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SK3 (small conductance calcium-activated potassium channel 3) also known as K Ca 2.3 is a protein that in humans is encoded by the KCNN3 gene . [ 5 ] [ 6 ]
SK3 is a small-conductance calcium-activated potassium channel partly responsible for the calcium -dependent after hyperpolarisation current (I AHP ). It belongs to a family of channels known as small-conductance potassium channels , which consists of three members – SK1 , SK2 and SK3 (encoded by the KCNN1, 2 and 3 genes respectively), which share a 60-70% sequence identity . [ 7 ] These channels have acquired a number of alternative names, however a NC- IUPHAR has recently achieved consensus on the best names, K Ca 2.1 (SK1), K Ca 2.2 (SK2) and K Ca 2.3 (SK3). [ 6 ] Small conductance channels are responsible for the medium and possibly the slow components of the I AHP .
K Ca 2.3 contains 6 transmembrane domains , a pore-forming region, and intracellular N - and C- termini [ 7 ] [ 8 ] and is readily blocked by apamin . The gene for K Ca 2.3, KCNN3, is located on chromosome 1q 21.
K Ca 2.3 is found in the central nervous system (CNS), muscle , liver , pituitary , prostate , kidney , pancreas and vascular endothelium tissues. [ 9 ] K Ca 2.3 is most abundant in regions of the brain , but has also been found to be expressed in significant levels in many other peripheral tissues, particularly those rich in smooth muscle , including the rectum , corpus cavernosum , colon , small intestine and myometrium . [ 7 ]
The expression level of KCNN3 is dependent on hormonal regulation, particularly by the sex hormone estrogen . Estrogen not only enhances transcription of the KCNN3 gene, but also affects the activity of K Ca 2.3 channels on the cell membrane . In GABAergic preoptic area neurons, estrogen enhanced the ability of α1 adrenergic receptors to inhibit K Ca 2.3 activity, increasing cell excitability. [ 10 ] Links between hormonal regulation of sex organ function and K Ca 2.3 expression have been established. The expression of K Ca 2.3 in the corpus cavernosum in patients undergoing estrogen treatment as part of gender reassignment surgery was found to be increased up to 5-fold. [ 7 ] The influence of estrogen on K Ca 2.3 has also been established in the hypothalamus , uterine and skeletal muscle . [ 10 ]
K Ca 2.3 channels play a major role in human physiology, particularly in smooth muscle relaxation. The expression level of K Ca 2.3 channels in the endothelium influences arterial tone by setting arterial smooth muscle membrane potential . The sustained activity of K Ca 2.3 channels induces a sustained hyperpolarisation of the endothelial cell membrane potential, which is then carried to nearby smooth muscle through gap junctions. [ 11 ] Blocking the K Ca 2.3 channel or suppressing K Ca 2.3 expression causes a greatly increased tone in resistance arteries, producing an increase in peripheral resistance and blood pressure .
Mutations in K Ca 2.3 are suspected to be a possible underlying cause for several neurological disorders , including schizophrenia , bipolar disorder , Alzheimer's disease , anorexia nervosa and ataxia [ 12 ] [ 13 ] [ 14 ] as well as myotonic muscular dystrophy . [ 15 ] | https://en.wikipedia.org/wiki/SK3 |
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Spindle and kinetochore-associated protein 2 is a protein that in humans is encoded by the SKA2 gene found in chromosome 17 . SKA2 is a part of a spindle and kinetochore associated complex also including SKA1 and SKA3 which is responsible for onset of the anaphase in mitosis by regulating chromosomal segregation. [ 5 ] [ 6 ]
SKA2 may function as a prognostic gene marker for identifying lung cancer [ 7 ] as well as a proposed biomarker for suicidal tendencies and post-traumatic stress disorders. [ 8 ] [ 9 ] The SKA2 gene contains one single-nucleotide polymorphism (SNP) rs7208505 located in the 3' UTR . This genetic variant containing a cytosine (existing in the less common allele) instead of thymine along with epigenetic modification (such as DNA methylation ) is correlated with suicidal tendencies and post-traumatic stress. [ 8 ]
SKA2 protein was first documented as a product of as hypothetical gene FAM33A part of a Spindle and Kinetochore (KT)- associated complex necessary for timely anaphase onset. SKA2 was identified as the partner of SKA1, hence the name in 2006. [ 6 ] Later on the 3rd component of the SKA complex was mass spectrometrically identified as C13Orf3 later referred to as SKA3. [ 10 ] This complex plays an important role in the cell during mitotic transition from the metaphase to the anaphase. [ 6 ]
SKA2 gene product is a 121 amino acid long chain and a molecular weight of 14,188 Da containing mainly 3 helices. [ 11 ] Homologues of SKA2 protein being very small are found in several vertebrates but absent in invertebrates. [ 6 ] This protein mainly localizes in the condensed chromosome and to the outer spindle and kinetochore microtubules during mitosis. [ 6 ] The SKA2 proteins localizes to the mitotic spindle and kinetochore associated proteins such as SKA1 and SKA3. [ 12 ]
The SKA2 is a part of the larger spindle and kinetochore complex which is a sub-complex of the outer kinetochore and binds to the microtubules. [ 6 ] [ 12 ] [ 13 ] This complex is essential for the correctly timed onset of anaphase during mitosis by helping in the chromosomal segregation [ 6 ] and aids in the movement of microspheres along a microtubule in a depolymerisation-coupled manner, since it is a direct component in the kinetochore-microtubule interface along with directly associating with the microtubules as assemblies. [ 13 ]
A reduced expression of SKA2 results in the loss of the complex from the kinetochore , however this loss of SKA-complex does not affect the overall structure of the Kinetochore yet the fibres show increased cold-sensitivity due to the loss. The cell goes through a prolonged delay in a metaphase-like state. [ 6 ] It has been concluded that SKA2 regulates the maintenance of the metaphase plate and silencing of the spindle checkpoint leading to the onset of anaphase during mitosis. [ 6 ] SKA2 also interacts with the glucocorticoid receptor aiding in the chaperoning of the receptor in the nucleus. [ 14 ]
The DNA methylation of SKA2 gene and the Single-nucleotide polymorphism rs7208505 genotype may have effects on suicidal behaviour according to linear model suggested by a study in 2014. The genotype rs7208505 contains a single nucleotide polymorphism (SNP) containing a Cytosine variant allele instead of Thymine present in the common allele. This SNP allows the dinucleotide repeat (CpG) elements to occur providing a gene segment for methylation. Thus DNA methylation alone may be the primary factor conferring risk of suicidal behaviour. A study of allele of rs7208505 in different ethnic groups along with numerous psychiatric diagnosis suggested that the variation in SKA2 may mediate risk for suicidal behaviours that progress to attempt to suicide. [ 8 ]
The SKA2 gene along with PRR11 gene as a pair is essential for the development of lung cancer . The pair of genes are separated by a 548 bp intergenic region, and having a classical head-to-head gene pair motif share a prototypical bidirectional promoter containing a common CCAAT element. [ 15 ] [ 16 ] This promoter is regulated by NF-Y is a sequence specific transcription factor and has long been considered an activator of genes since it contains particular properties suitable to regulate bidirectional promotor with the CCAAT box sequence. This bidirectional promoters couple expression of 2 genes (protein coding) involved in the same biochemical process to allow a synchronized temporal or environmental control.
The 2 genes SKA2 and PRR11 are vital for accelerated growth and motility of lung cancer cells and have prognostic value for patients. Along with SKA2 , PRR11 also plays a major role in regulating cell cycle progression but from the late S phase to mitosis. [ 6 ] [ 17 ] Thus, having vital roles to play in cell cycle progression at different stages, SKA2 and PRR11 may co-ordinately regulate lung cancer proliferation by deregulation of cell cycle progression. [ 7 ] Since the transcription of SKA2 gene produces the protein coding mRNA SKA2 along with 2 other introns miRNA301a and miRNAA454 , hence the function of the gene is not limited to production of a protein. [ 7 ] These introns participate in tumorigenesis since miRNA301a regulates PTEN , NKRF , SMAD4 and PIAS3 and miRNAA454 targets SMAD4 playing an oncogenic role in human colon cancer. [ 18 ] | https://en.wikipedia.org/wiki/SKA2 |
SK channels ( small conductance calcium-activated potassium channels ) are a subfamily of calcium-activated potassium channels . [ 1 ] They are so called because of their small single channel conductance in the order of 10 pS . [ 2 ] SK channels are a type of ion channel allowing potassium cations to cross the cell membrane and are activated (opened) by an increase in the concentration of intracellular calcium through N-type calcium channels . Their activation limits the firing frequency of action potentials and is important for regulating afterhyperpolarization in the neurons of the central nervous system as well as many other types of electrically excitable cells . This is accomplished through the hyperpolarizing leak of positively charged potassium ions along their concentration gradient into the extracellular space. This hyperpolarization causes the membrane potential to become more negative. [ 3 ] SK channels are thought to be involved in synaptic plasticity and therefore play important roles in learning and memory. [ 4 ]
SK channels are expressed throughout the central nervous system . They are highly conserved in mammals as well as in other organisms such as Drosophila melanogaster and Caenorhabditis elegans . [ 5 ] SK channels are specifically involved in the medium afterhyperpolarizing potential (mAHP). They affect both the intrinsic excitability of neurons and synaptic transmission. They are also involved in calcium signaling. [ 6 ] SK channel activation can mediate neuroprotection in various models of cell death. [ 6 ] [ 7 ] [ 8 ] SK channels control action potential discharge frequency in hippocampal neurons, midbrain dopaminergic neurons, dorsal vagal neurons, sympathetic neurons, nucleus reticularis thalamic neurons, inferior olive neurons, spinal and hypoglossal motoneurons, mitral cells in the olfactory bulb, and cortical neurons. [ 3 ]
SK potassium channels share the same basic architecture with Shaker-like voltage-gated potassium channels . [ 9 ] Four subunits associate to form a tetramer . Each of the subunits has six transmembrane hydrophobic alpha helical domains (S1-S6). A loop between S5 and S6—called the P-loop —provides the pore-forming region that always faces the center of the channel. [ 10 ] Each of the subunits has six hydrophobic alpha helical domains that insert into the cell membrane. A loop between the fifth and sixth transmembrane domains forms the potassium ion selectivity filter . SK channels may assemble as homotetrameric channels or as heterotetrameric channels, consisting of more than one SK channel subtype. In addition, SK potassium channels are tightly associated with the protein calmodulin , which accounts for the calcium sensitivity of these channels. [ 9 ] [ 11 ] Calmodulin participates as a subunit of the channel itself, bound to the cytoplasmic C-terminus region of the peptide called the calmodulin binding domain (CaMBD). [ 12 ]
Additional association of the phosphorylating kinase CK2 and dephosphorylating phosphatase PP2A on the cytoplasmic face of the protein allow for enriched Ca 2+ -sensitivity—and thus—kinetics modulation. [ 13 ] CK2 serves to phosphorylate the SKCa-bound CaM at the T80 residue, rather than the channel helices themselves, to reduce calcium sensitivity. This may only be accomplished when the channel pore is closed. PP2A dephosphorylates this residue upon CK2 inhibition. [ 12 ] The selectivity filter of all SK channel subtypes—whether SK1, SK2, SK3, or SK4—is highly conserved and reflects the selectivity seen in any potassium channel , a GYGD amino acid residue sequence on the pore-forming loop. [ 14 ] These channels are considered to be voltage-independent, as they possess only two of seven positively charged amino acid residues that are typically seen in a prototypical voltage-gated potassium channel . [ 10 ]
The SK channel family contains 4 members – SK1 , SK2 , SK3 , and SK4 . SK4 is often referred to as IK (Intermediate conductance) due to its higher conductance 20 – 80 pS. [ 15 ]
The SK channel gating mechanism is controlled by intracellular calcium levels. [ 5 ] Calcium enters the cell via voltage activated calcium channels as well as through NMDA receptors. [ 3 ] Calcium does not directly bind to the SK channel. Even in the absence of calcium, the SK channel binds to the C-lobe of the protein calmodulin (CaM). When the N-lobe binds calcium, it traps the S4-S5 linker on the intracellular subunit of the SK channel. When each of the four S4-S5 linkers are bound to the N-lobe of calmodulin, the SK channel changes conformation. Calmodulin pushes the S4-S5 linker to allow the expansion of the S6 bundle crossing, leading to opening of the pore. The idea that this transitions the channel from a tetramer of monomers to a folded dimer of dimers, which results in rotation of the CaM-binding domains is now abandoned, and the most recent observations are not compatible with the proposal that this rotation causes the mechanical opening of the channel gate. [ 5 ] The time constant of SK channel activation is approximately 5 ms. When calcium levels are depleted, the time constant for channel deactivation ranges from 15–60 ms. [ 16 ]
All SK channels can be pharmacologically blocked by quaternary ammonium salts of a plant-derived neurotoxin bicuculline . [ 17 ] In addition, SK channels (SK1-SK3) but not SK4 (IK) are sensitive to blockade by the bee toxin apamin , [ 18 ] and the scorpion venoms tamapin and charybdotoxin (ChTx), all via competitive antagonism for access to the mouth of the pore formation. [ 19 ] All known blockers compete for roughly the same binding site, the pore, in all subtypes. This provides a physical blockage to the channel pore. [ 20 ] Since all blockers are universal to all three types of SK channels, there is an incredibly narrow therapeutic window that does not allow for blocking of a specific SK channel subtype. [ 13 ] Quaternary ammonium salts like bicuculline and tetraethylammonium (TEA) enter the pore via the selectivity filter by acting as a potassium mimic in the dehydration step of pore permeation. [ 20 ]
The following molecules are other toxins and organic compounds that also inhibit all three small SK channel subtypes to any (even minimal) degree: [ 13 ]
Allosteric modulators of small SK channels work by changing the apparent calcium sensitivity of the channels. Examples include:
In dendritic spines, SK channels are directly coupled to NMDA receptors. In addition to being activated by calcium flow through voltage-gated calcium channels, SK channels can be activated by calcium flowing through NMDA receptors, which occurs after depolarization of the postsynaptic membrane. [ 12 ] Experiments using apamin have shown that specifically blocking SK channels can increase learning and long-term potentiation . In addition, brain-derived neurotrophic factor (BDNF) causes the down-regulation of SK channels, which facilitates long-term potentiation. Increasing SK channel activity has the opposite effect and serves to impair learning . [ 5 ] An increase in SK channel activity that occurs over time may be related to decreases in plasticity and memory that is seen with aging. [ 24 ]
The dysfunction of potassium channels, including SK channels, is thought to play a role in the pathogenesis of Parkinson's disease (PD), a progressive neurodegenerative disorder .
SK channel blockers control the firing rate (the number of action potentials produced by a neuron in a given time) and the firing pattern (the way action potentials are allocated throughout time) through their production of m-AHP. SK channel activators decrease the firing rate, neuron sensitivity to excitatory stimuli, mediating neuroprotection, whereas SK channel blockers increase the firing rate and sensitivity to excitatory stimuli. [ 25 ] This has important implications as to the function of dopaminergic neurons. [ 25 ] For example, the amount of dopamine released by midbrain dopaminergic neurons is much higher when the frequency of firing increases than when they fire at a constant rate.
SK channels are widely expressed in midbrain dopaminergic neurons. Multiple pharmacological techniques have been used to adjust SK affinity for calcium ions, thereby modulating the excitability of substantia nigra dopaminergic neurons. Blockage of SK channels in vivo increases the firing rate of substantia nigra cells, which increases the amount of dopamine released from the synaptic terminals. [ 25 ] When a large amount of dopamine accumulates in the cytosol, cell damage is induced due to the build-up of free radicals and damage to mitochondria.
In addition, techniques have been used to modulate SK channels in order to alter the dopamine phenotype of neurons. After the loss of TH+ ( tyrosine hydroxylase -positive) substantia nigra compacta (SNc) neurons due to Parkinson’s-induced neurodegeneration, the number of these neurons can partially recover via a cell phenotype "shift" from TH- (tyrosine hydroxylase-negative) to TH+. The number of TH+ neurons can be altered by SK channel modulation; to be specific, the infusion of SK agonists into substantia nigra increases the number of TH+ neurons, whereas the infusion of SK antagonist decreases the number of TH+ neurons. The reason for this relationship between SK channels and TH expression may be due to neuroprotection against dopamine toxicity . [ 25 ]
Two contradictory methods have been suggested as therapeutic options for the improvement of PD symptoms:
Inhibition of SK channels
Facilitation of SK channels | https://en.wikipedia.org/wiki/SK_channel |
The SLAC bag model is a simple theoretical model for a possible structure for hadrons . The MIT bag model is another similar model. [ 1 ] The "SLAC" in the name stands for Stanford Linear Accelerator Center .
The chiral bag model is a variant of the MIT bag model that couples pions to the bag boundary, with the pion field being modeled by the skyrmion . In this model, the boundary condition is that the axial vector current is continuous across the boundary, with free (non-interacting) quarks on the inside, obeying the boundary condition.
This nuclear physics or atomic physics –related article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/SLAC_bag_model |
The SLJ900/32 or otherwise known as the Iron Monster [ 4 ] is a superheavy launching gantry and one of the largest and most ubiquitous in the world. At over 90 meters in length, the SLJ900/32 is also one of the world's longest terrestrial vehicles. It is built by the Beijing Wowjoint Machinery Company and designed by the Shijiazhuang Railway Design Institute . [ 1 ] [ 3 ]
The SLJ900/32 as aforementioned, is 91 metres (299 ft) long, 7 metres (23 ft) wide, 9 m (29 ft 6 in) tall and weighs around 580 tonnes (640 short tons). [ 4 ] Compared to conventional cranes which require clear land and are typically only able to lift a few meters of bridge material per-lift, the SLJ900/32 is capable of lifting an entire large segment of bridging material (some of which weigh around 800 to 950 tons) in a relatively compact manner without the hassle of interference such as trees or rocks. [ 5 ]
Construction process is done via the vehicle picking up a new pre-cast section of concrete underneath its "belly" and carrying it all the way from the very edge of the bridge to the installation point, where it will be connected to a predetermined pillar. [ 4 ] [ 6 ] Then, using a pneumatic structure, the machine is moored to the first pillar to extend to the second one, anchoring to it, and places the beam. [ 4 ] [ 3 ] The process would repeat itself until the bridge's foundations are completed.
The vehicle moves on a large 64x wheel drive system, which in itself is divided into four sections of 16 wheels each (forming two trucks, one at each end). [ 4 ] [ 1 ] Each of the sections can rotate up to 90 degrees allowing the machine to drive sideways for efficiency when picking up beams. [ 6 ] The vehicle can maintain a top speed of 8 km/h (5 mph) unloaded, and 5 km/h (3 mph) carrying a bridge segment. [ 7 ]
Each vehicle's operational life is capable of building up to 730 spans before retiring. [ 6 ] | https://en.wikipedia.org/wiki/SLJ900/32 |
The SLOSS debate was a debate in ecology and conservation biology during the 1970's and 1980's as to whether a s ingle l arge o r s everal s mall (SLOSS) reserves were a superior means of conserving biodiversity in a fragmented habitat . Since its inception, multiple alternate theories have been proposed. There have been applications of the concept outside of the original context of habitat conservation .
In 1975, Jared Diamond suggested some "rules" for the design of protected areas, based on Robert MacArthur and E. O. Wilson 's book The Theory of Island Biogeography . One of his suggestions was that a single large reserve was preferable to several smaller reserves whose total areas were equal to the larger.
Since species richness increases with habitat area, as established by the species area curve , a larger block of habitat would support more species than any of the smaller blocks. This idea was popularised by many other ecologists, and has been incorporated into most standard textbooks in conservation biology, and was used in real-world conservation planning. This idea was challenged by Wilson's former student Daniel Simberloff , who pointed out that this idea relied on the assumption that smaller reserves had a nested species composition — it assumed that each larger reserve had all the species presented in any smaller reserve. If the smaller reserves had unshared species, then it was possible that two smaller reserves could have more species than a single large reserve. [ 1 ]
Simberloff and Abele expanded their argument in subsequent paper in the journal The American Naturalist stating neither ecological theory nor empirical data exist to support the hypothesis that subdividing a nature reserve would increase extinction rates, basically negating Diamond as well as MacArthur and Wilson. Bruce A. Wilcox and Dennis D. Murphy responded with a key paper "Conservation strategy - effects of fragmentation on extinction" pointing out flaws in their argument while providing a comprehensive definition of habitat fragmentation . Wilcox and Murphy also argued that habitat fragmentation is probably the major threat to the loss of global biological diversity.
This helped set the stage for fragmentation research as an important area of conservation biology . [ 2 ] The SLOSS debate ensued as to the extent to which smaller reserves shared species with one another, leading to the development of nested subset theory by Bruce D. Patterson and Wirt Atmar in the 1980s and to the establishment of the Biological Dynamics of Forest Fragments Project (BDFFP) near Manaus , Brazil in 1979 by Thomas Lovejoy and Richard Bierregaard .
In 1986, Michael E. Soulé and Daniel Simberloff proposed that the SLOSS debate was irrelevant and that a three step process was the ideal way to determine reserve size. [ 3 ] The proposed steps were to firstly decide the species whose presence was most important to the reserves biodiversity, secondly, decide how many of the species were required for the species to survive, and lastly, based on other metapopulation densities, estimate how much space is needed to sustain the required number of individuals.
The purpose of the debate itself is in regards to conservation planning and is currently used in most spatial allotment planning.
The SLOSS debate has come in to play in urban planning concerning green spaces with considerations extending beyond biodiversity to human well being. [ 4 ] The concept can also be applied to other aspects of city planning.
The general consensus of the SLOSS debate is that neither option fits every situation and that they must all be evaluated on a case to case basis in accordance to the conservation goal to decide the best course of action. [ 5 ] [ 6 ]
In the field of metapopulation ecology, modelling works suggest that the SLOSS debate should be refined and cannot be solved without explicit spatial consideration of dispersal and environmental dynamics. In particular, a large number of small patches may be optimal to long-term species persistence only if the species range increases with the number of patches. [ 7 ]
In conservation biology and conservation genetics , metapopulations (i.e. connected groups of sub-populations) are considered to be more stable if they are larger, or have more populations. [ 8 ] This is because although individual small populations may go extinct due to stochastic processes of environment or biology (such as genetic drift and inbreeding ), they can be recolonized by rare migrants from other surviving populations. Thus several small populations could be better than a single large: if a catastrophe wipes out a single big population, the species goes extinct, but if some regional populations in a large metapopulation get wiped out, recolonization from the rest of the metapopulation can ensure their eventual survival. In cases of habitat loss , when the loss is dispersed, few large reserves are best, when the loss is in clusters, multiple small reserves are best. [ 9 ] | https://en.wikipedia.org/wiki/SLOSS_debate |
Smart hoMes for All ( SM4All ) is an international scientific research project funded by the European Community . It started on September 1, 2008, and will end on August 31, 2011. The SM4All project aims at studying and developing an innovative middleware platform for inter-working of smart embedded services in immersive and personcentric environments, through the use of composability and semantic techniques, in order to guarantee dynamicity, dependability and scalability, while preserving the privacy and security of the platform and its users. This is applied to the challenging scenario of private/home/building in presence of users with different abilities and needs (e.g., young able bodied aged and disabled). [ 1 ]
In the design of the SM4All platform, there will be a specific focus on ontologies for describing service capabilities, to be used for obtaining the dynamic configuration and composition of the services, while preserving the privacy of the users. Within this project an innovative middleware platform for inter-working of smart embedded services by leveraging on peer-to-peer (P2P) technologies will be investigated. In particular, in the SM4All project, P2P, service orientation and context-awareness are merged in novel ways in order to define general reference architecture for embedded middleware targeted to immersive scenarios, among which the domotics and home-care have been selected as showcases. [ 2 ]
P2P systems (P2P) have become a popular technique to design large-scale distributed applications in unmanaged inter-domain settings, such as file sharing or chat systems, thanks to their capabilities to self-organize and evenly split the load among peers. [ 3 ] The platform is inherently scalable and able to resist to devices’ churn and failures, while preserving the privacy of its human users as well as the security of the whole environment. The embedded systems are specialized computers used to control equipment such as the smart homes. [ 1 ] To enable interoperation among heterogeneous devices and to provide a service-oriented basis, the project considers XML based protocols such as Web services and Universal Plug and Play (UPnP). [ 4 ]
For example, a woman wants to take a bath. She enters this goal into the computer. Something happens then: The temperature in the bathroom will rise. The water runs in the bathtub with the preferred temperature. The cupboard opens to offer towels. If the woman is disabled, her nurse will be informed by the system.
In SM4All, the focus is on the process-oriented composition of stateful services. The idea is that a triggering condition in the home or a desire of the user can trigger the execution of a complex process. The process is defined in the moment that it needs to be executed. It automatically composes services available on home devices and appliances. The execution of the process thus depends on the context of the home, of its inhabitant and the available services. To achieve this it is necessary to identify the home context, to discover available devices and services and to compose them at execution time. In the SM4All project we consider Automated planning and scheduling approaches for the composition such as the "Roman Model" [ 5 ] and the "Barbarian" constraint based approach. [ 6 ]
Two techniques adopted in the SM4All project are: | https://en.wikipedia.org/wiki/SM4All |
SMBH, Inc. is a full-service structural engineering firm located in Columbus, Ohio . Providing structural engineering services for architects , contractors and building owners, SMBH, Inc. has experience designing educational facilities, medical centers, courthouses and commercial and residential buildings. Since 1972, SMBH, Inc. has served the architectural and construction communities in Ohio and surrounding states. SMBH, Inc. has worked with architectural firms such as Graham Gund 's Gund Partnership, Mack Scogin Merrill Elam Architects, Peter Eisenman , and Robert A.M. Stern .
SMBH, Inc. located in Columbus, Ohio, was founded in 1972 as a structural engineering firm for the architectural industry. Founded as Lantz and Jones, the firm changed its name to Lantz Jones and Nebraska, Inc. in 1975 to reflect a change in ownership. [ 2 ] Lantz Jones and Nebraska had offices in Charleston, West Virginia and Stuart, Florida . SMBH, Inc. still performs work in these areas, but now operates out of the Columbus, Ohio office. During the past two decades, the ownership has transitioned from Bill Lantz, Tom Jones and Jim Nebraska to Stephen J. Metz, Bob Baumann, and Jon Beier. The ownership transition prompted the name change to Shelley Metz Baumann Hawk, Inc. in 2005 and in 2013, the company name was shortened to SMBH, Inc. [ 3 ] In March 2013, Bill Shelley stepped down from his role as president of the company. [ 4 ] He was replaced by Stephen Metz. [ 4 ]
SMBH, Inc. has worked on the following projects: Franklin County Courthouse, located in Columbus, Ohio, the William Oxley Thompson Memorial Library , located on Ohio State University campus, [ 5 ] the Polaris Hilton Conference Center, located in Columbus, Ohio, Limited Brands World Headquarters & Distribution Center, located in Columbus, Ohio, Hocking College Residence Hall, located on the Hocking College campus, the Austin Eldon Knowlton School of Architecture, located on The Ohio State University campus, [ 6 ] Grange Insurance Headquarters Expansion Office and Parking Garage, located in downtown Columbus, Ohio, Nationwide Children’s Hospital Research Building 3, located in Columbus, Ohio, Broad Street United Methodist Church, located in Columbus, Ohio, [ 7 ] Farmer School of Business , located at Miami University, Ohio School for the Deaf / Ohio State School for the Blind , located in Columbus, Ohio, Linden-McKinley High School , Columbus, Ohio Public Schools, the South High Rise residence halls located on the campus of the Ohio State University, [ 8 ] [ 9 ] and the Morris Hospital, located in Morris, Illinois. [ 10 ]
SMBH, Inc. has been involved with sustainable and Leadership in Energy and Environmental Design (LEED) certified projects, as well as team members who are LEED Accredited Professionals.
Examples of green building and sustainable design includes work on the following projects: Student Academic Services Office Building; Columbus, Ohio, Franklin County Courthouse, Columbus, Ohio; [ 11 ] West Side Family Health Center, Columbus, Ohio; Grange Insurance Audubon Center, Columbus, Ohio; Columbus State Community College – Academic Center E, Delaware, Ohio; Ohio School for the Blind/Ohio State School for the Deaf, Columbus, Ohio; Mid Ohio Food Bank, Columbus, Ohio; Hocking College – Energy Institute, Logan, Ohio ; Miami University – Farmer School of Business Building, Oxford, Ohio .
SMBH, Inc. are members of the following associations: American Council of Engineering Companies (ACEC), American Institute of Architects (AIA) - Columbus, Ohio, American Institute of Architects (AIA)- West Virginia, American Institute of Steel Construction (AISC), American Concrete Institute (ACI), American Society of Civil Engineers (ASCE), International Concrete Repair Institute (ICRI), National Trust for Historic Preservation , Post-Tensioning Institute (PTI), Structural Engineers Association of Ohio (SEAo0), Tilt-Up Concrete Association (TCA). | https://en.wikipedia.org/wiki/SMBH,_Inc. |
SMBRelay and SMBRelay2 are computer programs that can be used to carry out SMB man-in-the-middle (mitm) attacks on Windows machines. They were written by Sir Dystic of Cult of the Dead Cow (cDc) and released March 21, 2001 at the @lantacon convention in Atlanta , Georgia . More than seven years after its release, Microsoft released a patch that fixed the hole exploited by SMBRelay. [ 1 ] [ 2 ] This fix only fixes the vulnerability when the SMB is reflected back to the client. If it is forwarded to another host, the vulnerability can be still exploited. [ 3 ] [ 4 ]
SMBrelay receives a connection on UDP port 139 and relays the packets between the client and server of the connecting Windows machine to the originating computer's port 139. It modifies these packets when necessary.
After connecting and authenticating, the target's client is disconnected and SMBRelay binds to port 139 on a new IP address . This relay address can then be connected to directly using "net use \\192.1.1.1" and then used by all of the networking functions built into Windows. The program relays all of the SMB traffic, excluding negotiation and authentication. As long as the target host remains connected, the user can disconnect from and reconnect to this virtual IP .
SMBRelay collects the NTLM password hashes and writes them to hashes.txt in a format usable by L0phtCrack for cracking at a later time.
As port 139 is a privileged port and requires administrator access for use, SMBRelay must run as an administrator access account. However, since port 139 is needed for NetBIOS sessions, it is difficult to block.
According to Sir Dystic, "The problem is that from a marketing standpoint, Microsoft wants their products to have as much backward compatibility as possible; but by continuing to use protocols that have known issues, they continue to leave their customers at risk to exploitation... These are, yet again, known issues that have existed since day one of this protocol. This is not a bug but a fundamental design flaw. To assume that nobody has used this method to exploit people is silly; it took me less than two weeks to write SMBRelay." [ 5 ]
SMBRelay2 works at the NetBIOS level across any protocol to which NetBIOS is bound (such as NBF or NBT ). It differs from SMBrelay in that it uses NetBIOS names rather than IP addresses.
SMBRelay2 also supports man-in-the-middling to a third host. However, it only supports listening on one name at a time. | https://en.wikipedia.org/wiki/SMBRelay |
SMC proteins represent a large family of ATPases that participate in many aspects of higher-order chromosome organization and dynamics. SMC proteins are widely conserved across bacteria, archaea, and eukaryotes. In eukaryotes, they function as the core ATPase subunits of large protein complexes such as condensin, cohesin, and SMC5/6. [ 1 ] [ 2 ] [ 3 ] [ 4 ]
The term SMC derives from a mutant strain of Saccharomyces cerevisiae named smc1 (stability of mini-chromosomes 1), which was identified based on its defect in maintaining the stability of mini-chromosomes. [ 5 ] After the gene product of SMC1 was characterized, [ 6 ] and homologous proteins were found to be essential for chromosome structure and dynamics in many organisms, the acronym SMC was redefined to stand for "Structural Maintenance of Chromosomes". [ 7 ]
Eukaryotes have at least six SMC proteins in individual organisms, and they form three distinct heterodimers with specialized functions:
The pairings of SMC proteins in eukaryotes, SMC1-SMC3, SMC2–SMC4, and SMC5–SMC6, are highly specific and invariant; no exceptions to these combinations have been reported to date. Sequence comparisons reveal that SMC1 and SMC4, as well as SMC2 and SMC3, share a high degree of similarity, while SMC5 and SMC6 form a more distinct clade (Figure 1). [ 14 ] It is hypothesized that the last eukaryotic common ancestor (LECA) possessed all six SMC proteins. While SMC1–4 are conserved in all known eukaryotic species, some lineages (such as the ciliate Tetrahymena thermophila ) have lost SMC5 and SMC6 during evolution, [ 15 ] suggesting that the SMC5/6 complex may not be strictly essential for eukaryotic cell viability.
In addition to the six subtypes, some organisms have variants of SMC proteins. For instance, mammals have a meiosis -specific variant of SMC1, known as SMC1β. [ 16 ] The nematode Caenorhabditis elegans has an SMC4-variant that has a specialized role in dosage compensation . [ 17 ]
The following table shows the SMC proteins names for several model organisms and vertebrates: [ 18 ]
The evolutionary origin of SMC proteins is ancient, and homologs are widely conserved in both bacteria and archaea . [ 15 ]
In a broader sense, several proteins with structural similarities to SMC are considered members of the SMC superfamily.
The subunit composition of SMC protein complexes varies across domains of life. The table below and Figures 2 & 3 summarize the representative complexes found in eukaryotes and prokaryotes .
All SMC dimers, whether of eukaryotic or prokaryotic origin, associate with a kleisin subunit. In condensins and cohesin , the kleisin subunit is further associated with a pair of HEAT-repeat subunits. [ 40 ] Notably, the eukaryotic SMC5/6 complex contains "kite" (kleisin interacting tandem winged-helix elements) subunits [ 41 ] instead of HEAT-repeat subunits, [ 40 ] making it structurally more similar to prokaryotic complexes such as SMC–ScpAB, MukBEF , and MksBEF. However, unlike their typically homodimeric prokaryotic counterparts, both the SMC and kite subunits in the SMC5/6 complex are heterodimeric, resulting in a more elaborate subunit architecture. The SMC5/6 complex and the Wadjet complex (JetABCD) each possess an additional catalytic subunit: the SUMO ligase Nse2 in SMC5/6, [ 42 ] and the nuclease JetD in JetABCD. [ 29 ] [ 30 ] MukBEF and JetABC form higher-order assemblies through dimerization mediated by their kleisin subunits, a configuration often referred to as a "dimer-of-dimers".
SMC proteins are 1,000-1,500 amino-acid long. They have a modular structure that is composed of the following domains:
SMC dimers form a V-shaped molecule with two long coiled-coil arms (Figure 4). [ 43 ] [ 44 ] To make such a unique structure, an SMC protomer is self-folded through anti-parallel coiled-coil interactions, forming a rod-shaped molecule. At one end of the molecule, the N-terminal and C-terminal domains form an ATP -binding domain. The other end is called a hinge domain. Two protomers then dimerize through their hinge domains and assemble a V-shaped dimer. [ 45 ] [ 46 ] The length of the coiled-coil arms is ~50 nm long. Such long "antiparallel" coiled coils are very rare and found only among SMC proteins (and their relatives such as Rad50). The ATP-binding domain of SMC proteins is structurally related to that of ABC transporters , a large family of transmembrane proteins that actively transport small molecules across cellular membranes. It is thought that the cycle of ATP binding and hydrolysis modulates the cycle of closing and opening of the V-shaped molecule. Still, the detailed mechanisms of action of SMC proteins remain to be determined.
The formation of an SMC protein complex involves the association of an SMC dimer with non-SMC subunits (Figure 4). First, the N-terminal domain of the kleisin subunit binds to the neck region (a segment of the coiled coil near the head domain) of one SMC protein [ 47 ] [ 48 ] [ 49 ] , while its C-terminal domain binds to the cap region (part of the head domain) of the other SMC subunit [ 50 ] [ 49 ] . These interactions result in the formation of a ring-like architecture. As a consequence, the SMC–kleisin trimer adopts an asymmetric configuration. Accordingly, the SMC subunit bound at the N-terminal domain of the kleisin is sometimes referred to as the nSMC, while the one bound at the C-terminal domain is called the kSMC. Finally, two HEAT-repeat subunits (or two KITE subunits depending on the complex) associate with the central region of the kleisin, completing the assembly of the holo-complex.
SMC protein complexes are involved in a wide range of chromosome-related functions, and each complex is thought to possess distinct molecular activities tailored to its specific role.
At the same time, based on their evolutionary origins and conserved structural features, it has been suggested that certain molecular activities may be shared across multiple SMC complexes.
For example, several SMC complexes are known to exhibit DNA entrapment activity, in which DNA is topologically entrapped within the ring-like structure formed by their long coiled-coil arms. This activity has been demonstrated in cohesin, [ 51 ] [ 52 ] condensin, [ 53 ] [ 54 ] [ 55 ] and the SMC5/6 complex. [ 56 ]
More recent studies have highlighted DNA loop extrusion as a conserved molecular activity shared by many SMC protein complexes. Single-molecule analyses have demonstrated that condensin , [ 57 ] cohesin , [ 58 ] [ 59 ] the SMC5/6 complex, [ 60 ] and Wadjet [ 61 ] are capable of extruding DNA loops in an ATP-dependent manner. During loop extrusion, the ATPase cycle of the SMC subunits is thought to be coupled with dynamic and multivalent interactions between various subunits and DNA. These interactions likely occur in multiple modes, making the molecular mechanism of loop extrusion highly complex and still incompletely understood. [ 62 ] [ 63 ]
Several genetic disorders have been linked to mutations in genes encoding components or regulators of SMC protein complexes:
Active research on SMC proteins began in the 1990s. As global interest in this field increased, international meetings dedicated to SMC proteins have been held regularly since the 2010s. These meetings, which are organized approximately every two years, cover a wide range of topics reflecting the diverse functions of SMC protein complexes, from bacterial chromosome segregation to human genetic disorders. | https://en.wikipedia.org/wiki/SMC_protein |
SMIF ( Standard Mechanical Interface ) is a wafer carrier used in semiconductor wafer fabrication and cleanroom environments. The isolation technology was developed in the 1980s by a group known as the "micronauts" at Hewlett-Packard in Palo Alto . It is a SEMI standard. [ 1 ]
The purpose of SMIF pods is to isolate wafers from contamination by providing a miniature environment with controlled airflow, pressure and particle count. SMIF pods can be accessed by automated mechanical interfaces on production equipment. The wafers therefore remain in a carefully controlled environment whether in the SMIF pod or in a tool, without being exposed to the surrounding airflow.
Each SMIF pod contains a wafer cassette in which the wafers are stored horizontally. The bottom surface of the pod is the opening door, and when a SMIF pod is placed on a load port, the bottom door and cassette are lowered into the tool so that the wafers can be removed.
Both wafers and reticles can be handled by SMIF pods in a semiconductor fabrication environment. Used in lithographic tools, reticles or photomasks contain the image that is exposed on a coated wafer in one processing step of a complete integrated semiconductor manufacturing cycle. Because reticles are linked so directly with wafer processing, they also require steps to protect them from contamination or from being the source of contamination in the litho tool.
SMIF is typically used for wafers no larger than 200mm. The equivalent for 300mm wafers is the FOUP ( F ront O pening U nified P od). The greater flexibility of 300mm wafers means that it is not feasible to use SMIF technology and designs for 300mm, hence the reason for the emergence of FOUPs. Several FOUP SEMI standards, including SEMI E47.1-1106, [ 2 ] are related to both 300 and 450 mm wafers.
The core development team was led by Ulrich Kaempf as engineering manager, under the direction of Mihir Parikh. The core team that developed the technology was driven by Barclay Tullis, who held most of the patents, with Dave Thrasher, who later joined the Silicon Valley Group, and Thomas Atchison, a member of the technical staff under direction of Barclay Tullis. Mihir later provided the technology to SEMI, and then licensed a copy for himself, and spun out Asyst Technologies to provide the technology commercially. Asyst technology subsequent acquire by Brooks Automation in their Versaport. The interface is the same after being acquired | https://en.wikipedia.org/wiki/SMIF_(interface) |
SMILES arbitrary target specification (SMARTS) is a language for specifying substructural patterns in molecules . The SMARTS line notation is expressive and allows extremely precise and transparent substructural specification and atom typing.
SMARTS is related to the SMILES line notation that is used to encode molecular structures and like SMILES was originally developed by David Weininger and colleagues at The Pomona College Medicinal Chemistry Project (MedChem). A SMARTS software search engine named GENIE was used as an additional user-specified search filter in the MedChem database searching tool MERLIN. GENIE was also used in the MedChem interpreted language GCL (GENIE Control Language), where input was a list of structures. In GCL, a SMARTS specification was used as an expression that could be used in control flow statements. For example "for (SMARTS) {...}" would loop over each substructure (of the currently examined structure) that matched a SMARTS specification. Additional SMARTS development was made at Daylight Chemical Information Systems, Inc, which is a private company that was spun out of the software side of MedChem.
The most comprehensive descriptions of the SMARTS language can be found in Daylight's SMARTS theory manual, [ 1 ] tutorial [ 2 ] and examples. [ 3 ] OpenEye Scientific Software has developed their own version of SMARTS which differs from the original Daylight version in how the R descriptor (see cyclicity below) is defined.
Atoms can be specified by symbol or atomic number. Aliphatic carbon is matched by [C] , aromatic carbon by [c] and any carbon by [#6] or [C,c] . The wild card symbols * , A and a match any atom, any aliphatic atom and any aromatic atom respectively. Implicit hydrogens are considered to be a characteristic of atoms and the SMARTS for an amino group can be written as [NH2] . Charge is specified by the descriptors + and - as exemplified by the SMARTS [nH+] (protonated aromatic nitrogen atom) and [O-]C(=O)c (deprotonated aromatic carboxylic acid ).
A number of bond types can be specified: - (single), = (double), # (triple), : (aromatic) and ~ (any).
The X and D descriptors are used to specify the total numbers of connections (including implicit hydrogen atoms) and connections to explicit atoms, respectively. Thus [CX4] matches carbon atoms with bonds to any four other atoms while [CD4] matches quaternary carbon.
As originally defined by Daylight, the R descriptor is used to specify ring membership. In the Daylight model for cyclic systems, the smallest set of smallest rings (SSSR) [ 4 ] is used as a basis for ring membership. For example, indole is perceived as a 5-membered ring fused with a 6-membered ring rather than a 9-membered ring. The two carbon atoms that make up the ring fusion would match [cR2] and the other carbon atoms would match [cR1] .
The SSSR model has been criticised by OpenEye [ 5 ] who, in their implementation of SMARTS, use R to denote the number of ring bonds for an atom. The two carbon atoms in the ring fusion match [cR3] and the other carbons match [cR2] in the OpenEye implementation of SMARTS. Used without a number, R specifies an atom in a ring in both implementations, for example [CR] (aliphatic carbon atom in ring).
Lower case r specifies the size of the smallest ring of which the atom is a member. The carbon atoms of the ring fusion would both match [cr5] . Bonds can be specified as cyclic, for example C@C matches directly bonded atoms in a ring.
Four logical operators allow atom and bond descriptors to be combined. The 'and' operator ; can be used to define a protonated primary amine as [N;H3;+][C;X4] . The 'or' operator , has a higher priority so [c,n;H] defines (aromatic carbon or aromatic nitrogen) with implicit hydrogen. The 'and' operator & has higher priority than , so [c,n&H] defines aromatic carbon or (aromatic nitrogen with implicit hydrogen).
The 'not' operator ! can be used to define unsaturated aliphatic carbon as [C;!X4] and acyclic bonds as *-!@* .
Recursive SMARTS allow detailed specification of an atom's environment. For example, the more reactive (with respect to electrophilic aromatic substitution ) ortho and para carbon atoms of phenol can be defined as [$(c1c([OH])cccc1),$(c1ccc([OH])cc1)] .
A number of illustrative examples of SMARTS have been assembled by Daylight.
The definitions of hydrogen bond donors and acceptors used to apply Lipinski's Rule of Five [ 6 ] are easily coded in SMARTS. Donors are defined as nitrogen or oxygen atoms that have at least one directly bonded hydrogen atom:
Acceptors are defined as nitrogen or oxygen:
A simple definition of aliphatic amines that are likely to protonate at physiological pH can be written as the following recursive SMARTS:
In real applications the CX4 atoms would need to be defined more precisely to prevent matching against electron withdrawing groups such as CF 3 that would render the amine insufficiently basic to protonate at physiological pH .
SMARTS can be used to encode pharmacophore elements such as anionic centers. In the following example, recursive SMARTS notation is used to combine acid oxygen and tetrazole nitrogen in a definition of oxygen atoms that are likely to be anionic under normal physiological conditions.
The SMARTS above would only match the acid hydroxyl and the tetrazole N−H. When a carboxylic acid deprotonates the negative charge is delocalised over both oxygen atoms and it may be desirable to designate both as anionic. This can be achieved using the following SMARTS.
The precise and transparent substructural specification that SMARTS allows has been exploited in a number of applications.
Substructural filters defined in SMARTS have been used [ 7 ] to identify undesirable compounds when performing strategic pooling of compounds for high-throughput screening. The REOS (rapid elimination of swill) [ 8 ] procedure uses SMARTS to filter out reactive, toxic and otherwise undesirable moieties from databases of chemical structures.
RECAP [ 9 ] (Retrosynthetic Combinatorial Analysis Procedure) uses SMARTS to define bond types. RECAP is a molecule editor which generates fragments of structures by breaking bonds of defined types and the original link points in these are specified using isotopic labels. Searching databases of biologically active compounds for occurrences of fragments allows privileged structural motifs to be identified. The Molecular Slicer [ 10 ] is similar to RECAP and has been used to identify fragments that are commonly found in marketed oral drugs.
The Leatherface program [ 11 ] is a general purpose molecule editor which allows automated modification of a number of substructural features of molecules in databases, including protonation state, hydrogen count, formal charge, isotopic weight and bond order. The molecular editing rules used by Leatherface are defined in SMARTS. Leatherface can be used to standardise tautomeric and ionization states and to set and enumerate these in preparation of databases [ 12 ] for virtual screening . Leatherface has been used in Matched molecular pair analysis , which enables the effects of structural changes (e.g. substitution of hydrogen with chlorine) to be quantified, [ 13 ] over a range of structural types.
ALADDIN [ 14 ] is a pharmacophore matching program that uses SMARTS to define recognition points (e.g. neutral hydrogen bond acceptor) of pharmacophores. A key problem in pharmacophore matching is that functional groups that are likely to be ionised at physiological pH are typically registered in their neutral forms in structural databases. The ROCS shape matching program allows atom types to be defined using SMARTS. [ 15 ] | https://en.wikipedia.org/wiki/SMILES_arbitrary_target_specification |
SMIL Timesheets is a style sheet language which is intended for use as an external timing stylesheet for the Synchronized Multimedia Integration Language (SMIL), and is meant to separate the timing and presentation from the content inside the markup of another language (for instance, an SMIL Timesheet can be used to time an SMIL-enabled slideshow).
SMIL Timesheets 1.0 was released as a W3C Working Draft on 10 January 2008, with editors from members of the SYMM Working Group (under the W3C Synchronized Multimedia Activity committee). [ 1 ] On 29 March 2012, SMIL Timesheets 1.0 was moved out of the draft stage and was published. [ 2 ] [ 3 ] However, due to the lack of SMIL adoption, other alternatives have been implemented, including the use of CSS Animations to externally time and animate HTML pages into interactive slideshows.
This computing article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/SMIL_Timesheets |
An SMS gateway or MMS gateway allows a computer (also known as a Server) to send or receive text messages in the form of Short Message Service (SMS) or Multimedia Messaging Service (MMS) transmissions between local and/or international telecommunications networks. In most cases, SMS and MMS are eventually routed to a mobile phone through a wireless carrier. SMS gateways are commonly used as a method for person-to-person to device-to-person (also known as application-to-person) communications. Many SMS gateways support content and media conversions from email , push, voice, and other formats.
Several mobile telephone network operators have true fixed-wire SMS services. These are based on extensions to the European Telecommunications Standards Institute (ETSI) Global System for Mobile Communications (GSM) SMS standards and allow messaging between any mix of fixed and mobile equipment. These use frequency-shift keying to transfer the message between the terminal and the Short Message Service Center (SMSC). Terminals are usually based on Digital Enhanced Cordless Telecommunications (DECT), but wired handsets and wired text-only (no voice) devices exist. Messages are received by the terminal recognising that the Caller ID is that of the SMSC and going off-hook silently to receive the message.
A direct-to-mobile gateway is a device that has built-in wireless GSM connectivity. It allows SMS text messages to be sent and/or received by email, from Web pages or from other software applications by acquiring a unique identifier from the mobile phone's Subscriber Identity Module , or "SIM card". Direct-to-mobile gateways are different from SMS aggregators because they are installed on an organization's own network and connect to a local mobile network.
The connection to the mobile network is made by acquiring a SIM card number from the mobile operator and installing it in the gateway. Typically, direct-to-mobile gateway appliances are used for hundreds to thousands of text messages per month. More modern appliances now offer the capability of sending up to 100,000 messages each day. Several vendors that have historically provided GSM Gateway equipment for voice also have SMS capability. Some are more primitive than others. The more capable devices are designed with SIM management to regulate the number of SMS messages per SIM, ODBC to connect to a database, and HTTP interfaces to interact with third-party applications.
GSM gateway equipment is covered by the Wireless Telegraphy Act in the UK and can legally be used by any business to send SMS to their own customers or prospects when using their own gateway equipment. In Canada, SMS gateway providers are regulated by the Canadian Wireless Telecommunications Association (CWTA/txt.ca).
In India, it is regulated by the Telecom Regulatory Authority of India (TRAI).
In Pakistan, it is regulated by the Pakistan Telecommunication Authority (PTA).
A direct-to- short message service centre (SMSC) gateway is a software application, or a component within a software application, that connects directly to a mobile operator's SMSC via the Internet or direct leased line connections. The Short Message Peer-to-Peer (SMPP) protocol is typically used to convey SMS between an application and the SMSC. Direct-to-SMSC gateways are used by SMS aggregators to provide SMS services to their clients and large businesses who can justify such use. They are typically employed for high volume messaging and require a contract directly with a mobile operator.
An SMS gateway typically sits between the end-user who needs to send/receive SMS and a mobile network's SMSC. Such gateways provide their customers with a choice of protocols, including HTTP, SMTP, Short Message Peer-to-Peer and Web Services. Providers of SMS gateway services include SMS aggregators and mobile operators. SMS gateways are also available as part of messaging services such as AOL, ICQ and others.
In order to send/receive messages with mobile subscribers, an SMS gateway connects with (i) mobile network SMSCs and/or (ii) other SMS gateways. It is, therefore, possible that an SMS gateway has a combination of connections with mobile network SMSCs and connections with other SMS gateways in order to provide its services. However, there is an increasing potential for delivery problems with SMS with increasing number of SMS gateways in the delivery chain.
Text messages can be sent from a personal computer to mobile devices via an SMS gateway or Multimedia Messaging Service (MMS) gateway, using the most popular email client programs, such as Outlook, Thunderbird, and so on. The messages must be sent in ASCII "text-only" mode. If they are sent in HTML mode or using non-ASCII characters, they will most likely appear as nonsense on the recipient's mobile telephone.
Before the message can be sent, one must determine the domain of the mobile carrier's SMS gateway. For example, if one wants to send a message to a mobile telephone in the United States serviced by AT&T, and the telephone number is +1 415-123-4567, the email would be addressed as
To determine the SMS gateway domain, e.g. , txt.att.net , may require research - but most users know who their carrier is. The telephone number in this example for a US number is expressed as ten (10) digits, without the country code (1) and without dashes or other separator characters when composing the email address. The country code is not needed, as the 10-digit telephone number, together with the email domain, are sufficient to send the email from any location in the world.
It is useful to perform a character count before sending the message to ensure that it is within the 160-character limit. If it exceeds the limit, the SMS gateway should break the message into a set of consecutive 160-character, or shorter, messages to the mobile equipment, although breaks may occur in the middle of words.
A message sent with an email client can be simultaneously addressed to multiple mobile telephones - just as text messages sent in the usual manner between mobile telephones can be sent to multiple recipients.
SMS gateway domains for other carriers (US-based):
SMS gateway domains for Canadian carriers:
(Discontinued as of December 1, 2024 [19] )
There are several applications for SMS gateways, including: | https://en.wikipedia.org/wiki/SMS_gateway |
SMS hubbing is a new [ when? ] structure for the international flow of SMS between operators, reshaping the way that international mobile inter-operability works by implementing hubs to intermediate the SMS traffic and to offer a larger SMS coverage.
The GSM Association (GSMA) found in SMS Hubbing the solution to a problem that limits the continuing growth of international SMS, culminating to the development of the SMS Hubbing trials in 2006, part of the Open Connectivity project. This initiative created a new structure for international SMS interoperability, as well as developed standards and requirements that SMS hubs should follow. [ 1 ]
Regardless of the maturity of the operator or number of subscribers, each subscriber expects to be able to send an SMS to other subscribers, regardless of country and mobile network.
The lack of complete international SMS interoperability is caused by the way the GSM world is interconnected: each operator has a need to establish SMS interworking with all other mobile operators, meaning that international SMS can only transit from one operator to another if there is a bi-lateral roaming agreement in place.
While SMS interoperability is limited to bi-lateral interworking / roaming agreements between operators, it is unlikely that full international SMS reach will be achieved by setting up more and more agreements, which are time-consuming and costly to put in place. In addition to that, the revenue benefits of an extra interworking connection might not justify the investment required to set it up in the first place.
SMS hubbing enables a broad international SMS coverage for mobile operators (“client operators”) through the connection to independent hubs, who have multiple agreements in place with other operators, therefore being able to route messages on behalf of the client operators.
SMS Hubbing works with the same concept of voice connectivity model: rather than relying on costly and multiple individual agreements, voice traffic flows via telehouses, which are basically hubs for voice. In the same way, many operators connect to hubs to transit MMS messages, in an attempt to fix the many interoperability problems with this messaging technology. SMS Hubbing is about simplifying the SMS interworking system, by replacing much of the unproductive, identical investments in international agreements made traditionally by mobile operators. As well as this, SMS Hubbing is about providing a higher level of service to SMS, by introducing end-to-end quality of service through Service Level Agreements (SLAs) .
It is clear that SMS Hubbing does not replace bilateral agreements. Every operator has the need to establish roaming agreements in order to provide subscribers with the possibility to roam outside their home network. Outside this frame of main roaming agreements that generate the majority of international traffic for voice and messaging, it makes sense for mobile operators to allocate SMS traffic that belongs to non-connected destinations to an SMS hub.
With the SMS Hubbing model, an operator looking to increase their international SMS coverage does not need to manage multiple bi-lateral agreements. Mobile operators can simplify this by connecting to a hub. The SMS Hubbing model reduces complexity for operators, as well the cost for SMS interworking agreements. Mobile subscribers also take advantage of an enlarged SMS reach, being able to send and receive message to all countries and networks.
Ubiquity and simplicity in increasing SMS coverage
SMS Hubbing allows operators to manage a single legal, technical and billing relationship rather than hundreds of additional roaming agreements for SMS messaging only.
Mobile operators have been gradually outsourcing non-core functions to invest on areas that need a closer management of the operator, as well as focusing on areas that have a direct interface to customers. The hub concept follows this trend, removing a costly and complex area of technical interface and replacing it with a more efficient and effective outsourced solution.
Under the GSMA's SMS Hubbing structure, a hub will negotiate a transit fee with an originating operator on a per-SMS basis for the use of the hub. As is the usual practice, the originating operator will also pay a termination fee to the terminating operator, also on a per-SMS basis.
Beyond SMS, hubbing can be applied in different areas, such as MMS. Because of many interoperability problems, many operators generally connect to an MMS hub, which route the messages more efficiently on behalf of the operator. | https://en.wikipedia.org/wiki/SMS_hubbing |
SMS spoofing is a technology which uses the short message service (SMS), available on most mobile phones and personal digital assistants , to set who the message appears to come from by replacing the originating mobile number (Sender ID) with alphanumeric text. Spoofing has both legitimate uses (setting the company name from which the message is being sent, setting your own mobile number, or a product name) and illegitimate uses (such as impersonating another person, company, product). This can also send "mysterious" messages that look like they are from legitimate numbers or contacts.
SMS Spoofing occurs when a sender manipulates address information. Often it is done in order to impersonate a user that has roamed onto a foreign network and is submitting messages to the home network. Frequently, these messages are addressed to destinations outside the home network – with the home SMSC essentially being “hijacked” to send messages into other networks. In advanced cases they can even hijack existing contacts in a phone. In other words, the hijacker's message can appear to be coming from any number.
The impact of this activity is threefold:
The legitimate use cases for SMS spoofing include:
An SMS Spoofing attack is often first detected by an increase in the number of SMS errors encountered during a bill-run. These errors are caused by the spoofed subscriber identities. Operators can respond by blocking different source addresses in their Gateway- MSCs , but fraudsters can change addresses easily to by-pass these measures. If fraudsters move to using source addresses at a major interconnect partner, it may become unfeasible to block these addresses, due to the potential impact on normal interconnect services.
In 2007, the UK premium rate regulator, PhonepayPlus (formerly ICSTIS) concluded a public consultation on anonymous SMS, in which they stated they were not averse to the operation of such services. However, in 2008 PhonePayPlus introduced new regulation covering anonymous SMS, requiring anonymous SMS service providers to send a follow-up message to the recipient stating that a spoofed SMS has been sent to them, and operate a complaints helpline.
If a user can prove that their SMS sessions have been spoofed, they should contact both law enforcement and their cellular provider , who should be able to track where the SMS messages were actually sent from. A user may also modify the phone's settings so that only messages from authorized numbers are allowed. This is not always effective since hackers could be impersonating the user's friends as well. | https://en.wikipedia.org/wiki/SMS_spoofing |
Selective microfluidics-based ligand enrichment followed by sequencing (SMiLE-seq) is a technique developed for the rapid identification of DNA binding specificities and affinities of full length monomeric and dimeric transcription factors in a fast and semi-high-throughput fashion.
SMiLE-seq works by loading in vitro transcribed and translated “bait” transcription factors into a microfluidic device in combination with DNA molecules . Bound transcription factor-DNA complexes are then isolated from the device, which is followed by sequencing and then sequence data analysis to characterize binding motifs. Specialized software is used to determine the DNA binding properties of monomeric or dimeric transcription factors to help predict their in vivo DNA binding activity.
SMiLE-seq combines three important functions differing from existing techniques: (1) The use of capillary pumps to optimize the loading of samples, (2) Trapping molecular interactions on the surface of the microfluidic device through immunocapture of target transcription factors, (3) Enabling the selection of DNA that is specifically bound to transcription factors from a pool of random DNA sequences . [ 1 ]
Elucidating the regulatory mechanisms used to govern essential cellular processes is an important branch of research. Cellular regulatory networks can be very complex and often involve the coordination of multiple processes that begin with the modulation of gene expression . The binding of transcription factor molecules to DNA, either alone or in combination with other transcription factors, is used to control gene expression in response to both intra- and extracellular stimuli.
Characterizing the binding mechanisms and specificities of transcription factors to specific regions of DNA – and identifying these transcription factors – is a fundamental component of the process of resolving cellular regulatory dynamics. [ 2 ] Before the introduction of SMiLE-seq technology, ChIP-seq (chromatin immunoprecipitation sequencing) and HT- SELEX (high throughput systematic evolution of ligands by exponential enrichment) technologies were used to successfully characterize nearly 500 transcription factor-DNA binding interactions. [ 1 ]
It is estimated that fewer than 50% of the transcription factors present in humans have been described in previous techniques. The development of SMiLE-seq technology has provided an additional method with the potential to facilitate identification and characterization of previously undescribed transcription factor-DNA binding interactions. [ 1 ]
SMiLE-seq uses a microfluidic device into which transcription factors, which have been transcribed and translated in vitro , are loaded. Transcription factor samples (~0.3 ng) are modified by the addition of an enhanced green fluorescent protein (eGFP) tag and combined with both target double-stranded DNA molecules (~8 pmol) tagged with Cyanine Dye5 (Cy5) and a double-stranded competitive DNA model, poly-dIdC, which operates as a negative control to limit spurious binding interactions.
When multiple transcription factors are simultaneously analyzed (e.g., when characterization of potential heterodimeric binding interactions is performed), each transcription factor is tagged with a correspondingly unique fluorescent tag. Samples are pumped through the microfluidic device in a passive, twenty-minute process that utilizes capillary action in a series of parallel channels. eGFP-tagged transcription factors are immunocaptured using anchored biotinylated anti-eGFP antibodies.
Mechanical depression of a button traps bound transcription factor-DNA complexes, and fluorescent analysis is performed. Fluorescent readouts that identify the presence of multiple fluorescent tags associated with a single antibody indicate heterodimeric binding interactions. The presence of DNA is confirmed by Cy5 signal detection. A polydimethylsiloxane membrane on the button surface captures successfully bound transcription factor-DNA complexes, while unbound transcription factors and targets are washed away.
Following the removal of unbound components, bound DNA molecules are collected, pooled, and amplified. Sequencing is subsequently performed using NextSeq 500 or HiSeq2000 sequencing lanes. Sequence data is used to develop a seed sequence, which is then probed for functional motifs using a uniquely developed hidden Markov model -based software pipeline. [ 1 ]
The use of microfluidics in SMiLE-seq offers three main advantages when compared to current techniques used to measure protein-DNA interactions (e.g., ChIP-seq, HT-SELEX, and protein binding microarrays ).
The ability of many transcription factors to bind DNA is dependent on heterodimer formation, and therefore requires the presence of a specific dimer partner for binding. This has been shown to yield incomplete results if transcription factors are individually tested. Heterodimer combinations have been shown to range from 3000 to 25000, and many remain uncharacterized.
A technology like SMiLE-seq, which is able to detect these dimeric interactions, may help broaden current knowledge and characterization of transcription factor-DNA binding profiles. Additionally, previous technologies have used transcription factor probes in their truncated form, which may reduce their ability to bind and dimerize. SMiLE-seq enables robust identification of DNA binding specificities of full length, previously uncharacterized transcription factors. Furthermore, SMiLE-seq is able to identify transcription factor binding sites over a wide range of binding affinities, which represents a significant limitation of other technologies.
The primary limitation of SMiLE-seq is that the technique can only be used to characterize the binding interactions of previously identified transcription factors, as the method requires in vitro transcription and translation of the transcription factors prior to their combination with DNA molecules. Additionally, previous studies have shown that fluorescent protein tags can affect the binding affinity of proteins to their targets. [ 5 ]
The effect of the specific fluorescent protein tags on binding affinity would have to be investigated to determine whether this would impact specific protein-DNA interactions found using this technology. Further development of SMiLE-seq may involve modifying transcription factor expression conditions to increase the success of analysis. [ 1 ] | https://en.wikipedia.org/wiki/SMiLE-Seq |
In coordination chemistry , the S N 1cB (conjugate base) mechanism describes the pathway by which many metal amine complexes undergo substitution, that is, ligand exchange. Typically, the reaction entails reaction of a polyamino metal halide with aqueous base to give the corresponding polyamine metal hydroxide: [ 1 ]
The rate law for the reaction is:
The rate law is deceptive: hydroxide serves not as a nucleophile but as a base to deprotonate the coordinated ammonia. Simultaneously with deprotonation, the halide dissociates . Water binds to the coordinatively unsaturated complex followed by proton transfer to give the hydroxy complex. The conjugate base resulting from deprotonation of the amine is rarely observed. [ 2 ] | https://en.wikipedia.org/wiki/SN1CB_mechanism |
The unimolecular nucleophilic substitution ( S N 1 ) reaction is a substitution reaction in organic chemistry . The Hughes-Ingold symbol of the mechanism expresses two properties—"S N " stands for " nucleophilic substitution ", and the "1" says that the rate-determining step is unimolecular . [ 1 ] [ 2 ] Thus, the rate equation is often shown as having first-order dependence on the substrate and zero-order dependence on the nucleophile . This relationship holds for situations where the amount of nucleophile is much greater than that of the intermediate. Instead, the rate equation may be more accurately described using steady-state kinetics . The reaction involves a carbocation intermediate and is commonly seen in reactions of secondary or tertiary alkyl halides under strongly basic conditions or, under strongly acidic conditions, with secondary or tertiary alcohols . With primary and secondary alkyl halides, the alternative S N 2 reaction occurs. In inorganic chemistry , the S N 1 reaction is often known as the dissociative substitution . This dissociation pathway is well-described by the cis effect . A reaction mechanism was first introduced by Christopher Ingold et al. in 1940. [ 3 ] This reaction does not depend much on the strength of the nucleophile, unlike the S N 2 mechanism. This type of mechanism involves two steps. The first step is the ionization of alkyl halide in the presence of aqueous acetone or ethyl alcohol. This step provides a carbocation as an intermediate.
In the first step of S N 1 mechanism, a carbocation is formed which is planar and hence attack of nucleophile (second step) may occur from either side to give a racemic product, but actually complete racemization does not take place. This is because the nucleophilic species attacks the carbocation even before the departing halides ion has moved sufficiently away from the carbocation. The negatively charged halide ion shields the carbocation from being attacked on the front side, and backside attack, which leads to inversion of configuration, is preferred. Thus the actual product no doubt consists of a mixture of enantiomers but the enantiomers with inverted configuration would predominate and complete racemization does not occur. [ 4 ]
An example of a reaction taking place with an S N 1 reaction mechanism is the hydrolysis of tert-butyl bromide forming tert -butanol :
This S N 1 reaction takes place in three steps:
Although the rate law of the S N 1 reaction is often regarded as being first order in alkyl halide and zero order in nucleophile, this is a simplification that holds true only under certain conditions. While it, too, is an approximation, the rate law derived from the steady state approximation (SSA) provides more insight into the kinetic behavior of the S N 1 reaction. Consider the following reaction scheme for the mechanism shown above:
Though a relatively stable tertiary carbocation , tert -butyl cation is a high-energy species that is present only at very low concentration and cannot be directly observed under normal conditions. Thus, the SSA can be applied to this species:
(1) Steady state assumption: d [ tBu + ] d t = 0 = k 1 [ tBuBr ] − k − 1 [ tBu + ] [ Br − ] − k 2 [ tBu + ] [ H 2 O ] {\displaystyle {\frac {d[{\text{tBu}}^{+}]}{dt}}=0=k_{1}[{\text{tBuBr}}]-k_{-1}[{\text{tBu}}^{+}][{\text{Br}}^{-}]-k_{2}[{\text{tBu}}^{+}][{\text{H}}_{2}{\text{O}}]}
(2) Concentration of t-butyl cation, based on steady state assumption: [ tBu + ] = k 1 [ tBuBr ] k − 1 [ Br − ] + k 2 [ H 2 O ] {\displaystyle [{\text{tBu}}^{+}]={\frac {k_{1}[{\text{tBuBr}}]}{k_{-1}[{\text{Br}}^{-}]+k_{2}[{\text{H}}_{2}{\text{O}}]}}}
(3) Overall reaction rate, assuming rapid final step: d [ tBuOH ] d t = k 2 [ tBu + ] [ H 2 O ] {\displaystyle {\frac {d[{\text{tBuOH}}]}{dt}}=k_{2}[{\text{tBu}}^{+}][{\text{H}}_{2}{\text{O}}]}
(4) Steady state rate law, by plugging (2) into (3): d [ tBuOH ] d t = k 1 k 2 [ tBuBr ] [ H 2 O ] k − 1 [ Br − ] + k 2 [ H 2 O ] {\displaystyle {\frac {d[{\text{tBuOH}}]}{dt}}={\frac {k_{1}k_{2}[{\text{tBuBr}}][{\text{H}}_{2}{\text{O}}]}{k_{-1}[{\text{Br}}^{-}]+k_{2}[{\text{H}}_{2}{\text{O}}]}}}
Under normal synthetic conditions, the entering nucleophile is more nucleophilic than the leaving group and is present in excess. Moreover, kinetic experiments are often conducted under initial rate conditions (5 to 10% conversion) and without the addition of bromide, so [ Br − ] {\displaystyle [{\text{Br}}^{-}]} is negligible. For these reasons, k − 1 [ Br − ] ≪ k 2 [ H 2 O ] {\displaystyle k_{-1}[{\text{Br}}^{-}]\ll k_{2}[{\text{H}}_{2}{\text{O}}]} often holds. Under these conditions, the SSA rate law reduces to:
rate = d [ tBuOH ] d t = k 1 k 2 [ tBuBr ] [ H 2 O ] k 2 [ H 2 O ] = k 1 [ tBuBr ] {\displaystyle {\text{rate}}={\frac {d[{\text{tBuOH}}]}{dt}}={\frac {k_{1}k_{2}[{\text{tBuBr}}][{\text{H}}_{2}{\text{O}}]}{k_{2}[{\text{H}}_{2}{\text{O}}]}}=k_{1}[{\text{tBuBr}}]}
the simple first-order rate law described in introductory textbooks. Under these conditions, the concentration of the nucleophile does not affect the rate of the reaction, and changing the nucleophile (e.g. from H 2 O to MeOH) does not affect the reaction rate, though the product is, of course, different. In this regime, the first step (ionization of the alkyl bromide) is slow, rate-determining, and irreversible, while the second step (nucleophilic addition) is fast and kinetically invisible.
However, under certain conditions, non-first-order reaction kinetics can be observed. In particular, when a large concentration of bromide is present while the concentration of water is limited, the reverse of the first step becomes important kinetically. As the SSA rate law indicates, under these conditions there is a fractional (between zeroth and first order) dependence on [H 2 O], while there is a negative fractional order dependence on [Br – ]. Thus, S N 1 reactions are often observed to slow down when an exogenous source of the leaving group (in this case, bromide) is added to the reaction mixture. This is known as the common ion effect and the observation of this effect is evidence for an S N 1 mechanism (although the absence of a common ion effect does not rule it out). [ 6 ] [ 7 ]
The S N 1 mechanism tends to dominate when the central carbon atom is surrounded by bulky groups because such groups sterically hinder the S N 2 reaction. Additionally, bulky substituents on the central carbon increase the rate of carbocation formation because of the relief of steric strain that occurs. The resultant carbocation is also stabilized by both inductive stabilization and hyperconjugation from attached alkyl groups. The Hammond–Leffler postulate suggests that this, too, will increase the rate of carbocation formation. The S N 1 mechanism therefore dominates in reactions at tertiary alkyl centers.
An example of a reaction proceeding in a S N 1 fashion is the synthesis of 2,5-dichloro-2,5-dimethylhexane from the corresponding diol with concentrated hydrochloric acid : [ 8 ]
As the alpha and beta substitutions increase with respect to leaving groups, the reaction is diverted from S N 2 to S N 1.
The carbocation intermediate formed in the reaction's rate determining step (RDS) is an sp 2 hybridized carbon with trigonal planar molecular geometry. This allows two different ways for the nucleophilic attack, one on either side of the planar molecule. If neither approach is favored, then these two ways occur equally, yielding a racemic mixture of enantiomers if the reaction takes place at a stereocenter. [ 9 ] This is illustrated below in the S N 1 reaction of S-3-chloro-3-methylhexane with an iodide ion, which yields a racemic mixture of 3-iodo-3-methylhexane:
However, an excess of one stereoisomer can be observed, as the leaving group can remain in proximity to the carbocation intermediate for a short time and block nucleophilic attack. This stands in contrast to the S N 2 mechanism, which is a stereospecific mechanism where stereochemistry is always inverted as the nucleophile comes in from the rear side of the leaving group.
Two common side reactions are elimination reactions and carbocation rearrangement . If the reaction is performed under warm or hot conditions (which favor an increase in entropy), E1 elimination is likely to predominate, leading to formation of an alkene . At lower temperatures, S N 1 and E1 reactions are competitive reactions and it becomes difficult to favor one over the other. Even if the reaction is performed cold, some alkene may be formed. If an attempt is made to perform an S N 1 reaction using a strongly basic nucleophile such as hydroxide or methoxide ion, the alkene will again be formed, this time via an E2 elimination . This will be especially true if the reaction is heated. Finally, if the carbocation intermediate can rearrange to a more stable carbocation, it will give a product derived from the more stable carbocation rather than the simple substitution product.
Since the S N 1 reaction involves formation of an unstable carbocation intermediate in the rate-determining step (RDS), anything that can facilitate this process will speed up the reaction. The normal solvents of choice are both polar (to stabilize ionic intermediates in general) and protic solvents (to solvate the leaving group in particular). Typical polar protic solvents include water and alcohols, which will also act as nucleophiles, and the process is known as solvolysis.
The Y scale correlates solvolysis reaction rates of any solvent ( k ) with that of a standard solvent (80% v/v ethanol / water ) ( k 0 ) through
with m a reactant constant (m = 1 for tert -butyl chloride ) and Y a solvent parameter. [ 10 ] For example, 100% ethanol gives Y = −2.3, 50% ethanol in water Y = +1.65 and 15% concentration Y = +3.2. [ 11 ] | https://en.wikipedia.org/wiki/SN1_reaction |
The bimolecular nucleophilic substitution ( S N 2 ) is a type of reaction mechanism that is common in organic chemistry . In the S N 2 reaction, a strong nucleophile forms a new bond to an sp 3 -hybridised carbon atom via a backside attack, all while the leaving group detaches from the reaction center in a concerted (i.e. simultaneous) fashion.
The name S N 2 refers to the Hughes-Ingold symbol of the mechanism: "S N " indicates that the reaction is a nucleophilic substitution , and "2" that it proceeds via a bimolecular mechanism, which means both the reacting species are involved in the rate-determining step . What distinguishes S N 2 from the other major type of nucleophilic substitution, the S N 1 reaction , is that the displacement of the leaving group, which is the rate-determining step, is separate from the nucleophilic attack in S N 1.
The S N 2 reaction can be considered as an organic-chemistry analogue of the associative substitution from the field of inorganic chemistry .
The reaction most often occurs at an aliphatic sp 3 carbon center with an electronegative , stable leaving group attached to it, which is frequently a halogen (often denoted X). The formation of the C–Nu bond, due to attack by the nucleophile (denoted Nu), occurs together with the breakage of the C–X bond. The reaction occurs through a transition state in which the reaction center is pentacoordinate and approximately sp 2 -hybridised.
The S N 2 reaction can be viewed as a HOMO–LUMO interaction between the nucleophile and substrate. The reaction occurs only when the occupied lone pair orbital of the nucleophile donates electrons to the unfilled σ* antibonding orbital between the central carbon and the leaving group . Throughout the course of the reaction, a p orbital forms at the reaction center as the result of the transition from the molecular orbitals of the reactants to those of the products. [ 1 ]
To achieve optimal orbital overlap, the nucleophile attacks 180° relative to the leaving group, resulting in the leaving group being pushed off the opposite side and the product formed with inversion of tetrahedral geometry at the central atom.
For example, the synthesis of macrocidin A, a fungal metabolite , involves an intramolecular ring closing step via an S N 2 reaction with a phenoxide group as the nucleophile and a halide as the leaving group, forming an ether . [ 2 ] Reactions such as this, with an alkoxide as the nucleophile, are known as the Williamson ether synthesis .
If the substrate that is undergoing S N 2 reaction has a chiral centre , then inversion of configuration ( stereochemistry and optical activity ) may occur; this is called the Walden inversion . For example, 1-bromo-1-fluoroethane can undergo nucleophilic attack to form 1-fluoroethan-1-ol, with the nucleophile being an HO − group. In this case, if the reactant is levorotatory, then the product would be dextrorotatory, and vice versa. [ 3 ]
The four factors that affect the rate of the reaction, in the order of decreasing importance, are: [ 4 ] [ 5 ]
The substrate plays the most important part in determining the rate of the reaction. For S N 2 reaction to occur more quickly, the nucleophile must easily access the sigma antibonding orbital between the central carbon and leaving group.
S N 2 occurs more quickly with substrates that are more sterically accessible at the central carbon, i.e. those that do not have as much sterically hindering substituents nearby. Methyl and primary substrates react the fastest, followed by secondary substrates. Tertiary substrates do not react via the S N 2 pathway, as the greater steric hindrance between the nucleophile and nearby groups of the substrate will leave the S N 1 reaction to occur first.
Substrates with adjacent pi C=C systems can favor both S N 1 and S N 2 reactions. In S N 1, allylic and benzylic carbocations are stabilized by delocalizing the positive charge. In S N 2, however, the conjugation between the reaction centre and the adjacent pi system stabilizes the transition state. Because they destabilize the positive charge in the carbocation intermediate, electron-withdrawing groups favor the S N 2 reaction. Electron-donating groups favor leaving-group displacement and are more likely to react via the S N 1 pathway. [ 1 ]
Like the substrate, steric hindrance affects the nucleophile's strength. The methoxide anion, for example, is both a strong base and nucleophile because it is a methyl nucleophile, and is thus very much unhindered. tert -Butoxide , on the other hand, is a strong base, but a poor nucleophile, because of its three methyl groups hindering its approach to the carbon. Nucleophile strength is also affected by charge and electronegativity : nucleophilicity increases with increasing negative charge and decreasing electronegativity. For example, OH − is a better nucleophile than water, and I − is a better nucleophile than Br − (in polar protic solvents). In a polar aprotic solvent, nucleophilicity increases up a column of the periodic table as there is no hydrogen bonding between the solvent and nucleophile; in this case nucleophilicity mirrors basicity. I − would therefore be a weaker nucleophile than Br − because it is a weaker base. Verdict - A strong/anionic nucleophile always favours S N 2 manner of nucleophillic substitution.
Good leaving groups on the substrate lead to faster S N 2 reactions. A good leaving group must be able to stabilize the electron density that comes from breaking its bond with the carbon center. This leaving group ability trend corresponds well to the p K a of the leaving group's conjugate acid (p K aH ); the lower its p K aH value, the faster the leaving group is displaced.
Leaving groups that are neutral, such as water , alcohols ( R−OH ), and amines ( R−NH 2 ), are good examples because of their positive charge when bonded to the carbon center prior to nucleophilic attack. Halides ( Cl − , Br − , and I − , with the exception of F − ), serve as good anionic leaving groups because electronegativity stabilizes additional electron density; the fluoride exception is due to its strong bond to carbon.
Leaving group reactivity of alcohols can be increased with sulfonates , such as tosylate ( − OTs ), triflate ( − OTf ), and mesylate ( − OMs ). Poor leaving groups include hydroxide ( − OH ), alkoxides ( − OR ), and amides ( − NR 2 ).
The Finkelstein reaction is one S N 2 reaction in which the leaving group can also act as a nucleophile. In this reaction, the substrate has a halogen atom exchanged with another halogen. As the negative charge is more-or-less stabilized on both halides, the reaction occurs at equilibrium.
The solvent affects the rate of reaction because solvents may or may not surround a nucleophile, thus hindering or not hindering its approach to the carbon atom. [ 6 ] Polar aprotic solvents , like tetrahydrofuran , are better solvents for this reaction than polar protic solvents because polar protic solvents will hydrogen bond to the nucleophile, hindering it from attacking the carbon with the leaving group. A polar aprotic solvent with low dielectric constant or a hindered dipole end will favour S N 2 manner of nucleophilic substitution reaction. Examples: dimethylsulfoxide , dimethylformamide , acetone , etc. In parallel, solvation also has a significant impact on the intrinsic strength of the nucleophile, in which strong interactions between solvent and the nucleophile, found for polar protic solvents , furnish a weaker nucleophile. In contrast, polar aprotic solvents can only weakly interact with the nucleophile, and thus, are to a lesser extent able to reduce the strength of the nucleophile. [ 7 ] [ 8 ]
The rate of an S N 2 reaction is second order , as the rate-determining step depends on the nucleophile concentration, [Nu − ] as well as the concentration of substrate, [RX]. [ 1 ]
This is a key difference between the S N 1 and S N 2 mechanisms. In the S N 1 reaction the nucleophile attacks after the rate-limiting step is over, whereas in S N 2 the nucleophile forces off the leaving group in the limiting step. In other words, the rate of S N 1 reactions depend only on the concentration of the substrate while the S N 2 reaction rate depends on the concentration of both the substrate and nucleophile. [ 1 ]
It has been shown [ 9 ] that except in uncommon (but predictable cases) primary and secondary substrates go exclusively by the S N 2 mechanism while tertiary substrates go via the S N 1 reaction. There are two factors which complicate determining the mechanism of nucleophilic substitution reactions at secondary carbons:
The examples in textbooks of secondary substrates going by the S N 1 mechanism invariably involve the use of bromide (or other good nucleophile) as the leaving group have confused the understanding of alkyl nucleophilic substitution reactions at secondary carbons for 80 years [3] . Work with the 2-adamantyl system (S N 2 not possible) by Schleyer and co-workers, [ 11 ] the use of azide (an excellent nucleophile but very poor leaving group) by Weiner and Sneen, [ 12 ] [ 13 ] the development of sulfonate leaving groups (non-nucleophilic good leaving groups), and the demonstration of significant experimental problems in the initial claim of an S N 1 mechanism in the solvolysis of optically active 2-bromooctane by Hughes et al. [ 14 ] [3] have demonstrated conclusively that secondary substrates go exclusively (except in unusual but predictable cases) by the S N 2 mechanism.
A common side reaction taking place with S N 2 reactions is E2 elimination : the incoming anion can act as a base rather than as a nucleophile, abstracting a proton and leading to formation of the alkene . This pathway is favored with sterically hindered nucleophiles. Elimination reactions are usually favoured at elevated temperatures [ 15 ] because of increased entropy . This effect can be demonstrated in the gas-phase reaction between a phenolate and a simple alkyl bromide taking place inside a mass spectrometer : [ 16 ] [ 17 ]
With ethyl bromide , the reaction product is predominantly the substitution product. As steric hindrance around the electrophilic center increases, as with isobutyl bromide, substitution is disfavored and elimination is the predominant reaction. Other factors favoring elimination are the strength of the base. With the less basic benzoate substrate, isopropyl bromide reacts with 55% substitution. In general, gas phase reactions and solution phase reactions of this type follow the same trends, even though in the first, solvent effects are eliminated.
A development attracting attention in 2008 concerns a S N 2 roundabout mechanism observed in a gas-phase reaction between chloride ions and methyl iodide with a special technique called crossed molecular beam imaging . When the chloride ions have sufficient velocity, the initial collision of it with the methyl iodide molecule causes the methyl iodide to spin around once before the actual S N 2 displacement mechanism takes place. [ 18 ] [ 19 ] [ 20 ] | https://en.wikipedia.org/wiki/SN2_reaction |
In computing , SNA (Sandybridge's New Acceleration) is a graphics acceleration architecture for the X.Org Server developed by Intel as a replacement for UXA . [ 1 ]
This computing article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/SNA_(computer_graphics) |
Thiazyl trifluoride is a chemical compound of nitrogen , sulfur , and fluorine , having the formula NSF 3 . It exists as a stable, colourless gas, and is an important precursor to other sulfur-nitrogen-fluorine compounds. [ 2 ] It has tetrahedral molecular geometry around the sulfur atom, and is regarded to be a prime example of a compound that has a sulfur-nitrogen triple bond . [ 3 ]
NSF 3 can be synthesised by the fluorination of thiazyl fluoride , NSF, with silver(II) fluoride , AgF 2 :
or by the oxidative decomposition of FC(O)NSF 2 by silver(II) fluoride: [ 4 ]
It is also a product of the oxidation of ammonia by S 2 F 10 . [ 5 ]
Direct fluorination of mercury difluorosulfinimide (Hg(NSF 2 ) 2 ) does not give thiazyl trifluoride, but instead the isomeric fluoriminosulfur difluoride (F 2 SNF). [ 6 ]
NSF 3 is much more stable than thiazyl fluoride, does not react with ammonia and hydrogen chloride , and only reacts with sodium at 400 °C. [ 7 ] However, the fluoride ligands are labile, and can be displaced by secondary amines . [ 6 ] Thiazyl trifluoride reacts with carbonyl fluoride ( COF 2 ) in the presence of hydrogen fluoride to form pentafluorosulfanyl isocyanate ( SF 5 NCO ). [ 8 ] | https://en.wikipedia.org/wiki/SNF3 |
The SNOX process is a process which removes sulfur dioxide , nitrogen oxides and particulates from flue gases . The sulfur is recovered as concentrated sulfuric acid and the nitrogen oxides are reduced to free nitrogen. The process is based on the well-known wet sulfuric acid process (WSA), a process for recovering sulfur from various process gasses in the form of commercial quality sulfuric acid (H 2 SO 4 ). [ 1 ] [ 2 ] [ 3 ]
The SNOX process is based on catalytic reactions and does not consume water or absorbents. Neither does it produce any waste, except for the separated dust.
In addition the process can handle other sulfurous waste streams. This is highly interesting in refineries, where e.g. hydrogen sulfide (H 2 S) gas, sour water stripper gas and Claus tail gas can be led to the SNOX plant, and thereby investment in other waste gas handling facilities can be saved.
The SNOX process includes the following steps:
The SNOX process developed by Haldor Topsoe has been specifically designed for power and steam generation plants to remove sulfur and nitrogen oxides from combustion of heavy residuals, petroleum coke , sour gasses , or other waste products from refineries.
Today, refineries are struggling to find ways to dispose of their increasing amount of sulfurous streams and waste products. Large amounts of high-sulfur residuals, particularly heavy oil and petroleum coke, are being produced and sold as fuel to the marine market or the cement industry. These off-take markets are, however, changing due to environmental constraints, and new markets have to be identified. One attractive option would be to use these residual fuels to produce power and steam, leaving behind the issue of emissions to be addressed. The SNOX technology is especially suitable for cleaning flue gases from combustion of high-sulfur fuels in refineries. The SNOX process is a very energy-efficient way to convert the NOx in the flue gas into nitrogen and the SOx into concentrated sulfuric acid of commercial quality without using any absorbents and without producing waste products or waste water. Along with the flue gases, other sulfurous waste streams from a refinery can be treated, such as H 2 S gas, sour water stripping (SWS) gas, Claus tail gas and elemental sulfur, potentially turning this technology into a complete sulfur management system.
Possible configurations:
The SNOX process can be applied for treatment of flue gases from combustion of primarily high-sulfur fuels in power stations, refinery and other industrial boilers and for treatment of other waste gases containing sulfur compounds and nitrogen oxides.
The first full scale plant treating 1,000,000 Nm³/h flue gas from a 300 MW coal-fired power plant in Denmark was started up in 1991.
The largest SNOX plant in operation treats 1,200,000 Nm³/h flue gas from four petroleum coke fired boilers at a refinery in Sicily, Italy .
The process catalytically reduces both the SO 2 and the NO x in flue gases by more than 95% and with integration of the recovered heat from the WSA condenser it is reported to have lower operating costs than conventional technologies. [ 4 ] [ 5 ]
Recycling of hot combustion air from the SNOX plants to the boilers in combination with high pressure steam production in the SNOX plants increase the thermal efficiency and output of the boilers, resulting in a proportional reduction in CO 2 emission.
In several places there is a need for both electric power and sulfuric acid. A cheap high-sulfur fuel such as petroleum coke can be used for power generation, while the flue gas is cleaned in an SNOX plant producing sulfuric acid. Elemental sulfur is fired in the SNOX plant in order to produce the desired amount of sulfuric acid. | https://en.wikipedia.org/wiki/SNOX_process |
Single nucleotide polymorphism annotation ( SNP annotation) is the process of predicting the effect or function of an individual SNP using SNP annotation tools. In SNP annotation the biological information is extracted, collected and displayed in a clear form amenable to query. SNP functional annotation is typically performed based on the available information on nucleic acid and protein sequences . [ 1 ]
Single nucleotide polymorphisms (SNPs) play an important role in genome wide association studies because they act as primary biomarkers . SNPs are currently the marker of choice due to their large numbers in virtually all populations of individuals. The location of these biomarkers can be tremendously important in terms of predicting functional significance, genetic mapping and population genetics . [ 3 ] Each SNP represents a nucleotide change between two individuals at a defined location. SNPs are the most common genetic variant found in all individual with one SNP every 100–300 bp in some species . [ 4 ] Since there is a massive number of SNPs on the genome , there is a clear need to prioritize SNPs according to their potential effect in order to expedite genotyping and analysis. [ 5 ]
Annotating large numbers of SNPs is a difficult and complex process, which need computational methods to handle such a large dataset. Many tools available have been developed for SNP annotation in different organisms: some of them are optimized for use with organisms densely sampled for SNPs (such as humans ), but there are currently few tools available that are species non-specific or support non-model organism data. The majority of SNP annotation tools provide computationally predicted putative deleterious effects of SNPs. These tools examine whether a SNP resides in functional genomic regions such as exons, splice sites, or transcription regulatory sites, and predict the potential corresponding functional effects that the SNP may have using a variety of machine-learning approaches. But the tools and systems that prioritize functionally significant SNPs, suffer from few limitations: First, they examine the putative deleterious effects of SNPs with respect to a single biological function that provide only partial information about the functional significance of SNPs. Second, current systems classify SNPs into deleterious or neutral group. [ 6 ]
Rare variants are defined as single nucleotide polymorphisms (SNPs) with a minor allele frequency (MAF) of less than 0.01. [ 7 ] As a consequence, training data for the corresponding prediction methods may be different and hence one should be careful to select the appropriate tool for a specific purpose. For the purposes of this article, "SNP" will be used to mean both SNP and SNV, but readers should bear in mind the differences.
For SNP annotation, many kinds of genetic and genomic information are used. Based on the different features used by each annotation tool, SNP annotation methods may be split roughly into the following categories:
Genomic information from surrounding genomic elements is among the most useful information for interpreting the biological function of an observed variant. Information from a known gene is used as a reference to indicate whether the observed variant resides in or near a gene and if it has the potential to disrupt the protein sequence and its function. Gene based annotation is based on the fact that non-synonymous mutations can alter the protein sequence and that splice site mutation may disrupt the transcript splicing pattern. [ 8 ]
Knowledge base annotation is done based on the information of gene attribute, protein function and its metabolism . In this type of annotation more emphasis is given to genetic variation that disrupts the protein function domain, protein-protein interaction and biological pathway . The non-coding region of genome contain many important regulatory elements including promoter , enhancer and insulator, any kind of change in this regulatory region can change the functionality of that protein. [ 9 ] The mutation in DNA can change the RNA sequence and then influence the RNA secondary structure , RNA binding protein recognition and miRNA binding activity. [ 10 ] [ 11 ]
This method mainly identifies variant function based on the information whether the variant loci are in the known functional region that harbor genomic or epigenomic signals. The function of non-coding variants are extensive in terms of the affected genomic region and they involve in almost all processes of gene regulation from transcriptional to post translational level [ 12 ]
Transcriptional gene regulation process depends on many spatial and temporal factors in the nucleus such as global or local chromatin states, nucleosome positioning, TF binding, enhancer/promoter activities. Variant that alter the function of any of these biological processes may alter the gene regulation and cause phenotypic abnormality. [ 13 ] Genetic variants that located in distal regulatory region can affect the binding motif of TFs, chromatin regulators and other distal transcriptional factors, which disturb the interaction between enhancer/silencer and its target gene. [ 14 ]
Alternative splicing is one of the most important components that show functional complexity of genome. Modified splicing has significant effect on the phenotype that is relevance to disease or drug metabolism. A change in splicing can be caused by modifying any of the components of the splicing machinery such as splice sites or splice enhancers or silencers. [ 15 ] Modification in the alternative splicing site can lead to a different protein form which will show a different function. Humans use an estimated 100,000 different proteins or more, so some genes must be capable of coding for a lot more than just one protein. Alternative splicing occurs more frequently than was previously thought and can be hard to control; genes may produce tens of thousands of different transcripts, necessitating a new gene model for each alternative splice.
Mutations in the untranslated region (UTR) affect many post-transcriptional regulation . Distinctive structural features are required for many RNA molecules and cis-acting regulatory elements to execute effective functions during gene regulation. SNVs can alter the secondary structure of RNA molecules and then disrupt the proper folding of RNAs, such as tRNA/mRNA/lncRNA folding and miRNA binding recognition regions. [ 16 ]
Single nucleotide variant can also affect the cis-acting regulatory elements in mRNA's to inhibit/promote the translation initiation. Change in the synonymous codons region due to mutation may affect the translation efficiency because of codon usage biases. The translation elongation can also be retarded by mutations along the ramp of ribosomal movement. In the post-translational level, genetic variants can contribute to proteostasis and amino acid modifications. However, mechanisms of variant effect in this field are complicated and there are only a few tools available to predict variant's effect on translation related modifications. [ 8 ]
Non-synonymous is the variant in exons that change the amino acid sequence encoded by the gene, including single base changes and non frameshift indels. It has been extremely investigated the function of non-synonymous variants on protein and many algorithms have been developed to predict the deleteriousness and pathogenesis of single nucleotide variants (SNVs). Classical bioinformatics tools, such as SIFT, Polyphen and MutationTaster , successfully predict the functional consequence of non-synonymous substitution. [ 17 ] [ 18 ] [ 19 ] [ 20 ] PopViz webserver provides a gene-centric approach to visualize the mutation damage prediction scores (CADD, SIFT, PolyPhen-2) or the population genetics (minor allele frequency) versus the amino acid positions of all coding variants of a certain human gene. [ 21 ] PopViz is also cross-linked with UniProt database, where the protein domain information can be found, and to then identify the predicted deleterious variants fall into these protein domains on the PopViz plot. [ 21 ]
Comparative genomics approaches were used to predict the function-relevant variants under the assumption that the functional genetic locus should be conserved across different species at an extensive phylogenetic distance. On the other hand, some adaptive traits and the population differences are driven by positive selections of advantageous variants, and these genetic mutations are functionally relevant to population specific phenotypes. Functional prediction of variants’ effect in different biological processes is pivotal to pinpoint the molecular mechanism of diseases/traits and direct the experimental validation. [ 8 ]
To annotate the vast amounts of available NGS data, currently a large number of SNPs annotation tools are available. Some of them are specific to specific SNPs while others are more general. Some of the available SNPs annotation tools are as follows SNPeff, Ensembl Variant Effect Predictor (VEP), ANNOVAR, FATHMM, PhD-SNP, PolyPhen-2, SuSPect, F-SNP, AnnTools, SeattleSeq, SNPit, SCAN, Snap, SNPs&GO, LS-SNP, Snat, TREAT, TRAMS, Maviant, MutationTaster , SNPdat, Snpranker, NGS – SNP, SVA, VARIANT, SIFT, LIST-S2, PhD-SNP and FAST-SNP. The functions and approaches used in SNPs annotation tools are listed below.
[ 22 ]
[ 23 ]
Variant annotation tools use machine learning algorithms to predict variant annotations. Different annotation tools use different algorithms. Common algorithms include:
A large number of variant annotation tools are available for variant annotation. The annotation by different tools does not always agree amongst each other, as the defined rules for data handling differ between applications. It is frankly impossible to perform a perfect comparison of the available tools. Not all tools have the same input and output nor the same functionality. Below is a table of major annotation tools and their functional area.
CompleteGenomics,
GFF3-SOLiD,
SOAPsnp, MAQ,
CASAVA
GATK BED
[ 52 ]
Different annotations capture diverse aspects of variant function. [ 53 ] Simultaneous use of multiple, varied functional annotations could improve rare variants association analysis power of whole exome and whole genome sequencing studies. [ 54 ] Some tools have been developed to enable functionally-informed phenotype-genotype association analysis for common and rare variants by incorporating functional annotations in biobank-scale cohorts. [ 55 ] [ 56 ] [ 57 ] [ 58 ]
The next generation of SNP annotation webservers can take advantage of the growing amount of data in core bioinformatics resources and use intelligent agents to fetch data from different sources as needed. From a user's point of view, it is more efficient to submit a set of SNPs and receive results in a single step, which makes meta-servers the most attractive choice. [ 59 ] However, if SNP annotation tools deliver heterogeneous data covering sequence, structure, regulation, pathways, etc., they must also provide frameworks for integrating data into a decision algorithms, and quantitative confidence measures so users can assess which data are relevant and which are not. [ 59 ] | https://en.wikipedia.org/wiki/SNP_annotation |
In molecular biology , SNP array is a type of DNA microarray which is used to detect polymorphisms within a population. A single nucleotide polymorphism (SNP), a variation at a single site in DNA , is the most frequent type of variation in the genome. Around 335 million SNPs have been identified in the human genome , [ 1 ] 15 million of which are present at frequencies of 1% or higher across different populations worldwide. [ 2 ]
The basic principles of SNP array are the same as the DNA microarray. These are the convergence of DNA hybridization , fluorescence microscopy , and solid surface DNA capture. The three mandatory components of the SNP arrays are: [ 3 ]
The ASO probes are often chosen based on sequencing of a representative panel of individuals: positions found to vary in the panel at a specified frequency are used as the basis for probes. SNP chips are generally described by the number of SNP positions they assay. Two probes must be used for each SNP position to detect both alleles; if only one probe were used, experimental failure would be indistinguishable from homozygosity of the non-probed allele. [ 4 ]
An SNP array is a useful tool for studying slight variations between whole genomes . The most important clinical applications of SNP arrays are for determining disease susceptibility [ 5 ] and for measuring the efficacy of drug therapies designed specifically for individuals. [ 6 ] In research, SNP arrays are most frequently used for genome-wide association studies . [ 7 ] Each individual has many SNPs. SNP-based genetic linkage analysis can be used to map disease loci, and determine disease susceptibility genes in individuals. The combination of SNP maps and high density SNP arrays allows SNPs to be used as markers for genetic diseases that have complex traits . For example, genome-wide association studies have identified SNPs associated with diseases such as rheumatoid arthritis [ 8 ] and prostate cancer . [ 9 ] A SNP array can also be used to generate a virtual karyotype using software to determine the copy number of each SNP on the array and then align the SNPs in chromosomal order. [ 10 ]
SNPs can also be used to study genetic abnormalities in cancer. For example, SNP arrays can be used to study loss of heterozygosity (LOH). LOH occurs when one allele of a gene is mutated in a deleterious way and the normally-functioning allele is lost. LOH occurs commonly in oncogenesis. For example, tumor suppressor genes help keep cancer from developing. If a person has one mutated and dysfunctional copy of a tumor suppressor gene and his second, functional copy of the gene gets damaged, they may become more likely to develop cancer. [ 11 ]
Other chip-based methods such as comparative genomic hybridization can detect genomic gains or deletions leading to LOH. SNP arrays, however, have an additional advantage of being able to detect copy-neutral LOH (also called uniparental disomy or gene conversion). Copy-neutral LOH is a form of allelic imbalance. In copy-neutral LOH, one allele or whole chromosome from a parent is missing. This problem leads to duplication of the other parental allele. Copy-neutral LOH may be pathological. For example, say that the mother's allele is wild-type and fully functional, and the father's allele is mutated. If the mother's allele is missing and the child has two copies of the father's mutant allele, disease can occur.
High density SNP arrays help scientists identify patterns of allelic imbalance. These studies have potential prognostic and diagnostic uses. Because LOH is so common in many human cancers, SNP arrays have great potential in cancer diagnostics. For example, recent SNP array studies have shown that solid tumors such as gastric cancer and liver cancer show LOH, as do non-solid malignancies such as hematologic malignancies , ALL , MDS , CML and others. These studies may provide insights into how these diseases develop, as well as information about how to create therapies for them. [ 12 ]
Breeding in a number of animal and plant species has been revolutionized by the emergence of SNP arrays. The method is based on the prediction of genetic merit by incorporating relationships among individuals based on SNP array data. [ 13 ] This process is known as genomic selection. Crop-specific arrays find use in agriculture. [ 14 ] [ 15 ] | https://en.wikipedia.org/wiki/SNP_array |
SNP genotyping is the measurement of genetic variations of single nucleotide polymorphisms (SNPs) between members of a species. It is a form of genotyping , which is the measurement of more general genetic variation. SNPs are one of the most common types of genetic variation. An SNP is a single base pair mutation at a specific locus , usually consisting of two alleles (where the rare allele frequency is > 1%). SNPs are found to be involved in the etiology of many human diseases and are becoming of particular interest in pharmacogenetics . Because SNPs are conserved during evolution, they have been proposed as markers for use in quantitative trait loci ( QTL ) analysis and in association studies in place of microsatellites . The use of SNPs is being extended in the HapMap project, which aims to provide the minimal set of SNPs needed to genotype the human genome. SNPs can also provide a genetic fingerprint for use in identity testing. [ 1 ] The increase of interest in SNPs has been reflected by the furious development of a diverse range of SNP genotyping methods.
Several applications have been developed that interrogate SNPs by hybridizing complementary DNA probes to the SNP site. The challenge of this approach is reducing cross-hybridization between the allele-specific probes. This challenge is generally overcome by manipulating the hybridization stringency conditions. [ 1 ]
Dynamic allele-specific hybridization (DASH) genotyping takes advantage of the differences in the melting temperature in DNA that results from the instability of mismatched base pairs. The process can be vastly automated and encompasses a few simple principles. [ citation needed ]
In the first step, a genomic segment is amplified and attached to a bead through a PCR reaction with a biotinylated primer. In the second step, the amplified product is attached to a streptavidin column and washed with NaOH to remove the unbiotinylated strand. An allele-specific oligonucleotide is then added in the presence of a molecule that fluoresces when bound to double-stranded DNA. The intensity is then measured as temperature is increased until the melting temperature (Tm) can be determined. A SNP will result in a lower than expected Tm. [ 2 ]
Because DASH genotyping is measuring a quantifiable change in Tm, it is capable of measuring all types of mutations, not just SNPs. Other benefits of DASH include its ability to work with label free probes and its simple design and performance conditions. [ citation needed ]
SNP detection through molecular beacons makes use of a specifically engineered single-stranded oligonucleotide probe. The oligonucleotide is designed such that there are complementary regions at each end and a probe sequence located in between. This design allows the probe to take on a hairpin, or stem-loop, structure in its natural, isolated state. Attached to one end of the probe is a fluorophore and to the other end a fluorescence quencher. Because of the stem-loop structure of the probe, the fluorophore is close to the quencher, thus preventing the molecule from emitting any fluorescence. The molecule is also engineered such that only the probe sequence is complementary to the genomic DNA that will be used in the assay (Abravaya et al. 2003).
If the probe sequence of the molecular beacon encounters its target genomic DNA during the assay, it will anneal and hybridize. Because of the length of the probe sequence, the hairpin segment of the probe will be denatured in favour of forming a longer, more stable probe-target hybrid. This conformational change permits the fluorophore and quencher to be free of their tight proximity due to the hairpin association, allowing the molecule to fluoresce.
If on the other hand, the probe sequence encounters a target sequence with as little as one non-complementary nucleotide, the molecular beacon will preferentially stay in its natural hairpin state and no fluorescence will be observed, as the fluorophore remains quenched.
The unique design of these molecular beacons allows for a simple diagnostic assay to identify SNPs at a given location. If a molecular beacon is designed to match a wild-type allele and another to match a mutant of the allele, the two can be used to identify the genotype of an individual. If only the first probe's fluorophore wavelength is detected during the assay then the individual is homozygous to the wild type. If only the second probe's wavelength is detected then the individual is homozygous to the mutant allele. Finally, if both wavelengths are detected, then both molecular beacons must be hybridizing to their complements and thus the individual must contain both alleles and be heterozygous.
In high-density oligonucleotide SNP arrays , hundreds of thousands of probes are arrayed on a small chip, allowing for many SNPs to be interrogated simultaneously. [ 1 ] Because SNP alleles only differ in one nucleotide and because it is difficult to achieve optimal hybridization conditions for all probes on the array, the target DNA has the potential to hybridize to mismatched probes. This is addressed somewhat by using several redundant probes to interrogate each SNP. Probes are designed to have the SNP site in several different locations as well as containing mismatches to the SNP allele. By comparing the differential amount of hybridization of the target DNA to each of these redundant probes, it is possible to determine specific homozygous and heterozygous alleles. [ 1 ] Although oligonucleotide microarrays have a comparatively lower specificity and sensitivity, the scale of SNPs that can be interrogated is a major benefit. The Affymetrix Human SNP 5.0 GeneChip performs a genome-wide assay that can genotype over 500,000 human SNPs (Affymetrix 2007)..
A broad range of enzymes including DNA ligase , DNA polymerase and nucleases have been employed to generate high-fidelity SNP genotyping methods.
Restriction fragment length polymorphism (RFLP) is considered to be the simplest and earliest method to detect SNPs. SNP-RFLP makes use of the many different restriction endonucleases and their high affinity to unique and specific restriction sites. By performing a digestion on a genomic sample and determining fragment lengths through a gel assay it is possible to ascertain whether or not the enzymes cut the expected restriction sites. A failure to cut the genomic sample results in an identifiably larger than expected fragment implying that there is a mutation at the point of the restriction site which is rendering it protection from nuclease activity.
The combined factors of the high complexity of most eukaryotic genomes, the requirement for specific endonucleases, the fact that the exact mutation cannot necessarily be resolved in a single experiment, and the slow nature of gel assays make RFLP a poor choice for high throughput analysis.
Tetra-primer amplification refractory mutation system PCR, or ARMS-PCR, employs two pairs of primers to amplify two alleles in one PCR reaction. The primers are designed such that the two primer pairs overlap at a SNP location but each match perfectly to only one of the possible SNPs. The basis of the invention is that unexpectedly, oligonucleotides with a mismatched 3'-residue will not function as primers in the PCR under appropriate conditions. [ 3 ] As a result, if a given allele is present in the PCR reaction, the primer pair specific to that allele will produce product but not to the alternative allele with a different SNP. The two primer pairs are also designed such that their PCR products are of a significantly different length allowing for easily distinguishable bands by gel electrophoresis or melt temperature analysis. [ 4 ] [ 5 ] In examining the results, if a genomic sample is homozygous, then the PCR products that result will be from the primer that matches the SNP location and the outer opposite-strand primer, as well from the two outer primers. If the genomic sample is heterozygous, then products will result from the primer of each allele and their respective outer primer counterparts as well as the outer primers.
An alternative strategy is to run multiple qPCR reactions with different primer sets that target each allele separately. Well-designed primers will amplify their target SNP at a much earlier cycle than the other SNPs. This allows more than two alleles to be distinguished, although an individual qPCR reaction is required for each SNP. To achieve high enough specificity, the primer sequence may require placement of an artificial mismatch near its 3'-end, which is an approach generally known as Taq-MAMA. [ 6 ]
Flap endonuclease (FEN) is an endonuclease that catalyzes structure-specific cleavage. This cleavage is highly sensitive to mismatches and can be used to interrogate SNPs with a high degree of specificity [ 7 ]
In the basic Invader assay , a FEN called cleavase is combined with two specific oligonucleotide probes, that together with the target DNA, can form a tripartite structure recognized by cleavase. [ 7 ] The first probe, called the Invader oligonucleotide is complementary to the 3’ end of the target DNA. The last base of the Invader oligonucleotide is a non-matching base that overlaps the SNP nucleotide in the target DNA. The second probe is an allele-specific probe which is complementary to the 5’ end of the target DNA, but also extends past the 3’ side of the SNP nucleotide. The allele-specific probe will contain a base complementary to the SNP nucleotide. If the target DNA contains the desired allele, the Invader and allele-specific probes will bind to the target DNA forming the tripartite structure. This structure is recognized by cleavase, which will cleave and release the 3’ end of the allele-specific probe. If the SNP nucleotide in the target DNA is not complementary to the allele-specific probe, the correct tripartite structure is not formed and no cleavage occurs. The Invader assay is usually coupled with fluorescence resonance energy transfer (FRET) system to detect the cleavage event. In this setup, a quencher molecule is attached to the 3’ end and a fluorophore is attached to the 5’ end of the allele-specific probe. If cleavage occurs, the fluorophore will be separated from the quencher molecule generating a detectable signal. [ 7 ]
Only minimal cleavage occurs with mismatched probes making the Invader assay highly specific. However, in its original format, only one SNP allele could be interrogated per reaction sample and it required a large amount of target DNA to generate a detectable signal in a reasonable time frame. [ 7 ] Several developments have extended the original Invader assay. By carrying out secondary FEN cleavage reactions, the Serial Invasive Signal Amplification Reaction (SISAR) allows both SNP alleles to be interrogated in a single reaction. SISAR Invader assay also requires less target DNA, improving the sensitivity of the original Invader assay. [ 7 ] The assay has also been adapted in several ways for use in a high-throughput format. In one platform, the allele-specific probes are anchored to microspheres. When cleavage by FEN generates a detectable fluorescent signal, the signal is measured using flow-cytometry. The sensitivity of flow-cytometry, eliminates the need for PCR amplification of the target DNA (Rao et al. 2003). These high-throughput platforms have not progressed beyond the proof-of-principle stage and so far the Invader system has not been used in any large scale SNP genotyping projects. [ 7 ]
Primer extension is a two step process that first involves the hybridization of a probe to the bases immediately upstream of the SNP nucleotide followed by a ‘mini-sequencing’ reaction, in which DNA polymerase extends the hybridized primer by adding a base that is complementary to the SNP nucleotide. This incorporated base is detected and determines the SNP allele (Goelet et al. 1999; Syvanen 2001). Because primer extension is based on the highly accurate DNA polymerase enzyme, the method is generally very reliable. Primer extension is able to genotype most SNPs under very similar reaction conditions making it also highly flexible. The primer extension method is used in a number of assay formats. These formats use a wide range of detection techniques that include MALDI-TOF Mass spectrometry (see Sequenom ) and ELISA -like methods. [ 1 ]
Generally, there are two main approaches which use the incorporation of either fluorescently labeled dideoxynucleotides (ddNTP) or fluorescently labeled deoxynucleotides (dNTP). With ddNTPs, probes hybridize to the target DNA immediately upstream of SNP nucleotide, and a single, ddNTP complementary to the SNP allele is added to the 3’ end of the probe (the missing 3'-hydroxyl in didioxynucleotide prevents further nucleotides from being added). Each ddNTP is labeled with a different fluorescent signal allowing for the detection of all four alleles in the same reaction. With dNTPs, allele-specific probes have 3’ bases which are complementary to each of the SNP alleles being interrogated. If the target DNA contains an allele complementary to the probe's 3’ base, the target DNA will completely hybridize to the probe, allowing DNA polymerase to extend from the 3’ end of the probe. This is detected by the incorporation of the fluorescently labeled dNTPs onto the end of the probe. If the target DNA does not contain an allele complementary to the probe's 3’ base, the target DNA will produce a mismatch at the 3’ end of the probe and DNA polymerase will not be able to extend from the 3' end of the probe. The benefit of the second approach is that several labeled dNTPs may get incorporated into the growing strand, allowing for increased signal. However, DNA polymerase in some rare cases, can extend from mismatched 3’ probes giving a false positive result. [ 1 ]
A different approach is used by Sequenom ' s iPLEX SNP genotyping method, which uses a MassARRAY mass spectrometer. Extension probes are designed in such a way that 40 different SNP assays can be amplified and analyzed in a PCR cocktail. The extension reaction uses ddNTPs as above, but the detection of the SNP allele is dependent on the actual mass of the extension product and not on a fluorescent molecule. This method is for low to medium high throughput, and is not intended for whole genome scanning.
The flexibility and specificity of primer extension make it amenable to high throughput analysis. Primer extension probes can be arrayed on slides allowing for many SNPs to be genotyped at once. Broadly referred to as arrayed primer extension (APEX), this technology has several benefits over methods based on differential hybridization of probes. Comparatively, APEX methods have greater discriminating power than methods using this differential hybridization, as it is often impossible to obtain the optimal hybridization conditions for the thousands of probes on DNA microarrays (usually this is addressed by having highly redundant probes). However, the same density of probes cannot be achieved in APEX methods, which translates into lower output per run. [ 1 ]
Illumina Incorporated's Infinium assay is an example of a whole-genome genotyping pipeline that is based on primer extension method. In the Infinium assay, over 100,000 SNPs can be genotyped. The assay uses hapten-labelled nucleotides in a primer extension reaction. The hapten label is recognized by anti-bodies, which in turn are coupled to a detectable signal (Gunderson et al. 2006).
APEX-2 is an arrayed primer extension genotyping method which is able to identify hundreds of SNPs or mutations in parallel using efficient homogeneous multiplex PCR (up to 640-plex) and four-color single-base extension on a microarray. The multiplex PCR requires two oligonucleotides per SNP/mutation generating amplicons that contain the tested base pair. The same oligonucleotides are used in the following step as immobilized single-base extension primers on a microarray (Krjutskov et al. 2008).
Taq DNA polymerase's 5’-nuclease activity is used in the TaqMan assay for SNP genotyping. The TaqMan assay is performed concurrently with a PCR reaction and the results can be read in real-time as the PCR reaction proceeds (McGuigan & Ralston 2002). The assay requires forward and reverse PCR primers that will amplify a region that includes the SNP polymorphic site. Allele discrimination is achieved using FRET combined with one or two allele-specific probes that hybridize to the SNP polymorphic site. The probes will have a fluorophore linked to their 5’ end and a quencher molecule linked to their 3’ end. While the probe is intact, the quencher will remain in close proximity to the fluorophore, eliminating the fluorophore's signal. During the PCR amplification step, if the allele-specific probe is perfectly complementary to the SNP allele, it will bind to the target DNA strand and then get degraded by 5’-nuclease activity of the Taq polymerase as it extends the DNA from the PCR primers. The degradation of the probe results in the separation of the fluorophore from the quencher molecule, generating a detectable signal. If the allele-specific probe is not perfectly complementary, it will have lower melting temperature and not bind as efficiently. This prevents the nuclease from acting on the probe (McGuigan & Ralston 2002).
Since the TaqMan assay is based on PCR, it is relatively simple to implement. The TaqMan assay can be multiplexed by combining the detection of up to seven SNPs in one reaction. However, since each SNP requires a distinct probe, the TaqMan assay is limited by the how close the SNPs can be situated. The scale of the assay can be drastically increased by performing many simultaneous reactions in microtitre plates. Generally, TaqMan is limited to applications that involve interrogating a small number of SNPs since optimal probes and reaction conditions must be designed for each SNP (Syvanen 2001).
DNA ligase catalyzes the ligation of the 3' end of a DNA fragment to the 5' end of a directly adjacent DNA fragment. This mechanism can be used to interrogate a SNP by hybridizing two probes directly over the SNP polymorphic site, whereby ligation can occur if the probes are identical to the target DNA. In the oligonucleotide ligase assay, two probes are designed; an allele-specific probe which hybridizes to the target DNA so that its 3' base is situated directly over the SNP nucleotide and a second probe that hybridizes the template upstream (downstream in the complementary strand) of the SNP polymorphic site providing a 5' end for the ligation reaction. If the allele-specific probe matches the target DNA, it will fully hybridize to the target DNA and ligation can occur. Ligation does not generally occur in the presence of a mismatched 3' base. Ligated or unligated products can be detected by gel electrophoresis, MALDI-TOF mass spectrometry or by capillary electrophoresis for large-scale applications. [ 1 ] With appropriate sequences and tags on the oligonucleotides, high-throughput sequence data can be generated from the ligated products and genotypes determined (Curry et al., 2012). The use of large numbers of sample indexes allows high-throughput sequence data on hundreds of SNPs in thousands of samples to be generated in a small portion of a high-throughput sequencing run. This is a massive genotyping by sequencing technology (MGST). [ citation needed ]
The characteristic DNA properties of melting temperature and single stranded conformation have been used in several applications to distinguish SNP alleles. These methods very often achieve high specificity but require highly optimized conditions to obtain the best possible results.
Single-stranded DNA (ssDNA) folds into a tertiary structure. The conformation is sequence dependent and most single base pair mutations will alter the shape of the structure. When applied to a gel, the tertiary shape will determine the mobility of the ssDNA, providing a mechanism to differentiate between SNP alleles. This method first involves PCR amplification of the target DNA. The double-stranded PCR products are denatured using heat and formaldehyde to produce ssDNA. The ssDNA is applied to a non-denaturing electrophoresis gel and allowed to fold into a tertiary structure. Differences in DNA sequence will alter the tertiary conformation and be detected as a difference in the ssDNA strand mobility (Costabile et al. 2006). This method is widely used because it is technically simple, relatively inexpensive and uses commonly available equipment. However compared to other SNP genotyping methods, the sensitivity of this assay is lower. It has been found that the ssDNA conformation is highly dependent on temperature and it is not generally apparent what the ideal temperature is. Very often the assay will be carried out using several different temperatures. There is also a restriction on the length of fragment because the sensitivity drops when sequences longer than 400 bp are used (Costabile et al. 2006).
The temperature gradient gel electrophoresis (TGGE) or temperature gradient capillary electrophoresis (TGCE) method is based on the principle that partially denatured DNA is more restricted and travels slower in a porous material such as a gel. This property allows for the separation of DNA by melting temperature. To adapt these methods for SNP detection, two fragments are used; the target DNA which contain the SNP polymorphic site being interrogated and an allele-specific DNA sequence, referred to as the normal DNA fragment. The normal fragment is identical to the target DNA except potentially at the SNP polymorphic site, which is unknown in the target DNA. The fragments are denatured and then reannealed. If the target DNA has the same allele as the normal fragment, homoduplexes will form that will have the same melting temperature. When run on the gel with a temperature gradient, only one band will appear. If the target DNA has a distinct allele, four products will form following the reannealing step; homoduplexes consisting of target DNA, homoduplexes consisting of normal DNA and two heterduplexes of each strand of target DNA hybridized with the normal DNA strand. These four products will have distinct melting temperatures and will appear as four bands in the denaturing gel. [ 1 ]
Denaturing high performance liquid chromatography (DHPLC) uses reversed-phase HPLC to interrogate SNPs. The key to DHPLC is the solid phase which has differential affinity for single and double-stranded DNA. In DHPLC, DNA fragments are denatured by heating and then allowed to reanneal. The melting temperature of the reannealed DNA fragments determines the length of time they are retained in the column. [ 8 ] Using PCR, two fragments are generated; target DNA containing the SNP polymorphic site and an allele-specific DNA sequence, referred to as the normal DNA fragment. This normal fragment is identical to the target DNA except potentially at the SNP polymorphic site, which is unknown in the target DNA. The fragments are denatured and then allowed to gradually reanneal. The reannaled products are added to the DHPLC column. If the SNP allele in the target DNA matches the normal DNA fragment, only identical homoduplexes will form during the reannealing step. If the target DNA contains a different SNP allele than the normal DNA fragment, heteroduplexes of the target DNA and normal DNA containing a mismatched polymorphic site will form in addition to homoduplexes. The mismatched heteroduplexes will have a different melting temperature than the homoduplexes and will not be retained in the column as long. This generates a chromatograph pattern that is distinctive from the pattern that would be generated if the target DNA fragment and normal DNA fragments were identical. The eluted DNA is detected by UV absorption. [ 8 ]
DHPLC is easily automated as no labeling or purification of the DNA fragments is needed. The method is also relatively fast and has a high specificity. One major drawback of DHPLC is that the column temperature must be optimized for each target in order to achieve the right degree of denaturation. [ 1 ]
High Resolution Melting analysis is the simplest PCR-based method to understand. Basically, the same thermodynamic properties that allowed for the gel techniques to work apply here, and in real-time. A fluorimeter monitors the post-PCR denaturation of the entire dsDNA amplicon. You make primers specific to the site you want to amplify. You "paint" the amplicon with a double-strand specific dye, included in the PCR mix. The ds-specific dye integrates itself into the PCR product. In essence, the entire amplicon becomes a probe. This opens up new possibilities for discovery. Either you position the primers very close to either side of the SNP in question (small amplicon genotyping, Liew, 2004) or amplify a larger region (100-400bp in length) for scanning purposes. For simple genotyping of an SNP, it is easier to just make the amplicon small to minimize the chances you mistake one SNP for another. The melting temperature (Tm) of the entire amplicon is determined and most homozygotes are sufficiently different (in the better instruments) in Tm to genotype. Heterozygotes are even easier to differentiate because they have heteroduplexes generated (refer to the gel-based explanations) which broadens the melt transition and usually gives two discernible peaks. Amplicon melting using a fluorescently-labeled primer has been described (Gundry et al., 2003) but is less practical than using ds-specific dyes due to the cost of the fluorogenic primer.
Scanning of larger amplicons is based on the same principles as outlined above. However, melting temperature and the overall shape of the melting curve become informative. For amplicons >c.150bp there are often >2 melting peaks, each of which can vary, depending on the DNA template composition. Numerous investigators have been able to successfully eliminate the majority of their sequencing through melt-based scanning, allowing accurate locus-based genotyping of large numbers of individuals. [ 9 ] Many investigators have found scanning for mutations using high resolution melting as a viable and practical way to study entire genes.
DNA mismatch-binding proteins can distinguish single nucleotide mismatches and thus facilitate differential analysis of SNPs. For example, MutS protein from Thermus aquaticus binds different single nucleotide mismatches with different affinities and can be used in capillary electrophoresis to differentiate all six sets of mismatches (Drabovich & Krylov 2006).
SNPlex is a proprietary genotyping platform sold by Applied Biosystems .
Surveyor nuclease is a mismatch endonuclease enzyme that recognizes all base substitutions and small insertions/deletions (indels), and cleaves the 3′ side of mismatched sites in both DNA strands.
Next-generation sequencing technologies such as pyrosequencing sequence less than 250 bases in a read which limits their ability to sequence whole genomes. However, their ability to generate results in real-time and their potential to be massively scaled up makes them a viable option for sequencing small regions to perform SNP genotyping. Compared to other SNP genotyping methods, sequencing is in particular, suited to identifying multiple SNPs in a small region, such as the highly polymorphic Major Histocompatibility Complex region of the genome. [ 1 ] | https://en.wikipedia.org/wiki/SNP_genotyping |
SNPedia (pronounced "snipedia") is a wiki -based bioinformatics web site that serves as a database of single nucleotide polymorphisms (SNPs). Each article on a SNP provides a short description, links to scientific articles and personal genomics web sites, as well as microarray information about that SNP. Thus SNPedia may support the interpretation of results of personal genotyping from, e.g., 23andMe and similar companies. [ 1 ]
SNPedia is a semantic wiki , powered by MediaWiki and the Semantic MediaWiki extension.
SNPedia was created, and is run by, geneticist Greg Lennon [ 2 ] and programmer Mike Cariaso, [ 3 ] who at the time of the site's founding were both located in Bethesda, Maryland . [ 4 ]
As of 27 June 2019 [update] , the website has 537 medical conditions [ 5 ] and 109,729 SNPs in its database. [ 6 ] The number of SNPs in SNPedia has doubled roughly once every 14 months since August 2007. [ 7 ]
On 7 September 2019, MyHeritage announced that they acquired both SNPedia and Promethease. All non-European raw genetic data files previously uploaded to Promethease, and not deleted by users by 1 Nov 2019, are to be copied to MyHeritage and the users will receive a free MyHeritage account with paid level of services, including Cousin Matching and Ethnicities. [ 8 ]
An associated computer program called Promethease, also developed by the SNPedia team, allows users to compare personal genetics results against the SNPedia database, generating a report with information about a person's attributes, such as propensity to diseases, based on the presence of specific SNPs within their genome. [ 3 ]
In May 2008 Cariaso, using Promethease, won an online contest sponsored by 23andMe to determine as much information as possible about an anonymous woman based only on her genome. Cariaso won in all three categories of "accuracy, creativity and cleverness". [ 9 ] In 2009, the anonymous woman ("Lilly Mendel") was revealed to be 23andMe co-founder Linda Avey , allowing a direct comparison between her actual traits and those predicted by Promethease a year earlier. [ 10 ]
In a June 2008 article on personal genomics, a doctor from the Southern Illinois University School of Medicine said:
The availability of online tools such as SNPedia means we are now in the position where the patient often knows more about their risk implications than their doctor [...] [ 11 ]
In January 2011, technology journalist Ronald Bailey posted the full result of his Promethease report online. Writing about his decision in Reason magazine, he stated:
We are fast approaching an era in which genetic information is no longer exclusive or medicalized. Instead, as screening costs plummet and our knowledge about genetics expands, virtually everyone will soon be able to have their genotypes at their fingertips. Knowing and sharing that information will enhance, not jeopardize, our sense of ourselves, change the way we consume medicine and plan for the future, and influence how we relate to each other. [ 12 ]
Members of the medical community have criticised Promethease for technical complexity and a poorly defined "magnitude" scale that causes misconceptions, confusion and panic among its users. [ 13 ] [ 14 ] [ 15 ] | https://en.wikipedia.org/wiki/SNPedia |
SNPlex is a platform for SNP genotyping sold by Applied Biosystems (ABI). It is based on capillary electrophoresis to separate varying fragments of DNA , which allows the assay to be performed on ABI's 3730xl DNA analyzers . Currently, up to 48 SNPs can be genotyped in a single reaction. [ 1 ]
This genetics article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/SNPlex |
SNV calling from NGS data is any of a range of methods for identifying the existence of single nucleotide variants (SNVs) from the results of next generation sequencing (NGS) experiments. These are computational techniques, and are in contrast to special experimental methods based on known population-wide single nucleotide polymorphisms (see SNP genotyping ). Due to the increasing abundance of NGS data, these techniques are becoming increasingly popular for performing SNP genotyping, with a wide variety of algorithms designed for specific experimental designs and applications. [ 1 ] In addition to the usual application domain of SNP genotyping, these techniques have been successfully adapted to identify rare SNPs within a population, [ 2 ] as well as detecting somatic SNVs within an individual using multiple tissue samples. [ 3 ]
Most NGS based methods for SNV detection are designed to detect germline variations in the individual's genome. These are the mutations that an individual biologically inherits from their parents, and are the usual type of variants searched for when performing such analysis (except for certain specific applications where somatic mutations are sought). Very often, the searched for variants occur with some (possibly rare) frequency, throughout the population, in which case they may be referred to as single nucleotide polymorphisms (SNPs). Technically the term SNP only refers to these kinds of variations, however in practice they are often used synonymously with SNV in the literature on variant calling. In addition, since the detection of germline SNVs requires determining the individual's genotype at each locus, the phrase "SNP genotyping" may also be used to refer to this process. However this phrase may also refer to wet-lab experimental procedures for classifying genotypes at a set of known SNP locations.
The usual process of such techniques are based around: [ 1 ]
The usual output of these procedures is a VCF file.
In an ideal error free world with high read coverage , the task of variant calling from the results of a NGS data alignment would be simple; at each locus (position on the genome) the number of occurrences of each distinct nucleotide among the reads aligned at that position can be counted, and the true genotype would be obvious; either AA if all nucleotides match allele A , BB if they match allele B , or AB if there is a mixture. However, when working with real NGS data this sort of naive approach is not used, as it cannot account for the noise in the input data. [ 4 ] The nucleotide counts used for base calling contain errors and bias, both due do the sequenced reads themselves, and the alignment process. This issue can be mitigated to some extent by sequencing to a greater depth of read coverage, however this is often expensive, and many practical studies require making inferences on low coverage data. [ 1 ]
Probabilistic methods aim to overcome the above issue, by producing robust estimates of the probabilities of each of the possible genotypes, taking into account noise, as well as other available prior information that can be used to improve estimates. A genotype can then be predicted based on these probabilities, often according to the MAP estimate.
Probabilistic methods for variant calling are based on Bayes' theorem . In the context of variant calling, Bayes' Theorem defines the probability of each genotype being the true genotype given the observed data, in terms of the prior probabilities of each possible genotype, and the probability distribution of the data given each possible genotype. The formula is:
In the above equation:
Given the above framework, different software solutions for detecting SNVs vary based on how they calculate the prior probabilities P ( G ) {\displaystyle P(G)} , the error model used to model the probabilities P ( D ∣ G ) {\displaystyle P(D\mid G)} , and the partitioning of the overall genotypes into separate sub-genotypes, whose probabilities can be individually estimated in this framework. [ 5 ]
The calculation of prior probabilities depends on available data from the genome being studied, and the type of analysis being performed. For studies where good reference data containing frequencies of known mutations is available (for example, in studying human genome data), these known frequencies of genotypes in the population can be used to estimate priors. Given population wide allele frequencies, prior genotype probabilities can be calculated at each locus according to the Hardy–Weinberg equilibrium . [ 6 ] In the absence of such data, constant priors can be used, independent of the locus. These can be set using heuristically chosen values, possibly informed by the kind of variations being sought by the study. Alternatively, supervised machine-learning procedures have been investigated that seek to learn optimal prior values for individuals in a sample, using supplied NGS data from these individuals. [ 4 ]
The error model used in creating a probabilistic method for variant calling is the basis for calculating the P ( D ∣ G ) {\displaystyle P(D\mid G)} term used in Bayes' theorem. If the data was assumed to be error free, then the distribution of observed nucleotide counts at each locus would follow a binomial distribution , with 100% of nucleotides matching the A or B allele respectively in the AA and BB cases, and a 50% chance of each nucleotide matching either A or B in the AB case. However, in presence of noise in the read data this assumption is violated, and the P ( D ∣ G ) {\displaystyle P(D\mid G)} values need to account for the possibility that erroneous nucleotides are present in the aligned reads at each locus.
A simple error model is to introduce a small error to the data probability term in the homozygous cases, allowing a small constant probability that nucleotides which don't match the A allele are observed in the AA case, and respectively a small constant probability that nucleotides not matching the B allele are observed in the BB case. However more sophisticated procedures are available which attempt to more realistically replicate the actual error patterns observed in real data in calculating the conditional data probabilities. For instance, estimations of read quality (measured as Phred quality scores) have been incorporated in these calculations, taking into account the expected error rate in each individual read at a locus. [ 7 ] Another technique that has successfully been incorporated into error models is base quality recalibration, where separate error rates are calculated – based on prior known information about error patterns – for each possible nucleotide substitution. Research shows that each possible nucleotide substitution is not equally likely to show up as an error in sequencing data, and so base quality recalibration has been applied to improve error probability estimates. [ 6 ]
In the above discussion, it has been assumed that the genotype probabilities at each locus are calculated independently; that is, the entire genotype is partitioned into independent genotypes at each locus, whose probabilities are calculated independently. However, due to linkage disequilibrium the genotypes of nearby loci are in general not independent. As a result, partitioning the overall genotype instead into a sequence of overlapping haplotypes allows these correlations to be modelled, resulting in more precise probability estimates through the incorporation of population-wide haplotype frequencies in the prior. The use of haplotypes to improve variant detection accuracy has been applied successfully, for instance in the 1000 Genomes Project . [ 8 ]
As an alternative to probabilistic methods, heuristic methods exist for performing variant calling on NGS data. Instead of modelling the distribution of the observed data and using Bayesian statistics to calculate genotype probabilities, variant calls are made based on a variety of heuristic factors, such as minimum allele counts, read quality cut-offs, bounds on read depth, etc. Although they have been relatively unpopular in practice in comparison to probabilistic methods, in practice due to their use of bounds and cut-offs they can be robust to outlying data that violate the assumptions of probabilistic models. [ 9 ]
An important part of the design of variant calling methods using NGS data is the DNA sequence used as a reference to which the NGS reads are aligned. In human genetics studies, high quality references are available, from sources such as the HapMap project , [ 10 ] which can substantially improve the accuracy of the variant calls made by variant calling algorithms. As a bonus, such references can be a source of prior genotype probabilities for Bayesian-based analysis. However, in the absence of such a high quality reference, experimentally obtained reads can first be assembled in order to create a reference sequence for alignment. [ 1 ]
Various methods exist for filtering data in variant calling experiments, in order to remove sources of error/bias. This can involve the removal of suspicious reads before performing alignment and/or filtering of the list of variants returned by the variant calling algorithm.
Depending on the sequencing platform used, various biases may exist within the set of sequenced reads. For instance, strand bias can occur, where there is a highly unequal distribution of forward vs reverse directions in the reads aligned in some neighborhood. Additionally, there may occur an unusually high duplication of some reads (for instance due to bias in PCR ). Such biases can result in dubious variant calls – for instance if a fragment containing a PCR error at some locus is over amplified due to PCR bias, that locus will have a high count of the false allele, and may be called as a SNV – and so analysis pipelines frequently filter calls based on these biases. [ 1 ]
In addition to methods that align reads from individual sample(s) to a reference genome in order to detect germline genetic variants, reads from multiple tissue samples within a single individual can be aligned and compared in order to detect somatic variants. These variants correspond to mutations that have occurred de novo within groups of somatic cells within an individual (that is, they are not present within the individual's germline cells). This form of analysis has been frequently applied to the study of cancer , where many studies are designed around investigating the profile of somatic mutations within cancerous tissues. Such investigations have resulted in diagnostic tools that have seen clinical application, and are used to improve scientific understanding of the disease, for instance by the discovery of new cancer-related genes, identification of involved gene regulatory networks and metabolic pathways , and by informing models of how tumors grow and evolve. [ 11 ]
Until recently, software tools for carrying out this form of analysis have been heavily underdeveloped, and were based on the same algorithms used to detect germline variations. Such procedures are not optimized for this task, because they do not adequately model the statistical correlation between the genotypes present in multiple tissue samples from the same individual. [ 3 ]
More recent investigations have resulted in the development of software tools especially optimized for the detection of somatic mutations from multiple tissue samples. Probabilistic techniques have been developed that pool allele counts from all tissue samples at each locus, and using statistical models for the likelihoods of joint-genotypes for all the tissues, and the distribution of allele counts given the genotype, are able to calculate relatively robust probabilities of somatic mutations at each locus using all available data. [ 3 ] [ 12 ] In addition there has recently been some investigation in machine learning based techniques for performing this analysis. [ 13 ] [ 14 ] [ 15 ] [ 16 ]
In 2021, the Sequencing Quality Control Phase 2 Consortium [ 17 ] has published a number of studies that investigated the effects of sample preparations, sequencing library kits, sequencing platforms, and bioinformatics workflows on the accuracy of somatic SNV detection [ 18 ] based on a pair of tumor-normal cell lines that the Consortium has established as the reference samples, data, and call sets. [ 19 ] | https://en.wikipedia.org/wiki/SNV_calling_from_NGS_data |
NGC 2525 is a barred spiral galaxy located in the constellation Puppis . It is located at a distance of about 70 million light years from Earth, which, given its apparent dimensions, means that NGC 2525 is about 60,000 light years across. It was discovered by William Herschel on February 23, 1791. [ 4 ]
The galaxy has a bar and two main spiral arms with high surface brightness. HII regions are observed in the arms. The brightest stars of the galaxy have apparent magnitude around 22. Its nucleus is small and bright. [ 5 ] In the centre of the galaxy is predicted to lie a supermassive black hole whose mass is estimated to be between 1.1 and 44 million solar masses , based on the spiral arm pitch angle. [ 6 ] [ 7 ]
One supernova has been observed in NGC 2525, SN 2018gv . It was discovered on by Kōichi Itagaki on 15 January 2018 at magnitude 16.5, [ 8 ] and it was identified spectrographically as a type Ia supernova 10 to 15 days before maximum. [ 9 ] The supernova was also observed by ATLAS on 2018 January 14.5 UT at magnitude 18.1. [ 10 ] It reached a peak magnitude of 12.8. ESA/Hubble released a video of the supernova in October 2020. [ 11 ] [ 12 ] | https://en.wikipedia.org/wiki/SN_2018gv |
In chemistry , S N i ( substitution nucleophilic internal ) refers to a specific, regio-selective but not often encountered reaction mechanism for nucleophilic aliphatic substitution . The name was introduced by Cowdrey et al. in 1937 to label nucleophilic reactions which occur with retention of configuration, [ 1 ] but later was employed to describe various reactions that proceed with a similar mechanism.
A typical representative organic reaction displaying this mechanism is the chlorination of alcohols with thionyl chloride , or the decomposition of alkyl chloroformates , the main feature is retention of stereochemical configuration. Some examples for this reaction were reported by Edward S. Lewis and Charles E. Boozer in 1952. [ 2 ] Mechanistic and kinetic studies were reported few years later by various researchers. [ 3 ] [ 4 ]
Thionyl chloride first reacts with the alcohol to form an alkyl chloro sulfite , actually forming an intimate ion pair . The second step is the loss of a sulfur dioxide molecule and its replacement by the chloride, which was attached to the sulphite group. The difference between S N 1 and S N i is actually that the ion pair is not completely dissociated , and therefore no real carbocation is formed, which else would lead to a racemisation. [ citation needed ]
This reaction type is linked to many forms of neighbouring group participation , for instance the reaction of the sulfur or nitrogen lone pair in sulfur mustard or nitrogen mustard to form the cationic intermediate .
This reaction mechanism is supported by the observation that addition of pyridine to the reaction leads to inversion . The reasoning behind this finding is that pyridine reacts with the intermediate sulfite replacing chlorine. The dislodged chlorine has to resort to nucleophilic attack from the rear as in a regular nucleophilic substitution. [ 3 ]
In the complete picture for this reaction the sulfite reacts with a chlorine ion in a standard S N 2 reaction with inversion of configuration. When the solvent is also a nucleophile such as dioxane two successive S N 2 reactions take place and the stereochemistry is again retention . With standard S N 1 reaction conditions the reaction outcome is retention via a competing S N i mechanism and not racemization and with pyridine added the result is again inversion . [ 5 ] [ 3 ] | https://en.wikipedia.org/wiki/SNi |
In mathematics , SO(5) , also denoted SO 5 (R) or SO(5,R) , is the special orthogonal group of degree 5 over the field R of real numbers , i.e. ( isomorphic to) the group of orthogonal 5×5 matrices of determinant 1.
SO(5) is a subgroup of the direct Euclidean group E + (5) , the group of direct isometries , i.e., isometries preserving orientation , of R 5 , consisting of elements which leave the origin fixed.
More precisely, we have:
where T is the translational group of R 5 .
SO(5) is a simple Lie group of dimension 10.
This geometry-related article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/SO(5) |
Sulfuryl chloride is an inorganic compound with the formula SO 2 Cl 2 . At room temperature , it is a colorless liquid with a pungent odor. Sulfuryl chloride is not found in nature, as can be inferred from its rapid hydrolysis .
Sulfuryl chloride is commonly confused with thionyl chloride , SOCl 2 . The properties of these two sulfur oxychlorides are quite different: sulfuryl chloride is a source of chlorine whereas thionyl chloride is a source of chloride ions. An alternative IUPAC name is sulfuryl dichloride .
Sulfur is tetrahedral in SO 2 Cl 2 and the oxidation state of the sulfur atom is +6, as in sulfuric acid .
SO 2 Cl 2 is prepared by the reaction of sulfur dioxide and chlorine in the presence of a catalyst , such as activated carbon . [ 2 ]
The product can be purified by fractional distillation .
Sulfuryl chloride was first prepared in 1838 by the French chemist Henri Victor Regnault . [ 3 ]
Older routes include oxidation of thionyl chloride:
Sulfuryl chloride reacts with water , releasing hydrogen chloride gas and sulfuric acid :
For sulfuryl chloride, this happens at room temperature, but the related sulfuryl fluoride does not hydrolyse at temperatures up to 150 °C.
SO 2 Cl 2 will also decompose when heated to or above 100 °C, about 30 °C above its boiling point.
Upon standing, SO 2 Cl 2 decomposes to sulfur dioxide and chlorine , which gives the older samples a slightly yellowish color. [ 2 ]
SO 2 Cl 2 can be used as a source of chlorine in alkane chlorination, initiated by chemicals (usually a peroxide) or light: [ 4 ]
Sulfuryl chloride is used as a source of Cl 2 . Because it is a pourable liquid, it is considered more convenient than Cl 2 to dispense.
Sulfuryl chloride is used in the conversion of C−H to C−Cl adjacent to activating substituents such as carbonyls and sulfoxides: [ 5 ] [ 6 ]
It also chlorinates alkanes , alkenes , alkynes , aromatics , ethers (such as tetrahydrofuran ) and epoxides . Such reactions occur under free radical conditions using an initiator such as AIBN . It convert thiols or disulfides into the corresponding sulfenyl chlorides : [ 7 ]
Occasionally, sulfinyl chlorides result from such reactions. [ 8 ] SO 2 Cl 2 can also convert alcohols to alkyl chlorides . In industry, sulfuryl chloride is most used in producing pesticides. Phosphorus pentachloride is prepared by the reaction of white phosphorus with sulfuryl chloride.
Sulfuryl chloride can also be used to treat wool to prevent shrinking.
Sulfuryl chloride is toxic, corrosive, and acts as a lachrymator . It releases hydrogen chloride upon contact with water, as well as donor solvents such as dimethyl sulfoxide and dimethylformamide . | https://en.wikipedia.org/wiki/SO2Cl2 |
Sulfuryl chloride fluoride is a chemical compound with the formula S O 2 Cl F . It is a colorless, easily condensed gas. It is a tetrahedral molecule.
Liquified sulfuryl chloride fluoride is employed as a solvent for highly oxidizing compounds. [ 1 ]
The laboratory-scale synthesis begins with the preparation of potassium fluorosulfite : [ 2 ]
This salt is then chlorinated to give sulfuryl chloride fluoride [ 3 ]
Further heating (180 °C) of potassium fluorosulfite with the sulfuryl chloride fluoride gives sulfuryl fluoride .
Alternatively, sulfuryl chloride fluoride can be prepared without using gases as starting materials by treating sulfuryl chloride with ammonium fluoride or potassium fluoride in trifluoroacetic acid . [ 4 ] | https://en.wikipedia.org/wiki/SO2ClF |
Sulfuryl fluoride (also spelled sulphuryl fluoride ) is an inorganic compound with the formula SO 2 F 2 . It is an easily condensed gas and has properties more similar to sulfur hexafluoride than sulfuryl chloride , being resistant to hydrolysis even up to 150 °C. [ 3 ] It is neurotoxic and a potent greenhouse gas , but is widely used as a fumigant insecticide to control termites .
The molecule is tetrahedral with C 2v symmetry . The S-O distance is 140.5 pm, S-F is 153.0 pm. As predicted by VSEPR , the O-S-O angle is more open than the F-S-F angle, 124° and 97°, respectively. [ 3 ]
One synthesis begins with the preparation of potassium fluorosulfite: [ 4 ]
This salt is then chlorinated to give sulfuryl chloride fluoride :
Heating the sulfuryl chloride fluoride with potassium fluorosulfite at 180 °C gives the desired product: [ 5 ]
Heating metal fluorosulfonate salts also gives this molecule: [ 3 ]
It can be prepared by direct reaction of fluorine with sulfur dioxide :
On a laboratory scale, sulfuryl fluoride has been conveniently prepared from 1,1'-sulfonyldiimidazole, in the presence of potassium fluoride and acid. [ 6 ] [ 7 ]
Sulfuryl fluoride is unreactive toward molten sodium metal. [ 3 ] Similarly it is slow to hydrolyze, but eventually converts to sulfur trioxide . [ 8 ] [ 9 ]
Sulfuryl fluoride gas is a precursor to fluorosulfates and sulfamoyl fluorides : [ 10 ]
Originally developed by the Dow Chemical Company , sulfuryl fluoride is in widespread use as a structural fumigant insecticide to control drywood termites , particularly in warm-weather portions of the southwestern and southeastern United States and in Hawaii. It has a non-specific mode of action ( IRAC group 8C). Less commonly, it can also be used to control rodents , powderpost beetles , deathwatch beetles , bark beetles , and bedbugs . Its use has increased as a replacement for methyl bromide , which was phased out because of harm to the ozone layer. It is an alternative to the use of phosphine , which is acutely toxic. [ 11 ]
During application, the building is enclosed and filled with the gas for a period of time, usually at least 16–18 hours, sometimes as long as 72 hours. The building must then be ventilated, generally for at least 6 hours, before occupants can return. California regulations are such that the tent will be on for three to five days, which includes ventilation. In the US, sulfuryl fluoride must be transported in a vehicle marked with "Inhalation Hazard 2" placards. [ 12 ] [ 13 ] Most states require a license or certification for the individual applying the fumigant.
The concentration is continuously monitored and maintained at the specified level using electronic equipment. Possible leakages are also checked by low range electronic detectors. Reentry to the home is allowed when the concentration level is at or below 5 ppm. [ 14 ] Sulfuryl fluoride is colorless and odorless, however, during the fumigation process, a warning agent called chloropicrin is first released into the building to ensure that no occupants remain. Tent fumigation is the most effective treatment for the extermination of known and unknown infestations of wood-destroying insects. Heat is the only other approved method for whole structure treatment for termites in California. [ 15 ] Sulfuryl fluoride provides no protection from future infestations, although heavy re-infestation can take several years since drywood termites have slower growing colonies than ground termites.
Sulfuryl fluoride is marketed in the U.S. by three manufacturers, under four different brand names. Vikane (Dow) (EPA Reg. No. 62719- 4-ZA) has been commercially available since the early 1960s, with Zythor (marketed by competitor Ensystex of North Carolina) (EPA Reg. No. 81824- 1-AA) being more recently introduced gradually as its use is approved by individual states (in Florida circa 2004, but not in California until October 2006, for example). Sulfuryl fluoride has been marketed as a post-harvest fumigant for dry fruits, nuts, and grains under the trade name ProFume (U.S. EPA Reg. No. 62719- 376-AA). [ 16 ] Most recently Drexel Chemical Company has registered Master Fume (EPA Reg. No. 19713-596-AA) for the structural market, competing against Vikane and Zythor . [ 17 ]
Inhalation of sulfuryl fluoride is hazardous and may result in respiratory irritation, pulmonary edema , nausea, abdominal pain, central nervous system depression, numbness in the extremities, muscle twitching, seizures, and death. [ 18 ] [ 19 ] [ 20 ] These high exposures occurred when people entered into structures illegally during fumigation or after insufficient aeration. Epidemiological studies showed that fumigation workers who used sulfuryl fluoride showed neurological effects, which included reduced performance on cognitive tests and pattern memory tests, and reduced olfactory function. [ 21 ]
In 1987, an elderly couple was exposed to sulfuryl fluoride in their house already cleared for reentry. [ 21 ] While the fumigation company opened windows and doors, and aerated the house with fans, sulfuryl fluoride level was not measured. It was not detected when the air was sampled 12 days after aeration. The couple experienced weakness, nausea and shortness of breath that evening. The man suffered a seizure and died the following day. His wife's condition got worse with pulmonary edema, and she died after a cardiovascular arrest 6 days later.
In 2015, a 10-year-old boy suffered severe brain damage and lost function of his left arm and leg after his home was treated with sulfuryl fluoride and insufficiently aerated, prompting a criminal investigation by the Department of Justice and the Florida Department of Agricultural and Consumer Services. [ 22 ] Two pest control workers later pled guilty to charges of misuse of the pesticide resulting in the boy's poisoning, and were each sentenced to one year in prison. [ 23 ]
In 2016, a 24-year-old man who allegedly entered an apartment that was being fumigated in Fremont, California to commit a burglary was exposed to sulfuryl fluoride and chloropicrin and died shortly thereafter. According to a police officer, he experienced labored breathing and was sweating before he collapsed just a few steps from the first floor window of the apartment he allegedly burglarized. [ 24 ]
In April 2024, In Pompano Beach Florida, two company pesticide workers died. The owner was also hospitalized but survived. [ 25 ]
Based on the first high frequency, high precision, in situ atmospheric and archived air measurements, sulfuryl fluoride has an atmospheric lifetime of 30–40 years, [ 8 ] much longer than the 5 years earlier estimated. [ 26 ]
Sulfuryl fluoride has been reported to be a greenhouse gas which is about 4000–5000 times more efficient in trapping infrared radiation (per kg) than carbon dioxide (per kg). [ 8 ] [ 27 ] [ 28 ] The amount of sulfuryl fluoride released into the atmosphere is about 2000 metric tons per year. [ 8 ] The most important loss process of sulfuryl fluoride is dissolution of atmospheric sulfuryl fluoride in the ocean followed by hydrolysis. | https://en.wikipedia.org/wiki/SO2F2 |
Sulfuryl chloride fluoride is a chemical compound with the formula S O 2 Cl F . It is a colorless, easily condensed gas. It is a tetrahedral molecule.
Liquified sulfuryl chloride fluoride is employed as a solvent for highly oxidizing compounds. [ 1 ]
The laboratory-scale synthesis begins with the preparation of potassium fluorosulfite : [ 2 ]
This salt is then chlorinated to give sulfuryl chloride fluoride [ 3 ]
Further heating (180 °C) of potassium fluorosulfite with the sulfuryl chloride fluoride gives sulfuryl fluoride .
Alternatively, sulfuryl chloride fluoride can be prepared without using gases as starting materials by treating sulfuryl chloride with ammonium fluoride or potassium fluoride in trifluoroacetic acid . [ 4 ] | https://en.wikipedia.org/wiki/SO2FCl |
Sulfamic acid , also known as amidosulfonic acid , amidosulfuric acid , aminosulfonic acid , sulphamic acid and sulfamidic acid , is a molecular compound with the formula H 3 NSO 3 . This colourless, water-soluble compound finds many applications. Sulfamic acid melts at 205 °C before decomposing at higher temperatures to water , sulfur trioxide , sulfur dioxide and nitrogen . [ 2 ]
Sulfamic acid (H 3 NSO 3 ) may be considered an intermediate compound between sulfuric acid (H 2 SO 4 ), and sulfamide (H 4 N 2 SO 2 ), effectively replacing a hydroxyl (–OH) group with an amine (–NH 2 ) group at each step. This pattern can extend no further in either direction without breaking down the sulfonyl (–SO 2 –) moiety. Sulfamates are derivatives of sulfamic acid.
Sulfamic acid is produced industrially by treating urea with a mixture of sulfur trioxide and sulfuric acid (or oleum ). The conversion is conducted in two stages, the first being sulfamation :
In this way, approximately 96,000 tonnes were produced in 1995. [ 3 ]
The compound is well described by the formula H 3 NSO 3 , not the tautomer H 2 NSO 2 (OH). The relevant bond distances are 1.44 Å for the S=O and 1.77 Å for the S–N. The greater length of the S–N is consistent with a single bond. [ 5 ] Furthermore, a neutron diffraction study located the hydrogen atoms, all three of which are 1.03 Å distant from the nitrogen. [ 4 ] In the solid state, the molecule of sulfamic acid is well described by a zwitterionic form.
The crystalline solid is indefinitely stable under ordinary storage conditions, however, aqueous solutions of sulfamic acid slowly hydrolyse to ammonium bisulfate , according to the following reaction:
Its behaviour resembles that of urea , (H 2 N) 2 CO. Both feature amino groups linked to electron-withdrawing centres that can participate in delocalised bonding . Both liberate ammonia upon heating in water, with urea releasing CO 2 while sulfamic acid releases sulfuric acid .
Sulfamic acid is a moderately strong acid, K a = 0.101 (p K a = 0.995). Because the solid is not hygroscopic , it is used as a standard in acidimetry (quantitative assays of acid content).
Double deprotonation can be effected in liquid ammonia to give the anion HNSO 2− 3 . [ 6 ]
With nitrous acid , sulfamic acid reacts to give nitrogen :
while with concentrated nitric acid , it affords nitrous oxide : [ 7 ]
The reaction of excess hypochlorite ions with sulfamic acid or a sulfamate salt gives rise reversibly to both N -chlorosulfamate and N , N -dichlorosulfamate ions. [ 8 ] [ 9 ] [ 10 ]
Consequently, sulfamic acid is used as hypochlorite scavenger in the oxidation of aldehydes with chlorite such as the Pinnick oxidation .
Upon heating sulfamic acid will react with alcohols to form the corresponding organosulfates . It is more expensive than other reagents for doing this, such as chlorosulfonic acid or oleum , but is also significantly milder and will not sulfonate aromatic rings. Products are produced as their ammonium salts. Such reactions can be catalyzed by the presence of urea . [ 10 ] Without the presence of any catalysts, sulfamic acid will not react with ethanol at temperatures below 100 °C.
An example of this reaction is the production 2-ethylhexyl sulfate, a wetting agent used in the mercerisation of cotton, by combining sulfamic acid with 2-ethylhexanol .
Sulfamic acid is mainly a precursor to sweet-tasting compounds. Reaction with cyclohexylamine followed by addition of NaOH gives C 6 H 11 NHSO 3 Na, sodium cyclamate . Related compounds are also sweeteners , such as acesulfame potassium .
Sulfamates have been used in the design of many types of therapeutic agents such as antibiotics , nucleoside/nucleotide human immunodeficiency virus (HIV) reverse transcriptase inhibitors , HIV protease inhibitors (PIs), anticancer drugs ( steroid sulfatase and carbonic anhydrase inhibitors), anti-epileptic drugs, and weight loss drugs . [ 11 ]
Sulfamic acid is used as an acidic cleaning agent and descaling agent sometimes pure or as a component of proprietary mixtures, typically for metals and ceramics . For cleaning purposes, there are different grades based on application such as GP Grade, SR Grade and TM Grade. It is frequently used for removing rust and limescale , replacing the more volatile and irritating hydrochloric acid , which is cheaper. It is often a component of household descalant, for example, Lime-A-Way Thick Gel contains up to 8% sulfamic acid and has pH 2.0–2.2, [ 12 ] or detergents used for removal of limescale . When compared to most of the common strong mineral acids , sulfamic acid has desirable water descaling properties, low volatility, and low toxicity. It forms water-soluble salts of calcium, nickel, and ferric iron.
Sulfamic acid is preferable to hydrochloric acid in household use, due to its intrinsic safety. If inadvertently mixed with hypochlorite based products such as bleach , it does not form chlorine gas, whereas the most common acids would; the reaction ( neutralisation ) with ammonia , produces a salt, as depicted in the section above.
It also finds applications in the industrial cleaning of dairy and brewhouse equipment. Although it is considered less corrosive than hydrochloric acid , corrosion inhibitors are often added to the commercial cleansers of which it is a component. It can be used as a descalant for descaling home coffee and espresso machines and in denture cleaners.
According to the label on the consumer product, the silver cleaning product TarnX contains thiourea , a detergent , and sulfamic acid. | https://en.wikipedia.org/wiki/SO3NH3 |
SOBER1 is an enzyme that catalyzes the biochemical reaction of deacetylation . [ 1 ] The SOBER ( S uppressor o f Avr B sT- e licited r esistance) 1 protein is conserved in plants and it suppresses the plant's ability to carry out the hypersensitive response against infection by certain pathogenic effector proteins from the YopJ family. [ 2 ] SOBER1 belongs to the protein superfamily of α/β hydrolases and possesses a canonical serine / histidine / aspartate catalytic triad to carry out the deacetylation reaction. There have been contradicting reports about SOBER1's potential phospholipase activity, with one study claiming phospholipase A 2 activity of the protein [ 3 ] and another study being unable to reproduce this result. [ 1 ]
Members of the SOBER1 family are considered closely related to acyl-protein thioesterases , judged by their protein structure . [ 2 ] However, a change in their amino acid sequence renders SOBER1's biochemical properties into a deacetylase; in particular the hydrophobic tunnel, which is found in acyl-protein thioesterases, is impaired by additional amino acids in the lid structure of SOBER1, creating a new surface for binding of the acetyl group . [ 1 ]
So far, the following proteins have been identified as SOBER1 targets : AvrBsT; ACIP1. | https://en.wikipedia.org/wiki/SOBER1 |
PBr 3 , Br 2
Thionyl bromide is the chemical compound SOBr 2 . It is less stable and less widely used than its chloride analogue, thionyl chloride , but engages in similar reactions. [ 3 ]
It is prepared by the action of hydrogen bromide on thionyl chloride, [ 4 ] although the corresponding reaction at higher pH (i.e. alkali bromides) proceeds only with difficulty: [ 1 ]
Phosphorus trichlorodibromide (but not phosphorus pentabromide !) converts sulfur dioxide to thionyl bromide. Thionyl chlorobromide appears to be a key intermediate in these syntheses, but has not been isolated. [ 1 ]
Thionyl bromide will convert alcohols to alkyl bromides and carboxylic acids to acyl bromides. Unlike with thionyl chloride, stoichiometric bases are problematic activating agents, because free bromide anions decompose thionyl bromide to tribromide , sulfur dioxide , and sulfur . [ 1 ]
It can be used for brominations of certain α,β-unsaturated carbonyl compounds. [ 5 ]
It may occasionally be used as a solvent. [ 6 ] [ 7 ]
SOBr 2 hydrolyzes readily in air to release dangerous fumes of sulfur dioxide and hydrogen bromide .
Decomposition to bromine and sulfur monoxide does not occur except at elevated temperatures. [ 1 ]
This inorganic compound –related article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/SOBr2 |
Thionyl chloride is an inorganic compound with the chemical formula SOCl 2 . It is a moderately volatile , colourless liquid with an unpleasant acrid odour. Thionyl chloride is primarily used as a chlorinating reagent, with approximately 45,000 tonnes (50,000 short tons) per year being produced during the early 1990s, [ 5 ] but is occasionally also used as a solvent. [ 6 ] [ 7 ] [ 8 ] It is toxic, reacts with water, and is also listed under the Chemical Weapons Convention as it may be used for the production of chemical weapons .
Thionyl chloride is sometimes confused with sulfuryl chloride , SO 2 Cl 2 , but the properties of these compounds differ significantly. Sulfuryl chloride is a source of chlorine whereas thionyl chloride is a source of chloride ions.
The major industrial synthesis involves the reaction of sulfur trioxide and sulfur dichloride . [ 9 ] This synthesis can be adapted to the laboratory by heating oleum to slowly distill the sulfur trioxide into a cooled flask of sulfur dichloride. [ 10 ]
Other methods include syntheses from:
The second of the above five reactions also affords phosphorus oxychloride (phosphoryl chloride), which resembles thionyl chloride in many of its reactions. They may be separated by distillation, since thionyl chloride boils at a much lower temperature than phosphoryl chloride. [ citation needed ]
SOCl 2 adopts a trigonal pyramidal molecular geometry with C s molecular symmetry . This geometry is attributed to the effects of the lone pair on the central sulfur(IV) center.
In the solid state SOCl 2 forms monoclinic crystals with the space group P2 1 /c. [ 11 ]
Thionyl chloride has a long shelf life, however "aged" samples develop a yellow hue, possibly due to the formation of disulfur dichloride . It slowly decomposes to S 2 Cl 2 , SO 2 and Cl 2 at just above the boiling point. [ 9 ] [ 12 ] Thionyl chloride is susceptible to photolysis , which primarily proceeds via a radical mechanism. [ 13 ] Samples showing signs of ageing can be purified by distillation under reduced pressure, to give a colourless liquid. [ 14 ]
Thionyl chloride is mainly used in the industrial production of organochlorine compounds , which are often intermediates in pharmaceuticals and agrichemicals. It usually is preferred over other reagents, such as phosphorus pentachloride , as its by-products (HCl and SO 2 ) are gaseous, which simplifies purification of the product.
Many of the products of thionyl chloride are themselves highly reactive and as such it is involved in a wide range of reactions.
Thionyl chloride reacts exothermically with water to form sulfur dioxide and hydrochloric acid :
By a similar process it also reacts with alcohols to form alkyl chlorides . If the alcohol is chiral the reaction generally proceeds via an S N i mechanism with retention of stereochemistry; [ 15 ] however, depending on the exact conditions employed, stereo-inversion can also be achieved. Historically the use of SOCl 2 with pyridine was called the Darzens halogenation , but this name is rarely used by modern chemists.
Reactions with an excess of alcohol produce sulfite esters , which can be powerful methylation , alkylation and hydroxyalkylation reagents. [ 16 ]
For example, the addition of SOCl 2 to amino acids in methanol selectively yields the corresponding methyl esters. [ 17 ]
Classically, it converts carboxylic acids to acyl chlorides : [ 18 ] [ 19 ] [ 20 ]
The reaction mechanism has been investigated: [ 21 ]
With primary amines, thionyl chloride gives sulfinylamine derivatives (RNSO), one example being N - sulfinylaniline . Thionyl chloride reacts with primary formamides to form isocyanides [ 22 ] and with secondary formamides to give chloro iminium ions; as such a reaction with dimethylformamide will form the Vilsmeier reagent . [ 23 ]
By an analogous process, primary amides will react with thionyl chloride to form imidoyl chlorides , with secondary amides also giving chloro iminium ions. These species are highly reactive and can be used to catalyse the conversion of carboxylic acids to acyl chlorides; [ 24 ] they are also exploited in the Bischler–Napieralski reaction as a means of forming isoquinolines .
Primary amides will continue on to form nitriles if heated ( Von Braun amide degradation ). [ 25 ]
Thionyl chloride has also been used to promote the Beckmann rearrangement of oximes .
Thionyl chloride converts phosphonic acids and phosphonates into phosphoryl chlorides . It is for this type of reaction that thionyl chloride is listed as a Schedule 3 compound, as it can be used in the "di-di" method of producing G-series nerve agents . For example, thionyl chloride converts dimethyl methylphosphonate into methylphosphonic acid dichloride , which can be used in the production of sarin and soman .
As SOCl 2 reacts with water it can be used to dehydrate various metal chloride hydrates, such magnesium chloride ( MgCl 2 ·6H 2 O ), aluminium chloride ( AlCl 3 ·6H 2 O ), and iron(III) chloride ( FeCl 3 ·6H 2 O ). [ 9 ] This conversion involves treatment with refluxing thionyl chloride and follows the following general equation: [ 31 ]
If an exces SOCl2 is used to dehydrate aluminium trichloride, it will form an adduct (1 molecule of thionyl chloride for each molecule of the aluminium trichloride dimer).
Thionyl chloride is a component of lithium–thionyl chloride batteries , [ 37 ] where it acts as the positive electrode (in batteries: cathode ) with lithium forming the negative electrode ( anode ); the electrolyte is typically lithium tetrachloroaluminate . The overall discharge reaction is as follows:
These non-rechargeable batteries have advantages over other forms of lithium batteries such as a high energy density, a wide operational temperature range, and long storage and operational lifespans. However, their high cost, non-rechargeability, and safety concerns have limited their use. The contents of the batteries are highly toxic and require special disposal procedures; additionally, they may explode if shorted. The technology was used on the 1997 Sojourner Mars rover.
SOCl 2 is highly reactive and can violently release hydrochloric acid upon contact with water and alcohols. It is also a controlled substance under the Chemical Weapons Convention , where it is listed as a Schedule 3 substance, since it is used in the manufacture of G-series nerve agents [ citation needed ] and the Meyer and Meyer–Clarke methods of producing sulfur-based mustard gases . [ 38 ]
In 1849, the French chemists Jean-François Persoz and Bloch, and the German chemist Peter Kremers (1827–?), independently first synthesized thionyl chloride by reacting phosphorus pentachloride with sulfur dioxide . [ 39 ] [ 40 ] However, their products were impure: both Persoz and Kremers claimed that thionyl chloride contained phosphorus, [ 41 ] and Kremers recorded its boiling point as 100 °C (instead of 74.6 °C). In 1857, the German-Italian chemist Hugo Schiff subjected crude thionyl chloride to repeated fractional distillations and obtained a liquid which boiled at 82 °C and which he called Thionylchlorid . [ 42 ] In 1859, the German chemist Georg Ludwig Carius noted that thionyl chloride could be used to make acid anhydrides and acyl chlorides from carboxylic acids and to make alkyl chlorides from alcohols . [ 43 ] | https://en.wikipedia.org/wiki/SOCl2 |
Thionyl tetrafluoride , also known as sulfur tetrafluoride oxide , is an inorganic compound with the formula S O F 4 . It is a colorless gas .
The shape of the molecule is a distorted trigonal bipyramid , with the oxygen found on the equator. The atoms on the equator have shorter bond lengths than the fluorine atoms on the axis. In the gas-phase, the sulfur-oxygen bond is 1.409 Å . The S−F bond on the axis has length 1.596 Å and the S−F bond on the equator has length 1.539 Å. The angle between the equatorial fluorine atoms is 112.8°. The angle between axial fluorine and oxygen is 97.7°. The angle between oxygen and equatorial fluorine is 123.6° and between axial and equatorial fluorine is 85.7°. [ 2 ] Slight variations of bonds lengths and angles has been observed in solid-state by X-ray analysis. [ 3 ] The fluorine atoms only produce one NMR line, probably because they exchange positions . [ 1 ] It is isoelectronic with phosphorus pentafluoride .
Thionyl fluoride reacting with fluorine gas can produce thionyl tetrafluoride. [ 1 ] This was how the gas was first discovered by Moissan and Lebeau in 1902. They identified the formula by the pressure changes resulting from the reaction. Silver fluoride and platinum are capable of catalyzing the reaction.
It can also be formed the reaction of silver difluoride with thionyl fluoride at 392 °F (200 °C), [ 4 ] or by electrolyzing hydrogen fluoride with a solution of sulfur dioxide , which also made oxygen difluoride and sulfuryl fluoride . Thionyl chloride or thionyl fluoride electrolyzed with hydrogen fluoride produced even more of the gas. [ 5 ]
Thionyl tetrafluoride reacts with water to make hydrofluoric acid , sulfurofluoridic acid , and sulfuryl difluoride . Mercury can strip off fluoride to make thionyl fluoride and mercurous fluoride . Strong bases result in formation of fluoride and fluorosulfate ions. [ 1 ]
Reactions with the strong Lewis acids , such as AsF 5 and SbF 5 , result in the formation of trifluorosulfoxonium cation [SOF 3 ] + and the corresponding salts [SOF 3 ] + [AsF 6 ] − (trifluorosulfoxonium hexafluoroarsenate(V)) and [SOF 3 ] + [SbF 6 ] − (trifluorosulfoxonium hexafluoroantimonate(V)), respectively. [ 6 ]
Thionyl tetrafluoride can be used in click chemistry through reactions with primary amines known as sulfur(VI) fluoride exchange (SuFEx). [ 7 ] This kind of reaction was the first "click" reaction to generate a three-dimensional core. | https://en.wikipedia.org/wiki/SOF4 |
SOLAR-C (official name " High-sensitivity Solar Ultraviolet Spectroscopic Satellite " [ 1 ] ) is a planned Sun-observing satellite being developed by the Japan Aerospace Exploration Agency (JAXA), the National Astronomical Observatory of Japan (NAOJ), and international collaborators. It will be the follow-up to the Hinode (SOLAR-B) and Yohkoh (SOLAR-A) missions and will carry the EUV High-throughput Spectroscopic Telescope (EUVST) and the Solar Spectral Irradiance Monitor (SoSpIM). [ 2 ] [ 3 ] [ 4 ] [ 5 ] [ 6 ] It is scheduled to launch in fiscal year 2028. [ 7 ]
The mission aims to study the sun, its effects on Earth and the Solar System , and the mechanisms behind hot plasma formation. The satellite will also analyse the Sun's UV radiation spectrum. [ 8 ] [ 9 ] | https://en.wikipedia.org/wiki/SOLAR-C |
The SOLIDAC ( Solid-state Automatic Computer ) was a 50 kHz mini-computer at Glasgow University , built by Barr & Stroud in the late 1950s; Some early computer music was created on the system. [ 1 ]
The machine is currently housed in the National Museums Scotland Collection Centre in Granton, Edinburgh. [ 2 ]
This computing article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/SOLIDAC |
The SOPHIE (Spectrographe pour l’Observation des Phénomènes des Intérieurs stellaires et des Exoplanètes, literally meaning "spectrograph for the observation of the phenomena of the stellar interiors and of the exoplanets") échelle spectrograph is a high-resolution echelle spectrograph installed on the 1.93m reflector telescope at the Haute-Provence Observatory located in south-eastern France. The purpose of this instrument is asteroseismology [ 1 ] and extrasolar planet detection by the radial velocity method . It builds upon and replaces the older ELODIE spectrograph . This instrument was made available for use by the general astronomical community October 2006. [ 2 ]
The electromagnetic spectrum wavelength range is from 387.2 to 694.3 nanometers. The spectrograph is fed from the Cassegrain focus through either one of two separate optical fiber sets, yielding two different spectral resolutions (HE and HR modes). The instrument is entirely computer-controlled. A standard data reduction pipeline automatically processes the data upon every CCD readout cycle.
HR mode is the high resolution mode. This mode incorporates a 40 micrometre exit slit to achieve high spectral resolution of R = 75000.
HE mode is the high efficiency mode. This mode is used when a higher throughput is desired particularly in the case of faint objects spectral resolution is set to R = 40000.
The R2 échelle diffraction grating has 52.65 grooves per millimeter and was manufactured by Richardson Gratings. It is blazed at 65° and its size is 20.4 cm x 40.8 cm. It is mounted in a fixed configuration. The spectrum is projected onto the E2V Technologies type 44-82 CCD detector of 4096 x 2048 pixels kept at a constant temperature of –100 °C. This grating yields 41 spectral orders , of which 39 are currently extracted, to obtain wavelengths between 387.2 nm and 694.3 nm. [ 2 ]
In HE mode , a signal-to-noise ratio (per pixel) of 27 was reached in 90 min for an object of magnitude 14.5 in the V band .
The stability of the instrument can be described by the lowest dispersion possible for radial velocity observations, in m/s. In HR mode the short term stability has been measured to be 1.3 m/s, [ 2 ] while it is 2 m/s for longer timescales. [ 3 ] | https://en.wikipedia.org/wiki/SOPHIE_échelle_spectrograph |
The SOS chromotest is a biological assay to assess the genotoxic potential of chemical compounds. The test is a colorimetric assay which measures the expression of genes induced by genotoxic agents in Escherichia coli , by means of a fusion with the structural gene for β-galactosidase . The test is performed over a few hours in columns of a 96-well microplate with increasing concentrations of test samples. This test was developed as a practical complement or alternative to the traditional Ames test assay for genotoxicity , which involves growing bacteria on agar plates and comparing natural mutation rates to mutation rates of bacteria exposed to potentially mutagenic compounds or samples. The SOS chromotest is comparable in accuracy and sensitivity to established methods such as the Ames test and is a useful tool to screen genotoxic compounds, which could prove carcinogenic in humans, in order to single out chemicals for further in-depth analysis. [ 1 ] [ 2 ]
As with other bacterial gentoxicity and mutagenicity assays, compounds requiring metabolic activation for activity can be investigated with the addition of S9 microsomal rat liver extract.
The SOS response plays a central role in the response of E. coli to genotoxic compounds because it responds to a wide array of chemical agents. Triggering of this system can and has been used as an early sign of DNA damage. Two genes play a key role in the SOS response: lexA encodes a repressor for all the genes in the system, and recA encodes a protein able to cleave the LexA repressor upon activation by an SOS inducing signal (caused in this case by the presence of a genotoxic compound). Although the exact mechanism of the SOS response is still unknown, it is induced when DNA lesions perturb or stop DNA replication. . [ 3 ]
Various end-points are possible indicators of the triggering of the SOS system; activation of the RecA protein, cleavage of the LexA repressor, expression of any of the SOS genes, etc. One of the simplest assays consists of monitoring the expression of an SOS gene by means of fusion with lacZ, the structural gene for E. coli β-galactosidase.
The SOS chromotest consists of incubating the E. coli with increasing concentrations of the chemical to be tested. After allowing time for protein synthesis, β-galactosidase activity is assayed using a simple colorimetric assay. By including a lactose analog which yields a colored compound upon degradation, an easily observable or quantifiable change in colour is used as a metric. Since the chemical tested may inhibit protein synthesis at higher concentrations, which would lead to an underestimation of B-galactosidase induction, alkaline phosphatase is assayed simultaneously with β-galactosidase in order to scale the data to survivability of the cells.
The assay can easily be completed in a number of hours. If using a micro-plate reader, the test is quantitative and dose-response curves have an initial linear region. The slope of this linear region allows unequivocal association of each compound with a single parameter, the SOS-inducing potency (SOSIP), which reflects the inducing activity of the compound. [ 4 ]
This assay provides both a qualitative (visible observation of colour gradient) for screening purposes, or quantitative measurement (spectrophotometry) for calculation of commonly accepted metrics. In the quantitative assay, the dose-response (colour production linked to beta-galactosidase production) of a compound is plotted, with the slope of the initial linear region used as a universal parameter, the SOS-inducing potency (SOSIP), which reflects the ability of a compound to induce the SOS response (measured indirectly through production of beta-galactosidase and the breakdown of a lactose analog). Typically, the lactose analog is X-Gal , which produces a blue colour when cleaved by beta-galactosidase. The dose response is also scaled by the survival of cells, measured through the breakdown of alkaline phosphatase (which produces a yellow colour), allowing for the calculation of the SOSIP.
Although the SOSIP is a concentration-based metric, the same method can be used for complex environmental mixtures where the concentration or even compounds of interest are unknown. Through the calculation of the intermediate SOS-induction factor (SOSIF), which can be plotted against dilution in the same manner in order to give an illustration of the dose-response without analytical measurements of samples beforehand.
THE SOS chromotest is considered to be the most simple and rapid short-term test for genotoxicity. It serves as a useful and cost effective complement to the traditional Ames test for a number of reasons. Firstly, because of its simplicity and rapidity, the SOS chromotest may be used as a screening test for a large number of potentially genotoxic compounds. Secondly, it may allow the detection of genotoxic chemicals which yield false negatives in the Ames test (such as estradiol, a compound of growing concern). Thirdly, it can prove an effective method to discriminate false positive results in the Ames test. | https://en.wikipedia.org/wiki/SOS_chromotest |
SPAdes (St. Petersburg genome assembler ) [ 1 ] is a genome assembly algorithm which was designed for single cell and multi-cells bacterial data sets. Therefore, it might not be suitable for large genomes projects. [ 1 ] [ 2 ]
SPAdes works with Ion Torrent , PacBio , Oxford Nanopore , and Illumina paired-end, mate-pairs and single reads . [ 1 ] SPAdes has been integrated into Galaxy pipelines by Guy Lionel and Philip Mabon. [ 3 ]
Studying the genome of single cells will help to track changes that occur in DNA over time or associated with exposure to different conditions. Additionally, many projects such as Human Microbiome Project and antibiotics discovery would greatly benefit from Single-cell sequencing (SCS). [ 4 ] [ 5 ] SCS has an advantage over sequencing DNA extracted from large number of cells. The problem of averaging out the significant variations between cells can be overcome by using SCS. [ 6 ] Experimental and computational technologies are being optimized to allow researchers to sequence single cells. For instance, amplification of DNA extracted from a single cell is one of the experimental challenges. To maximize the accuracy and quality of SCS, a uniform DNA amplification is needed. It was demonstrated that using multiple annealing and looping-based amplification cycles ( MALBAC ) for DNA amplification generates less biasness compared to polymerase chain reaction ( PCR ) or multiple displacement amplification (MDA). [ 7 ] Furthermore, it has been recognized that the challenges facing SCS are computational rather than experimental. [ 8 ] Currently available assembler, such as Velvet , [ 9 ] String Graph Assembler (SGA) [ 10 ] and EULER-SR, [ 11 ] were not designed to handle SCS assembly. [ 2 ] Assembly of single cell data is difficult due to non-uniform read coverage, variation in insert length, high levels of sequencing errors and chimeric reads. [ 8 ] [ 12 ] [ 13 ] Therefore, the new algorithmic approach, SPAdes, was designed to address these issues.
SPAdes uses k-mers for building the initial de Bruijn graph and on following stages it performs graph-theoretical operations which are based on graph structure, coverage and sequence lengths. Moreover, it adjusts errors iteratively. [ 2 ] The stages of assembly in SPAdes are: [ 2 ]
SPAdes was designed to overcome the problems associated with the assembly of single cell data as follows: [ 2 ]
1. Non-uniform coverage .
SPAdes utilizes multisized de Bruijn graph which allows employing different values of k. It has been suggested to use smaller values of k in low-coverage regions to minimize fragmentation, and larger values of k in high coverage regions to decrease repeat collapsing (Stage 1 above).
2. Variable insert sizes of paired-end reads . SPAdes employs the basic concept of paired de Bruijn graphs. However, paired de Bruijn works well on paired-end reads with fixed insert size. Therefore, SPAdes estimates 'distances' instead of using 'insert sizes'. Distance (d) of a paired-end read is defined as, for a read length L, d = insert size – L. By utilizing k-bimer adjustment approach, distances are exactly estimated. A k-bimer consisting of k-mers ‘α’ and ‘β’ together with the estimated distance between them in a genome (α|β,d). This approach breaks the paired–end reads into pairs of k-mers which are transformed to define pairs of edges (biedges) in the de Bruijn graphs. These sets of biedges are involved in the estimation of distances between edges paths between k-mers α and β. By clustering, the optimal distance estimate is chosen from each cluster (stage 2, above).
To construct paired de Bruijn graph, the rectangle graphs are employed in SPAdes (stage 3). Rectangle graphs approach was first introduced in 2012 [ 15 ] to construct paired de Bruijn graphs with doubtful distances.
3. Bulge, tips and chimeras . Bulges and tips occur due to errors in the middle and ends of reads, respectively. A chimeric connection joins two unrelated substrings of the genome. SPAdes identifies these based on graph topology, the length and coverage of the non-branching paths included in them. SPAdes keeps a data structure to be able to backtrack all corrections or removals.
SPAdes modifies the previously used bulge removal approach [ 16 ] and iterative de Bruijn graph approach from Peng et al (2010) [ 17 ] and creates a new approach called ‘‘bulge corremoval’’, which stands for bulge correction and removal.
The bulge corremoval algorithm can be summarized as follows: a simple bulge is formed by two small and similar paths (P and Q) connecting the same hubs. If P is a non-branching path (h-path), then SPAdes maps every edge in P to an edge projection in Q and removes P from the graph, as a result the coverage of Q increases.
Unlike other assemblers, which use a fixed coverage cut-off bulge removal, SPAdes removes or projects the h-paths with low coverage step by step. This is achieved by employing gradually increasing cut-off thresholds and iterating through all h-paths in increasing order of coverage (for bulge corremoval and chimeric removal) or length (for tip removal).
Moreover, in order to guarantee that no new sources/sinks are introduced to the graph, SPAdes deletes an h-path (in chimeric h-path removal) or projects (in bulge corremoval) only if its start and end vertices have at least two outgoing and ingoing edges . This helps to remove low coverage h-paths occurring from sequencing errors and chimeric reads but not from repeats.
SPAdes is composed of the following tools: [ 1 ]
A study [ 18 ] compared several genome assemblers on single cell E. coli samples. These assemblers are EULER-SR, [ 11 ] Velvet, [ 9 ] SOAPdenovo, [ 19 ] Velvet-SC, EULER+ Velvet-SC (E+V-SC), [ 16 ] IDBA-UD [ 20 ] and SPAdes.
It was demonstrated that IDBA-UD and SPAdes performed the best. [ 18 ] SPAdes had the largest NG50 (99,913, NG50 statistics is the same as the N50 except that the genome size is used rather than the assembly size). [ 21 ] Moreover, using E. coli reference genome, [ 22 ] SPAdes assembled the highest percentage of genome (97%) and the highest number of complete genes (4,071 out of 4,324). [ 18 ] The assemblers’ performances were as follows: [ 18 ]
IDBA-UD < Velvet < E+V-SC < SPAdes < EULER-SR < Velvet-SC < SOAPdenovo
SPAdes > IDBA-UD >>> E+V-SC > EULER-SR >Velvet >Velvet-SC > SOAPdenovo
IDBA-UD > SPAdes > > EULER-SR > Velvet= E+V-SC > Velvet-SC > SOAPdenovo
SPAdes > IDBA-UD > E+V-SC > Velvet-SC > EULER-SR > SOAPdenovo > Velvet
E+V-SC = Velvet = Velvet-SC < SOAPdenovo < IDBA-UD < SPADes < EULER-SR | https://en.wikipedia.org/wiki/SPAdes_(software) |
The SPC file format is a file format for storing spectroscopic data. [ 1 ]
The SPC file format is a file format in which all kinds of spectroscopic data, including among others infrared spectra , Raman spectra and UV/VIS spectra . The format can be regarded as a database with records of variable length and each record stores a different kind of data (instrumental information, information on one spectrum of a dataset, the spectrum itself or extra logs). [ 2 ] It was invented by Galactic Industries as generic file format for its programs. Their original specification was implemented in 1986, but a more versatile format was created in 1996. [ 3 ]
Galactic Industries was purchased by Thermo Fisher Scientific who now maintain and develop the GRAMS Software Suite for which the format was defined. They provide free tools and libraries to allow developers to create and maintain SPC files consistently. [ 4 ]
This file format is not in plaintext, such as XML or CSV, but is a binary format and is therefore not readable with a standard text editor but requires a special reader or software to interpret the file data. The Environmental Protection Agency publishes a free spectra reader called ShowSPC that is open to the public for reading spectra data. [ 5 ] Additionally, a company AnalyzeIQ produces a free SPC to CSV converter aptly titled SPC2CSV, an open-source project OpenSpectralWorks [ 6 ] is an alternative free reader, as well as SpectraGryph which has analytic and display capabilities for reading SPC files. [ 7 ] The Essential FTIR software offers a file reader that can read, display, analyze and export .spc files as well as many other spectroscopy file formats. [ 8 ] | https://en.wikipedia.org/wiki/SPC_file_format |
SPEAR pesticides (Species At Risk) is a trait based biological indicator system for streams which quantitatively links pesticide contamination to the composition of macroinvertebrate communities. [ 1 ] The approach uses species traits that characterize the ecological requirements posed by pesticide contamination in running waters. Therefore, it is highly specific and only slightly influenced by other environmental factors. [ 2 ] SPEAR pesticides is linked to the quality classes of the EU Water Framework Directive (WFD) [ 3 ]
SPEARpesticides has been first developed for Central Germany [ 1 ] and updated. [ 4 ] SPEAR pesticides was adapted and validated for streams and mesocosms worldwide and provides the first ecotoxicological approach to specifically determine the ecological effects of pesticides on aquatic invertebrate communities. Argentina, [ 5 ] Australia [ 6 ] [ 7 ] Denmark, [ 8 ] [ 9 ] Finland, [ 9 ] France, [ 9 ] Germany, [ 1 ] [ 9 ] [ 10 ] Kenya, [ 11 ] Switzerland, USA, [ 12 ] Russia [ 13 ] Mesocosms. [ 14 ]
SPEAR pesticides estimates pesticide effects and contamination. The calculation is based on monitoring data of invertebrate communities as ascertained for the EU Water Framework Directive (WFD) . A simplified version of SPEAR pesticides is included in the ASTERICS software for assessing the ecological quality of rivers. A detailed analysis is enabled by the free SPEAR Calculator . The SPEAR Calculator provides most recent information on species traits and allows specific user settings.
The SPEAR pesticides index is computed as relative abundance of vulnerable 'SPecies At Risk' (SPEAR) to be affected by pesticides. Relevant species traits comprises the physiological sensitivity towards pesticides, generation time, migration ability and exposure probability. The indicator value of SPEAR pesticides at a sampling site is calculated as follows:
S P E A R p e s t i c i d e s = ∑ i = 1 n log ( 4 x i + 1 ) y ∑ i = 1 n log ( 4 x i + 1 ) {\displaystyle SPEAR_{pesticides}={\frac {\sum _{i=1}^{n}\log(4x_{i}+1)y}{\sum _{i=1}^{n}\log(4x_{i}+1)}}}
with n = number of taxa; x i = abundance of taxon i; y = 1 if taxon i is classified as SPEAR-sensitive; y = 0 if taxon i is classified as SPEAR-insensitive.
An application is available for the calculation. Web address of SPEAR calculator | https://en.wikipedia.org/wiki/SPEARpesticides |
SPEEDAC , the SPE rry E lectronic D igital A utomatic C omputer, was an early digital computer built by Sperry Corporation in 1953. [ 1 ]
It used 800 vacuum tubes and had magnetic drum storage of 4096 18-bit words . [ 1 ] [ 2 ]
This computing article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/SPEEDAC |
The SPEX ( Spectropolarimeter for Planetary Exploration ) is a single-channel, high-precision polarimeter for the characterization of planetary atmospheres. [ 1 ] It is intended for planetary science missions, but it could, with minor modifications, also be used for Earth observation by a microsatellite , such as the Dutch FAST-D project. [ 2 ]
This astronomy -related article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/SPEX_(astronomy) |
SPE John Franklin Carll Award is one of the Society of Petroleum Engineers ' (SPE) highest prizes, established in 1956. It recognizes contributions of applications of engineering practices in petroleum development and recovery. The prize is named in honor of John Franklin Carll , a geologist of the 19th century, who was involved with writing reports on oil and gas surveys.
This engineering-related article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/SPE_John_Franklin_Carll_Award |
SPHEREx ( Spectro-Photometer for the History of the Universe, Epoch of Reionization, and Ices Explorer ) [ 4 ] is a near-infrared space observatory that will perform an all-sky survey to measure the near-infrared spectra of approximately 450 million galaxies . In February 2019, SPHEREx was selected by NASA for its next Medium-Class Explorers mission, beating out two competing mission concepts: Arcus and FINESSE . [ 5 ] [ 6 ] SPHEREx launched on 11 March 2025 on a Falcon 9 Block 5 rocket alongside the PUNCH microsatellites from Vandenberg Space Force Base . [ 2 ] [ 3 ] The principal investigator is James Bock at California Institute of Technology (Caltech) in Pasadena, California .
SPHEREx will use a spectrophotometer to perform an all-sky survey that will measure near-infrared spectra from 0.75 to 5.0 micrometers. It will employ a single instrument with a single observing mode and no moving parts to map the entire sky (in 96
different color bands, far exceeding the color resolution of previous all-sky maps [ 5 ] ) four times during its nominal 25-month mission; the crucial technology is a linear variable filter , [ 7 ] as demonstrated by LEISA on New Horizons . [ 8 ]
It will classify galaxies according to redshift accuracy, categorizing approximately 450 million galaxies and fitting measured spectra to a library of galaxy templates. Specifically, SPHEREx will probe signals from the intra-halo light and from the epoch of reionization . [ 7 ] It would explore what drove the early universe inflation , explore the origin and history of galaxies, and explore the origin of water in planetary systems. [ 7 ] [ 9 ] [ 10 ]
SPHEREx will complement the Euclid and planned Nancy Grace Roman Space Telescope spectroscopic surveys. High precision redshift information of foreground galaxies provided by SPHEREx in correspondence with weak gravitational lensing measurements of background galaxies from Euclid and Nancy Grace Roman Space Telescope will allow direct measurement of the dark matter distribution surrounding the foreground galaxies. [ 11 ] The SPHEREx low redshift survey allows its measurement of inflationary parameters to be mostly independent, thus providing a new line of evidence. [ 10 ] [ 7 ]
The triple mirror telescope has an aperture diameter of 20 centimeters with a 3.5° × 11° field of view and six 2K × 2K mercury cadmium telluride (HgCdTe) photodetector arrays. [ 12 ] [ 8 ] Each 2K × 2K focal-plane array is covered with a linear variable filter, providing narrow-band response with a band center that varies along one axis of the array. SPHEREx obtains spectra through multiple exposures, placing a given source at multiple positions in the field of view, where it is measured at multiple wavelengths by repointing the spacecraft. [ 8 ]
The SPHEREx spacecraft and telescope were provided by BAE Systems Inc. Space & Mission Systems division (previously Ball Aerospace & Technologies ) while the payload was developed by Caltech and NASA's Jet Propulsion Laboratory . The Korea Astronomy and Space Science Institute supplied a non-flight cryogenic test chamber. [ 13 ] [ 14 ] [ 15 ]
The SPHEREx proposal was submitted to NASA on 19 December 2014, and it was selected for further conceptual development (Phase A) on 30 July 2015 for the Small Explorer program (SMEX). [ 16 ] [ 17 ] The detailed concept study report was submitted to NASA on 19 July 2016, but it was not selected for SMEX. An enhanced version of SPHEREx was submitted on 15 December 2016 as a Medium-Class Explorer (MIDEX), and it was selected as a finalist in August 2017, along two other competing missions: Arcus , and Fast Infrared Exoplanet Spectroscopy Survey Explorer (FINESSE). [ 6 ] Each team received US$2 million to refine their mission concepts over nine-months. [ 6 ]
SPHEREx was selected as the winner in February 2019, and the mission has been approved to proceed with construction and launch. [ 5 ] Medium-Class Explorer mission costs are capped at US$250 million, not including the launch vehicle. [ 6 ] As of April 2020, the preliminary total cost of the mission is approximately US$395 million to US$427 million. [ 18 ] The 2020 estimates include the costs of the launch vehicle and NASA reserves that are not part of the cost cap.
On 7 January 2021, NASA announced that the mission has entered Phase C, which means that the early design plans have been approved and teams can begin the final design and assemble hardware and software; and that launch is expected between June 2024 and April 2025. [ 19 ] On 4 February 2021, NASA announced they had selected the SpaceX Falcon 9 to launch the spacecraft, and total cost of the launch would be US$98.8 million. [ 20 ] In August 2022 NASA announced that the 4 microsatellites of the PUNCH constellation would be launched as rideshare payloads together with SPHEREx. [ 21 ] The mission launched on 11 March 2025. [ 2 ] First light was on April 2025. [ 22 ] Regular science operation started on 1 May 2025. [ 23 ] | https://en.wikipedia.org/wiki/SPHEREx |
SPI-4.2 is a version of the System Packet Interface published by the Optical Internetworking Forum . It was designed to be used in systems that support OC-192 SONET interfaces and is sometimes used in 10 Gigabit Ethernet based systems.
SPI-4 is an interface for packet and cell transfer between a physical layer (PHY) device and a link layer device, for aggregate bandwidths of OC-192 Asynchronous Transfer Mode and Packet over SONET/SDH (POS), as well as 10 Gigabit Ethernet applications.
SPI-4 has two types of transfers—Data when the RCTL signal is deasserted; Control when the RCTL signal is asserted. The transmit and receive data paths include, respectively, (TDCLK, TDAT[15:0],TCTL) and (RDCLK, RDAT[15:0], RCTL). The transmit and receive FIFO status channels include (TSCLK, TSTAT[1:0]) and (RSCLK, RSTAT[1:0]) respectively.
A typical application of SPI-4.2 is to connect a framer device to a network processor . It has been widely adopted by the high speed networking marketplace.
The interface consists of (per direction):
The clocking is source-synchronous and operates around 700 MHz. Implementations of SPI-4.2 have been produced which allow somewhat higher clock rates. This is important when overhead bytes are added to incoming packets.
PMC-Sierra made the original OIF contribution for SPI-4.2. That contribution was based on the PL-4 specification that was developed by PMC-Sierra in conjunction with the SATURN Development Group .
The physical layer of SPI-4.2 is very similar to the HyperTransport 1.x interface, although the logical layers are very different.
This computing article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/SPI-4.2 |
SPIKE ( Signaling Pathways Integrated Knowledge Engine ) is a database of highly curated interactions for particular human pathways. [ 1 ]
SPIKE was developed by Ron Shamir 's computational biology group in cooperation with the group of Yosef Shiloh, an Israel Prize recipient for his research in systems biology, and the group of Karen Avraham , a leading researcher of human deafness , all from Tel Aviv University .
This Biological database -related article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/SPIKE_(database) |
SPINE stands for strep–protein interaction experiment . SPINE is a powerful tool to detect protein–protein interactions in vivo. The bait protein has to be expressed with a Strep-tag under the conditions when the potential interaction partners are presumably present in the cells. The addition of formaldehyde links the bait protein to its potential interaction partners. The bait protein together with its potential interaction partners can then be isolated using a Strep-Tactin Sepharose column. The cross-links between the bait protein and the potential interaction partner can be cleaved by heating the samples in Laemmli buffer. Finally, the co-purified interaction partner can be separated by SDS PAGE and identified by mass spectrometry.
This molecular or cell biology article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/SPINE_(molecular_biology) |
SPOT is a GPS tracking device that uses the Globalstar satellite network [ 1 ] to provide text messaging and GPS tracking (depending on the subscription type purchased). [ 2 ] [ 3 ] It has a coverage area that includes a large portion of the planet, with the exception of extreme northern and southern latitudes and parts of the Pacific Ocean. [ 4 ] Depending on the product, SPOT can send and receive communications.
The device is sold by SPOT LLC, a subsidiary of Globalstar . [ 5 ]
With the purchase of a subscription, SPOT allows short (41 character [ 6 ] ) user-defined text messages which can be sent to a list of telephone numbers and e-mail addresses. This subscription also allows users to push their location to emergency services. Users can share their location and messages based on their account preference, alerting friends and family to their whereabouts.
In early 2018, SPOT launched the SPOT X, a two-way satellite messaging device with GPS location tracking, navigational capabilities, social media linking and direct communication options to emergency services. In February 2023, Kurt Knutsson of CyberGuy Report at Fox News included Spot X in a review of "the 5 best" personal locator beacons (PLB). [ 7 ]
As of 2019, SPOT has successfully helped initiate more than 6,000 rescues in 100 countries. [ 5 ]
This article relating to communication is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/SPOT_Satellite_Messenger |
The SPRESI data collection is one of the largest databases for organic chemistry worldwide. The database covers the scientific literature from 1974 to 2014, focusing on organic synthesis . It contains information on 5.8 million chemical structures and 4.6 million chemical reactions abstracted from 700,000 references.
Since 1974 the data collection has been jointly built by VINITI (All-Russian Institute of Scientific and Technical Information of the Russian Academy of Sciences, based in Moscow) and ZIC (Zentrale Informationsverarbeitung Chemie, based in east Berlin, up to 1989) and the data are now maintained by the VINITI Institute. Since 1990 InfoChem GmbH, part of DeepMatter Group , based in Munich, Germany, has been the distributor of this data collection and developed the database SPRESIweb and the app SPRESImobile.
The SPRESI database contains information on organic substances, including coverage of reactions, structures and properties. Over 32 million records of factual data, such as physical properties (boiling/melting points, refractive indexes, etc.), reaction conditions (catalysts, yields, etc.) and keywords have also been abstracted. Links to the literature in which the substances are described are also given.
The SPRESI data collection can be accessed online via the web-application SPRESI web , developed and distributed by InfoChem. Alternatively the complete set or subsets of the database can be acquired as raw data in SDF/RDF chemical file format .
Roth, Dana L. (2005). "SPRESIweb 2.1, a Selective Chemical Synthesis and Reaction Database". J. Chem. Inf. Model . 45 (5). American Chemical Society: 1470– 1473. doi : 10.1021/ci050274b .
Atkins, Peter W.; Eds. Garcia-Martinez, Javier; Serrano-Torregrosa, Elena (2015). Chemistry education: Best practices opportunities and trends . John Wiley and Sons. p. 624. ISBN 978-3-527-33605-0 . | https://en.wikipedia.org/wiki/SPRESI_database |
SQL:2016 or ISO/IEC 9075:2016 (under the general title "Information technology – Database languages – SQL") is the eighth revision of the ISO (1987) and ANSI (1986) standard for the SQL database query language . It was formally adopted in December 2016. [ 1 ] The standard consists of 9 parts which are described in some detail in SQL . The next version is SQL:2023 .
SQL:2016 introduced 44 new optional features. [ 2 ] 22 of them belong to the JSON functionality, ten more are related to polymorphic table functions. The additions to the standard include:
This computing article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/SQL:2016 |
SQL:2023 or ISO/IEC 9075:2023 (under the general title "Information technology – Database languages – SQL") is the ninth edition of the ISO (1987) and ANSI (1986) standard for the SQL database query language . It was formally adopted in June 2023.
SQL:2023 includes new and updated features. [ 1 ] The changes can be grouped into three main areas:
SQL/PGQ reduces the difference in functionality between relational DBMSs and native graph DBMSs. Basically, this new feature makes it easier to query data in tables as if it were in a graph database , providing a possibly more intuitive alternative to writing complex join queries. [ 4 ]
In comparison, the GQL standard for graph DBMSs adds graph updates, querying multiple graphs, and queries that return a graph result rather than a binding table. [ 5 ]
This computing article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/SQL:2023 |
SQLf is a SQL extended with fuzzy set theory application for expressing flexible ( fuzzy ) queries to traditional (or ″Regular″) Relational Databases. Among the known extensions proposed to SQL, at the present time, this is the most complete, because it allows the use of diverse fuzzy elements in all the constructions of the language SQL. [ 1 ] [ 2 ]
SQLf is the only known proposal of flexible query system allowing linguistic quantification over set of rows in queries, achieved through the extension of SQL nesting and partitioning structures with fuzzy quantifiers. It also allows the use of quantifiers to qualify the quantity of search criteria satisfied by single rows. Several mechanisms are proposed for query evaluation, [ 3 ] the most important being the one based on the derivation principle. [ 4 ] This consists in deriving classic queries that produce, given a threshold t , a t -cut of the result of the fuzzy query, so that the additional processing cost of using a fuzzy language is diminished.
The fundamental querying structure of SQLf is the multi-relational block. The conception of this structure is based on the three basic operations of the relational algebra : projection , cartesian product and selection , and the application of fuzzy sets’ concepts. The result of a SQLf query is a fuzzy set of rows that is a fuzzy relation instead of a regular relation.
A basic block in SQLf consists of a SELECT clause, a FROM clause and an optional WHERE clause. The semantic of this query structure is:
The following is an example of a SELECT query that returns a list of hotels that are cheap. The query retrieves all rows from the Hotels table that satisfice the fuzzy predicate cheap defined by the fuzzy set μ =( ∞ , ∞ , 25, 30). The result is sorted in descending order by the membership degree of the query. | https://en.wikipedia.org/wiki/SQLf |
A SQUID ( superconducting quantum interference device ) is a very sensitive magnetometer used to measure extremely weak magnetic fields , based on superconducting loops containing Josephson junctions .
SQUIDs are sensitive enough to measure fields as low as 5×10 −18 T with a few days of averaged measurements. [ 1 ] Their noise levels are as low as 3 f T· Hz − 1 ⁄ 2 . [ 2 ] For comparison, a typical refrigerator magnet produces 0.01 tesla (10 −2 T), and some processes in animals produce very small magnetic fields between 10 −9 T and 10 −6 T. SERF atomic magnetometers, invented in the early 2000s are potentially more sensitive and do not require cryogenic refrigeration but are orders of magnitude larger in size (~1 cm 3 ) and must be operated in a near-zero magnetic field.
There are two main types of SQUID: direct current (DC) and radio frequency (RF). RF SQUIDs can work with only one Josephson junction ( superconducting tunnel junction ), which might make them cheaper to produce, but are less sensitive.
The DC SQUID was invented in 1964 by Robert Jaklevic, John J. Lambe, James Mercereau, and Arnold Silver of Ford Research Labs [ 3 ] after Brian Josephson postulated the Josephson effect in 1962, and the first Josephson junction was made by John Rowell and Philip Anderson at Bell Labs in 1963. [ 4 ] It has two Josephson junctions in parallel in a superconducting loop. It is based on the DC Josephson effect. In the absence of any external magnetic field, the input current I {\displaystyle I} splits into the two branches equally. If a small external magnetic field is applied to the superconducting loop, a screening current, I s {\displaystyle I_{s}} , begins to circulate the loop that generates the magnetic field canceling the applied external flux, and creates an additional Josephson phase which is proportional to this external magnetic flux. [ 5 ] The induced current is in the same direction as I {\displaystyle I} in one of the branches of the superconducting loop, and is opposite to I {\displaystyle I} in the other branch; the total current becomes I / 2 + I s {\displaystyle I/2+I_{s}} in one branch and I / 2 − I s {\displaystyle I/2-I_{s}} in the other. As soon as the current in either branch exceeds the critical current, I c {\displaystyle I_{c}} , of the Josephson junction , a voltage appears across the junction.
Now suppose the external flux is further increased until it exceeds Φ 0 / 2 {\displaystyle \Phi _{0}/2} , half the magnetic flux quantum . Since the flux enclosed by the superconducting loop must be an integer number of flux quanta, instead of screening the flux the SQUID now energetically prefers to increase it to Φ 0 {\displaystyle \Phi _{0}} . The current now flows in the opposite direction, opposing the difference between the admitted flux Φ 0 {\displaystyle \Phi _{0}} and the external field of just over Φ 0 / 2 {\displaystyle \Phi _{0}/2} . The current decreases as the external field is increased, is zero when the flux is exactly Φ 0 {\displaystyle \Phi _{0}} , and again reverses direction as the external field is further increased. Thus, the current changes direction periodically, every time the flux increases by additional half-integer multiple of Φ 0 {\displaystyle \Phi _{0}} , with a change at maximum amperage every half-plus-integer multiple of Φ 0 {\displaystyle \Phi _{0}} and at zero amps every integer multiple.
If the input current is more than I c {\displaystyle I_{c}} , then the SQUID always operates in the resistive mode. The voltage, in this case, is thus a function of the applied magnetic field and the period equal to Φ 0 {\displaystyle \Phi _{0}} . Since the current-voltage characteristic of the DC SQUID is hysteretic, a shunt resistance, R {\displaystyle R} is connected across the junction to eliminate the hysteresis (in the case of copper oxide based high-temperature superconductors the junction's own intrinsic resistance is usually sufficient). The screening current is the applied flux divided by the self-inductance of the ring. Thus Δ Φ {\displaystyle \Delta \Phi } can be estimated as the function of Δ V {\displaystyle \Delta V} (flux to voltage converter) [ 6 ] [ 7 ] as follows:
The discussion in this section assumed perfect flux quantization in the loop. However, this is only true for big loops with a large self-inductance. According to the relations, given above, this implies also small current and voltage variations. In practice the self-inductance L {\displaystyle L} of the loop is not so large. The general case can be evaluated by introducing a parameter
where i c {\displaystyle i_{c}} is the critical current of the SQUID. Usually λ {\displaystyle \lambda } is of order one. [ 8 ]
The RF SQUID was invented in 1967 by Robert Jaklevic, John J. Lambe, Arnold Silver, and James Edward Zimmerman at Ford. [ 7 ] It is based on the AC Josephson effect and uses only one Josephson junction. It is less sensitive compared to DC SQUID but is cheaper and easier to manufacture in smaller quantities. Most fundamental measurements in biomagnetism , even of extremely small signals, have been made using RF SQUIDS. [ 9 ] [ 10 ] The RF SQUID is inductively coupled to a resonant tank circuit. [ 11 ] Depending on the external magnetic field, as the SQUID operates in the resistive mode, the effective inductance of the tank circuit changes, thus changing the resonant frequency of the tank circuit. These frequency measurements can be easily taken, and thus the losses which appear as the voltage across the load resistor in the circuit are a periodic function of the applied magnetic flux with a period of Φ 0 {\displaystyle \Phi _{0}} . For a precise mathematical description refer to the original paper by Erné et al. [ 6 ] [ 12 ]
The traditional superconducting materials for SQUIDs are pure niobium or a lead alloy with 10% gold or indium , as pure lead is unstable when its temperature is repeatedly changed. To maintain superconductivity, the entire device needs to operate within a few degrees of absolute zero , cooled with liquid helium . [ 13 ]
High-temperature SQUID sensors were developed in the late 1980s. [ 14 ] They are made of high-temperature superconductors , particularly YBCO , and are cooled by liquid nitrogen which is cheaper and more easily handled than liquid helium. They are less sensitive than conventional low temperature SQUIDs but good enough for many applications. [ 15 ]
In 2006, A proof of concept was shown for CNT-SQUID sensors built with an aluminium loop and a single walled carbon nanotube Josephson junction. [ 16 ] The sensors are a few 100 nm in size and operate at 1K or below. Such sensors allow to count spins. [ 17 ]
In 2022 a SQUID was constructed on magic angle twisted bilayer graphene (MATBG) [ 18 ] [ 19 ]
The extreme sensitivity of SQUIDs makes them ideal for studies in biology. Magnetoencephalography (MEG), for example, uses measurements from an array of SQUIDs to make inferences about neural activity inside brains. Because SQUIDs can operate at acquisition rates much higher than the highest temporal frequency of interest in the signals emitted by the brain (kHz), MEG achieves good temporal resolution. Another area where SQUIDs are used is magnetogastrography , which is concerned with recording the weak magnetic fields of the stomach. A novel application of SQUIDs is the magnetic marker monitoring method, which is used to trace the path of orally applied drugs. In the clinical environment SQUIDs are used in cardiology for magnetic field imaging (MFI), which detects the magnetic field of the heart for diagnosis and risk stratification.
Probably the most common commercial use of SQUIDs is in magnetic property measurement systems (MPMS). These are turn-key systems, made by several manufacturers, that measure the magnetic properties of a material sample which typically has a temperature between 300 mK and 400 K. [ 20 ] With the decreasing size of SQUID sensors since the last decade, such sensor can equip the tip of an AFM probe. Such device allows simultaneous measurement of roughness of the surface of a sample and the local magnetic flux. [ 21 ]
For example, SQUIDs are being used as detectors to perform magnetic resonance imaging (MRI). While high-field MRI uses precession fields of one to several teslas, SQUID-detected MRI uses measurement fields that lie in the microtesla range. In a conventional MRI system, the signal scales as the square of the measurement frequency (and hence precession field): one power of frequency comes from the thermal polarization of the spins at ambient temperature, while the second power of field comes from the fact that the induced voltage in the pickup coil is proportional to the frequency of the precessing magnetization. In the case of untuned SQUID detection of prepolarized spins, however, the NMR signal strength is independent of precession field, allowing MRI signal detection in extremely weak fields, on the order of Earth's magnetic field. SQUID-detected MRI has advantages over high-field MRI systems, such as the low cost required to build such a system, and its compactness. The principle has been demonstrated by imaging human extremities, and its future application may include tumor screening. [ 22 ]
Another application is the scanning SQUID microscope , which uses a SQUID immersed in liquid helium as the probe. The use of SQUIDs in oil prospecting , mineral exploration , [ 23 ] earthquake prediction and geothermal energy surveying is becoming more widespread as superconductor technology develops; they are also used as precision movement sensors in a variety of scientific applications, such as the detection of gravitational waves . [ 24 ] A SQUID is the sensor in each of the four gyroscopes employed on Gravity Probe B in order to test the limits of the theory of general relativity . [ 1 ]
A modified RF SQUID was used to observe the dynamical Casimir effect for the first time. [ 25 ] [ 26 ]
SQUIDs constructed from super-cooled niobium wire loops are used as the basis for D-Wave Systems 2000Q quantum computer . [ 27 ]
One of the largest uses of SQUIDs is to read out superconducting Transition-edge sensors . Hundreds of thousands of multiplexed SQUIDs coupled to transition-edge sensors are presently being deployed to study the Cosmic microwave background , for X-ray astronomy , to search for dark matter made up of Weakly interacting massive particles , and for spectroscopy at Synchrotron light sources .
Advanced SQUIDS called near quantum-limited SQUID amplifiers form the basis of the Axion Dark Matter Experiment (ADMX) at the University of Washington. Axions are a prime candidate for cold dark matter . [ 28 ]
A potential military application exists for use in anti-submarine warfare as a magnetic anomaly detector (MAD) fitted to maritime patrol aircraft . [ 29 ]
SQUIDs are used in superparamagnetic relaxometry (SPMR), a technology that utilizes the high magnetic field sensitivity of SQUID sensors and the superparamagnetic properties of magnetite nanoparticles . [ 30 ] [ 31 ] These nanoparticles are paramagnetic; they have no magnetic moment until exposed to an external field where they become ferromagnetic. After removal of the magnetizing field, the nanoparticles decay from a ferromagnetic state to a paramagnetic state, with a time constant that depends upon the particle size and whether they are bound to an external surface. Measurement of the decaying magnetic field by SQUID sensors is used to detect and localize the nanoparticles. Applications for SPMR may include cancer detection. [ 32 ] | https://en.wikipedia.org/wiki/SQUID |
SRAS (spatially resolved acoustic spectroscopy) a non-destructive acoustic microscopy microstructural-crystallographic characterization technique commonly used in the study of crystalline or polycrystalline materials. The technique can provide information about the structure and crystallographic orientation of the material. [ 1 ] Traditionally, the information provided by SRAS has been acquired by using diffraction techniques in electron microscopy - such as EBSD . The technique was patented in 2005, EP patent 1910815 .
SRAS measures the surface acoustic wave velocity across a specimen, the surface acoustic wave (SAW) velocity is in turn a function of the material state, including parameters such as crystallographic orientation, elastic constants , temperature and stress.
In a SRAS measurement, as in most laser ultrasound techniques, two lasers are used, one for the generation of acoustic waves and one for the subsequent detection of these waves. Considering first the generation of acoustic waves, an optical amplitude grating, illuminated by the a short pulse pump laser (typically ~1ns), is imaged onto the sample surface. The incident light is thermoelastically absorbed, creating surface acoustic waves, such as Rayleigh waves . As the laser pulse contains a broad range of frequencies, only the frequencies which match the grating spacing and acoustic velocity of that sample point will be generated. Using a second, continuous wave, laser these surface acoustic waves can then be measured through a number of interferometry techniques. Detection is usually achieved by optical beam deflection.
As Rayleigh waves are non-dispersive the phase velocity of the acoustic wave can be found by v = f λ {\displaystyle v=f\lambda }
where λ {\displaystyle \lambda } is the distance between the grating fringes imaged onto the sample surface and f {\displaystyle f} is the dominant frequency of the wave packet, found by fast Fourier transform .
As the measurement probes the frequency of the wave packet, which does not change along the propagation length, the measured SAW velocity is determined by only the properties of the specimen at the area where the grating pattern is imaged, unlike more traditional time of flight measurements that are influenced by the sample properties along the propagation length. This makes SRAS robust and immune to the aberrating and scattering effects of the microstructure.
By raster scanning the sample, making measurements at several points across the surface, multi-megapixel images of the SAW velocity can be built up - providing rich microstructural maps. On samples with a good surface finish measurements can be made without averaging, allowing samples to be rapidly scanned. In-theory, means the acquisition rate is limited only by the repetition rate of the pump laser; modern laser repetition rates can exceed 10 kHz. As the measurements do not require a vacuum chamber or acoustic couplant there is little restriction, beyond the limit of scanning stages, to the size of sample which can be interrogated. The elastic anisotropy of most engineering materials means the acoustic response is a function of the loading direction. Hence, a unique velocity map exists for each propagation direction of the SAW direction. It is possible to combine multiple velocity maps to improve contrast between grains.
An acoustic slowness surface can be determined for each pixel by propagating the acoustic wave in several directions. Having measured the SAW velocity in multiple directions the challenge is then to convert this information into the measurement of crystallographic orientation. The direct calculation of the orientation from velocity is a difficult problem. However, the numerical calculation of the SAW velocity as a function of SAW velocity is relatively simple, as first outlined by Farnell. Therefore, a database of possible slowness surfaces can be pre-calculated and compared to the measurement values. For each measurement pixel the orientation is given by the orientation of the pre-calculated velocity surface which best matches the measured data. These maps can spatially describe the crystal orientation of the material being interrogated and can be used to examine microtexture and sample morphology. The technique is applicable to any crystal structure, however transverse isotropy means the full orientation cannot be determined in hexagonal materials, such as titanium . [ 2 ]
In order to calculate the predicted SAW velocity of the sample, the materials density and elastic constants must be known. Elastic constants are typically measured by ultrasonic techniques such as resonant ultrasound spectroscopy , with well-established values for most common engineering materials. However, it is possible to attempt the full inverse problem to determine both the elastic constants and crystallographic orientation from only the measured SAW velocity. [ 3 ]
From orientation data, a wealth of information can be devised that aids in the understanding of the sample's microstructure and processing history. Recent developments include understanding: the prior texture of parent phases at elevated temperature; the storage and residual deformation after mechanical testing; the population of various microstructural features, including precipitates and grain boundary character.
SRAS++ utilises SRAS imaging to provide the raw measurement of single grain velocity surfaces, this is input to a novel inverse solver that mitigates the problem of the inversion being very ill-conditioned, by simultaneously solving for multiple uniquely orientated grains at once in a brute-force approach. This allows simultaneous determination of the elastic constants and crystallographic orientation. Furthermore, this technique has the potential to work on polycrystalline materials with minimal preparation and is capable of high accuracy, with the potential to realise errors in the determination of elastic constants values of less than 1 GPa.
Smooth mirror-like surfaces provide specular reflections , allowing easy detection of the acoustic wave. However, as surfaces become rougher the reflections become more diffuse , making detection of the acoustic wave more challenging for two reasons. Firstly, the reflected beam is spread out in a cone, as this cone increases in diameter less light is returned to the system - decreasing detection efficiency. Secondly, the light which is returned to the detector no longer exabits a gaussian intensity, instead the interfering wave fronts create a stochastic speckle pattern . However, many engineering processes impart an optically rough surface, for example additive manufacturing or forging , and there is a desire to make measurements on such components in their 'as manufactured state'. To achieve this, an interferometric technique compatible with rough surfaces is required. For example, a Fabry–Pérot interferometer - which is inherently tolerant to speckle, two-wave mixing - which can adapt to the speckle pattern, or a speckle knife edge detector. [ 6 ] With the use of such detection techniques, it is possible to make SRAS measurements on optically rough surfaces. [ 7 ] | https://en.wikipedia.org/wiki/SRAS |
SRD5A3-CDG (also known as CDG syndrome type Iq, CDG-Iq, CDG1Q or Congenital disorder of glycosylation type 1q) is a rare, non X-linked congenital disorder of glycosylation (CDG) [ 1 ] due to a mutation in the steroid 5 alpha reductase type 3 gene. It is one of over 150 documented types of Congenital disorders of Glycosylation. [ 2 ] Like many other CDGs, SRD5A3 is ultra-rare, with around 38 documented cases in the world. [ 3 ]
It is an inheritable autosomal recessive disorder that causes developmental delays and problems with vision. The gene is located at 4q12, which is the long (q) arm of chromosome 4 at position 12. [ 4 ]
SRD5A3-CDG is characterized by a highly variable phenotype . [ 5 ] Typical clinical manifestations include:
Less common manifestations may include: [ citation needed ]
The protein encoded by the SRD5A3 gene is involved in the production of androgen 5-alpha-dihydrotestosterone (DHT) from testosterone, and maintenance of the androgen-androgen receptor activation pathway. [ 7 ]
This protein is also necessary for the conversion of polyprenol into dolichol, which is required for the synthesis of dolichol-linked monosaccharides and the oligosaccharide precursor used for N-linked glycosylation of proteins. Dolichol is a key building block in the body's glycosylation process. [ 8 ] Typically, the dolichol generated is further modified into dolichol-linked oligosaccharide (DLO) by the addition of phosphates and sugars. Complex sugar molecules get added to DLO and are then transferred onto proteins. When insufficient DLO is produced in the body, many proteins are inadequately glycosylated. [ citation needed ]
Both glycosylation defects and an accumulation of polyprenol have been observed in SRD5A3-CDG patients and mouse models, and it is not currently known whether the disease is caused due to incorrect glycosylation, polyprenol accumulation, or a combination of the two. [ citation needed ]
Confirmation of clinical diagnosis for SRD5A3-CDG requires genetic testing and gene sequencing to identify deleterious mutations in the SRD5A3 gene. Other diagnostic tools include Isoelectrofocusing of Transferrin (TIEF), an assay from transferrin levels in blood, to screen for N-glycosylation defects [ 9 ] which occur in CDGs. A CDG blood analysis test using mass spectrometry technology is also available. [ citation needed ]
As SRD5A3-CDG is also an inheritable disorder, [ 10 ] parental genetic testing can indicate if one or both of the parents are carriers of the faulty gene. The gene is recessive in nature, so if both parents are carriers of the condition, there is a 25% chance that the offspring will have SRD5A3-CDG. [ citation needed ]
At present, there is no available treatment for SRD5A3-CDG. However, the disorder can be managed and some of the symptoms can be treated. [ 11 ] Some eye problems that manifest with SRD5A3-CDG can be surgically corrected and coagulation disorders may be treated. [ citation needed ]
The quality of life is mainly determined by the nature and the degree of the brain and eye involvement. Ongoing care and management for individuals with SRD5A3-CDG typically includes a combination of physical therapy (to alleviate issues pertaining to reduced muscle tone, mobility, etc.), occupational therapy (for vision and speech impairments) and palliative measures, where needed. [ citation needed ]
When a genetic risk or anomaly is identified, parents may have access to counselling to prepare them for any special needs their child may have and approaches on managing their condition as they grow. [ citation needed ]
SRD5A3-CDG is an ultra-rare disorder with a frequency of less than 1 in 10 million. [ 12 ] As of 2018, there were at least 38 reported cases of SRD5A3-CDG from 26 different families. While the exact number of patients worldwide is unknown, most recorded cases so far have been reported from Afghanistan, the Czech Republic, Iran, Pakistan, Poland, Puerto Rico and Turkey. [ 13 ]
SRD5A3-CDG is caused by a single-gene mutation, which makes it an attractive candidate for gene therapy. However, due to the extreme rarity of the disorder, research around it has been limited. [ citation needed ]
Research has predominantly been focused on two types of research models: Cell-based models and model organisms . [ 14 ]
Common cell-based models include patient cells such as fibroblast cells derived from skin samples (patient-derived fibroblasts [PDFs]), induced pluripotent stem cells (iPSCs) created by reprogramming fibroblasts, and specialized cells, such as neurons derived from stem cell differentiation. Patient-derived cell models are important preclinical model systems as they contain the same genome and mutation(s) as the patient, allowing researchers to assess potential therapies for individual patients early on in the drug development process. For SRD5A3-CDG, patient-derived cell models could be crucial in understanding the impact of polyprenol reductase enzyme deficiency and be used to investigate various treatment options such as dietary supplementation, novel or repurposed drugs and gene therapy. [ citation needed ]
Model organisms like worms, zebrafish and mice have been genetically modified to study the impact of several mutations, including those in the SRD5A3 gene. Researchers in the United States and France have been working on genetically modified mice that have SRD5A3 mutations limited to the cerebellum region of their brain. [ 15 ] These mice are viable, show CDG symptoms in the brain, and are part of planned studies for new experimental treatments. [ citation needed ] | https://en.wikipedia.org/wiki/SRD5A3-CDG |
The SRM Engine Suite is an engineering software tool used for simulating fuels , combustion and exhaust gas emissions in internal combustion engine (IC engine) applications. It is used worldwide by leading IC engine development organisations and fuel companies. The software is developed, maintained and supported by CMCL Innovations, [ 1 ] Cambridge, U.K.
The software has been applied to simulate almost all engine applications and all transportation fuel combinations with many examples [ 2 ] published in numerous leading peer-reviewed journals, a brief summary of these articles is presented here. [ 3 ]
The software is based on the stochastic reactor model (SRM), [ 17 ] which is stated in terms of a weighted stochastic particle ensemble. SRM is particular useful in the context of engine modelling [ 18 ] as the dynamics of the particle ensemble includes detailed chemical kinetics whilst accounting for inhomogeneity in composition and temperature space arising from on-going fuel injection , heat transfer and turbulence mixing events. Through this coupling, heat release profiles and in particular the associated exhaust gas emissions ( Particulates , NOx , Carbon monoxide , Unburned hydrocarbon etc .) can be predicted more accurately than if using the more conventional approaches of standard homogenous and multi-zone reactor methods. [ 3 ]
The software can be coupled as a plug-in into 1D engine cycle software tools, [ 3 ] are capable of simulating the combustion and emissions during closed volume period of the cycle ( combustion , TDC and negative valve overlap).
An advanced Application programming interface enables for the model to be coupled with a user-defined codes such as 3D-CFD [ 19 ] or control [ 14 ] software. | https://en.wikipedia.org/wiki/SRM_Engine_Suite |
SRT-1720 is an experimental drug that was studied by Sirtris Pharmaceuticals intended as a small-molecule activator of the sirtuin subtype SIRT1 . The compound has been studied in animals, but safety and efficacy in humans have not been established.
In animal models of obesity and diabetes SRT1720 was found to improve insulin sensitivity and lower plasma glucose levels in fat, muscle and liver tissue, and increase mitochondrial and metabolic function . [ 1 ] In mice rendered obese and diabetic by feeding a high-fat, high-sugar diet, a study performed at the National Institute of Aging found that feeding chow infused with the highest dose of SRT1720 beginning at one year of age increased mean lifespan by 18%, and maximum lifespan by 5%, as compared to other short-lived obese, diabetic mice; however, treated animals still lived substantially shorter lives than normal-weight mice fed normal chow with no drug. [ 2 ] In a later study, SRT1720 increased mean lifespan of obese, diabetic mice by 21.7%, similar to the earlier study, but there was no effect on maximum lifespan in this study. [ 3 ] In normal-weight mice fed a standard rodent diet, SRT1720 increased mean lifespan by just 8.8%, and again had no effect on maximum lifespan. [ 3 ]
Since the discovery of SRT1720, the claim that this compound is a SIRT1 activator has been questioned [ 4 ] [ 5 ] [ 6 ] and further defended. [ 7 ] [ 8 ]
Although SRT1720 is not currently undergoing clinical development, a related compound, SRT2104 , reached Phase II human trials for metabolic diseases. [ 9 ]
This drug article relating to the gastrointestinal system is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/SRT-1720 |
SRT-2104 is an experimental drug that was studied by Sirtris Pharmaceuticals as a small-molecule activator of the sirtuin subtype SIRT1 . The compound progressed to Phase II human trials for Type II diabetes before development was discontinued, however it continues to be widely used in animal research into the functions of SIRT1. [ 1 ] [ 2 ] [ 3 ] [ 4 ] [ 5 ]
This pharmacology -related article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/SRT-2104 |
SRTX is a Canadian material science and technology company based in Montreal, Quebec . [ 1 ] [ 2 ] [ 3 ] Founded by entrepreneur Katherine Homuth, SRTX is best known for the development of the Sheertex rip-resist knit that is used to produce sheer tights, swimwear , and waterproof membranes for other types of apparel. [ 1 ] SRTX specializes in producing textile components and apparel made using the polymer UHMWPE (ultra-high molecular weight polyethylene). [ 1 ] [ 3 ] It was founded in 2017. [ 1 ] [ 2 ] [ 3 ]
SRTX was established in 2017, Katherine Homuth in Muskoka, Ontario in Canada. [ 1 ] [ 4 ] The company initially gained attention through a successful Kickstarter campaign under the name Sheerly Genius, which aimed to manufacture hosiery with a focus on product durability . [ 5 ] [ 6 ] [ 7 ]
The first prototypes of the Sheertex knit were produced in 2017 with the goal of producing a pair of tights that would not rip. [ 8 ] The company was accepted into its first Y Combinator program in Fall 2017. [ 8 ] It became part of Y Combinator's Winter 2018 batch. [ 9 ] [ 10 ] Sheerly Genius Pantyhose were named one of TIME Magazine ' s Best Inventions in Fall 2018. [ 11 ] [ 12 ] [ 13 ]
The company was eventually renamed from Sheerly Genius to Sheertex to reflect its flagship product. [ 4 ] [ 14 ] [ 15 ] More recently, it was rebranded as SRTX. [ 12 ]
By 2020, SRTX had 200 employees. [ 16 ]
SRTX expanded into wholesale in 2023 and began selling products through retailers such as H&M and Cos . [ 17 ] The company also began selling products through the QVC shopping channel . [ 1 ] In 2024, it was reported that SRTX had become B Corp-certified . [ 17 ]
In 2023, the company launched Watertex, a line of swimsuits and other fast-drying, hydrophobic apparel products made using UHMWPE . [ 1 ]
SRTX’s flagship product is Sheertex sheer pantyhose, which is designed to resist tearing and snagging. [ 18 ] [ 19 ] [ 20 ] Sheertex is sold in several styles and colors. [ 19 ] [ 21 ]
The company currently operates two plants in Montreal. [ 1 ] SRTX has also developed a manufacturing software platform named Cortex, which automates manufacturing operations and reduces environmental impacts. [ 2 ] | https://en.wikipedia.org/wiki/SRTX |
Single Radio Voice Call Continuity ( SRVCC ) provides an interim solution for handing over VoLTE (Voice over LTE) calls, which use the IMS system, to be made to 2G/3G networks. The voice calls on LTE network are meant to be packet switched. [ 1 ] To make it inter operable with existing networks, these calls are to be handed over to Circuit switched calls in GSM/WCDMA networks. QoS is ensured by SRVCC operators for calls made.
3GPP also standardized SRVCC to provide easy handovers from LTE network to GSM/UMTS network. | https://en.wikipedia.org/wiki/SRVCC |
In biochemistry and molecular biology , saline-sodium citrate (SSC) buffer is used as a hybridization buffer , to control stringency for washing steps in protocols for Southern blotting , in situ hybridization , DNA Microarray or Northern blotting . 20X SSC may be used to prevent drying of agarose gels during a vacuum transfer.
A 20X stock solution consists of 3 M sodium chloride and 300 m M trisodium citrate (adjusted to pH 7.0 with HCl ).
This biochemistry article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/SSC_buffer |
SSPC-SP13/NACE No. 6 Surface Preparation of Concrete is a SSPC and NACE International joint standard that covers the preparation of concrete surfaces prior to the application of protective coating or lining systems. This standard should be used by specifiers, applicators, inspectors, and other who are responsible for defining a standard degree of cleanliness, strength, profile, and dryness of prepared concrete surfaces prior to the application of a protective coating system.
This standards - or measurement -related article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/SSPC-SP13/NACE_No._6 |
ST2-PT (Single Transition-to-single Transition Polarization Transfer) is a method of sensitivity enhancement in NMR spectroscopy, developed by K.V. Pervushin, G. Wider, and K. Wüthrich in 1998.
This method affords a √ 2 sensitivity enhancement for kinetically stable amide 15N–1H groups in proteins .
[ 1 ]
This nuclear magnetic resonance –related article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/ST2-PT |
The ST2 cardiac biomarker (also known as soluble interleukin 1 receptor-like 1 ) is a protein biomarker of cardiac stress encoded by the IL1RL1 gene. ST2 signals the presence and severity of adverse cardiac remodeling and tissue fibrosis , which occurs in response to myocardial infarction , acute coronary syndrome , or worsening heart failure . [ 1 ] [ 2 ]
ST2 provides prognostic information that is independent of other cardiac biomarkers such as BNP , NT-proBNP , highly sensitive troponin , GDF-15 , and galectin-3 . [ 3 ] One study indicated that discrimination is independent of age, body mass index , history of heart failure, anemia and impaired kidney function or sex. [ 4 ]
ST2 is a member of the interleukin 1 receptor family. The ST2 protein has two isoforms and is directly implicated in the progression of cardiac disease: a soluble form (referred to as soluble ST2 or sST2) and a membrane-bound receptor form (referred to as the ST2 receptor or ST2L). When the myocardium is stretched, the ST2 gene is upregulated, increasing the concentration of circulating soluble ST2. [ 3 ] The ligand for ST2 is the cytokine interleukin-33 (IL-33). Binding of IL-33 to the ST2 receptor, in response to cardiac disease or injury, such as an ischemic event, elicits a cardioprotective effect resulting in preserved cardiac function. This cardioprotective IL-33 signal is counterbalanced by the level of soluble ST2, which binds IL-33 and makes it unavailable to the ST2 receptor for cardioprotective signaling. As a result, the heart is subjected to greater stress in the presence of high levels of soluble ST2.
Published and peer-reviewed findings indicate that ST2 is a predictor of mortality at presentation. [ 5 ] Studies have shown patients with ST2 levels above a clinical threshold consistently have a much higher risk of mortality while, equally important, patients with ST2 levels below threshold have a very low risk of mortality. [ 6 ] [ 7 ] Although it has been shown that ST2 concentrations correlate with heart failure severity [ 8 ] there is no level that perfectly separates patients with and without heart failure for disease diagnosis. However, as a prognostic marker it has been clearly shown that patients are at a higher risk of adverse outcomes when ST2 levels are above a cutoff value of 35 ng/mL. [ 6 ]
ST2 is a strong predictor of cardiovascular death and risk of developing new heart failure in ST Elevation Myocardial Infarction (STEMI) & NSTE-ACS patients. In patients presenting with Acute Coronary Syndrome (ACS), those in the highest quartile (above 35 ng/ml) have more than 3 times higher risk of cardiovascular death and new heart failure at 30 days, than those in the lower quartiles. At one year, there is a relative risk of 2.3 for adverse outcomes. [ 9 ]
ST2 is an active participant in the cardiac remodeling pathway and could identify which patients will respond to Eplerenone , or other therapies that reverse myocardial fibrosis . [ 10 ]
ST2 is measured by an immunoassay , commercially marketed as the Presage ST2 Assay by Critical Diagnostics of San Diego, California. [ 14 ] The assay has Food and Drug Administration approval and a CE Mark . [ 15 ] | https://en.wikipedia.org/wiki/ST2_cardiac_biomarker |
STAAD or ( STAAD.Pro ) is a structural analysis and design software application originally developed by Research Engineers International (REI) in 1997. In late 2005, Research Engineers International was bought by Bentley Systems . [ 1 ] [ 2 ] STAAD stands for STructural Analysis And Design. [ 3 ]
STAAD.Pro is one of the most widely used structural analysis and design software products worldwide. It can apply more than 90 international steel, concrete, timber and aluminium design codes.
It can make use of various forms of analysis from the traditional static analysis to more recent analysis methods like p-delta analysis, geometric non-linear analysis, Pushover analysis (Static-Non Linear Analysis) or a buckling analysis. It can also make use of various forms of dynamic analysis methods from time history analysis to response spectrum analysis. The response spectrum analysis feature is supported for both user defined spectra as well as a number of international code specified spectra.
Additionally, STAAD.Pro is interoperable with applications such as RAM Connection, AutoPIPE, SACS and many more engineering design and analysis applications to further improve collaboration between the different disciplines involved in a project. STAAD can be used for analysis and design of all types of structural projects from plants, buildings, and bridges to towers, tunnels, metro stations, water/wastewater treatment plants and more.
Analytical model can be created using the ribbon-based user interface, by editing the command file or by importing several other files types like dxf, cis/2 etc. The model geometry can even be generated from the data of macro-enabled applications (like Microsoft Excel, Microstation etc.) by using Macros.
Physical modeling has been a significant feature included in the program. STAAD.Pro Physical Modeler takes advantage of physical modeling to simplify modeling of a structure, which in turn more accurately reflects the process of building a model. Beams and surfaces are placed in the model on the scale of which they would appear in the physical world. A column may span multiple floors and a surface represents an entire floor of a building, for example. A joint is then generated anywhere two physical objects meet in the model (as well as at the free ends of cantilevered members, for convenience).
STAAD Building Planner is a module that enables seamless generation of building models that can be analyzed and designed thereafter in the program itself. Operations like defining geometry, making changes in the geometric specifications are matters of only few clicks in this workflow..
Steel AutoDrafter workflow extracts planar drawings and material take-off from a structural steel model prepared in STAAD.Pro. It produces excellent quality plans at any level and sections in any of the orthogonal directions.
The general philosophy governing the design of bridges is that, subject to a set of loading rules and constraints, the worst effects due to load application should be established and designed against. The process of load application can be complex as governing rules can impose interdependent parameters such as loaded length on a lane, lane factors, and load intensity. To obtain the maximum design effects, engineers have to try many loading situations on a trial and error basis.
This leads to the generation of many live load application instances (and a large volume of output data) that then must be combined with dead load and other effects, as well. Bridge Deck is used to minimize the load application process while complying with national code requirements.
The program is based on the use of influence surfaces, which are generated by STAAD.Pro as part of the loading process. An influence surface for a given effect on a bridge deck relates its value to movement of a unit load over the point of interest. The influence surface is a three-dimensional form of an influence line for a single member (or, in other words, it is a 2D influence function).
STAAD.Pro will automatically generate influence surfaces for effects such as bending moments for elements, deflection in all the degrees of freedom of nodes, and support reactions. The user then instruct the program to utilize the relevant influence surfaces and, with due regards to code requirements, optimize load positions to obtain the maximum desired effects.
The Advanced Concrete Design workflow provides direct access for STAAD.Pro models to leverage the power of the RCDC application. This is a standalone application, which is operated outside the STAAD.Pro environment, but requires a model and results data from a suitable analysis.
The model should typically be formed from beams and columns (plates are currently not supported). RCDC can be used to design the following objects: Pile Caps, Footings, Columns and walls, Beams, Slabs.
As the projects progresses, each design created in RCDC is retained and displayed when RCDC is re-entered, so that previous designs can be recalled and/or continued.
Detailed drawings and BBS of excellent quality can be generated as required and they are quite ready to be sent for execution.
The STAAD.Pro Advanced Slab Design workflow is an integrated tool that works from within the STAAD.Pro environment. Concrete slabs can be defined, and the data can be transferred to RAM Concept.
The data passed into RAM Concept includes the geometry, section and material properties, loads and combination information, and analysis results.
Eurocode 8: Part 1 contains specific requirements and recommendations for building structures that are to be constructed in seismic regions. Essentially, these fundamental requirements have been provided to ensure that the structures can sustain the seismic loads without collapse and also – where required– avoid suffering unacceptable damage and can continue to function after an exposure to a seismic event.
This STAAD.Pro workflow is used to check if the structure conforms to the basic geometric recommendations made in Eurocode 8 (EC8). This workflow is in addition to the normal post-processing workflow which gives the various analysis results. These checks are intended to give you a "feel" for the structure and are not mandatory to proceed to the design phase.
OpenSTAAD is a library of exposed functions enabling engineers access STAAD.Pro’s internal functions and routines as well as its graphical commands. With OpenSTAAD, one can use VBA macros to perform such tasks as automating repetitive modeling or post-processing tasks or embedding customized design routines. Following an open architecture paradigm, OpenSTAAD was built using ATL, COM, and COM+ standards as specified by Microsoft. This allows OpenSTAAD to be used in a macro application like Microsoft Excel or Autodesk AutoCAD. OpenSTAAD can also be used to link STAAD data to Web-based applications using ActiveX, HTML, and ASP. Through the in-built Macro Editor, one can leverage the functionalities of OpenSTAAD and automate the analysis and design workflows, thereby eliminating the chance of occurrence of potential errors due to manual intervention and reducing the required time for execution of the whole workflow (as compared to the manual execution time), to a large extent. | https://en.wikipedia.org/wiki/STAAD |
STANAG 4427 on Configuration Management in System Life Cycle Management is the Standardization Agreement (STANAG) of NATO nations on how to do configuration management (CM) on defense systems. The STANAG, and its supporting NATO publications, provides guidance on managing the configuration of products and services. It is unique in its full life cycle perspective, requiring a Life Cycle CM Plan, and in its approach to contracting for CM, using an ISO standard as the base, and building-up additional requirements (as opposed to the classical tailoring-down).
STANAG 4427 is NATO’s agreement on how to do configuration management on defense systems. Edition 1 was originally promulgated in 1997 and updated with Edition 2 in 2007. The first iteration of the Standardization Agreement was entitled Introduction of Allied Configuration Management Publications (ACMPs), and it called on ratifying nations to use seven NATO publications (ACMP 1-7) as the agreed upon contractual clauses for configuration management.
In 2010, NATO undertook to review and revise the STANAGs and ACMPs with two major assignments: make the NATO guidance useful and extend the guidance through the full project life cycle. This work resulted in the promulgation of STANAG 4427 Edition 3, Configuration Management in System Life Cycle Management, in 2014. As of 2017, it has been ratified by 19 nations.
With Edition 3, NATO published three new ACMPs: ACMP-2000, Policy on Configuration Management; ACMP-2009, Guidance on Configuration Management; and ACMP-2100, Configuration Management Contractual Requirements. This trio of publications uses a civil standard as the platform ( ISO 10007 ), requires the acquirer to prepare and maintain a Life Cycle CM Plan for the system, to use a combination of governance and insight that is required to achieve the specific system objectives, and to build-up contractual requirements based on defined needs, rather than boilerplates.
NATO publications covered by STANAG 4427 Edition 3 [ 1 ]
Copies of NATO Configuration Management publications are available, for free, at the NATO Standardization Office web sites below, or at this site: | https://en.wikipedia.org/wiki/STANAG_4427_on_CM |
STARAN in the information technology industry might be the first commercially available computer designed around an associative memory . The STARAN computer was designed and built by Goodyear Aerospace Corporation . It is a content-addressable parallel processor (CAPP), a type of parallel processor which uses content-addressable memory . STARAN is a single instruction, multiple data array processor with a 4x256 1-bit processing element (PE) computer [ clarify ] . The STARAN machines became available in 1972.
Goodyear Aerospace later developed the MPP based on similar principles but with a larger and wider processor array.
This computing article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/STARAN |
STARlight is a computer simulation ( Monte Carlo ) event generator program to simulate ultra-peripheral collisions among relativistic nuclei. [ 1 ] [ 2 ] It simulates both photonuclear and two-photon interactions . It can simulate multiple interactions among a single ion pair, such as vector meson photoproduction accompanied by mutual Coulomb excitation .
These reactions are currently the primary method of studying photo-nuclear and two-photon interactions.
STARlight was initially written in the late 1990s, in FORTRAN . [ 3 ] After a period of expansion to include additional final states, etc. it was recoded into C++ in the early 2000s. The code is now hosted on the Hepforge code repository. [ 4 ]
STARlight has been used by both STAR and PHENIX , at RHIC , and at the ALICE , CMS , ATLAS and LHC-b experiment at the Large Hadron Collider , for simulations of ultra-peripheral collisions.
STARlight is designed to handle complex reactions involving multiple photon exchange between a single ion pair. These reactions are important at heavy ion colliders, because, with the large nuclear charges, the probability of multi-photon interactions in near grazing collisions (impact parameter b just slightly above twice the nuclear radius) is large. STARlight does this by calculating cross-sections in an impact-parameter dependent formalism. [ 5 ] [ 6 ]
One of its major successes was the successful prediction of the cross-sections for ρ 0 photoproduction at both RHIC [ 7 ] and the LHC. [ 8 ] It also accurately predicted the cross-section for e + e − pair production at RHIC [ 9 ] and the LHC, [ 10 ] using lowest order quantum electrodynamics. The latter reaction is important because it shows that there are no large higher order corrections, as could be expected because of the large nuclear charge. In both of the RHIC results, the presence of neutrons in downstream zero-degree calorimeters was used in the trigger, selecting events with impact parameters less than about 40 fermi; these events were then searched for photoproduced ρ 0 .
A detailed description of the code is available. [ 11 ] | https://en.wikipedia.org/wiki/STARlight |
3WWT , 1BF5 , 1YVL , 2KA6
6772
20846
ENSG00000115415
ENSMUSG00000026104
P42224
P42225
NM_007315 NM_139266
NM_001205313 NM_001205314 NM_009283 NM_001357627
NP_009330 NP_644671
n/a
Signal transducer and activator of transcription 1 ( STAT1 ) is a transcription factor which in humans is encoded by the STAT1 gene . It is a member of the STAT protein family. [ 5 ]
All STAT molecules are phosphorylated by receptor associated kinases, that causes activation, dimerization by forming homo- or heterodimers and finally translocate to nucleus to work as transcription factors. Specifically STAT1 can be activated by several ligands such as Interferon alpha (IFNα), Interferon gamma (IFNγ), Epidermal Growth Factor (EGF), Platelet Derived Growth Factor (PDGF), Interleukin 6 (IL-6), or IL-27. [ 6 ]
Type I interferons (IFN-α, IFN-ß) bind to receptors, cause signaling via kinases, phosphorylate and activate the Jak kinases TYK2 and JAK1 and also STAT1 and STAT2. STAT molecules form dimers and bind to ISGF3G/IRF-9, which is Interferon stimulated gene factor 3 complex with Interferon regulatory Factor 9. [ 7 ] This allows STAT1 to enter the nucleus. [ 8 ] STAT1 has a key role in many gene expressions that cause survival of the cell, viability or pathogen response. There are two possible transcripts (due to alternative splicing) that encode 2 isoforms of STAT1. [ 9 ] [ 10 ] STAT1α, the full-length version of the protein, is the main active isoform, responsible for most of the known functions of STAT1. STAT1ß, which lacks a portion of the C-terminus of the protein, is less-studied, but has variously been reported to negatively regulate activation of STAT1 or to mediate IFN-γ-dependent anti-tumor and anti-infection activities. [ 11 ] [ 12 ] [ 13 ]
STAT1 is involved in upregulating genes due to a signal by either type I , type II , or type III interferons . In response to IFN-γ stimulation, STAT1 forms homodimers or heterodimers with STAT3 that bind to the GAS (Interferon- G amma- A ctivated S equence) promoter element; in response to either IFN-α or IFN-β stimulation, STAT1 forms a heterodimer with STAT2 that can bind the ISRE ( I nterferon- S timulated R esponse E lement) promoter element. [ 14 ] In either case, binding of the promoter element leads to an increased expression of ISG ( I nterferon- S timulated G enes). [ 15 ]
Expression of STAT1 can be induced with diallyl disulfide , a compound in garlic. [ 16 ]
Mutations in the STAT1 molecule can be gain of function (GOF) or loss of function (LOF). Both of them can cause different phenotypes and symptoms. Recurring common infections are frequent in both GOF and LOF mutations. In humans STAT1 has been particularly under strong purifying selection when populations shifted from hunting and gathering to farming, because this went along with a change in the pathogen spectrum. [ 17 ]
STAT1 loss of function, therefore STAT1 deficiency can have many variants. There are two main genetic impairments that can cause response to interferons type I and III. First there can be autosomal recessive partial or even complete deficiency of STAT1. That causes intracellular bacterial diseases or viral infections and impaired IFN a, b, g and IL27 responses are diagnosed. In partial form there can also be found high levels of IFNg in blood serum. When tested from whole blood, monocytes do not respond to BCG and IFNg doses with IL-12 production. In complete recessive form there is a very low response to anti-viral and antimycotical medication. Second, partial STAT1 deficiency can also be an autosomal dominant mutation; phenotypically causing impaired IFNg responses and causing patients to suffer with selective intracellular bacterial diseases (MSMD). [ 18 ]
In knock-out mice prepared in the 90s, a low amount of CD4 + and CD25 + regulatory T-cells and almost no IFNa, b and g response was discovered, which lead to parasital, viral and bacterial infections. The very first reported case of STAT1 deficiency in human was an autosomal dominant mutation and patients were showing propensity to mycobacterial infections. [ 9 ] Another case reported was about an autosomal recessive form. 2 related patients had a homozygous missense STAT1 mutation which caused impaired splicing, therefore a defect in mature protein. Patients had partially damaged response to both IFNa and IFNg. Scientists now claim that recessive STAT1 deficiency is a new form of primary immunodeficiency and whenever a patient suffers sudden, severe and unexpected bacterial and viral infections, should be considered as potentially STAT1 deficient. [ 19 ] [ 20 ]
Interferons induce the formation of two transcriptional activators: gamma-activating factor (GAF) and interferon-stimulated gamma factor 3 (ISGF3). A natural heterozygous germline STAT1 mutation associated with susceptibility to mycobacterial but not viral disease was found in two unrelated patients with unexplained mycobacterial disease. [ 21 ] This mutation caused a loss of GAF and ISGF3 activation but was dominant for one cellular phenotype and recessive for the other. It impaired the nuclear accumulation of GAF but not of ISGF3 in cells stimulated by interferons, implying that the antimycobacterial but not the antiviral effects of human interferons are mediated by GAF. More recently, two patients have been identified with homozygous STAT-1 mutations who developed both post–BCG vaccination disseminated disease and lethal viral infections. The mutations in these patients caused a complete lack of STAT-1 and resulted in a lack of formation of both GAF and ISGF3. [ 22 ]
Gain of function mutation was first discovered in patients with chronic mucocutaneous candidiasis (CMC). This disease is characteristic with its symptoms as persistent infections of the skin, mucosae - oral or genital and nails infections caused by Candida , mostly Candida albicans . CMC may very often result from primary immunodeficiency. Patients with CMC often suffer also with bacterial infections (mostly Staphylococcus aureus ), also with infections of the respiratory system and skin. In these patients we can also find viral infections caused mostly by Herpesviridae , that also affect the skin. The mycobacterial infections are often caused by Mycobacterium tuberculosis or environmental bacteria. Very common are also autoimmune symptoms like type 1 diabetes , cytopenia, regression of the thymus or systemic lupus erythematosus . When T-cell deficient, these autoimmune díseases are very common. CMC was also reported as a common symptom in patients with hyper immunoglobulin E syndrome (hyper-IgE) and with autoimmune polyendocrine syndrome type I. There was reported an interleukin 17A role, because of low levels of IL-17A producing T-cells in CMC patients.
With various genomic and genetic methods was discovered, that a heterozygous gain of function mutation of STAT1 is a cause of more than a half CMC cases. This mutation is caused by defect in the coiled-coil domain, domain that binds DNA, N-terminal domain or SH2 domain. Because of this there is increased phosphorylation because of impossible dephosphorylation in nucleus. These processes are dependent on cytokines like interferon alpha or beta, interferon gamma or interleukin 27. As mentioned above, low levels of interleukin 17A were observed, therefore impaired the Th17 polarization of the immune response.
Patients with STAT1 gain of function mutation and CMC poorly or not at all respond to treatment with azole drugs such as Fluconazole , Itraconazole or Posaconazole . Besides common viral and bacterial infections, these patients develop autoimmunities or even carcinomas. It is very complicated to find a treatment because of various symptoms and resistances, inhibitors of JAK/STAT pathway such as Ruxolitinib are being tested and are a possible choice of treatment for these patients. [ 23 ] [ 6 ] [ 24 ]
STAT1 has been shown to interact with: | https://en.wikipedia.org/wiki/STAT1 |
2KA4
6773
20847
ENSG00000170581
ENSMUSG00000040033
P52630
Q9WVL2
NM_001385114 NM_001385115
NM_019963
NP_005410 NP_938146
n/a
Signal transducer and activator of transcription 2 is a protein that in humans is encoded by the STAT2 gene . [ 5 ] [ 6 ] It is a member of the STAT protein family. This protein is critical to the biological response of type I interferons (IFNs). [ 7 ] It functions as a transcription factor downstream of type I interferons. STAT2 sequence identity between mouse and human is only 68%. [ 8 ]
The protein encoded by this gene is a member of the STAT protein family. In response to cytokines and growth factors, STAT family members are phosphorylated by the receptor associated kinases, and then form homo- or heterodimers that translocate to the cell nucleus where they act as transcription activators. In response to IFN , this protein forms a complex with STAT1 and IFN regulatory factor family protein p48 ( IRF9 ) and form ISGF-3 (IFN-stimulated gene factor-3), in which this protein acts as a transactivator, but lacks the ability to bind DNA directly. [ 9 ] The protein mediates innate antiviral activity. Mutations in this gene result in Immunodeficiency 44. [ 10 ] ISGF-3 proceeds the activation of genes via the IFN-stimulated response element (ISRE). ISRE-driven genes include Ly-6C, the double-stranded RNA kinase (PKR), 2´ to 5´ oligoadenylate synthase (OAS), MX and potentially MHC class I. [ 11 ] Transcription adaptor P300/CBP (EP300/CREBBP) has been shown to interact specifically with this protein, which is thought to be involved in the process of blocking IFN-alpha response by adenovirus. [ 6 ]
STAT2 knockout mice are unresponsive to type I IFN and extremely vulnerable to viral infection. They indicate the loss of the type I IFN autocrine loop and several defects in macrophages and T cell responses. Stat2-/- cells show differences in the biological response to IFN-α. [ 7 ]
STAT2 has been shown to interact with:
In double knockout STAT2 mice, an increased proliferation of M1, M2, and M1/M2 coexpressing macrophages during influenza-bacterial super-infection is observed. The bacterial clearance was also impaired by neutralization of IFN-γ (M1) and Arginase-1 (M2) what suggests that pulmonary macrophages expressing a mixed M1/M2 phenotype promote bacterial control during influenza-bacterial super-infection. Therefore the STAT2 signaling is associated with suppressing macrophage activation and bacterial control during influenza-bacterial super-infection. [ 24 ] These mice demonstrate no developmental defects. The knockout STAT2 and double knockout STAT mice in Vesicular stromatitis Indiana virus (VSV) model produce at least 10 times more virus plaque-forming units than the wild type (WT). [ 25 ] IFN-α pretreatment supplied protection in WT and STAT2 +/- cells but not in double knockout STAT2 cells. IFN-γ pretreatment did not provide any antiviral response during infection of VSV. [ 26 ] This finding could be explained by the reduced level of STAT1 in cells of STAT2 knockout mice. [ 7 ] Additionally, the double knockout STAT2 mice are more sensitive to mouse cytomegalovirus (MCMV), severe fever thrombocytopenia syndrome virus, influenza virus, dengue virus (DNV) and Zika virus than control mice, which suggests that STAT2 plays a critical role in the suppression of virus replication in mice. [ 27 ] [ 28 ] [ 29 ] [ 30 ]
AR STAT2 deficiency was first time observed in 2 siblings. After routine immunization with measles-mump-rubella, one sibling developed disseminated vaccine-strain measles (MMR) but recovered and second sibling died in infancy from a viral infection due to primary immunodeficiency disorder. Later, the results showed that siblings were homozygous for absent expression of gene for STAT2. Patients with AR STAT2 deficiency have mutations which bring substitutions at important splice sites what leads to defected splicing and premature stop codons leading to a loss of expression of an interferon-stimulated gene. The typical clinical phenotype is disseminated infection after immunization with the live attenuated MMR vaccine. Some patients had also an onset of severe disease in infancy like infection with RSV , norovirus , coxsackievirus , adenovirus or enterovirus . One of the patients had CNS disease after the primary infection with EBV. EBV suppression was delayed in peripheral blood and cerebrospinal fluid as type I interferon signalling plays important role in the initial immune response against EBV. [ 31 ] During next 3 years, PCR test showed persistent EBV presence in blood as well as in cerebrospinal fluid despite anti-EBV IgG. CMV and VZV infections were severe as well in few patients. The virus infection was treated by high-dose of intravenous immunoglobulin (IVIG) after which patients recovered and became afebrile within 24 hours. IVIG has anti-inflammatory effect and suggests that the passive immunization could help to control the ongoing viral infections. Therefore, the monthly IgG therapy could be beneficial for patients with STAT2 deficiency during childhood, until their adaptive immune system has sufficiently developed. From the age 5 years, the frequency and severity of viral infections decreased and the age of 10 years the patients were mostly off all medication. In general, the patients with STAT2 deficiency are relatively healthy with no specific defects in their adaptive immunity or developmental abnormalities. These findings show that type I IFN signaling trough ISGF3 is not essential for host defense against the majority of common childhood viral pathogens. Despite a profoundly defective innate IFN response and evident susceptibility to some viral infections, STAT2-deficient individuals can live a relatively healthy life. [ 32 ]
It was also reported a homozygous STAT2 missense mutation (R148W/Q) which results to a STAT2 gain of function underlying fatal early-onset autoinflammation in three patients. This mutation leads to a persistent type I IFN response due to defective binding of the mutated STAT2 to ubiquitin specific peptidase 1 (USP18) which is an essential in the negative autofeedback loop where USP18 sterically hinders the binding of JAK1 to IFNAR1. [ 33 ] [ 34 ] Therefore complete AR STAT2 deficiency usually causes disseminated LAV infection and recurrent natural viral infections. Penetrance is not complete for several viral infections and for complicated live measles vaccine disease. [ 35 ] These observation suggest that the phenotype of AR STAT2 deficiency could range from asymptomatic (the healthy adult) to fatal (childhood death from a crushing viral disease). The phenotype is less severe than human complete AR STAT1 deficiency but more severe than IFNAR1 or IFNAR2 deficiency. The human phenotype is less severe than in mice.
This article incorporates text from the United States National Library of Medicine , which is in the public domain . | https://en.wikipedia.org/wiki/STAT2 |
5AX3
6774
20848
ENSG00000168610
ENSMUSG00000004040
P40763
P42227
NM_001369514 NM_001369516 NM_001369517 NM_001369518 NM_001369519 NM_001369520
NM_011486 NM_213659 NM_213660
NP_001356443 NP_001356445 NP_001356446 NP_001356447 NP_001356448 NP_001356449
NP_035616 NP_998824 NP_998825
Signal transducer and activator of transcription 3 ( STAT3 ) is a transcription factor which in humans is encoded by the STAT3 gene . [ 5 ] It is a member of the STAT protein family.
STAT3 is a member of the STAT protein family. In response to cytokines and growth factors , STAT3 is phosphorylated by receptor-associated Janus kinases (JAK), forms homo- or heterodimers, and translocates to the cell nucleus where it acts as a transcription activator . Specifically, STAT3 becomes activated after phosphorylation of tyrosine 705 in response to such ligands as interferons , epidermal growth factor (EGF), interleukin (IL-)5 and IL-6 . Additionally, activation of STAT3 may occur via phosphorylation of serine 727 by mitogen-activated protein kinases (MAPK) [ 6 ] and through c-src non-receptor tyrosine kinase. [ 7 ] [ 8 ] STAT3 mediates the expression of a variety of genes in response to cell stimuli, and thus plays a key role in many cellular processes such as cell growth and apoptosis . [ 9 ]
STAT3-deficient mouse embryos cannot develop beyond embryonic day 7, when gastrulation begins. [ 10 ] It appears that at these early stages of development, STAT3 activation is required for self-renewal of embryonic stem cells (ESCs). Indeed, LIF , which is supplied to murine ESC cultures to maintain their undifferentiated state, can be omitted if STAT3 is activated through some other means. [ 11 ]
STAT3 is essential for the differentiation of the TH17 helper T cells, which have been implicated in a variety of autoimmune diseases . [ 12 ] During viral infection, mice lacking STAT3 in T-cells display impairment in the ability to generate T-follicular helper (Tfh) cells and fail to maintain antibody based immunity. [ 13 ]
STAT3 caused upregulation in E-selectin, a factor in metastasis of cancers. [ 14 ]
Hyperactivation of STAT3 occurs in COVID-19 infection and other viral infections. [ 15 ] [ 16 ]
Loss-of-function mutations in the STAT3 gene result in hyperimmunoglobulin E syndrome , associated with recurrent infections as well as disordered bone and tooth development. [ 17 ]
Gain-of-function mutations in the STAT3 gene have been reported to cause multi-organ early onset auto-immune diseases; such as thyroid disease, diabetes, intestinal inflammation, and low blood counts, [ 18 ] while constitutive STAT3 activation is associated with various human cancers and commonly suggests poor prognosis. [ 19 ] [ 20 ] [ 21 ] [ 22 ] It has anti-apoptotic as well as proliferative effects. [ 19 ]
STAT3 can promote oncogenesis by being constitutively active through various pathways as mentioned elsewhere. A tumor suppressor role of STAT3 has also been reported. [ 23 ] [ 24 ] [ 25 ] In the report on human glioblastoma tumor, or brain cancer, STAT3 was shown to have an oncogenic or a tumor suppressor role depending upon the mutational background of the tumor. A direct connection between the PTEN-Akt-FOXO axis (suppressive) and the leukemia inhibitory factor receptor beta (LIFRbeta)-STAT3 signaling pathway (oncogenic) was shown. Overactivation of STAT3 promotes tumor survival and reduces sensitivity to temozolomide (TMZ), the standard chemotherapy for this cancer. Systemic inhibition of STAT3, however, risks immune dysregulation, complicating its therapeutic targeting. Recent studies highlight a non-coding RNA transcribed from a STAT3 enhancer region, termed TMZR1-eRNA, which regulates STAT3 expression. Silencing TMZR1-eRNA reduces STAT3 mRNA and protein levels, sensitizing glioblastoma cells to TMZ-induced cell death. Mechanistically, TMZR1-eRNA enhances STAT3 promoter activity, creating a feedback loop that sustains STAT3 expression. Importantly, TMZR1-eRNA expression is minimal in healthy brain tissue and peripheral blood cells, suggesting its suppression could offer a tumor-specific strategy to overcome chemoresistance with reduced off-target effects compared to direct STAT3 inhibitors [ 26 ]
Increased activity of STAT3 in cancer cells, leads to changes in the function of protein complexes that control expression of inflammatory genes, with result profound change in the secretome and the cell phenotypes, their activity in the tumor, and their capacity for metastasis. [ 27 ]
STAT3 has been shown to interact with:
Niclosamide seems to inhibit the STAT3 signalling pathway. [ 57 ]
Nicotinamide (a type of vitamin B 3 ) naturally inhibits STAT3. [ 58 ] However NAC ( Acetylcysteine ) inhibits STAT3 inhibitors. [ 59 ] | https://en.wikipedia.org/wiki/STAT3 |
6775
20849
ENSG00000138378
ENSMUSG00000062939
Q14765
P42228
NM_001243835 NM_003151
NM_011487 NM_001308266
NP_001230764 NP_003142
NP_001295195 NP_035617
Signal transducer and activator of transcription 4 ( STAT4 ) is a transcription factor belonging to the STAT protein family, composed of STAT1 , STAT2 , STAT3 , STAT4 , STAT5A , STAT5B , STAT6 . [ 5 ] STAT proteins are key activators of gene transcription which bind to DNA in response to cytokine gradient. [ 6 ] STAT proteins are a common part of Janus kinase (JAK)- signalling pathways, activated by cytokines.STAT4 is required for the development of Th1 cells from naive CD4+ T cells [ 7 ] and IFN-γ production in response to IL-12 . [ 8 ] There are two known STAT4 transcripts, STAT4α and STAT4β, differing in the levels of interferon-gamma (IFN-γ )production downstream. [ 9 ]
Human as well murine STAT4 genes lie next to STAT1 gene locus suggesting that the genes arose by gene duplication . [ 5 ] STAT proteins have six functional domains : 1. N-terminal interaction domain – crucial for dimerization of inactive STATs and nuclear translocation; 2.helical coiled coil domain – association with regulatory factors; 3. central DNA-binding domain – binding to the enhancer region of IFN-γ activated sequence (GAS) family genes; 4. linker domain – assisting during the DNA binding process; 5. Src homology 2 (SH2) domain – critical for specific binding to the cytokine receptor after tyrosine phosphorylation; 6. C-terminal transactivation domain – triggering the transcriptional process. [ 10 ] [ 11 ] The length of the protein is 748 amino acids, and the molecular weight is 85 941 Dalton . [ 12 ]
Distribution of STAT4 is restricted to myeloid cells , thymus and testis . [ 5 ] In resting human T cells it is expressed at very low levels, but its production is amplified by PHA stimulation. [ 8 ]
Pro-inflammatory cytokine IL-12 is produced in heterodimer form by B cells and antigen-presenting cells . Binding of IL-12 to IL-12R, which is composed of two different subunits (IL12Rβ1 and IL12Rβ2), leads to the interaction of IL12Rβ1 and IL12Rβ2 with JAK2 and TYK2, which is followed by phosphorylation of STAT4 tyrosine 693. The pathway then induces IFNγ production and Th1 differentiation. STAT4 is critical in promotion of antiviral response of natural killer (NK) cell by targeting of promotor regions of Runx1 and Runx3. [ 13 ]
Secreted by leukocytes, respectively fibroblasts, IFNα IFNβ together regulate antiviral immunity, cell proliferation and anti-tumor effects. [ 14 ] In viral infection signalling pathway, either of IFNα or β binds to IFN receptor (IFNAR), composed of IFNAR1 and IFNAR2, immediately followed by the phosphorylation of STAT1, STAT4 and IFN target genes. [ 15 ] During the initial phase of viral infection in NK cells, STAT1 activation is replaced by the activation of STAT4.
Monocytes, activated dendritic cells (DC) and macrophages stimulate the accumulation of IL-23 after exposure to molecules of Gram-positive/negative bacteria or viruses. Receptor for IL-23 contains IL12β 1 and IL23R subunits, which upon binding of IL-23 promotes the phosphorylation STAT4. The presence of IL12β 1 enables similar, although weaker downstream activity as compared to IL-12. During chronic inflammation, IL-23/STAT4 signalling pathway is involved in the induction of differentiation and expansion of Th17 pro-inflammatory T helper cells. [ 16 ]
Additionally, other cytokines like IL2, IL 27, IL35, IL18 and IL21 are known to activate STAT4.
In cells with progressively increasing expression of IL12 and IL6, SOCSs production and activity suppress cytokine signalling and phosphorylation of JAK-STAT pathways in a negative feedback loop. [ 17 ]
Other suppressors of the pathways are: protein inhibitor of activated STAT (PAIS) (regulation of transcriptional activity in the nucleus, observed in STAT4-DNA binding complex), protein tyrosine phosphatase (PTP) (removal of phosphate groups from phosphorylated tyrosine in JAK/STAT pathway proteins), STAT-interacting LIM protein (SLIM) (STAT ubiquitin E3 ligase blocking the phosphorylation of STAT4) or microRNA (miRNA) (degradation of STAT4 mRNA and its post-transcriptional regulation). [ 11 ]
STAT4 binds to hundreds of sites in the genome, [ 18 ] among others to the promoters of genes for cytokines ( IFN-γ , TNF ), receptors ( IL18R1 , IL12rβ2 , IL18RAP ), and signaling factors ( MYD88 ). [ 18 ]
STAT4 is involved in several autoimmune and cancer diseases in animal models humans, significantly in the disease progression and pathology. STAT4 were significantly increased in patients with colitis ulcerative [ 19 ] and skin T cells of psoriatic patients. [ 20 ] Moreover, STAT4 -/- mice developed less severe experimental autoimmune encephalo-myelitis (EAE) than the wild type mice. [ 21 ] [ 22 ]
Intronic single nucleotide polymorphism (SNP) mostly in third intron of the STAT4 has shown to be associated with immune dysregulation and autoimmunity including systemic lupus erythematosus (SLE) [ 23 ] and rheumatoid arthritis [ 24 ] as well as Sjögren's disease (SD), [ 25 ] systemic sclerosis , [ 26 ] psoriasis [ 27 ] and also type-1 diabetes . [ 28 ] High incident of STAT4 genetic polymorphisms and susceptibility to autoimmune diseases is a reason to consider the STAT4 as general autoimmune disease susceptibility locus. [ 29 ] | https://en.wikipedia.org/wiki/STAT4 |
Signal transducer and activator of transcription 5 ( STAT5 ) refers to two highly related proteins , STAT5A and STAT5B , which are part of the seven-membered STAT family of proteins. Though STAT5A and STAT5B are encoded by separate genes , the proteins are 90% identical at the amino acid level. [ 1 ] STAT5 proteins are involved in cytosolic signalling and in mediating the expression of specific genes. [ 2 ] Aberrant STAT5 activity has been shown to be closely connected to a wide range of human cancers , [ 3 ] and silencing this aberrant activity is an area of active research in medicinal chemistry . [ 4 ]
In order to be functional, STAT5 proteins must first be activated. This activation is carried out by kinases associated with transmembrane receptors : [ 3 ]
In the activation pathway illustrated to the left, the ligand involved is a cytokine and the specific kinase taking part in activation is JAK . The dimerized STAT5 represents the active form of the protein, which is ready for translocation into the nucleus .
Once in the nucleus, the dimers bind to STAT5 response elements , inducing transcription of specific sets of genes. Upregulation of gene expression by STAT5 dimers has been observed for genes dealing with: [ 2 ]
Activated STAT5 dimers are, however, short-lived and the dimers are made to undergo rapid deactivation. Deactivation may be carried out by a direct pathway, removing the phosphate groups using phosphatases like PIAS or SHP-2 for example, or by an indirect pathway, which involves reducing cytokine signalling. [ 6 ]
STAT5 has been found to be constitutively phosphorylated in cancer cells, [ 4 ] implying that the protein is always present in its active form. This constant activation is brought about either by mutations or by aberrant expressions of cell signalling, resulting in poor regulation, or complete lack of control, of the activation of transcription for genes influenced by STAT5. This leads to constant and increased expression of these genes. For example, mutations may lead to increased expression of anti-apoptotic genes, the products of which actively prevent cell death. The constant presence of these products preserves the cell in spite of it having become cancerous, causing the cell to eventually become malignant .
Attempts at treatment for cancer cells with constitutively phosphorylated STAT5 have included both indirect and direct inhibition of STAT5 activity. While more medicinal work has been done in indirect inhibition, this approach can lead to increased toxicity in cells and can also result in non-specific effects, both of which are better handled by direct inhibition. [ 4 ]
Indirect inhibition targets kinases associated with STAT5, or targets proteases that carry out terminal truncation of proteins. Different inhibitors have been designed to target different kinases:
Direct inhibition of STAT5 activity makes use of small molecule inhibitors that prevent STAT5 from properly binding to DNA or prevent proper dimerization. The inhibiting of DNA binding utilizes RNA interference , [ 10 ] antisense oligodeoxynucleotide, [ 10 ] and short hairpin RNA . [ 11 ] The inhibition of proper dimerization, on the other hand, is brought about by the use of small molecules that target the SH2 domain. Recent work on drug development in the latter field have proved particularly effective. [ 12 ] | https://en.wikipedia.org/wiki/STAT5 |
1OJ5 , 4Y5W , 4Y5U
6778
20852
ENSG00000166888
ENSMUSG00000002147
P42226
P52633
NM_001178078 NM_001178079 NM_001178080 NM_001178081 NM_003153
NM_009284
NP_001171549 NP_001171550 NP_001171551 NP_001171552 NP_003144
NP_033310
Signal transducer and activator of transcription 6 ( STAT6 ) is a transcription factor that belongs to the Signal Transducer and Activator of Transcription (STAT) family of proteins. [ 5 ] The proteins of STAT family transmit signals from a receptor complex to the nucleus and activate gene expression . Similarly as other STAT family proteins, STAT6 is also activated by growth factors and cytokines . STAT6 is mainly activated by cytokines interleukin-4 and interleukin-13 . [ 5 ]
In the human genome , STAT6 protein is encoded by the STAT6 gene, located on the chromosome 12q13.3-q14.1. [ 6 ] The gene encompasses over 19 kb and consists of 23 exons . [ 7 ] STAT6 shares structural similarity with the other STAT proteins and is composed of the N-terminal domain , DNA binding domain , SH3- like domain, SH2 domain and transactivation domain (TAD). [ 7 ]
STAT proteins are activated by the Janus family (JAKs) tyrosine kinases in response to cytokine exposure. [ 8 ] STAT6 is activated by cytokines interleukin-4 (IL-4), and interleukin-13 (IL-13) with their receptors that both contain the α subunit of the IL-4 receptor (IL-4Rα). [ 8 ] Tyrosine phosporylation of STAT6 after stimulation by IL-4 results in the formation of STAT6 homodimers that bind specific DNA elements via a DNA-binding domain. [ 5 ] [ 9 ]
STAT6-mediated signaling pathway is required for the development of T-helper type 2 (Th2) cells and Th2 immune response. [ 8 ] Expression of Th2 cytokines, including IL-4 , IL-13 , and IL-5 , was reduced in STAT6-deficient mice. [ 5 ] STAT 6 protein is crucial in IL4 mediated biological responses. It was found that STAT6 induce the expression of BCL2L1/BCL-X(L), which is responsible for the anti-apoptotic activity of IL4. IL-4 stimulates the phosphorylation of IL-4 receptor, which recruits cytosolic STAT6 by its SH2 domain and STAT6 is phosphorylated on tyrosine 641 (Y641) by JAK1 , which results in the dimerization and nuclear translocation of STAT6 to activate target genes. [ 10 ] Knockout studies in mice suggested the roles of this gene in differentiation of T helper 2 (Th2), expression of cell surface markers, and class switch of immunoglobulins . [ 11 ]
Activation of STAT6 signaling pathway is necessary in macrophage function, and is required for the M2 subtype activation of macrophages. [ 12 ] [ 13 ] [ 14 ] STAT6 protein also regulates other transcription factor as Gata3 , which is important regulator of Th2 differentiation. [ 5 ] STAT6 is also required for the development of IL-9 -secreting T cells . [ 5 ]
STAT6 also plays a critical role in Th2 lung inflammatory responses including clearance of parasitic infections and in the pathogenesis of asthma. [ 8 ] Th2-cell derived cytokines as IL-4 and IL-13 induce the production of IgE which is a major mediator in allergic response. [ 9 ] Association studies searching for relation of polymorphisms in STAT6 with IgE level or asthma discovered a few polymorphisms significantly associated with examined traits. Only two polymorphisms showed repeatedly significant clinical association and/or functional effect on STAT6 function (GT repeats in exon 1 and rs324011 polymorphism in intron 2). [ 7 ]
STAT6 has been shown to interact with: | https://en.wikipedia.org/wiki/STAT6 |
Members of the signal transducer and activator of transcription ( STAT ) protein family are intracellular transcription factors that mediate many aspects of cellular immunity , proliferation , apoptosis and differentiation . They are primarily activated by membrane receptor-associated Janus kinases (JAK). Dysregulation of this pathway is frequently observed in primary tumors and leads to increased angiogenesis which enhances the survival of tumors and immunosuppression . Gene knockout studies have provided evidence that STAT proteins are involved in the development and function of the immune system and play a role in maintaining immune tolerance and tumor surveillance.
The first two STAT proteins were identified in the interferon system. There are seven mammalian STAT family members that have been identified: STAT1 , STAT2 , STAT3 , STAT4 , STAT5 ( STAT5A and STAT5B ), and STAT6 .
STAT1 homodimers are involved in type II interferon signalling, and bind to the GAS (Interferon- G amma A ctivated S equence) promoter to induce expression of interferon stimulated genes (ISG). In type I interferon signaling, STAT1-STAT2 heterodimer combines with IRF 9 ( I nterferon R esponse F actor) to form ISGF 3 ( I nterferon S timulated G ene F actor), which binds to the ISRE ( I nterferon- S timulated R esponse E lement) promoter to induce ISG expression.
All seven STAT proteins share a common structural motif consisting of an N-terminal domain followed by a coiled-coil , DNA-binding domain , linker, Src homology 2 (SH2) , and a C-terminal transactivation domain . Much research has focused on elucidating the roles each of these domains play in regulating different STAT isoforms. Both the N-terminal and SH2 domains mediate homo or heterodimer formation, while the coiled-coil domain functions partially as a nuclear localization signal (NLS). Transcriptional activity and DNA association are determined by the transactivation and DNA-binding domains, respectively.
Extracellular binding of cytokines or growth factors induce activation of receptor-associated Janus kinases , which phosphorylate a specific tyrosine residue within the STAT protein promoting dimerization via their SH2 domains . The phosphorylated dimer is then actively transported to the nucleus via an importin α/β ternary complex. Originally, STAT proteins were described as latent cytoplasmic transcription factors as phosphorylation was thought to be required for nuclear retention. However, unphosphorylated STAT proteins also shuttle between the cytosol and nucleus, and play a role in gene expression. Once STAT reaches the nucleus, it binds to a consensus DNA-recognition motif called gamma-activated sites (GAS) in the promoter region of cytokine - inducible genes and activates transcription. The STAT protein can be dephosphorylated by nuclear phosphatases , which leads to inactivation of STAT and subsequent transport out of the nucleus by an exportin - RanGTP complex. | https://en.wikipedia.org/wiki/STAT_protein |
STEAM education is an approach to teaching STEM subjects that incorporates artistic skills like creative thinking and design . [ 1 ] [ 2 ] The name derives from the acronym STEM , with an A added to stand for arts . STEAM programs aim to teach students innovation , to think critically , and to use engineering or technology in imaginative designs or creative approaches to real-world problems while building on students' mathematics and science base. [ 3 ] [ 4 ] [ 5 ]
Examples of state-based STEAM programs as guidance or related resources: [ 6 ]
Georgia Institute of Technology (Georgia Tech) in collaboration with its Center for Education Integrating Science, Mathematics and Computing (CEISMC) created the GoSTEAM program. GoSTEAM is a program that integrates art and music into STEM focused curriculum for students in the K–12 ( kindergarten to twelfth grade studies). [ 13 ] [ 14 ]
The Journal of STEAM Education (J-STEAM) is a free and open-access journal that is peer-reviewed by an international team of reviewers. It is an online publication and is published by the STEAM Education Research Association. The journal publishes articles from a range of topics in educational research and related disciplines. As the J-STEAM, it has an emphasis on the integration of STEAM topics, namely Science, Technology, Engineering, Art, and Mathematics. [ 15 ]
STEM subjects can incorporate art to assist teaching STEM, where art is a tool for STEM in the form of STEAM education. However, some criticism holds that art and STEM subjects should be of equal value in the education process. [ 18 ] | https://en.wikipedia.org/wiki/STEAM_education |
Stimulated emission depletion ( STED ) microscopy is one of the techniques that make up super-resolution microscopy . It creates super-resolution images by the selective deactivation of fluorophores , minimizing the area of illumination at the focal point, and thus enhancing the achievable resolution for a given system. [ 1 ] It was developed by Stefan W. Hell and Jan Wichmann in 1994, [ 2 ] and was first experimentally demonstrated by Hell and Thomas Klar in 1999. [ 3 ] Hell was awarded the Nobel Prize in Chemistry in 2014 for its development. In 1986, V.A. Okhonin [ 4 ] (Institute of Biophysics, USSR Academy of Sciences, Siberian Branch, Krasnoyarsk) had patented the STED idea. [ 5 ] This patent was unknown to Hell and Wichmann in 1994.
STED microscopy is one of several types of super resolution microscopy techniques that have recently been developed to bypass the diffraction limit of light microscopy to increase resolution. STED is a deterministic functional technique that exploits the non-linear response of fluorophores commonly used to label biological samples in order to achieve an improvement in resolution, that is to say STED allows for images to be taken at resolutions below the diffraction limit. This differs from the stochastic functional techniques such as photoactivated localization microscopy (PALM) and stochastic optical reconstruction microscopy (STORM) as these methods use mathematical models to reconstruct a sub diffraction limit from many sets of diffraction limited images.
In traditional microscopy, the resolution that can be obtained is limited by the diffraction of light . Ernst Abbe developed an equation to describe this limit. The equation is:
where D is the diffraction limit, λ is the wavelength of the light, and NA is the numerical aperture , or the refractive index of the medium multiplied by the sine of the angle of incidence. n describes the refractive index of the specimen, α measures the solid half‐angle from which light is gathered by an objective, λ is the wavelength of light used to excite the specimen, and NA is the numerical aperture. To obtain high resolution (i.e. small d values), short wavelengths and high NA values (NA = n sinα) are optimal. [ 6 ] This diffraction limit is the standard by which all super resolution methods are measured. Because STED selectively deactivates the fluorescence, it can achieve resolution better than traditional confocal microscopy. Normal fluorescence occurs by exciting an electron from the ground state into an excited electronic state of a different fundamental energy level (S0 goes to S1) which, after relaxing back to the vibrational ground state (of S1), emits a photon by dropping from S1 to a vibrational energy level on S0. STED interrupts this process before the photon is released. The excited electron is forced to relax into a higher vibration state than the fluorescence transition would enter, causing the photon to be released to be red-shifted as shown in the image to the right. [ 7 ] Because the electron is going to a higher vibrational state, the energy difference of the two states is lower than the normal fluorescence difference. This lowering of energy raises the wavelength, and causes the photon to be shifted farther into the red end of the spectrum. This shift differentiates the two types of photons, and allows the stimulated photon to be ignored.
To force this alternative emission to occur, an incident photon must strike the fluorophore. This need to be struck by an incident photon has two implications for STED. First, the number of incident photons directly impacts the efficiency of this emission, and, secondly, with sufficiently large numbers of photons fluorescence can be completely suppressed. [ 8 ] To achieve the large number of incident photons needed to suppress fluorescence, the laser used to generate the photons must be of a high intensity. Unfortunately, this high intensity laser can lead to the issue of photobleaching the fluorophore. Photobleaching is the name for the destruction of fluorophores by high intensity light.
STED functions by depleting fluorescence in specific regions of the sample while leaving a center focal spot active to emit fluorescence. This focal area can be engineered by altering the properties of the pupil plane of the objective lens. [ 9 ] [ 10 ] [ 11 ] The most common early example of these diffractive optical elements, or DOEs, is a torus shape used in two-dimensional lateral confinement shown below. The red zone is depleted, while the green spot is left active. This DOE is generated by a circular polarization of the depletion laser, combined with an optical vortex . The lateral resolution of this DOE is typically between 30 and 80 nm. However, values down to 2.4 nm have been reported. [ 12 ] Using different DOEs, axial resolution on the order of 100 nm has been demonstrated. [ 13 ] A modified Abbe's equation describes this sub diffraction resolution as:
D = λ 2 n sin α 1 + I I sat = λ 2 N A 1 + σ {\displaystyle \mathrm {D} ={\frac {\lambda }{2n\sin {\alpha }{\sqrt {1+{\frac {I}{I_{\text{sat}}}}}}}}={\frac {\lambda }{\mathrm {2NA} {\sqrt {1+\sigma }}}}}
Where n {\textstyle n} is the refractive index of the medium, I {\textstyle I} is the intracavity intensity and I sat {\textstyle I_{\text{sat}}} is the saturation intensity . Where σ {\textstyle \sigma } is the saturation factor expressing the ratio of the applied (maximum) STED intensity to the saturation intensity, σ = I max / I sat {\textstyle \sigma =I_{\text{max}}/I_{\text{sat}}} . [ 6 ] [ 14 ]
To optimize the effectiveness of STED, the destructive interference in the center of the focal spot needs to be as close to perfect as possible. That imposes certain constraints on the optics that can be used.
Early on in the development of STED, the number of dyes that could be used in the process was very limited. Rhodamine B was named in the first theoretical description of STED. [ 2 ] As a result, the first dyes used were laser emitting in the red spectrum. To allow for STED analysis of biological systems, the dyes and laser sources must be tailored to the system. This desire for better analysis of these systems has led to living cell STED and multicolor STED, but it has also demanded more and more advanced dyes and excitation systems to accommodate the increased functionality. [ 7 ]
One such advancement was the development of immunolabeled cells. These cells are STED fluorescent dyes bound to antibodies through amide bonds. The first use of this technique coupled MR-121SE, a red dye, with a secondary anti-mouse antibody. [ 8 ] Since that first application, this technique has been applied to a much wider range of dyes including green emitting, Atto 532, [ 15 ] [ 16 ] [ 17 ] and yellow emitting, Atto 590, [ 18 ] as well as additional red emitting dyes. In addition, Atto 647N was first used with this method to produce two-color STED. [ 19 ]
Over the last several years, STED has developed from a complex and highly specific technique to a general fluorescence method. As a result, a number of methods have been developed to expand the utility of STED and to allow more information to be provided.
From the beginning of the process, STED has allowed fluorescence microscopy to perform tasks that had been only possible using electron microscopy. As an example, STED was used for the elucidation of protein structure analysis at a sub-organelle level. The common proof of this level of study is the observation of cytoskeletal filaments. In addition, neurofilaments , actin , and tubulin are often used to compare the resolving power of STED and confocal microscopes. [ 20 ] [ 21 ] [ 22 ]
Using STED, a lateral resolution of 70 – 90 nm has been achieved while examining SNAP25 , a human protein that regulates membrane fusion. This observation has shown that SNAP25 forms clusters independently of the SNARE motif's functionality, and binds to clustered syntaxin. [ 23 ] [ 24 ] Studies of complex organelles, like mitochondria, also benefit from STED microscopy for structural analysis. Using custom-made STED microscopes with a lateral resolution of fewer than 50 nm, mitochondrial proteins Tom20 , VDAC1 , and COX2 were found to distribute as nanoscale clusters. [ 25 ] [ 26 ] Another study used a homemade STED microscopy and DNA binding fluorescent dye, measured lengths of DNA fragments much more precisely than conventional measurement with confocal microscopy . [ 27 ]
Due to its function, STED microscopy can often be used with other high-resolution methods. The resolution of both electron and atomic force microscopy is even better than STED resolution, but by combining atomic force with STED, Shima et al. were able to visualize the actin cytoskeleton of human ovarian cancer cells while observing changes in cell stiffness. [ 28 ]
Multicolor STED was developed in response to a growing problem in using STED to study the dependency between structure and function in proteins. To study this type of complex system, at least two separate fluorophores must be used. Using two fluorescent dyes and beam pairs, colocalized imaging of synaptic and mitochondrial protein clusters is possible with a resolution down to 5 nm [18]. Multicolor STED has also been used to show that different populations of synaptic vesicle proteins do not mix of escape synaptic boutons. [ 29 ] [ 30 ] By using two color STED with multi-lifetime imaging, three channel STED is possible.
Early on, STED was thought to be a useful technique for working with living cells. [ 13 ] Unfortunately, the only way for cells to be studied was to label the plasma membrane with organic dyes. [ 29 ] Combining STED with fluorescence correlation spectroscopy showed that cholesterol -mediated molecular complexes trap sphingolipids , but only transiently. [ 31 ] However, only fluorescent proteins provide the ability to visualize any organelle or protein in a living cell. This method was shown to work at 50 nm lateral resolution within Citrine-tubulin expressing mammalian cells. [ 32 ] [ 33 ] In addition to detecting structures in mammalian cells, STED has allowed for the visualization of clustering YFP tagged PIN proteins in the plasma membrane of plant cells. [ 34 ]
Recently, multicolor live-cell STED was performed using a pulsed far-red laser and CLIPf-tag and SNAPf-tag expression. [ 35 ]
Superficial layers of mouse cortex can be repetitively imaged through a cranial window. [ 36 ] This allows following the fate and shape of individual dendritic spines for many weeks. [ 37 ] With two-color STED, it is even possible to resolve the nanostructure of the postsynaptic density in life animals. [ 38 ]
Super-resolution requires small pixels, which means more spaces to acquire from in a given sample, which leads to a longer acquisition time. However, the focal spot size is dependent on the intensity of the laser being used for depletion. As a result, this spot size can be tuned, changing the size and imaging speed. A compromise can then be reached between these two factors for each specific imaging task. Rates of 80 frames per second have been recorded, with focal spots around 60 nm. [ 1 ] [ 39 ] Up to 200 frames per second can be reached for small fields of view. [ 40 ]
Photobleaching can occur either from excitation into an even higher excited state, or from excitation in the triplet state. To prevent the excitation of an excited electron into another, higher excited state, the energy of the photon needed to trigger the alternative emission should not overlap the energy of the excitation from one excited state to another. [ 41 ] This will ensure that each laser photon that contacts the fluorophores will cause stimulated emission, and not cause the electron to be excited to another, higher energy state. Triplet states are much longer lived than singlet states, and to prevent triplet states from exciting, the time between laser pulses needs to be long enough to allow the electron to relax through another quenching method, or a chemical compound should be added to quench the triplet state. [ 20 ] [ 42 ] [ 43 ] | https://en.wikipedia.org/wiki/STED_microscopy |
The STEPS Centre (Social, Technological and Environmental Pathways to Sustainability) was an interdisciplinary research centre hosted at the University of Sussex , funded by the Economic and Social Research Council . The Centre's research brought together development studies with science and technology studies . It was launched at Portcullis House in London on 25 June 2007 [ 1 ] and closed in 2022. [ citation needed ]
The STEPS Centre described its aim as to "highlight, reveal and contribute to just and democratic pathways to sustainability that include the needs, knowledge and perspectives of poor and marginalised people". Based at the Institute of Development Studies (IDS) and the Science Policy Research Unit ( SPRU ) at the University of Sussex , the centre worked with partners in Africa, Asia and Latin America. [ citation needed ]
Professor Ian Scoones [ 2 ] and Professor Andy Stirling [ 3 ] were its co-directors. Professor Melissa Leach [ 4 ] [ 5 ] stepped down as STEPS Director in 2014 to become the Director of the Institute of Development Studies . [ 6 ]
The STEPS Centre's research investigated the politics of sustainability in various domains, including climate change, food systems, urbanization, and technology. [ 7 ] It focused on the perspectives and needs of marginalized people, particularly in poor countries and settings, as well as methodologies for including these priorities in policy appraisal and decision-making. [ 8 ]
In the final four years of its research program, the STEPS Centre focused on a series of themes with implications for the politics of sustainability. These themes included transformations and social change, uncertainty and other forms of incertitude, multiple perspectives on nature and the environment, and methodologies for research and appraisal. [ citation needed ]
The STEPS Centre's pathways approach [ 9 ] aims to understand the complex, non-linear interactions between social, technological and environmental systems. Some pathways may threaten poor peoples' livelihoods and health while others create opportunities for sustainability. [ citation needed ]
The pathways approach draws attention to the influence of power in determining which narratives and problem framings are dominant in areas such as climate policy, conservation, technological innovation or agriculture, which pathways are pursued or neglected, and the appropriateness of different methodologies to highlight uncertainties, plural perspectives and values, and alternative actions. [ citation needed ]
A paper published in 2007 entitled Pathways to Sustainability: an Overview of the STEPS Centre Approach [ 10 ] outlined the STEPS Centre approach to understanding dynamic systems and their governance. The paper laid out the ingredients of the STEPS Centre's work, including linking diverse social and natural science perspectives, connecting theory, policy and practice and an engaged, interactive approach to communications. Promoting pathways to sustainability that meet the perspectives and priorities of poor and marginalised groups is the heart of the pathways approach. [ citation needed ]
Among the STEPS Centre's projects are:
• Innovation, Sustainability, Development: A New Manifesto (40 years on from the Sussex Manifesto )
• Crop, disease and innovation in Kenya - Maize and farming system dynamics in areas affected by climate change
• Urbanisation in Asia - urbanisation and sustainability on the expanding peri-urban fringe of Delhi, India
• Rethinking regulation - assumptions and realities of drug and seed regulation in China and Argentina
• Risk, uncertainty and technology - framing and responses to risks and uncertainties in areas of rapid scientific and technological advance
• Epidemics, livelihoods and politics - HIV-AIDS, SARS, 'avian flu, BSE - procedures for addressing epidemics that support rather than compromise poor people
By Leach. M, Scoones, I. and Stirling, A. (2010) ISBN 978-1-84971-093-0
By Leach. M., Scoones, I. and Stirling, A. (2007) ISBN 978-1-85864-656-5
By Scoones, I., Leach, M., Smith, A., Stagl, S., Stirling, A. and Thompson, J. (2007) ISBN 978-1-85864-650-3
By Leach, M., Bloom, G., Ely, A., Nightingale, P., Scoones, I., Shah, E. and Smith, A. (2007) – ISBN 978-1-85864-651-0
By Stirling, A., Leach, M., Mehta, L., Scoones, I., Smith, A., Stagl, S. and Thompson, J. (2007) ISBN 978-1-85864-652-7
By Thompson, J., Millstone, E., Scoones, I., Ely, A., Marshall, F., Shah, E.and Stagl, S. (2007) ISBN 978-1-85864-653-4
By Bloom, G., Edström, J., Leach, M., Lucas, H., MacGregor, H., Standing, H. and Waldman, L. (2007) ISBN 978-1-85864-654-1
By Mehta, L., Marshall, F., Movik, S., Stirling, A., Shah, E., Smith, A. and Thompson, J. (2007) ISBN 978-1-85864-655-8
By Krätli, S. (2008) The ISBN printed in the document (978 1 85864 699 5) is invalid, causing a checksum error.
By Melissa Leach, Ian Scoones (2006) Demos pamphlet ISBN 1-84180-162-3 | https://en.wikipedia.org/wiki/STEPS_Centre |
STO- n G basis sets are minimal basis sets used in computational chemistry , more specifically in ab initio quantum chemistry methods , to calculate the molecular orbitals of chemical systems within Hartree-Fock theory or density functional theory . The basis functions are linear combinations of n {\displaystyle n} primitive Gaussian-type orbitals (GTOs) that are fitted to single Slater-type orbitals (STOs). They were first proposed by John Pople and n {\displaystyle n} originally took the values 2 – 6. A minimal basis set is where only sufficient orbitals are used to contain all the electrons in the neutral atom. Thus, for the hydrogen atom, only a single 1s orbital is needed, while for a carbon atom, 1s, 2s and three 2p orbitals are needed.
STO- n {\displaystyle n} G basis sets consist of one STO for each orbital in the neutral atom (with suitable parameter ζ {\displaystyle \zeta } ) for each atom in the system to be described (e.g. molecule). The STOs assigned to a particular atom are centered around its nucleus. Therefore, the number of basis functions for each atom depends on its type. The STO- n {\displaystyle n} G basis sets are available for all atoms from hydrogen up to xenon. [ 1 ] [ 2 ]
Each STO (both core and valence orbitals) ψ m l {\displaystyle \psi _{ml}} , where m {\displaystyle m} is the principal quantum number and l {\displaystyle l} is the angular momentum quantum number, is approximated by a linear combination of n {\displaystyle n} primitive GTOs ϕ l α m j {\displaystyle \phi _{l\alpha _{mj}}} with exponents α m j {\displaystyle \alpha _{mj}} : [ 3 ]
ψ m l STO − n G = ∑ j = 1 n c m l j ϕ l α j . {\displaystyle \psi _{ml}^{{\text{STO}}-n{\text{G}}}=\sum _{j=1}^{n}c_{mlj}\phi _{l\alpha _{j}}.}
The expansion coefficients c m l j {\displaystyle c_{mlj}} and exponents α m j {\displaystyle \alpha _{mj}} are fitted with the least squares method (this differs from the more common procedure, where they are chosen to give the lowest energy) to all STOs within the same shell m {\displaystyle m} simultaneously. Note that all ψ m l STO − n G {\displaystyle \psi _{ml}^{{\text{STO}}-n{\text{G}}}} within the same shell m {\displaystyle m} (e.g. 2s and 2p) share the same exponents, i.e. they do not depend on the angular momentum, which is a special feature of this basis set and allows more efficient computation. [ 4 ]
The fit between the GTOs and the STOs is often reasonable, except near to the nucleus: STOs have a cusp at the nucleus, while GTOs are flat in that region. [ 5 ] [ 6 ] Extensive tables of parameters have been calculated for STO-1G through STO-6G for s orbitals through g orbitals [ 7 ] and can be downloaded from the Basis Set Exchange. [ 2 ]
The STO-2G basis set is a linear combination of 2 primitive Gaussian functions. The original coefficients and exponents for first-row and second-row atoms are given as follows (for ζ = 1 {\displaystyle \zeta =1} ). [ 4 ]
For general values of ζ {\displaystyle \zeta } , one can use the scaling law ψ m l ζ ( r ) = ζ 3 / 2 ψ m l 1 ( ζ r ) {\displaystyle \psi _{ml}^{\zeta }(\mathbf {r} )=\zeta ^{3/2}\psi _{ml}^{1}(\zeta \mathbf {r} )} to approximate general STOs with ζ ≠ 1 {\displaystyle \zeta \neq 1} .
The STO-3G basis set is the most commonly used among the STO- n {\displaystyle n} G basis sets and is a linear combination of 3 primitive Gaussian functions. The coefficients and exponents for first-row and second-row atoms are given as follows (for ζ = 1 {\displaystyle \zeta =1} ). [ 3 ]
The exact energy of the 1s electron of H atom is −0.5 hartree, given by a single Slater-type orbital with exponent 1.0. The following table illustrates the increase in accuracy as the number of primitive Gaussian functions increases from 3 to 6 in the basis set. [ 4 ]
The most widely used basis set of this group is STO-3G, which is used for large systems and for preliminary geometry determinations. However, they are not suited for accurate ab-initio calculations due to their lack of flexibility in radial direction. For such tasks, larger basis sets are needed, such as the Pople basis sets . | https://en.wikipedia.org/wiki/STO-nG_basis_sets |
[Swedish] Tactical (Fighting Command) and Air Defence Control System [ 1 ] ( Swedish : Stridsledning och luftbevakning, STRIL , lit. 'Combat control and air surveillance') in forms of STRIL 50 (operational in the 1950s) and STRIL 60 (operational in the 1960s, 1970s and 1980s) were integrated systems for aerial warfare control including early warning radar and ground-controlled interception . The systems depended on radar and radio as primary technologies but STRIL 50 was based on manual control while STRIL 60 applied the usage of early digital computers .
STRIL 60, designed in cooperation with Marconi Company , were in the very frontline of providing combat critical information to airborne aircraft, the Saab 35 Draken and Saab J32 Lansen fighter aircraft, by means of digital telemetry links with direct presentation of target guidance data on dedicated gauges on the cockpit instrument panel. The uplink to the aircraft could resist heavy jamming and the Swedish Air Force was first in the world to provide digital combat guidance that would remain reliable in a hostile and interfered radio environment.
The computerised command and control system in combination with the datalink brought the time from target detection to guidance commands reaching a fighter aircraft down to 5–6 seconds.
In the Stril 50 system with manual plotting and voice communication this had been 30–60 seconds. [ 2 ]
Eventually, the Saab 37 Viggen aircraft system also utilized STRIL 60 but target presentation in the cockpit was then replaced by digital computer displays instead of the mechanical gauges used on the Draken.
In the 1990s, STRIL 60 was replaced by STRIL 90 which is a modern combat control system integrated with the Saab S100B Argus combat control/surveillance and SAAB JAS 39 Gripen multi-role combat aircraft.
This article about the Cold War is a stub . You can help Wikipedia by expanding it .
This article about the military of Sweden is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/STRIL |
In molecular biology, STRING ( Search Tool for the Retrieval of Interacting Genes/Proteins ) is a biological database and web resource of known and predicted protein–protein interactions . [ 1 ] [ 2 ] [ 3 ] [ 4 ] [ 5 ] [ 6 ]
The STRING database contains information from numerous sources, including experimental data, computational prediction methods and public text collections. It is freely accessible and it is regularly updated. The resource also serves to highlight functional enrichments in user-provided lists of proteins, using a number of functional classification systems such as GO , Pfam and KEGG . The latest version 11b contains information on about 59 million proteins from more than 12,000 organisms. [ 7 ] STRING has been developed by a consortium of academic institutions including CPR , EMBL , KU , SIB , TUD and UZH .
Protein–protein interaction networks are an important ingredient for the system-level understanding of cellular processes.
Such networks can be used for filtering and assessing functional genomics data and for providing an intuitive platform for annotating structural, functional and evolutionary properties of proteins.
Exploring the predicted interaction networks can suggest new directions for future experimental research and provide cross-species predictions for efficient interaction mapping. [ 8 ]
The data is weighted and integrated and a confidence score is calculated for all protein interactions. Results of the various computational predictions can be inspected from different designated views. There are two modes of STRING: Protein-mode and COG -mode. Predicted interactions are propagated to proteins in other organisms for which interaction has been described by inference of orthology . A web interface is available to access the data and to give a fast overview of the proteins and their interactions. A plug-in for cytoscape to use STRING data is available.
Another possibility to access data STRING is to use the application programming interface (API) by constructing a URL that contain the request.
Like many other databases that store protein association knowledge, STRING imports data from experimentally derived protein–protein interactions through literature curation. Furthermore, STRING also store computationally predicted interactions from: (i) text mining of scientific texts, (ii) interactions computed from genomic features, and
(iii) interactions transferred from model organisms based on orthology. [ 9 ]
All predicted or imported interactions are benchmarked against a common reference of functional partnership as annotated by KEGG (Kyoto Encyclopedia of Genes and Genomes).
STRING imports protein association knowledge from databases of physical interaction and databases of curated biological pathway knowledge
( MINT , HPRD , BIND , DIP , BioGRID , KEGG , Reactome , IntAct , EcoCyc , NCI-Nature Pathway Interaction Database , GO ).
Links are supplied to the originating data of the respective experimental repositories and database resources.
A large body of scientific texts ( SGD , OMIM , FlyBase , PubMed ) are parsed to search for statistically relevant co-occurrences of gene names. | https://en.wikipedia.org/wiki/STRING |
STRO-1 ( Stro-1 in mouse, rat, etc.) is a gene for a protein marker of mesenchymal stem cells (MSC). Molecular mass of Stro-1 is 75kD. The name STRO-1 is firstly proposed in the 1990s' as the name of an anti- CD34 +-mesenchymal-stem-cell monoclonal antibody . The name "STRO-1" consists of STRO, which means mesenchyme , and "1", which means it's the first isolated monoclonal antibody to identify mesenchymal stem cells. The term "STRO-1" then was applied to the antigen for this antibody. In human body, STRO-1 exists in many organs, like lung and liver. [ 1 ] [ 2 ] [ 3 ]
This biochemistry article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/STRO-1 |
An STR multiplex system is used to identify specific short tandem repeats (STRs). STR polymorphisms are genetic markers that may be used to identify a DNA sequence .
The FBI analyses 13 specific STR loci for their database. These may be used in many areas of genetics in addition to their forensic uses.
One can think of a STR multiplex system as a collection of specific STRs which are positionally conserved on a target genome. Hence these can be used as markers. A number of different STRs along with their loci in a particular genome can be used for genotyping .
For example, the STR multiplex system AmpFlSTR Profiler Plus which analyses nine different STRs (3S1358, vWA, FGA, D8S1179, D21S11, D18S51, D5S818, D13S317, D7S820) plus Amelogenin for sex determination is used for human identification purposes. [ 1 ]
This biochemistry article is a stub . You can help Wikipedia by expanding it .
This law enforcement –related article is a stub . You can help Wikipedia by expanding it .
This forensics -related article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/STR_multiplex_system |
The STSat-1 ( Science and Technology Satellite-1 ), formerly known as KAISTSat-4 (Korea Advanced Institute of Science and Technology Satellite-4), is an ultraviolet telescope in a satellite . It is funded by the Korea Aerospace Research Institute (KARI), and was launched on 27 September 2003, from Plesetsk Cosmodrome by a Kosmos-3M launch vehicle, [ 2 ] into an Earth orbit with a height between 675 and 695 km. [ 1 ] [ 3 ]
STSat-1 is a low-cost KAIST / KAIST Satellite Technology Research Center (SaTReC) satellite technology demonstration mission, funded by the Ministry of Science and Technology (MOST) of South Korea , a follow-up mission in the KITSAT program. STSat-1 is a South Korean astrophysical satellite that was launched by a Kosmos 3M launch vehicle from Plesetsk at 06:11:44 UTC on 27 September 2003. The 106 kg satellite carries a special UV imaging spectrograph to monitor gas clouds in the Galaxy . It will complete a full sky mapping in about a year, by scanning a one-degree strip every day. Additionally, it may also aim the telescope downward to image auroral displays. [ 3 ] | https://en.wikipedia.org/wiki/STSat-1 |
Several hundred metals, compounds, alloys and ceramics possess the property of superconductivity at low temperatures. The SU(2) color quark matter adjoins the list of superconducting systems. Although it is a mathematical abstraction, its properties are believed to be closely related to the SU(3) color quark matter , which exists in nature when ordinary matter is compressed at supranuclear densities above ~ 0.5 × 10 39 nucleon/cm 3 .
Superconducting materials are characterized by the loss of resistance and two parameters: a critical temperature T c and a critical magnetic field that brings the superconductor to its normal state. In 1911, H. Kamerlingh Onnes discovered the superconductivity of mercury at a temperature below 4 K. Later, other substances with superconductivity at temperatures up to 30 K were found. Superconductors prevent the penetration of the external magnetic field into the sample when the magnetic field strength is less than the critical value. This effect was called the Meissner effect . High-temperature superconductivity was discovered in the 1980s. Of the known compounds, the highest critical temperature T с = 135 K belongs to HgBa 2 Ca 2 Cu 3 O 8+ x .
Low-temperature superconductivity has found a theoretical explanation in the model of John Bardeen , Leon Cooper , and John Robert Schrieffer ( BCS theory ). [ 1 ] The physical basis of the model is the phenomenon of Cooper pairing of electrons. Since a pair of electrons carries an integer spin, the correlated states of the electrons can form a Bose–Einstein condensate. An equivalent formalism was developed by Nikolay Bogoliubov [ 2 ] and John George Valatin . [ 3 ]
Cooper pairing of nucleons takes place in ordinary nuclei. The effect manifests itself in the Bethe–Weizsacker mass formula , the last pairing term of which describes the correlation energy of two nucleons. Because of the pairing, the binding energy of even–even nuclei systematically exceeds the binding energy of odd–even and odd–odd nuclei.
The superfluid phase of neutron matter exists in neutron stars. The superfluidity is described by the BCS model with a realistic nucleon-nucleon interaction potential. By increasing the density of nuclear matter above the saturation density, quark matter is formed. It is expected that dense quark matter at low temperatures is a color superconductor. [ 4 ] [ 5 ] [ 6 ] In the case of the SU(3) color group, a Bose–Einstein condensate of the quark Cooper pairs carries an open color. To meet the requirement of confinement , a Bose–Einstein condensate of colorless 6-quark states is considered, [ 5 ] or the projected BCS theory is used. [ 7 ] [ 8 ]
The BCS formalism is applicable without modifications to the description of quark matter with color group SU(2), where Cooper pairs are colorless. The Nambu–Jona-Lasinio model predicts the existence of the superconducting phase of SU(2) color quark matter at high densities. [ 9 ] This physical picture is confirmed in the Polyakov–Nambu–Jona-Lasinio model, [ 10 ] and also in lattice QCD models, [ 11 ] [ 12 ] in which the properties of cold quark matter can be described based on the first principles of quantum chromodynamics . The possibility of modeling on the lattices of two-color QCD at finite chemical potentials for even numbers of the quark flavors is associated with the positive-definiteness
of the integral measure and the absence of a sign problem . | https://en.wikipedia.org/wiki/SU(2)_color_superconductivity |
SU-8 is a commonly used epoxy -based negative photoresist . Negative refers to a photoresist whereby the parts exposed to UV become cross-linked, while the remainder of the film remains soluble and can be washed away during development.
As shown in the structural diagram, SU-8 derives its name from the presence of 8 epoxy groups. This is a statistical average per moiety . It is these epoxies that cross-link to give the final structure.
It can be made into a viscous polymer that can be spun or spread over a thickness ranging from below 1 micrometer up to above 300 micrometers, or Thick Film Dry Sheets (TFDS) for lamination up to above 1 millimetre thick. Up to 500 μm, the resist can be processed with standard contact lithography . [ 1 ] Above 500 μm, absorption leads to increasing sidewall undercuts and poor curing at the substrate interface. It can be used to pattern high aspect ratio structures. An aspect ratio of (> 20) has been achieved with the solution formulation [ 2 ] and (> 40) has been demonstrated from the dry resist. [ 3 ] Its maximum absorption is for ultraviolet light with a wavelength of the i-line : 365 nm (it is not practical to expose SU-8 with g-line ultraviolet light). When exposed, SU-8's long molecular chains cross-link , causing the polymerisation of the material. SU-8 series photoresists use gamma-butyrolactone or cyclopentanone as the primary solvent.
SU-8 was originally developed as a photoresist for the microelectronics industry, to provide a high-resolution mask for fabrication of semiconductor devices.
It is now mainly used in the fabrication of microfluidics (mainly via soft lithography , but also with other imprinting techniques such as nanoimprint lithography [ 4 ] ) and microelectromechanical systems parts. It is also one of the most biocompatible materials known [ 5 ] and is often used in bio-MEMS for life science applications. [ 6 ]
SU-8 is composed of Bisphenol A Novolac epoxy that is dissolved in an organic solvent ( gamma-butyrolactone GBL or cyclopentanone , depending on the formulation) and up to 10 wt% of mixed Triarylsulfonium/hexafluoroantimonate salt as the photoacid generator. [ 7 ]
SU-8 absorbs light in the UV region, allowing fabrication of relatively thick (hundreds of micrometers) structures with nearly vertical side walls. The fact that a single photon can trigger multiple polymerizations makes the SU-8 a chemically amplified resist which is polymerized by photoacid generation. [ 8 ] The light irradiated on the resist interacts with the salt in the solution, creating hexafluoroantimonic acid that then protonates the epoxides groups in the resin monomers. The monomer are thus activated but the polymerization will not proceed significantly until the temperature is raised as part of the post-expose bake. It is at this stage that the epoxy groups in the resin cross-link to form the cured structure. When fully cured, the high crosslinking degree gives to the resist its excellent mechanical properties. [ 9 ]
The processing of SU-8 is similar to other negative resists with particular attention on the control of the temperature in the baking steps. The baking times depend on the SU-8 layer thickness; the thicker the layer, the longer the baking time. The temperature is controlled during the baking in order to reduce stress formation in the thick layer (leading to cracks ) as the solvent evaporates.
The soft bake is the most important of the bake steps for stress formation. It is performed after spin coating . Its function is to remove the solvent from the resist and make the layer solid. Typically at least 5% of the solvent remains in the layer after the soft bake, however the thicker the coating, the harder it becomes to remove the solvent, as evaporating solvent through thick layers becomes increasingly difficult with coating thickness. The bake is performed on a programmable hot plate to reduce the skinning effect of solvent depletion at the surface creating a dense layer which makes the remainder of the solvent more difficult to remove. In order to reduce stress, the bake procedure is generally a two-step process made up of holding at 65 °C before ramping to 95 °C and holding again for a time dependent on the layer thickness. The temperature is then lowered slowly to room temperature .
When dry films are used, the photoresist is laminated rather than spin-coated. As this formulation is essentially solventless (less than 1% solvent remaining), it does not require a soft bake step and does not suffer stress or skinning. For enhanced adhesion , a post lamination bake can be added. This step is carried out in a similar way to the solution based resist - i.e. holding at 65 °C then 95 °C, the time dependent on film thickness.
After this stage the SU-8 layer can now be exposed. Typically this is through a photomask with an inverse pattern, as the resist is negative. The exposure time is a function of exposure dose and film thickness. After exposure the SU-8 needs to be baked again to complete the polymerization. This baking step is not as critical as the prebake but the rising of the temperature (again to 95 °C) needs to be slow and controlled. At this point the resist is ready to be developed.
The main developer for SU-8 is 1-methoxy-2-propanol acetate . [ 10 ] Development time is primarily a function of SU-8 thickness.
After exposing and developing, its highly cross-linked structure gives it high stability to chemicals and radiation damage - hence the name "resist". Cured cross-linked SU-8 shows very low levels of outgassing in a vacuum . [ 11 ] [ 12 ] However it is very difficult to remove, and tends to outgas in an unexposed state. [ 13 ]
SU-8 2000 series resists use cyclopentanone for the primary solvent and can be used to create films between 0.5 and 100 μm in thickness. This formulation may offer improved adhesion on some substrates versus the original formulation. [ 14 ]
SU-8 3000 series resists also use cyclopentanone for the primary solvent and are designed to be spun into thicker films ranging from 2 to 75 μm in a single coat. [ 14 ]
SU-8 GLM2060 series of low-stress photoresist consist of epoxy GBL and silica formulation CTE 14. [ 15 ]
SU-8 GCM3060 Series of GERSTELTEC conductive SU8 with nanoparticles of silver. [ 15 ]
SU-8 GMC10xx Series of GERSTELTEC colored SU8 Red, Bleau, Green, black and others. [ 15 ]
SU-8 GMJB10XX Series of GERSTELTEC low viscosities epoxy for inkjet applications. [ 15 ]
SU8 GM10XX Series of Classic GERSTELTEC epoxy. [ 16 ]
Its polymerization process proceeds upon photoactivation of a photoacid generator (triarylsulfonium salts, for example) and subsequent post exposure baking. The polymerization process it a cationic chain growth, which takes place by ring opening polymerization of the epoxide groups.
SUEX is a Thick Dry Film Sheet (TDFS) which is a solventless formulation applied by lamination. As this formulation is a dry sheet, there is high uniformity, no edge-bead [ 17 ] formation and very little waste. These sheets come in a range of thicknesses from 100 μm to over 1mm. [ 18 ] DJMicrolaminates also sell a thinner range, ADEX TFDS, which are available in thicknesses from 5 μm through to 75 μm. [ 18 ] | https://en.wikipedia.org/wiki/SU-8_photoresist |
The SUCRE ( [ˈsukɾe] ; Spanish : Sistema Unitario de Compensación Regional , "Unified System for Regional Compensation") was a regional currency proposed for commercial exchanges between members of the regional trade bloc Bolivarian Alliance for the Americas (ALBA), which was created as an alternative to the Free Trade Agreement of the Americas (FTAA). The SUCRE was intended to replace the US dollar as a medium of exchange .
The SUCRE was first used as a virtual currency in 2010 in two transactions between Ecuador and Venezuela . [ 1 ] International trade between member states in SUCRE reached its maximum in 2012 with 2,646 transactions worth almost 1,066 million US dollars. In each following year trade in SUCRE shrank. In 2015 there were 752 transactions worth around 345 million dollars. [ 2 ]
The treaty explicitly limited the backing assets of the basket of currencies to financial securities denominated in the respective currencies of the member states. Prohibition of alternative forms of currency backing (such as commodity backing) presented an inequity for Ecuador that, alone in the group, does not have its own national currency (it uses the US dollar ). [ citation needed ]
In the case of ALBA members Dominica , Saint Vincent and the Grenadines , and Antigua and Barbuda , the new currency posed a dilemma as they are already a member of the Eastern Caribbean Currency Union and use the East Caribbean dollar , [ 3 ] although none of them had agreed to the treaty establishing the SUCRE and the regional payments clearinghouse. [ 4 ]
The SUCRE is named after Antonio José de Sucre , a leading figure in Latin America 's independence struggle. Agreement [ 5 ] in general terms for the currency was declared in 2009. The formal treaty [ 4 ] establishing the regional payments clearinghouse was signed by the six Latin American presidents in Cochabamba , Bolivia , on October 17, 2009. (The former currency of Ecuador , one of the SUCRE's users, was also called the sucre , but was abandoned and replaced by the US dollar after the economic crisis in 1999).
This currency has code XSU in ISO 4217 standard currency list. ISO 4217 Standard definition:
In 2013 Uruguay joined the currency. [ 6 ]
In 2018, the government of Venezuela proposed using the Petro , instead, for trade within ALBA. [ 7 ] [ 8 ] | https://en.wikipedia.org/wiki/SUCRE |
In molecular biology , the single-domain protein SUI1 is a translation initiation factor often found in the fungus, Saccharomyces cerevisiae (Baker's yeast) but it is also found in other eukaryotes and prokaryotes as well as archaea . It is otherwise known as Eukaryotic translation initiation factor 1 ( eIF1 ) in eukaryotes or YciH in bacteria. [ 1 ]
SUI1 is a translation initiation factor that directs the ribosome to the translation start site, helped by eIF2 and the initiator Met - tRNA i Met . [ 2 ] SUI1 ensures that translation initiation commences from the correct start codon (usually AUG), by stabilizing the pre-initiation complex around the start codon. SUI1 promotes a high initiation fidelity for the AUG codon, discriminating against non-AUG codons. [ 3 ]
In E. coli however, it seems that the SUI1 homolog YciH is an inhibitor of translation during stress instead. [ 4 ]
The primary structure of the SUI1 protein is made up of 108 amino acids . The protein domain has a structure made of a seven-bladed beta-propeller and it also contains a C-terminal alpha helix . [ 5 ] Homologues of SUI1 have been found [ 6 ] in mammals , insects and plants . SUI1 is also evolutionary related to proteins from Escherichia coli (yciH), Haemophilus influenzae (HI1225) and Methanococcus vannielii . [ 5 ] | https://en.wikipedia.org/wiki/SUI1 |
Stackable Unified Module Interconnect Technology ( SUMIT ) is a connector between expansion buses independent of motherboard form factor. Boards featuring SUMIT connectors are usually used in "stacks" where one board sits on top of another.
It was published by the Small Form Factor Special Interest Group . [ 1 ] [ 2 ] [ 3 ]
Two identical connectors carry the signals specified by the standard. Commonly referred to as SUMIT A & SUMIT B, designers have the option of designing with either both SUMIT A and B, or just SUMIT A. The signals carried within each connector is as follows:
SUMIT A:
SUMIT B:
As of August 2009, three board form factors used the SUMIT connectors for embedded applications: ISM or SUMIT-ISM [90mm × 96mm], Pico-ITXe [72mm × 100mm], and Pico-I/O [60mm × 72mm].
This computing article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/SUMIT |
SUMO enzymatic cascade catalyzes the dynamic posttranslational modification process of sumoylation (i.e. transfer of SUMO protein to other proteins). The Small Ubiquitin-related Modifier, SUMO-1 , [ 1 ] [ 2 ] is a ubiquitin-like family member that is conjugated to its substrates through three discrete enzymatic steps (see the figure on the right): activation, involving the E1 enzyme ( SAE1 / SAE2 ); [ 3 ] conjugation, involving the E2 enzyme ( UBE2I ); [ 4 ] [ 5 ] substrate modification, through the cooperation of the E2 and E3 [ 6 ] protein ligases. [ 7 ]
SUMO pathway modifies hundreds of proteins that participate in diverse cellular processes. [ 8 ] SUMO pathway is the most studied ubiquitin -like pathway that regulates a wide range of cellular events, [ 9 ] evidenced by a large number of sumoylated proteins identified in more than ten large-scale studies. [ 10 ] [ 11 ] [ 12 ] [ 13 ] [ 14 ] [ 15 ] [ 16 ] [ 17 ] [ 18 ] [ 19 ] [ 20 ] [ excessive citations ] | https://en.wikipedia.org/wiki/SUMO_enzymes |
C-MORE : SUPER HI-CAT (Center for Microbial Oceanography - Research and Education: Survey of Underwater Plastic Ecosystem Response Hawaii to California Transit)
The SUPER HI-CAT research cruise was the first effort to study the microbial communities and the biogeochemistry associated with the Great Pacific Garbage Patch .[1] The study was conducted aboard the RV Kilo Moana (T-AGOR-26) between August 25, 2008 and September 5, 2008 by researchers from University of Hawaiʻi at Mānoa , Oregon State University , and the Algalita Marine Research Foundation . [ 1 ]
Previous research on the Plastic Patch had mostly focused on the effects of the plastic pieces on jellyfish , fish , sea turtles , and seabirds . Relatively little was known about how this type of marine debris would affect the microbial communities that make up 98% of the biomass in the ocean and control oceanic biogeochemistry. [ 2 ] During this cruise, 30 sites were sampled. At 15 of these sites, a modified surface net called a manta trawl [ 3 ] was used to collect plastic pieces, while water samples were collected from the upper 200 meters of the ocean. At the other 15 stations, only the surface waters were sampled. This study will allow researchers to begin to determine whether biofilms are forming on the plastic particles, whether the microbes living on the particles are different from the free-living planktonic organisms, and what effect these communities might have on the oceanic carbon cycle and nitrogen cycle .
This geochemistry article is a stub . You can help Wikipedia by expanding it .
This oceanography article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/SUPER_HI-CAT |
simian vacuolating virus 40, SV40
SV40 is an abbreviation for simian vacuolating virus 40 or simian virus 40 , a polyomavirus that is found in both monkeys and humans . Like other polyomaviruses, SV40 is a DNA virus that is found to cause tumors in humans and animals, but most often persists as a latent infection. SV40 has been widely studied as a model eukaryotic virus, leading to many early discoveries in eukaryotic DNA replication [ 1 ] and transcription . [ 2 ]
Following contamination of polio vaccine batches in the 1950s and 1960s, SV40 came under suspicion as a possible cancer risk, but no subsequent increased cancer rate was observed, making such a risk unlikely. Nevertheless SV40 has become a cause célèbre for anti-vaccination activists, who have blamed it for multiple ills, including cancer and HIV/AIDS . [ 3 ]
The hypothesis that SV40 might cause cancer in humans was a particularly controversial area of research, fuelled by the historical contamination of some batches of polio vaccine with SV40 in the 1950s and 1960s. [ 4 ] "Persuasive evidence now indicates that SV40 is causing infections in humans today and represents an emerging pathogen." [ 5 ] However "It appears unlikely that SV40 infection alone is sufficient to cause human malignancy..." [ 6 ]
It has been suggested that SV40 may act as a co-carcinogen with crocidolite asbestos to cause mesothelioma . [ 7 ] [ 8 ]
Some vaccines made in the US between 1955 and 1961 were found to be contaminated with SV40, from the growth medium and from the original seed strain. Population level studies did not show extensive evidence of increase in cancer incidence as a result of exposure, [ 9 ] though SV40 has been extensively studied. [ 10 ] A thirty-five year follow-up did not find excess numbers of cancers associated with SV40. [ 11 ]
Due to its high tissue tropism , biotechnology companies seek to utilize modified SV40 based vectors as a viral vector for gene therapy . In these helper dependent virus or packaging cell line assisted produced vectors the SV40 large T antigen and SV40 small T antigen are removed. [ 12 ] [ 13 ] [ 14 ]
SV40 consists of an unenveloped icosahedral virion with a closed circular double-stranded DNA genome [ 15 ] of 5.2 kb. [ 16 ] Structurally, SV40 is composed of 72 pentamers of major capsid protein VP1, with each VP1 pentamers harboring one minor capsid protein, either VP2 or VP3. The virion undergoes receptor-mediated endocytosis after binding to the ganglioside GM1 on the cell membrane. [ 17 ] Penetration into the cell is through a caveolin vesicle . The endosome carrying SV40 fuses with the ER membrane to deliver the virus into the lumen of the ER. Resident ER proteins induce structural changes to initiate a disassembly process of the VP1 capsid shell. SV40 then exploits components of Endoplasmic-reticulum-associated protein degradation machinery to penetrate the ER membrane and get extracted into the cytosol. [ 18 ] A dynein motor complex adaptor, BICD2 , disassembles the virion further, [ 19 ] before components of the LINC complex target the virion to the nuclear membrane for subsequent entry. [ 20 ] Inside the cell nucleus , the cellular RNA polymerase II acts to promote early gene expression. This results in an mRNA that is spliced into two segments. The small and large T antigens result from this. The large T antigen has two functions: 5% goes to the plasma cell membrane and 95% returns to the nucleus. Once in the nucleus the large T antigen binds three viral DNA sites, I, II and III. Binding of sites I and II autoregulates early RNA synthesis . Binding to site II takes place in each cell cycle. Binding site I initiates DNA replication at the origin of replication . Early transcription gives two spliced RNAs that are both 19s. Late transcription gives both a longer 16s, which synthesizes the major viral capsid protein VP1; and the smaller 19s, which gives VP2 and VP3 through leaky scanning . All of the proteins, besides the 5% of large T, return to the nucleus because assembly of the viral particle happens there. A putative late protein VP4 has been reported to act as a viroporin facilitiating release of viral particles and resulting in cytolysis ; [ 21 ] [ 22 ] however the presence and role of VP4 have been disputed. [ 23 ] [ 24 ]
SV40 is capable of multiplicity reactivation (MR). [ 25 ] [ 26 ] MR is the process by which two or more virus genomes containing otherwise lethal damage interact within an infected cell to form a viable virus genome. Yamamato and Shimojo observed MR when SV40 virions were irradiated with UV light and allowed to undergo multiple infection of host cells. [ 25 ] Hall studied MR when SV 40 virions were exposed to the DNA crosslinking agent 4, 5', 8-trimethylpsoralen. [ 26 ] Under conditions in which only a single virus particle entered each host cell, approximately one DNA cross-link was lethal to the virus and could not be repaired. In contrast, when multiple viral genomes infected a host cell, psoralen -induced DNA cross-links were repaired; that is, MR occurred. Hall suggested that the virions with cross-linked DNA were repaired by recombinational repair. [ 26 ] Michod et al. reviewed numerous examples of MR in different viruses and suggested that MR is a common form of sexual interaction that provides the advantage of recombinational repair of genome damages. [ 27 ]
The early promoter for SV40 contains three elements. The TATA box is located approximately 20 base-pairs upstream from the transcriptional start site. The 21 base-pair repeats contain six GC boxes and are the site that determines the direction of transcription. Also, the 72 base-pair repeats are transcriptional enhancers . When the SP1 protein interacts with the 21 base-pair repeats, it binds either the first or the last three GC boxes. Binding the first three initiates early expression , binding the last three initiates late expression. The function of the 72 base-pair repeats is to enhance the amount of stable RNA and increase the rate of synthesis. This is done by binding ( dimerization ) with the AP-1 transcription factor to give a primary transcript that is 3' polyadenylated and 5' capped. [ citation needed ]
SV40 is dormant and is asymptomatic in rhesus monkeys . The virus has been found in many macaque populations in the wild, where it rarely causes disease. However, in monkeys that are immunodeficient —due to, for example, infection with simian immunodeficiency virus —SV40 acts much like the human JC and BK polyomaviruses, producing kidney disease and sometimes a demyelinating disease similar to progressive multifocal leukoencephalopathy . In other species, particularly hamsters , SV40 causes a variety of tumors, generally sarcomas. In rats, the oncogenic SV40 large T antigen was used to establish a brain tumor model for primitive neuroectodermal tumor and medulloblastoma . [ 28 ]
The molecular mechanisms by which the virus reproduces and alters cell function were previously unknown, and research into SV40 vastly increased biologists' understanding of gene expression and the regulation of cell growth. [ citation needed ]
SV40 was first identified by Ben Sweet and Maurice Hilleman in 1960 when they found that between 10 and 30% of polio vaccines in the US were contaminated with SV40. [ 29 ] In 1962, Bernice Eddy described the SV40 oncogenic function inducing sarcoma and ependymomas in hamsters inoculated with monkeys cells infected with SV40. [ 30 ] The complete viral genome was sequenced by Weissman at Yale University (US) [ 31 ] in 1978 and also by Fiers and his team at the University of Ghent ( Belgium ). [ 32 ]
SV40 has become a totemic subject among anti-vaccination activists, where its presence in contaminated vaccine is accused of being a cause of a cancer "epidemic" and of being responsible for HIV/AIDS . [ 3 ] | https://en.wikipedia.org/wiki/SV40 |
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