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2 } } ) \ ln ( 1 - { x \ over x _ { max } } ) - { c _ { 0 } \ over 2b _ { 0 } } x ^ { 2 } - ( { d _ { 0 } \ over b _ { 0 } } + { c _ { 0 } a _ { 0 } \ over b _ { 0 } ^ { 2 } } ) x } where a0, b0, c0, d0, and e0 are constants determined by the system, x is the film thickness, and xmax is the maximum value of film thickness, which can be determined experimentally. another model for interfacial polymerization of capsules, or encapsulation, is also described : t = a 0 r m i n 5 e 0 i 4 + b 0 r m i n 4 e 0 i 3 + c 0 r m i n 2 e 0 i 2 + d 0 r m i n e 0 i 1 { \ displaystyle t = a _ { 0 } { r _ { min } } ^ { 5 } e _ { 0 } i _ { 4 } + b _ { 0 } { r _ { min } } ^ { 4 } e _ { 0 } i _ { 3 } + c _ { 0 } { r _ { min } } ^ { 2 } e _ { 0 } i _ { 2 } + d _ { 0 } { r _ { min } } e _ { 0 } i _ { 1 } } where a0, b0, c0, d0, e0, i1, i2, i3, and i4 are constants determined by the system and rmin is the minimum value of the inside diameter of the polymeric capsule wall. there are several assumptions made by these and similar models, including but not limited to uniformity of monomer concentration, temperature, and film density, and second - order reaction kinetics. = = applications = = interfacial polymerization has found much use in industrial applications, especially as a route to synthesize conducting polymers for electronics. conductive polymers synthesized by interfacial polymerization such as polyaniline ( pani ), polypyrrole ( ppy ), poly ( 3, 4 - ethylenedioxythiophene ), and polythiophene ( pth ) have found applications as chemical sensors, fuel cells, supercapacitors, and nanoswitches. =
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, poly ( 3, 4 - ethylenedioxythiophene ), and polythiophene ( pth ) have found applications as chemical sensors, fuel cells, supercapacitors, and nanoswitches. = = = sensors = = = pani nanofibers are the most commonly used for sensing applications. these nanofibers have been shown to detect various gaseous chemicals, such as hydrogen chloride ( hcl ), ammonia ( nh3 ), hydrazine ( n2h4 ), chloroform ( chcl3 ), and methanol ( ch3oh ). pani nanofibers can be further fined - tuned by doping and modifying the polymer chain conformation, among other methods, to increase selectivity to certain gases. a typical pani chemical sensor consists of a substrate, an electrode, and a selective polymer layer. pani nanofibers, like other chemiresistors, detect by a change in electrical resistance / conductivity in response to the chemical environment. = = = fuel cells = = = ppy - coated ordered mesoporouscarbon ( omc ) composites can be used in direct methanol fuel cell applications. the polymerization of ppy onto the omc reduces interfacial electrical resistances without altering the open mesopore structure, making ppy - coated omc composites a more ideal material for fuel cells than plain omcs. = = = separation / purification membranes = = = composite polymer films synthesized via a liquid - solid interface are the most commonly used to synthesize membranes for reverse osmosis and other applications. one added benefits of using polymers prepared by interfacial polymerization is that several properties, such as pore size and interconnectivity, can be fined - tuned to create a more ideal product for specific applications. for example, synthesizing a polymer with a pore size somewhere between the molecular size of hydrogen gas ( h2 ) and carbon dioxide ( co2 ) results in a membrane selectively - permeable to h2, but not to co2, effectively separating the compounds. = = = cargo - loading micro - and nanocapsules = = = compared to previous methods of capsule synthesis, interfacial polymerization is an easily modified synthesis that results in capsules with a wide range of properties and functionalities. once synthesized, the capsules can enclose drugs, quantum dots, and other nanoparticles, to list a few examples.
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polymerization is an easily modified synthesis that results in capsules with a wide range of properties and functionalities. once synthesized, the capsules can enclose drugs, quantum dots, and other nanoparticles, to list a few examples. further fine - tuning of the chemical and topological properties of these polymer capsules could prove an effective route to create drug - delivery systems. = = see also = = polymerization interfacial polycondensation = = references = =
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enzymatic methyl - seq or em - seq is a laboratory technique for high - throughput profiling of dna methylation at a single - nucleotide resolution across the genome. em - seq is a c - to - t chemistry where non - methylated cytosines ( c ) are converted into uracil ( u ) through enzymatic conversion before sequencing and read as thymine ( t ). this enzymatic conversion of cytosine to uracil is achieved through two sets of enzymatic reactions using three enzymes tet2, t4 - bgt and apobec3a. the method primarily detects 5 - methylcytosine ( 5mc ), the most common form of dna methylation in mammals, but can also detect 5 - hydroxymethylcytosine ( 5hmc ) as both are protected from deamination in the standard protocol. enzymatic conversion has reduced dna damage and loss than bisulfite - treated libraries generally leading to higher quality sequencing libraries characterized by greater complexity and yield, often achievable from smaller quantities of input dna. = = history = = em - seq was developed by researchers from new england biolabs as an alternative to whole genome bisulfite sequencing ( wgbs ) and related bisulfite - based methods. milder enzymatic reaction conditions were intended to improve the quality and yield of sequencing libraries, especially when working with limited or degraded dna samples, compared to harsh chemical treatment of bisulfite causing significant dna fragmentation and degradation. the method was published in 2021 in genome research by vaisvila and colleagues, many of whom were affiliated with neb. following its publication and validation, the em - seq method was commercialized by neb, making standardized kits available for research purposes. = = mechanism = = the em - seq protocol involves the following sequential enzymatic treatment of the input dna : oxidation of methylated cytosines : the enzyme tet2 ( tet methylcytosine dioxygenase 2 ) is used to oxidize 5mc and 5hmc. tet2 iteratively oxidizes 5mc to 5hmc, then to 5 - formylcytosine ( 5fc ), and finally to 5 - carboxylcytosine ( 5cac ). this oxidation step serves primarily to protect the originally methylated cytosines from subsequent deamination. deamination of unmodified cytos
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##fc ), and finally to 5 - carboxylcytosine ( 5cac ). this oxidation step serves primarily to protect the originally methylated cytosines from subsequent deamination. deamination of unmodified cytosines : an apobec ( apolipoprotein b mrna editing enzyme, catalytic polypeptide - like ) deaminase enzyme is then used. this enzyme specifically deaminates unmodified cytosine ( c ) bases, converting them into uracil ( u ). crucially, the oxidized forms of methylated cytosines ( like 5cac ) are resistant to apobec - mediated deamination. the dna is then amplified using pcr. during amplification, uracil bases ( derived from unmethylated cytosines ) are read as thymine ( t ) by the dna polymerase. the protected, originally methylated cytosines ( now primarily 5cac or other tet2 oxidation products ) are generally read as cytosine ( c ). the amplified library is subjected to dna sequencing. by comparing the sequenced reads to a reference genome, positions where a c is retained indicate an originally methylated cytosine ( 5mc or 5hmc ), while positions where a c has been converted to a t indicate an originally unmethylated cytosine. = = applications = = dna methylation profiling is widely used in the fields of epigenetics research and is explored for potential diagnostic uses for diseases such as cancer. as such, em - seq provides an alternative approach where traditional approaches are insufficient or higher quality data is desired. for example, analysis of clinical samples with limited or degraded dna, such as cfdna for non - invasive monitoring or ffpe tissues from archival collections. = = see also = = dna methylation 5 - methylcytosine ( 5mc ) 5 - hydroxymethylcytosine ( 5hmc ) bisulfite sequencing epigenetics tet enzymes apobec whole genome sequencing = = references = =
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cc chemokine receptors ( or beta chemokine receptors ) are integral membrane proteins that specifically bind and respond to cytokines of the cc chemokine family. they represent one subfamily of chemokine receptors, a large family of g protein - linked receptors that are known as seven transmembrane ( 7 - tm ) proteins since they span the cell membrane seven times. to date, ten true members of the cc chemokine receptor subfamily have been described. these are named ccr1 to ccr10 according to the iuis / who subcommittee on chemokine nomenclature. = = mechanism = = the cc chemokine receptors all work by activating the g protein gi. = = types = = = = = overview table = = = = = = ccr1 = = = ccr1 was the first cc chemokine receptor identified and binds multiple inflammatory / inducible ( see inducible gene ) cc chemokines ( including ccl4, ccl5, ccl6, ccl14, ccl15, ccl16 and ccl23 ). in humans, this receptor can be found on peripheral blood lymphocytes and monocytes. there is some suggestion that this chemokine receptor is restricted to memory t - cells within the lymphocyte pool. this receptor is also designated cluster of differentiation marker cd191. = = = ccr2 = = = ccr2 can interact with ccl2, ccl8 and ccl16 and has been identified on the surface of monocytes, activated memory t cells, b cells, and basophils in humans, and also in peritoneal macrophages in mice. ccr2 is also designated cd192. = = = ccr3 = = = ccr3 is a receptor for multiple inflammatory / inducible cc chemokines, including ccl11, ccl26, ccl7, ccl13, ccl15, ccl24 and ccl5 that attract eosinophils, and ccl28 that attracts b and t lymphocytes to mucosal tissues. it is most highly expressed in both eosinophils and basophils, but can also be found in th1 and th2 cells and airway epithelial cells. thus ccr3 plays a role in allergic reactions. ccr3 is also known as cd193. = =
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and basophils, but can also be found in th1 and th2 cells and airway epithelial cells. thus ccr3 plays a role in allergic reactions. ccr3 is also known as cd193. = = = ccr4 = = = ccr4 is expressed on th2 t lymphocytes and is up - regulated by t cell receptor activation. however, some reports suggest a role for this receptor also in trafficking of dendritic cells. the cc chemokines ccl3, ccl5, ccl17 and ccl22 signal through this receptor. = = = ccr5 = = = ccr5 is expressed on several cell types including peripheral blood - derived dendritic cells, cd34 + hematopoietic progenitor cells and certain activated / memory th1 lymphocytes. this receptor is well defined as a major coreceptor implicated in susceptibility to hiv - 1 infection and disease. this receptor has several cc chemokine ligands including ccl2, ccl3, ccl4, ccl5, ccl11, ccl13, ccl14 and ccl16. = = = ccr6 = = = ccr6, a receptor for ccl20, is expressed on unactivated memory t - cells and some dendritic cells. ccr6 is also expressed on th17 cells. ccr6 is down - regulated in activated t - cells. = = = ccr7 = = = ccr7 is a highly important receptor with a role in trafficking of b and t lymphocytes and dendritic cells to and across high endothelial venules and positioning those cells correctly in t cell zones of secondary lymphoid organs. its ligands include the related chemokines ccl19 and ccl21, ( previously called elc and slc ). = = = ccr8 = = = ccr8 is associated with th2 lymphocytes and is therefore found predominantly in the thymus ( in humans ) although some expression can be found in the brain, spleen, lymph node, and monocytes at the nucleotide level. the ligands for this receptor are ccl1 and ccl16 = = = ccr9 = = = ccr9 was previously called orphan receptor gpr 9 - 6 and is very highly expressed in thymus ( on both immature and mature t
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ligands for this receptor are ccl1 and ccl16 = = = ccr9 = = = ccr9 was previously called orphan receptor gpr 9 - 6 and is very highly expressed in thymus ( on both immature and mature t - cells ) while low in lymph nodes and spleen. ccr9 is also abundant in the gut, with its expression associated with t cells of the intestine. the specific ligand of this receptor is ccl25 to note, the chemokine binding protein d6 had previously been named ccr9, but this molecule is a scavenger receptor not a true ( signaling ) chemokine receptor. = = = ccr10 = = = ccr10 is receptor for ccl27 and ccl28 that was originally called orphan receptor gpr2. ccr10 has been implicated in inflammation of the skin, and has been shown to recruit regulatory t cells ( tregs ) to mucosal layers. = = = ccr11 = = = this molecule was originally designated ccr11 due to its ability to bind several cc chemokines ( including ccl19, ccl21 and ccl25 ) and its structural similarity to chemokine receptors. however, due to the inability of this molecule ( also known as ccrl1 and ccx ckr ) to generate a signal following ligand interaction, it has been suggested that it is a scavenger receptor for chemokines and not a bona fide chemokine receptor. thus ccrl1 should not be called ccr11 under the guidelines of the iuis / who subcommittee on chemokine nomenclature. = = references = = = = external links = = " chemokine receptors ". iuphar database of receptors and ion channels. international union of basic and clinical pharmacology. archived from the original on 2016 - 03 - 03. retrieved 2008 - 11 - 25.
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xenopus egg extract is a lysate that is prepared by crushing the eggs of the african clawed frog xenopus laevis. it offers a powerful cell - free ( or in vitro ) system for studying various cell biological processes, including cell cycle progression, nuclear transport, dna replication and chromosome segregation. it is also called xenopus egg cell - free system or xenopus egg cell - free extract. = = history = = the first frog egg extract was reported in 1983 by lohka and masui. this pioneering work used eggs of the northern leopard frog rana pipiens to prepare an extract. later, the same procedure was applied to eggs of xenopus laevis, becoming popular for studying cell cycle progression and cell cycle - dependent cellular events. extracts derived from eggs of the japanese common toad bufo japonicus or of the western clawed frog xenopus tropicalis have also been reported. = = basics of extract preparation = = the cell cycle of unfertilized eggs of x. laevis is arrested highly synchronously at metaphase of meiosis ii. upon fertilization, the metaphase arrest is released by the action of ca2 + ions released from the endoplasmic reticulum, thereby initiating early embryonic cell cycles that alternates s phase ( dna replication ) and m phase ( mitosis ). = = = m phase extract = = = unfertilized eggs in a buffer containing the ca2 + chelator egta ( ethylene glycol tetraacetic acid ) are packed into a centrifuge tube. after removing excess buffer, the eggs are crushed by centrifugation ( ~ 10, 000 g ). a soluble fraction that appears between the lipid cap and the yolk is called an m phase extract. this extract contains a high level of cyclin b - cdk1. when demembranated sperm nuclei are incubated with this extract, it undergoes a series of structural changes and is eventually converted into a set of m phase chromosomes with bipolar spindles. = = = s phase ( interphase ) extract = = = when cacl₂ is added to an m - phase xenopus egg extract at a concentration sufficient to override residual egta ( typically several hundred micromolar ), it triggers rapid inactivation of maturation promoting factor ( mpf ). this occurs through cyclin b degradation by the proteasome and induces
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concentration sufficient to override residual egta ( typically several hundred micromolar ), it triggers rapid inactivation of maturation promoting factor ( mpf ). this occurs through cyclin b degradation by the proteasome and induces cell cycle progression from metaphase to anaphase, and eventually into s phase. the resulting extract is referred to as an s - phase extract or interphase extract. upon the addition of sperm chromatin to an s - phase extract, nuclear assembly is initiated : membrane vesicles accumulate around decondensed chromatin, fuse to form a nuclear envelope, and produce fully functional nuclei. active nuclear transport occurs across the nuclear envelope, and dna replication is initiated within the reconstituted nuclei. because these extracts contain abundant mrna and ribosomes, protein translation also takes place. thus, this cell - free system can faithfully recapitulate many cellular events characteristic of proliferating cells. a notable exception is transcription, which does not occur in this system. this reflects the natural state of the xenopus egg and early embryo, where transcription is largely repressed from the meiotic stages through to the blastula stage after fertilization. = = different types of egg extract = = = = = cycling extract = = = cycling extract is a cell - free system derived from xenopus eggs that autonomously undergoes repeated s phase and m phase cycles. it is prepared by artificially inducing intracellular responses that mimic fertilization, typically through calcium ionophore treatment or electrical stimulation of unfertilized eggs, followed by mechanical crushing of the eggs. this extract has been instrumental in elucidating fundamental mechanisms of cell cycle regulation. for example, it revealed that entry into m phase depends on the translation of cyclin b, which in turn activates maturation promoting factor ( mpf ). cycling extracts are primarily used to study the regulation of cell cycle progression. = = = high - speed supernatant ( hss ) = = = high - speed supernatant ( hss ) is a fraction obtained by ultracentrifuging a conventional xenopus egg extract at 100, 000 – 200, 000 × g, which removes membrane components and ribosomes, leaving a solution enriched in soluble proteins. although hss lacks the capacity to support nuclear assembly or protein translation, it can partially recapitulate chromatin structural changes in a cell cycle – dependent manner. it is particularly suitable for protein purification. = = = nucle
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soluble proteins. although hss lacks the capacity to support nuclear assembly or protein translation, it can partially recapitulate chromatin structural changes in a cell cycle – dependent manner. it is particularly suitable for protein purification. = = = nucleoplasmic extract ( npe ) = = = nucleoplasmic extract ( npe ) is prepared from xenopus egg extracts by first assembling nuclei in s - phase extract through the addition of a high concentration of sperm chromatin ( ~ 10, 000 nuclei per μl ). the reaction mixture is then centrifuged without dilution to separate the nuclei, which form a distinct layer at the top. this nuclear fraction is collected and further centrifuged at high speed, yielding a soluble supernatant ( nucleoplasm ) and a pellet containing nuclear membranes and chromatin. the supernatant is referred to as the nucleoplasmic extract ( npe ). when dna is pre - incubated in s - phase hss and then npe is added, dna replication can be initiated without the need for nuclear envelope formation — a significant distinction from standard s - phase extract protocols, where replication initiation requires nuclear assembly. this system has enabled high - resolution analysis of replication initiation mechanisms. moreover, npe supports efficient replication of plasmid dna and other non - sperm - derived templates. leveraging this property, researchers have also used npe to investigate dna repair pathways using exogenously damaged dna substrates. = = discoveries made using egg extracts = = purification of m - phase promoting factor ( mpf ) elucidation of the role of synthesis and degradation of cyclin b in cell cycle progression discovery that degradation of a protein ( s ) other than cyclin b is necessary for initiating chromosome segregation discovery of a mechanism of spindle assembly that depends on chromatin, but not centrosomes proposal of a dna replication licensing system and identification of its responsible factor identification of importin α / β responsible for nuclear transport discovery of the condensin complex essential for mitotic chromosome assembly identification of the cohesin complex essential for sister chromatid cohesion more recently, the egg extracts have been used to study reprogramming of differentiated nuclei, physical properties of spindles and nuclei, and theoretical understanding of cell cycle control. = = see also = = yoshio masui cell cycle cdk1 cyclin dna replication nuclear transport spindle apparatus condensin cohesin
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nuclei, physical properties of spindles and nuclei, and theoretical understanding of cell cycle control. = = see also = = yoshio masui cell cycle cdk1 cyclin dna replication nuclear transport spindle apparatus condensin cohesin = = references = =
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golden gate cloning or golden gate assembly is a molecular cloning method that allows a researcher to simultaneously and directionally assemble multiple dna fragments into a single piece using type iis restriction enzymes and t4 dna ligase. this assembly is performed in vitro. most commonly used type iis enzymes include bsai, bsmbi, and bbsi. unlike standard type ii restriction enzymes like ecori and bamhi, these enzymes cut dna outside of their recognition sites and, therefore, can create non - palindromic overhangs. since 256 potential overhang sequences are possible, multiple fragments of dna can be assembled by using combinations of overhang sequences. in practice, this means that golden gate cloning is typically scarless. additionally, because the final product does not have a type iis restriction enzyme recognition site, the correctly - ligated product cannot be cut again by the restriction enzyme, meaning the reaction is essentially irreversible. this has multiple benefits, the first is that it is possible to do digestion and ligation of the dna fragments in a single reaction, in contrast to conventional cloning methods where these reactions are separate. the second is higher efficiency because the end product cannot be cut again by the restriction enzyme. a typical thermal cycler protocol oscillates between 37 °c ( optimal for restriction enzymes ) and 16 °c ( optimal for ligases ) many times. while this technique can be used for a single insert, researchers have used golden gate cloning to assemble many pieces of dna simultaneously. = = seamless cloning = = scar sequences are common in multiple segment dna assembly. in the multisegment assembly method gateway, segments are added into the donor with additional att sequences, which overlap in those added segments, and this results in the segments separated by the att sequences. in biobrick assembly, an eight - nucleotide scar sequence, which codes for a tyrosine and a stop codon, is left between every segment added into the plasmid. golden gate assembly uses type iis restriction enzymes cutting outside their recognition sequences. also, the same type iis restriction enzyme can generate copious different overhangs on the inserts and the vector ; for instance, bsai creates 256 four - basepair overhangs. if the overhangs are carefully designed, the segments are ligated without scar sequences between them, and the final construct can be quasi - scarless, where the restriction enzyme sites remain on both sides of the insert. as additional segments can be
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. if the overhangs are carefully designed, the segments are ligated without scar sequences between them, and the final construct can be quasi - scarless, where the restriction enzyme sites remain on both sides of the insert. as additional segments can be inserted into the vectors without scars within an open reading frame, golden gate is widely used in protein engineering. = = plasmid design = = although golden gate cloning speeds up multisegment cloning, careful design of donor and recipient plasmids is required. scientists at new england biolabs have successfully demonstrated the assembly of 35 fragments via a single - tube golden gate assembly reaction. critical to this method of assembly, the vector backbone of the destination plasmid and all the assembly fragments are flanked by type iis restriction enzyme recognition sites, as this subtype of restriction enzymes cut downstream from their recognition sites. after cutting, each assembly active piece of dna has unique overhangs that anneal to the next fragment of dna in the planned assembly and become ligated, building the assembly. while it is also possible for an overhang to anneal back to its original complementary overhang associated with the upstream recognition site and become ligated, re - forming the original sequence, this will be susceptible to further cutting throughout the assembly reaction. = = cloning standards = = restriction enzyme dna assembly has cloning standards to minimize the change in cloning efficiency and the function of the plasmid, which can be caused by compatibility of the restriction sites on the insert and those on the vector. golden gate assembly's cloning standards have two tiers. first - tier golden gate assembly constructs the single - gene construct by adding in genetic elements such as promoter, open reading frames, and terminators. then, second - tier golden gate assembly combine several constructs made in first - tier assembly to make a multigene construct. to achieve second - tier assembly, modular cloning ( moclo ) system and goldenbraid2. 0 standard are used. = = = moclo system = = = modular cloning, or moclo, is an assembly method introduced in 2011 by ernst weber et al., whereby using type iis restriction sites, the user can ligate at least six dna parts together into a backbone in a one - pot reaction. it is a method based on golden gate assembly, where type iis restriction enzymes cleave outside of their recognition site to one side, allowing for removal of those restriction sites from the
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dna parts together into a backbone in a one - pot reaction. it is a method based on golden gate assembly, where type iis restriction enzymes cleave outside of their recognition site to one side, allowing for removal of those restriction sites from the design. this helps eliminate excess base pairs, or scars, from forming between dna parts. however, in order to ligate together properly, moclo utilizes a set of 4 - base pair fusion sites, which remain between parts after ligation, forming 4 - base pair scars between dna parts in the final dna sequence following ligation of two or more parts. moclo utilizes a parallel approach, where all constructs from tier - one ( level 0 modules ) have restriction sites for bpii on both sides of the inserts. the vector ( also known as " destination vector " ), where genes will be added, has an outward - facing bsai restriction site with a drop - out screening cassette. lacz is a common screening cassette, where it is replaced by the multigene construct on the destination vector. each tier - one construct and the vector have different overhangs on them yet complementary to the overhang of the next segment, and this determines the layout of the final multigene construct. golden gate cloning usually starts with level 0 modules. however, if the level 0 module is too large, cloning will start from level - 1 fragments, which have to be sequenced, to help cloning the large construct. if starting from level - 1 fragments, the level 0 modules do not need to be sequenced again, whereas if starting from level 0 modules, the modules must be sequenced. = = = = level 0 modules = = = = level 0 modules are the base for moclo system, where they contain genetic elements like a promoter, a 5'untranslated region ( utr ), a coding sequence, and a terminator. for the purpose of golden gate cloning, the internal sequences of level 0 modules should not contain type iis restriction enzymes sites for bsai, bpii, and esp3i while surrounded by two bsai restriction sites in inverted orientation. level 0 modules without type iis restriction sites flanking can add the bsai sites during the process of golden gate cloning. if the level 0 modules contains any unwanted restriction site, they can be mutated in silico by removing one nucleotide from the type iis restriction site. in this process, one needs to make sure that the introduced
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gate cloning. if the level 0 modules contains any unwanted restriction site, they can be mutated in silico by removing one nucleotide from the type iis restriction site. in this process, one needs to make sure that the introduced mutation will not affect the genetic function encoded by the sequence of interest. a silent mutation in the coding sequence is preferred, for it neither changes the protein sequence nor the function of the gene of interest. = = = = = level - 1 fragments = = = = = level - 1 fragments are used to help cloning large level 0 modules. to clone level - 1 fragments, blunt - end cloning with restriction ligation can be used. the vector used in cloning level - 1 fragments cannot contain type iis restriction site bpii that is used for the following assembly step. moreover, the vector should also have a different selection marker from the destination vector in next assembly step, for example, if spectinomycin resistance is used in level 0 modules, level - 1 fragments should have another antibiotic resistance like ampicillin. = = = = level 1 constructs = = = = the level 1 destination vector determines the position and orientation of each gene in the final construct. there are fourteen available level 1 vectors, which differ only by the sequence of the flanking fusion sites while being identical in the internal fusion sites. hence, all vectors can assemble the same level 0 parts. as all level 1 vectors are binary plasmids, they are used for agrobacterium mediated temporary expression in plants. = = = = level 2 constructs = = = = level 2 vectors have two inverted bpii sites from the insertion of level 1 modules. the upstream fusion site is compatible to a gene cloned in level 1 vector while the downstream fusion site has a universal sequence. each cloning allows 2 - 6 genes to be inserted in the same vector. adding more genes in one cloning step is not recommended, for this would result in incorrect constructs. on one hand, this can induce more restriction sites in the construct, where this open construct allows additional genes be added. on the other hand, this can also eliminate restriction sites, where this close construct stop the further addition of genes. therefore, constructs of more than six genes need successive cloning steps, which requires end - linkers containing bsai or bsmbi internal restriction sites and blue or purple markers. each cloning step needs to alternate the restriction site and the marker. furthermore, two restriction enzymes are needed,
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need successive cloning steps, which requires end - linkers containing bsai or bsmbi internal restriction sites and blue or purple markers. each cloning step needs to alternate the restriction site and the marker. furthermore, two restriction enzymes are needed, where bpii is used for releasing level 1 modules from level 1 constructs and bsai / bsmbi is for digesting and opening the recipient level 2 - n plasmid. when screening, the correct colonies should alternate from blue to purple every cloning step, but if a " closed " end - linker is used, the colonies will be white. = = = = level m constructs = = = = level m vectors are similar to level 2 vectors, but have a bsai site located upstream of the two inverted bpii sites. when one or several genes are cloned in a level m vector, a second bsai is added at the end of the construct via a level m end - linker ( ref ). this allows a fragment containing all assembled genes to be excised from the vector and subcloned in a next level of cloning ( level p ). = = = = level p constructs = = = = level p vectors are similar to level m constructs except that the bpii sites are replaced by bsai sites and the bsai sites are replaced by bpii sites. several level m constructs with compatible fusion sites can be subcloned into a level p vector in one step. theoretically, as many as 36 genes can be assembled in one construct using 6 parallel level m reactions ( each required for assembly of 6 genes per level m construct ) followed by one final level p reaction. in practice, fewer genes are usually assembled as most cloning projects do not require so many genes. the structure of level m and p vectors is designed in a such as way that genes cloned in level p constructs can be further assembled in level m vectors. repeated cloning in level m and p vectors forms a loop that can be repeated indefinitely to assemble progressively large constructs. = = = goldenbraid = = = in standard golden gate cloning, the restriction sites from the previous tier construct cannot be reused. to add more genes to the construct, restriction sites of a different type iis restriction enzyme need to be added to the destination vector. this can be done using either level 2, or m and p. a variant version of level m and p is also provided by goldenbraid. goldenbraid overcomes the problem of
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##s restriction enzyme need to be added to the destination vector. this can be done using either level 2, or m and p. a variant version of level m and p is also provided by goldenbraid. goldenbraid overcomes the problem of designing numerous destination vectors by having a double loop, which is the " braid, " to allow binary assembly of multiple constructs. there are two levels of destination plasmids, level α and level ω. each level of plasmids can be used as entry plasmids for the other level of plasmids for multiple times because both levels of plasmids have different type iis restriction sites that are in inverted orientation. for counterselection, the two levels of plasmids differ in their antibiotic resistance markers. = = = golden mutagenesis = = = the golden gate cloning principle can also be applied to perform mutagenesis termed golden mutagenesis. the technology is easy to implement as a web tool is available for primer design ( https : / / msbi. ipb - halle. de / goldenmutagenesisweb / ) and the vectors are deposited at addgene ( http : / / www. addgene. org / browse / article / 28196591 / ). = = name = = the name golden gate assembly comes from a proposal of yuri gleba. it shall refer on the one hand to the gateway technology, on the other hand picture the higher precision with a bridge connecting the streets of two shores seamlessly. one of the most well known bridges is the golden gate bridge in san francisco. = = references = =
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in the data analysis of time series, time warp edit distance ( twed ) is a measure of similarity ( or dissimilarity ) between pairs of discrete time series, controlling the relative distortion of the time units of the two series using the physical notion of elasticity. in comparison to other distance measures, ( e. g. dtw ( dynamic time warping ) or lcs ( longest common subsequence problem ) ), twed is a metric. its computational time complexity is o ( n 2 ) { \ displaystyle o ( n ^ { 2 } ) }, but can be drastically reduced in some specific situations by using a corridor to reduce the search space. its memory space complexity can be reduced to o ( n ) { \ displaystyle o ( n ) }. it was first proposed in 2009 by p. - f. marteau. = = definition = = δ λ, ν ( a 1 p, b 1 q ) = m i n { δ λ, ν ( a 1 p − 1, b 1 q ) + γ ( a p ′ → λ ) d e l e t e i n a δ λ, ν ( a 1 p − 1, b 1 q − 1 ) + γ ( a p ′ → b q ′ ) m a t c h o r s u b s t i t u t i o n δ λ, ν ( a 1 p, b 1 q − 1 ) + γ ( λ → b q ′ ) d e l e t e i n b { \ displaystyle \ delta _ { \ lambda, \ nu } ( a _ { 1 } ^ { p }, b _ { 1 } ^ { q } ) = min { \ begin { cases } \ delta _ { \ lambda, \ nu } ( a _ { 1 } ^ { p - 1 }, b _ { 1 } ^ { q } ) + \ gamma ( a _ { p } ^ {'} \ to \ lambda ) & { \ rm { delete \ in \ a } } \ \ \ delta _ { \ lambda, \ nu } ( a _ { 1 } ^ { p - 1 }, b _ { 1 } ^ { q - 1 } ) + \ gamma ( a _ { p } ^ {'} \ to b _ { q } ^ {'} ) & { \ rm { match \ or \ substitution } } \ \ \ delta _ { \ lambda, \ nu } ( a _ { 1 }
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_ { p } ^ {'} \ to b _ { q } ^ {'} ) & { \ rm { match \ or \ substitution } } \ \ \ delta _ { \ lambda, \ nu } ( a _ { 1 } ^ { p }, b _ { 1 } ^ { q - 1 } ) + \ gamma ( \ lambda \ to b _ { q } ^ {'} ) & { \ rm { delete \ in \ b } } \ end { cases } } } whereas γ ( α p ′ → λ ) = d l p ( a p ′, a p − 1 ′ ) + ν ⋅ ( t a p − t a p − 1 ) + λ { \ displaystyle \ gamma ( \ alpha _ { p } ^ {'} \ to \ lambda ) = d _ { lp } ( a _ { p } ^ {'}, a _ { p - 1 } ^ {'} ) + \ nu \ cdot ( t _ { a _ { p } } - t _ { a _ { p - 1 } } ) + \ lambda } γ ( α p ′ → b q ′ ) = d l p ( a p ′, b q ′ ) + d l p ( a p − 1 ′, b q − 1 ′ ) + ν ⋅ ( | t a p − t b q | + | t a p − 1 − t b q − 1 | ) { \ displaystyle \ gamma ( \ alpha _ { p } ^ {'} \ to b _ { q } ^ {'} ) = d _ { lp } ( a _ { p } ^ {'}, b _ { q } ^ {'} ) + d _ { lp } ( a _ { p - 1 } ^ {'}, b _ { q - 1 } ^ {'} ) + \ nu \ cdot ( | t _ { a _ { p } } - t _ { b _ { q } } | + | t _ { a _ { p - 1 } } - t _ { b _ { q - 1 } } | ) } γ ( λ → b q ′ ) = d l p ( b p ′, b p − 1 ′ ) + ν ⋅ ( t b q − t b q − 1 ) + λ { \ displaystyle \ gamma ( \ lambda \ to b _ { q } ^ {'} ) = d _ { lp } ( b _ { p }
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) + ν ⋅ ( t b q − t b q − 1 ) + λ { \ displaystyle \ gamma ( \ lambda \ to b _ { q } ^ {'} ) = d _ { lp } ( b _ { p } ^ {'}, b _ { p - 1 } ^ {'} ) + \ nu \ cdot ( t _ { b _ { q } } - t _ { b _ { q - 1 } } ) + \ lambda } whereas the recursion δ λ, ν { \ displaystyle \ delta _ { \ lambda, \ nu } } is initialized as : δ λ, ν ( a 1 0, b 1 0 ) = 0, { \ displaystyle \ delta _ { \ lambda, \ nu } ( a _ { 1 } ^ { 0 }, b _ { 1 } ^ { 0 } ) = 0, } δ λ, ν ( a 1 0, b 1 j ) = ∞ f o r j ≥ 1 { \ displaystyle \ delta _ { \ lambda, \ nu } ( a _ { 1 } ^ { 0 }, b _ { 1 } ^ { j } ) = \ infty \ { \ rm { { for \ } j \ geq 1 } } } δ λ, ν ( a 1 i, b 1 0 ) = ∞ f o r i ≥ 1 { \ displaystyle \ delta _ { \ lambda, \ nu } ( a _ { 1 } ^ { i }, b _ { 1 } ^ { 0 } ) = \ infty \ { \ rm { { for \ } i \ geq 1 } } } with a 0 ′ = b 0 ′ = 0 { \ displaystyle a'_ { 0 } = b'_ { 0 } = 0 } = = = implementations = = = an implementation of the twed algorithm in c with a python wrapper is available at twed is also implemented into the time series subsequence search python package ( tssearch for short ) available at [ 1 ]. an r implementation of twed has been integrated into the traminer, a r package for mining, describing and visualizing sequences of states or events, and more generally discrete sequence data. additionally, cutwed is a cuda - accelerated implementation of twed which uses an improved algorithm due to g. wright ( 2020 ). this method is linear in memory and massively parallelized. cutwed is written in cuda c / c + +
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cutwed is a cuda - accelerated implementation of twed which uses an improved algorithm due to g. wright ( 2020 ). this method is linear in memory and massively parallelized. cutwed is written in cuda c / c + +, comes with python bindings, and also includes python bindings for marteau's reference c implementation. = = = = python = = = = backtracking, to find the most cost - efficient path : = = = = matlab = = = = backtracking, to find the most cost - efficient path : = = references = = marteau, p. ; f. ( 2009 ). " time warp edit distance with stiffness adjustment for time series matching ". ieee transactions on pattern analysis and machine intelligence. 31 ( 2 ) : 306 – 318. arxiv : cs / 0703033. doi : 10. 1109 / tpami. 2008. 76. pmid 19110495. s2cid 10049446.
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in cryptography, a public key certificate, also known as a digital certificate or identity certificate, is an electronic document used to prove the validity of a public key. the certificate includes the public key and information about it, information about the identity of its owner ( called the subject ), and the digital signature of an entity that has verified the certificate's contents ( called the issuer ). if the device examining the certificate trusts the issuer and finds the signature to be a valid signature of that issuer, then it can use the included public key to communicate securely with the certificate's subject. in email encryption, code signing, and e - signature systems, a certificate's subject is typically a person or organization. however, in transport layer security ( tls ) a certificate's subject is typically a computer or other device, though tls certificates may identify organizations or individuals in addition to their core role in identifying devices. tls, sometimes called by its older name secure sockets layer ( ssl ), is notable for being a part of https, a protocol for securely browsing the web. in a typical public - key infrastructure ( pki ) scheme, the certificate issuer is a certificate authority ( ca ), usually a company that charges customers a fee to issue certificates for them. by contrast, in a web of trust scheme, individuals sign each other's keys directly, in a format that performs a similar function to a public key certificate. in case of key compromise, a certificate may need to be revoked. the most common format for public key certificates is defined by x. 509. because x. 509 is very general, the format is further constrained by profiles defined for certain use cases, such as public key infrastructure ( x. 509 ) as defined in rfc 5280. = = types of certificate = = = = = tls / ssl server certificate = = = the transport layer security ( tls ) protocol – as well as its outdated predecessor, the secure sockets layer ( ssl ) protocol – ensures that the communication between a client computer and a server is secure. the protocol requires the server to present a digital certificate, proving that it is the intended destination. the connecting client conducts certification path validation, ensuring that : the subject of the certificate matches the hostname ( not to be confused with the domain name ) to which the client is trying to connect. a trusted certificate authority has signed the certificate. the subject field of the certificate must identify the primary hostname of the server as the common
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matches the hostname ( not to be confused with the domain name ) to which the client is trying to connect. a trusted certificate authority has signed the certificate. the subject field of the certificate must identify the primary hostname of the server as the common name. the hostname must be publicly accessible, not using private addresses or reserved domains. a certificate may be valid for multiple hostnames ( e. g., a domain and its subdomains ). such certificates are commonly called subject alternative name ( san ) certificates or unified communications certificates ( ucc ). these certificates contain the subject alternative name field, though many cas also put them into the subject common name field for backward compatibility. if some of the hostnames contain an asterisk ( * ), a certificate may also be called a wildcard certificate. once the certification path validation is successful, the client can establish an encrypted connection with the server. internet - facing servers, such as public web servers, must obtain their certificates from a trusted, public certificate authority ( ca ). = = = tls / ssl client certificate = = = client certificates authenticate the client connecting to a tls service, for instance to provide access control. because most services provide access to individuals, rather than devices, most client certificates contain an email address or personal name rather than a hostname. in addition, the certificate authority that issues the client certificate is usually the service provider to which client connects because it is the provider that needs to perform authentication. some service providers even offer free ssl certificates as part of their packages. while most web browsers support client certificates, the most common form of authentication on the internet is a username and password pair. client certificates are more common in virtual private networks ( vpn ) and remote desktop services, where they authenticate devices. = = = email certificate = = = in accordance with the s / mime protocol, email certificates can both establish the message integrity and encrypt messages. to establish encrypted email communication, the communicating parties must have their digital certificates in advance. each must send the other one digitally signed email and opt to import the sender's certificate. some publicly trusted certificate authorities provide email certificates, but more commonly s / mime is used when communicating within a given organization, and that organization runs its own ca, which is trusted by participants in that email system. = = = self - signed and root certificates = = = a self - signed certificate is a certificate with a subject that matches
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when communicating within a given organization, and that organization runs its own ca, which is trusted by participants in that email system. = = = self - signed and root certificates = = = a self - signed certificate is a certificate with a subject that matches its issuer, and a signature that can be verified by its own public key. self - signed certificates have their own limited uses. they have full trust value when the issuer and the sole user are the same entity. for example, the encrypting file system on microsoft windows issues a self - signed certificate on behalf of the encrypting user and uses it to transparently decrypt data on the fly. the digital certificate chain of trust starts with a self - signed certificate, called a root certificate, trust anchor, or trust root. a certificate authority self - signs a root certificate to be able to sign other certificates. an intermediate certificate has a similar purpose to the root certificate – its only use is to sign other certificates. however, an intermediate certificate is not self - signed. a root certificate or another intermediate certificate needs to sign it. an end - entity or leaf certificate is any certificate that cannot sign other certificates. for instance, tls / ssl server and client certificates, email certificates, code signing certificates, and qualified certificates are all end - entity certificates. = = = subject alternative name certificate = = = subject alternative name ( san ) certificates are an extension to x. 509 that allows various values to be associated with a security certificate using a subjectaltname field. these values are called subject alternative names ( sans ). names include : email addresses ip addresses uris dns names : this is usually also provided as the common name rdn within the subject field of the main certificate. directory names : alternative distinguished names to that given in the subject. other names, given as a general name or universal principal name : a registered object identifier followed by a value. rfc 2818 ( may 2000 ) specifies subject alternative names as the preferred method of adding dns names to certificates, deprecating the previous method of putting dns names in the commonname field. google chrome version 58 ( march 2017 ) removed support for checking the commonname field at all, instead only looking at the sans. as shown in the picture of wikimedia's section on the right, the san field can contain wildcards. not all vendors support or endorse mixing wildcards into san certificates. = = = wildcard certificate = = = a public
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shown in the picture of wikimedia's section on the right, the san field can contain wildcards. not all vendors support or endorse mixing wildcards into san certificates. = = = wildcard certificate = = = a public key certificate which uses an asterisk * ( the wildcard ) in its domain name fragment is called a wildcard certificate. through the use of *, a single certificate may be used for multiple sub - domains. it is commonly used for transport layer security in computer networking. for example, a single wildcard certificate for https : / / *. example. com will secure all these subdomains on the https : / / *. example. com domain : payment. example. com contact. example. com login - secure. example. com www. example. com instead of getting separate certificates for subdomains, you can use a single certificate for all main domains and subdomains and reduce cost. because the wildcard only covers one level of subdomains ( the asterisk doesn't match full stops ), these domains would not be valid for the certificates : test. login. example. com example. com note possible exceptions by cas, for example wildcard - plus cert by digicert contains an automatic " plus " property for the naked domain example. com. = = = = limitations = = = = only a single level of subdomain matching is supported in accordance with rfc 2818. it is not possible to get a wildcard for an extended validation certificate. a workaround could be to add every virtual host name in the subject alternative name ( san ) extension, the major problem being that the certificate needs to be reissued whenever a new virtual server is added. ( see transport layer security § support for name - based virtual servers for more information. ) wildcards can be added as domains in multi - domain certificates or unified communications certificates ( ucc ). in addition, wildcards themselves can have subjectaltname extensions, including other wildcards. for example, the wildcard certificate *. wikipedia. org has *. m. wikimedia. org as a subject alternative name. thus it secures www. wikipedia. org as well as the completely different website name meta. m. wikimedia. org. rfc 6125 argues against wildcard certificates on security grounds, in particular " partial wildcards ". = = = = further examples = = = = the wildcard applies only to one level of the domain
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m. wikimedia. org. rfc 6125 argues against wildcard certificates on security grounds, in particular " partial wildcards ". = = = = further examples = = = = the wildcard applies only to one level of the domain name. *. example. com matches sub1. example. com but not example. com and not sub2. sub1. domain. com the wildcard may appear anywhere inside a label as a " partial wildcard " according to early specifications f *. domain. com is ok. it will match frog. domain. com but not frog. super. domain. com baz *. example. net is ok and matches baz1. example. net * baz. example. net is ok and matches foobaz. example. net b * z. example. net is ok and matches buzz. example. net however, use of " partial - wildcard " certs is not recommended. as of 2011, partial wildcard support is optional, and is explicitly disallowed in subjectaltname headers that are required for multi - name certificates. all major browsers have deliberately removed support for partial - wildcard certificates ; they will result in a " ssl _ error _ bad _ cert _ domain " error. similarly, it is typical for standard libraries in programming languages to not support " partial - wildcard " certificates. for example, any " partial - wildcard " certificate will not work with the latest versions of both python and go. thus, do not allow a label that consists entirely of just a wildcard unless it is the left - most label sub1. *. domain. com is not allowed. a cert with multiple wildcards in a name is not allowed. *. *. domain. com a cert with * plus a top - level domain is not allowed. *. com too general and should not be allowed. * international domain names encoded in ascii ( a - label ) are labels that are ascii - encoded and begin with xn - -. urls with international labels cannot contain wildcards. xn - - caf - dma. com is cafe. com xn - - caf - dma *. com is not allowed lw *. xn - - caf - dma. com is allowed = = = other certificates = = = emv certificate : emv is a payment method based on a technical standard for payment cards, payment terminals and automated teller machines ( atm )
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*. xn - - caf - dma. com is allowed = = = other certificates = = = emv certificate : emv is a payment method based on a technical standard for payment cards, payment terminals and automated teller machines ( atm ). emv payment cards are preloaded with a card issuer certificate, signed by the emv certificate authority to validate authenticity of the payment card during the payment transaction. code - signing certificate : certificates can validate apps ( or their binaries ) to ensure they were not tampered with during delivery. qualified certificate : a certificate identifying an individual, typically for electronic signature purposes. these are most commonly used in europe, where the eidas regulation standardizes them and requires their recognition. role - based certificate : defined in the x. 509 certificate policy for the federal bridge certification authority ( fbca ), role - based certificates " identify a specific role on behalf of which the subscriber is authorized to act rather than the subscriber ’ s name and are issued in the interest of supporting accepted business practices. " group certificate : defined in the x. 509 certificate policy for the federal bridge certification authority ( fbca ), for " cases where there are several entities acting in one capacity, and where non - repudiation for transactions is not desired. " = = common fields = = these are some of the most common fields in certificates. most certificates contain a number of fields not listed here. note that in terms of a certificate's x. 509 representation, a certificate is not " flat " but contains these fields nested in various structures within the certificate. serial number : used to uniquely identify the certificate within a ca's systems. in particular this is used to track revocation information. subject : the entity a certificate belongs to : a machine, an individual, or an organization. issuer : the entity that verified the information and signed the certificate. not before : the earliest time and date on which the certificate is valid. usually set to a few hours or days prior to the moment the certificate was issued, to avoid clock skew problems. not after : the time and date past which the certificate is no longer valid. key usage : the valid cryptographic uses of the certificate's public key. common values include digital signature validation, key encipherment, and certificate signing. extended key usage : the applications in which the certificate may be used. common values include tls server authentication, email protection, and code signing. public key
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key. common values include digital signature validation, key encipherment, and certificate signing. extended key usage : the applications in which the certificate may be used. common values include tls server authentication, email protection, and code signing. public key : a public key belonging to the certificate subject. signature algorithm : this contain a hashing algorithm and a digital signature algorithm. for example " sha256rsa " where sha256 is the hashing algorithm and rsa is the signature algorithm. signature : the body of the certificate is hashed ( hashing algorithm in " signature algorithm " field is used ) and then the hash is signed ( signature algorithm in the " signature algorithm " field is used ) with the issuer's private key. = = = example = = = this is an example of a decoded ssl / tls certificate retrieved from ssl. com's website. the issuer's common name ( cn ) is shown as ssl. com ev ssl intermediate ca rsa r3, identifying this as an extended validation ( ev ) certificate. validated information about the website's owner ( ssl corp ) is located in the subject field. the x509v3 subject alternative name field contains a list of domain names covered by the certificate. the x509v3 extended key usage and x509v3 key usage fields show all appropriate uses. = = usage in the european union = = in the european union, ( advanced ) electronic signatures on legal documents are commonly performed using digital signatures with accompanying identity certificates. however, only qualified electronic signatures ( which require using a qualified trust service provider and signature creation device ) are given the same power as a physical signature. = = certificate authorities = = in the x. 509 trust model, a certificate authority ( ca ) is responsible for signing certificates. these certificates act as an introduction between two parties, which means that a ca acts as a trusted third party. a ca processes requests from people or organizations requesting certificates ( called subscribers ), verifies the information, and potentially signs an end - entity certificate based on that information. to perform this role effectively, a ca needs to have one or more broadly trusted root certificates or intermediate certificates and the corresponding private keys. cas may achieve this broad trust by having their root certificates included in popular software, or by obtaining a cross - signature from another ca delegating trust. other cas are trusted within a relatively small community, like a business, and are distributed by other mechanisms like windows group
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broad trust by having their root certificates included in popular software, or by obtaining a cross - signature from another ca delegating trust. other cas are trusted within a relatively small community, like a business, and are distributed by other mechanisms like windows group policy. certificate authorities are also responsible for maintaining up - to - date revocation information about certificates they have issued, indicating whether certificates are still valid. they provide this information through online certificate status protocol ( ocsp ) and / or certificate revocation lists ( crls ). some of the larger certificate authorities in the market include identrust, digicert, and sectigo. = = root programs = = some major software contain a list of certificate authorities that are trusted by default. this makes it easier for end - users to validate certificates, and easier for people or organizations that request certificates to know which certificate authorities can issue a certificate that will be broadly trusted. this is particularly important in https, where a web site operator generally wants to get a certificate that is trusted by nearly all potential visitors to their web site. the policies and processes a provider uses to decide which certificate authorities their software should trust are called root programs. the most influential root programs are : microsoft root program apple root program mozilla root program oracle java root program adobe aatl adobe approved trust list and eutl root programs ( used for document signing ) browsers other than firefox generally use the operating system's facilities to decide which certificate authorities are trusted. so, for instance, chrome on windows trusts the certificate authorities included in the microsoft root program, while on macos or ios, chrome trusts the certificate authorities in the apple root program. edge and safari use their respective operating system trust stores as well, but each is only available on a single os. firefox uses the mozilla root program trust store on all platforms. the mozilla root program is operated publicly, and its certificate list is part of the open source firefox web browser, so it is broadly used outside firefox. for instance, while there is no common linux root program, many linux distributions, like debian, include a package that periodically copies the contents of the firefox trust list, which is then used by applications. root programs generally provide a set of valid purposes with the certificates they include. for instance, some cas may be considered trusted for issuing tls server certificates, but not for code signing certificates. this is indicated with a set of trust bits in a root certificate storage system. =
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set of valid purposes with the certificates they include. for instance, some cas may be considered trusted for issuing tls server certificates, but not for code signing certificates. this is indicated with a set of trust bits in a root certificate storage system. = = revocation = = a certificate may be revoked before it expires, which signals that it is no longer valid. without revocation, an attacker would be able to exploit such a compromised or misissued certificate until expiry. hence, revocation is an important part of a public key infrastructure. revocation is performed by the issuing certificate authority, which produces a cryptographically authenticated statement of revocation. for distributing revocation information to clients, timeliness of the discovery of revocation ( and hence the window for an attacker to exploit a compromised certificate ) trades off against resource usage in querying revocation statuses and privacy concerns. if revocation information is unavailable ( either due to accident or an attack ), clients must decide whether to fail - hard and treat a certificate as if it is revoked ( and so degrade availability ) or to fail - soft and treat it as unrevoked ( and allow attackers to sidestep revocation ). due to the cost of revocation checks and the availability impact from potentially - unreliable remote services, web browsers limit the revocation checks they will perform, and will fail - soft where they do. certificate revocation lists are too bandwidth - costly for routine use, and the online certificate status protocol presents connection latency and privacy issues. other schemes have been proposed but have not yet been successfully deployed to enable fail - hard checking. = = website security = = the most common use of certificates is for https - based web sites. a web browser validates that an https web server is authentic, so that the user can feel secure that his / her interaction with the web site has no eavesdroppers and that the web site is who it claims to be. this security is important for electronic commerce. in practice, a web site operator obtains a certificate by applying to a certificate authority with a certificate signing request. the certificate request is an electronic document that contains the web site name, company information and the public key. the certificate provider signs the request, thus producing a public certificate. during web browsing, this public certificate is served to any web browser that connects to the web site and proves to the web browser that the provider believes it has issued a certificate to the owner of the web site. as an example
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a public certificate. during web browsing, this public certificate is served to any web browser that connects to the web site and proves to the web browser that the provider believes it has issued a certificate to the owner of the web site. as an example, when a user connects to https : / / www. example. com / with their browser, if the browser does not give any certificate warning message, then the user can be theoretically sure that interacting with https : / / www. example. com / is equivalent to interacting with the entity in contact with the email address listed in the public registrar under " example. com ", even though that email address may not be displayed anywhere on the web site. no other surety of any kind is implied. further, the relationship between the purchaser of the certificate, the operator of the web site, and the generator of the web site content may be tenuous and is not guaranteed. at best, the certificate guarantees uniqueness of the web site, provided that the web site itself has not been compromised ( hacked ) or the certificate issuing process subverted. a certificate provider can opt to issue three types of certificates, each requiring its own degree of vetting rigor. in order of increasing rigor ( and naturally, cost ) they are : domain validation, organization validation and extended validation. these rigors are loosely agreed upon by voluntary participants in the ca / browser forum. = = = validation levels = = = = = = = domain validation = = = = a certificate provider will issue a domain - validated ( dv ) certificate to a purchaser if the purchaser can demonstrate one vetting criterion : the right to administratively manage the affected dns domain ( s ). = = = = organization validation = = = = a certificate provider will issue an organization validation ( ov ) class certificate to a purchaser if the purchaser can meet two criteria : the right to administratively manage the domain name in question, and perhaps, the organization's actual existence as a legal entity. a certificate provider publishes its ov vetting criteria through its certificate policy. = = = = extended validation = = = = to acquire an extended validation ( ev ) certificate, the purchaser must persuade the certificate provider of its legal identity, including manual verification checks by a human. as with ov certificates, a certificate provider publishes its ev vetting criteria through its certificate policy. until 2019, major browsers such as chrome and firefox generally offered users a visual indication of the legal identity when a site presented
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a human. as with ov certificates, a certificate provider publishes its ev vetting criteria through its certificate policy. until 2019, major browsers such as chrome and firefox generally offered users a visual indication of the legal identity when a site presented an ev certificate. this was done by showing the legal name before the domain, and a bright green color to highlight the change. most browsers deprecated this feature providing no visual difference to the user on the type of certificate used. this change followed security concerns raised by forensic experts and successful attempts to purchase ev certificates to impersonate famous organizations, proving the inefficiency of these visual indicators and highlighting potential abuses. = = = weaknesses = = = a web browser will give no warning to the user if a web site suddenly presents a different certificate, even if that certificate has a lower number of key bits, even if it has a different provider, and even if the previous certificate had an expiry date far into the future. where certificate providers are under the jurisdiction of governments, those governments may have the freedom to order the provider to generate any certificate, such as for the purposes of law enforcement. subsidiary wholesale certificate providers also have the freedom to generate any certificate. all web browsers come with an extensive built - in list of trusted root certificates, many of which are controlled by organizations that may be unfamiliar to the user. each of these organizations is free to issue any certificate for any web site and have the guarantee that web browsers that include its root certificates will accept it as genuine. in this instance, end users must rely on the developer of the browser software to manage its built - in list of certificates and on the certificate providers to behave correctly and to inform the browser developer of problematic certificates. while uncommon, there have been incidents in which fraudulent certificates have been issued : in some cases, the browsers have detected the fraud ; in others, some time passed before browser developers removed these certificates from their software. the list of built - in certificates is also not limited to those provided by the browser developer : users ( and to a degree applications ) are free to extend the list for special purposes such as for company intranets. this means that if someone gains access to a machine and can install a new root certificate in the browser, that browser will recognize websites that use the inserted certificate as legitimate. for provable security, this reliance on something external to the system has the consequence that any public key certification scheme has to rely on some special setup assumption, such as the existence of a certificate
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browser will recognize websites that use the inserted certificate as legitimate. for provable security, this reliance on something external to the system has the consequence that any public key certification scheme has to rely on some special setup assumption, such as the existence of a certificate authority. = = = usefulness versus unsecured web sites = = = in spite of the limitations described above, certificate - authenticated tls is considered mandatory by all security guidelines whenever a web site hosts confidential information or performs material transactions. this is because, in practice, in spite of the weaknesses described above, web sites secured by public key certificates are still more secure than unsecured http : / / web sites. = = standards = = the national institute of standards and technology ( nist ) computer security division provides guidance documents for public key certificates : sp 800 - 32 introduction to public key technology and the federal pki infrastructure sp 800 - 25 federal agency use of public key technology for digital signatures and authentication = = see also = = authorization certificate pretty good privacy = = references = = = = works cited = = chung, taejoong ; lok, jay ; chandrasekaran, balakrishnan ; choffnes, david ; levin, dave ; maggs, bruce m. ; mislove, alan ; rula, john ; sullivan, nick ; wilson, christo ( 2018 ). " is the web ready for ocsp must - staple? " ( pdf ). proceedings of the internet measurement conference 2018. pp. 105 – 118. doi : 10. 1145 / 3278532. 3278543. isbn 9781450356190. s2cid 53223350. larisch, james ; choffnes, david ; levin, dave ; maggs, bruce m. ; mislove, alan ; wilson, christo ( 2017 ). " crlite : a scalable system for pushing all tls revocations to all browsers ". 2017 ieee symposium on security and privacy ( sp ). pp. 539 – 556. doi : 10. 1109 / sp. 2017. 17. isbn 978 - 1 - 5090 - 5533 - 3. s2cid 3926509. sheffer, yaron ; saint - andre, pierre ; fossati, thomas ( november 2022 ). recommendations for secure use of transport layer security ( tls ) and datagram transport layer security ( dtls ). doi : 10. 17487 / rfc9325. rfc
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, pierre ; fossati, thomas ( november 2022 ). recommendations for secure use of transport layer security ( tls ) and datagram transport layer security ( dtls ). doi : 10. 17487 / rfc9325. rfc 9325. smith, trevor ; dickinson, luke ; seamons, kent ( 2020 ). " let's revoke : scalable global certificate revocation ". proceedings 2020 network and distributed system security symposium. doi : 10. 14722 / ndss. 2020. 24084. isbn 978 - 1 - 891562 - 61 - 7. s2cid 211268930.
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in chemistry, a regular solution is a solution whose entropy of mixing is equal to that of an ideal solution with the same composition, but is non - ideal due to a nonzero enthalpy of mixing. such a solution is formed by random mixing of components of similar molar volume and without strong specific interactions, and its behavior diverges from that of an ideal solution by showing phase separation at intermediate compositions and temperatures ( a miscibility gap ). its entropy of mixing is equal to that of an ideal solution with the same composition, due to random mixing without strong specific interactions. for two components δ s m i x = − n r ( x 1 ln x 1 + x 2 ln x 2 ) { \ displaystyle \ delta s _ { mix } = - nr ( x _ { 1 } \ ln x _ { 1 } + x _ { 2 } \ ln x _ { 2 } ) \, } where r { \ displaystyle r \, } is the gas constant, n { \ displaystyle n \, } the total number of moles, and x i { \ displaystyle x _ { i } \, } the mole fraction of each component. only the enthalpy of mixing is non - zero, unlike for an ideal solution, while the volume of the solution equals the sum of volumes of components. = = features = = a regular solution can also be described by raoult's law modified with a margules function with only one parameter α { \ displaystyle \ alpha } : p 1 = x 1 p 1 ∗ f 1, m { \ displaystyle \ p _ { 1 } = x _ { 1 } p _ { 1 } ^ { * } f _ { 1, m } \, } p 2 = x 2 p 2 ∗ f 2, m { \ displaystyle \ p _ { 2 } = x _ { 2 } p _ { 2 } ^ { * } f _ { 2, m } \, } where the margules function is f 1, m = e x p ( α x 2 2 ) { \ displaystyle \ f _ { 1, m } = { \ rm { exp } } ( \ alpha x _ { 2 } ^ { 2 } ) \, } f 2, m = e x p ( α x 1 2 ) { \ displaystyle \ f _ { 2, m } = { \ rm { exp } } ( \ alpha x _ { 1 } ^ {
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} ) \, } f 2, m = e x p ( α x 1 2 ) { \ displaystyle \ f _ { 2, m } = { \ rm { exp } } ( \ alpha x _ { 1 } ^ { 2 } ) \, } notice that the margules function for each component contains the mole fraction of the other component. it can also be shown using the gibbs - duhem relation that if the first margules expression holds, then the other one must have the same shape. a regular solutions internal energy will vary during mixing or during process. the value of α { \ displaystyle \ alpha } can be interpreted as w / rt, where w = 2u12 - u11 - u22 represents the difference in interaction energy between like and unlike neighbors. in contrast to ideal solutions, regular solutions do possess a non - zero enthalpy of mixing, due to the w term. if the unlike interactions are more unfavorable than the like ones, we get competition between an entropy of mixing term that produces a minimum in the gibbs free energy at x1 = 0. 5 and the enthalpy term that has a maximum there. at high temperatures, the entropic term in the free energy of mixing dominates and the system is fully miscible, but at lower temperatures the g ( x1 ) curve will have two minima and a maximum in between. this results in phase separation. in general there will be a temperature where the three extremes coalesce and the system becomes fully miscible. this point is known as the upper critical solution temperature or the upper consolute temperature. in contrast to ideal solutions, the volumes in the case of regular solutions are no longer strictly additive but must be calculated from partial molar volumes that are a function of x1. the term was introduced in 1927 by the american physical chemist joel henry hildebrand. = = see also = = solid solution = = references = =
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photopharmacology is an emerging multidisciplinary field that combines photochemistry and pharmacology. built upon the ability of light to change the pharmacokinetics and pharmacodynamics of bioactive molecules, it aims at regulating the activity of drugs in vivo by using light. the light - based modulation is achieved by incorporating molecular photoswitches such as azobenzene and diarylethenes or photocages such as o - nitrobenzyl, coumarin, and bodipy compounds into the pharmacophore. this selective activation of the biomolecules helps prevent or minimize off - target activity and systemic side effects. moreover, light being the regulatory element offers additional advantages such as the ability to be delivered with high spatiotemporal precision, low to negligible toxicity, and the ability to be controlled both qualitatively and quantitatively by tuning its wavelength and intensity. = = history = = though photopharmacology is a relatively new field, the concept of using light in therapeutic applications came into practice a few decades ago. photodynamic therapy ( pdt ) is a well - established clinically practiced protocol in which photosensitizers are used to produce singlet oxygen for destroying diseased or damaged cells or tissues. optogenetics is another method that relies on light for dynamically controlling biological functions especially brain and neural. though this approach has proven useful as a research tool, its clinical implementation is limited by the requirement for genetic manipulation. mainly, these two techniques laid the foundation for photopharmacology. today, it is a rapidly evolving field with diverse applications in both basic research and clinical medicine which has the potential to overcome some of the challenges limiting the range of applications of the other light - guided therapies. figure 1. schematic representation of the mechanism of ( a ) photopharmacology ( b ) photodynamic therapy, and ( c ) optogenetics. the discovery of natural photoreceptors such as rhodopsins in the eye inspired the biomedical and pharmacology research community to engineer light - sensitive proteins for therapeutic applications. the development of synthetic photoswitchable molecules is the most significant milestone in the history of light - delivery systems. scientists are continuing with their efforts to explore new photoswitches and delivery strategies with enhanced performance to target different biological molecules such as ion channels, nucleic acid, and enzyme receptors. photopharma
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milestone in the history of light - delivery systems. scientists are continuing with their efforts to explore new photoswitches and delivery strategies with enhanced performance to target different biological molecules such as ion channels, nucleic acid, and enzyme receptors. photopharmacology research progressed from in vitro to in vivo studies in a significantly short period of time yielding promising results in both forms. clinical trials are underway to assess the safety and efficacy of these photopharmacological therapies further and validate their potential as an innovative drug delivery approach. = = mechanism of action = = molecular photoswitches are utilized in the field of photopharmacology, where the energetics of a molecule can be reversibly controlled with light to achieve spatial and temporal resolution of a particular effect. photoswitches may function by undergoing photoisomerization through which light is used to conformationally adapt a molecule to a biological site, or through an environmental effect where an external factor such as a solvent effect or hydrogen bonding can selectively allow or quench an emissive state within a molecule. to visualize photophysical processes, a useful depiction is the jablonski diagram. this is a diagram which depicts electronic and vibrational energy levels within a molecule as vertical levels and shows the possible relaxation pathways from excited states. typically, the ground state is referred to as s0, and is drawn at the bottom of the figure with nearby vibrational excitations just above it. an absorption will promote an electron into the s1 state at any vibrational energy level, or into a higher order excited state if the absorbed energy has enough magnitude. the excited state can then undergo internal conversion which is the electronic relaxation to a lower state with the same vibrational energetics or vibrational relaxation within a state. this may be followed by an intersystem crossing wherein the electron undergoes a spin flip, or a radiative or nonradiative decay back to the ground state. one example of an organic compound that undergoes photoisomerization is azobenzene. the structure is two phenyl rings joined with a n = n double bond and is the simplest aryl azo compound. azobenzene and its derivatives have two accessible absorbance bands : the s1 state from a n - π * transition which can be excited into using blue light, and the s2 state from a π - π * transition that can be excited into using ultraviolet light. azobenzene and its derivatives have two isomers, trans and cis.
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- π * transition which can be excited into using blue light, and the s2 state from a π - π * transition that can be excited into using ultraviolet light. azobenzene and its derivatives have two isomers, trans and cis. the trans isomer, having the phenyl rings on opposite sides of the azo double bond, is the thermally preferred isomer as there is less stereoelectronic distortion and more delocalization present. however, excitation of the trans isomer to the s2 state facilitates a shift to the cis isomer. the s1 absorption is associated with a conversion back to the trans isomer. in this way, azobenzene and its derivatives can act as reversible stores of energy by maintaining a strained configuration in the cis isomer. modifications of the substituents on azobenzene allow the energetics of these absorptions to be tuned, and if they are engineered such that the two absorption bands overlap a single wavelength of light can be used to flip between them. there are a number of similar photoswitches which isomerize between e and z configurations across an azo group ( for instance, azobenzene and azopyrazole ) or an ethylene bridge ( for instance, stilbene and hemithioindigo ). alternatively, photoswitches may themselves be emissive and exhibit environmental control over their properties. one such example is a class of ruthenium polypyridyl coordination complexes. typically they contain two bidentate bipyridine or phenanthroline ligands and an extended phenanthroline - phenazine bidentate ligand such as dipyrido [ 3, 2 - a : 2, 3 - c ] phenazine ( dppz ). these complexes have an accessible metal to ligand charge transfer excited state ( 1mlct ) which undergoes rapid intersystem crossing to a 3mlct state due to the strong spin - orbit coupling of the ruthenium center. these excited states are localized on the extended ligand phenazine nitrogens, and emission occurs from the 3mlct state. hydrogen bonding interactions such as the presence of water around these nitrogen atoms stabilizes the 3mlct state, quenching the emission process. thus, by controlling whether an aqueous or otherwise protic polar solvent is present, emissive behaviors can be “ turned on / off ”, and alternation between “ bright
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the 3mlct state, quenching the emission process. thus, by controlling whether an aqueous or otherwise protic polar solvent is present, emissive behaviors can be “ turned on / off ”, and alternation between “ bright states ” and “ dark states ” is facilitated. this light switch behavior makes these and similar complexes of recent interest in photopharmacological applications such as photodynamic therapy. = = molecules = = as previously mentioned, photopharmacology relies on the use of molecular photoswitches being incorporated into the structure of biologically active molecules which allows their potency to be controlled optically. they are introduced into the structure of bioactive compounds via insertion, extension, or bioisosteric replacement. these incorporations can be supported by structural considerations of the molecule or sar ( structure - activity relationship ) analysis to determine the optimal position. some examples of photoswitchable molecules commonly used in photopharmacology are azobenzenes, diarylethenes, and photocages. = = = azobenzenes = = = azobenzenes are a class of photoswitchable molecules and are used in photopharmalogical applications for their reversible photoisomerization, as described in the previous section. an example of a photoswitchable molecule that uses azobenzene is phototrexate. phototrexate is an inhibitor of human dihydrofolate reductase and is an analogue of methotrexate, a chemotherapy agent. when in its photoactive cis form, phototrexate has been shown to be a potent antifolate and is relatively inactive when in the trans form. the azologization, or incorporation of azobenzene, of methotrexate allows for control of cytotoxic activity and is considered a step forward in developing targeted anticancer drugs with localized efficacy. = = = diarylethenes = = = diarylethene photoswitches have reversible cyclization and cycloreversion reactions that are photoinduced. they are a class of compounds that have aromatic functional groups bonded to each end of a carbon - carbon double bond. an example of this class of molecule that is used in photopharmacology is stilbene. under the influence of light, stilbene switches between its two isomers ( e and z ). figure 4. figure showing stilbene isomerizations under light from e to z.
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used in photopharmacology is stilbene. under the influence of light, stilbene switches between its two isomers ( e and z ). figure 4. figure showing stilbene isomerizations under light from e to z. diarylethenes have been shown to have some advantages over the more researched azobenzenes switches, such as thermal irreversibility, high photoswitching efficiency, favorable cellular stability, and low toxicity. diarylethenes have been shown to have promise in fields other than photopharmacology as well. these fields include optical data storage, optoelectronic devices, supramolecular self - assembly and anti - counterfeiting. = = = photocages = = = a class of substances known as photocages contain “ photosensitive groups, also known as'photoremovable protecting groups ", from which target substances are released upon exposure to specific wavelengths of light ”. the photosensitive groups physically and chemically protect the target from being released until the molecule undergoes photoreaction. due to these interactions with light, they are commonly used molecules in photopharmacology. more recently, they have played an important role in photoactivated chemotherapy ( pact ). in pact, photocages utilize a photoremovable protecting group that protects cytotoxic drugs until the bond is cleaved via light interaction and the cytotoxic drug is released. some well - known photocages include “ o - nitrobenzyl derivatives, coumarin derivatives, bodipy, xanthene derivatives, quinone and diarylenes derivatives ”. however, there are limitations with using photocages in clinical applications as there are not many ppgs that can be used in vivo. this is due to ppg - payload conjugates needing to have acceptable solubility and biological inertness for biocompatibility and the need for efficient uncaging above 600 nm. figure 5. example of a photocage release system activated by nir. = = application = = photopharmacology, the use of light to control the activity of drugs, has emerged as a promising approach to drug delivery and therapy. by harnessing the power of light, researchers can achieve precise control over drug release and activation, offering new possibilities for targeted and personalized treatments. this subsection explores the application of photopharmacology in drug delivery, focusing on recent advancements and potential clinical applications
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the power of light, researchers can achieve precise control over drug release and activation, offering new possibilities for targeted and personalized treatments. this subsection explores the application of photopharmacology in drug delivery, focusing on recent advancements and potential clinical applications. in one study, researchers designed hdac inhibitors which can be activated or deactivated with light, providing precise therapeutic control. this approach could reduce the side effects of traditional chemotherapy by targeting inhibitors to specific body areas, potentially leading to more effective and personalized cancer treatments. in another study, the researchers developed a strategy to attach a photoswitchable group to a common antibiotic ; ciprofloxacin. by attaching the photoswitchable group, researchers can control the activity of ciprofloxacin with light. this approach could potentially lead to new ways of treating bacterial infections, with the ability to switch the antibiotic's activity on and off as needed. in this paper an in vitro protocol to test different light wavelengths on human cancer cell lines is developed, finding that blue light most effectively inhibited cell growth. this suggests that photopharmacology could offer new cancer treatment options by targeting specific light wavelengths to modulate drug activity in tumor cells. another application of photopharmacology is developing a luminescent photocorm grafted on carboxymethyl chitosan, which, when exposed to light, releases carbon monoxide ( co ) to induce apoptotic death in colorectal cancer cells, demonstrating precise control over co release for targeted cancer therapy. researchers developed a toolbox of photoswitchable antagonists that can interact with gpcrs, a class of proteins involved in various cellular processes. by using light to switch the activity of these antagonists, researchers can control the interaction between the antagonists and gpcrs in real time. this approach allows for precise modulation of gpcr activity, which could lead to new insights into cellular signaling pathways and potential therapeutic applications. in another application by using light to control the assembly of nanopores, researchers can potentially regulate the flow of ions or molecules through these nanopores. this approach could have applications in various fields, including sensing, drug delivery, and nanotechnology. another paper reports on the use of photopharmacology to control drug activity ; multifunctional fibers in the study deliver light and drugs to specific body areas. implanted fibers activate light - responsive drugs, altering their structure, and offering precise drug delivery for conditions needing exact timing or dosage. in
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to control drug activity ; multifunctional fibers in the study deliver light and drugs to specific body areas. implanted fibers activate light - responsive drugs, altering their structure, and offering precise drug delivery for conditions needing exact timing or dosage. in another study, ligands were designed to switch their binding mode to g - quadruplex dna upon exposure to visible light. this method could potentially modulate the activity of g - quadruplex dna, crucial in gene expression and telomere maintenance, offering new therapeutic avenues, particularly in cancer treatment. the study underscores photopharmacology's promise in targeting specific dna structures, suggesting g - quadruplex dna as a viable target for future photopharmacological interventions. another study developed photoactivatable antibody - photocorm conjugates targeting human ovarian cancer cells, releasing co upon light exposure to diminish cell viability. this approach offers precise cancer cell targeting while minimizing harm to healthy tissue, showcasing the potential of photopharmacology in cancer therapy. in another paper, a photoactivatable compound that binds to and modulates the activity of the cry1 protein, regulating the mammalian circadian clock, was developed. by using light to control the compound's activity, researchers can potentially treat circadian rhythm disorders and related health conditions by modulating the function of cry1. photopharmacology involves using light to control the activity of drugs. in another application researchers used photopharmacology to control drug release and focus on a drug interacting with tubulin, visualizing its release in real time with time - resolved serial crystallography. this technique offers insights into drug - tubulin interactions and demonstrates the potential for designing drugs with precise actions. = = future directions = = the future of photopharmacology holds immense promise. it has the potential to revolutionize conventional drug therapy offering new avenues for precision medicine, treating neurological disorders, and in the field of oncology and ophthalmology. additionally, it holds promise for the field of regenerative medicine where photoswitches can be used to modulate the activity of signaling pathways for targeted tissue repair and regeneration. photopharmacology will continue to grow and expand with the new discoveries and advances happening in other related fields such as synthetic chemistry, biology, nanotechnology, pharmacology, and bioengineering. while the potential of photopharmacology is vast, some challenges must be addressed to make it a clinical reality. one challenge
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other related fields such as synthetic chemistry, biology, nanotechnology, pharmacology, and bioengineering. while the potential of photopharmacology is vast, some challenges must be addressed to make it a clinical reality. one challenge is the development of stable and biocompatible photoswitches that are selective for their target receptors without cross - activity. it is particularly important that these photoswitchables have their absorbance bands fall within the wavelength range of 650 nm to 900 nm. hence, optimum molecular designing of photoswitches is required to achieve the characteristics mentioned above and desired level of performance. at present, photopharmacology uses a rational drug design approach based on studying the structure - activity relationship, however, a phenotypic screening for photoswitchable drugs could also be beneficial. in order to achieve good spatial - temporal control over drug activity there should be a significant difference between the activity of isomers. however, understanding the structural changes during the biological effects induced by photoswitching is limited. this scarcity of knowledge is also a challenge for the growth of this field, as it hampers the optimization of the activity and potency of the isomers to obtain the expected outcomes during applications. the biggest challenge in photopharmacology is finding appropriate and effective ways to deliver light to deep tissues in the body and tissues avoiding issues such as scattering and absorption. various strategies have been attempted in this regard, one being the development of photoswitchable ligands that respond to deep - tissue penetrating wavelengths like red or infrared light. moreover, some recent preclinical studies have spurred the development of wireless, compact or injectable, and remotely controllable devices capable of delivering light to neural tissues with minimal damage. there are novel optofluidic systems that can simultaneously regulate both drug delivery and light activity at specific sites. although external delivery of light is the most preferred method, the use of internal exogenous light sources such as luminescent compounds where light would be delivered directly at the site of action. this could avoid the issues related to light penetration and also enhance the degree of selectivity. in addition, this creates the opportunity to use photopharmacology as a theranostic approach that combines targeted drug delivery and molecular imaging. = = references = =
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fertiberia is a spanish company in the chemical sector whose activity is focused on the production of fertilizers, ammonia and other derived products, and is currently the largest fertilizer manufacturer in spain. the company is also the head of the fertiberia group, a conglomerate made up of several subsidiaries with a presence in countries such as algeria, portugal and france. = = history = = = = = origins = = = in 1962, the public limited company " fertilizantes de iberia " ( fertiberia ) was founded for the construction of several fertilizer factories in a coruna, huelva and castellon. entities such as the bank of bilbao, the gulf oil corporation and the international development & investment company participated in its creation. the company became closely linked to the development of the chemical park of huelva in the 1970s, where one of its factories was located. in 1974, the union explosivos rio tinto ( ert ) group, which had a strong presence in the chemical park, absorbed fertiberia. as a result of this strategic relationship, the huelva plant of fertiberia came to be supplied with pyrites obtained from the rio tinto mines. in 1989, the assets of the ert group were integrated into the ercros holding company. the latter proceeded to a reorganization of its fertilizer division, from which the company fesa - enfersa was born, which at the time was one of the largest private fertilizer companies in spain. despite its pre - eminent position, in 1992 both fesa - enfersa and its parent company ercros went into receivership, due to the large debt they accumulated. = = = grupo fertiberia = = = in 1995 the villar mir group took control of the assets of fesa - enfersa, which would form the basis for the re - foundation of fertiberia. from then on, a process of consolidation and expansion began, which led to the purchase of sefanitro ( 1996 ), quimica del estroncio ( 2002 ) and fercampo ( 2012 ), as well as the creation of new subsidiaries in different areas. this would lead fertiberia to become the main spanish fertilizer company, with presence in france and portugal. however, as part of the internal reorganization process, some production plants in cartagena, seville and barakaldo were also closed in 2003 – 2004. in 2020
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##ia to become the main spanish fertilizer company, with presence in france and portugal. however, as part of the internal reorganization process, some production plants in cartagena, seville and barakaldo were also closed in 2003 – 2004. in 2020, the swedish - german group triton partners took control of fertiberia. = = structure = = the company currently has several production centers throughout spain : palos de la frontera, huelva, puertollano, sagunto and aviles. the huelva factory, located in the chemical park area, is the most important of all the fertiberia group's factories. fertiberia also has a series of warehouses and logistics centers. the head office is located in madrid, specifically in agustin de foxa street. = = references = = = = bibliography = = alvarez, santiago ( 1968 ). sobre galicia ( in spanish ). paris : editions de la librairie du globe. arenas posadas, carlos ( 2017 ). " riotinto, el declive de un mito minero ( 1954 - 2003 ) ". revista de historia industrial ( in spanish ) ( 69 ). barcelona : universidad de barcelona : 109 – 142. issn 1132 - 7200. fabregas, didac ( 1997 ). espana en la encrucijada : evolucion o involucion ( in spanish ). ediciones del bronce. ferrero blanco, maria dolores ( 2000 ). " un modelo de mineria contemporanea : huelva, del colonialismo a la mundializacion ". universidad de huelva ( in spanish ). salmon, keith g. ( 1995 ). the modern spanish economy. transformation and integration into europe. pinter publishers. sumpsi, jose maria ; barcelo, luis vicente ( 1996 ). la ronda uruguay y el sector agroalimentario espanol ( in spanish ). madrid : ministerio de comercio y turismo. tomas, carmen ; alonso, ignacio ( 1993 ). el provocador. carlos solchaga, de la reconversion industrial a la crisis economica y social ( in spanish ). ediciones temas de hoy. yravedra, vicente ( 1999 ). " fertilizantes, 70 anos de evolucion ( 1929 - 1999 ) " ( pdf ). agricultura. rev
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. ediciones temas de hoy. yravedra, vicente ( 1999 ). " fertilizantes, 70 anos de evolucion ( 1929 - 1999 ) " ( pdf ). agricultura. revista agropecuaria y ganadera ( in spanish ) ( 806 ). editorial agricola espanola : 778 – 789. issn 0002 - 1334. = = external links = = official website ( available in different languages, including english ).
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vocabulary mismatch is a common phenomenon in the usage of natural languages, occurring when different people name the same thing or concept differently. furnas et al. ( 1987 ) were perhaps the first to quantitatively study the vocabulary mismatch problem. their results show that on average 80 % of the times different people ( experts in the same field ) will name the same thing differently. there are usually tens of possible names that can be attributed to the same thing. this research motivated the work on latent semantic indexing. the vocabulary mismatch between user created queries and relevant documents in a corpus causes the term mismatch problem in information retrieval. zhao and callan ( 2010 ) were perhaps the first to quantitatively study the vocabulary mismatch problem in a retrieval setting. their results show that an average query term fails to appear in 30 - 40 % of the documents that are relevant to the user query. they also showed that this probability of mismatch is a central probability in one of the fundamental probabilistic retrieval models, the binary independence model. they developed novel term weight prediction methods that can lead to potentially 50 - 80 % accuracy gains in retrieval over strong keyword retrieval models. further research along the line shows that expert users can use boolean conjunctive normal form expansion to improve retrieval performance by 50 - 300 % over unexpanded keyword queries. = = techniques that may reduce mismatch = = stemming full - text indexing instead of only indexing keywords or abstracts use of controlled vocabularies in both indexing and retrieval, such as taxonomies or ontologies indexing text on inbound links from other documents ( or other social tagging ) query expansion. a 2012 study by zhao and callan using expert created manual conjunctive normal form queries has shown that searchonym expansion in the boolean conjunctive normal form is much more effective than the traditional bag of word expansion e. g. rocchio expansion. translation - based models = = references = =
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the rosiwal scale is a hardness scale in mineralogy, with its name given in memory of the austrian geologist august karl rosiwal. the rosiwal scale attempts to give more quantitative values of scratch hardness, unlike the mohs scale which is a qualitative measurement with relative values. the rosiwal method ( also called the delesse - rosiwal method ) is a method of petrographic analysis and is performed by scratching a polished surface under a known load using a scratch - tip with a known geometry. the hardness is calculated by finding the volume of removed material, but this measurement can be difficult and must sample a large enough number of grain in order to have statistical significance. = = rosiwal scale values = = measures the scratch hardness of a mineral expressed on a quantitative scale. these measurements must be performed in a laboratory, since the surfaces must be flat and smooth. the base value of the rosiwal scale is defined as corundum set to 1000 ( unitless ). = = see also = = hardness august karl rosiwal friedrich mohs = = references = = = = = bibliography = = = the great encyclopedia of minerals 451 photographs, 520 pages 20'5 x 29'2 cm. original : artia, prague 1986 catalan version : editorial susaeta sa 1989, isbn 978 - 84 - 30515 - 85 - 1 ( printed in czechoslovakia ) accurate mineralogy. de lapparent, a. : 1965 paris minerals and study how to them. dana l. hurlbut, s. : new york 1949 schone und seltene mineral. hofmann and f. karpinski, j. : 1980 leipzig corduant, william s. " the hardness of minerals and rocks ". lapidary digest c. 1990. = = external links = = hardness minerals geotopo xxi : description of program content hardness and toughness archived 2010 - 10 - 24 at the wayback machine glossary of technical mining
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the copper coulometer is a coulometer consisting of two identical copper electrodes immersed in a slightly acidic ph - buffered solution of copper ( ii ) sulfate ( copper - copper ( ii ) sulfate electrode ). passing of current through the element leads to the anodic dissolution of the metal on anode and simultaneous deposition of copper ions on the cathode. these reactions have 100 % efficiency over a wide range of current density. = = calculation = = the amount of electric charge ( quantity of electricity ) passed through the cell can easily be determined by measuring the change in mass of either electrode and calculating : q = z c u δ m f m c u { \ displaystyle q = { \ frac { z _ { cu } \ delta mf } { m _ { cu } } } }, where : q { \ displaystyle q } is the quantity of electricity ( coulombs ) δ m { \ displaystyle \ delta m } is the mass transported ( gm ) z c u { \ displaystyle z _ { cu } } is the charge of the copper ions, equal to + 2 f { \ displaystyle f } is the faraday constant ( 96485. 3383 coulombs per mole ) m c u { \ displaystyle m _ { cu } } is the atomic weight of copper, equal to 63. 546 grams per mole. although this apparatus is interesting from a theoretical and historical point of view, present - day electronic measurement of time and electric current provide in their multiplication the amount of passed coulombs much easier, with greater precision, and in a shorter period of time than is possible by weighing the electrodes. = = see also = = mercury coulometer coulometry = = references = =
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the chu or chu script is a writing system used in the state of chu during the spring and autumn and warring states periods. the script was one of the different ancient writing systems used by various countries in china prior to the unification of the world by emperor qin shi huang and the implementation of the policy of writing in the same language. it is also known as the “ chu system of simplified palm script ” because most of the excavated texts are on silk, in addition to bamboo and wooden slips. = = characteristics = = the chu script was one of the six scripts used by the six shandong states ( qi, chu, yan, han, wei, and zhao ), and was widely used during the spring and autumn and warring states periods of ancient china, but was banned after the qin state annexed the six states and standardized the scripts, and then its use was drastically reduced and ultimately died out. since the 1950s, there have been a number of artifacts written in pre - qin and early qin - han scripts on silk and silk unearthed in various places, including the “ wulipai bamboo kan ” from the chu tomb in changsha, the “ wangshan bamboo kan ” from the wangshan chu tomb in jiangling, the “ xinyang bamboo kan ” from the chu tomb at changtaiguan in xinyang, henan, the palm script unearthed from the han tomb of mawangdui in 1973, and the “ yumeng nyinghudi qin kan ” unearthed from the qin tomb in 1975. the scripts in these texts are in the process of transition between seal script and clerical script. therefore, it is extremely difficult to interpret them accurately. one example of the difficulties in interpretation is the character “ ”, whose form is difficult to relate imaginatively to the concept of “ tiger ”, and which in certain contexts actually means “ ”, both in terms of the change in the character form and the way “ ” is written as the first person “ ”. both the change of character form and the way the character “ tiger ” is written as the first person “ ” indicate that the ancient scripts were used very differently from today's. at the same time, the scripts were similar to those of today. at the same time, scripts and usages similar to today's are not uncommon, and the shaanxi provincial bureau of cultural relics describes on its official website the similarities and differences in the relationship between the chu script “ 馬 ” which is much the same as the modern script “ 馬 ”.
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to today's are not uncommon, and the shaanxi provincial bureau of cultural relics describes on its official website the similarities and differences in the relationship between the chu script “ 馬 ” which is much the same as the modern script “ 馬 ”. the unearthed jianfu are presumed to record a number of texts and books that have been lost in ancient times, and deciphering and research is ongoing. = = see also = = mawangdui han tomb - han tombs excavated after 1972 whose artifacts are exhibited in the same museum. = = references = = = = external links = = 南 省 博 hunan provincial museum archived 2006 - 09 - 03 at the wayback machine - 南 省 博 方 ) 西 古 代 文 明 天 下 一 at the wayback machine ( archived 2016 - 12 - 01 ) - how to get the english version of listed site 。 内 文 と 国 文 の 比 か されている 。
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a corporate spin - off, also known as a spin - out, starburst or hive - off, is a type of corporate action where a company " splits off " a section as a separate business or creates a second incarnation, even if the first is still active. it is distinct from a sell - off, where a company sells a section to another company or firm in exchange for cash or securities. = = characteristics = = spin - offs are divisions of companies or organizations that then become independent businesses with assets, employees, intellectual property, technology, or existing products that are taken from the parent company. shareholders of the parent company receive equivalent shares in the new company in order to compensate for the loss of equity in the original stocks. however, shareholders may then buy and sell stocks from either company independently ; this potentially makes investment in the companies more attractive, as potential share purchasers can invest narrowly in the portion of the business they think will have the most growth. in contrast, divestment can also sever one business from another, but the assets are sold off rather than retained under a renamed corporate entity. many times, the management team of the new company are from the same parent organization. often, a spin - off offers the opportunity for a division to be backed by the company but not be affected by the parent company's image or history, giving potential to take existing ideas that had been languishing in an old environment and help them grow in a new environment. spin - offs also allow high - growth divisions, once separated from other low - growth divisions, to command higher valuation multiples. in most cases, the parent company or organization offers support doing one or more of the following : investing equity in the new firm being the first customer of the spin - off that helps create cash flow providing incubation space ( desk, chairs, phones, internet access, etc. ) providing legal, finance, or technology services all the support from the parent company is provided with the explicit purpose of helping the spin - off grow. one of the most critical antecedents of corporate spin off or corporate entrepreneurship rests upon its ceo ’ s ability to articulate a compelling vision can strengthen emotional bonds within the top management team, helping to foster corporate spin off or corporate entrepreneurship. = = = u. s. securities and exchange commission = = = the united states securities and exchange commission's ( sec ) definition of " spin - off " is more precise. spin - offs occur when the equity owners of the parent company receive equity stakes in
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u. s. securities and exchange commission = = = the united states securities and exchange commission's ( sec ) definition of " spin - off " is more precise. spin - offs occur when the equity owners of the parent company receive equity stakes in the newly spun off company. for example, when agilent technologies was spun off from hewlett - packard ( hp ) in 1999, the stockholders of hp received agilent stock. a company not considered a spin - off in the sec's definition ( but considered by the sec as a technology transfer or licensing of technology to the new company ) may also be called a spin - off in common usage. = = = other definitions = = = a second definition of a spin - out is a firm formed when an employee or group of employees leaves an existing entity to form an independent start - up firm. the prior employer can be a firm, a university, or another organization. spin - outs typically operate at arm's length from the previous organizations and have independent sources of financing, products, services, customers, and other assets. in some cases, the spin - out may license technology from the parent or supply the parent with products or services ; conversely, they may become competitors. such spin - outs are important sources of technological diffusion in high - tech industries. terms such as hive - up, hive down or hive across are sometime used for transferring a business to a parent company, a subsidiary company or a fellow subsidiary. = = reasons for spin - offs = = one of the main reasons for what the economist has dubbed the 2011 " starburst revival " is that " companies seeking buyers for parts of their business are not getting good offers from other firms, or from private equity ". for example, foster's group, an australian beverage company, was prepared to sell its wine business. however, due to the lack of a decent offer, it decided to spin off the wine business, which is now called treasury wine estates. = = = conglomerate discount = = = according to the economist, another driving force of the proliferation of spin - offs is what it calls the " conglomerate discount " — that " stockmarkets value a diversified group at less than the sum of its parts ". = = examples = = some examples of spin - offs ( according to the sec definition ) : guidant was spun off from eli lilly and company in 1994, formed from lilly's medical devices and diagnostics division. agilent technologies spun off from hewlett - packard ( hp ) in 1999
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offs ( according to the sec definition ) : guidant was spun off from eli lilly and company in 1994, formed from lilly's medical devices and diagnostics division. agilent technologies spun off from hewlett - packard ( hp ) in 1999, formed from hp's former test - and - measurement equipment division. later in 2014, keysight was spun off from agilent technologies. expedia group was spun off from microsoft in 1999, with its eponymous subsidiary expedia. dreamworks animation was spun off from dreamworks pictures in 2004. in turn, dreamworks animation was acquired by comcast and nbcuniversal in 2016. covidien was spun off from tyco international in 2007. te connectivity was spun off from tyco international in 2007. cenovus energy was spun off from encana ( now ovintiv ) in 2009. aol was a time warner spin - off in 2009 ; this effectively was a demerger, as aol had previously merged into time warner. ocean rig was spun off from dryships in september 2011. news corporation's publishing operations ( and its broadcasting operations in australia ) were spun off as news corp in 2013. the previous news corporation's remaining media properties were retained under the name 21st century fox. in turn, 21st century fox was acquired by the walt disney company in 2019, but most of its broadcast and cable properties ( the fox broadcast network, fox news channel, fox business network and fox sports ) were spun off to the new fox corporation while disney retained the film and television production units. after being acquired by sega, index corporation's video game operations were re - branded as atlus, the name of a predecessor company, while its contents and solution businesses were spun off as a new company using the index corporation name in 2013. mallinckrodt pharmaceuticals was spun off from covidien in 2013. viacom was spun off from cbs in 1971, but were later re - merged in 2019 as viacomcbs, now paramount global. fortive, envista and veralto were spun off from danaher in 2016, 2019 and 2023 respectively. in south korea, the then - cj e & m ( now cj enm entertainment division ) spun off its drama production and distribution division into a new subsidiary company called studio dragon in may 2016. examples following the second definition of spin - out : fairchild semiconductor was a spin - out of shockley transistor ; the founders were shockley's " traitorous eight "
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distribution division into a new subsidiary company called studio dragon in may 2016. examples following the second definition of spin - out : fairchild semiconductor was a spin - out of shockley transistor ; the founders were shockley's " traitorous eight " intel was in turn a spin - out of fairchild, as were many firms in the semiconductor industry = = = academia = = = an example of companies created by technology transfer or licensing : since 1997, oxford university innovation has helped create more than 70 spin - out companies, and now, on average, every two months a new company is spun out of " academic research generated within and owned by the university of oxford ". over £266 million in external investment has been raised by spin - out companies since 2000, and five are currently listed on the london stock exchange's alternative investment market. = = see also = = demerger divestment equity carve - out stub ( stock ) successor company = = references = = = = further reading = = eirma ( 2003 ) " innovation through spinning in and out ", research technology management, vol. 46, 63 – 64. rene rohrbeck ; mario dohler ; heinrich arnold ( 20 april 2009 ). " creating growth with externalization of r & d results — the spin ‐ along approach ". global business and organizational excellence. 28 ( 4 ) : 44 – 51. doi : 10. 1002 / joe. 20267. issn 1932 - 2054. wikidata q104832450. rohrbeck, r., holzle k. and h. g. gemunden ( 2009 ) : " opening up for competitive advantage : how deutsche telekom creates an open innovation ecosystem ", r & d management, vol. 39, s. 420 – 430. = = external links = =
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a microbial cyst is a resting or dormant stage of a microorganism, that can be thought of as a state of suspended animation in which the metabolic processes of the cell are slowed and the cell ceases all activities like feeding and locomotion. many groups of single - celled, microscopic organisms, or microbes, possess the ability to enter this dormant state. encystment, the process of cyst formation, can function as a method for dispersal and as a way for an organism to survive in unfavorable environmental conditions. these two functions can be combined when a microbe needs to be able to survive harsh conditions between habitable environments ( such as between hosts ) in order to disperse. cysts can also be sites for nuclear reorganization and cell division, and in parasitic species they are often the infectious stage between hosts. when the encysted microbe reaches an environment favorable to its growth and survival, the cyst wall breaks down by a process known as excystation. environmental conditions that may trigger encystment include, but are not limited to : lack of nutrients or oxygen, extreme temperatures, desiccation, adverse ph, and presence of toxic chemicals which are not conducive for the growth of the microbe. = = history and terminology = = the idea that microbes could temporarily assume an alternate state of being to withstand changes in environmental conditions began with antonie van leeuwenhoek ’ s 1702 study on animalcules, currently known as rotifers : “'i have often placed the animalcules i have before described out of the water, not leaving the quantity of a grain of sand adjoining to them, in order to see whether when all the water about them was evaporated and they were exposed to the air their bodies would burst, as i had often seen in other animalcules. but now i found that when almost all the water was evaporated, so that the creature could no longer be covered with water, nor move itself as usual, it then contracted itself into an oval figure, and in that state it remained, nor could i perceive that the moisture evaporated from its body, for it preserved its oval and round shape, unhurt. " leeuwenhoek later continued his work with rotifers to discover that when he returned the dried bodies to their preferred aquatic conditions, they resumed their original shape and began swimming again. these observations did not gain traction with the general microbiological community of the time,
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later continued his work with rotifers to discover that when he returned the dried bodies to their preferred aquatic conditions, they resumed their original shape and began swimming again. these observations did not gain traction with the general microbiological community of the time, and the phenomena as leeuwenhoek observed it was never given a name. in 1743, john turberville needham observed the revival of the encysted larval stage of the wheat parasite, anguillulina tritici and later published these findings in new microscopal discoveries ( 1745 ). several others repeated and expanded upon this work, informally referring to their studies on the “ phenomenon of reviviscence. ” in the late 1850s, reviviscence became embroiled in the debate surrounding the theory of spontaneous generation of life, leading two highly involved scientists on either side of the issue to call upon the biological society of france for an independent review of their opposing conclusions on the matter. doyere, who believed rotifers could be desiccated and revitalized, and pouchet, who believed they could not, allowed independent observers of various scientific backgrounds to observe and attempt to replicate their findings. the resulting report leaned toward the arguments made by pouchet, with notable dissension from the main author who blamed his framing of the issue in the report on fear of religious retribution. despite the attempt by doyere and pouchet to conclude debate on the topic of resurrection, investigations continued. in 1872, wilhelm preyer introduced the term ‘ anabiosis ’ ( return to life ) to describe the revitalization of viable, lifeless organisms to an active state. this was quickly followed by schmidt ’ s 1948 proposal of the term ‘ abiosis, ’ leading to some confusion between terms describing the beginning of life from non - living elements, viable lifelessness, and nonliving components that are necessary for life. as part of his 1959 review of leeuwenhoek ’ s original findings and the evolution of the science surrounding microbial cysts and other forms of metabolic suspension, d. keilin proposed the term ‘ cryptobiosis ’ ( latent life ) to describe : “... the state of an organism when it shows no visible signs of life and when its metabolic activity becomes hardly measurable, or comes reversibly to a standstill. ” as microbial research began to gain popularity exponentially, details about ciliated protist physiology and cyst formation led to increased curiosity about the role of encyst
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becomes hardly measurable, or comes reversibly to a standstill. ” as microbial research began to gain popularity exponentially, details about ciliated protist physiology and cyst formation led to increased curiosity about the role of encystment in the life cycle of ciliates and other microbes. the realization that no one category of microscopic organism ‘ owns ’ the ability to form metabolically dormant cysts necessitates the term ‘ microbial cyst ’ to describe the physical object as it exists in all its forms. also important in the generation of the term, is the delineation of endospores and microbial cysts as different forms of cryptobiosis or dormancy. endospores exhibit more extreme isolation from their environment in terms of cell wall thickness, impermeability to substrates, and presence of dipicolinic acid, a compound known to confer resistance to extreme heat. microbial cysts have been likened to modified vegetative cells with the addition of a specialized capsule. importantly, encystment is a process observed to precede cell division, while the formation of an endospore involves non - reproductive cellular division. the study of the encystment process was mostly confined to the 1970s and'80s, resulting in the lack of understanding of genetic mechanisms and additional defining characteristics, though they are generally thought to follow a different formation sequence than endospores. = = formation and composition of the cyst wall = = indicators of cyst formation in ciliated protists include varying degrees of ciliature resorption, with some ciliates losing both cilia and the membranous structures supporting them while others maintain kinetosomes and / or microtubular structures. de novo synthesis of cyst wall precursors in the endoplasmic reticulum also frequently indicate a ciliate is undergoing encystment. the composition of the cyst wall is variable in different organisms. the cyst walls of bacteria are formed by the thickening of the normal cell wall with added peptidoglycan layers. the walls of protozoan cysts are made of chitin, a type of glycopolymer. the cyst wall of some ciliated protists is composed of four layers, ectocyst, mesocyst, endocyst, and the granular layer. the ectocyst is the outer layer and contains a plug - like structure through which
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ciliated protists is composed of four layers, ectocyst, mesocyst, endocyst, and the granular layer. the ectocyst is the outer layer and contains a plug - like structure through which the vegetative cell reemerges during excystation. interior to the ectocyst, the thick mesocyst is compact yet stratified in density. chitinase treatments indicate the presence of chitin in the mesocyst of some ciliate species, but this compositional characteristic appears to be highly heterogeneous. the thin endocyst, interior to the mesocyst, is less dense than the ectocyst and is believed to be composed of proteins. the innermost granular layer lies directly outside the pellicle and is composed of de novo synthesized precursors of granular material. = = cyst formation across species = = = = = in bacteria = = = in bacteria ( for instance, azotobacter sp. ), encystment occurs by changes in the cell wall ; the cytoplasm contracts and the cell wall thickens. various members of the azotobacteraceae family have been shown to survive in an encysted form for up to 24 years. the extremophile rhodospirillum centenum, an anoxygenic, photosynthetic, nitrogen - fixing bacterium that grows in hot springs was found to form cysts in response to desiccation as well. bacteria do not always form a single cyst. varieties of cysts formation events are known. rhodospirillum centenum can change the number of cysts per cell, usually ranging from four to ten cells per cyst depending on the environment. some species of filamentous cyanobacteria have been known to form heterocysts to escape levels of oxygen concentration detrimental to their nitrogen fixing processes. this process is distinct from other types of microbial cysts in that the heterocysts are often produced in a repeating pattern within a filament composed of several vegetative cells, and once formed, heterocysts cannot return to a vegetative state. = = = in protists = = = protists, especially protozoan parasites, are often exposed to very harsh conditions at various stages in their life cycle. for example, entamoeba histolytica, a common intestinal parasite that
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in protists = = = protists, especially protozoan parasites, are often exposed to very harsh conditions at various stages in their life cycle. for example, entamoeba histolytica, a common intestinal parasite that causes dysentery, has to endure the highly acidic environment of the stomach before it reaches the intestine and various unpredictable conditions like desiccation and lack of nutrients while it is outside the host. an encysted form is well suited to survive such extreme conditions, although protozoan cysts are less resistant to adverse conditions compared to bacterial cysts. cytoplasmic dehydration, high autophagic activity, nuclear condensation, and decrease of cell volume are all indicators of encystment initiation in ciliated protists. in addition to survival, the chemical composition of certain protozoan cyst walls may play a role in their dispersal. the sialyl groups present in the cyst wall of entamoeba histolytica confer a net negative charge to the cyst which prevents its attachment to the intestinal wall thus causing its elimination in the feces. other protozoan intestinal parasites like giardia lamblia and cryptosporidium also produce cysts as part of their life cycle ( see oocyst ). due to the hard outer shell of the cyst, cryptosporidium and giardia are resistant to common disinfectants used by water treatment facilities such as chlorine. in some protozoans, the unicellular organism multiplies during or after encystment and releases multiple trophozoites upon excystation. many additional species of protists have been shown to exhibit encystment when confronted with unfavorable environmental conditions. = = = in rotifers = = = rotifers also produce diapause cysts, which are different from quiescent ( environmentally triggered ) cysts in that the process of their formation begins before environmental conditions have deteriorated to unfavorable levels and the dormant state may extend past the restoration of ideal conditions for microbial life. food limited females of some synchaeta pectinata strains produce unfertilized diapausing eggs with a thicker shell. fertilized diapausing eggs can be produced in both food limited and non - food limited conditions, indicative of a bet - hedging mechanism for food availability or perhaps an adaptation to variation in food levels throughout
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##using eggs with a thicker shell. fertilized diapausing eggs can be produced in both food limited and non - food limited conditions, indicative of a bet - hedging mechanism for food availability or perhaps an adaptation to variation in food levels throughout a growing season. = = pathology = = while the cyst component itself is not pathogenic, the formation of a cyst is what gives giardia its primary tool of survival and its ability to spread from host to host. ingestion of contaminated water, foods, or fecal matter gives rise to the most commonly diagnosed intestinal disease, giardiasis. whereas it was previously believed that encystment only served a purpose for the organism itself, it has been found that protozoan cysts have a harboring effect. common pathogenic bacteria can also be found taking refuge in the cyst of free - living protozoa. survival times for bacteria in these cysts range from a few days to a few months in harsh environments. not all bacteria are guaranteed to survive in the cyst formation of a protozoan ; many species of bacteria are digested by the protozoan as it undergoes cystic growth. = = see also = = cryptobiosis spore ( in bacteria, fungi and algae ) endospore ( in firmicute bacteria ) resting spore ( in fungi ) trophozoite = = references = =
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endothelial lipase ( lipg ) is a form of lipase secreted by vascular endothelial cells in tissues with high metabolic rates and vascularization, such as the liver, lung, kidney, and thyroid gland. the lipg enzyme is a vital component to many biological processes. these processes include lipoprotein metabolism, cytokine expression, and lipid composition in cells. unlike the lipases that hydrolyze triglycerides, endothelial lipase primarily hydrolyzes phospholipids. due to the hydrolysis specificity, endothelial lipase contributes to multiple vital systems within the body. on the contrary to the beneficial roles that lipg plays within the body, endothelial lipase is thought to play a potential role in cancer and inflammation. knowledge obtained in vitro and in vivo suggest the relations to these conditions, but human interaction knowledge lacks due to the recent discovery of endothelial lipase. endothelial lipase was first characterized in 1999. the two independent research groups which are notable for this discovery cloned the endothelial lipase gene and identified the novel lipase secreted from endothelial cells. the anti - atherosclerosis opportunity through alleviating plaque blockage and prospective ability to raise high - density lipoprotein ( hdl ) have gained endothelial lipase recognition. = = discovery = = in 1999, the identification of endothelial lipase was independently discovered by two research groups. the first group at rhone - poulenc rorer cloned and characterized a new member of the triacylglyerol ( tg ) family. when this novel endothelial lipase was over - expressed in mice, the concentrations of hdl cholesterol and apolipoprotein a - i in plasma decreased. a second group at stanford university independently cloned this same endothelial lipase from human umbilical vein endothelial cells, human coronary artery endothelial cells and rodent endothelial - like yolk sacs. suppression subtractive hybridization was used to isolate the genes. the genes were then compared and aligned. two cdna fragments expressed the lipase gene and endothelial properties. northern blot analysis documented the samples. the suggested relation to metabolism and vascular disease was attributed to tissue selective expression in endothelial cells. = = structure = = endothelial lipase is a protein that belongs triglyceride lipase category. this protein is
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documented the samples. the suggested relation to metabolism and vascular disease was attributed to tissue selective expression in endothelial cells. = = structure = = endothelial lipase is a protein that belongs triglyceride lipase category. this protein is encoded by the lipg gene. endothelial lipase is secreted from vascular endothelial cells, being the only lipase to date. the primary secretion is that of a 55kda protein which is secreted to a 68kda protein after post - translational glycosylation. lipg functions as it binds to proteoglycans. lipg also has the potential for additional cleavage. the additional cleavage would result in inactivity of the 40 kda protein n - terminal 40 kda and 28 kda c - terminal. lipg has the capability to form a protein dimer prior to secretion which causes dimerization to appear. the addition reaction of the same compound and molecules enhances the resistance to cleavage and limited activity is sustained. = = biological function = = = = = metabolism = = = the site of endothelial lipase enzymatic activity is the surface of endothelial cells. lipg regulates lipoprotein metabolism through the hydrolysis of hdl phospholipids. this high - density lipoprotein is an amphipathic lipid, meaning the lipid is composed of both a hydrophobic and a hydrophilic component. cholesterol has a four - ring structure and is an isoprenoid - based hydrocarbon. although cholesterol lacks the phosphate head group, cholesterol's hydroxyl component interacts with water, categorizing cholesterol as amphipathic. hdl cholesterol provides extreme benefits to the body and is vital in sustaining the fluidity of natural membranes. hdl cholesterol must be maintained at a certain level to ensure normal cell growth and reproduction. the hdl capability of absorption of cholesterol and transport to the liver, aids in the removal of cholesterol in the body. on the contrary, low - density lipoprotein ( ldl ) cholesterol works in opposition. ldl cholesterol does not transport cholesterol out of the body but rather serves as a foundation for cholesterol buildup. ldl should be kept low in the body to avoid cholesterol buildup in arteries. when hdl are hydrolyzed, the turnover rate of hdl increases and cho
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body but rather serves as a foundation for cholesterol buildup. ldl should be kept low in the body to avoid cholesterol buildup in arteries. when hdl are hydrolyzed, the turnover rate of hdl increases and cholesterol levels in plasma decrease. this hydrolysis allows for the acceleration or continuation of cholesterol removal from the body to avoid a buildup. following the hydrolysis of hdl, free fatty acid lipid precursors are taken up. these lipids are then utilized in other phospholipid catabolism. in summation, endothelial lipase is said to be a pivotal component in metabolism through high - density lipoprotein hydrolysis. = = = vascular biology = = = endothelial lipase is linked to potential treatment and improvement of atherosclerosis. atherosclerosis is a vascular disease which is caused by arterial plaque buildup. cholesterol, fat, calcium, and other components contribute to the formation of plaque in the blood. plaque is detrimental to vascular heath because it narrows and stiffens the arteries, causing a lack of oxygen - rich blood flow. hdl increase serves as a treatment for atherosclerosis. the hydrolysis of hdl leads to the transportation of cholesterol to the liver. the filtration system of the liver aids in the removal of cholesterol from the body. therefore, the cholesterol level in the plasma will decrease. thus, endothelial lipase synthesis of hdl could provide an adequate opportunity to increase hdl levels. data suggests that endothelial lipase inhibition should increase the plasma hdl, primarily in patients with low hdl - c levels. an increased risk of atherosclerosis is associated with low levels of hdl. although a functional correlation can be drawn, there is little clinical evidence to provide support to the suggested potential benefits in vascular pathophysiology. = = references = = = = external links = = endothelial + lipase, + human at the u. s. national library of medicine medical subject headings ( mesh )
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command and control ( abbr. c2 ) is a " set of organizational and technical attributes and processes... [ that ] employs human, physical, and information resources to solve problems and accomplish missions " to achieve the goals of an organization or enterprise, according to a 2015 definition by military scientists marius vassiliou, david s. alberts, and jonathan r. agre. the term often refers to a military system. versions of the united states army field manual 3 - 0 circulated circa 1999 define c2 in a military organization as the exercise of authority and direction by a properly designated commanding officer over assigned and attached forces in the accomplishment of a mission. a 1988 nato definition is that command and control is the exercise of authority and direction by a properly designated individual over assigned resources in the accomplishment of a common goal. an australian defence force definition, similar to that of nato, emphasises that c2 is the system empowering designated personnel to exercise lawful authority and direction over assigned forces for the accomplishment of missions and tasks. the australian doctrine goes on to state : " the use of agreed terminology and definitions is fundamental to any c2 system and the development of joint doctrine and procedures. the definitions in the following paragraphs have some agreement internationally, although not every potential ally will use the terms with exactly the same meaning. " = = overview = = = = = us perspective = = = the us department of defense dictionary of military and associated terms defines command and control as : " the exercise of authority and direction by a properly designated commander over assigned and attached forces in the accomplishment of the mission. also called c2. source : jp 1 ". the edition of the dictionary " as amended through april 2010 " elaborates, " command and control functions are performed through an arrangement of personnel, equipment, communications, facilities, and procedures employed by a commander in planning, directing, coordinating, and controlling forces and operations in the accomplishment of the mission. " however, this sentence is missing from the " command and control " entry for the edition " as amended through 15 august 2014. " commanding officers are assisted in executing these tasks by specialized staff officers and enlisted personnel. these military staff are a group of officers and enlisted personnel that provides a bi - directional flow of information between a commanding officer and subordinate military units. the purpose of a military staff is mainly that of providing accurate, timely information which by category represents information on which command decisions are based. the key application is that of decisions that effectively manage unit resources. while information flow toward the commander is a priority, information that is
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a military staff is mainly that of providing accurate, timely information which by category represents information on which command decisions are based. the key application is that of decisions that effectively manage unit resources. while information flow toward the commander is a priority, information that is useful or contingent in nature is communicated to lower staffs and units. = = = computer security industry = = = this term is also in common use within the computer security industry and in the context of cyberwarfare. here the term refers to the influence an attacker has over a compromised computer system that they control. for example, a valid usage of the term is to say that attackers use " command and control infrastructure " to issue " command and control instructions " to their victims. advanced analysis of command and control methodologies can be used to identify attackers, associate attacks, and disrupt ongoing malicious activity. = = derivative terms = = there is a plethora of derivative terms that emphasize various aspects, uses, and sub - domains of c2. these terms are accompanied by numerous associated abbreviations. for example, in addition to c2, command and control is often abbreviated as c2 and sometimes as c & c " command and control " have been coupled with : collaboration communication / communications computers / computing electronic warfare interoperability reconnaissance surveillance target acquisition and others. some of the more common variations include : ac2 - aviation command & control c2i – command, control & intelligence c2i – command, control & information ( a less common usage ) r2c2i - rapid advanced manufacturing, command, control & intelligence [ developed by sicdrone ] c2is – command and control information systems c2isr – c2i plus surveillance and reconnaissance c2istar – c2 plus istar ( intelligence, surveillance, target acquisition, and reconnaissance ) c3 – command, control & communication ( human activity focus ) c3 – command, control & communications ( technology focus ) c3 – consultation, command, and control [ nato ] c3i – 4 possibilities ; the most common is command, control, communications and intelligence c3istar – c3 plus istar c3isrew – c2isr plus communications plus electronic warfare ( technology focus ) c3ms - cyber command and control mission system c3 / sa - c3 plus situational awareness c4, c4i, c4isr, c4istar, c4isrew, c4istarew – plus computers ( technology focus ) or computing ( human activity focus ) c4i2 – command, control, communications, computers,
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c4i, c4isr, c4istar, c4isrew, c4istarew – plus computers ( technology focus ) or computing ( human activity focus ) c4i2 – command, control, communications, computers, intelligence, and interoperability c5i – command, control, communications, computers, collaboration and intelligence c5i – command, control, communications, computers, cyber and intelligence ( us army ) c6isr – command, control, communications, computers, cyber - defense and combat systems and intelligence, surveillance, and reconnaissance mdc2 - multi - domain command and control nc2 − nuclear command and control nc3 − nuclear command and control and communications and others. command : the exercise of authority based upon certain knowledge to attain an objective. control : the process of verifying and correcting activity such that the objective or goal of command is accomplished. communication : ability to exercise the necessary liaison to exercise effective command between tactical or strategic units to command. computers : the computer systems and compatibility of computer systems. also includes data processing. intelligence : includes collection as well as analysis and distribution of information. = = command and control centers = = a command and control center is typically a secure room or building in a government, military or prison facility that operates as the agency's dispatch center, surveillance monitoring center, coordination office and alarm monitoring center all in one. command and control centers are operated by a government or municipal agency. various branches of the us military such as the us coast guard and navy have command and control centers. they are also common in many large correctional facilities. a command and control center that is used by a military unit in a deployed location is usually called a " command post ". a warship has a combat information center for tactical control of the ship's resources, but commanding a fleet or joint operation requires additional space for commanders and staff plus c4i facilities provided on a flagship ( e. g., aircraft carriers ), sometimes a command ship or upgraded logistics ship such as uss coronado. = = command and control warfare = = command and control warfare encompasses all the military tactics that use communications technology. it can be abbreviated as c2w. an older name for these tactics is " signals warfare ", derived from the name given to communications by the military. newer names include information operations and information warfare. the following techniques are combined : cyber operations with the physical destruction of enemy communications facilities. the objective is to deny information to the enemy and so disrupt its command and control capabilities.
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to communications by the military. newer names include information operations and information warfare. the following techniques are combined : cyber operations with the physical destruction of enemy communications facilities. the objective is to deny information to the enemy and so disrupt its command and control capabilities. at the same time precautions are taken to protect friendly command and control capabilities against retaliation. in addition to targeting the enemy's command and control, information warfare can be directed to the enemy's politicians and other civilian communications. electronic warfare ( ew ) military deception operations security ( opsec ) psychological operations ( psyop ) psychological warfare = = see also = = us and other nato specific : other military institute of telecommunications and information technologies = = references = = = = = citations = = = = = = sources = = = = = external links = = command and control definitions and procedures, uk college of policing international command and control institute understanding command and control by d. s. alberts and r. e. hayes ( 2006 )
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wsdma ( wideband space division multiple access ) is a high bandwidth channel access method, developed for multi - transceiver systems such as active array antennas. wsdma is a beamforming technique suitable for overlay on the latest air - interface protocols including wcdma and ofdm. wsdma enabled systems can determine the angle of arrival ( aoa ) of received signals to spatially divide a cell sector into many sub - sectors. this spatial awareness provides information necessary to maximise carrier to noise + interference ratio ( cnir ) link budget, through a range of digital processing routines. wsdma facilitates a flexible approach to how uplink and downlink beamforming is performed and is capable of spatial filtering known interference generating locations. = = key features = = transmit and receive beam shaping and steering multiple sub - sector path processing spatial interference filtering sector activity scan = = characteristics and principles of operation = = = = = active panel antenna calibration = = = active panel antenna systems, comprising a planar array of micro - radios and associated antenna element, rely upon a comprehensive calibration scheme which is able to correct inter - path signal mismatches in phase, amplitude and latency. this facilitates precise control of the uplink and downlink rf beam pattern and avoids distortion effects that occur in the absence of calibration. = = = multiple sub - sector path processing = = = by dividing the cell sector into a number of sub - sector beams, wsdma provides the network with spatially filtered signals, maximising link budget through improved antenna gain and interference mitigation. this allows for mobile users in the cell to reduce their uplink power transmission, thereby further reducing interference and minimising both base station and ue power consumption. wsdma provides simultaneous sector - wide and sub - sector beam processing to improve link performance in multipath environments. sub - sector beam processing can optimise changing user demographics within the cell sector. = = = downlink wsdma = = = downlink wsdma provides an optimised rf beam pattern, reducing interference in overlap regions of adjacent cell sectors. long term statistical based adjustment can optimise cell patterns depending on the user population density per spatial region serviced by the cell. = = see also = = wcdma ofdm smart antennas beamforming 3g mimo = = references = = " beamforming : a versatile approach to spatial filtering " b. d. v. veen and k. m. buckley..
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also = = wcdma ofdm smart antennas beamforming 3g mimo = = references = = " beamforming : a versatile approach to spatial filtering " b. d. v. veen and k. m. buckley.. ieee assp magazine, apr. 1988. w - cdma and cdma2000 for 3g mobile networks. m. r. karim, m. sarraf l. lengierand r. farrell. amplitude and phase mismatch calibration testbed for 2x2 tower - top antenna array system. china - ireland conference on information and communications technologies 2007.
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supply - chain sustainability is the management of environmental, social and economic impacts and the encouragement of good governance practices, throughout the lifecycles of goods and services. there is a growing need for integrating sustainable choices into supply - chain management. an increasing concern for sustainability is transforming how companies approach business. whether motivated by their customers, corporate values or business opportunity, traditional priorities such as quality, efficiency and cost regularly compete for attention with concerns such as working conditions and environmental impact. a sustainable supply chain seizes value chain opportunities and offers significant competitive advantages for early adopters and process innovators. = = background = = supply chains are critical links that connect an organization ’ s inputs to its outputs. traditional challenges have included lowering costs, ensuring just - in - time delivery, and shrinking transportation times to allow better reaction to business challenges. however, the increasing environmental, social and economic costs of these networks and growing consumer pressure for eco - friendly products has led many organizations to look at supply chain sustainability as a new measure of profitable logistics management. this shift is reflected by an understanding that sustainable supply chains mean profitable supply chains. many companies are limited to measuring the sustainability of their own business operations and are unable to extend this evaluation to their suppliers and customers. this makes determining their true environmental and social costs highly challenging. however much progress has been made in defining supply chain sustainability and benchmarking tools are now available that enable sustainability action plans to be developed and implemented. a study conducted in 2017 researched the correlation between supply chain position ( how close or far the firm is from the end user in the supply chain ) and firm performance. the study findings concluded that suppliers located farther upstream in the supply chain ( farther from the end user ), had the most to gain financially from sustainable supply chain management. = = = environmental impact = = = climate change poses a new risk to supply chains and a need to increase their resilience. as companies are setting carbon footprint targets, suppliers ’ operations are responsible for 65 % to 95 % of a company ’ s total emissions. these environmental impacts are evident across industries, for example, food and beverage companies are particularly vulnerable to the impacts of climate change as changing weather patterns can disrupt agricultural production. measuring supply chain resilience on factors such as natural resource availability, infrastructure, financial resources, and social safety networks among others, can help them respond to challenges and create better supply chains in the process. = = = social impact = = = besides sustainability and resilience, an ethical supply chain is imperative to ensure corporate social responsibility
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resources, and social safety networks among others, can help them respond to challenges and create better supply chains in the process. = = = social impact = = = besides sustainability and resilience, an ethical supply chain is imperative to ensure corporate social responsibility and adhere to a supplier code of conduct. the work environment for the workers should be congenial and must not violate the basic human rights. for instance, companies like nike and apple, which outsource manufacturing of their products to other countries like china, have been under the scanner for workplace conditions and wages of their workers. consumers increasingly demand transparency and traceability in supply chains, especially where disturbing social breakdowns occur, such as with forced labour and child labour for globally traded goods. forced labor, understood as work that is performed involuntarily or under coercion, occurs in different industries, often upstream in the supply chain with limited visibility to buyers, customers, and end - users. for example, in the united states, the 2010 dodd – frank wall street reform and consumer protection act requires manufacturers to audit their supply chains and report use of conflict minerals to the securities and exchange commission. = = = governance impact = = = governance practices in global supply chains can pose risks to supply chain sustainability, alongside social and environmental factors. governance factors include guidelines and procedures for countries and corporations. buyers screen their supply chains for appropriate governance practices such as a company ’ s purpose, the role and makeup of boards of directors, shareholder rights and how corporate performance is measured. = = = stakeholders = = = the purchasing power held by buyers, gives them significant influence over their vendors or suppliers ’ business practices. companies in the role of buyers acquire goods or services through organizational functions such as purchasing, procurement, or sourcing, typically for use or consumption in their own organization. suppliers or vendors typically sell their goods or services to the next link in the supply chain. buyers might thus interface with only one tier of their suppliers, while their supply chain spans across complex tiers of suppliers upstream. progress has been made in the sustainable procurement space as companies help suppliers design and implement sustainability programs that directly support the companies ’ own goals. buyers are working to achieve sustainability goals by setting standards for their suppliers ’ performance and treating sustainability performance similar to other business considerations such as cost, quality, and timeliness. one of the key requirements of successful sustainable supply chains is collaboration. the practice of collaboration — such as sharing distribution to reduce waste by ensuring that half - empty vehicles do not get sent out and that deliveries to the
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cost, quality, and timeliness. one of the key requirements of successful sustainable supply chains is collaboration. the practice of collaboration — such as sharing distribution to reduce waste by ensuring that half - empty vehicles do not get sent out and that deliveries to the same address are on the same truck — is not widespread because many companies fear a loss of commercial control by working with others. investment in alternative modes of transportation — such as use of canals and airships — can play an important role in helping companies reduce the cost and environmental impact of their deliveries. = = drivers for supply chain sustainability = = as of 2021, a growing number of companies see supply chain sustainability as a strategic business matter. a business strategy for supply chain environmental performance can deliver measurable environmental benefits for the company and its stakeholders. a sustainable sourcing strategy positions the company for increasing demands of higher disclosure and investor scrutiny, more environmentally focused consumers, and scarce resources. sustainable procurement is a key concern for investors, through movements such as socially responsible investing. leading investment firms such as blackrock use their influence to bring supply chain sustainability on the agenda. customers and consumers also demand supply chain responsibility and sustainability as part of a company ’ s value proposition under a growing ethical consumerism movement. consumers ’ purchasing behaviors reflect this trend as 70 % say they are willing to pay a 5 % price premium for products produced by more - sustainable means. during global supply chain disruptions following the covid - 19 pandemic, sustainable supply chains have been shown to be more resilient and have lower supplier risk. recent research in the indian manufacturing sector underscores the importance of sustainable innovation in supply chains, highlighting'financial availability for innovation'and'technical expertise availability and investment in r & d for green practices'as key factors. this study emphasizes the need for broader, empirical research to understand the evolving role of sustainable innovation in enhancing supply chain sustainability, especially in emerging economies. = = application of supply chain sustainability = = companies looking to implement sustainable strategies down its supply chain should also look upstream. to elaborate, if a company is able to choose between various suppliers, it can for example use its purchasing power to get its suppliers in compliance with its green supply chain standards. in managing suppliers, companies must measure that inputs from suppliers are of high quality, and the usage of water and energy is minimized leading to less pollution, defects and over production. they also must audit their supplier base and make sure that they are improving the supply chain metrics additionally, fostering collaborative partnerships with suppliers to promote transparency and
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the usage of water and energy is minimized leading to less pollution, defects and over production. they also must audit their supplier base and make sure that they are improving the supply chain metrics additionally, fostering collaborative partnerships with suppliers to promote transparency and innovation can further enhance sustainability efforts throughout the supply chain. when measuring sustainability in supply chains, consistent measurements which can be replicated and compared are crucial to encourage consumer trust. environmental and social change often takes time to measure and must be considered by private companies or governments over a long term period to accurately assess the results. some companies utilize supplier scorecards to determine suppliers ’ sustainability performance. this can be accomplished by conducting life - cycle assessments or surveys to help determine their sustainability practices. another strategy is to award suppliers for their improvement on their sustainability performance, for instance, by developing new materials sourced from waste or by making operations more energy efficient. = = = software = = = digital technology has increased companies ’ capability to collaborate with large numbers of suppliers. as supply - chain sustainability becomes a more critical business issue, the need for reliable and robust data from suppliers increases. whilst some existing business systems can collect some sustainability data, most large businesses will look to dedicated software providers for more specific sustainability functionality. in order for businesses to determine the degree of sustainability impact of their business model, they must have the data to support it. harvard business school created the impact - weighted accounts initiative ( iwai ) to assess the degree of impact that many large companies have on social, environmental, and economic areas. impact data comes from long term research on specific, measurable topics that can be applied to future changes within a company or system. impact data is often more sparse or inaccessible than it should be, which allows institutions such as hbs to hold companies accountable in their supply chains and encourage greater transparency. transparency in the supply chain influences how consumers view and support companies, so improving data driven sustainability efforts can positively affect supply chain business. a company ’ s negative impact on environmental or social areas may show in their stock market value, exposing their true values to investors. while impact data is probably one of the better ways of assessing a company ’ s long term impacts, it is important to note that data collection for impact assessment is a lengthy process and not all companies can spend long periods of time measuring their impact without making changes. because of this, simple, credible alternatives to long term impact assessments are necessary for some businesses. = = = on - site audits = = = in addition to digital tools, on - site audits can
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time measuring their impact without making changes. because of this, simple, credible alternatives to long term impact assessments are necessary for some businesses. = = = on - site audits = = = in addition to digital tools, on - site audits can be an effective tool to verify social and environmental compliance at supplier sites. on - site audits can certify a supplier ’ s compliance with an external standard, such as sa8000, iso 14001, smeta 4 - pillar, and others. audits can also assess compliance with internal policies and guidelines set by a business partner, for example through a supplier code of conduct. depending on the auditing standard, buyers might choose to audit their suppliers directly, or send auditors from a third - party auditing firm to supplier sites. = = challenges in achieving supply chain sustainability goals = = despite companies being increasingly focused on working with suppliers that help them achieve their sustainability goals, challenges continue to persist. suppliers further up the supply chain generally lack the maturity, tools, and capabilities to manage and drive environmental and social improvements. when faced with workplace issues such as sexual harassment, retaliation by superiors, and a hazardous environment, lower tiered suppliers typically have a poor response plan, or no plan at all. in cases where a plan is established, suppliers are unable to implement it and train their employees accordingly due to a workforce consisting of nearly 50 % temporary workers. as you move further upstream in the supply chain, a company loses more oversight over suppliers. companies do not directly operate with lower tiered suppliers, and there is generally no contractual relationship in place between the two. this makes it increasingly difficult for companies to manage sustainability upstream. additionally, lower tiered suppliers operate in relative obscurity compared to the companies they supply, so they tend not to face the same level of scrutiny if failing to meet sustainability standards. many companies have thousands of suppliers, making it difficult for those in charge of driving supply chain sustainability to know where to begin and focus their efforts. they may not have access to the right data or may lack the authority to effect real change. additionally, in striving to be more socially responsible, a company can inadvertently make it harder for smaller, diverse suppliers to compete with the larger, more established ones. generally, the larger suppliers are better equipped to drive sustainability improvements compared with smaller ones. in rewarding the larger suppliers with larger contracts and reducing business or even severing ties with the smaller ones to achieve sustainability goals, companies make their supplier base less diverse and put the smaller
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are better equipped to drive sustainability improvements compared with smaller ones. in rewarding the larger suppliers with larger contracts and reducing business or even severing ties with the smaller ones to achieve sustainability goals, companies make their supplier base less diverse and put the smaller suppliers at a disadvantage. = = see also = = fair stone standard sustainable procurement = = references = =
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in computer science, graph traversal ( also known as graph search ) refers to the process of visiting ( checking and / or updating ) each vertex in a graph. such traversals are classified by the order in which the vertices are visited. tree traversal is a special case of graph traversal. = = redundancy = = unlike tree traversal, graph traversal may require that some vertices be visited more than once, since it is not necessarily known before transitioning to a vertex that it has already been explored. as graphs become more dense, this redundancy becomes more prevalent, causing computation time to increase ; as graphs become more sparse, the opposite holds true. thus, it is usually necessary to remember which vertices have already been explored by the algorithm, so that vertices are revisited as infrequently as possible ( or in the worst case, to prevent the traversal from continuing indefinitely ). this may be accomplished by associating each vertex of the graph with a " color " or " visitation " state during the traversal, which is then checked and updated as the algorithm visits each vertex. if the vertex has already been visited, it is ignored and the path is pursued no further ; otherwise, the algorithm checks / updates the vertex and continues down its current path. several special cases of graphs imply the visitation of other vertices in their structure, and thus do not require that visitation be explicitly recorded during the traversal. an important example of this is a tree : during a traversal it may be assumed that all " ancestor " vertices of the current vertex ( and others depending on the algorithm ) have already been visited. both the depth - first and breadth - first graph searches are adaptations of tree - based algorithms, distinguished primarily by the lack of a structurally determined " root " vertex and the addition of a data structure to record the traversal's visitation state. = = graph traversal algorithms = = note. — if each vertex in a graph is to be traversed by a tree - based algorithm ( such as dfs or bfs ), then the algorithm must be called at least once for each connected component of the graph. this is easily accomplished by iterating through all the vertices of the graph, performing the algorithm on each vertex that is still unvisited when examined. = = = depth - first search = = = a depth - first search ( dfs ) is an algorithm for traversing a finite graph. dfs visits the child vertices before visiting the sibling vertices ; that is, it traverse
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##ited when examined. = = = depth - first search = = = a depth - first search ( dfs ) is an algorithm for traversing a finite graph. dfs visits the child vertices before visiting the sibling vertices ; that is, it traverses the depth of any particular path before exploring its breadth. a stack ( often the program's call stack via recursion ) is generally used when implementing the algorithm. the algorithm begins with a chosen " root " vertex ; it then iteratively transitions from the current vertex to an adjacent, unvisited vertex, until it can no longer find an unexplored vertex to transition to from its current location. the algorithm then backtracks along previously visited vertices, until it finds a vertex connected to yet more uncharted territory. it will then proceed down the new path as it had before, backtracking as it encounters dead - ends, and ending only when the algorithm has backtracked past the original " root " vertex from the very first step. dfs is the basis for many graph - related algorithms, including topological sorts and planarity testing. = = = = pseudocode = = = = input : a graph g and a vertex v of g. output : a labeling of the edges in the connected component of v as discovery edges and back edges. procedure dfs ( g, v ) is label v as explored for all edges e in g. incidentedges ( v ) do if edge e is unexplored then w ← g. adjacentvertex ( v, e ) if vertex w is unexplored then label e as a discovered edge recursively call dfs ( g, w ) else label e as a back edge = = = breadth - first search = = = a breadth - first search ( bfs ) is another technique for traversing a finite graph. bfs visits the sibling vertices before visiting the child vertices, and a queue is used in the search process. this algorithm is often used to find the shortest path from one vertex to another. = = = = pseudocode = = = = input : a graph g and a vertex v of g. output : the closest vertex to v satisfying some conditions, or null if no such vertex exists. procedure bfs ( g, v ) is create a queue q enqueue v onto q mark v while q is not empty do w ← q. dequeue ( ) if w is what we are looking for then return w for all edges e in g.
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g, v ) is create a queue q enqueue v onto q mark v while q is not empty do w ← q. dequeue ( ) if w is what we are looking for then return w for all edges e in g. adjacentedges ( w ) do x ← g. adjacentvertex ( w, e ) if x is not marked then mark x enqueue x onto q return null = = applications = = breadth - first search can be used to solve many problems in graph theory, for example : finding all vertices within one connected component ; cheney's algorithm ; finding the shortest path between two vertices ; testing a graph for bipartiteness ; cuthill – mckee algorithm mesh numbering ; ford – fulkerson algorithm for computing the maximum flow in a flow network ; serialization / deserialization of a binary tree vs serialization in sorted order ( allows the tree to be re - constructed in an efficient manner ) ; maze generation algorithms ; flood fill algorithm for marking contiguous regions of a two dimensional image or n - dimensional array ; analysis of networks and relationships. = = graph exploration = = the problem of graph exploration can be seen as a variant of graph traversal. it is an online problem, meaning that the information about the graph is only revealed during the runtime of the algorithm. a common model is as follows : given a connected graph g = ( v, e ) with non - negative edge weights. the algorithm starts at some vertex, and knows all incident outgoing edges and the vertices at the end of these edges — but not more. when a new vertex is visited, then again all incident outgoing edges and the vertices at the end are known. the goal is to visit all n vertices and return to the starting vertex, but the sum of the weights of the tour should be as small as possible. the problem can also be understood as a specific version of the travelling salesman problem, where the salesman has to discover the graph on the go. for general graphs, the best known algorithms for both undirected and directed graphs is a simple greedy algorithm : in the undirected case, the greedy tour is at most o ( ln n ) - times longer than an optimal tour. the best lower bound known for any deterministic online algorithm is 10 / 3. unit weight undirected graphs can be explored with a competitive ration of 2 − ε, which is already a tight bound on tadpole graphs. in the directed case, the greedy tour is at most ( n − 1
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is 10 / 3. unit weight undirected graphs can be explored with a competitive ration of 2 − ε, which is already a tight bound on tadpole graphs. in the directed case, the greedy tour is at most ( n − 1 ) - times longer than an optimal tour. this matches the lower bound of n − 1. an analogous competitive lower bound of ω ( n ) also holds for randomized algorithms that know the coordinates of each node in a geometric embedding. if instead of visiting all nodes just a single " treasure " node has to be found, the competitive bounds are θ ( n2 ) on unit weight directed graphs, for both deterministic and randomized algorithms. = = universal traversal sequences = = a universal traversal sequence is a sequence of instructions comprising a graph traversal for any regular graph with a set number of vertices and for any starting vertex. a probabilistic proof was used by aleliunas et al. to show that there exists a universal traversal sequence with number of instructions proportional to o ( n5 ) for any regular graph with n vertices. the steps specified in the sequence are relative to the current node, not absolute. for example, if the current node is vj, and vj has d neighbors, then the traversal sequence will specify the next node to visit, vj + 1, as the ith neighbor of vj, where 1 ≤ i ≤ d. = = see also = = external memory graph traversal = = references = =
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attempto controlled english ( ace ) is a controlled natural language, i. e. a subset of standard english with a restricted syntax and restricted semantics described by a small set of construction and interpretation rules. it has been under development at the university of zurich since 1995. in 2013, ace version 6. 7 was announced. ace can serve as knowledge representation, specification, and query language, and is intended for professionals who want to use formal notations and formal methods, but may not be familiar with them. though ace appears perfectly natural — it can be read and understood by any speaker of english — it is in fact a formal language. ace and its related tools have been used in the fields of software specifications, theorem proving, proof assistants, text summaries, ontologies, rules, querying, medical documentation and planning. here are some simple examples : every woman is a human. a woman is a human. a man tries - on a new tie. if the tie pleases his wife then the man buys it. ace construction rules require that each noun be introduced by a determiner ( a, every, no, some, at least 5,... ). regarding the list of examples above, ace interpretation rules decide that ( 1 ) is interpreted as universally quantified, while ( 2 ) is interpreted as existentially quantified. sentences like " women are human " do not follow ace syntax and are consequently not valid. interpretation rules resolve the anaphoric references in ( 3 ) : the tie and it of the second sentence refer to a new tie of the first sentence, while his and the man of the second sentence refer to a man of the first sentence. thus an ace text is a coherent entity of anaphorically linked sentences. the attempto parsing engine ( ape ) translates ace texts unambiguously into discourse representation structures ( drs ) that use a variant of the language of first - order logic. a drs can be further translated into other formal languages, for instance acerules with various semantics, owl, and swrl. translating an ace text into ( a fragment of ) first - order logic allows users to reason about the text, for instance to verify, to validate, and to query it. = = overview = = as an overview of the current version 6. 6 of ace this section : briefly describes the vocabulary gives an account of the syntax summarises the handling of ambiguity explains the processing of anaphoric references. = = = vocabulary = = = the
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= as an overview of the current version 6. 6 of ace this section : briefly describes the vocabulary gives an account of the syntax summarises the handling of ambiguity explains the processing of anaphoric references. = = = vocabulary = = = the vocabulary of ace comprises : predefined function words ( e. g. determiners, conjunctions ) predefined phrases ( e. g. " it is false that... ", " it is possible that... " ) content words ( e. g. nouns, verbs, adjectives, adverbs ). = = = grammar = = = the grammar of ace defines and constrains the form and the meaning of ace sentences and texts. ace's grammar is expressed as a set of construction rules. the meaning of sentences is described as a small set of interpretation rules. a troubleshooting guide describes how to use ace and how to avoid pitfalls. = = = = ace texts = = = = an ace text is a sequence of declarative sentences that can be anaphorically interrelated. furthermore, ace supports questions and commands. = = = = simple sentences = = = = a simple sentence asserts that something is the case — a fact, an event, a state. the temperature is −2 °c. a customer inserts 2 cards. a card and a code are valid. simple ace sentences have the following general structure : subject + verb + complements + adjuncts every sentence has a subject and a verb. complements ( direct and indirect objects ) are necessary for transitive verbs ( insert something ) and ditransitive verbs ( give something to somebody ), whereas adjuncts ( adverbs, prepositional phrases ) are optional. all elements of a simple sentence can be elaborated upon to describe the situation in more detail. to further specify the nouns customer and card, we could add adjectives : a trusted customer inserts two valid cards. possessive nouns and of - prepositional phrases : john's customer inserts a card of mary. or variables as appositions : john inserts a card a. other modifications of nouns are possible through relative sentences : a customer who is trusted inserts a card that he owns. which are described below since they make a sentence composite. we can also detail the insertion event, e. g. by adding an adverb : a customer inserts some cards manually. or, equivalently : a customer manually inserts some cards. or, by adding
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they make a sentence composite. we can also detail the insertion event, e. g. by adding an adverb : a customer inserts some cards manually. or, equivalently : a customer manually inserts some cards. or, by adding prepositional phrases : a customer inserts some cards into a slot. we can combine all of these elaborations to arrive at : john's customer who is trusted inserts a valid card of mary manually into a slot a. = = = = composite sentences = = = = composite sentences are recursively built from simpler sentences through coordination, subordination, quantification, and negation. note that ace composite sentences overlap with what linguists call compound sentences and complex sentences. = = = = = coordination = = = = = coordination by and is possible between sentences and between phrases of the same syntactic type. a customer inserts a card and the machine checks the code. there is a customer who inserts a card and who enters a code. a customer inserts a card and enters a code. an old and trusted customer enters a card and a code. note that the coordination of the noun phrases a card and a code represents a plural object. coordination by or is possible between sentences, verb phrases, and relative clauses. a customer inserts a card or the machine checks the code. a customer inserts a card or enters a code. a customer owns a card that is invalid or that is damaged. coordination by and and or is governed by the standard binding order of logic, i. e. and binds stronger than or. commas can be used to override the standard binding order. thus the sentence : a customer inserts a visacard or inserts a mastercard, and inserts a code. means that the customer inserts a visacard and a code, or alternatively a mastercard and a code. = = = = = subordination = = = = = there are four constructs of subordination : relative sentences, if - then sentences, modality, and sentence subordination. relative sentences starting with who, which, and that allow to add detail to nouns : a customer who is trusted inserts a card that he owns. with the help of if - then sentences we can specify conditional or hypothetical situations : if a card is valid then a customer inserts it. note the anaphoric reference via the pronoun it in the then - part to the noun phrase a card in the if - part.
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sentences we can specify conditional or hypothetical situations : if a card is valid then a customer inserts it. note the anaphoric reference via the pronoun it in the then - part to the noun phrase a card in the if - part. modality allows us to express possibility and necessity : a trusted customer can / must insert a card. it is possible / necessary that a trusted customer inserts a card. sentence subordination comes in various forms : it is true / false that a customer inserts a card. it is not provable that a customer inserts a card. a clerk believes that a customer inserts a card. = = = = = quantification = = = = = quantification allows us to speak about all objects of a certain class ( universal quantification ), or to denote explicitly the existence of at least one object of this class ( existential quantification ). the textual occurrence of a universal or existential quantifier opens its scope that extends to the end of the sentence, or in coordinations to the end of the respective coordinated sentence. to express that all involved customers insert cards we can write every customer inserts a card. this sentence means that each customer inserts a card that may, or may not, be the same as the one inserted by another customer. to specify that all customers insert the same card — however unrealistic that situation seems — we can write : a card is inserted by every customer. or, equivalently : there is a card that every customer inserts. to state that every card is inserted by a customer we write : every card is inserted by a customer. or, somewhat indirectly : for every card there is a customer who inserts it. = = = = = negation = = = = = negation allows us to express that something is not the case : a customer does not insert a card. a card is not valid. to negate something for all objects of a certain class one uses no : no customer inserts more than 2 cards. or, there is no : there is no customer who inserts a card. to negate a complete statement one uses sentence negation : it is false that a customer inserts a card. these forms of negation are logical negations, i. e. they state that something is provably not the case. negation as failure states that a state of affairs cannot be proved, i. e. there is no information whether the state of affairs is the case
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negations, i. e. they state that something is provably not the case. negation as failure states that a state of affairs cannot be proved, i. e. there is no information whether the state of affairs is the case or not. it is not provable that a customer inserts a card. = = = = queries = = = = ace supports two forms of queries : yes / no - queries and wh - queries. yes / no - queries ask for the existence or non - existence of a specified situation. if we specified : a customer inserts a card. then we can ask : does a customer insert a card? to get a positive answer. note that interrogative sentences always end with a question mark. with the help of wh - queries, i. e. queries with query words, we can interrogate a text for details of the specified situation. if we specified : a trusted customer inserts a valid card manually in the morning in a bank. we can ask for each element of the sentence with the exception of the verb. who inserts a card? which customer inserts a card? what does a customer insert? how does a customer insert a card? when does a customer enter a card? where does a customer enter a card? queries can also be constructed by a sequence of declarative sentences followed by one interrogative sentence, for example : there is a customer and there is a card that the customer enters. does a customer enter a card? = = = = commands = = = = ace also supports commands. some examples : john, go to the bank! john and mary, wait! every dog, bark! a brother of john, give a book to mary! a command always consists of a noun phrase ( the addressee ), followed by a comma, followed by an uncoordinated verb phrase. furthermore, a command has to end with an exclamation mark. = = = constraining ambiguity = = = to constrain the ambiguity of full natural language ace employs three simple means : some ambiguous constructs are not part of the language ; unambiguous alternatives are available in their place. all remaining ambiguous constructs are interpreted deterministically on the basis of a small number of interpretation rules. users can either accept the assigned interpretation, or they must rephrase the input to obtain another one. = = = = avoidance of ambiguity = = = = in natural language
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deterministically on the basis of a small number of interpretation rules. users can either accept the assigned interpretation, or they must rephrase the input to obtain another one. = = = = avoidance of ambiguity = = = = in natural language, relative sentences combined with coordinations can introduce ambiguity : a customer inserts a card that is valid and opens an account. in ace the sentence has the unequivocal meaning that the customer opens an account, as reflected by the paraphrase : a card is valid. a customer inserts the card. the customer opens an account. to express the alternative — though not very realistic — meaning that the card opens an account, the relative pronoun that must be repeated, thus yielding a coordination of relative sentences : a customer inserts a card that is valid and that opens an account. this sentence is unambiguously equivalent in meaning to the paraphrase : a card is valid. the card opens an account. a customer inserts the card. = = = = interpretation rules = = = = not all ambiguities can be safely removed from ace without rendering it artificial. to deterministically interpret otherwise syntactically correct ace sentences we use a small set of interpretation rules. for example, if we write : a customer inserts a card with a code. then with a code attaches to the verb inserts, but not to a card. however, this is probably not what we meant to say. to express that the code is associated with the card we can employ the interpretation rule that a relative sentence always modifies the immediately preceding noun phrase, and rephrase the input as : a customer inserts a card that carries a code. yielding the paraphrase : a card carries a code. a customer inserts the card. or — to specify that the customer inserts a card and a code — as : a customer inserts a card and a code. = = = anaphoric references = = = usually ace texts consist of more than one sentence : a customer enters a card and a code. if a code is valid then simplemat accepts a card. to express that all occurrences of card and code should mean the same card and the same code, ace provides anaphoric references via the definite article : a customer enters a card and a code. if the code is valid then simplemat accepts the card. during the processing of the ace text, all anaphoric references are replaced by the most recent and most specific accessible noun phrase
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the definite article : a customer enters a card and a code. if the code is valid then simplemat accepts the card. during the processing of the ace text, all anaphoric references are replaced by the most recent and most specific accessible noun phrase that agrees in gender and number. as an example of " most recent and most specific ", suppose an ace parser is given the sentence : a customer enters a red card and a blue card. then : the card is correct. refers to the second card, while : the red card is correct. refers to the first card. noun phrases within if - then sentences, universally quantified sentences, negations, modality, and subordinated sentences cannot be referred to anaphorically from subsequent sentences, i. e. such noun phrases are not " accessible " from the following text. thus for each of the sentences : if a customer owns a card then he enters it. every customer enters a card. a customer does not enter a card. a customer can enter a card. a clerk believes that a customer enters a card. we cannot refer to a card with : the card is correct. anaphoric references are also possible via personal pronouns : a customer enters a card and a code. if it is valid then simplemat accepts the card. or via variables : a customer enters a card x and a code y. if y is valid then simplemat accepts x. anaphoric references via definite articles and variables can be combined : a customer enters a card x and a code y. if the code y is valid then simplemat accepts the card x. note that proper names like simplemat always refer to the same object. = = see also = = gellish natural language processing natural language programming structured english cleartalk, another machine - readable knowledge representation language inform 7, a programming language with english syntax = = references = = = = external links = = official website, project attempto
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boiling - point elevation is the phenomenon whereby the boiling point of a liquid ( a solvent ) will be higher when another compound is added, meaning that a solution has a higher boiling point than a pure solvent. this happens whenever a non - volatile solute, such as a salt, is added to a pure solvent, such as water. the boiling point can be measured accurately using an ebullioscope. = = explanation = = the boiling point elevation is a colligative property, which means that boiling point elevation is dependent on the number of dissolved particles but not their identity. it is an effect of the dilution of the solvent in the presence of a solute. it is a phenomenon that happens for all solutes in all solutions, even in ideal solutions, and does not depend on any specific solute – solvent interactions. the boiling point elevation happens both when the solute is an electrolyte, such as various salts, and a nonelectrolyte. in thermodynamic terms, the origin of the boiling point elevation is entropic and can be explained in terms of the vapor pressure or chemical potential of the solvent. in both cases, the explanation depends on the fact that many solutes are only present in the liquid phase and do not enter into the gas phase ( except at extremely high temperatures ). the vapor pressure affects the solute shown by raoult's law while the free energy change and chemical potential are shown by gibbs free energy. most solutes remain in the liquid phase and do not enter the gas phase, except at very high temperatures. in terms of vapor pressure, a liquid boils when its vapor pressure equals the surrounding pressure. a nonvolatile solute lowers the solvent ’ s vapor pressure, meaning a higher temperature is needed for the vapor pressure to equalize the surrounding pressure, causing the boiling point to elevate. in terms of chemical potential, at the boiling point, the liquid and gas phases have the same chemical potential. adding a nonvolatile solute lowers the solvent ’ s chemical potential in the liquid phase, but the gas phase remains unaffected. this shifts the equilibrium between phases to a higher temperature, elevating the boiling point. = = relationship between freezing - point depression = = freezing - point depression is analogous to boiling point elevation, though the magnitude of freezing - point depression is higher for the same solvent and solute concentration. these phenomena extend the liquid range of a solvent in the presence of a solute. = = related
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freezing - point depression is analogous to boiling point elevation, though the magnitude of freezing - point depression is higher for the same solvent and solute concentration. these phenomena extend the liquid range of a solvent in the presence of a solute. = = related equations for calculating boiling point = = the extent of boiling - point elevation can be calculated by applying clausius – clapeyron relation and raoult's law together with the assumption of the non - volatility of the solute. the result is that in dilute ideal solutions, the extent of boiling - point elevation is directly proportional to the molal concentration ( amount of substance per mass ) of the solution according to the equation : δtb = kb · bc where the boiling point elevation, is defined as tb ( solution ) − tb ( pure solvent ). kb, the ebullioscopic constant, which is dependent on the properties of the solvent. it can be calculated as kb = rtb2m / δhv, where r is the gas constant, and tb is the boiling temperature of the pure solvent [ in k ], m is the molar mass of the solvent, and δhv is the heat of vaporization per mole of the solvent. bc is the colligative molality, calculated by taking dissociation into account since the boiling point elevation is a colligative property, dependent on the number of particles in solution. this is most easily done by using the van't hoff factor i as bc = bsolute · i, where bsolute is the molality of the solution. the factor i accounts for the number of individual particles ( typically ions ) formed by a compound in solution. examples : i = 1 for sugar in water i = 1. 9 for sodium chloride in water, due to the near full dissociation of nacl into na + and cl− ( often simplified as 2 ) i = 2. 3 for calcium chloride in water, due to nearly full dissociation of cacl2 into ca2 + and 2cl− ( often simplified as 3 ) non integer i factors result from ion pairs in solution, which lower the effective number of particles in the solution. equation after including the van't hoff factor δtb = kb · bsolute · i the above formula reduces precision at high concentrations, due to nonideality of the solution. if the solute is volatile, one of the key assumptions used in deriving the formula is not true because the equation derived is
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· bsolute · i the above formula reduces precision at high concentrations, due to nonideality of the solution. if the solute is volatile, one of the key assumptions used in deriving the formula is not true because the equation derived is for solutions of non - volatile solutes in a volatile solvent. in the case of volatile solutes, the equation can represent a mixture of volatile compounds more accurately, and the effect of the solute on the boiling point must be determined from the phase diagram of the mixture. in such cases, the mixture can sometimes have a lower boiling point than either of the pure components ; a mixture with a minimum boiling point is a type of azeotrope. = = = ebullioscopic constants = = = values of the ebullioscopic constants kb for selected solvents : = = uses = = together with the formula above, the boiling - point elevation can be used to measure the degree of dissociation or the molar mass of the solute. this kind of measurement is called ebullioscopy ( latin - greek " boiling - viewing " ). however, superheating is a factor that can affect the precision of the measurement and would be challenging to avoid because of the decrease in molecular mobility. therefore, δtb would be hard to measure precisely even though superheating can be partially overcome by the invention of the beckmann thermometer. in reality, cryoscopy is used more often because the freezing point is often easier to measure with precision. = = see also = = colligative properties freezing - point depression duhring's rule list of boiling and freezing information of solvents = = references = =
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