114-480: Sarin ( NATO designation GB [short for G-series , "B"]) is an extremely toxic organophosphorus compound . A colourless, odourless liquid , it is used as a chemical weapon due to its extreme potency as a nerve agent . Exposure can be lethal even at very low concentrations, where death can occur within one to ten minutes after direct inhalation of a lethal dose, due to suffocation from respiratory paralysis, unless antidotes are quickly administered. People who absorb
228-497: A covalent bond with the particular serine residue at the active site. Fluoride is the leaving group , and the resulting organo-phosphoester is robust and biologically inactive . Its mechanism of action resembles that of some commonly used insecticides , such as malathion . In terms of biological activity, it resembles carbamate insecticides, such as Sevin , and the medicines pyridostigmine , neostigmine , and physostigmine . Controlled studies in healthy men have shown that
342-524: A confrontation between US Defense Secretary Robert Gates and countries such as Poland, Spain, the Netherlands, Turkey, and Germany with Gates calling on the latter to contribute more and the latter believing the organization has overstepped its mandate in the conflict. In his final policy speech in Brussels on 10 June, Gates further criticized allied countries in suggesting their actions could cause
456-488: A delay ranging from hours to several weeks, in cases where exposure is limited but no antidote is applied. Sarin has a high volatility (ease with which a liquid can turn into vapour) relative to similar nerve agents, making inhalation very easy, and may even absorb through the skin. A person's clothing can release sarin for about 30 minutes after it has come in contact with sarin gas, which can lead to exposure of other people. Treatment measures have been described. Treatment
570-500: A direct comparison to the respiratory LCt 50 : Sarin is a chiral molecule because it has four chemically distinct substituents attached to the tetrahedral phosphorus center. The S P form (the (–) optical isomer ) is the more active enantiomer due to its greater binding affinity to acetylcholinesterase . The P-F bond is easily broken by nucleophilic agents, such as water and hydroxide. At high p H , sarin decomposes rapidly to nontoxic phosphonic acid derivatives. It
684-436: A gorge leading to the active site. All 14 amino acids in the aromatic gorge are highly conserved across different species. Among the aromatic amino acids, tryptophan 84 is critical and its substitution with alanine results in a 3000-fold decrease in reactivity. The gorge is approximately 20 angstroms deep and five angstroms wide. The esteratic subsite, where acetylcholine is hydrolyzed to acetate and choline, contains
798-460: A longer period after exposure than the methods described above. Fluoride reactivation is a technique that has been explored since at least the early 2000s. This technique obviates some of the deficiencies of older procedures. Sarin not only reacts with the water in the blood plasma through hydrolysis (forming so-called 'free metabolites'), but also reacts with various proteins to form 'protein adducts'. These protein adducts are not so easily removed from
912-561: A major reform of France's military position, culminating with the return to full membership on 4 April 2009, which also included France rejoining the NATO Military Command Structure , while maintaining an independent nuclear deterrent. The 2014 Russian annexation of Crimea led to strong condemnation by all NATO members, and was one of the seven times that Article 4 , which calls for consultation among NATO members, has been invoked. Prior times included during
1026-631: A no-fly zone over Libya shortly afterwards, beginning with Opération Harmattan by the French Air Force on 19 March. On 20 March 2011, NATO states agreed on enforcing an arms embargo against Libya with Operation Unified Protector using ships from NATO Standing Maritime Group 1 and Standing Mine Countermeasures Group 1 , and additional ships and submarines from NATO members. They would "monitor, report and, if needed, interdict vessels suspected of carrying illegal arms or mercenaries ". On 24 March, NATO agreed to take control of
1140-506: A non-lethal dose and do not receive immediate medical treatment may suffer permanent neurological damage. Sarin is widely considered a weapon of mass destruction . Production and stockpiling of sarin was outlawed as of April 1997 by the Chemical Weapons Convention of 1993, and it is classified as a Schedule 1 substance . Like some other nerve agents that affect the neurotransmitter acetylcholine , sarin attacks
1254-587: A nontoxic 0.43 mg oral dose administered in several portions over a 3-day interval caused average maximum depressions of 22 and 30%, respectively, in plasma and erythrocyte acetylcholinesterase levels. A single acute 0.5 mg dose caused mild symptoms of intoxication and an average reduction of 38% in both measures of acetylcholinesterase activity. Sarin in blood is rapidly degraded either in vivo or in vitro . Its primary inactive metabolites have in vivo serum half-lives of approximately 24 hours. The serum level of unbound isopropyl methylphosphonic acid (IMPA),
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#17327723624761368-759: A peaceful German reunification. A June 2016 Levada Center poll found that 68 percent of Russians think that deploying NATO troops in the Baltic states and Poland – former Eastern bloc countries bordering Russia – is a threat to Russia. In contrast, 65 percent of Poles surveyed in a 2017 Pew Research Center report identified Russia as a "major threat", with an average of 31 percent saying so across all NATO countries, and 67 percent of Poles surveyed in 2018 favour US forces being based in Poland. Of non- CIS Eastern European countries surveyed by Gallup in 2016, all but Serbia and Montenegro were more likely than not to view NATO as
1482-527: A protective alliance rather than a threat. A 2006 study in the journal Security Studies argued that NATO enlargement contributed to democratic consolidation in Central and Eastern Europe. China also opposes further expansion. Member states pay for NATO's three common funds (the civil and military budgets and the security investment programme) based on a cost-sharing formula that includes per capita gross national income and other factors. In 2023–2024,
1596-511: A quick-reaction force was deployed to the area. The Bosnian War began in 1992, as a result of the breakup of Yugoslavia . The deteriorating situation led to United Nations Security Council Resolution 816 on 9 October 1992, authorizing its member-states to enforce a previously declared no-fly zone under the United Nations Protection Force over central Bosnia and Herzegovina. NATO complied and started enforcing
1710-922: A red line . However, there were no such plans to deploy missiles in Ukraine. The Russian Foreign Ministry drafted a treaty that would forbid Ukraine or any former Soviet state from ever joining NATO. Secretary-General Stoltenberg replied that the decision is up to Ukraine and NATO members, adding "Russia has no veto, Russia has no say, and Russia has no right to establish a sphere of influence to try to control their neighbors". NATO offered to improve communications with Russia and discuss missile placements and military exercises, as long as Russia withdrew troops from Ukraine's borders. Instead, Russia invaded Ukraine in February 2022. Ukraine applied for NATO membership in September 2022 after Russia proclaimed it had annexed
1824-425: A sarin hydrolysis product, ranged from 2–135 μg/L in survivors of a terrorist attack during the first four hours post-exposure. Sarin or its metabolites may be determined in blood or urine by gas or liquid chromatography , while acetylcholinesterase activity is usually measured by enzymatic methods. A newer method called "fluoride regeneration" or "fluoride reactivation" detects the presence of nerve agents for
1938-430: A short shelf life. Therefore, it is usually stored as two separate precursors that produce sarin when combined. Sarin's shelf life can be extended by increasing the purity of the precursor and intermediates and incorporating stabilizers such as tributylamine . In some formulations, tributylamine is replaced by diisopropylcarbodiimide (DIC), allowing sarin to be stored in aluminium casings. In binary chemical weapons ,
2052-744: A strategic re-evaluation of NATO's purpose, nature, tasks, and focus on the continent. In October 1990, East Germany became part of the Federal Republic of Germany and the alliance, and in November 1990, the alliance signed the Treaty on Conventional Armed Forces in Europe (CFE) in Paris with the Soviet Union. It mandated specific military reductions across the continent, which continued after
2166-426: A study on Solanum lycopersicum (tomato) identified 87 SlAChE genes containing GDSL lipase/acylhydrolase domain. The study also showed up-and down-regulation of SlAChE genes under salinity stress condition. Some marine fungi have been found to produce compounds that inhibit AChE. However, the specific role and mechanisms of AChE in fungi are not as well-studied as in mammals. The presence and role of AChE in bacteria
2280-472: A synthetic acetylcholine antagonist , has been suggested as an alternative to atropine due to its better blood–brain barrier penetration and higher efficacy. Sarin is a potent inhibitor of acetylcholinesterase , an enzyme that degrades the neurotransmitter acetylcholine after it is released into the synaptic cleft . In vertebrates, acetylcholine is the neurotransmitter used at the neuromuscular junction, where signals are transmitted between neurons from
2394-509: A weapon). IMPA then degrades into methylphosphonic acid (MPA), which can also be produced by other organophosphates. Sarin with residual acid degrades after a period of several weeks to several months. The shelf life can be shortened by impurities in precursor materials . According to the CIA , some Iraqi sarin had a shelf life of only a few weeks, owing mostly to impure precursors. Along with nerve agents such as tabun and VX , sarin can have
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#17327723624762508-506: Is Mir-132 microRNA , which may limit inflammation in the brain by silencing the expression of this protein and allowing ACh to act in an anti-inflammatory capacity. It has also been shown that the main active ingredient in cannabis, tetrahydrocannabinol , is a competitive inhibitor of acetylcholinesterase. AChE is found in many types of conducting tissue: nerve and muscle, central and peripheral tissues, motor and sensory fibers, and cholinergic and noncholinergic fibers. The activity of AChE
2622-408: Is 172 μg/kg. Sarin is highly toxic, whether by contact with the skin or breathed in. The toxicity of sarin in humans is largely based on calculations from studies with animals. The lethal concentration of sarin in air is approximately 28–35 mg per cubic meter per minute for a two-minute exposure time by a healthy adult breathing normally (exchanging 15 liters of air per minute, lower 28 mg/m value
2736-424: Is almost always manufactured as a racemic mixture (a 1:1 mixture of its enantiomeric forms) as this involves a much simpler synthesis while providing an adequate weapon. A number of production pathways can be used to create sarin. The final reaction typically involves attachment of the isopropoxy group to the phosphorus with an alcoholysis with isopropyl alcohol . Two variants of this final step are common. One
2850-584: Is encoded by a single AChE gene while some invertebrates have multiple acetylcholinesterase genes. Note higher vertebrates also encode a closely related paralog BCHE (butyrylcholinesterase) with 50% amino acid identity to ACHE. Diversity in the transcribed products from the sole mammalian gene arises from alternative mRNA splicing and post-translational associations of catalytic and structural subunits. There are three known forms: T (tail), R (read through), and H (hydrophobic). The major form of acetylcholinesterase found in brain, muscle, and other tissues, known as
2964-707: Is for general population). This number represents the estimated lethal concentration for 50% of exposed victims, the LCt 50 value. The LCt 95 or LCt 100 value is estimated to be 40–83 mg per cubic meter for exposure time of two minutes. Calculating effects for different exposure times and concentrations requires following specific toxic load models. In general, brief exposures to higher concentrations are more lethal than comparable long time exposures to low concentrations. There are many ways to make relative comparisons between toxic substances. The list below compares sarin to some current and historic chemical warfare agents, with
3078-463: Is higher in motor neurons than in sensory neurons. Acetylcholinesterase is also found on the red blood cell membranes, where different forms constitute the Yt blood group antigens . Acetylcholinesterase exists in multiple molecular forms, which possess similar catalytic properties, but differ in their oligomeric assembly and mode of attachment to the cell surface. In mammals, acetylcholinesterase
3192-618: Is hypothesized in other species. It is thought to be involved in the stress response and, possibly, inflammation. The nomenclatural variations of ACHE and of cholinesterases generally are discussed at Cholinesterase § Types and nomenclature . For acetylcholine esterase (AChE), reversible inhibitors are those that do not irreversibly bond to and deactivate AChE. Drugs that reversibly inhibit acetylcholine esterase are being explored as treatments for Alzheimer's disease and myasthenia gravis , among others. Examples include tacrine and donepezil . Exposure to acetylcholinesterase inhibitors
3306-402: Is not well-documented. During neurotransmission , ACh is released from the presynaptic neuron into the synaptic cleft and binds to ACh receptors on the post-synaptic membrane, relaying the signal from the nerve. AChE is concentrated in the synaptic cleft, where it terminates the signal transmission by hydrolyzing ACh. The liberated choline is taken up again by the pre-synaptic neuron and ACh
3420-517: Is primarily involved in the termination of impulse transmission at cholinergic synapses by rapid hydrolysis of the neurotransmitter acetylcholine. In non-vertebrates, AChE plays a similar role in nerve conduction processes at the neuromuscular junction. It is usually located in the membranes of these animals and controls ionic currents in excitable membranes. In plants, the biological functions of AChE are less clear, and its existence has been recognized by indirect evidence of its activity. For instance,
3534-406: Is synthesized by combining with acetyl-CoA through the action of choline acetyltransferase . A cholinomimetic drug disrupts this process by acting as a cholinergic neurotransmitter that is impervious to acetylcholinesterase's lysing action. Drugs or toxins that inhibit AChE lead to persistence of high concentrations of ACh within synapses, leading to increased cholinergic signaling within
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3648-478: Is the hydrophilic species, which forms disulfide-linked oligomers with collagenous , or lipid -containing structural subunits. In the neuromuscular junctions AChE expresses in asymmetric form which associates with ColQ or subunit. In the central nervous system it is associated with PRiMA which stands for Proline Rich Membrane anchor to form symmetric form. In either case, the ColQ or PRiMA anchor serves to maintain
3762-432: Is the most toxic of the four G-Series nerve agents made by Germany. The compound, which followed the discovery of the nerve agent tabun , was named in honor of its discoverers: chemist Gerhard S chrader , chemist Otto A mbros , chemist Gerhard R itter [ de ] , and from Heereswaffenamt Hans-Jürgen von der L in de. In mid-1939, the formula for the agent was passed to the chemical warfare section of
3876-421: Is the primary cholinesterase in the body. It is an enzyme that catalyzes the breakdown of acetylcholine and some other choline esters that function as neurotransmitters : It is found at mainly neuromuscular junctions and in chemical synapses of the cholinergic type, where its activity serves to terminate cholinergic synaptic transmission . It belongs to the carboxylesterase family of enzymes. It
3990-434: Is the primary target of inhibition by organophosphorus compounds such as nerve agents and pesticides . AChE is a hydrolase that hydrolyzes choline esters. It has a very high catalytic activity—each molecule of AChE degrades about 5,000 molecules of acetylcholine (ACh) per second, approaching the limit allowed by diffusion of the substrate . The active site of AChE comprises two subsites—the anionic site and
4104-430: Is the reaction of methylphosphonyl difluoride with isopropyl alcohol, which produces a racemic mixture of sarin enantiomers with hydrofluoric acid as a byproduct: The second process, known as the "Di-Di" process, uses equimolar quantities of methylphosphonyl difluoride (Difluoro) and methylphosphonyl dichloride (Dichloro). This reaction gives sarin, hydrochloric acid and others minors byproducts. The Di-Di process
4218-446: Is typically with the antidotes atropine and pralidoxime . Atropine, an antagonist to muscarinic acetylcholine receptors , is given to treat the physiological symptoms of poisoning. Since muscular response to acetylcholine is mediated through nicotinic acetylcholine receptors , atropine does not counteract the muscular symptoms. Pralidoxime can regenerate cholinesterases if administered within approximately five hours. Biperiden ,
4332-532: The 2022 Russian invasion of Ukraine , several NATO countries sent ground troops, warships and fighter aircraft to reinforce the alliance's eastern flank, and multiple countries again invoked Article 4. In March 2022, NATO leaders met at Brussels for an extraordinary summit which also involved Group of Seven and European Union leaders. NATO member states agreed to establish four additional battlegroups in Bulgaria, Hungary, Romania, and Slovakia, and elements of
4446-744: The Army of the Republika Srpska , after the Srebrenica genocide . Further NATO air strikes helped bring the Yugoslav Wars to an end, resulting in the Dayton Agreement in November 1995. As part of this agreement, NATO deployed a UN-mandated peacekeeping force, under Operation Joint Endeavor , named IFOR . Almost 60,000 NATO troops were joined by forces from non-NATO countries in this peacekeeping mission. This transitioned into
4560-643: The Belgian Congo be excluded from the treaty. French Algeria was, however, covered until its independence on 3 July 1962. Twelve of these thirty-two are original members who joined in 1949, while the other twenty joined in one of ten enlargement rounds. The three Nordic countries which joined NATO as founding members, Denmark, Iceland, and Norway, chose to limit their participation in three areas: there would be no permanent peacetime bases, no nuclear warheads and no Allied military activity (unless invited) permitted on their territory. However, Denmark allows
4674-728: The Federal Republic of Yugoslavia . During the crisis, NATO also deployed one of its international reaction forces, the ACE Mobile Force (Land) , to Albania as the Albania Force (AFOR), to deliver humanitarian aid to refugees from Kosovo. The campaign was and has been criticized over its civilian casualties , including the bombing of the Chinese embassy in Belgrade , and over whether it had legitimacy . The US,
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4788-579: The German Army Weapons Office , which ordered that it be brought into mass production for wartime use. Pilot plants were built, and a production facility was under construction (but was not finished) by the end of World War II . Estimates for total sarin production by Nazi Germany range from 500 kg to 10 tons. Though sarin, tabun , and soman were incorporated into artillery shells, Germany did not use nerve agents against Allied targets. Adolf Hitler refused to initiate
4902-456: The Goražde safe area, resulting in the bombing of a Bosnian Serb military command outpost near Goražde by two US F-16 jets acting under NATO direction. In retaliation, Serbs took 150 U.N. personnel hostage on 14 April. On 16 April a British Sea Harrier was shot down over Goražde by Serb forces. In August 1995, a two-week NATO bombing campaign, Operation Deliberate Force , began against
5016-732: The Gulf of Aden and the Indian Ocean from Somali pirates , and help strengthen the navies and coast guards of regional states. During the Libyan Civil War , violence between protesters and the Libyan government under Colonel Muammar Gaddafi escalated, and on 17 March 2011 led to the passage of United Nations Security Council Resolution 1973 , which called for a ceasefire, and authorized military action to protect civilians. A coalition that included several NATO members began enforcing
5130-640: The Iraq War and Syrian Civil War . At the 2014 Wales summit , the leaders of NATO's member states formally committed for the first time to spend the equivalent of at least two percent of their gross domestic products on defence by 2024, which had previously been only an informal guideline. At the 2016 Warsaw summit , NATO countries agreed on the creation of NATO Enhanced Forward Presence , which deployed four multinational battalion-sized battlegroups in Estonia, Latvia, Lithuania, and Poland. Before and during
5244-599: The NATO Response Force were activated for the first time in NATO's history. As of June 2022, NATO had deployed 40,000 troops along its 2,500-kilometre-long (1,550 mi) Eastern flank to deter Russian aggression. More than half of this number have been deployed in Bulgaria, Romania, Hungary, Slovakia, and Poland, which five countries muster a considerable combined ex-NATO force of 259,000 troops. To supplement Bulgaria's Air Force, Spain sent Eurofighter Typhoons ,
5358-792: The North Atlantic Treaty to include member territory in Europe, North America, Turkey, and islands in the North Atlantic north of the Tropic of Cancer . Attacks on vessels, aircraft and other forces in the North Atlantic (again, north of the Tropic of Cancer) and the Mediterranean Sea may also provoke an Article 5 response. During the original treaty negotiations, the United States insisted that colonies such as
5472-554: The Northwestern Syria offensive , which involved Syrian and suspected Russian airstrikes on Turkish troops , and risked direct confrontation between Russia and a NATO member. The 32 NATO members are: NATO has thirty-two members, mostly in Europe with two in North America. NATO's "area of responsibility", within which attacks on member states are eligible for an Article 5 response, is defined under Article 6 of
5586-781: The Partnership for Peace and the Mediterranean Dialogue initiative in 1994, the Euro-Atlantic Partnership Council in 1997, and the NATO–Russia Permanent Joint Council in 1998. At the 1999 Washington summit , Hungary , Poland , and the Czech Republic officially joined NATO, and the organization also issued new guidelines for membership with individualized " Membership Action Plans ". These plans governed
5700-626: The Syrian Civil War , after the downing of an unarmed Turkish F-4 reconnaissance jet , and after a mortar was fired at Turkey from Syria, and again in 2015 after threats by Islamic State of Iraq and the Levant to its territorial integrity. In 2008 the United Nations Secretary-General called on member-states to protect the ships of Operation Allied Provider [ de ; no ; ru ; uk ] , which
5814-534: The Syrian civil war . In April 2012, Turkish Prime Minister Recep Tayyip Erdoğan considered invoking Article 5 of the NATO treaty to protect Turkish national security in a dispute over the Syrian Civil War. The alliance responded quickly, and a spokesperson said the alliance was "monitoring the situation very closely and will continue to do so" and "takes it very seriously protecting its members." After
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#17327723624765928-617: The U.S. Space Force to maintain Pituffik Space Base , in Greenland. From the mid-1960s to the mid-1990s, France pursued a military strategy of independence from NATO under a policy dubbed "Gaullo-Mitterrandism". Nicolas Sarkozy negotiated the return of France to the integrated military command and the Defence Planning Committee in 2009, the latter being disbanded the following year. France remains
6042-491: The United Nations Security Council passed Resolution 1199 on 23 September 1998 to demand a ceasefire. Negotiations under US Special Envoy Richard Holbrooke broke down on 23 March 1999, and he handed the matter to NATO, which acted on protecting regional security and started a 78-day bombing campaign on 24 March 1999. Operation Allied Force targeted the military capabilities of what was then
6156-819: The Warsaw Pact , and has been involved in military operations in the Balkans , the Middle East , South Asia , and Africa . The organization's motto is animus in consulendo liber ( Latin for 'a mind unfettered in deliberation'). The organization's strategic concepts include deterrence . NATO's main headquarters are located in Brussels , Belgium, while NATO's military headquarters are near Mons , Belgium. The alliance has increased its NATO Response Force deployments in Eastern Europe, and
6270-668: The Western Union . Talks for a wider military alliance, which could include North America, also began that month in the United States, where their foreign policy under the Truman Doctrine promoted international solidarity against actions they saw as communist aggression, such as the February 1948 coup d'état in Czechoslovakia . These talks resulted in the signature of the North Atlantic Treaty on 4 April 1949 by
6384-430: The catalytic triad of three amino acids: serine 203, histidine 447 and glutamate 334. These three amino acids are similar to the triad in other serine proteases except that the glutamate is the third member rather than aspartate . Moreover, the triad is of opposite chirality to that of other proteases. The hydrolysis reaction of the carboxyl ester leads to the formation of an acyl-enzyme and free choline . Then,
6498-423: The central nervous system , autonomic ganglia and neuromuscular junctions . Irreversible inhibitors of AChE may lead to muscular paralysis , convulsions, bronchial constriction, and death by asphyxiation . Organophosphates (OP), esters of phosphoric acid, are a class of irreversible AChE inhibitors. Cleavage of OP by AChE leaves a phosphoryl group in the esteratic site, which is slow to be hydrolyzed (on
6612-717: The collapse of the Afghan government as the greatest debacle that NATO has suffered since its founding. In August 2004, during the Iraq War , NATO formed the NATO Training Mission – Iraq , a training mission to assist the Iraqi security forces in conjunction with the US-led MNF-I . The NATO Training Mission-Iraq (NTM-I) was established at the request of the Iraqi Interim Government under
6726-526: The nervous system by interfering with the degradation of the neurotransmitter acetylcholine at neuromuscular junctions . Death usually occurs as a result of asphyxia due to the inability to control the muscles involved in breathing. Initial symptoms following exposure to sarin are a runny nose , tightness in the chest, and constriction of the pupils . Soon after, the person will have difficulty breathing and experience nausea and drooling. This progresses to losing control of bodily functions, which may cause
6840-491: The peripheral nervous system to muscle fibres. Normally, acetylcholine is released from the neuron to stimulate the muscle, after which it is degraded by acetylcholinesterase , allowing the muscle to relax. A build-up of acetylcholine in the synaptic cleft , due to the inhibition of acetylcholinesterase, means the neurotransmitter continues to act on the muscle fibre, so that any nerve impulses are effectively continually transmitted. Sarin acts on acetylcholinesterase by forming
6954-606: The 1990s, the organization extended its activities into political and humanitarian situations that had not formerly been NATO concerns. During the breakup of Yugoslavia , the organization conducted its first military interventions in Bosnia from 1992 to 1995 and later Yugoslavia in 1999 . Politically, the organization sought better relations with the newly autonomous Central and Eastern European states, and diplomatic forums for regional cooperation between NATO and its neighbours were set up during this post-Cold War period, including
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#17327723624767068-599: The Czech Republic officially joined, and NATO issued new guidelines for membership, with individualized " Membership Action Plans ". These plans governed the addition of new members: Bulgaria, Estonia, Latvia, Lithuania, Romania, Slovakia, and Slovenia in 2004, Albania and Croatia in 2009, Montenegro in 2017, and North Macedonia in 2020. Finland and Sweden are the newest members, joining on 4 April 2023 and 7 March 2024 respectively, spurred on by Russia's invasion of Ukraine . Ukraine's relationship with NATO began with
7182-472: The ISAF mission throughout Afghanistan, and ISAF subsequently expanded the mission in four main stages over the whole of the country. On 31 July 2006, the ISAF additionally took over military operations in the south of Afghanistan from a US-led anti-terrorism coalition. Due to the intensity of the fighting in the south, in 2011 France allowed a squadron of Mirage 2000 fighter/attack aircraft to be moved into
7296-527: The NATO–Ukraine Action Plan in 2002. In 2010, under President Viktor Yanukovych , Ukraine re-affirmed its non-aligned status and renounced aspirations of joining NATO. During the 2014 Ukrainian Revolution , Russia occupied Crimea and supported armed separatists in eastern Ukraine . As a result, in December 2014 Ukraine's parliament voted to end its non-aligned status, and in 2019 it enshrined
7410-549: The Netherlands sent eight F-35 attack aircraft, and additional French and US attack aircraft would arrive soon as well. No military operations were conducted by NATO during the Cold War. Following the end of the Cold War, the first operations, Anchor Guard in 1990 and Ace Guard in 1991, were prompted by the Iraqi invasion of Kuwait . Airborne early warning aircraft were sent to provide coverage of southeastern Turkey, and later
7524-538: The UK, and most other NATO countries opposed efforts to require the UN Security Council to approve NATO military strikes, such as the action against Serbia in 1999, while France and some others claimed that the alliance needed UN approval. The US/UK side claimed that this would undermine the authority of the alliance, and they noted that Russia and China would have exercised their Security Council vetoes to block
7638-563: The United Kingdom, and the United States. Four new members joined during the Cold War: Greece (1952), Turkey (1952), West Germany (1955) and Spain (1982). Following the dissolution of the Soviet Union , many former Warsaw Pact and post-Soviet states sought membership. In 1990, the territory of the former East Germany was added with the reunification of Germany . At the 1999 Washington summit , Hungary, Poland, and
7752-440: The United States and Germany were the biggest contributors with 16.2% each. Member states pay for and maintain their own troops and equipment. They contribute to NATO operations and missions by committing troops and equipment on a voluntary basis. Since 2006, the goal has been for each country to spend at least 2 percent of its gross domestic product on its own defence; in 2014, a NATO declaration said that countries not meeting
7866-532: The Western Union's military structures and plans, including their agreements on standardizing equipment and agreements on stationing foreign military forces in European countries. In 1952, the post of Secretary General of NATO was established as the organization's chief civilian. That year also saw the first major NATO maritime exercises , Exercise Mainbrace and the accession of Greece and Turkey to
7980-464: The acyl-enzyme undergoes nucleophilic attack by a water molecule, assisted by the histidine 440 group, liberating acetic acid and regenerating the free enzyme. AChE is found in many biological species, including humans and other mammals, non-vertebrates, and plants. In humans, AChE is a cholinergic enzyme involved in the hydrolysis of the neurotransmitter acetylcholine (ACh) into its constituents, choline, and acetate. Overall, in mammals, AChE
8094-623: The alliance also mounted Operation Essential Harvest , a mission disarming ethnic Albanian militias in the Republic of Macedonia. As of 2023 , around 4,500 KFOR soldiers, representing 27 countries, continue to operate in the area. The September 11 attacks in the United States caused NATO to invoke Article 5 of the NATO Charter for the first time in the organization's history. The Article states that an attack on any member shall be considered to be an attack on all. The invocation
8208-401: The alliance on 7 March 2024. In addition, NATO recognizes Bosnia and Herzegovina , Georgia , and Ukraine as aspiring members. Enlargement has led to tensions with non-member Russia , one of the 18 additional countries participating in NATO's Partnership for Peace programme. Another nineteen countries are involved in institutionalized dialogue programmes with NATO. The Treaty of Dunkirk
8322-627: The area, to Kandahar , in order to reinforce the alliance's efforts. During its 2012 Chicago Summit , NATO endorsed a plan to end the Afghanistan war and to remove the NATO-led ISAF Forces by the end of December 2014. ISAF was disestablished in December 2014 and replaced by the follow-on training Resolute Support Mission . On 14 April 2021, NATO Secretary General Jens Stoltenberg said the alliance had agreed to start withdrawing its troops from Afghanistan by 1 May. Soon after
8436-546: The ban on 12 April 1993 with Operation Deny Flight . From June 1993 until October 1996, Operation Sharp Guard added maritime enforcement of the arms embargo and economic sanctions against the Federal Republic of Yugoslavia . On 28 February 1994, NATO took its first wartime action by shooting down four Bosnian Serb aircraft violating the no-fly zone. On 10 and 11 April 1994, the United Nations Protection Force called in air strikes to protect
8550-417: The body, and remain for a longer period of time than the free metabolites. One clear advantage of this process is that the period, post-exposure, for determination of sarin exposure is much longer, possibly five to eight weeks according to at least one study. As a nerve gas, sarin in its purest form is estimated to be 26 times more deadly than cyanide . The LD 50 of subcutaneously injected sarin in mice
8664-416: The chemical itself, various additives have been tried to combat the effects of the acid, such as: Another byproduct of these two chemical processes is diisopropyl methylphosphonate , formed when a second isopropyl alcohol reacts with the sarin itself and from disproportionation of sarin, when distilled incorrectly. The factor of its formation in esterification is that as the concentration of DF-DCl decreases,
8778-629: The collapse of the Warsaw Pact in February 1991 and the dissolution of the Soviet Union that December, which removed the de facto main adversaries of NATO. This began a drawdown of military spending and equipment in Europe. The CFE treaty allowed signatories to remove 52,000 pieces of conventional armaments in the following sixteen years, and allowed military spending by NATO's European members to decline by 28 percent from 1990 to 2015. In 1990, several Western leaders gave assurances to Mikhail Gorbachev that NATO would not expand further east, as revealed by memoranda of private conversations. In
8892-590: The combined militaries of all NATO members include around 3.5 million soldiers and personnel. All member states together cover an area of 25.07 million km (9.68 million sq. mi.) with a population of about 973 million people. Their combined military spending as of 2022 constituted around 55 percent of the global nominal total . Moreover, members have agreed to reach or maintain the target defence spending of at least two percent of their GDP by 2024. NATO formed with twelve founding members and has added new members ten times, most recently when Sweden joined
9006-407: The concentration of sarin increases, the probability of DIMP formation is greater. DIMP is a natural impurity of sarin, that is almost impossible to be eliminated, mathematically, when the reaction is a 1 mol-1 mol "one-stream". This chemical degrades into isopropyl methylphosphonic acid. The most important chemical reactions of phosphoryl halides is the hydrolysis of the bond between phosphorus and
9120-478: The country's southeast . Georgia was promised "future membership" during the 2008 summit in Bucharest, but US president Barack Obama said in 2014 that the country was not "currently on a path" to membership. Russia continued to politically oppose further expansion, seeing it as inconsistent with informal understandings between Soviet leader Mikhail Gorbachev and European and US negotiators that allowed for
9234-481: The demise of NATO. The German foreign ministry pointed to "a considerable [German] contribution to NATO and NATO-led operations" and to the fact that this engagement was highly valued by President Obama. While the mission was extended into September, Norway that day (10 June) announced it would begin scaling down contributions and complete withdrawal by 1 August. Earlier that week it was reported Danish air fighters were running out of bombs. The following week,
9348-595: The enzyme in the intercellular junction, ColQ for the neuromuscular junction and PRiMA for synapses. The other, alternatively spliced form expressed primarily in the erythroid tissues, differs at the C-terminus , and contains a cleavable hydrophobic peptide with a PI-anchor site. It associates with membranes through the phosphoinositide (PI) moieties added post-translationally. The third type has, so far, only been found in Torpedo sp. and mice although it
9462-502: The esteratic site for short periods of time (seconds to minutes) and are used to treat of a range of central nervous system diseases. Tetrahydroaminoacridine (THA) and donepezil are FDA-approved to improve cognitive function in Alzheimer's disease . Rivastigmine is also used to treat Alzheimer's and Lewy body dementia , and pyridostigmine bromide is used to treat myasthenia gravis . An endogenous inhibitor of AChE in neurons
9576-421: The esteratic subsite. The structure and mechanism of action of AChE have been elucidated from the crystal structure of the enzyme. The anionic subsite accommodates the positive quaternary amine of acetylcholine as well as other cationic substrates and inhibitors . The cationic substrates are not bound by a negatively charged amino acid in the anionic site, but by interaction of 14 aromatic residues that line
9690-544: The final substitution is selective for chloro over fluoro as the leaving group . Inert atmosphere and anhydrous conditions ( Schlenk techniques ) are used for synthesis of sarin and other organophosphates. As both reactions leave considerable acid in the product, sarin produced in bulk by these methods has a short half life without further processing, and would be corrosive to containers and damaging to weapons systems. Various methods have been tried to resolve these problems. In addition to industrial refining techniques to purify
9804-547: The first time in NATO's history that it took charge of a mission outside the north Atlantic area. ISAF was initially charged with securing Kabul and surrounding areas from the Taliban , al Qaeda and factional warlords, so as to allow for the establishment of the Afghan Transitional Administration headed by Hamid Karzai . In October 2003, the UN Security Council authorized the expansion of
9918-411: The fluoride. This P-F bond is easily broken by nucleophilic agents, such as water and hydroxide . At high pH , sarin decomposes rapidly to nontoxic phosphonic acid derivatives. The initial breakdown of sarin is into isopropyl methylphosphonic acid (IMPA), a chemical that is not commonly found in nature except as a breakdown product of sarin (this is useful for detecting the recent deployment of sarin as
10032-661: The goal of NATO membership in the Constitution . At the June 2021 Brussels Summit , NATO leaders affirmed that Ukraine would eventually join the Alliance, and supported Ukraine's right to self-determination without interference. In late 2021, there was another massive Russian military buildup near Ukraine's borders. On 30 November, Russian president Putin said Ukraine joining NATO, and the deployment of missile defense systems or long-range missiles in Ukraine, would be crossing
10146-572: The goal would "aim to move towards the 2 percent guideline within a decade". In July 2022, NATO estimated that 11 members would meet the target in 2023. On 14 February 2024, NATO Secretary General Jens Stoltenberg said that 18 member states would meet the 2% target in 2024. On 17 June 2024, prior to the 2024 Washington summit , Stoltenberg updated that figure and announced that a record 23 of 32 NATO member states were meeting their defense spending targets of 2% of their country's GDP. NATO added that defense spending for European member states and Canada
10260-936: The head of the Royal Navy said the country's operations in the conflict were not sustainable. By the end of the mission in October 2011, after the death of Colonel Gaddafi, NATO planes had flown about 9,500 strike sorties against pro-Gaddafi targets. A report from the organization Human Rights Watch in May 2012 identified at least 72 civilians killed in the campaign. Following a coup d'état attempt in October 2013, Libyan Prime Minister Ali Zeidan requested technical advice and trainers from NATO to assist with ongoing security issues. Use of Article 5 has been threatened multiple times and four out of seven official Article 4 consultations have been called due to spillover in Turkey from
10374-537: The member states of the Western Union plus the United States, Canada, Portugal, Italy, Norway, Denmark, and Iceland. Canadian diplomat Lester B. Pearson was a key author and drafter of the treaty. The North Atlantic Treaty was largely dormant until the Korean War initiated the establishment of NATO to implement it with an integrated military structure. This included the formation of Supreme Headquarters Allied Powers Europe (SHAPE) in 1951, which adopted many of
10488-520: The no-fly zone from the initial coalition, while command of targeting ground units remained with the coalition's forces. NATO began officially enforcing the UN resolution on 27 March 2011 with assistance from Qatar and the United Arab Emirates. By June, reports of divisions within the alliance surfaced as only eight of the 28 member states were participating in combat operations, resulting in
10602-496: The only NATO member outside the Nuclear Planning Group and, unlike the United States and the United Kingdom, will not commit its nuclear-armed submarines to the alliance. NATO was established on 4 April 1949 by the signing of the North Atlantic Treaty (Washington Treaty). The 12 founding members of the alliance were Belgium, Canada, Denmark, France, Iceland, Italy, Luxembourg, the Netherlands, Norway, Portugal,
10716-417: The order of days) and can become covalently bound. Irreversible AChE inhibitors have been used in insecticides (e.g., malathion ) and nerve gases for chemical warfare (e.g., Sarin and VX ). Carbamates , esters of N-methyl carbamic acid, are AChE inhibitors that hydrolyze in hours and have been used for medical purposes (e.g., physostigmine for the treatment of glaucoma ). Reversible inhibitors occupy
10830-579: The organization implements the North Atlantic Treaty , signed in Washington, D.C. , on 4 April 1949. NATO is a collective security system: its independent member states agree to defend each other against attacks by third parties. During the Cold War , NATO operated as a check on the threat posed by the Soviet Union . The alliance remained in place after the dissolution of the Soviet Union and
10944-636: The organization. Following the London and Paris Conferences , West Germany was permitted to rearm militarily, as they joined NATO in May 1955, which was, in turn, a major factor in the creation of the Soviet-dominated Warsaw Pact , delineating the two opposing sides of the Cold War . The building of the Berlin Wall in 1961 marked a height in Cold War tensions, when 400,000 US troops were stationed in Europe. Doubts over
11058-578: The person to vomit, defecate, and urinate. This phase is followed by twitching and jerking. Ultimately, the person becomes comatose and suffocates in a series of convulsive spasms . Common mnemonics for the symptomatology of organophosphate poisoning, including sarin, are the "killer Bs" of bronchorrhea and bronchospasm because they are the leading cause of death, and SLUDGE – salivation, lacrimation , urination, defecation, gastrointestinal distress, and emesis (vomiting). Death may follow in one to ten minutes after direct inhalation, but may also occur after
11172-502: The provisions of United Nations Security Council Resolution 1546 . The aim of NTM-I was to assist in the development of Iraqi security forces training structures and institutions so that Iraq can build an effective and sustainable capability that addresses the needs of the country. NTM-I was not a combat mission but is a distinct mission, under the political control of the North Atlantic Council . Its operational emphasis
11286-590: The security of shipping in general, which began on 4 October 2001. The alliance showed unity: on 16 April 2003, NATO agreed to take command of the International Security Assistance Force (ISAF), which included troops from 42 countries. The decision came at the request of Germany and the Netherlands, the two countries leading ISAF at the time of the agreement, and all nineteen NATO ambassadors approved it unanimously. The handover of control to NATO took place on 11 August, and marked
11400-525: The shooting down of a Turkish military jet by Syria in June 2012 and Syrian forces shelling Turkish cities in October 2012 resulting in two Article 4 consultations, NATO approved Operation Active Fence . In the past decade the conflict has only escalated. In response to the 2015 Suruç bombing , which Turkey attributed to ISIS , and other security issues along its southern border, Turkey called for an emergency meeting . The latest consultation happened in February 2020, as part of increasing tensions due to
11514-618: The smaller SFOR , which started with 32,000 troops initially and ran from December 1996 until December 2004, when operations were then passed onto the European Union Force Althea . Following the lead of its member states, NATO began to award a service medal, the NATO Medal , for these operations. In an effort to stop Slobodan Milošević 's Serbian-led crackdown on KLA separatists and Albanian civilians in Kosovo ,
11628-456: The strength of the relationship between the European states and the United States ebbed and flowed, along with doubts over the credibility of the NATO defence against a prospective Soviet invasion – doubts that led to the development of the independent French nuclear deterrent and the withdrawal of France from NATO's military structure in 1966. In 1982, the newly democratic Spain joined the alliance. The Revolutions of 1989 in Europe led to
11742-537: The strike on Yugoslavia , and could do the same in future conflicts where NATO intervention was required, thus nullifying the entire potency and purpose of the organization. Recognizing the post-Cold War military environment, NATO adopted the Alliance Strategic Concept during its Washington summit in April 1999 that emphasized conflict prevention and crisis management. Milošević finally accepted
11856-674: The subsequent addition of new alliance members. Article 5 of the North Atlantic treaty , requiring member states to come to the aid of any member state subject to an armed attack, was invoked for the first and only time after the September 11 attacks , after which troops were deployed to Afghanistan under the NATO-led ISAF . The organization has operated a range of additional roles since then, including sending trainers to Iraq , assisting in counter-piracy operations . The election of French president Nicolas Sarkozy in 2007 led to
11970-511: The terms of an international peace plan on 3 June 1999, ending the Kosovo War . On 11 June, Milošević further accepted UN resolution 1244 , under the mandate of which NATO then helped establish the KFOR peacekeeping force. Nearly one million refugees had fled Kosovo, and part of KFOR's mandate was to protect the humanitarian missions, in addition to deterring violence. In August–September 2001,
12084-512: The two precursors are stored separately in the same shell and mixed to form the agent immediately before or when the shell is in flight. This approach has the dual benefit of solving the stability issue and increasing the safety of sarin munitions. Sarin was discovered in 1938 in Wuppertal -Elberfeld in Germany by scientists at IG Farben who were attempting to create stronger pesticides; it
12198-486: The use of gases such as sarin as weapons. NATO The North Atlantic Treaty Organization ( NATO / ˈ n eɪ t oʊ / NAY -toh ; French : Organisation du traité de l'Atlantique nord , OTAN ), also called the North Atlantic Alliance , is an intergovernmental military alliance of 32 member states —30 European and 2 North American. Established in the aftermath of World War II ,
12312-470: The withdrawal of NATO troops started, the Taliban launched an offensive against the Afghan government , quickly advancing in front of collapsing Afghan Armed Forces . By 15 August 2021, Taliban militants controlled the vast majority of Afghanistan and had encircled the capital city of Kabul . Some politicians in NATO member states have described the chaotic withdrawal of Western troops from Afghanistan and
12426-483: Was confirmed on 4 October 2001 when NATO determined that the attacks were indeed eligible under the terms of the North Atlantic Treaty. The eight official actions taken by NATO in response to the attacks included Operation Eagle Assist and Operation Active Endeavour , a naval operation in the Mediterranean Sea designed to prevent the movement of terrorists or weapons of mass destruction, and to enhance
12540-574: Was distributing aid as part of the World Food Programme mission in Somalia. The North Atlantic Council and other countries, including Russia, China and South Korea, formed Operation Ocean Shield . The operation sought to dissuade and interrupt pirate attacks, protect vessels, and to increase the general level of security in the region. Beginning on 17 August 2009, NATO deployed warships in an operation to protect maritime traffic in
12654-568: Was on training and mentoring. The activities of the mission were coordinated with Iraqi authorities and the US-led Deputy Commanding General Advising and Training, who was also dual-hatted as the Commander of NTM-I. The mission officially concluded on 17 December 2011. Turkey invoked the first Article 4 meetings in 2003 at the start of the Iraq War . Turkey also invoked this article twice in 2012 during
12768-550: Was signed by France and the United Kingdom on 4 March 1947, during the aftermath of World War II and the start of the Cold War , as a Treaty of Alliance and Mutual Assistance in the event of possible attacks by Germany or the Soviet Union . In March 1948, this alliance was expanded in the Treaty of Brussels to include the Benelux countries, forming the Brussels Treaty Organization, commonly known as
12882-662: Was up 18% in the past year alone. Acetylcholinesterase 4EY7 , 4PQE , 1F8U , 3LII , 4BDT , 4M0E , 4M0F , 1VZJ , 2X8B , 1B41 , 4EY4 , 4EY5 , 4EY6 , 4EY8 , 5FOQ , 5HF9 , 5HF6 , 5FPQ , 5HF8 , 5HFA 43 11423 ENSG00000087085 ENSMUSG00000023328 P22303 P21836 NM_001367915 NM_001367917 NM_001367918 NM_001367919 NM_001290010 NM_009599 NP_001354846 NP_001354847 NP_001354848 NP_001276939 NP_033729 Acetylcholinesterase ( HGNC symbol ACHE ; EC 3.1.1.7; systematic name acetylcholine acetylhydrolase ), also known as AChE, AChase or acetylhydrolase ,
12996-451: Was used by the United States for the production of its unitary sarin stockpile. The scheme below shows a generic example that employs the Di-Di method as the final esterification step; in reality, the selection of reagents and reaction conditions dictate both product structure and yield. The choice of enantiomer of the mixed chloro fluoro intermediate displayed in the diagram is arbitrary, but
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