Neuromuscular-blocking drugs, or Neuromuscular blocking agents (NMBAs), block transmission at the neuromuscular junction, causing paralysis of the affected skeletal muscles. This is accomplished via their action on the post-synaptic acetylcholine (Nm) receptors.

In clinical use, neuromuscular block is used adjunctively to anesthesia to produce paralysis, firstly to paralyze the vocal cords, and permit endotracheal intubation, and secondly to optimize the surgical field by inhibiting spontaneous ventilation, and causing relaxation of skeletal muscles.  Because the appropriate dose of neuromuscular-blocking drug may paralyze muscles required for breathing (i.e., the diaphragm), mechanical ventilation should be available to maintain adequate respiration.

This  class  of  medications  helps  to  reduce  patient  movement,  breathing,  or  ventilator  dyssynchrony  and  allows  lower  insufflation  pressures  during  laparoscopy. It has several indications for use in the intense care unit.  It can help reduce hoarseness in voice as well as injury to the vocal cord during intubation. In addition, it plays an important role in facilitating mechanical ventilation in patients with poor lung function.

Patients are still aware of pain even after full conduction block has occurred; hence, general anesthetics and/or analgesics must also be given to prevent anesthesia awareness.

Nomenclature
Neuromuscular blocking drugs are often classified into two broad classes:
Pachycurares, which are bulky molecules with nondepolarizing activity
Leptocurares, which are thin and flexible molecules that tend to have depolarizing activity.

It is also common to classify them based on their chemical structure.
Acetylcholine, suxamethonium, and decamethonium
Suxamethonium was synthesised by connecting two acetylcholine molecules and has  the same number of heavy atoms between methonium heads as decamethonium.  Just like acetylcholine, succinylcholine, decamethonium and other polymethylene chains, of the appropriate length and with two methonium, heads have small trimethyl onium heads and flexible links. They all exhibit a depolarizing block.
 Aminosteroids

Pancuronium, vecuronium, rocuronium, rapacuronium, dacuronium, malouètine, duador, dipyrandium, pipecuronium, chandonium (HS-310), HS-342 and other HS- compounds are aminosteroidal agents. They have in  common the steroid structural base, which provides a rigid and bulky body. Most of the agents in this category would also be classified as non-depolarizing.
 Tetrahydroisoquinoline derivatives
Compounds based on the tetrahydroisoquinoline moiety such as atracurium, mivacurium, and doxacurium would fall in this category. They have a long and flexible chain between the onium heads, except for the double bond of mivacurium. D-tubocurarine and dimethyltubocurarine are also in this category. Most of the agents in this category would be classified as non-depolarizing.
 Gallamine and other chemical classes
Gallamine is a trisquaternary ether with three ethonium heads attached to a phenyl ring through an ether linkage. Many other different structures have been used for their muscle relaxant effect such as alcuronium (alloferin), anatruxonium, diadonium, fazadinium (AH8165) and tropeinium.
Novel NMB agents
In recent years much research has been devoted to new types of quaternary ammonium muscle relaxants. These are asymmetrical diester isoquinolinium compounds and bis-benzyltropinium compounds that are bistropinium salts of various diacids.  These classes have been developed to create muscle relaxants that are faster and shorter acting. Both the asymmetric structure of diester isoquinolinium compounds and the acyloxylated benzyl groups on the bisbenzyltropiniums destabilizes them and can lead to spontaneous breakdown and therefore possibly a shorter duration of action.

Classification
These drugs fall into two groups:

Non-depolarizing blocking agents: These agents constitute the majority of the clinically relevant neuromuscular blockers.  They act by competitively blocking the binding of ACh to its receptors, and in some cases, they also directly block the ionotropic activity of the ACh receptors.
Depolarizing blocking agents: These agents act by depolarizing the sarcolemma of the skeletal muscle fiber. This persistent depolarization makes the muscle fiber resistant to further stimulation by ACh.

Non-depolarizing blocking agents
A neuromuscular non-depolarizing agent is a form of neuromuscular blocker that does not depolarize the motor end plate.

The quaternary ammonium muscle relaxants belong to this class. Quaternary ammonium muscle relaxants are quaternary ammonium salts used as drugs for muscle relaxation, most commonly in anesthesia. It is necessary to prevent spontaneous movement of muscle during surgical operations. Muscle relaxants inhibit neuron transmission to muscle by blocking the nicotinic acetylcholine receptor. What they have in common, and is necessary for their effect, is the structural presence of quaternary ammonium groups, usually two. Some of them are found in nature and others are synthesized molecules.

Below are some more common agents that act as competitive antagonists against acetylcholine at the site of postsynaptic acetylcholine receptors.

Tubocurarine, found in curare of the South American plant Pareira, Chondrodendron tomentosum, is the prototypical non-depolarizing neuromuscular blocker. It has a slow onset (>5 min) and a long duration of action (30 mins). Side-effects include hypotension, which is partially explained by its effect of increasing histamine release, a vasodilator, as well as its effect of blocking autonomic ganglia.  It is excreted in the urine.

This drug needs to block about 70–80% of the ACh receptors for neuromuscular conduction to fail, and hence for effective blockade to occur. At this stage, end-plate potentials (EPPs) can still be detected, but are too small to reach the threshold potential needed for activation of muscle fiber contraction.

The speed of onset depends on the potency of the drug, greater potency is associated with slower onset of block. Rocuronium, with an ED95 of 0.3 mg/kg IV has a more rapid onset than Vecuronium with an ED95 of 0.05mg/kg. Steroidal compounds, such as rocuronium and vecuronium, are intermediate-acting drugs while Pancuronium and pipecuronium are long-acting drugs.

In larger clinical dose, some of the blocking agent can access the pore of the ion channel and cause blockage. This weakens neuromuscular transmission and diminishes the effect of acetylcholinesterase inhibitors (e.g. neostigmine). Nondepolarizing NBAs may also block prejunctional sodium channels which interfere with the mobilization of acetylcholine at the nerve ending.

Depolarizing blocking agents

A depolarizing neuromuscular blocking agent is a form of neuromuscular blocker that depolarizes the motor end plate. An example is succinylcholine. Depolarizing blocking agents work by depolarizing the plasma membrane of the muscle fiber, similar to acetylcholine.  However, these agents are more resistant to degradation by acetylcholinesterase, the enzyme responsible for degrading acetylcholine, and can thus more persistently depolarize the muscle fibers. This differs from acetylcholine, which is rapidly degraded and only transiently depolarizes the muscle.

There are two phases to the depolarizing block. During phase I (depolarizing phase), succinylcholine interacts with nicotinic receptor to open the channel and cause depolarization of the end plate, which later spread to and result in depolarization of adjacent membranes. As a result, there is disorganisation of contraction of muscle motor unit. This causes muscular fasciculations (muscle twitches) while they are depolarizing the muscle fibers.  Eventually, after sufficient depolarization has occurred, phase II (desensitizing phase) sets in and the muscle is no longer responsive to acetylcholine released by the motoneurons. At this point, full neuromuscular block has been achieved. Phase I block effect can be increased by cholinesterase inhibitors which further delay the action of metabolism and removal by cholinesterase.

Under continuous exposure to succinylcholine, the initial end plate depolarization is reduced, and repolarisation process is initiated. As a result of the widespread sustained depolarization the synapses ultimately begin repolarization. Once repolarized, the membrane is still less susceptible to additional depolarization (phase II block).

The prototypical depolarizing blocking drug is succinylcholine (suxamethonium). It is the only such drug used clinically. It has a rapid onset (30 seconds) but very short duration of action (5–10 minutes) because of hydrolysis by various cholinesterases (such as butyrylcholinesterase in the blood). The patient will experience fasciculation due to the depolarisation of muscle neurone fibres and seconds later, flaccid paralysis will occur. Succinylcholine was originally known as diacetylcholine because structurally it is composed of two acetylcholine molecules joined with a methyl group. Decamethonium is sometimes, but rarely, used in clinical practice.

It is indicated for rapid sequence intubation.

Dosing/onset of action
IV dose 1-1.5mg/kg or 3 to 5 x ED95

Paralysis occurs in one to two minutes.

Clinical duration of action (time from drug administration to recovery of single twich to 25% of baseline) is 7-12 minutes.

If IV access is unavailable, intramuscular administration 3-4mg/kg. Paralysis occurs at 4 minutes.

Use of succinylcholine infusion or repeated bolus administration increase the risk of Phase II block and prolonged paralysis. Phase II block occurs after large doses (>4mg/kg). This occurs when the post-synaptic membrane action potential returns to baseline in spite of the presence of succinylcholine and causes continued activation of nicotinic acetylcholine receptors.

Comparison of drugs
The main difference is in the reversal of these two types of neuromuscular-blocking drugs.
 Non-depolarizing blockers are reversed by acetylcholinesterase inhibitor drugs since non-depolarizing blockers are competitive antagonists at the ACh receptor so can be reversed by increases in ACh.
 The depolarizing blockers already have ACh-like actions, so these agents have prolonged effect under the influence of acetylcholinesterase inhibitors. Administration of depolarizing blockers initially produces fasciculations (a sudden twitch just before paralysis occurs). This is due to depolarization of the muscle. Also, post-operative pain is associated with depolarizing blockers.

The tetanic fade is the failure of muscles to maintain a fused tetany at sufficiently high frequencies of electrical stimulation.
 Non-depolarizing blockers have this effect on patients, probably by an effect on presynaptic receptors.
 Depolarizing blockers do not cause the tetanic fade. However, a clinically similar manifestation called Phase II block occurs with repeated doses of suxamethonium.
This discrepancy is diagnostically useful in case of intoxication of an unknown neuromuscular-blocking drug.

Physiology at the Neuromuscular Junction
Neuromuscular blocking agents exert their effect by modulating the signal transmission in skeletal muscles. An action potential is, in other words, a depolarisation in neurone membrane due to a change in membrane potential greater than the threshold potential leads to an electrical impulse generation. The electrical impulse travels along the pre-synaptic neurone axon to synapse with the muscle at the neuromuscular junction (NMJ) to cause muscle contraction.

When the action potential reaches the axon terminal, it triggers the opening of the calcium ion gated channels, which causes the influx of Ca2+. Ca2+ will stimulate the release of neurotransmitter in the neurotransmitter containing vesicles by exocytosis (vesicle fuses with the pre-synpatic membrane).

The neurotransmitter, acetylcholine(ACh) binds to the nicotinic receptors on the motor end plate, which is a specialised area of the muscle fibre's post-synaptic membrane. This binding causes the nicotinic receptor channels to open and allow the influx of Na+ into the muscle fibre.

Fifty percent of the released ACh is hydrolysed by acetylcholinesterase (AChE) and the remaining bind to the nicotinic receptors on the motor end plate. When ACh is degraded by AChE, the receptors are no longer stimulated and the muscle can be repolarised.

If enough Na+ enter the muscle fibre, it causes an increase in the membrane potential from its resting potential of -95mV to -50mV (above the threshold potential -55V) which causes an action potential to spread throughout the fibre. This potential travels along the surface of the sarcolemma. The sarcolemma is an excitable membrane that surrounds the contractile structures known as myofibrils that are located deep in the muscle fibre. For the action potential to reach the myofibrils, the action potential travels along the transverse tubules (T-tubules) that connects the sarcolemma and center of the fibre.

Later, action potential reaches the sarcoplasmic reticulum which stores the Ca2+  needed for muscle contraction and causes Ca2+ to be released from the sarcoplasmic reticulum.

Mechanism of action
Quaternary muscle relaxants bind to the nicotinic acetylcholine receptor and inhibit or interfere with the binding and effect of ACh to the receptor. Each ACh-receptor has two receptive sites and activation of the receptor requires binding to both of them. Each receptor site is located at one of the two α-subunits of the receptor. Each receptive site has two subsites, an anionic site that binds to the cationic ammonium head and a site that binds to the blocking agent by donating a hydrogen bond.

Non-depolarizing agents
A decrease in binding of acetylcholine leads to a decrease in its effect and neuron transmission to the muscle is less likely to occur. It is generally accepted that non-depolarizing agents block by acting as reversible competitive inhibitors. That is, they bind to the receptor as antagonists and that leaves fewer receptors available for acetylcholine to bind.

Depolarizing agents
Depolarizing agents produce their block by binding to and activating the ACh receptor, at first causing muscle contraction, then paralysis. They bind to the receptor and cause depolarization by opening channels just like acetylcholine does. This causes repetitive excitation that lasts longer than a normal acetylcholine excitation and is most likely explained by the resistance of depolarizing agents to the enzyme acetylcholinesterase. The constant depolarization and triggering of the receptors keeps the endplate resistant to activation by acetylcholine. Therefore, a normal neuron transmission to muscle cannot cause contraction of the muscle because the endplate is depolarized and thereby the muscle paralysed.

 Binding to the nicotinic receptor
Shorter molecules like acetylcholine need two molecules to activate the receptor, one at each receptive site. Decamethonium congeners, which prefer straight line conformations (their lowest energy state), usually span the two receptive sites with one molecule (binding inter-site). Longer congeners must bend when fitting receptive sites.

The greater energy a molecule needs to bend and fit usually results in lower potency.

Structural and conformational action relationship
Conformational study on neuromuscular blocking drugs is relatively new and developing. Traditional SAR studies do not specify environmental factors on molecules. Computer-based conformational searches assume that the molecules are in vacuo, which is not the case in vivo. Solvation models take into account the effect of a solvent on the conformation of the molecule. However, no system of solvation can mimic the effect of the complex fluid composition of the body.

The division of muscle relaxants to rigid and non-rigid is at most qualitative. The energy required for conformational changes may give a more precise and quantitative picture. Energy required for reducing onium head distance in the longer muscle relaxant chains may quantify their ability to bend and fit its receptive sites. Using computers it is possible to calculate the lowest energy state conformer and thus most populated and best representing the molecule. This state is referred to as the global minimum. The global minimum for some simple molecules can be discovered quite easily with certainty. Such as for decamethonium the straight line conformer is clearly the lowest energy state. Some molecules, on the other hand, have many rotatable bonds and their global minimum can only be approximated.

Molecular length and rigidity
Neuromuscular blocking agents need to fit in a space close to 2 nanometres, which resembles the molecular length of decamethonium. Some molecules of decamethonium congeners may bind only to one receptive site. Flexible molecules have a greater chance of fitting receptive sites. However, the most populated conformation may not be the best-fitted one. Very flexible molecules are, in fact, weak neuromuscular inhibitors with flat dose-response curves. On the other hand, stiff or rigid molecules tend to fit well or not at all. If the lowest-energy conformation fits, the compound has high potency because there is a great concentration of molecules close to the lowest-energy conformation. Molecules can be thin but yet rigid. Decamethonium for example needs relatively high energy to change the N-N distance.

In general, molecular rigidity contributes to potency, while size affects whether a muscle relaxant shows a polarizing or a depolarizing effect. Cations must be able to flow through the trans-membrane tube of the ion-channel to depolarize the endplate. Small molecules may be rigid and potent but unable to occupy or block the area between the receptive sites. Large molecules, on the other hand, may bind to both receptive sites and hinder depolarizing cations independent of whether the ion-channel is open or closed below. Having a lipophilic surface pointed towards the synapse enhances this effect by repelling cations. The importance of this effect varies between different muscle relaxants and classifying depolarizing from non-depolarizing blocks is a complex issue. The onium heads are usually kept small and the chains connecting the heads usually keep the N-N distance at 10 N or O atoms. Keeping the distance in mind the structure of the chain can vary (double bonded, cyclohexyl, benzyl, etc.)

Succinylcholine has a 10-atom distance between its N atoms, like decamethonium. Yet it has been reported that it takes two molecules, as with acetylcholine, to open one nicotinic ion channel. The conformational explanation for this is that each acetylcholine moiety of succinylcholine prefers the gauche (bent, cis) state. The attraction between the N and O atoms is greater than the onium head repulsion. In this most populated state, the N-N distance is shorter than the optimal distance of  ten carbon atoms and too short to occupy both receptive sites. This similarity between succinyl- and acetyl-choline also explains its acetylcholine-like side-effects.
Comparing molecular lengths, the pachycurares dimethyltubocurarine and d-tubocurarine both are very rigid and measure close to 1.8 nm in total length. Pancuronium and vecuronium measure 1.9 nm, whereas pipecuronium is 2.1 nm. The potency of these compounds follows the same rank of order as their length. Likewise, the leptocurares prefer a similar length. Decamethonium, which measures 2 nm, is the most potent in its category, whereas C11 is slightly too long. Gallamine despite having low bulk and rigidity is the most potent in its class, and it measures 1.9 nm. Based on this information one can conclude that the optimum length for neuromuscular blocking agents, depolarizing or not, should be 2 to 2.1 nm.

The CAR for long-chain bisquaternary tetrahydroisoquinolines like atracurium, cisatracurium, mivacurium, and doxacurium is hard to determine because of their bulky onium heads and large number of rotatable bonds and groups. These agents must follow the same receptive topology as others, which means that they do not fit between the receptive sites without bending. Mivacurium for example has a molecular length of 3.6 nm when stretched out, far from the 2 to 2.1 nm optimum. Mivacurium, atracurium, and doxacurium have greater N-N distance and molecular length than d-tubocurarine even when bent. To make them fit, they have flexible connections that give their onium heads a chance to position themselves beneficially. This bent N-N scenario probably does not apply to laudexium and decamethylene bisatropium, which prefer a straight conformation.

Beers and Reich's law
It has been concluded that acetylcholine and related compounds must be in the gauche (bent) configuration when bound to the nicotinic receptor. Beers and Reich's studies on cholinergic receptors in 1970 showed a relationship affecting whether a compound was muscarinic or nicotinic. They showed that the distance from the centre of the quaternary N atom to the van der Waals extension of the respective O atom (or an equivalent H-bond acceptor) is a determining factor. If the distance is 0.44 nm, the compound shows muscarinic properties—and if the distance is 0.59 nm, nicotinic properties dominate.)

Rational design
Pancuronium remains one of the few muscle relaxants logically and rationally designed from structure-action / effects relationship data. A steroid skeleton was chosen because of its appropriate size and rigidness. Acetylcholine moieties were inserted to increase receptor affinity. Although having many unwanted side-effects, a slow onset of action and recovery rate it was a big success and at the time the most potent neuromuscular drug available. Pancuronium and some other neuromuscular blocking agents block M2-receptors and therefore affect the vagus nerve, leading to hypotension and tachycardia. This muscarinic blocking effect is related to the acetylcholine moiety on the A ring on pancuronium. Making the N atom on the A ring tertiary, the ring loses its acetylcholine moiety, and the resulting compound, vecuronium, has nearly 100 times less affinity to muscarin receptors while maintaining its nicotinic affinity and a similar duration of action. Vecuronium is, therefore, free from cardiovascular effects. The D ring shows excellent properties validating Beers and Reich's rule with great precision. As a result, vecuronium has the greatest potency and specificity of all mono-quaternary compounds.

Potency
Two functional groups contribute significantly to aminosteroidal neuromuscular blocking potency, it is presumed to enable them to bind the receptor at two points. A bis-quaternary two point arrangement on A and D-ring (binding inter-site) or a D-ring acetylcholine moiety (binding at two points intra-site) are most likely to succeed. A third group can have variable effects. The quaternary and acetyl groups on the A and D ring of pipecuronium prevent it from binding intra-site (binding to two points at the same site). Instead, it must bind as bis-quaternary (inter-site). These structures are very dissimilar from acetylcholine and free pipecuronium from nicotinic or muscarinic side-effects linked to acetylcholine moiety. Also, they protect the molecule from hydrolysis by cholinesterases, which explain its nature of kidney excretion. The four methyl-groups on the quaternary N atoms make it less lipophilic than most aminosteroids. This also affects pipecuroniums metabolism by resisting hepatic uptake, metabolism, and biliary excretion. The length of the molecule (2.1 nm, close to ideal) and its rigidness make pipecuronium the most potent and clean one-bulk bis-quaternary. Even though the N-N distance (1.6 nm) is far away from what is considered ideal, its onium heads are well-exposed, and the quaternary groups help to bring together the onium heads to the anionic centers of the receptors without chirality issues.

Adding more than two onium heads in general does not add to potency. Though the third onium head in gallamine seems to help position the two outside heads near the optimum molecular length, it can interfere unfavorably and gallamine turns out to be a weak muscle relaxant, like all multi-quaternary compounds.
Considering acetylcholine a quaternizing group larger than methyl and an acyl group larger than acetyl would reduce the molecule's potency. The charged N and the carbonyl O atoms are distanced from structures they bind to on receptive sites and, thus, decrease potency. The carbonyl O in vecuronium for example is thrust outward to appose the H-bond donor of the receptive site. This also helps explain why gallamine, rocuronium, and rapacuronium are of relatively low potency.
In general, methyl quaternization is optimal for potency but, opposing this rule, the trimethyl derivatives of gallamine are of lower potency than gallamine. The reason for this is that gallamine has a suboptimal N-N distance. Substituting the ethyl groups with methyl groups would make the molecular length also shorter than optimal. Methoxylation of tetrahydroisoquinolinium agents seems to improve their potency. How methoxylation improves potency is still unclear.
Histamine release is a common attribute of benzylisoquinolinium muscle relaxants. This problem generally decreases with increased potency and smaller doses. The need for larger doses increases the degree of this side-effect. Conformational or structural explanations for histamine release are not clear.

Pharmacokinetics
 Metabolism and Hofmann elimination

Deacetylating vecuronium at position 3 results in a very active metabolite.  In the case of rapacuronium the 3-deacylated metabolite is even more potent than rapacuronium. As long as the D-ring acetylcholine moiety is unchanged they retain their muscle relaxing effect. Mono-quaternary aminosteroids produced with deacylation in position 17 on the other hand are generally weak muscle relaxants. In the development of atracurium the main idea was to make use of Hofmann elimination of the muscle relaxant in vivo. When working with bisbenzyl-isoquinolinium types of molecules, inserting proper features into the molecule such as an appropriate electron withdrawing group then Hofmann elimination should occur at conditions in vivo. Atracurium, the resulting molecule, breaks down spontaneously in the body to inactive compounds and being especially useful in patients with kidney or liver failure. Cis-atracurium is very similar to atracurium except it is more potent and has a weaker tendency to cause histamine release.

Structure relations to onset time

The effect of structure on the onset of action is not very well known except that the time of onset appears inversely related to potency. In general mono-quaternary aminosteroids are faster than bis-quaternary compounds, which means they are also of lower potency. A possible explanation for this effect is that drug delivery and receptor binding are of a different timescale. Weaker muscle relaxants are given in larger doses so more molecules in the central compartment must diffuse into the effect compartment, which is the space within the mouth of the receptor, of the body. After delivery to the effect compartment then all molecules act quickly. Therapeutically this relationship is very inconvenient because low potency, often meaning low specificity can decrease the safety margin thus increasing the chances of side-effects. In addition, even though low potency usually accelerates onset of action, it does not guaranty a fast onset. Gallamine, for example, is weak and slow. When fast onset is necessary then succinylcholine or rocuronium are usually preferable.

Elimination

Muscle relaxants can have very different metabolic pathways and it is important that the drug does not accumulate if certain elimination pathways are not active, for example in kidney failure.

Medical Use

Endotracheal intubation
Administration of neuromuscular blocking agents (NMBA) during anesthesia can facilitate endotracheal intubation. This can decrease the incidence of postintubation hoarseness and airway injury.

Short-acting neuromuscular blocking agents are chosen for endotracheal intubation for short procedures (< 30minutes), and neuromonitoring is required soon after intubation. Options include succinylcholine, rocuronium or vecuronium if sugammadex is available for rapid reversal block.

Any short or intermediate acting depolarizing neuromuscular blocking agents can be applied for endotracheal intubation for long procedures (≥ 30 minutes). Options include succinylcholine, rocuronium, vecuronium, mivacurium, atracurium and cisatracurium. The choice among these NMBA depends on availability, cost and patient parameters that affect drug metabolism.

Intraoperative relaxation can be maintained as necessary with additional dose of nondepolarizing NMBA.

Among all NMBA, Succinylcholine establish the most stable and fastest intubating conditions, thus is considered as the preferred NMBA for rapid sequence induction and intubation (RSII). Alternatives for succinylcholine for RSII include high dose rocuronium (1.2mg/kg which is a 4 X ED95 dose), or avoidance of NMBAs with a high dose remifentanil intubation.

Facilitation of surgery
Nondepolarizing NMBAs can be used to induce muscle relaxation that improves surgical conditions, including laparoscopic, robotic, abdominal and thoracic procedures. It can reduce patient movement, muscle tone, breathing or coughing against ventilator and allow lower insufflation pressure during laparoscopy. Administration of NMBAs should be individualized according to patient's parameters. However, many operations can be performed without the need to apply any NMBAs as adequate anesthesia during surgery can achieve many of the theoretical benefits of neuromuscular blockage.

Adverse effects
Since these drugs may cause paralysis of the diaphragm, mechanical ventilation should be at hand to provide respiration.

In addition, these drugs may exhibit cardiovascular effects, since they are not fully selective for the nicotinic receptor and hence may have effects on muscarinic receptors.  If nicotinic receptors of the autonomic ganglia or adrenal medulla are blocked, these drugs may cause autonomic symptoms.  Also, neuromuscular blockers may facilitate histamine release, which causes hypotension, flushing, and tachycardia.

Succinylcholine may also trigger malignant hyperthermia in rare cases in patients who may be susceptible.

In depolarizing the musculature, suxamethonium may trigger a transient release of large amounts of potassium from muscle fibers.  This puts the patient at risk for life-threatening complications, such as hyperkalemia and cardiac arrhythmias. Other effects include myalgia, increased intragastric pressure, increased intraocular pressure, increased intracranial pressure, cardiac dysrhythmias (bradycardia is the most common type) and allergic reactions. As a result, it is contraindicated for patients with susceptibility to malignant hyperthermia, denervating conditions, major burns after 48 hours, and severe hyperkalemia.

For nondepolarizing NMBAs except vecuronium, pipecuronium, doxacurium, cisatracurium, rocuronium and rapacuronium, they produce certain extent of cardiovascular effect. Moreover, Tubocurarine can produce hypotension effect while Pancuronium can lead to moderate increase in heart rate and small increase in cardiac output with little or no increase in systemic vascular resistance, which is unique in nondeploarizing NMBAs.

Certain drugs such as aminoglycoside antibiotics and polymyxin and some fluoroquinolones also have neuromuscular blocking action as their side-effect.

Interactions
Some drugs enhance or inhibit the response to NMBAs which require the dosage adjustment guided by monitoring.

Combination of NMBAs
In some clinical circumstances, succinylcholine may be administered before and after a nondepolarising NMBA or two different nondepolarising NMBAs are administered in sequence. Combining different NMBAs can result in different degrees of neuromuscular block and management should be guided with the use of a neuromuscular function monitor.

The administration of nondepolarising neuromuscular blocking agent has an antagonistic effect on the subsequent depolarising block induced by succinylcholine. If a nondepolarising NMBA is administered prior to succinycholine, the dose of succinylcholine must be increased.

The administration of succinylcholine on the subsequent administration of a nondepolarising neuromuscular block depends on the drug used. Studies have shown that administration of succinylcholien before a nondepolarising NMBA does not affect the potency of mivacurium or rocuronium. But for vecuronium and cisatracurium, it speeds up the onset, increases the potency and prolongs the duration of action.

Combining two nondepolarising NMBAs of the same chemical class (e.g. rocuronium and vecuronium) produces an additive effect, while combining two nondepolarising NMBAs of different chemical class (e.g. rocuronium and cisatracurium) produces a synergistic response.

Inhaled anesthetics

Inhaled anesthetics inhibit nicotinic acetylcholine receptors (nAChRs) and potentiate neuromuscular blockage with nondepolarising NMBAs. It depends on the type of volatile anesthetic (desflurane > sevoflurane > isoflurane > nitrous oxide), the concentration and the duration of exposure.

Antibiotics

Tetracycline, aminoglycosides, polymyxins and clindamycin potentiate neuromuscular blockage by inhibiting ACh release or desensitisation of post-synpatic nAChRs to ACh. This interaction happens mostly during maintenance of anesthesia. As antibiotics typically are given after a dose of NMBA, this interaction needs to be considered when re-dosing NMBA.

Anti-seizure drugs

Patients receiving chronic treatment are relatively resistance to nondepolarising NMBAs due to the accelerated clearance.

Lithium

Lithium is structurally similar to other cations such as sodium, potassium, magnesium and calcium, this causes lithium to activate potassium channels which inhibit neuromuscular transmission. Patients who take lithium can have a prolonged response to both depolarising and nondepolarising NMBAs.

Antidepressants

Sertraline and amitriptyline inhibit butyrylcholinesterase and cause prolonged paralysis. Mivacurium causes prolonged paralysis for patients chronically taking sertraline.

Local anesthetics (LAs)

LAs may enhance the effects of depolarisation and nondepolarising NMBAs through pre and post-synaptic interactions at the NMJ. It may result in blood levels high enough to potentiate NMBA-induced neuromuscular block. Epidurally administered levobupivacaine and mepivacaine potentiate amino-steroidal NMBAs and delay recovery from neuromuscular blockade.

Estimating effect
Methods for estimating the degree of neuromuscular block include valuation of muscular response to stimuli from surface electrodes, such as in the train-of-four test, wherein four such stimuli are given in rapid succession. With no neuromuscular blockade, the resultant muscle contractions are of equal strength, but gradually decrease in case of neuromuscular blockade. It is recommended during use of continuous-infusion neuromuscular blocking agents in intensive care.

Reversal
The effect of non-depolarizing neuromuscular-blocking drugs may be reversed with acetylcholinesterase inhibitors, neostigmine, and edrophonium, as commonly used examples. Of these, edrophonium has a faster onset of action than neostigmine, but it is unreliable when used to antagonize deep neuromuscular block. Acetylcholinesterase inhibitors increase the amount of acetylcholine in the neuromuscular junction, so a prerequisite for their effect is that the neuromuscular block is not complete, because in case every acetylcholine receptor is blocked then it does not matter how much acetylcholine is present.

Sugammadex is a newer drug for reversing neuromuscular block by rocuronium and vecuronium in general anaesthesia. It is the first selective relaxant binding agent (SRBA).

History
Curare is a crude extract from certain South American plants in the genera Strychnos and Chondrodendron, originally brought to Europe by explorers such as Walter Raleigh Edward Bancroft, a chemist and physician in the 16th century brought samples of crude curare from South America back to the Old-World. The effect of curare was experimented with by Sir Benjamin Brodie when he injected small animals with curare, and found that the animals stopped breathing but could be kept alive by inflating their lungs with bellows. This observation led to the conclusion that curare can paralyse the respiratory muscles. It was also experimented by Charles Waterton in 1814 when he injected three donkeys with curare. The first donkey was injected in the shoulder and died afterward. The second donkey had a tourniquet applied to the foreleg and was injected distal to the tourniquet. The donkey lived while the tourniquet was in place but died after it was removed. The third donkey after injected with curare appeared to be dead but was resuscitated using bellows. Charles Waterton's experiment confirmed the paralytic effect of curare.

It was known in the 19th century to have a paralysing effect, due in part to the studies of scientists like Claude Bernard. D-tubocurarine a mono-quaternary alkaloid was isolated from Chondrodendron tomentosum in 1942, and it was shown to be the major constituent in curare responsible for producing the paralysing effect. At that time, it was known that curare and, therefore, d-tubocurarine worked at the neuromuscular junction. The isolation of tubocurarine and its marketing as the drug Intocostrin led to more research in the field of neuromuscular-blocking drugs. Scientists figured out that the potency of tubocurarine was related to the separation distance between the two quaternary ammonium heads.

Neurologist Walter Freeman learned about curare and suggested to Richard Gill, a patient suffering from multiple sclerosis, that he try using it. Gill brought 25 pounds of raw curare from Ecuador. The raw curare was then given to Squibb and Sons to derive an effective antidote to curare. In 1942, Wintersteiner and Dutcher (two scientists working for Squibb and Sons) isolated the alkaloid d-tubocurarine. Soon after, they developed a preparation of curare called Intocostrin.

At the same time in Montreal, Harold Randall Griffith and his resident Enid Johnson at the Homeopathic Hospital administered curare to a young patient undergoing appendectomy. This was the first use of NMBA as muscle relaxant in anesthesia.

The 1940s, 1950s and 1960s saw the rapid development of several synthetic NMBA. Gallamine was the first synthetic NMBA used clinically. Further research led to the development of synthesized molecules with different curariform effects, depending on the distance between the quaternary ammonium groups. One of the synthesized bis-quaternaries was decamethonium a 10-carbon bis-quaternary compound. Following research with decamethonium, scientists developed suxamethonium, which is a double acetylcholine molecule that was connected at the acetyl end. The discovery and development of suxamethonium lead to a Nobel Prize in medicine in 1957. Suxamethonium showed different blocking effect in that its effect was achieved more quickly and augmented a response in the muscle before block. Also, tubocurarine effects were known to be reversible by acetylcholinesterase inhibitors, whereas decamethonium and suxamethonium block were not reversible.

Another compound malouétine that was a bis-quaternary steroid was isolated from the plant Malouetia bequaertiana and showed curariform activity. This led to the synthetic drug pancuronium, a bis-quaternary steroid, and subsequently other drugs that had better pharmacological properties. Research on these molecules helped improve understanding of the physiology of neurons and receptors.

Outdated treatment
Gallamine triethiodide is originally developed for preventing muscle contractions during surgical procedures. However, it is no longer marketed in the United States according to the FDA orange book.

See also
Ganglionic blocker
Cholinergic blocking drugs

References

External links

Muscle relaxants

Muscular system
Neurochemistry

Neuromuscular-blocking drug


Andrew Ketcham Barnett (1852–1914) was a mineral collector and dealer in Penzance, Cornwall, in the United Kingdom. He was Principal of the Penzance School of Mines (now part of the Camborne School of Mines), lectured on mining, and helped to build their mineral collection. He also served as Mayor of Penzance on seven occasions from 1906 to 1913.

Cooper writes of him:
"Barnett was born in Chacewater, Cornwall in 1852. He was an original member of the Mineralogical Society, a Fellow of the Geological Society from 1875, and President of the Royal Geological Society of Cornwall 1907–08, having been awarded their Bolitho Medal in 1906. His classes on mineralogy in 1873 led to the establishment of the Mining and Science School at Penzance of which he became Principal. He was mayor of Penzance seven times from 1906 to 1913. Active as a mineral dealer from at least 1876 to 1887 at Chyandour, Penzance, he specialized in local specimens and occasionally sold minerals brought back from Australia by "Cousin Jack." In the 1881 Census he described himself as an assayer. He is the author of the now-rare Elementary Inorganic Chemistry; lecture notes, ca. 1900."

References

1852 births
1914 deaths
Geologists from Cornwall
Mineralogists from Cornwall
People from Penzance
Fellows of the Geological Society of London
Mayors of places in Cornwall
People from Chacewater
Presidents of the Royal Geological Society of Cornwall

Andrew Ketcham Barnett


Saint-Jean-Baptiste Day (), also known in English as St John the Baptist Day is an official holiday in the Canadian province of Quebec. It takes place annually on June 24. Although, it is not the official name of this holiday, it is popularly known and called in Quebec, as the Fête nationale du Quebec (National Holiday of Quebec).

Originally a religious day, it was brought to Canada by French settlers in the 1600s, celebrating the traditional feast day of the Nativity of Saint John the Baptist. It was declared a public holiday in Quebec in 1925. In 1977, Quebec declared Saint-Jean-Baptiste Day the national day of Quebec.

Other Canadian provinces and territories also have their own official holidays celebrating the foundation of their provinces or territories. Saint-Jean-Baptiste Day differs from them, that it is today celebrated like a national day rather than a religious holiday, because it became highly politicized with the rise of Quebec nationalism and separatism. As a result, the religious symbolism of this day is largely forgotten, and acts as a counter holiday for Quebec nationalists and separatists against Canada Day.

Quebec
Quebec
Holidays of Canada
June events

Saint-Jean-Baptiste Day


Sir Leoline Jenkins (1625 – 1 September 1685) was a Welsh academic, diplomat involved in the negotiation of international treaties (e.g. Nimègue), jurist and politician. He was a clerical lawyer who served as Judge of the High Court of Admiralty from 1668 to 1685, and enjoyed a high reputation for judicial integrity. As a statesman he served as Secretary of State from 1680 to 1684.

Biography

He was originally from Llantrisant in south Wales, son of Leoline (an  anglicisation of Llewellyn) Jenkins, a small landowner. He himself spoke fluent Welsh, and was fond of quoting Welsh proverbs, sometimes to the bewilderment of his listeners. He went to school in the nearby town of Cowbridge and then to Jesus College, Oxford.

Civil War and Interregnum

He fought on the Royalist side during the English Civil War. On the failure of the Royalist cause, he retired to Glamorgan in 1648, and entered the household of the Welsh Royalist Sir John Aubrey, first of the Aubrey baronets, at Llantrithyd, as did his two most valuable patrons, Gilbert Sheldon, the future Archbishop of Canterbury, and Sir Francis Mansell, Jenkins' predecessor as Principal of Jesus College.

He set up a small private school for the education of Aubrey's son and other local boys, but it was broken up by Parliament in 1651 as a seminary for potential traitors. He moved with some of his pupils to Oxford, where he set up another school known popularly as "the Little Welsh Hall", but in 1655 he was forced to flee to the Continent. At the Restoration of Charles II he was made a fellow of Jesus College and became Principal on Mansell's retirement the following year.

Restoration

As Principal of Jesus College from 1661 to 1673, he was responsible for much construction work, including the college library. The position was one of several rewards he received from King Charles II of England for his loyalty to the Royalist cause during the English Civil War.

Judge
Due to his close friendship with Archbishop Sheldon, he was also created a judge, first of the consistory court of Westminster, then of the Arches Court and finally of the Court of Admiralty. As Judge of the Court of Admiralty he won Samuel Pepys' warm praise for his ability and integrity, although Pepys was told that his appointment had not been welcomed by the advocates at Doctors Commons. He played a crucial role in the development of English Admiralty law as a coherent body of legal principles.

He was also an expert on international law. On the death of the queen mother Henrietta Maria at Colombes in August 1669, Jenkins was sent to Paris to argue that the disposition of her personal property was governed by English, not French law: the result would be that the property would pass in its entirety to Charles II, rather than to his sister Henrietta, Duchess of Orleans, who would have been the beneficiary under French law. His arguments were successful and on his return to England, Charles rewarded him with a knighthood.

Diplomat
He was one of the Commissioners appointed to negotiate the abortive Union with Scotland in 1669. In the 1670s he spent much of his time on the Continent engaged in a number of diplomatic missions. Notably, he was England's principal representative at the Congress of Nijmegen (1676-1679) which brought to an end the Franco-Dutch War, and for a time the sole representative. Critics said that he was "in agony" at being left with the sole responsibility for making decisions. Certainly, as the English government ruefully admitted, Nijmegen was "far from being such a peace as his Majesty would have wished for", although the unsatisfactory outcome from the English point of view was largely due to the resentment of English interference by both French and Dutch representatives at the Congress, rather than to any blunder by Jenkins.

Secretary of State

Jenkins was made a privy counsellor in February 1680. During the Exclusion Crisis he vehemently opposed Exclusion, and acted as the effective Government leader in the Commons. After the failure of Exclusion he played a major role in the so-called "Tory Revenge", the 1681-4 campaign to crush the Whig opposition.

He served as Secretary of State for the Northern Department from 26 April 1680 to 2 February 1681 and Secretary of State for the Southern Department from 2 February 1681 to 14 April 1684. His major legislative achievements include authoring the Statute of Frauds (29 Cha. 2. c. 3) and the Statute of Distributions (22 & 23 Cha. 2. c. 10), dealing with the inheritance of personal property. Whilst Secretary of State, he was served by the Welsh lawyer (and former student of Jesus College) Owen Wynne, who has been called "an early example of the permanent civil servant."

As a Minister, if not noted for brilliance, he was hard-working and incorruptible. Though Gilbert Burnet found him "heavy and dull" he could show great spirit and determination when necessary. At a meeting of the Privy Council in October 1681, some of the Councillors, Jenkins wrote to a colleague, "were pleased to fall upon me" for not sharing with them important items of foreign policy. Jenkins staunchly defended the practice of keeping such information strictly confidential. He argued that the Secretaries of State "were not at liberty to carry any part of their intelligences to the Council, unless his Majesty directed it specifically": this was a rule which he had always followed and by which he was "indispensably bound".

In failing health, he retired in 1684 to his house at Hammersmith and died there the following year. He never married.

He is regarded as the second founder of the eminent Cowbridge Grammar School, renowned for its academic standards which he had himself attended. He is buried in the chapel of Jesus College, at which he had previously been a student before becoming Principal, and to which he bequeathed most of his estate.

Leoline Fellows

In his will, Jenkins stated: "It is but too obvious that the persons in Holy Orders employed in his Majesty's fleet at sea and foreign plantations are too few". To address this, he established two Fellowships at Jesus College, whose holders should serve as clergy "in any of his Majesty's fleets or in his Majesty's plantations" under the direction of the Lord High Admiral and the Bishop of London respectively. The last such fellow, Frederick de Winton, was appointed in 1876 and held his fellowship until his death in 1932. This category of fellowship was abolished in 1877 by the Oxford and Cambridge Universities Commission, without prejudice to the rights of existing holders such as de Winton.

References

External links

1625 births
1685 deaths
17th-century diplomats
17th-century Welsh judges
Alumni of Jesus College, Oxford
British Secretaries of State
English MPs 1661–1679
English MPs 1679
Fellows of Jesus College, Oxford
Founders of Welsh schools and colleges
Members of the pre-1707 Parliament of England for the University of Oxford
Members of the Privy Council of England
People from Llantrisant
People educated at Cowbridge Grammar School
People from Cowbridge
Principals of Jesus College, Oxford
Secretaries of State for the Northern Department
Secretaries of State for the Southern Department
Welsh diplomats
17th-century philanthropists
Knights Bachelor

Leoline Jenkins


Mason Cooley (1927 – July 25, 2002) was an American aphorist known for his witty aphorisms. One of these such aphorisms Cooley developed was "The time I kill is killing me."

He was professor emeritus of French, speech and world literature at the College of Staten Island. He was also an assistant professor of English at Columbia University from 1959 to 1967 and an adjunct professor from 1980 to 1988.

He received his B.A. from San Diego State University and his Ph.D. from Oxford.

1927 births
2002 deaths
San Diego State University alumni
Columbia University faculty
Aphorists
College of Staten Island faculty
Alumni of the University of Oxford
American expatriates in England

Mason Cooley


A trap door or trapdoor is a door in the ground or in a floor,  that one enters vertically. Some can open when someone is standing on it. People typically put small doors disguised as something normal to scare a person falling into a trapdoor. They can be used for malicious purposes like murder. However, they can be used to hide things from other people.

Trap doors are popular in mystery themed movies. The victim who falls down the trap door often is met with danger or a hidden treasure. A standard cliché deals with the victim finding himself in an alligator filled swamp (most famously seen in Scooby Doo cartoons).

Infrastructure

fi:Kattoluukku

Trap door


This is a list of people in blockchain technology, people who do work in the area of Blockchain and Cryptocurrency, in particular researchers, business people, and authors.

Some people that are notable as programmers are included here because they work in research as well as programming. A few of these people pre-date the invention of this technology; they are now regarded as people in blockchain technology because their work can be seen as leading to the invention of this technology.

A

 Gavin Andresen, former Bitcoin lead developer
 Andreas Antonopoulos, author of Mastering Bitcoin
 Jeremy Allaire, CEO and founder of the digital currency company Circle and Chairman of the Board of Brightcove

B

 Brian Behlendorf, Executive Director of Hyperledger Project
 Brendan Blumer, CEO of Block.One
 Vitalik Buterin, founder of Ethereum
 Adam Back, author of Hashcash and CEO of Blockstream

C

 Wences Casares, CEO of Xapo
 David Chaum, computer scientist, cryptographer and blockchain pioneer.

D

 Wei Dai, creator of b-money; inspired the creation of Bitcoin by Satoshi Nakamoto

F

 Hal Finney, the recipient of the first Bitcoin transaction

G

 David Gerard, author of Attack of the 50-foot Blockchain in 2017.
 Tony Gallippi, founder of BitPay, a global bitcoin payment service provider.

H

 Charles Hoskinson, co-founder of Ethereum and founder of Cardano

I
 Ruja Ignatova, founder of OneCoin, a pyramid scheme promoted as a cryptocurrency.

K
 Dave Kleiman associated with Craig Wright
Kofi Genfi, co-founder of Mazzuma

L

 Chris Larsen, CEO of Ripple
 Brad Garlinghouse, CEO of Ripple Labs

M

 Blythe Masters, CEO of Digital Asset Holdings

N

 Satoshi Nakamoto, the name used by the unknown person or people who designed bitcoin
Nii Osae Osae Dade, co-founder of Mazzuma

S

 Emin Gün Sirer, professor at Cornell University, who studies distributed and peer-to-peer systems
 Jorge Stolfi, Brazilian professor at the University of Campinas, cryptocurrency skeptic
 Nick Szabo, computer scientist, cryptographer, and legal scholar known for his research in digital contracts currencies.

T

 Alex Tapscott, co-author of Blockchain Revolution, CEO and founder of Northwest Passage Ventures, an advisory firm for early-stage blockchain companies
 Don Tapscott, co-author of Blockchain Revolution, CEO of Tapscott Group, co-founder of Blockchain Research Institute

V

Roger Ver, Bitcoin Foundation co-founder, promoter of Bitcoin Cash

W

 Zooko Wilcox-O'Hearn, creator of the crypto coin, Zcash
 Gavin Wood, co-founder of Ethereum
 Jihan Wu, co-founder of Bitmain

Z

 Micree Zhan, co-founder of Bitmain
 Changpeng Zhao, founder of exchange Binance

See also

 Blockchain
 Bitcoin
 List of bitcoin companies

References

Blockchain

List of people in blockchain technology


Richard Boden (born 4 January 1953, Birmingham) is a British television director and producer best known for his work on situation comedies including 'Allo 'Allo!, Blackadder Goes Forth, 2point4 Children, Life of Riley and The IT Crowd, the latter two of which he is also the producer. He is also the producer of The Walshes. Starting his career at the BBC, he was later Head of Comedy for Carlton and Central Television, before going freelance in 2001.

References

1953 births
Living people
English television directors
English television producers
BBC people

Richard Boden


Amas de Casa Desesperadas (Colombian-Ecuadorian version) is one of the Latin-tailored versions of Desperate Housewives, the Emmy and Golden Globe award-winning American television comedy-drama series created by Marc Cherry. It debuted on 21 May 2007 on Teleamazonas and on 1 October 2007 on RCN TV.

Basic settings
The show takes place on the fictional street of Manzanares. It follows the lives of four women, seen through the eyes of their dead neighbor - as they work through domestic struggles while several mysteries unfold in the background.

Cast
 Ana Maria Orozco as Susana Martinez
 Ruddy Rodríguez as Eugenia de Koppel (Season 1)
 Geraldine Zivic as Lina Yepes (Season 1)
 Sofía Vergara as Alicia Oviedo
 Lorena Meritano as Veronica Villa
 Marisol Romero as Gabriela Solis
 Carolina Gómez as Eugenia de Koppel (Season 2)
 Flora Martínez as Lina Yepes (Season 2)
 Diego Trujillo as Armando Koppel (who dies in Season 1)
 Diego Ramos as Miguel Delfino
 Víctor Mallarino as PabloOviedo
 Valeria Santa as Daniela Koppel
 Cristian Quezab as Andrés Koppel
 Valentina Acosta as Lucía Quiñónez
 Juan Manuel Gallego as Julián Oviedo
 Helena Mallarino as Felicidad Ruíz
 María Angélica Mallarino as Marta Ruíz
 Diana Guerrero Vélez as Domenica Koppet
 Julián Arango as Tomás Aguilar
 Rodrigo Guirao Díaz as Juan el Jardinero
 Juan Carlos Salazar as Carlos Solís
 Estefany Escobar as Alejandra Perreta
 Mario Moscoso as Leonardo Herrera
 María Cecilia Botero as Irene Peláez
 Tatiana Rentería as Luisa Quiñónez
 Jairo Camargo as Cristóbal Quiñónez

Writers and directors
 Production: Buena Vista International Television Latin America
 Production Companies: Pol-ka Productions (Argentina) and Vista Productions (Colombia)
 Countries: Colombia, Ecuador
 Colombian Executive Producers: Jaime Sánchez Cristo and Sofía Vergara
 Ecuadorean Executive Producers: Sebastián Corral and Claudia Cárdenas
 Direction: Sebastian Pivotto, Martin Desalvo
 General Direction: Víctor Mallarino
 Executive Production: Diego Andrasnik
 Executive Production Buena Vista International Television: Leonardo Aranguibel and Fernando Barbosa

External links

References

Comedy-drama television series
Desperate Housewives
2007 Colombian television series debuts
Non-American television series based on American television series
RCN Televisión original programming
Spanish-language television shows
Television shows set in Colombia
Television shows set in Ecuador

Amas de casa desesperadas (2007 TV series)


is a Japanese former actress. Her acting career began in early 2001, when she was cast for the lead role in the movie Platonic Sex among 12,083 applicants. Now she is probably best known for roles in various TV Dramas and tokusatsu shows such as Ultraseven X and Kamen Rider Kiva. She was represented by Watanabe Entertainment. In July 2011 she retired from show business, citing stress and a desire to resume a normal life as reasons for her decision.

Filmography

Television
Kamen Rider Kiva (TV Asahi, 2008) as Maya/Queen/Pearlshell Fangire (1986 Timeline)
Keishicho Sosa Ikka 9 Gakari 3 (TV Asahi, 2008) as Natsuki
Mikon Six Sisters 2 (CBC/TBS, 2008) as Hitoshi Atsushi (6th sister)
Ultraseven X (CBC/TBS, 2007) as Saeki Elea
Keishicho Sosa Ikka 9 Gakari 2 (TV Asahi, 2007) as Natsuki
Mikon Six Sisters (CBC/TBS, 2006) as Hitoshi Atsushi (6th sister)
Shin Ningen Kosaten (NHK, 2006) as a bad girl
Kekkon Dekinai Otoko (Fuji TV, 2006, ep4) as a guest in ep. 4
Oniyome Nikki (Fuji TV, 2005) as Nakagawa Yuki
Daisuki! Itsutsugo (TBS, 2004) as Nakagawa Kaori
Fantasma - Noroi no Yakata (TV Tokyo, 2004) as Asakura Yuka
Hagure Keiji Junjoha (TV Asahi, 2003)
Kyohansha (NTV, 2003)
Dobutsu no Oisha-san (TV Asahi, 2003) as Shimada Sayo
Sky High (TV Asahi, 2003) as a guest in ep. 2
Tokyo Niwatsuki Ikkodate (NTV, 2002)

Films
Girls life's (2009) as Miki
Tenshi no Koi (2009) as Naoko
Prisoner No. 07: Reina (JOSHÛ: 07-GÔ REINA) (2006)
Ori Nyosho Reika Shukan (2006)
Satsujinbachi - kirâ bî (Killer Bee) (2005)
Platonic Sex (2001) as Kadokura Aoi

Discography
"Rainy Rose (Queen Edit.)" as Maya/Queen/Pearlshell Fangire (1986 Timeline), 2009

External links
Official profile
Personal blog
Kagami Saki's Poetry Blog

References

1985 births
Living people
Japanese actresses
Japanese idols
Japanese female models

Saki Kagami


Felipe Andres Coronel (born February 19, 1978), better known by the stage name Immortal Technique, is an American rapper and activist. Most of his lyrics focus on controversial issues in global politics, from a radical left-wing perspective.

Immortal Technique seeks to retain control over his production, and has stated in his music that record companies, not artists themselves, profit the most from mass production and marketing of music. He claimed in an interview to have sold close to a combined total of 200,000 copies of his first three official releases.

Early life
Coronel was born in a military hospital in Lima. He is of mostly Amerindian descent, and also has Spanish, French and African ancestry. His family immigrated to Harlem, New York, in 1980 to escape the Peruvian Civil War. During his teenage years, he was arrested multiple times due in part to what he has said was "selfish and childish" behavior. He attended Hunter College High School on the Upper East Side of Manhattan, where his classmates included Chris Hayes and Lin-Manuel Miranda, whom he bullied, although the two later became friends. Shortly after enrolling in Pennsylvania State University, he was arrested and charged with assault-related offenses due to his involvement in an altercation between fellow students; the charges stemming from this incident led to him being incarcerated for a year.

After being paroled, he took political science classes at Baruch College in New York City for two semesters at the behest of his father, who allowed Coronel to live with him on the condition that he went to school. Honing his rapping skills in jail, and unable to find decent wage-paying employment after his release, he began selling his music on the streets of New York and battling with other MCs. This, coupled with his victories in numerous freestyle rap competitions of the New York underground hip hop scene such as Rocksteady Anniversary and Braggin Rites, led to his reputation as a ferocious Battle MC.

Musical career

2000–2005: Revolutionary Vol. 1 and Revolutionary Vol. 2

In 2001, Immortal Technique released his first album Revolutionary Vol. 1 without the help of a record label or distribution, instead using money earned from his rap battle triumphs. He also battled but lost to Posta Boy in 106 & Park's Freestyle Friday. Revolutionary Vol. 1 also contained the underground classic "Dance with the Devil". In November 2002, he was listed by The Source in its "Unsigned Hype" column, highlighting artists that are not signed to a record label. The following year, in September 2003, he received the coveted "Hip Hop Quotable" in The Source for a song entitled "Industrial Revolution" from his second album. Immortal Technique is the only rapper in history to have a "Hip Hop Quotable" while being unsigned. He released his second album Revolutionary Vol. 2 in 2003, which featured an intro and a spoken-word piece by death row inmate Mumia Abu-Jamal. In 2004 and 2005, Viper Records and Babygrande Records, respectively, re-released Immortal Technique's debut, Revolutionary Vol. 1, to make it available to a wider audience. "Point of No Return" from Revolutionary Vol 2 was used as the entrance theme for Rashad Evans during the UFC 88 Main Event between Chuck Liddell and Rashad Evans.

2005–present: The 3rd World, The Martyr and The Middle Passage

Between 2005 and 2007 Immortal Technique began working on The Middle Passage and The 3rd World, the two albums that would serve a follow-up to Revolutionary Vol. 2. The 3rd World, produced by DJ Green Lantern, was released in 2008. Emilee Woods, writing for RapReviews.com, reviewed the album positively, praising its "earnestly and skillfully delivered" material, and claiming that Technique had "finally found a comfort zone in the balance between lyricism and message."

He was also featured on several movie soundtracks and video game soundtracks, all the while touring relentlessly. In October 2011, Immortal Technique released The Martyr, a free compilation album of previously unreleased material and new tracks.

In an interview in 2020 with Latino USA, Immortal Technique discussed that he was working on writing a book. He also mentioned that he was in the process of creating a new album, but had faced setbacks because of the Covid-19 Pandemic.

Collaborations

The summer of 2005 saw the release of "Bin Laden", a vinyl single 12" featuring Mos Def and DJ Green Lantern. The single also contained a remix of the song featured Chuck D of Public Enemy and KRS-One. In early 2006, the song "Impeach the President", featuring Dead Prez and Saigon turned up in the mixtape "Alive on Arrival" DJ Green Lantern. This is a simple version of The Honeydrippers, 1973, in which Immortal Technique urged fans to organize a vote of censure against George W. Bush. In April 2009, a new song leaked on the internet named "Democratie Fasciste (Article 4)" by Brazilian-French rapper Rockin' Squat which featured Immortal Technique. The official release of the song and Rockin' Squat's album Confessions D'un Enfant Du Siècle Volume 2 was on May 12, 2009. The instrumental from the song was sampled from Wendy Rene's "After Laughter". The song expresses the inequalities of the Third World and revolutionary events throughout history against tyranny and oppression.

The song contains lyrics in English (Immortal Technique), French (Rockin' Squat) and brief shout outs in Spanish (Immortal Technique). This song is Immortal Technique's first official international collaboration.  In early 2009, it was announced that there would be a collaboration between Technique and UK underground artist Lowkey, on a single called "Voices of the Voiceless". On September 11, 2009, a "snippet" of the song was released on YouTube.  The preview was released ahead of its September 21 launch on iTunes, as part of a web-campaign that included updates, promotion and links on forums, E-Magazines and several social networking sites. The song's lyrics cover a broad range of issues that are familiar to listeners of both artists – racism, world revolution, war, socialism, government control, rape, famine, colonialism, Classism, self-determination and the war in Iraq.

Activism

Immortal Technique visits prisons to speak to youth and working with immigrant-rights activists, and raising money for children's hospitals overseas. He created a writing grant program for high-school students as well.

In June 2008, Immortal Technique partnered with Omeid International, a non-profit human rights organization, and dubbed the work as "The Green Light Project". With the profits of the album The 3rd World, he traveled to Kabul, Afghanistan to help Omeid build an orphanage, the Amin Institute, without corporate or external funding.

Other work

Films
Immortal Technique featured in Ice-T's documentary Something from Nothing: The Art of Rap.

The (R)evolution of Immortal Technique
A documentary about Immortal Technique was released in September 2011 and premiered at the Harlem Film Festival. It was released on DVD on July 10, 2012.

This Revolution

Immortal Technique appeared as himself in a docudrama film entitled This Revolution, which was recorded during the 2004 Republican National Convention in New York. The tape contains the protests surrounding the convention in the form of a documentary. It also featured Viper Records affiliates Akir and producer SouthPaw in roles.

Since then, Immortal Technique has taken control of Viper Records and has signed a distribution deal with Babygrande Records / E1 Entertainment to vent to their next album. SouthPaw has managed to establish himself as A&R of Viper Records.

Discography

Studio albums

Compilation album

Singles

References

External links

21st-century American rappers
Hardcore hip hop artists
Underground rappers
Hispanic and Latino American rappers
Rappers from Manhattan
Hip hop activists
Political music artists
American music industry executives
American socialists
Baruch College alumni
Pennsylvania State University alumni
American people convicted of assault
Musicians from Harlem
American people of indigenous peoples descent
American people of Peruvian descent
Musicians from Lima
Peruvian exiles
1978 births
Living people
Hunter College High School alumni

Immortal Technique


Manuela Maria Campanelli (born 1962 in Milan) is an Italian science journalist.  She has written articles for SuperQuark News, Focus, Oggi, OK Salute, Corriere della Sera, Donna & Mamma, and Corriere Medico e Doctor.

She is a graduate of the University of Milan (Biological Sciences) and earned a master's degree in Scientific Journalism from SISSA (Scuola Internazionale Superiore di Studi Avanzati) in Trieste, Italy.

Manuela Campanelli has won numerous prizes and awards, including the Voltolino Prize for Dissemination of Science in 1999, and the Novo Nordisk Media Prize for her article
"Living Well with Diabetes" in 2007.

With Luigi Ferini-Strambi (Fondazione San Raffaele del Monte Tabor) she wrote the book Un Sonno Perfetto (A Perfect Sleep), which discusses the causes and treatments of sleep disorders. With Arianna Banderali she wrote the book Ricette low cost: Mangiare bene e sano spendendo poco (Low-cost recipes: eating well and healthily while spending little).

Books by Manuela Campanelli
Ferini-Strambi, Luigi and Campanelli, Manuela M. (2008). Un sonno perfetto. I segreti per riposare, dormire, vivere meglio (A Perfect Sleep). 256 pages. (Sperling and Kupfer, )
Banderali, Arianna and Campanelli, M. (2010). Ricette low cost: Mangiare bene e sano spendendo poco (Low-cost recipes). 128 pages. (Edizioni red, )

External links
 Novo Nordisk Prizes -- 2007

1962 births
Living people
Journalists from Milan
Italian women journalists
20th-century Italian journalists
21st-century Italian journalists

Manuela Campanelli (science journalist)


Running Out of Time (; literal title: Hidden War) is a 1999 Hong Kong action thriller film produced and directed by Johnnie To and starring Andy Lau as a cancer-ridden criminal who challenges a police negotiator, played by Sean Lau, to a 72-hour battle of wits and courage. Andy Lau won his first Hong Kong Film Award for Best Actor in 2000 for his performance in the film. The film was followed by a sequel, Running Out of Time 2, which was released in 2001.

Plot

Cheung Wah is diagnosed as suffering from late-stage cancer and given four weeks to live by his doctor. As Chueng eats at a diner, Inspector Ho Sheung-sang, a police negotiator, has been called to the scene of a bank robbery standoff that's being bungled by his inept boss, Wong Kai-fat. Ho goes in to negotiate with the robbers. After goading them to release the injured hostages first, a man amongst the hostages stands up and shoots the robbers dead. The man claims to be an off-duty police officer, but Ho realizes that the man is the mastermind of the robbery. Ho convinces the man that it is impossible to shoot him and get away with it as his fingerprints would be all over the murder weapon. As Ho leaves the crime scene to grab some breakfast, a shot rings out and Ho tells Wong that the robbery mastermind has committed suicide.

Cheung takes an interest in Ho, who he discovers was a former member of the Special Duties Unit. Cheung then stages his own robbery of a finance company to get in contact with Ho. When Ho finally arrives, Cheung proposes that they play a three-day long game. Cheung shoots the finance company manager, and Ho and the police give chase until Cheung stalls them enough to make an escape with a bomb, which turns out to be fake. It is revealed the finance manager is still alive and was only shot with messy red looking paint. Cheung makes his escape by posing as a cop.

Ho meets with Cheung after posing as a taxi driver. Amazed at Ho's ploy, Cheung will admit defeat at the game if Ho can take him to the police station before three days are over. Cheung then pulls a gun and starts shooting out the window. When Ho slams the brakes, Cheung flees and jumps aboard to mini-bus.

Meanwhile, a man known only as Baldy is having a diamond that he had stolen appraised by the old man who was taking pictures of Ho earlier. The two Americans who stole the diamond for him ask for more money. Baldy pulls out his gun and points it at the old man, who confirms its authenticity. Baldy then kills the two Americans and takes the diamond. Ho returns to the finance company for further questioning, and sees Baldy entering the office space next door. He tries to get in, but it stopped by one of Baldy's men.

As Cheung watches a video feed of the vault at Baldy's office, he puts a screw inside a box. As he takes a drink, he coughs out blood. Ho tries to reason why Cheung held up the finance company and not the jewelry or antique stores in the building and why Cheung chose him for his game. As he leaves for the day, Ho receives a Cheung's package. He meets up with his friend, the Head of Interpol, who's given him information on Baldy, who's wanted for possession of explosives, and one Peter Cheung, the old man who took pictures of him and appraised the diamond. Peter Cheung was Baldy's boss until Baldy kicked him out.

More focused on the case, he skips having dinner with her to break into Baldy's office. When trying to get in, he's turned away by security, who's told by Wong that he's not on the case. Ho sneaks in anyway as Cheung watches him on video feeds. Using a packet of dairy creamer he took from security, Ho enters the finance company and finds the grate that Cheung's screw comes from. Going through the vents, he finds men that Baldy had to keep an eye on the diamond and Cheung's video equipment, which Cheung uses to give away Ho's entrance. Ho tries to escape, but Cheung calls him and leads him to an emergency door that turns out to be a dead end. Ho tries to pick the lock on the emergency door, which is opened by the guy who he encountered earlier when he tried to get into the office.

Knowing that Baldy will come down to get the diamond out of there, Cheung reveals a car identical to Baldy's. One of Baldy's henchmen sees the car, assuming that Baldy is in it. As the henchmen approaches towards the car, Cheung takes the diamond, posing as Baldy with the bald cap and knocks the henchmen out. Ho and Baldy's men give chase as Cheung flees away from them. As both Ho and Cheung get fired on by Baldy's men, the two are amazed at each other's resilience. They work together to get out of the predicament, but Ho realizes that now he's the one with a gun and Cheung is the one driving. Cheung reiterates that if Ho can get him to the police station, he wins. However, Cheung drives the car into a wall. After the collision, both men try their hardest to get the diamond as they both feel wobbly after the crash. Ho reaches towards the diamond but collapses, which lead to Cheung walking away with it. However, Cheung drops his painkilling pills while trying to get the diamond.

After Ho gets checked up, Wong, who thinks the pills are Ho's, tries to talk to him. Ho's Interpol friend comes and brings him more information on Peter Cheung, who died a year ago, and a photo of Cheung, his son. Cheung, who has been masquerading as his father, sends Baldy proof that he has the diamond and will give it back for $20 million HK. Ho meets with Cheung at the diner, asking why he's still playing with him even though he's got the diamond and has avenged his father. Ho gives him a minute to give him a good reason not to arrest him now. Cheung wants to have Ho arrest Baldy, but realizes that Ho isn't doing this for fame or a promotion. Cheung then taunts Ho, saying that he's beating Ho in their little game. Ho lets him leave so they can finish their game.

Cheung takes a bus, where he meets the woman from earlier again. The bus is pulled over by the police, and the woman invites Cheung over like before. She takes him to a restaurant, but he leaves when he starts coughing up blood.

Cheung has set the place to make the exchange for the diamond at a bowling alley, which is being staked out by Ho, Wong and the police. Ho bumps into the same henchman he's been running into, who still doesn't recognize him. Cheung has Ho make the exchange for him, but Baldy has Cheung, who's disguised as a woman, get the money. Ho tries to get Wong to check in on the money exchange, but Wong doesn't get the message. Cheung, who's taken out Baldy's man and the cop while getting the money, takes off his disguise and makes the exchange himself, telling Ho that the "woman" is conning him. Baldy takes Cheung's bag, which holds a bowling ball, and throws it on the floor in rage, revealing diamonds inside. The police move in and arrest Baldy for stealing the diamonds from the finance company next door.

Cheung leaves the scene with the diamond and the money. Ho catches up with Cheung, finally arrests him and prepares to take him to the police station. Cheung reveals another "bomb" and pulls out another detonator like the one before. Ho calls him on his bluff and presses the detonator, which starts a timer on the bomb. Cheung, who knows he's going to die soon, wishes that he not die in a jail cell, so Ho stops and gets out of the car, seeing as Cheung is dying in the car. The timer reaches zero, which starts up the car and Cheung escapes again. When Wong berates Ho for letting Cheung get away again, Ho simply ignores him and goes to grab something to eat. Cheung, playing dead, drives away, smiling.

Ho reads in the newspaper that someone using his name donated HK$20 million to a children's cancer foundation. He hops on a bus and meets the woman Cheung kept running into wearing the diamond. Ho admires the diamond, though she brushes it off as something cheap. He asks who gave it to her, and she says she hasn't seen him in a while. Ho tells her to hold on to it.

Cast
 Andy Lau as Cheung Wah
 Sean Lau as Inspector Ho Sheung-sang
 Yoyo Mung as Leung Yuen-ting (Girl on the Mini Bus)
 Waise Lee as Baldy
 Benz Hui as Chief Inspector Wong Kai-fat
 Lam Suet as Baldy's Henchman
 Ruby Wong as Head of the Interpol
 Ai Wai as Cop at bank
 Hung Wai-leung as Mr. Lee
 Lam Wai-kin as Mr. Hui - Negotiator
 Law Ching-ting as Baldy's thug
 Lee Sau-kei as Cheung's doctor
 So Yan-tin as Ho's subordinate
 Robert Sparks as an American Diamond Dealer
 Wong Wan-woo as Office building security guard
 Yau Man-shing as Bank Robber
 Yee Tin-hung as Bank robber

Awards and nominations

Notes

External links

1999 films
1999 action thriller films
1999 crime thriller films
Hong Kong action thriller films
Hong Kong crime thriller films
Police detective films
1990s Cantonese-language films
China Star Entertainment Group films
Milkyway Image films
Films about cancer
Hong Kong films about revenge
Films directed by Johnnie To
Films set in Hong Kong
Films shot in Hong Kong
Films with screenplays by Yau Nai-hoi
1990s Hong Kong films

Running Out of Time (1999 film)


Manuel Mondragón (1859–1922) was a Mexican military officer who played a prominent role in the Mexican Revolution. He graduated from the Mexican Military Academy as an artillery officer in 1880. He designed the world's first gas-operated semi-automatic rifle, the M1908 rifle, and a 75mm howitzer. General Mondragón was the father of a model, artist and poet Carmen Mondragón, better known as Nahui Ollin.

Porfiriato
As an adolescent Mondragón entered the Military Academy of Chapultepec, where he specialised in artillery.  Upon finishing his studies, he worked developing military materiel.  He modified the French 75mm howitzer, earning a name for himself among Porfirist military circles.  He perfected a repeating rifle and a 75mm howitzer (the Saint-Chamond-Mondragón), both of which still bear his name.  In 1904 he wrote a manual Description and employment of the instruments for preparing and executing fires, and in 1910 Description of rapid-fire 75mm materiel.  In 1907 he was named Director of the Department of Artillery.

He initiated a project on military organic law, based on mandatory military service, and as professor of the Military Academy released a work in 1910 entitled Defense of the Coasts.  The artillery at the ports of Salina Cruz on the Pacific and Puerto México on the Gulf are due to his efforts.

As a military officer during the Porfirato, he worked against the Maderista movement.  In September 1911, he took leave from the Federal Army, but in 1913 returned, reincorporated in the army to support Gregorio Ruiz in the anti-Maderista rebellion of the Decena trágica.

Mexican Revolution
At the side of General Bernardo Reyes and General Félix Díaz, Mondragón assisted in the start of the coup, known as the Ten Tragic Days, against democratically-elected President of Mexico Francisco I. Madero in February 1913. He allied with General Victoriano Huerta. When Huerta seized presidency, Mondragón was named Secretary of War and the Navy. He served in this position only a short time, resigning in June amid accusations from prominent Huertist politicians and public opinion of his culpability in the advance of revolutionary forces opposed Huerta's regime, due to his incompetence and poor planning in the campaign against them.

Following these accusations, Victoriano Huerta expelled Mondragón from Mexico, heeding the rumor of a plot to overthrow him. Mondragón left for Spain, where the government of France awarded him the Légion d'honneur. General Manuel Mondragón died in exile in San Sebastián in 1922.

Bibliography
 Francisco Naranjo. Diccionario biográfico Revolucionario. Imprenta Editorial "Cosmos", Mexico, 1935. .

1859 births
1922 deaths
Firearm designers
Mexican generals
Mexican inventors
Mexican Secretaries of Defense
People from Ixtlahuaca de Rayón
People of the Mexican Revolution
Porfiriato

Manuel Mondragón


Winged Victory is a 1943 play by Moss Hart, created and produced by the U.S. Army Air Forces during World War II as a morale booster and as a fundraiser for the Army Emergency Relief Fund. Hart adapted the play for a 1944 motion picture directed by George Cukor.

Plot summary
Winged Victory tells the story of a group of recruits struggling to make it through pilot training.  The trainees are a cross-section of American young men.  Their personal lives, their families and sweethearts make up a small part of the story, but most of the drama focuses on training and camaraderie. Music plays a large part in the play, and most of the huge cast were primarily members of a chorus under the direction of famed choral leader Leonard de Paur.  Among the musical numbers are "My Little Dream Book of Memories," and the stirring title anthem, "Winged Victory".

Background
Upon recommendation of Lt. Col. Dudley S. Dean, who had been approached with the idea by talent agent Irving Lazar and Lt. Benjamin Landis, Air Forces Commanding General Henry H. Arnold commissioned famed playwright Hart to create a stage drama that would depict both the training and work of airmen and also the commitment and devotion to duty with which they carried out this work. Arnold gave Hart complete access to Air Forces resources.

Hart traveled the United States visiting Air Forces bases and seeing firsthand how training was carried out.  He then wrote an extremely patriotic and uplifting stage play based on his research.  Hart partnered with Irving Lazar to produce the play and to gather actors for the huge (nearly 300) cast.  Casting calls went out not only to well-known names but to Army units around the country for Air Forces personnel with theatrical or performing background.  All male personnel involved with the show were service members of the U.S. Army Air Forces and were billed with their actual ranks.  Among the then-notable or eventually-to-become-notable members of the cast and crew were Keith Andes, Alan Baxter, Don Beddoe, Whit Bissell, The Blackburn Twins, Sascha Brastoff, Red Buttons, Lee J. Cobb, Mario Lanza, Mark Daniels, Leonard De Paur, Brad Dexter, John Forsythe, Peter Lind Hayes, Harry Horner, Richard Travis, Karl Malden, Billy and Bobby Mauch, Kevin McCarthy, Gary Merrill, Ray Middleton, Barry Nelson, Edmond O'Brien, Walter Reed, George Reeves, Martin Ritt, Archie Robbins, David Rose, Henry Rowland, Alfred Ryder, Howard Shoup, Henry and Jack Slate, Claude Stroud, Don Taylor, and Victor Sen Yung.  Most of the relatively few roles for women in the play were portrayed by wives of the actors.

Production

The play opened in Boston, Massachusetts in the fall of 1943, in a pre-Broadway run, and was a huge success.  It then opened in New York at the 44th Street Theatre on 20 November 1943 and became a smash hit, playing to over 350,000 people in 226 performances.  During the New York run, performers in the show also toured local military camps, providing entertainment to the troops.  A number of Winged Victory actors also rehearsed and produced a production of the play Yellow Jack by Sidney Howard, under the direction of Martin Ritt, which played briefly and simultaneously on Broadway.  The successful run of Winged Victory on Broadway ended only in order that the entire cast travel to Hollywood to appear in the film version.

Adaptation

Twentieth Century Fox purchased the rights and contracted the full cast and in the summer of 1944 produced a film version (which featured a few actors who had not been in the play, including Lon McCallister and Judy Holliday), under the direction of George Cukor.

Tour
Following filming, the company embarked on a national tour of the play, performing 445 times for over 800,000 people in Los Angeles, San Francisco, Denver, Kansas City, Chicago, Detroit, Baltimore (where the theatre proved too small to admit the huge section of a bomber, part of the set for one scene), Washington D.C., and Richmond. At tour's end in April, 1945, the cast and crew were dispersed throughout the Army Air Forces, many of them transferring to the First Motion Picture Unit in California, there to make training films. The Winged Victory company (officially known as the 31st AAF Base Unit) officially disbanded in November 1945.

Due both to its enormous cast and staging demands as well as to the extremely era-specific nature of the play, Winged Victory is one of the biggest hits in Broadway history never to have a second production anywhere.

References

External links

1943 plays
Plays by Moss Hart
Aviation plays

Winged Victory (play)


Andrew George Little  (28 September 1863 – 22 October 1945) was an English historian, specialising in the Franciscans (known as the Greyfriars) in medieval England. He was Professor of History at the University College of South Wales, Cardiff, between 1898 and 1901 (having previously been the college's first history lecturer there since 1892). He was thereafter a visiting lecturer (1903–20) and then reader (1920–32)  in palaeography at the University of Manchester. He was president of the Historical Association from 1926 to 1929, and was elected a Fellow of the British Academy in 1922.

Select publications
For a full bibliography down to 1938, see An address presented to Andrew George Little, with a bibliography of his writings (1938). His books included:

 The Grey Friars in Oxford (Oxford: Clarendon Press for the Oxford Historical Society, 1892).
 Mediaeval Wales, Chiefly in the Twelfth and Thirteenth Centuries (London: T. Fisher Unwin, 1902).
 Initia Operum Latinorum quae Saeculis XIII., XIV., XV. Attribuuntur (Manchester: Manchester University Press, 1904).
 Edition of Thomas of Eccleston, Tractatus de adventu Fratrum Minorum in Angliam (Manchester: Manchester University Press, 1909).
 Studies in English Franciscan History (Manchester: Manchester University Press, 1917) – based on the Ford Lectures he gave at the University of Oxford in 1916
 (Edited based on material by Paul Sabatier) Speculum Perfectionis, 2 vols. (Manchester: British Society for Franciscan Studies, 1928–31).
 (Co-authored with Father Franz Pelster) Oxford Theology and Theologians, c. a.d. 1282–1302 (Oxford: Clarendon Press for the Oxford Historical Society, 1934)

References

Further reading

 F. M. Powicke, "Andrew George Little, 1863–1945", Proceedings of the British Academy, vol. 31 (1945), pp. 335–56.
 J. R. H. Moorman, "A. G. Little: Franciscan historian", The Church Quarterly Review, vol. 144 (1947), pp. 17–27.

1863 births
1945 deaths
19th-century British historians
Fellows of the British Academy
20th-century British historians
Academics of Cardiff University

Andrew George Little


The People's Union of Estonia () was a political party in Estonia. Its last leader was Margo Miljand.

In the 2003 parliamentary election, the party collected 64,463 votes, which made 13.0% share of all votes and 13 mandates out of 101. In 2007's election, this dropped to 39,211 votes (7.1% of the total, a drop of 5.9%), and six seats in the Riigikogu, a loss of 7. It has dropped from fourth to sixth place among parties, having been bested by the Social Democratic Party and (narrowly) by the Greens.

History
The party was founded on 29 September 1994 in Tallinn under the name of Estonian Country People's Party (Eesti Maarahva Erakond, EME). On 18 October 1999 the party was renamed to People's Union of Estonia. On 10 June 2000 the People's Union merged with the Estonian Country Union (Eesti Maaliit, EML) and with the Estonian Party of Pensioners and Families (Eesti Pensionäride ja Perede Erakond, EPPE), becoming the largest political party in Estonia. Another merger with the New Estonia Party (Erakond Uus Eesti) in 2003 resulted in further growth of membership. In 2010, there were more than 9,000 official members in the People's Union of Estonia.

The People's Union of Estonia was an agrarian party with populist, social democratic influences. Consequently, the party experienced difficulties in gaining wider support in cities and big towns. The last couple of years brought along some changes. The representation of the People's Union in towns (including the capital Tallinn) grew and they started to work on involving Russian-speaking minority in political activities. Russian Association of the People's Union was founded in 2005. The People's Union had a youth organisation called the Youth of the People's Union (Rahvaliidu Noored), which had approximately 3000 members.

On the European level the People's Union was a member of the Alliance for Europe of the Nations, but did not have any representatives in the European Parliament. The official organ of the Union was The Caring Estonia (Hooliv Eesti).

The first Chairman of the party was the previous President of the Republic of Estonia, Arnold Rüütel. On 10 June 2000 Villu Reiljan became the new Chairman of the People's Union. He served also as the Minister of Environment when the People's Party participated in the Reform Party's coalition government.

The Union was a member of Estonian government coalitions from 1995 to 1999 and from 2003 to 2007. From 2003 to 2005 they were in government together with the Estonian Reform Party and the Union for the Republic - Res Publica. Following a vote of no confidence against the government of Prime Minister Juhan Parts and Parts' subsequent resignation from the post of Prime Minister, they took part in formation of the new coalition where Res Publica was replaced with the Estonian Centre Party (see Andrus Ansip's cabinet).

In 2003 Estonian parliamentary election the party collected 64,463 votes, which made 13% share of all votes and 13 mandates out of 101. In comparison with previous election in 1999 they gained 6 additional seats in the Estonian Parliament. The representation of the party grew to 16 seats in 2005 when Toomas Alatalu, Robert Lepikson and Jaanus Marrandi, former members of the Estonian Centre Party decided to join the People's Union. After Robert Lepikson's death on 1 July 2005 the People's Party lost a seat, because he was elected in Centre Party list, and his replacement came therefore from the CPE list.

In local elections on 16 October 2005 the People's Union was also rather successful, winning 4 seats in Tallinn City Council and becoming part of coalitions in Tartu, Pärnu and Viljandi. In Tallinn the candidates of the People's Union ran in the list of the Social Democratic Party which has fueled speculations about the possible merger of the two parties. Chairmen of both parties have declared those speculations groundless.

Following the People's Party's poor performance in the March 2007 parliamentary elections, it was not reappointed to the coalition government, which continued to be led by the Reform Party. The Center Party and the People's Party were replaced by the Social Democrats and Pro Patria/Res Publica.

After continued worsening of election results, ERL started to look for a possible merging partner; in 2010, talks with the Social Democratic Party were successfully concluded, and a special congress on merging ERL into the SDE was to be held on 23 May 2010. However, at the party congress, only 172 delegates out of 412 supported the deal; it was considered likely that the ERL would merge with the Centre Party instead. Following the failed merger attempt, leading ERL members left the party and joined the SDE. Since defections (three MPs joined the SDE, one the Reform Party and one Center Party) the ERL had only 1 MP left, which means that it did not have a faction status.

In the 2011 parliamentary election, the ERL did not pass 5% threshold and became an extra-parliamentary party.

Finally, on 24 March 2012, the party merged with the Estonian Patriotic Movement into the Conservative People's Party of Estonia. In an earlier 2006 press release, the Patriotic Movement had characterized the People's Union (and Center Party) as traitors. According to surveys carried out by TNS Emor, the party has lost all its support (0% in April and May 2012).

Electoral results

Parliamentary elections

European Parliament elections

References

External links
Official website (in Estonian)
Youth organisation (in Estonian)

1994 establishments in Estonia
2012 disestablishments in Estonia
Centrist parties in Estonia
Defunct agrarian political parties
Defunct political parties in Estonia
Political parties disestablished in 2012
Political parties established in 1994

People's Union of Estonia


Larry Ryan Squire (born May 4, 1941) is a professor of psychiatry, neurosciences, and psychology at the University of California, San Diego, and a Senior Research Career Scientist at the Veterans Affairs Medical Center, San Diego.  He is a leading investigator of the neurological bases of memory, which he studies using animal models and human patients with memory impairment.

Education
Squire received a B.A. from Oberlin College, where he studied with Celeste McCollough and a Ph.D. from the Massachusetts Institute of Technology, where he studied under the mentorship of Peter Schiller and Hans-Lukas Teuber.  He subsequently completed a postdoctoral fellowship at Albert Einstein College of Medicine.

Career
Next Squire accepted a position as a faculty member at the University of California San Diego, where he has remained since. His publications include more than 480 research articles and two books: Memory and Brain (Oxford Press, 1987) and Memory: From Mind to Molecules with Eric Kandel (Roberts & Co., 2nd Ed, 2009). He is also senior editor of the textbook, Fundamental Neuroscience, now in its 4th Edition and editor-in-chief of The History of Neuroscience in Autobiography (now in eight volumes).

Larry Squire illuminated the anatomy and phenotype of human memory impairment, identified the anatomical components of the medial temporal lobe memory system (with Stuart Zola), pioneered the biological distinction between declarative and nondeclarative memory, explored the conscious and unconscious memory systems of the mammalian brain, and helped establish the standard account of memory consolidation.

Honors and awards
In 1993–1994, Squire served as president of the Society for Neuroscience. He is an elected member of the National Academy of Sciences as of 1993, and served on the governing Council from 2009 to 2012.  He has also been elected to the American Academy of Arts and Sciences, American Philosophical Society as of 1996, and National Academy of Medicine (formerly The Institute of Medicine) as of 2000.

He received the Charles A. Dana Award for Pioneering Achievements in Health in 1993, the Distinguished Scientific Contribution Award from the American Psychological Association in 1993, the William James Fellow of the Association for Psychological Science in 1994, the William Middleton Award from the United States Department of Veterans Affairs in 1994, the Metlife Foundation Award for Medical Research in Alzheimer's Disease in 1999,  the Karl Spencer Lashley Award from the American Philosophical Society in 1995, "for his seminal contribution to the delineation of implicit and explicit memory systems in the brain", the McGovern Award from the American Association for the Advancement of Science in 2004, the Herbert Crosby Warren Medal from the Society of Experimental Psychologists in 2007, the Award for Scientific Reviewing from the National Academy of Sciences in 2012, and the Goldman-Rakic Prize from the Brain & Behavior Research Foundation in 2012.

He received an honorary degree from the University of Basel.

Noted publications (from a total list of 500+)
 Memory and Brain New York ; Oxford : Oxford University Press, 1987. XII, 315 p.
 Memory: from Mind to Molecules, 2nd Edition, with Eric Kandel. Greenwood Village: Roberts & Co.
 Fundamental Neuroscience. 4th ed. San Diego, CA : Academic Press, 2012. (Issued in 1998, 2003 and 2008.) 1426 p. avec CD
 Squire, L. R. (2009).  "Memory and Brain Systems: 1969-2009."  The Journal of Neuroscience, 29, 12711–12716.
 Wixted, J. T. & Squire, L. R.  (2011). "The Medial Temporal Lobe and the Attributes of Memory." Trends in Cognitive Sciences, 15, 210–217.
 Squire, L. R. & Wixted, J. (2011). "The Cognitive Neuroscience of Human Memory since H.M.", Annual Review of Neuroscience, 34, 259–288.
 Insausti, R., Annese, J. Amaral, D. G., Squire, L. R. (2013).  "Human Amnesia and the Medial Temporal Lobe Illuminated by Neuropsychological and  Neurohistological Findings for Patient E.P.", Proceedings of the National Academy of Sciences, US, 110, E1953-E1962.

References

Living people
20th-century American psychologists
American cognitive neuroscientists
Memory researchers
21st-century American psychologists
Members of the United States National Academy of Sciences
Fellows of the American Academy of Arts and Sciences
Fellows of the American Association for the Advancement of Science
Fellows of the Society of Experimental Psychologists
Oberlin College alumni
Massachusetts Institute of Technology alumni
Albert Einstein College of Medicine alumni
University of California, San Diego faculty
Neuropsychologists
Scientists from California
Members of the American Philosophical Society
1941 births
Members of the National Academy of Medicine

Larry Squire