began offering the General Motors Hydra-Matic 4-speed automatic transmission in their 1950 model year vehicles. This offering continued through the 1954 model year. Lincoln service information calls for "Lincoln Automatic Transmission Fluid". This fluid met the GM Hydra-Matic Drive fluid specifications.
This Fluid was First Used in the Following Transmissions :
Every automatic transmission produced by any vehicle manufacturer (Oldsmobile, Cadillac, Buick, Chevrolet, Pontiac, GMC, Ford, Mercury, Lincoln, Chrysler, Dodge, Desoto, Packard, and Studebaker) used GM Type "A" transmission fluids in their transmissions from 1949 to 1958.
In 1950, 11 years after GM released the Hydra-Matic 4-speed automatic transmission and its special Hydra-Matic Automatic Transmission Fluid , Ford released their first fully automatic transmission; the 1951 Fordomatic 3-speed transmission. [ 2 ] This new fully automatic transmission used the GM Type "A" automatic transmission fluid specification. Ford and hundreds of other resellers, became a licensed reseller of the GM Type "A" fluid with an Armor Qualification number. The Type "A" fluid was marketed under the Ford brand name.
This Fluid was First Used in the Following Transmissions :
In 1959, Ford released their own Type-A automatic transmission fluid specification (M2C33-A) and stopped using GM fluid specifications for their in-house transmissions. The Ford M2C33-A fluid had GM Type "A" Suffix "A" characteristics. Transmission fluid service life was fairly short, and frequent transmission oil changes were required.
In 1959, Ford released an updated automatic transmission fluid specification Type-B (M2C33-B). The Ford M2C33-B fluid had GM Type "A" Suffix "A" characteristics. As with the previous specification, transmission fluid service life was fairly short, and frequent transmission oil changes were required.
In 1960, Ford introduced the Type-D (M2C33-D) specification for service fluid use in 1960 model-year vehicles. This fluid specification change provided better oxidation control, anti-wear performance, and higher static capacity capabilities were also included. Oxidation control of the fluid was measured by a new Merc-O-Matic oxidation test.
This fluid was first used in the following transmissions:
In 1967, Ford introduced a new fluid specification, the Type-F fluid (M2C33-F). [ 3 ] This fluid provided a high static coefficient of friction which resulted in harsh shifting.
The Type-F fluid specification was intended to produce a “lifetime” fluid that would never need to be changed. This is the first of many Ford “lifetime” fluids. The 1974 Ford Car Shop Manual reads "The automatic transmission is filled at the factory with "lifetime" fluid. If it is necessary to add or replace fluid, use only fluids that meet Ford Specification M2C33F.
In 1972, Ford of Europe introduced a new fluid specification, the Type-G fluid (M2C33-G). [ 4 ] This fluid was used through 1981.
This fluid was first used in the following transmissions:
In September 1974, Ford introduced a new fluid specification, the Type-CJ fluid (M2C138-CJ). This fluid provided smoother shifting and less gear noise by with higher dynamic friction characteristics. The Ford Type-CJ fluid specification also met the GM Dexron -II(D) and earlier fluid specifications. Ford was a licensed GM Dexron-II(D) vendor.
The Ford Type-CJ fluid was compatible with GM Dexron II(D) specifications. This compatibility may suggest to some that all Ford, Mercon, and Dexron fluids are compatible; this is not correct. Always use the factory-recommended fluid for your transmission. (See the Aftermarket Automatic Transmission Fluids section below)
This fluid was first used in the following transmissions:
As a result of the 1973 OPEC Oil Embargo and fuel shortages, the U.S. government created the Corporate Average Fuel Economy (CAFE) regulations in 1975. The regulations were to be fully implemented by the 1978 model year. The automotive industry responded by changing to three typically unused transmission technologies:
The introduction of the TCC led to customer complaints of a shudder while driving. All vehicle manufacturers made changes to their ATF specifications and the controls of their TCC to try and alleviate the problem. GM released the Dexron-II (D) fluid specification in 1978 and Chrysler released the ATF+2 fluid specification in 1980, and Ford released the Type-H fluid (M2C166-H) specification in June 1981.
The Type-H fluid specification provided improved friction characteristics in lock-up torque converters (reducing shudder during application and release). With this new specification, Ford introduced the aluminum beaker oxidation test (ABOT) to replace the older Merc-O-Matic oxidation test.
The Ford Type-H fluid was compatible with GM Dexron II(D) specifications. This compatibility may suggest to some that all Ford, Mercon, and Dexron fluids are compatible; this is not correct. Always use the factory-recommended fluid for your transmission. (See the Aftermarket Automatic Transmission Fluids section below)
This fluid was first used in the following transmissions:
In January 1987, Ford released the original Mercon fluid specification (M2C185-A). Mercon became a trademarked fluid with the qualification and licensing of fluids to ensure quality in the marketplace. This original Mercon Specification was backward compatible with the 1981 Ford Type-H fluid and the 1958 GM Type "A" Suffix "A" fluid.
NOTICE: This version of Mercon was compatible with GM's Dexron-II(D) and later formulations were compatible with Dexron-III(H); however, Future versions of Mercon (Mercon V, Mercon SP, Mercon LV, Mercon ULV) are not compatible with GM's Dexron-III(H) or any newer version of Dexron (Dexron-VI, Dexron HP, Dexron ULV).
This fluid was first used in the following transmissions:
In 1996, Ford released the Mercon "V" fluid specification (M2C202-B). [ 5 ] Ford Technical Service Bulletin (TSB) 06-14-04 indicates that Mercon "V" is to replace the original Mercon fluid. [ 6 ]
This fluid was first used in the following transmissions:
The Mercon "V" specification was revised in 2002 (M2C919-E). This revised fluid was first used in the following transmissions:
In August 2001, Ford released the Mercon "SP" fluid specification (M2C919-D). [ 7 ]
Ford SSM 21114 (November 26, 2009) indicates that Mercon Replace "SP" is to be replaced with Mercon LV on Torqshift transmissions from the 2003 through 2008 model years. This SSM does not apply to the ZF 6HP26 transmission.
This fluid first used in the following transmissions:
In December 2005, Ford released the Mercon "LV" fluid specification (M2C938-A). [ 8 ]
This fluid was first used in the following transmissions:
This specification was revised in 2007 for use in the following transmissions:
This specification was revised again in 2010 (M2C938-A2) and was optimized for anti-Squawk performance of clutches. This revised fluid was first used in the following transmissions:
The fluid specification for Mercon-ULV (Ultra-Low Viscosity) was introduced on January 2, 2014. Mercon ULV is composed of a Group 3+ Base oil and additives needed for the proper operation of the 2017 and above Ford 10R80 and the GM 10L90 10-Speed rear wheel drive automatic transmission.
This transmission and the transmission fluid specification was co-developed by Ford and GM. The current specification that defines the fluid is FORD WSS-M2C949-A. [ 10 ] This fluid is also marketed as Dexron ULV.
NOTICE: The quart containers of Mercon ULV must be shaken to stir up the additives before pouring. This fluid is not backward compatible with any previous fluids.
This fluid was first used in the following transmissions:
The 1967 Ford Type-F fluid specification was intended to produce a “lifetime” fluid which would never need to be changed. This was the first of many Ford “lifetime” fluids. The 1974 Ford Car Shop Manual reads "The automatic transmission is filled at the factory with "lifetime" fluid. If it is necessary to add or replace fluid, use only fluids which meet Ford Specification M2C33F. Many other transmission manufacturers have followed with their own "Lifetime" automatic transmission fluids".
Lifetime automatic transmission fluids made from higher quality base oil and an additive package are more chemically stabile, less reactive, and do not experience oxidation as easily as lower quality fluids made from lower quality base oil and an additive package. Therefore, higher quality transmission fluids can last a long time in normal driving conditions (Typically 100,000 miles (160,000 km) or more).
The definition of 'Lifetime Fluid" differs from transmission manufacturer to transmission manufacturer. Always consult the vehicle maintenance guide for the proper service interval for the fluid in your transmission and your driving conditions.
2018 Ford F-150 Example: According to the Scheduled Maintenance Guide of a 2018 Ford F-150 with "Lifetime Fluid" could have three different fluid service intervals depending on how the vehicle is driven: [ 11 ]
1. Normal Driving
Under these driving conditions, the automatic transmission fluid needs to be serviced after every 150,000 miles (240,000 km).
2. Severe Driving
Under these driving conditions, the automatic transmission fluid needs to be serviced after every 30,000 miles (48,000 km).
3. Extreme Driving
Under these driving conditions, the automatic transmission fluid needs to be serviced also after every 30,000 miles. | https://en.wikipedia.org/wiki/MERCON |
MERMOZ (also, MERMOZ project and Monitoring planEtary suRfaces with Modern pOlarimetric characteriZation ) is an astrobiology project [ 1 ] [ 2 ] designed to remotely detect biosignatures of life . [ 3 ] [ 4 ] [ 5 ] [ 6 ] [ 7 ] [ 8 ] [ 9 ] [ 10 ] Detection is based on molecular homochirality , a characteristic property of the biochemicals of life . The aim of the project is to remotely identify and characterize life on the planet Earth from space, and to extend this technology to other solar system bodies and exoplanets . The project began in 2018, and is a collaboration of the University of Bern , University of Leiden and Delft University of Technology . [ 3 ] [ 4 ] [ 5 ] [ 6 ] [ 7 ] [ 8 ] [ 9 ] [ 10 ]
According to a member of the research team, “When light is reflected by biological matter, a part of the light’s electromagnetic waves will travel in either clockwise or counterclockwise spirals ... This phenomenon is called circular polarization and is caused by the biological matter’s homochirality.” These unique spirals of light indicate living materials; whereas, non-living materials do not reflect such unique spirals of light, according to the researchers. [ 8 ]
The research team conducted feasibility studies, using a newly designed detection instrument, based on circular spectropolarimetry, and named FlyPol+ (an upgrade from the original FlyPol ), by flying in a helicopter at an altitude of 2 km (1.2 mi) and velocity of 70 km/h (43 mph) for 25 minutes. The results were successful in remotely detecting living material, and quickly (within seconds) distinguishing living material from non-living material. The researchers concluded: "Circular spectropolarimetry can be a powerful technique to detect life beyond Earth, and we emphasize the potential of utilizing circular spectropolarimetry as a remote sensing tool to characterize and monitor in detail the vegetation physiology and terrain features of Earth itself." [ 4 ]
The researchers next expect to scan the Earth from the International Space Station (ISS) with their detection instruments. [ 5 ] One consequence of further successful studies is a possible pathfinder space mission, scheduled to launch in 2024. [ 7 ]
This spacecraft or satellite related article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/MERMOZ |
MEROPS is an online database for peptidases (also known as proteases, proteinases and proteolytic enzymes) and their inhibitors. [ 2 ] The classification scheme for peptidases was published by Rawlings & Barrett in 1993, [ 3 ] and that for protein inhibitors by Rawlings et al. in 2004. [ 4 ] The most recent version, MEROPS 12.5, was released in September 2023. [ 5 ]
The classification is based on similarities at the tertiary and primary structural levels. Comparisons are restricted to that part of the sequence directly involved in the reaction, which in the case of a peptidase must include the active site , and for a protein inhibitor the reactive site. The classification is hierarchical: sequences are assembled into families, and families are assembled into clans. Each peptidase, family, and clan has a unique identifier.
The families of peptidases are constructed by comparisons of amino acid sequences. A family is assembled around a type example , the sequence of a well-characterized peptidase or inhibitor. All other sequences in the family must be related to the family type example, either directly or through a transitive relationship involving one or more sequences already shown to be family members. Typically, FastA or BlastP is used to establish sequence relationships, with an expect value of 0.001 or lower taken to be statistically significant . HMMER or psi-blast searches are used for adding sequences which are distantly related to a family. Each family is identified by a letter representing the catalytic type of the peptidases it contains followed by an arbitrary unique number.
Some families are divided into subfamilies due to evidence of very ancient divergence within the family. The divergence corresponds to more than 150 accepted point mutations per 100 amino acid residues.
The similarity in three-dimensional structures supports the evidence that many of the families do share common ancestry with others. "Clan" is used to describe such a group of families. A clan is also assembled around a type example, this being the structure of a well-characterized peptidase or inhibitor. A family is included in a clan if the tertiary structure of a family member can be shown to be related to that of the clan type example. Typically, DALI is used to establish clan membership, with a z score of 6.00 standard deviation units or above considered to be statistically significant. For peptidases, other evidence to indicate that families are related when a tertiary structure is absent includes the same order of catalytic residues in the sequences.
Each family, clan, peptidase, and inhibitor has a unique identifier. Description and example of identifiers are shown in the table below. | https://en.wikipedia.org/wiki/MEROPS |
The MERSI protocol is a cache coherency and memory coherence protocol used by the PowerPC G4 . [ 1 ] The protocol consists of five states, Modified (M), Exclusive (E), Read Only or Recent (R), Shared (S) and Invalid (I). The M, E, S and I states are the same as in the MESI protocol . The R state is similar to the E state in that it is constrained to be the only clean, valid, copy of that data in the computer system. Unlike the E state, the processor is required to initially request ownership of the cache line in the R state before the processor may modify the cache line and transition to the M state. In both the MESI and MERSI protocols, the transition from the E to M is silent. [ 2 ]
For any given pair of caches, the permitted states of a given cache line are as follows:
This computing article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/MERSI_protocol |
METIS is a software package for graph partitioning that implements various multilevel algorithms . [ 1 ] [ 2 ] METIS' multilevel approach has three phases and comes with several algorithms for each phase:
The final partition computed during the third phase (the refined partition projected onto G 0 ) is a partition of the original graph.
According to Metis authors Karypis and Kumar, "Metis is the Greek word for wisdom. Metis was a titaness in Greek mythology. She was the consort of Zeus and the mother of Athena. She presided over all wisdom and knowledge". [ 3 ]
This algorithms or data structures -related article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/METIS |
METI International , known simply as METI , is a non-profit research organization founded in July 2015 by Douglas Vakoch [ 1 ] that creates and transmits interstellar messages to attempt to communicate with extraterrestrial civilizations . [ 2 ] [ 3 ] [ 4 ] [ 5 ] [ 6 ] It is based in San Francisco, California. [ 7 ] [ 5 ]
METI targets nearby stars and researches the nature of the messages to send. [ 1 ] [ 8 ] On October 16, 17, and 18, 2017, it sent a message consisting of a scientific and mathematical tutorial to the red dwarf Luyten's Star , just over 12 light years from Earth. [ 9 ] [ 10 ] [ 11 ] The message was sent from a radio transmitter at the EISCAT research facility in Tromsø , Norway. [ 12 ]
METI's aim is to build an interdisciplinary community to design interstellar messages, within the context of the evolution of intelligence and language. [ 13 ] In May 2016, it convened the meeting “The Intelligence Of SETI: Cognition And Communication In Extraterrestrial Intelligence” in Puerto Rico. [ 2 ] [ 4 ] In May 2018 in Los Angeles, it held “Language in the Cosmos” in conjunction with the International Space Development Conference . [ 13 ] [ 14 ] to examine the connection between astrobiology and linguistics . [ 8 ] On March 22, 2017, it held a workshop in Paris examining the question "What is life?" from an extraterrestrial perspective. [ 15 ]
METI also conducts an optical search of extraterrestrial intelligence (SETI). [ 16 ] [ 2 ] Its optical observatory in Panama looks for laser pulses from advanced civilizations. It has examined anomalous stars like the nearby red dwarf star Ross 128 , [ 17 ] as well as HD 164595 , 94 light years from Earth. [ 16 ] None of the searches has yielded evidence of artificial signals. [ 16 ] [ 17 ]
American scientist and science-fiction author David Brin has questioned "whether small groups of zealots should bypass all institutions, peer critique, risk appraisal or public opinion, to shout ‘yoohoo’ into a potentially hazardous cosmos" and so force a fait accompli on humanity. [ 18 ]
Numerous other authors and scientists have expressed similar concerns, generally known as the Dark forest hypothesis of ETI, including Stephen Hawking . [ 19 ] [ 20 ] Of particular interest in science fiction is Cixin Liu 's Remembrance of Earth's Past , exploring the theory and some of its implications. [ 21 ] [ 22 ]
Notable members of METI's Board of Directors and Advisory Council include: | https://en.wikipedia.org/wiki/METI_International |
The METLIN Metabolite and Chemical Entity Database [ 1 ] [ 2 ] [ 3 ] is the largest repository of experimental tandem mass spectrometry [ 4 ] and neutral loss [ 5 ] data acquired from standards. The tandem mass spectrometry data on over 930,000 molecular standards (as of December, 2023) [ 6 ] [ 7 ] [ 8 ] [ 9 ] [ 10 ] is provided to facilitate the identification of chemical entities from tandem mass spectrometry experiments. In addition to the identification of known molecules, it is also useful for identifying unknowns [ 3 ] using its similarity searching technology. [ 11 ] All tandem mass spectrometry data comes from the experimental analysis of standards at multiple collision energies and in both positive and negative ionization modes.
METLIN [ 12 ] serves as a data management system to assist in metabolite and chemical entity identification by providing public access to its repository of comprehensive MS/MS and neutral loss data. [ 7 ] [ 3 ] [ 5 ] METLIN's annotated list of molecular standards include metabolites and other chemical entities, searching METLIN can be done based on a molecule's tandem mass spectrometry data, neutral loss masses, precursor mass, chemical formula, and structure within the METLIN website. Each molecule is linked to outside resources such as the Kyoto Encyclopedia of Genes and Genomes ( KEGG ) for further reference and inquiry. The METLIN database was developed and is maintained solely by the Siuzdak laboratory at The Scripps Research Institute .
Since its initial implementation in the early 2000s, [ 2 ] the freely available METLIN website has collected comments and suggestions for improvements from users in the biotechnology, pharmaceutical and academic communities ultimately resulting in functionally useful technology for metabolomics as well as hundreds of thousands of other molecular entities. [ 7 ] The METLIN interface allows researchers to readily search the database and characterize metabolites and other compounds through features such as accurate mass, single and multiple fragment searching, neutral loss and full spectrum search capabilities. The similarity searching feature introduced in 2008 [ 11 ] was designed to expedite the identification process of unknown molecules.
Also, METLIN has been used to create a novel multiple reaction monitoring (MRM) library of precursor to fragment ion transitions. [ 13 ] The METLIN-MRM transition repository for small-molecule quantitative tandem mass spectrometry was designed to facilitate data sharing across different instruments and laboratories. [ 13 ]
The METLIN database is implemented in the cloud to enable users throughout the world. [ 7 ] [ 12 ] In addition to expanding the tandem mass spectrometry database, METLIN is designed to search tandem mass spectrometry data, precursor mass, chemical formulas, compound names among other search capabilities. METLIN has also been implemented with cognitive computing applications. [ 14 ] The tandem MS high-resolution ESI-QTOF MS/MS data on now over 930,000 distinct chemical entities, includes mass spectral collision-induced dissociation data at four different collision energies, in both positive and negative ionization modes. [ 7 ] [ 9 ] [ 15 ] | https://en.wikipedia.org/wiki/METLIN |
METRIC (Mapping EvapoTranspiration at high Resolution with Internalized Calibration) is a computer model developed by the University of Idaho , that uses Landsat satellite data to compute and map evapotranspiration (ET). [ 1 ] [ 2 ] [ 3 ] METRIC calculates ET as a residual of the surface energy balance, where ET is estimated by keeping account of total net short wave and long wave radiation at the vegetation or soil surface, the amount of heat conducted into soil, and the amount of heat convected into the air above the surface. The difference in these three terms represents the amount of energy absorbed during the conversion of liquid water to vapor, which is ET. METRIC expresses near-surface temperature gradients used in heat convection as indexed functions of radiometric surface temperature, thereby eliminating the need for absolutely accurate surface temperature and the need for air-temperature measurements.
The surface energy balance is internally calibrated using ground-based reference ET that is based on local weather or gridded weather data sets to reduce computational biases inherent to remote sensing -based energy balance. Slope and aspect functions and temperature lapsing are used for application to mountainous terrain. METRIC algorithms are designed for relatively routine application by trained engineers and other technical professionals who possess a familiarity with energy balance and basic radiation physics. The primary inputs for the model are short-wave and long-wave thermal images from a satellite e.g., Landsat and MODIS , a digital elevation model , and ground-based weather data measured within or near the area of interest. ET “maps” i.e., images via METRIC provide the means to quantify ET on a field-by-field basis in terms of both the rate and spatial distribution. The use of surface energy balance can detect reduced ET caused by water shortage .
In the decade since Idaho introduced METRIC, it has been adopted for use in Montana, California, New Mexico, Utah, Wyoming, Texas, Nebraska, [ 4 ] Colorado, Nevada, and Oregon. The mapping method has enabled these states to negotiate Native American water rights ; assess agriculture to urban water transfers ; manage aquifer depletion , monitor water right compliance; and protect endangered species . [ 5 ] | https://en.wikipedia.org/wiki/METRIC |
Meteorin-like/Meteorin-Beta (Metrnl)/IL-41 , also known as subfatin and cometin, is a small (~27kDa) secreted cytokine, protein encoded by a gene called meteorin-like ( METRNL ). [ 1 ]
Lower serum levels of Metrnl might be a risk factor for developing coronary artery disease and type 2 diabetes mellitus [ 2 ] [ 3 ] | https://en.wikipedia.org/wiki/METRNL |
A MEX file is a type of computer file that provides an interface between MATLAB or Octave and functions written in C , C++ or Fortran . It stands for "MATLAB executable".
When compiled, MEX files are dynamically loaded and allow external functions to be invoked from within MATLAB or Octave as if they were built-in functions.
To support the development of MEX files, both MATLAB and Octave offer external interface functions that facilitate the transfer of data between MEX files and the workspace. In addition to MEX files, Octave has its format using its native API , with better performance. [ 1 ]
This computing article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/MEX_file |
A hexafluoride is a chemical compound with the general formula QX n F 6 , QX n F 6 m− , or QX n F 6 m+ . Many molecules fit this formula. An important hexafluoride is hexafluorosilicic acid (H 2 SiF 6 ), which is a byproduct of the mining of phosphate rock . In the nuclear industry , uranium hexafluoride (UF 6 ) is an important intermediate in the purification of this element.
Cationic hexafluorides exist but are rarer than neutral or anionic hexafluorides. Examples are the hexafluorochlorine (ClF 6 + ), and hexafluorobromine (BrF 6 + ) cations . [ 1 ]
Many elements form anionic hexafluorides. Members of commercial interest are hexafluorophosphate (PF 6 − ) and hexafluorosilicate (SiF 6 2− ).
Many transition metals form hexafluoride anions. Often the monoanions are generated by reduction of the neutral hexafluorides. For example, PtF 6 − arises by reduction of PtF 6 by O 2 . Because of its highly basic nature and its resistance to oxidation, the fluoride ligand stabilizes some metals in otherwise rare high oxidation states, such as hexafluorocuprate(IV) , CuF 2− 6 and hexafluoronickelate(IV) , NiF 2− 6 .
Seventeen elements are known to form binary hexafluorides. [ 2 ] Nine of these elements are transition metals , three are actinides , four are chalcogens , and one is a noble gas . Most hexafluorides are molecular compounds with low melting and boiling points . Four hexafluorides (S, Se, Te, and W) are gases at room temperature (25 °C) and a pressure of 1 atm , two are liquids (Re, Mo), and the others are volatile solids. The group 6 , chalcogen , and noble gas hexafluorides are colourless, but the other hexafluorides have colours ranging from white, through yellow, orange, red, brown, and grey, to black.
The molecular geometry of binary hexafluorides is generally octahedral , although some derivatives are distorted from O h symmetry . For the main group hexafluorides, distortion is pronounced for the 14-electron noble gas derivatives. Distortions in gaseous XeF 6 are caused by its non-bonding lone pair , according to VSEPR theory . In the solid state, it adopts a complex structure involving tetramers and hexamers. According to quantum chemical calculations, ReF 6 and RuF 6 should have tetragonally distorted structures (where the two bonds along one axis are longer or shorter than the other four), but this has not been verified experimentally. [ 3 ]
Polonium hexafluoride is known, but not well-studied. It could not be made from 210 Po, but using the longer-lived isotope 208 Po and reacting it with fluorine found a volatile product that is almost certainly PoF 6 . [ 2 ] The quoted boiling point in the table below is a prediction.
The hexafluorides have a wide range of chemical reactivity. Sulfur hexafluoride is nearly inert and non-toxic due to steric hindrance (the six fluorine atoms are arranged so tightly around the sulfur atom that it is extremely difficult to attack the bonds between the fluorine and sulfur atoms). It has several applications due to its stability, dielectric properties, and high density. Selenium hexafluoride is nearly as unreactive as SF 6 , but tellurium hexafluoride is not very stable and can be hydrolyzed by water within 1 day. Also, both selenium hexafluoride and tellurium hexafluoride are toxic, while sulfur hexafluoride is non-toxic. In contrast, metal hexafluorides are corrosive, readily hydrolyzed, and may react violently with water. Some of them can be used as fluorinating agents . The metal hexafluorides have a high electron affinity , which makes them strong oxidizing agents. [ 8 ] Platinum hexafluoride in particular is notable for its ability to oxidize the dioxygen molecule, O 2 , to form dioxygenyl hexafluoroplatinate , and for being the first compound that was observed to react with xenon (see xenon hexafluoroplatinate ).
Some metal hexafluorides find applications due to their volatility. Uranium hexafluoride is used in the uranium enrichment process to produce fuel for nuclear reactors . Fluoride volatility can also be exploited for nuclear fuel reprocessing . Tungsten hexafluoride is used in the production of semiconductors through the process of chemical vapor deposition . [ 9 ]
Radon hexafluoride ( RnF 6 ), the heavier homologue of xenon hexafluoride , has been studied theoretically, [ 10 ] but its synthesis has not yet been confirmed. Higher fluorides of radon may have been observed in experiments where unknown radon-containing products distilled together with xenon hexafluoride , and perhaps in the production of radon trioxide: these may have been RnF 4 , RnF 6 , or both. [ 11 ] It is likely that the difficulty in identifying higher fluorides of radon stems from radon being kinetically hindered from being oxidised beyond the divalent state. This is due to the strong ionicity of RnF 2 and the high positive charge on Rn in RnF + . Spatial separation of RnF 2 molecules may be necessary to clearly identify higher fluorides of radon, of which RnF 4 is expected to be more stable than RnF 6 due to spin–orbit splitting of the 6p shell of radon (Rn IV would have a closed-shell 6s 2 6p 2 1/2 configuration). [ 12 ] The ionicity of the Rn–F bond may also result in a strongly fluorine-bridged structure in the solid, so that radon fluorides may not be volatile. [ 2 ] Continuing the trend, the heavier oganesson hexafluoride should be unbound. [ 2 ]
Krypton hexafluoride ( KrF 6 ) has been predicted to be stable, but has not been synthesised due to the extreme difficulty of oxidising krypton beyond Kr(II). [ 13 ] The synthesis of americium hexafluoride ( AmF 6 ) by the fluorination of americium(IV) fluoride ( AmF 4 ) was attempted in 1990, [ 14 ] but was unsuccessful; there have also been possible thermochromatographic identifications of it and curium hexafluoride (CmF 6 ), but it is debated if these are conclusive. [ 2 ] Palladium hexafluoride ( PdF 6 ), the lighter homologue of platinum hexafluoride , has been calculated to be stable, [ 15 ] but has not yet been produced; the possibility of silver (AgF 6 ) and gold hexafluorides (AuF 6 ) has also been discussed. [ 2 ] Chromium hexafluoride ( CrF 6 ), the lighter homologue of molybdenum hexafluoride and tungsten hexafluoride , was reported, but has been shown to be a mistaken identification of the known pentafluoride ( CrF 5 ). [ 16 ] | https://en.wikipedia.org/wiki/MF6 |
MG-RAST , an open-source web application server, facilitates automatic phylogenetic and functional analysis of metagenomes . It stands as one of the largest repositories for metagenomic data, employing the acronym for Metagenomic Rapid Annotations using Subsystems Technology (MG-RAST). This platform utilizes a pipeline that automatically assigns functions to metagenomic sequences, conducting sequence comparisons at both nucleotide and amino acid levels. Users benefit from phylogenetic and functional insights into the analyzed metagenomes, along with tools for comparing different datasets. MG-RAST also offers a RESTful API for programmatic access.
Argonne National Laboratory from the University of Chicago created and maintains this server. As of December 29, 2016, MG-RAST had analyzed a substantial 60 terabase-pairs of data from over 150,000 datasets. Notably, more than 23,000 of these datasets are publicly available. Computational resources are currently sourced from the DOE Magellan cloud at Argonne National Laboratory, Amazon EC2 Web services, and various traditional clusters.
MG-RAST was developed to serve as a free, public resource dedicated to the analysis and storage of metagenome sequence data. It addresses a key bottleneck in metagenome analysis by eliminating the dependence on high-performance computing for annotating data.
The significance of MG-RAST becomes evident in metagenomic and metatranscriptomic studies, where the processing of large datasets often requires computationally intensive analyses. With the substantial reduction in sequencing costs in recent years, scientists can generate vast amounts of data. However, the limiting factor has shifted to computing costs. For example, a recent University of Maryland study estimated a cost exceeding $5 million per terabase using their CLOVR metagenome analysis pipeline. As sequence datasets' size and number continue to grow, the associated analysis costs are expected to rise.
Beyond analysis, MG-RAST functions as a repository tool for metagenomic data. Metadata collection and interpretation are crucial for genomic and metagenomic studies. MG-RAST addresses challenges related to the exchange, curation, and distribution of this information. The system has embraced minimal checklist standards and biome-specific environmental packages established by the Genomics Standards Consortium. Furthermore, MG-RAST provides a user-friendly uploader for capturing metadata at the time of data submission.
[ 1 ]
The MG-RAST application provides a comprehensive suite of services, including automated quality control, annotation, comparative analysis, and archiving for metagenomic and amplicon sequences. It utilizes a combination of various bioinformatics tools to achieve these functionalities. Originally designed for metagenomic data analysis, MG-RAST also extends support to amplicon sequences (16S, 18S, and ITS) and metatranscriptome (RNA-seq) sequences processing. However, it's important to note that MG-RAST currently lacks the capability to predict coding regions from eukaryotes, limiting its utility for eukaryotic metagenome analysis.
The MG-RAST pipeline can be segmented into five distinct stages:
The MG-RAST pipeline incorporates a series of steps for quality control and artifacts removal, ensuring robust processing of metagenomic and metatranscriptome datasets. The initial stage involves trimming low-quality regions using SolexaQA and eliminating reads with inappropriate lengths. In the case of metagenome and metatranscriptome datasets, a dereplication step is introduced to enhance data processing efficiency.
The subsequent step employs DRISEE (Duplicate Read Inferred Sequencing Error Estimation) to evaluate sample sequencing errors by measuring Artificial Duplicate Reads (ADRs). This assessment contributes to enhancing the accuracy of downstream analyses.
Finally, the pipeline offers the option to screen reads using the Bowtie aligner. It identifies and removes reads that exhibit matches close to the genomes of model organisms, including fly, mouse, cow, and human. This step aids in refining the dataset by filtering out reads associated with potential contaminants or unintended sequences.
In the gene identification process, MG-RAST employs a machine learning approach known as FragGeneScan. This method is utilized to identify gene sequences within the metagenomic or metatranscriptomic data.
For the identification of ribosomal RNA sequences, MG-RAST initiates a BLAT search against a reduced version of the SILVA database. This step allows the system to pinpoint and categorize ribosomal RNA sequences within the dataset, contributing to a more detailed understanding of the biological composition of the analyzed metagenomes or metatranscriptomes.
To identify the putative functions and annotations of the genes, MG-RAST follows a multi-step process. Initially, it builds clusters of proteins at a 90% identity level using the UCLUST implementation in QIIME. The longest sequence within each cluster is then selected for further analysis.
For the similarity analysis, MG-RAST employs sBLAT, a parallelized version of the BLAT algorithm using OpenMP. The search is conducted against a protein database derived from the M5nr, which integrates nonredundant sequences from various databases such as GenBank, SEED, IMG, UniProt, KEGG, and eggNOGs.
In the case of reads associated with rRNA sequences, a clustering step is performed at a 97% identity level. The longest sequence from each cluster is chosen as the representative and is used for a BLAT search against the M5rna database. This database integrates sequences from SILVA, Greengenes, and RDP, providing a comprehensive reference for the analysis of ribosomal RNA sequences.
The data feeds several key products, primarily abundance profiles. These profiles summarize and reorganize the information found in the similarity files in a more easily digestible format.
Finally, the obtained abundance profiles are loaded into the respective databases.
G-RAST isn't just a powerhouse for metagenome analysis, it's also a treasure trove for data exploration. Dive into a diverse toolbox for visualizing and comparing metagenome profiles across various datasets. Filter based on specifics like composition, quality, functionality, or sample type to tailor your search. Delve deeper with statistical inferences and ecological analyses – all within the user-friendly web interface. | https://en.wikipedia.org/wiki/MG-RAST |
MGI or MGI Tech is a Chinese biotechnology company , [ 3 ] which provides a line of products and technologies that serves the genetic sequencing , genotyping and gene expression , and proteomics markets. Its headquarters are located in Shenzhen , Guangdong , China.
In 2016, MGI was founded as a subsidiary of BGI Group . [ 4 ] [ 5 ] It manufactures high-throughput genetic sequencing systems and other products for use in the life sciences and health care sectors. [ 6 ] [ 7 ] As of July 2022, the company's operation is divided into two primary business segments: genetic sequencers and laboratory automation systems. [ 8 ] [ 9 ]
MGI was a subsidiary of BGI Group before, it was spun out and listed on the Shanghai stock exchange in 2022. [ 10 ]
In May 2020, MGI raised $1 billion in series B funding from IDG Capital and CPE China Fund. [ 11 ] [ 12 ] In December 2020, the company submitted its IPO application to Shanghai Stock Exchange STAR Market . [ 13 ] [ 14 ] In September 2021, the company has won the approval for its IPO on Shanghai Stock Exchange STAR Market’s high-tech board. [ 15 ]
In 2024, MGI lost more than a third of its market capitalization after the US Congress introduced legislation to prohibit American health data being sent to China. [ 16 ]
In March 2013, Complete Genomics was acquired by BGI Group. [ 17 ] After the acquisition, Complete Genomics moved to San Jose , and in June 2018 became part of MGI. [ 18 ] [ 19 ] The acquisition was one of the outcomes of $1.5 billion 'collaborative funds' i.e., '10 years loan' which was initially provided by China Development Bank to acquire all 128 of Illumina, Inc. 's newest and fastest next-generation sequencers including HiSeq 2000. [ 20 ]
The company is known for manufacturing DNA sequencers based on low-cost DNA nanoball sequencing technologies which was refined further after the acquisition of Complete Genomics. [ 21 ] [ 22 ] The refinement included combinatorial probe anchor synthesis technologies which involves loading DNA nanoballs (DNBs) onto a patterned array chip using a fluidic system. Subsequently, a sequencing primer is added to the adaptor region of the DNBs in order to hybridize them. [ 23 ]
On October 31, 2019, the Chairman of the Senate Finance Committee, Chuck Grassley , and Senator Marco Rubio wrote a joint letter to Alex Azar , the Secretary of the Department of Health and Human Services and Seema Verma , the Administrator of the Centers for Medicare & Medicaid Services (CMS) raised their concerns against MGI, regarding the circumstances under which the CMS may finance it to process American citizens' genomic or exome data. [ 24 ]
MGI asserted that it is “a supplier of instruments and consumables for customers to use in their own labs” and does not provide any genomic sequencing services. “MGI does not own, control, handle, or even access samples or genetic data, only MGI’s customers do. There is no risk that MGI will have access to any health records or genetic data from customers,” the company stated. [ 25 ]
In November 2021, a federal jury in California concluded that MGI America (in its capacity as an affiliate of BGI Group) had infringed Illumina, Inc.'s patents. Accordingly, they awarded Illumina damages of $8 million. [ 26 ]
In March 2022, Illumina persuaded a U.S. District Judge to prolong the restriction on MGI America selling its CoolMPS sequencers in the United States for six months until August 2022, when Illumina's patent expires. [ 27 ]
Complete Genomics , a research subsidiary of MGI, filed a lawsuit in May 2019, alleging that Illumina's "two-channel" DNA sequencing chemistry violates two patents for the technology that deduces the identification of each nucleotide from two signals. The NovaSeq 6000, the NextSeq 500/550/550x, and 1000/2000 Series, as well as the MiniSeq, were all the focus of the lawsuit against Illumina. Additionally, it targeted Illumina's cluster generation & sequencing, and library preparation kits, all of which are interoperable with one or more platforms. [ 28 ]
In May 2022, A jury in Delaware concluded that Illumina's “two-channel” sequencing chemistry infringes on two patents owned by MGI Tech through its subsidiary Complete Genomics. As a result of this finding, the jury awarded $333.8 million in damages to the company. The jury also dismissed Illumina's assertions that the patents were invalid. The verdict also invalidated three of Illumina's patents that the firm had asserted in a countersuit claiming MGI Tech had infringed on Illumina's patents. [ 29 ] | https://en.wikipedia.org/wiki/MGI_(company) |
MHC multimers are oligomeric forms of MHC molecules , designed to identify and isolate T-cells with high affinity to specific antigens amid a large group of unrelated T-cells. [ 1 ] Multimers generally range in size from dimers to octamers; however, some companies use even higher quantities of MHC per multimer. Multimers may be used to display class 1 MHC , class 2 MHC , or nonclassical molecules (e.g. CD1d ) from species such as monkeys, mice, and humans.
Since T-cell receptors have a low affinity for their MHC counterparts, it was historically problematic to label T cells effectively using single MHC-T-cell interactions. [ 2 ] However, in 1996 it was proposed by John Altman to use a complex of multiple MHC molecules to form a more stable bond between corresponding T-cells. [ 3 ]
The most commonly used MHC multimers are tetramers. [ 3 ] These are typically produced by biotinylating soluble MHC monomers, which are typically produced recombinantly in eukaryotic or bacterial cells. These monomers then bind to a backbone, such as streptavidin or avidin , creating a tetravalent structure. These backbones are conjugated with fluorochromes to subsequently isolate bound T-cells via flow cytometry . [ 4 ]
MHC multimers allow for a previously unattainable level of specificity in antigen-specific T-cell detection and isolation. This ability gives rise to several clinical applications. MHC multimers allow for ex vivo selection and proliferation of T-cells specific to viral or tumor-related antigens, which can then be reintroduced to augment the immune system. MHC multimers can also be used to eliminate graft-originating T-cells on transplant organs, ex vivo. MHC multimers may also be used to eliminate harmful or unwanted T-cells in vivo, such as those that target self cells and lead to autoimmune disease. [ 4 ] [ 5 ] [ 6 ] Cancer immunotherapy and vaccine development can also be largely influenced by this technology. [ 7 ]
MHC tetramers consist of four MHC molecules, a tetramerization agent and a fluorescently labeled protein (usually streptavidin). Streptavidins have also been generated with 6 or 12 binding sites for MHC. [ 8 ] MHC tetramers are used to identify and label specific T-cells by epitope specific binding, allowing the antigen specific immune response to be analyzed in both animal model and in human. [ 9 ] MHC tetramers were originally developed using MHC class I molecules for the recognition of cytotoxic T cells , [ 10 ] [ 11 ] but over the last decade they have allowed for the recognition of CD4 T cells by a wide variety of antigens. Tetramer assays are used for single-cell phenotyping and cell counting, and offer an important advantage over other methods, such as ELISPOT and single-cell PCR because they enable the recovery and further study of sorted cells. As a flow-cytometry-based application, tetramers are also easy to use and have a short assay time, similar to Antibody-based flow cytometry studies. [ 4 ]
MHC tetramers are used in studies of pathogen immunity and vaccine development, in evaluation of antitumor responses, in allergy monitoring and desensitization studies, and in autoimmunity. [ 4 ] [ 12 ] They provide an ideal means to characterize the T cells that respond to a vaccine, and they have been used to test T cell responses in many vaccine systems, including influenza , [ 13 ] yellow fever , [ 14 ] tuberculosis , [ 15 ] HIV / SIV [ 16 ] and a large number of cancer vaccine trials, [ 17 ] including melanoma and chronic myeloid leukemia . [ 18 ] Class II tetramers have been used for analysis of a variety of human CD4 T cell responses to pathogens, including influenza A , Borrelia , Epstein–Barr virus , CMV , Mycobacterium tuberculosis , human T-lymphotropic virus 1 , hepatitis C , anthrax , severe acute respiratory syndrome virus, human papillomavirus , and HIV. [ 4 ] Tetramer variants have been developed that, either radiolabelled or coupled to a toxin such as saporin , can be injected into live mice to modulate or even deplete specific T cell populations. [ 19 ] [ 20 ] Peptide–MHC tetramers have also been used therapeutically. [ 21 ] For instance, cytomegalovirus-specific T cells have been enriched to high levels of purity using magnetic bead-based enrichment for use as a therapy for stem cell transplant patients. [ 12 ]
Pentamers consist of five MHC-peptide headgroups, arranged in a planar configuration so that, unlike MHC tetramers, all of the headgroups can contact the CD8+ T cell. The headgroups are connected via flexible linkers to a coiled-coil multimerization domain, which in turn is connected to five fluorescent or biotin tags. Pentamers are available with APC, R-PE, or biotin labelling, and also unlabelled with separate tags for long-term storage. Pentamers offer enhanced brightness and avidity of staining compared with other multimer reagents.
MHC pentamers have been used in the detection of antigen-specific CD8+ T cells in flow cytometry, [ 12 ] and are cited in over 750 peer reviewed publications [1] , including several in the journals Nature [ 22 ] and Science . [ 23 ] [ 24 ] MHC pentamers can also be used in tissue staining, [ 25 ] and in magnetic isolation of antigen-specific T cells. [ 26 ]
While pentamers are licensed for research use only, in 2009 a special dispensation was granted for a team to use them for isolating EBV-specific T cells for mother-daughter transfer, for lifesaving treatment of EBV-associated lymphoma in the daughter. [ 27 ]
Pentamers are available for antigens from the following disease areas: adenovirus , HCV , malaria , SIV , autoimmune disease , HIV , transplantation antigens, trypanosoma , cancer , HPV , tuberculosis , chlamydia , HTLV , vaccinia , CMV , influenza , VSV , EBV , LCMV , RSV , West Nile virus , HBV , Listeria , Sendai virus , yellow fever . Custom specificity pentamers may also be commissioned.
Pentamers are currently used in research by academia, industry and clinicians, and research using pentamers has appeared in the international media [2] [3] on several occasions.
A form of MHC multimer developed and trademarked by the Danish biotechnology company, Immudex in 2002. Dextramer reagents are fluorescently labeled with FITC, PE or APC, and contain MHC molecules attached to a dextran backbone, which are used to detect antigen-specific T-cells in fluid cells and solid tissue samples using flow cytometry. These T-cells contain T-cell receptors (TCR) that recognize a specific MHC-peptide complex displayed on the surface of antigen presenting cells allowing for detection, isolation, and quantification of these specific T-cell populations due to an improved signal-to-noise ratio not present in prior generations of multimers. [ 3 ] [ 12 ] [ 28 ]
Dextramer ® reagents have been developed with a larger number of MHC-peptides for various human, mouse, and rhesus macaque genes involved in diseases including but not limited to: cancer , HIV , Epstein–Barr virus (EBV), cytomegalovirus (CMV), LCMV, human papillomavirus (HPV), BK polyomavirus , HTLV, hepatitis , mycobacterium , and graft-versus-host disease .
Dextramer technology is currently used in academic and clinical research due to their increased specificity and binding affinity, which allows for increased avidity for specific T-cells and enhances staining intensity. This advantage is a result of the increased ability of Dextramers to bind multiple times to a single T-cell, improving the stability of this interaction as compared with other multimer technologies such as pentamers and tetramers. Further applications include the ability to isolate antigen specific T-cell populations as well as in situ detection using immunohistochemistry (IHC) for various disease states (e.g. solid tumors). These reagents are therefore important for future drug and vaccine development. [ 1 ] [ 12 ] [ 28 ] [ 29 ] [ 30 ]
Immudex developed a CMV Dextramer ® assay for exploratory detection and quantification of CD8+ T-cells in blood samples, covering a broad range of epitopes to assist with screening and monitoring CMV progression in future clinical settings. [ 31 ] MHC Dextramer ® reagents are available with MHC class I and MHC class II molecules. [ 32 ] | https://en.wikipedia.org/wiki/MHC_multimer |
MHEG-5 , or ISO / IEC 13522–5, [ 1 ] is part of a set of international standards relating to the presentation of multimedia information, standardised by the Multimedia and Hypermedia Experts Group (MHEG). It is most commonly used as a language to describe interactive television services.
MHEG-5 is a licence-free and public standard for interactive TV middleware that is used both to send and receive interactive TV signals. It allows a wide range of TV-centric interactive services to be deployed. It is used by Freeview and Freesat in the UK, Freeview in New Zealand, TVB in Hong Kong, Freeview in Australia, Saorview in Ireland and has been specified in South Africa.
Recent [ when? ] work by the DTG in the UK has led to the development of the MHEG-5 Interaction Channel (MHEG-IC), which enables an extension of broadcast interactive services to be delivered via an IP connection. The principles behind the MHEG-IC are to provide a seamless viewer experience of broadcast delivered content augmented with content delivered over IP as an extension of the channel or network. Broadcasters have full editorial control of the user experience. The MHEG-IC gives access to streamed on-demand video content in addition to traditional text and graphics as well as the ability to support secure transactions.
MHEG-5 is an object-based declarative programming language which can be used to describe a presentation of text, images and video. An MHEG-5 application consists of a number of Scenes which the user of the application can move between. Each Scene lists the items of text and graphics to be presented and can contain blocks of procedural code which are executed in response to one of a predefined set of events such as keys being pressed, timers firing or content being successfully loaded into memory. These blocks of code consist of elementary actions which can perform operations such as changing the text displayed by a text object , or starting a video clip playing.
MHEG-5 specifies a hierarchy of classes that are available to the application author. Unlike in object oriented languages, it is not possible for new classes to be defined. The standard defines two representations of MHEG applications, one of which is textual and the other is represented in ASN.1 . Applications are normally written in the textual notation and then encoded into ASN.1 for interpretation by the MHEG engine .
MHEG-5 is suited to programming interactive kiosks and interactive television services.
MHEG-5 has been selected as the mandatory interactivity engine for CI+ compliant TVs (and other CI+ devices).
The MHEG-5 language itself is just that, a language. To be useful in any particular context, the language needs to be profiled .
A broadcast profile of the language has been standardized by ETSI , forming ETSI standard ES 202 184.
In the United Kingdom , MHEG-5 is used to provide interactive services for digital television such as the BBCs Ceefax replacement service, BBC Red Button . The full specification of how MHEG-5 is used in the context of the UK Freeview platform is the UK Profile of MHEG-5 . MHEG is also used on Freesat for its programming guide in addition to the DVB EIT, as opposed to the OpenTV platform used on Sky.
In New Zealand , the same profile as in UK is used, with minor additions for the Maori language and its use of the guide key on certified Freeview receivers. The guide receiver key is used to activate the MHEG-5 programming guide; this however disables use of the more compatible and faster loading DVB EIT guide feature. In Australia, this guide practice was adopted for the phase 2 Freeview and VAST receivers referenced by the label Freeview EPG .
In Hong Kong, TVB has also selected MHEG-5 for interactive services available on its digital-only channels. [ 2 ]
Ireland has selected MHEG-5 (v1.06) middleware for interactive services as a recommended feature of its Minimum Receiver Requirements for DTT in Ireland. [ 3 ] The name for Ireland's free digital service is Saorview .
Note: You can download the PDF version of above image from http://mheg5.net/down/class.pdf . | https://en.wikipedia.org/wiki/MHEG-5 |
MIDACO ( Mixed Integer Distributed Ant Colony Optimization ) is a software package for numerical optimization based on evolutionary computing .
MIDACO was created in collaboration of European Space Agency and EADS Astrium to solve constrained mixed-integer non-linear (MINLP) space applications. [ 1 ] [ 2 ] MIDACO holds several record solutions on interplanetary spaceflight trajectory design problems [ 3 ] [ 4 ] [ 5 ] [ 6 ] made publicly available by European Space Agency . MIDACO is included in software packages like TOMLAB , [ 7 ] Astos , [ 8 ] and SigmaXL. [ 9 ]
This software article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/MIDACO |
MIKE 11 is a computer program that simulates flow and water level, water quality and sediment transport in rivers, flood plains , irrigation canals, reservoirs and other inland water bodies. MIKE 11 is a 1-dimensional river model. It was developed by DHI .
MIKE 11 has long been known as a software tool with advanced interface facilities.
The new generation of MIKE 11 combines the features and experiences from the mike11
MIKE 11 ‘Classic’ period, with the powerful Windows based user interface including graphical editing facilities and improved computational speed gained by the full utilization of 32-bit technology.
The computational core of MIKE 11 is a hydrodynamic simulation engine, and this is complemented by a wide range of additional modules and extensions covering almost all conceivable aspects of river modeling.
HD module : provides fully dynamic solution to the complete nonlinear 1-D Saint Venant equations , diffusive wave approximation and kinematic wave approximation, Muskingum method and Muskingum-Cunge method for simplified channel routing. It can automatically adapt to subcritical flow and supercritical flow . It has ability to simulate standard hydraulic structures such as weirs , culverts , bridges , pumps , energy loss and sluice gates .
GIS Extension : an extension of ArcMap from ESRI providing features for catchment/river delineation, cross-section and Digital Elevation Model (DEM) data, pollution load estimates, flood visualisation/animation as 2D maps and results presentation/analysis using Temporal Analyst .
RR module : a rainfall runoff module, including the unit hydrograph method (UHM), a lumped conceptual continuous hydrological model and a monthly soil moisture accounting model. It includes an auto-calibration tool to estimate model parameter based on statistic data of comparison of simulated water levels/discharges and observations.
SO module : a structure operation module. It simulates operational structures such as sluice gates , weirs , culverts , pumps , bridges with operating strategies.
DB module : a dam break module. It provides complete facilities for definition of dam geometry, breach development in time and space as well as failure mode.
AUTOCAL module : an automatic calibration tool. It allows automisation of the calibration process for a wide range of parameters, including rainfall runoff parameters, Manning's number, head loss coefficients, water quality parameters etc.
AD module : an advection dispersion module. It simulates transport and spreading of conservative pollutants and constituents as well as heat with linear decay.
ST/GST module : a noncohesive sediment module. It simulates transport, erosion and deposition of non-cohesive and graded noncohesive sediments, including simulations of river morphology.
ACS module : a cohesive sediment module. It has 3-layer bed description, including quasi-2D erosion.
MIKE ECO Lab module : provides ecological modeling. It can simulate BOD / DO , Ammonia , Nitrate , Eutrophication , heavy metals and Wetlands . It includes standard templates that are well documented and have been used extensively in numerous applications worldwide. Based on predefined process templates, one can develop his/her own templates.
MIKE 11 Stratified module : models vertical density differences such as salinity or temperature in two-layer or multi-layered stratified water bodies.
MIKE 11 Real Time module : a simulation package and GIS front-end for setting up operational flood forecasting systems. It includes real-time updating and kalman filtering.
MIKE 11 has been used in hundreds of application around the world. Its main application areas are flood analysis and alleviation design, real-time flood forecasting, dam break analysis, optimisation of reservoir and canal gate/structure operations, ecological and water quality assessments in rivers and wetlands, sediment transport and river morphology studies, salinity intrusion in rivers and estuaries. | https://en.wikipedia.org/wiki/MIKE_11 |
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