title: Aza-Cope rearrangement

text:
Rearrangements, especially those that can participate in cascade reactions, such as the aza-Cope rearrangements, are of high practical as well as conceptual importance in organic chemistry, due to their ability to quickly build structural complexity out of simple starting materials. The aza-Cope rearrangements are examples of heteroatom versions of the Cope rearrangement, which is a [3,3]-sigmatropic rearrangement that shifts single and double bonds between two allylic components. In accordance with the Woodward-Hoffman rules, thermal aza-Cope rearrangements proceed suprafacially. Aza-Cope rearrangements are generally classified by the position of the nitrogen in the molecule (see figure):

The first example of an aza-Cope rearrangement was the ubiquitous cationic 2-aza-Cope rearrangement, which takes place at temperatures 100-200 °C lower than the Cope rearrangement due to the facile nature of the rearrangement. The facile nature of this rearrangement is attributed both to the fact that the cationic 2-aza-Cope is inherently thermoneutral, meaning there's no bias for the starting material or product, as well as to the presence of the charged heteroatom in the molecule, which lowers the activation barrier.  Less common are the 1-aza-Cope rearrangement and the 3-aza-Cope rearrangement, which are the microscopic reverse of each other. The 1- and 3-aza-Cope rearrangements have high activation barriers and limited synthetic applicability, accounting for their relative obscurity.

To maximize its synthetic utility, the cationic 2-aza-Cope rearrangement is normally paired with a thermodynamic bias toward one side of the rearrangement. The most common and synthetically useful strategy couples the cationic 2-aza-Cope rearrangement with a Mannich cyclization, and is the subject of much of this article. This tandem aza-Cope/Mannich reaction is characterized by its mild reaction conditions, diastereoselectivity, and wide synthetic applicability.  It provides easy access to acyl-substituted pyrrolidines, a structure commonly found in natural products such as alkaloids, and has been used in the synthesis of a number of them, notably strychnine and crinine. Larry E. Overman and coworkers have done extensive research on this reaction.

The cationic 2-aza-Cope rearrangement

The cationic 2-aza-Cope rearrangement, most properly called the 2-azonia-[3,3]-sigmatropic rearrangement, has been thoroughly studied by Larry E. Overman and coworkers. It is the most extensively studied of the aza-Cope rearrangements due to the mild conditions required to carry the arrangement out, as well as for its many synthetic applications, notably in alkaloid synthesis.  Thermodynamically, the general 2-aza-Cope rearrangement does not have a product bias, as the bonds broken and formed are equivalent in either direction of the reaction, similar to the Cope rearrangement. The presence of the ionic nitrogen heteroatom accounts for the more facile rearrangement of the cationic 2-aza-Cope rearrangement in comparison to the Cope rearrangement. Hence, it is often paired with a thermodynamic sink to bias a rearrangement product.

In 1950, Horowitz and Geissman reported the first example of the 2-aza-Cope rearrangement, a surprising result in a failed attempt to synthesize an amino alcohol. This discovery identified the basic mechanism of the rearrangement, as the product was most likely produced through a nitrogen analog of the Cope rearrangement. Treatment of an allylbenzylamine (A) with formic acid and formaldehyde leads to an amino alcohol (B). The amino alcohol converts to an imine under addition of acid (C), which undergoes the cationic 2-aza-Cope rearrangement (D). Water hydrolyses the iminium ion to an amine (E). Treating this starting material with only formaldehyde showed that alkylation of the amine group occurred after the cationic 2-aza-Cope rearrangement, a testament to the quick facility of the rearrangement.

Due to the mild heating conditions of the reaction carried out, unlike the more stringent ones for a purely hydrocarbon Cope rearrangement, this heteroatomic Cope rearrangement introduced the hypothesis that having a positive charge on a nitrogen in the cope rearrangement significantly reduces the activation barrier for the rearrangement.

Reaction mechanism

Rate acceleration due to positively charged nitrogen

The aza-Cope rearrangements are predicted by the Woodward-Hoffman rules to proceed suprafacially. However, while never explicitly studied, Overman and coworkers have hypothesized that, as with the base-catalyzed oxy-Cope rearrangement, the charged atom distorts the sigmatropic rearrangement from a purely concerted reaction mechanism (as expected in the Cope rearrangement), to one with partial diradical/dipolar character, due to delocalization of the positive charge onto the allylic fragment, which weakens the allylic bond. This results in a lowered activation barrier for bond breaking. Thus the cationic-aza-Cope rearrangement proceeds more quickly than more concerted processes such as the Cope rearrangement.

Transition state and stereochemistry
The cationic 2-aza-Cope rearrangement is characterized by its high stereospecificity, which arises from its high preference for a chair transition state.   In their exploration of this rearrangement's stereospecificity, Overman and coworkers used logic similar to the classic Doering and Roth experiments, which showed that the Cope rearrangement prefers a chair conformation.  By using the cationic 2-aza-Cope/Mannich reaction on pyrrolizidine precursors, they showed that pyrrolizidines with cis substituents from E-alkenes and trans substituents from Z-alkenes are heavily favored, results that are indicative of a chair transition state.  If a boat transition state was operative, the opposite results would have been obtained (detailed in image below).  As is the trend with many reactions, conversion of the Z-enolate affords lower selectivity due to 1,3 diaxial steric interactions between the enolate and the ring, as well as the fact that substituents prefer quasi-equatorial positioning.  This helps explain the higher temperatures required for Z-enolate conversion.
The boat transition state is even less favored by the cationic-2-aza-Cope rearrangement than it is for the Cope rearrangement: in analogous situations to where the Cope rearrangement takes on a boat transition state, the aza-Cope rearrangement continues in the chair geometry. These results are in accord with computational chemistry results, which further assert that the transition state is under kinetic control.
 Significantly, these stereochemical experiments imply that the cationic 2-aza-Cope rearrangement (as well as Mannich cyclization) occur faster than enol or iminium tautomerization. If they were not, no meaningful stereochemistry would have been observed, highlighting the facility of this fast reaction.

Additional considerations for stereochemistry
The aza-Cope/Mannich reaction, when participating in ring-expanding annulations, follows the stereochemistry dictated by the most favorable chair conformation, which generally places bulky substituents quasi-equatorially. The vinyl and amine components can have either syn or anti relationships when installed on a ring. This relationship is typically dictated by the amine substituent: bulky substituents lead to syn aza-Cope precursors.  While anti vinyl and amine substituents generally only have one favored transition state, leading to a cis fused ring system, the favored product of syn substituents can change, dictated by steric interactions with solvents or large N-substituents, which may take preference over bulky substituents and change the transition state.

For simple aza-Cope/Mannich reactions that do not participate in ring-expanding annulation, namely condensations of amino alcohols and ethers, bond rotation occurs more quickly than the Mannich cyclization, and racemic products are observed. This can be avoided by using a chiral auxiliary substituent on the amine. Reactions tethered to rings cannot undergo these bond rotations.

Possible thermodynamic sinks for biasing a rearrangement product
Horowitz and Geissman's first example demonstrates a possible thermodynamic sink to couple with the cationic 2-aza-Cope rearrangement, where the product is biased by the phenyl substituent through aryl conjugation, then captured by hydrolysis of the iminium. Other methods of biasing a product include using substituents which are more stable on substituted carbons, releasing ring strain (for instance, by pairing the rearrangement with cyclopropane opening), intramolecular trapping (pictured), and pairing the rearrangement with the Mannich cyclization.

The aza-Cope/Mannich reaction

The aza-Cope/Mannich reaction is a synthetically powerful reaction, as it is able to create complex cyclic molecules from simple starting materials.  This tandem reaction provides a thermodynamic bias towards one rearrangement product, as the Mannich cyclization is irreversible and its product, an acyl substituted pyrrolidine ring, more stable than that of the rearrangement.

The first aza-Cope/Mannich reaction
Overman and coworkers recognized that the cationic 2-aza-Cope rearrangement could potentially be synthetically powerful if an appropriate thermodynamic sink could be introduced.  Their logic was to incorporate a nucleophilic substituent into the starting material, namely an alcohol group, which acts only after rearrangement, converted into an enol primed to attack the iminium ion.

This first report of the reaction was a reaction between aldehydes and 2-alkoxy-3-butenamines, which formed an amino alcohol whose aza-Cope/Mannich reaction product was an acyl-substituted pyrrolidine ring. This simple procedure only involved mild heating for several hours. Significantly, the aza-Cope/Mannich reaction occurs in a single step with excellent yield. This procedure is easily applied to condensation of amino ethers (shown below), where the alcohol has been methylated first. After the aza-Cope/Mannich reaction is carried out, the ketone is formed by addition of NaOH. The amine, in this simple case, cannot form the iminium ion from basic ketones; subsequent methods found ways of incorporating ketones into the reaction. The utility of this reaction is evident in the fact that even when a less stable isomer is formed, the reaction proceeds, demonstrating its high thermodynamic favorability.

Reaction mechanism

The general product of the reaction can potentially occur via two separate pathways:  the aza-Cope/Mannich reaction, or an aza-Prins cyclization/pinacol rearrangement.
These mechanisms have different stereochemical properties, which elucidate the dominance of the aza-Cope/Mannich reaction. The aza-Cope/Mannich reaction forces each atom in the [1,5] diene analog to undergo sp2 hybridization, erasing the starting material's stereochemistry at the labelled R' position, while the aza-Prins/pinacol rearrangement retains stereochemistry at the labelled R' position, pointing to a simple test that reveals the active mechanism. An enantiomerically pure starting material at the "R'" position should lead to a racemic product if the dominant mechanism is the aza-Cope/Mannich reaction, while the stereochemistry should be retained if the dominant mechanism is an aza-Prins cyclization/pinacol rearrangement pathway. A simple experiment verified that the product was racemic, providing clear evidence of the aza-Cope Mannich reaction as the operative mechanism.  Further experiments verified this, using the knowledge that the carbenium ion formed in an aza-Prins/pinacol pathway would be effected by its substituent's ability to stabilize its positive charge, thus changing the reactivity of the pathway. However, a variety of substituents were shown to have little effect on the outcome of the reaction, again pointing to the aza-Cope Mannich reaction as the operative mechanism.
Recent literature from the Shanahan lab supports the rare aza-Prins/pinacol pathway only associated with significantly increased alkene nucleophilicity and iminium electrophilicity.

The aza-Cope/Mannich reaction shows high diastereoselectivity, generally in accordance the results of the stereochemical experiments elucidating the transition state of the cationic 2-aza-Cope rearrangement, which follows as this tandem reaction pathway was an integral part of these experiments. The stereochemistry of the rearrangement is slightly more complicated when the allyl and amine substituents are installed on a ring, and thus cis or trans to one another.

The aza-Cope/Mannich reaction starting material, the amino alcohol, can also be thought of as related to the oxy-Cope rearrangement (below), both for its rate acceleration due to ionic involvement, as well as the analogous enol collapsing function of the Mannich cyclization and the keto-enol tautomerization in the oxy-Cope rearrangement.

Synthetic applications of the 2-aza-Cope/Mannich reaction
The aza-Cope/Mannich reaction is often the most efficient way to synthesize pyrrolidine rings, and thus has a number of applications in natural product total syntheses.  Because of its diastereoselectivity this reaction has added to the catalog of asymmetric synthesis tools, as seen in the many examples of asymmetric alkaloids synthesized using the reaction. As we have seen in the first aza-Cope/Mannich reaction and in the elucidation of the reaction's stereochemistry, the aza-Cope/Mannich reaction can be used to form pyrrolidine rings and pyrrolizidine rings.  It can be used to create many additional ring structures useful in synthesis, such as indolizidine cycles and indole rings.

(−)-Strychnine total synthesis

The classic example demonstrating the utility of this reaction is the Overman synthesis of strychnine.  Strychnine is a naturally occurring highly poisonous alkaloid, found in the tree and climbing shrub genus Strychnos. Strychnine is commonly used as a small vertebrate pesticide.
The first strychnine total synthesis, by R. B. Woodward, represented a major step in natural product synthesis: no molecule approaching its complexity had been synthesized before. The next total syntheses were not reported until the late 1980s, using similar methods, namely by using an intermediate available by degradated strychnine. All of these syntheses used harsh conditions. The Overman synthesis sidesteps these problems, and is the first asymmetric total synthesis of strychnine, taking advantage of the diastereoselectivity and mild reaction conditions of the aza-Cope/Mannich reaction. The aza-Cope/Mannich reaction step proceeded in near quantitative yield. The Overman synthesis is accordingly several orders of magnitude more efficient than its predecessors.

Overman's synthesis of strychnine represents a useful example of the preparation of precursors necessary for the aza-Cope/Mannich rearrangement, representing effective usage of an epoxide ring opening. The key steps of the synthesis of the rearrangement substrate leading to the starting materials necessary for the aza-Cope/Mannich reaction included a Stille reaction to piece together two precursors, an epoxidation of a double bond using tert-Butyl hydroperoxide, a Wittig reaction to convert the ketone to an alkene, and a cyclization step. Amine alkylation (not shown), transforms the molecule to the rearrangement substrate. Significantly, this molecule shows the enantiomeric precision of the aza-Cope/Mannich reaction, as a simple enantiomeric starting material dictates the final enantiomer: the enantiomer of strychnine was produced by using the enantiomer of the starting material.

The Overman synthesis, with in-depth details of the synthesis of the rearrangement substrate, as well as the final steps of the reaction, is detailed here: Overman synthesis of (−)-strychnine.

Synthesis of (−)-crinine
Crinine is an alkaloid of the family Amaryllidaceae, and its asymmetric total synthesis was one of the first using the aza-Cope/Mannich reaction. This synthesis represents a significant step in the development of the aza-Cope/Mannich reaction, as it takes advantage of several of the most useful synthetic strategies characteristic of the reaction. This reaction takes advantage of the cationic-2-aza-Cope rearrangement's high diastereoselectivity, as well as usage of the cyanomethyl group to protect the amine during vinyllithium addition and as a leaving group to promote iminium formation, assisted by addition of silver nitrate.
This synthesis is one example of many of the cyanomethyl group providing a synthetically useful route towards pyrrolidine and indolizidine formation.

Synthesis of bridged tricyclic alkaloids
Overman and coworkers developed methods to synthesize complicated bridged tricyclic structures using the aza-Cope/Mannich reaction.  These aza-tricyclic structures are found in the complex Stemona alkaloid family, as well as in potential drugs such as some immunosuppressants.  The example shown is a facile reaction combining a 1-aza-bicyclo[2.2.1]heptane salt starting material with paraformaldehyde at 80 °C to form the pivotal aza-tricyclic structure of the Stemona alkaloid molecules.  Saliently, despite unfavorable orbital overlap due to the sterics of this ring system, the reaction proceeds with 94% yield, highlighting the power of this reaction even under unfavorable conditions.

General ring opening and expansion

The aza-Cope/Mannich reaction, when coupled with existing ring cycles, is often used to create indolizidine cycles (a pyrrolidine connected to a cyclohexane ring). This typical ring annulation, where the cyclopentane moiety is opened with the rearrangement and closed with the Mannich cyclization to form a six membered ring attached to a pyrrolidine ring, while the most popular aza-Cope/Mannich annulation, is not the only one. Seven-membered ring cycles are also possible to synthesize, as the enol and iminium ions stay in close enough proximity to undergo Mannich cyclization.  Macrocycle synthesis has not been reported using this reaction, due to the lack of proximity between the enol and iminium.
Vinyl oxazolidines can also be used as rearrangement substrates. This rearrangement first creates the vinyl oxazolidine from attack on the cyclohexanone by the aminobutenol, which then undergoes the aza-Cope/Mannich reaction using heat and acid (Lewis or protic).  This example breaks and then forms a five-membered ring.  More complex examples attach the oxazolidine to another ring, presenting additional methods for the formation of indolizidine cycles.

Scope of the aza-Cope/Mannich reaction
The aza-Cope/Mannich reaction has numerous advantages in comparison to other methods.  The gentle conditions of the reaction aren't matched: light heating, normally no higher than 80 °C, a wide range of solvents, and addition of 1 stoichiometric equivalent of acid, commonly camphorsulfonic acid (CSA) or a Lewis acid.  Other routes toward pyrrolidine synthesis cannot compete with the stereospecificity, widescale applications in structures containing pyrrolidine derivatives, and large scope of possible starting materials. The reaction exhibits high diastereoselectivity, and is robust, proceeding even when faced with poor orbital overlap in the transition state.

The advantages of the aza-Cope/Mannich reaction have motivated research on the synthesis of the starting materials for the reaction, which split into two main categories: amine addition and iminium formation (red) and installation of the vinyl substituent (blue).  A wide variety of N-substituents (R), alkyl and aryl, can be used in the reaction, some of which affect the stereochemical outcome of the reaction. Vinyl groups are generally limited to those which are either 1,1 or 1,2-Disubstituted (vinyl with substituents at R1, and R1,R2 respectively), with a wide range of electronic and steric variety tolerated.

Amine addition and iminium formation

Epoxide ring opening
The ring strain of epoxides provide useful methodology for installation of an amine group two atoms away from an alcohol group. The epoxide may be first broken by bromide nucleophilic attack.  Primary amines, aromatic amines, or lithium anilides can also be used as nucleophiles.  Protective O-methylation often follows this step and proceeds easily.

When sterics allow for attack on only the appropriate carbon (the terminal carbon as opposed to the second carbon), direct attack by an intramolecular nitrogen is effective, as is the case with strychnine synthesis.

Iminium ion formation
The most common way to generate the iminium ion from the installed amine is by adding formaldehyde or paraformaldehyde, which undergoes acid-catalyzed condensation to form the iminium. Overman's strychnine synthesis typifies this method.  Occasionally, intramolecular carbonyls are used.  Other methods for iminium ion formation include using cyanomethyl groups or using oxazolidines as carbonyl precursors.

Amine alkylation
Amine alkylation represents a common method to get to imine precursors. Amine alkylation by direct SN2 reaction is only occasionally useful in producing starting materials due to the high propensity of amines to overalkylate.
Reductive amination is a more common and effective alkylating procedure, typified in the first aza-Cope rearrangement.
The most useful and standard method of amine alkylation is to have the amine form an amide bond, and subsequently reduce it, often with lithium aluminium hydride.

Oxazolidine use
Ketones and sterically hindered aldehydes are not suitable for the basic aza-Cope/Mannich reaction, as the amine cannot form an iminium ion with them. Dehydrative oxazoline formation followed by heating in the presence of a full equivalent of acid present a way to get around this issue.
Overman has reported the use of oxizolidines to generate the iminium ion requisite for the reaction.  Upon formation, Overman showed that cyclohexanones can be used for the carbonyl component in pyrrolidine synthesis. This reaction proceeded with various forms of cyclohexanones. When an acyclic ketone was substituted, the reaction proceeded with low yield, highlighting the thermodynamic favorability of releasing cyclohexanone from the double bonded carbonyl, as it creates unfavorable bond strain in the chair conformation.  This represents one of the most convenient constructions of the 1-azaspiro[4,5]decane ring system, a useful natural product.

Installation of the vinyl substituent

Vinylation of ketones
Vinylation can offer additional synthetic advantages, allowing for expanded functionality of the reaction. Organolithium reagents are typically used.  Often, a substituent or protecting group will be added to the nitrogen, although this isn't always necessary.  The addition of lithium to the reaction has a major effect on starting material stereochemistry, as the nitrogen coordinates to it. Starting materials affected by this coordination generally result in anti aza-Cope precursors, while those that aren't, such as those containing highly substituted, sterically hindered amines, result in syn precursors.  Thus the nature of the nitrogen substituent is of high importance.

Cyanomethyl group use
Cyanomethyl groups represent an easy way to protect an iminium ion during allylic vinylation of the ketone. Cyanamide groups and analogs have been often used in the generation iminium ions.  They are typically installed by nucleophilic addition onto an iminium ion, generally produced by amine alkylation with formaldehyde.  The iminium ion is thus masked. It follows that usage of a cyanomethyl group provides an efficient way to control the aza-Cope/Mannich reaction. The cyanomethyl group protects the nitrogen at the 2-position during formation of the other allylic analog by logic similar to cyanide-type umpolung. It then later provides a good leaving group for formation of the iminium ion, in accordance with its usage in iminium ion generation. Iminium ion generation from cyanomethyl groups is normally promoted by addition of silver nitrate, although other silver and copper compounds have been used. This added step allows for more precise control of iminium ion generation. Importantly, these preparatory reactions must be carried out at -78 °C to prevent cyanomethyl/vinyllithium interaction.  This method also allows for many different possible N-substituents, and can be used to simplify the synthesis of octahydroindoles and pyrroles.

The 1- and 3-aza-Cope rearrangements

The 1- and 3-aza-Cope rearrangements are obscure in comparison to the cationic 2-aza-Cope rearrangement due to their activation energies, which are comparatively much higher than that of the cationic 2-aza-Cope rearrangement.

The 1- and 3-aza-Cope have a bias towards imine formation as opposed to enamine formation, as carbon-nitrogen π-bonding is stronger than carbon-nitrogen σ-bonding, meaning the 3-aza-Cope rearrangement is thermodynamically favored, while the 1-aza-Cope rearrangement is not: the imine is nearly 10kcal/mol less in energy.  Thus the 3-aza Cope's large activation barriers are kinetically based. Research on both the 1 and 3-aza-Cope rearrangements has focused on finding good driving forces to lowering the activation barriers.   Several versions of these rearrangements have been optimized for synthetic utility. The 1-aza-Cope rearrangement is normally paired with thermodynamic driving forces. The 3-aza-Cope rearrangements are generally performed cationically to lower the kinetic barrier to its thermodynamically favorable product.

These rearrangements follow much of the mechanistic logic of the cationic 2-Aza-Cope rearrangement. The 1- and 3-aza-Cope rearrangements both occur preferentially via chair transition states (and retain stereochemistry, similarly to the cationic 2-aza-Cope rearrangement), and are sped up with the introduction of a positive charge, as this gives the transition state more diradical/dipolar character. The 3-aza-Cope rearrangement (and thus also the 1-aza-Cope rearrangement, which goes through the same transition state)  is expected to show even less aromatic character in its transition state in comparison to the Cope rearrangement and cationic-2-aza-Cope rearrangement, contributing to the higher temperatures required (close to the temperatures required for the Cope rearrangement, at times even higher, from 170 to 300 degrees) to overcome the kinetic activation barriers for these arrangements.

The 3-aza-Cope rearrangement

The 3-aza-Cope reaction was discovered soon after the 2-aza-Cope rearrangement was identified, due to its analogous relationship to the Claisen rearrangement. Indeed, in early papers, this version of the aza-Cope rearrangement is often referred to as the amino-Claisen rearrangement, a misrepresentation of the rearrangement, as this would imply that both a nitrogen and oxygen are in the molecule. This rearrangement can be used to form heterocyclic rings involving carbon, most commonly piperidine.

One of the first examples of this arrangement was identified by Burpitt, who recognized the rearrangement occurring in ammonium salts, which, due to their charged nature, proceeded exothermically without addition of heat—importantly, without a tetrasubstituted nitrogen, the rearrangement did not proceed.  Following this logic, much of the research on the 3-aza-Cope rearrangement has focused on charged zwitterionic versions of this reaction, as the charge distribution helps lower the activation barrier: in certain cases, the rearrangement can occur at temperatures as low as -20 °C.

Hill and Gilman first reported a general uncharged 3-aza-Cope rearrangement in 1967. Upon creation of appropriately substituted enamines, intense heating afforded an almost complete rearrangement to the imine product.  However, this rearrangement pathway has limited utility.

The 1-aza-Cope rearrangement

The first discovered 1-aza-Cope reaction was a simple analog to the generic Cope reaction and required intense heat to overcome its large thermodynamic activation barrier; most subsequent work on the 1-aza-Cope rearrangement has thus focused on pairing the arrangement with a driving thermodynamic force to avoid these harsh reaction conditions. It has been hypothesized that the 1-aza-Cope rearrangement rate-determining transition state has partial diradical and dipolar transition state character due to the presence of the heteroatom.

Fowler and coworkers have come up with a scheme that mobilizes the 1-aza-Cope rearrangement as a synthetically useful route. Fowler and coworkers recognized that because the barrier for the reaction lies in the nitrogen's thermodynamic preference to stay as an imine, stabilizing the nitrogen could have a thermodynamically beneficial effect.  To that end, Fowler and coworkers installed a carbonyl group on the nitrogen, hypothesizing that the lone pair of the nitrogen would be stabilized by participation in an amide bond, and that the electronegativity of this amide group would lower the LUMO of the imine group, making the transition state more favorable.  Using this strategy, Fowler and coworkers were able to use the 1-aza-Cope rearrangement to create piperidine and pyridine derivatives. This strategy was shown to be relatively robust, allowing for the formation of products even when forced through a boat transition state, when perturbed with substituent effects, or put in competition with alternative rearrangements.  Also significant is the relative ease of production of the reactants, which uses a Diels-Alder reaction paired with relatively simple workup steps, allowing for syntheses using complex cycling.

Other methods of overcoming this thermodynamic barrier include pairing it with cyclopropane ring strain release, which allows the reaction to proceed at much lower temperatures.

References

Further reading

Rearrangement reactions
Name reactions


title: Barton, West Lancashire

text:
Barton is a small village in the county of Lancashire, England. It is approximately  west from Ormskirk, and less than  west from the A5147 road. Barton sits on the West Lancashire Coastal Plain, and is  from the Irish Sea coast. The village lies within the civil parish of Downholland.

Barton's listing in the 1086 Domesday Book shows Roger the Poitevin as lord and Tenant-in-chief. At the time Barton was in the Hundred of West Derby in the county of Cheshire.

The Manor of Barton was held by the Clifton family and, from about 1212, by the Barton family. The last Barton heiress, Fleetwood Barton (1595-1664) married into the Shuttleworth family (her first marriage to Viscount Molyneux was annulled). Her husband, Richard Shuttleworth of Gawthorpe Hall, supported the Parliamentary side in the English Civil War. The Shuttleworths held the manor until 1833, when it was sold to the Preston industrialist, George Jacson.

The village had its own Barton railway station, which opened in 1887. The line was closed completely in 1952.

See also
Listed buildings in Downholland

References

External links

Villages in Lancashire
Geography of the Borough of West Lancashire


title: Orhan Suda

text:
Orhan Suda (1 July 1916 – 15 December 1978) was a Turkish cyclist. He competed in the two events at the 1936 Summer Olympics and two events at the 1948 Summer Olympics.

References

External links

1916 births
1978 deaths
Turkish male cyclists
Olympic cyclists for Turkey
Cyclists at the 1936 Summer Olympics
Cyclists at the 1948 Summer Olympics
Sportspeople from Adapazarı
20th-century Turkish people


title: Tennessee State Route 197

text:
State Route 197 (SR 197) is a secondary west–east state road located in West Tennessee.

Route description

SR 197 starts at US 45 (SR 5) in Pinson in Madison County. It crosses the South Fork of the Forked Deer River and is called locally Ozier Road and  after approximately 2.5 miles passes Pinson Mounds. At 4.0 miles along its length it passes through Five Points and becomes Diamond Grove Road. Diamond Grove Road continues for 3.9 miles and then makes a right turn onto Mifflin Road and in 0.4 of a mile passes the southern terminus of SR 198 before passing into Chester County at the 10.3 mile mark or 2 miles from SR 198. It then terminates in Mifflin at SR 200.

Major intersections

References

External links

197
Transportation in Madison County, Tennessee
Transportation in Chester County, Tennessee


title: Belle Fourche Formation

text:
The Belle Fourche Formation or Belle Fourche Shale is a fossiliferous early Late-Cretaceous geologic formation classification in Wyoming. Named for outcrops in Belle Fourche River, Wyoming, this unit name is also used in Montana, North Dakota, and South Dakota.

The unit records the gradual opening and expansion of the Greenhorn Cycle of the Western Interior Seaway, and as such is lithologically identical to the Graneros Shale Formation (that is, it is the same formation under a different name).

See also

 List of fossiliferous stratigraphic units in Montana
 Paleontology in Montana
 Paleontology in North Dakota
 Paleontology in South Dakota
 Paleontology in Wyoming

References

Cretaceous Montana
Cretaceous geology of North Dakota
Cretaceous geology of South Dakota
Cretaceous geology of Wyoming


title: Klaus von Nichtssagend Gallery

text:
Klaus von Nichtssagend Gallery is a contemporary art gallery at 87 Franklin Street in the Tribeca neighborhood of New York City.

The gallery was founded in 2004 by Matthew Chase, Ingrid Bromberg Kennedy, Robert Hult, and Sam Wilson. The Gallery was originally located in a storefront space at 438 Union Avenue in the Williamsburg neighborhood of Brooklyn, NY. In 2011 the gallery moved to 54 Ludlow Street in Manhattan. In 2022, the gallery relocated to its current space at 87 Franklin Street. Klaus von Nichtssagend hosts an average of nine shows each year in two gallery rooms.

From the gallery's website:

Klaus von Nichtssagend Gallery opened as an artist-run project space in Williamsburg, Brooklyn in the fall of 2004. Run by three owner/directors, Sam Wilson, Ingrid Bromberg Kennedy, and Rob Hult, the gallery initially focused on emerging artists having their first shows in New York City. After moving to Manhattan in 2011, the gallery expanded its operations, continuing to develop the careers of those artists it had nurtured early on while adding new and established artists to its roster. Today the gallery continues to center artists in its programming, hosting solo and group exhibitions throughout the year.  In April 2022, the gallery relocated to a new space on Franklin Street in Tribeca.

References

External links
 Klaus von Nichtssagend Gallery
 KLAUSGALLERY.cloud Klaus von Nichtssagend Gallery's online viewing rooms and magazine
 KLAUSGALLERY.net – Klaus eBooks

Art museums and galleries in Manhattan
Art galleries established in 2004
2004 establishments in New York City
Contemporary art galleries in the United States


title: Ruby River Basin Group

text:
The Ruby River Basin Group is a geologic group in Montana. It preserves fossils dating back to the Paleogene period.

See also

 List of fossiliferous stratigraphic units in Montana
 Paleontology in Montana

References

Geologic groups of Montana
Paleogene stratigraphic units of North America


title: Kazım Bingen

text:
Kazım Bingen (born 5 May 1912, date of death unknown) was a Turkish cyclist. He competed in the individual and team road race events at the 1936 Summer Olympics.

References

External links

1912 births
Year of death missing
Turkish male cyclists
Olympic cyclists for Turkey
Cyclists at the 1936 Summer Olympics
Place of birth missing


"If He Can Fight Like He Can Love, Good Night Germany!" is a World War I song from the perspective of a woman confident that her boyfriend will be a good soldier because he was a good lover. It became a hit after it was released by The Farber Sisters in 1918.

The lyrics and cover art are in the public domain.

Composition
The song was composed by George W. Meyer, with words by Grant Clarke and Howard E. Rogers. It was published by Leo Feist Inc in New York City in 1918.

Performances
A top 20 song in 1918, the sheet music was repeatedly offered in a war edition with insets of the following performers Emma Carus, Flora Starr, Grace Wallace, and Rae Samuels.

References

External links
 View the song MP3 and sheet music cover here.
 https://digitalcommons.conncoll.edu/sheetmusic/1629/

Songs of World War I
Songs about Germany
1918 songs
Songs written by Grant Clarke
Songs written by George W. Meyer


title: David Frederick Markham

text:
David Frederick Markham MA (1800 – 31 March 1853) was a Canon of Windsor from 1827 to 1853

Career

He was educated at Westminster School and Christ Church, Oxford and graduated BA in 1821, MA in 1814.

He was appointed:
Assistant curate of Aberford 1823
Vicar of Addingham, Cumberland 1825 - 1826
Vicar of Stillingfleet, Yorkshire 1826 - 1838
Rector of Great Horkesley, Essex 1838 - 1853
Rural Dean of Dedham 1850

He was appointed to the fourth stall in St George's Chapel, Windsor Castle in 1827 and held the canonry until 1853.

He founded the Essex Antiquarian Society in 1852.

Notes

External links

1800 births
1853 deaths
Canons of Windsor
Alumni of Christ Church, Oxford


title: Kirkor Canbazyan

text:
Kirkor Canbazyan (9 March 1912 – 7 July 2002) was a Turkish cyclist. He competed in the individual and team road race events at the 1936 Summer Olympics.

References

External links

1912 births
2002 deaths
Turkish male cyclists
Olympic cyclists for Turkey
Cyclists at the 1936 Summer Olympics
Place of birth missing


title: Beara-Breifne Way

text:
The Beara-Breifne Way is a long-distance walking and cycling trail being developed from the Beara Peninsula in County Cork, Ireland, to Blacklion in the area of Breifne in County Cavan. The trail follows closely the line of the historical march of O’Sullivan Beare.

Route
The completed route will interconnect existing walking routes: The Beara Way, the Slí Gaeltacht Mhuscraí, the North Cork Way, the Ballyhoura Way, the Multeen Way, the Ormond Way, the Hymany Way, the Suck Valley Way, the Lung Lough Gara Way, the Miners Way and Historical Trail, the Leitrim Way and the Cavan Way. At Blacklion the walk continues as the Ulster Way.

References

Long-distance trails in the Republic of Ireland


title: Miloslav Loos

text:
Miloslav Loos (20 January 1914 – 2 March 2010) was a Czech cyclist. He competed in the individual and team road race events at the 1936 Summer Olympics. Before his death, he became the oldest living Czech Olympic competitor.

References

External links

1914 births
2010 deaths
Czech male cyclists
Olympic cyclists for Czechoslovakia
Cyclists at the 1936 Summer Olympics
Sportspeople from Prague


title: John James Majendie

text:
John James Majendie DD (1709–1783) was a Canon of Windsor from 1774 to 1783.

Life

His father, André Majendie, was a Huguenot minister who fled to England after the Edict of Nantes.

He lived at 10 Denmark Street London from 1758 to 1771.

He was appointed:
Tutor to the Prince of Wales and the Duke of York
Instructor of Queen Charlotte in the English language
Vicar of Stoke Prior 1769–1783
Prebendary of Netheravon in Wiltshire 1752–1783
Prebendary of the 8th Canonry at Worcester 1769–1774
 to the fifth stall in St George's Chapel, Windsor Castle in 1774 and held the canonry until his death.

He was elected a Fellow of the Royal Society in 1768.

He died at Weston, near Bath in 1783. His son Henry William Majendie became Bishop of Chester and Bishop of Bangor.

Notes

1709 births
1783 deaths
Canons of Windsor
Fellows of the Royal Society


title: Hans Leutelt

text:
Hans Leutelt (1 October 1914 – 1936) was a Czech cyclist. He competed in the individual and team road race events at the 1936 Summer Olympics.

References

External links

1914 births
1936 deaths
Czech male cyclists
Olympic cyclists for Czechoslovakia
Cyclists at the 1936 Summer Olympics
Place of birth missing


title: Article 50 (political party)

text:
Article 50 () was a Eurosceptic political party in the Netherlands. The party was founded by MEP Daniël van der Stoep in 2012. The name refers to article 50 of the Lisbon Treaty, of which the first sentence is "Any Member State may decide to withdraw from the Union in accordance with its own constitutional requirements", as well as article 50 of the Constitution of the Netherlands, which states that "[t]he States General shall represent the entire people of the Netherlands." On 27 January 2015, the party merged into For the Netherlands, and therefore Article 50 ceased to exist.

History
Daniël van der Stoep was elected into the European Parliament for the Party for Freedom (PVV) at the 2009 election. He resigned as an MEP on 17 August 2011, having caused a car crash when drunken driving, and was replaced by Auke Zijlstra. He was returned to the European Parliament on 14 December 2011, after the Treaty of Lisbon expanded the Parliament by eighteen MEPs. It was initially disputed Patricia van der Kammen should be elected. However, the PVV did not allow him to rejoin their delegation, and went on as an independent. In November 2012, Van der Stoep founded Article 50 with the intention of participating in the 2014 European Parliament election.

The party participated in several municipalities in the 2014 municipal elections, and won one seat in the municipal council of Weesp, where they promised to write out a referendum concerning the construction of a new mosque. In the 2014 European Parliament election, Article 50 gathered 24,069 votes, not enough for a seat. After the European Parliament election, the party expressed the desire to participate in the 2015 provincial elections and subsequent Senate election.

However, Van der Stoep dissolved the party's national leadership on 23 July 2014, causing the party's councillor in Weesp to split off. Later, Van der Stoep stepped down as party leader. On 27 January 2015, Article 50 merged with the party For the Netherlands, which had been founded by two other former PVV members the year before.

Electoral results

European Parliament

References

External links

Defunct nationalist parties in the Netherlands
Defunct political parties in the Netherlands
Eurosceptic parties in the Netherlands
Political parties established in 2012
2012 establishments in the Netherlands
Political parties disestablished in 2015
2015 disestablishments in the Netherlands


title: William Langford (priest)

text:
William Langford DD (d. 21 January 1814) was a Canon of Windsor from 1787 to 1814

Career
He was educated at King's College, Cambridge.

He was appointed:
Lower Master (Ostiarius) of Eton College 1775
Prebendary of the 3rd stall at Worcester 1785 - 1787
Vicar of Nether Stowey, 1796
Rector of Newdigate, Surrey
Vicar of Isleworth 1801
Fellow of Eton

He was appointed to the fifth stall in St George's Chapel, Windsor Castle in 1787 and held the canonry until 1814.

Notes

1814 deaths
Canons of Windsor
Alumni of King's College, Cambridge
Year of birth missing


title: Vilém Jakl

text:
Vilém Jakl (born 22 February 1915, date of death unknown) was a Czech cyclist. He competed in the individual and team road race events at the 1936 Summer Olympics.

References

External links

1915 births
Year of death missing
Czech male cyclists
Olympic cyclists for Czechoslovakia
Cyclists at the 1936 Summer Olympics
Place of birth missing


title: Alison Brady

text:
Alison Brady is a Brooklyn-based photographer known for her Sweet Affliction and What Remains Secret series. Born in Cleveland, Ohio, she graduated from the School of Visual Arts in 2006 with an MFA in Photography.

Brady's work has been featured in The New York Times, NY Arts Magazine, and Time Out New York. The New York Times Whitney Richardson wrote, "Her images are carefully structured to blend the familiar with the unknown — antique furniture and vintage fabrics juxtaposed with unnaturally twisted body forms — with the hope of getting viewers to ask one question: 'I know these objects, but why does this all feel so foreign?'" Her photography is featured in many private and public collections including Elton John's collection and the West Collection. Saatchi Gallery profiled her as an emerging artist of the week in 2007.

Her exhibition "Sincerely Yours" was pointed out as taking extensively from René Magritte's work. In 2016, Brady's photos from her 2011 exhibition, "Sincerely Yours", were used as the cover artwork of American post-punk / gothic rock band Damien Done's EP Stay Black. Other images from that exhibition were used as the cover artwork to the band's next three singles, "He Really Tried"/"And Now The Rain", "Curious Thing"/"Primitive" and "Everybody Loves You (When You're Dead)"/"Pretty Boy".

Sweet Affliction
Brady's Sweet Affliction series captures young women in domestic, nostalgic settings, while embracing both commonplace and carnal elements. In her review of the show, Roberta Smith of The New York Times wrote, "Ms. Brady's work deals rather explicitly and hilariously with the female predicament."

Solo exhibitions
 What Remains Secret, Rick Wester Fine Art (2014)
 Sincerely Yours, Hous Projects (2011)
 An Uncertain Nature, Massimo Audiello (2009)
 Sweet Affliction, Massimo Audiello (2007)

References

External links

 The New York Times interview with Alison Brady
 Saatchi Gallery

Living people
American women photographers
Artists from Cleveland
Photographers from Ohio
School of Visual Arts alumni
Year of birth missing (living people)
21st-century American women


title: Thomas Tjapaltjarri

text:
Thomas Tjapaltjarri (born Tamayinya Tjapangati, also often known as Tamlik) is an Australian Aboriginal artist. He and his brothers Warlimpirrnga and Walala have become well known as the Tjapaltjarri Brothers. Tjapaltjarri and his family became known as the last group of Aborigines to come into contact with modern, European society. They came out of the desert in 1984, and became known as "the last nomads".

Early life

Tjapaltjarri was born in the desert of Western Australia sometime in the 1960s. He and his family lived a traditional nomadic way of life on the western side of Lake Mackay. They had never come into contact with European society. Most other Pintupi families had been settled in remote towns to the east and west of their traditional country during the 1950s. Tjapaltjarri's father, Lanti (or "Joshua"), had lived for a short time at the mission in Balgo, but he had run away after getting into trouble for stealing food. It was his decision to stay in the desert, and he kept his family far away from the towns.

Tjapaltjarri's mother was named Nanu. He also had two other mothers, Papunya and Watjunka, who were his father's secondary wives. He had two younger sisters, Yalti and Yukultji, a younger half-brother Walala, and four other "siblings" (cousins by blood relation). His father died sometime around 1980. The family finally came into contact with outsiders in October 1984, and were settled at Kiwirrkurra. The event was big news at the time, and the family became famously known as "the last nomads". Tjapaltjarri was diagnosed with epilepsy shortly after this.

Painting
Tjapaltjarri began painting in December 1987, a few years after settling at Kiwirrkurra. His cousin Warlimpirrnga had already made a name for himself as an artist and he encouraged Tjapaltjarri to paint too. Tjapaltjarri and Walala joined the Papunya Tula artists, and they and Warlimpirrnga eventually gained fame internationally as the Tjapaltjarri Brothers. Although he normally paints using Tjapaltjarri as a surname, Tjapaltjarri's skin name is Tjapangati.

His paintings depict stories from the Pintupi dreaming. They are mostly about places and events in the Tingari cycle (a cycle of myths about the ancestors of the Pintupi). His designs are inspired by those painted on the body during ceremonies. He uses acrylic paints on canvas, sticking to earthy colours (black, white and ochres). He paints simple shapes with dotted lines, which is a style that his brothers also use.

He has had paintings shown in many exhibitions around Australia, and also in Switzerland, Germany, France and the United States. His larger paintings sell for at least A$6000 in Alice Springs and A$9500 in galleries in Melbourne and Sydney.

References

Other websites
Profile at the Red Desert Gallery
Tjapaltjarri Brothers: Walimpirrnga, Walala & Thomas Tjapaltjarri, an exhibition at the Japingka Indigenous Fine Art Gallery

Indigenous Australian artists
Artists from Western Australia
Living people
Australian painters
1960s births
Pintupi


title: S. Parker Gilbert

text:
Seymour Parker Gilbert III (November 15, 1933 – May 27, 2015) was Chairman of Board and President of Morgan Stanley from 1983 until 1990.

Career
While Gilbert was the Chairman of Board and President of Morgan Stanley from 1983 until 1990, the number of employees at the firm grew from 2,600 to 6,800.  Equity grew from $207 million to more than $2 Billion.  Gilbert led the company through an initial public offering in 1986. Gilbert joined Morgan Stanley in 1960 and became a partner in 1969.  He became a Managing Director in 1970.  In 1974, he became a member of the Management Committee.

Group of eight
In 2005, Gilbert joined with seven other former partners of Morgan Stanley to form the 'Group of Eight'.  The Group of Eight is widely credited with forcing the ouster of Philip J. Purcell and his replacement with John Mack.

Board of Directors and Trustees activity
Gilbert served on the board of directors of: Burlington Resources (1990–2001), ITT Corporation (1991–1995), ITT Industries (1995–1999), Morgan Stanley Group, Inc. (1986–1997), the New York Stock Exchange (1986–1990), Taubman Centers, Inc. (1992-2004), and Bessemer Securities.  He also served on the board of trustees of: the Pierpont Morgan Library, the Metropolitan Museum of Art, the Alfred P. Sloan Foundation and the Josiah Macy, Jr. Foundation.

Personal life
Gilbert was the son of diplomat Seymour Parker Gilbert.  Following the death of his father, Gilbert's mother married Harold Stanley, one of the founders of Morgan Stanley. Henry Sturgis Morgan, the other founder, was Gilbert's godfather.

Gilbert attended Buckley School and Hotchkiss School and graduated from Yale University in 1956 and served in the United States Army until 1959. With his wife Gail Auchincloss, he had three children.  His son, S. Parker Jr., known as Parker; a daughter, Lynn Tudor; and another son, the writer David Gilbert; as well as eight grandchildren. On May 27, 2015, Gilbert died in New York City at the age of 81 from chronic obstructive pulmonary disease.

References

External links
 Morgan Stanley Chairman to Retire
 Book Excerpt from Blue Blood & Mutiny: The Fight for the Soul of Morgan Stanley by Patricia Beard
 The Group of Eight
 Bloomberg TV Interview with James Gorman, John Mack & Parker Gilbert

1933 births
Businesspeople from New York City
Yale University alumni
2015 deaths
Morgan Stanley employees
20th-century American businesspeople
Buckley School (New York City) alumni
Hotchkiss School alumni


The 2014–15 Saint Louis Billikens women's basketball team represented the Saint Louis University during the 2014–15 college basketball season. Lisa Stone assumes the responsibility as head coach for her third season. The Billikens were members of the Atlantic 10 Conference and play their home games at the Chaifetz Arena. They finished the season 15–16, 7–9 in A-10 play to finish in a tie for eighth place. They advanced to the quarterfinals of the A-10 women's tournament where they lost to George Washington.

2014–15 media
All non-televised Billikens home games and conference road games will stream on the A-10 Digital Network.

Roster

Schedule

|-
!colspan=9 style="background:#0000FF; color:#FFFFFF;"| Exhibition

|-
!colspan=9 style="background:#FFFFFF; color:#0000FF;"| Regular Season

|-
!colspan=9 style="background:#0000FF; color:#FFFFFF;"| Atlantic 10 Tournament

Rankings
2014–15 NCAA Division I women's basketball rankings

See also
 2014–15 Saint Louis Billikens men's basketball team
 Saint Louis Billikens women's basketball

References

Saint Louis Billikens women's basketball seasons
Saint Louis
Saint Louis Billikens women's basketball
Saint Louis Billikens women's basketball


title: Ingvar Ericsson (cyclist)

text:
Ingvar Ericsson (5 January 1914 – 21 April 1995) was a Swedish cyclist. He competed in the individual and team road race events at the 1936 Summer Olympics.

References

External links

1914 births
1995 deaths
Swedish male cyclists
Olympic cyclists for Sweden
Cyclists at the 1936 Summer Olympics
Sportspeople from Uppsala


title: Berndt Carlsson

text:
Berndt Carlsson (7 April 1907 – 30 June 1991) was a Swedish cyclist. He competed in the individual and team road race events at the 1936 Summer Olympics.

References

External links

1907 births
1991 deaths
Swedish male cyclists
Olympic cyclists for Sweden
Cyclists at the 1936 Summer Olympics
People from Ödeshög Municipality
Sportspeople from Östergötland County


title: Dugarajapatnam Port

text:
Dugarajapatnam Port is a proposed seaport in Nellore district of Andhra Pradesh, India. Construction was expected to start in 2020 and finish in 2023. It will be controlled by the Union government, alongside Visakhapatnam Port in the state of Andhra Pradesh, and would cost nearly . The port is set up under India's Companies Act 1956 with equity participation of the government of Andhra Pradesh.

Relocation

The construction encountered certain objections as the sensitive ecosystem of Pulicat Lake and the satellite launching station ISRO of Sriharikota are very near to Duggarajapatnam. After environmental and forest clearances, the location was shifted to Vagarru at Tupilipalem village. Tupilipalem is located 20 km from Dugarajapatnam, but the port will be still be referred to as Dugarajapatnam Port. The district administration is taking steps to acquire approximately  of land at the new location.

References

Ports and harbours of Andhra Pradesh
Buildings and structures in Nellore district
Transport in Nellore district


title: Ted Clayton (cyclist)

text:
Ted Clayton (6 January 1911 – 20 December 1994) was a South African cyclist. He competed in the three events at the 1936 Summer Olympics.

References

External links

1911 births
1994 deaths
South African male cyclists
Commonwealth Games silver medallists for South Africa
Commonwealth Games bronze medallists for South Africa
Cyclists at the 1934 British Empire Games
Olympic cyclists for South Africa
Cyclists at the 1936 Summer Olympics
Sportspeople from Paddington
Cyclists from Greater London
English emigrants to South Africa
Commonwealth Games medallists in cycling
20th-century South African people
Medallists at the 1934 British Empire Games


title: Dorset (sheep)

text:
In the context of sheep, Dorset may refer to:

 the Dorset Down, a British sheep breed
 the Dorset Horn, a British sheep breed
 the Polish Modified Dorset, a Polish sheep breed developed at the University of Life Sciences in Poznań
 the Poll Dorset, an Australian sheep breed derived from the Dorset Horn
 the Polled Dorset, an American sheep breed derived from the Dorset Horn


title: Exitos De Al Hurricane

text:
Exitos De Al Hurricane ("La Mula Bronca") is the eleventh album released by the New Mexican musician Al Hurricane in 1980?.

The lead single "La Mula Bronca" is one of Al Hurricane's more recognized rancheras.

Track listing

References

Al Hurricane albums
New Mexico music albums


title: Ilinden (memorial)

text:
Ilinden, also known as Makedonium ( or ), is a monument in Kruševo, North Macedonia. It was officially opened on August 2 of 1974, on the 30th anniversary of the Second Session of the Anti-fascist Assembly for the National Liberation of Macedonia and the 71st anniversary of the 1903 Ilinden uprising. The designers of the monument are Jordan Grabuloski and Iskra Grabuloska.

It is dedicated to all the IMARO revolutionaries who participated in the Ilinden uprising, as well as communist Yugoslav partisans of the World War II in Yugoslav Macedonia (1941-1944).

Description
The monument's grounds cover . The building has a rounded shape with protruding oval windows. The upper windows are made of stained glass.

Inside the dome is the tomb of Nikola Karev, president of the Kruševo Republic, and the bust of the singer Toše Proeski. The interior of the dome has four windows, each facing a different direction including the locations associated with the Ilinden-related events ″Sliva″ Memorial, Bear stone and Pelagonija.

The memorial complex also features a plateau with series of sculptures named "Breaking the Chains", symbolizing freedom won in the liberation wars. There is also a crypt with the carved names and important events related to the period before, during and after the Ilinden uprising. The last component is the amphitheater decorated with colorful mosaics.

Gallery

See also
Kruševo Republic
List of World War II monuments and memorials in North Macedonia

References

External links

Buildings and structures completed in 1974
Monuments and memorials in North Macedonia
1974 sculptures
Kruševo Municipality
1974 establishments in Yugoslavia


title: Utah Department of Health

text:
The Utah Department of Health is the Government of Utah's body responsible for public health.

It is headquartered in the Cannon Health Building in Salt Lake City.

Services
In July 2014 the Utah Department of Health issued its first permits for hash oil.

In 2012 a major data breach allowed hackers to access the health data of 700,000 people in the Department of Health records.

Utah Department of Health enables consumer access to personal and family immunization records on-file with Utah State Immunization Information System (USIIS) through the Docket app.

References

External links

State departments of health of the United States
Medical and health organizations based in Utah


title: Da'Mon Merkerson

text:
Da’Mon Teshone Merkerson (born April 5, 1989) is an American football cornerback who is currently a free agent. He was signed by the Arizona Cardinals as an undrafted free agent in 2011. He played college football at Syracuse University.

Early years
Merkerson grew up in Passaic, New Jersey and attended St. Mary High School in Rutherford, New Jersey where he was a three-sport athlete. He played football, basketball and track. He was All county in football and track and field (400 Meter Dash). After switching back from wide receiver to cornerback in his senior season he found a home at cornerback. Tied for 8th in the Big East with passes defended. Merkerson helped lead the orange to victory against Kansas State in the Inaugural New Era Pinstripe Bowl.

Professional career

Arizona Cardinals
Merkerson signed with the Arizona Cardinals in July 2011, but he was released just 3 days later.

Arizona Rattlers
From 2012 to 2014, Merkerson had been a member of the Arizona Rattlers of the Arena Football League (AFL), helping the team win back-to-back ArenaBowl Championships.

References

External links
Syracuse bio
Arena Football League bio

1989 births
Living people
American football cornerbacks
Syracuse Orange football players
Arizona Rattlers players
Sportspeople from Passaic, New Jersey
Players of American football from Passaic County, New Jersey
African-American players of American football
21st-century African-American sportspeople
20th-century African-American people


title: First Album Live

text:
First Album Live is a live version of the self-titled first album by They Might Be Giants. The album was released in July 2014 in MP3 format at no charge on NoiseTrade All the songs were recorded during the band's 2013 tour.

Track listing

References

External links
https://noisetrade.com/theymightbegiants/first-album-live

2014 live albums
They Might Be Giants live albums
Idlewild Recordings live albums


title: Sycophaga

text:
Sycophaga is a mainly Afrotropical gall wasp genus of the superfamily Chalcidoidea that live on the section Sycomorus of the monoecious fig subgenus, Sycomorus, and one of several fig wasp genera to exploit its mutualism with Ceratosolen wasps.

They enter the fig during the receptive phase of development, and oviposit inside the short-style flowers. This induces the growth of endosperm tissue and the enlargement and ripening of the syconium which holds the wasp-bearing drupelets, without pollination taking place.

The genus can be characterized by having a long ovipositor, non-metallic coloration, a square mesoscutellum, and a long propodeum.

Species
The described species include:
 Sycophaga afflicta Grandi, 1916
 Sycophaga callani Grandi, 1955
 Sycophaga cyclostigma Waterston, 1916
 Sycophaga depressa Risbec, 1956
 Sycophaga gigantea Grandi, 1916
 Sycophaga gigas Mayr, 1906
 Sycophaga insularis Grandi, 1916
 Sycophaga silvestrii Grandi, 1916
 Sycophaga sycomori Linnaeus, 1758
 Sycophaga tenebrosa Grandi, 1917
 Sycophaga valentinae Grandi, 1952
 Sycophaga vicina Mayr, 1906
 Sycophaga viduata Grandi, 1916

References

External links

Hymenoptera genera
Agaonidae


title: Wiktor Olecki

text:
Wiktor Olecki (9 September 1909 – 1981) was a Polish cyclist. He competed in the individual and team road race events at the 1936 Summer Olympics.

References

External links

1909 births
1981 deaths
Polish male cyclists
Olympic cyclists for Poland
Cyclists at the 1936 Summer Olympics
Cyclists from Warsaw
20th-century Polish sportsmen


title: Blastesthia tessulatana

text:
Blastesthia tessulatana, the cone tortricid, is a species of moth of the family Tortricidae. It is found in the Near East, North Africa, Portugal, Spain, France, Germany, Italy, Switzerland, Albania, Bulgaria, Greece and on Malta, Sicily, Sardinia and Cyprus.

The wingspan is 13–17 mm. Adults are on wing from April to August.

The larvae feed on Cupressaceae species, including Cupressus sempervirens. They feed on the cones of their host plant.  Larvae can be found from September to April.

References

Moths described in 1871
Eucosmini


title: Danube Army (Russian Empire, 1916)

text:
The Russian Danube Army was a World War I Russian field army that fought on the Romanian Front.

Field management was established in November 1916, when the Dobruja Army was disbanded after the loss of the Cernavodă-Constanța line (following the Second Battle of Cobadin) to the German-Bulgarian-Ottoman Army under command of August von Mackensen.

The army consisted of:
 the 47th Army Corps (General Vasiliy Artemiev)
61st Infantry Division (General Panteleimon Simanskiy)
115th Infantry Division (General Aleksandr Freiman)
3rd Caucasian Rifle Division (General Feliks Iozefovich)
3rd Don Cossack Division (General Aleksandr Dolgorukov)
27th Mortar Artillery Battalion
 the 6th Cavalry Corps (General Aleksandr Pavlov)
12th Cavalry Division (General Carl Gustaf Emil Mannerheim)
Trans-Amur Horse Division (General Georgiy Rozalion-Soshalskiy)
4th Armed Vehicle Division (Lieutenant Colonel Orest Zhelyabuzhskiy)
10th Armed Vehicle Detachment
11th Armed Vehicle Detachment
12th Armed Vehicle Detachment

The commander of the Army was General Vladimir Viktorovich Sakharov.

In December 1916, the Army was renamed to the 6th Army and became part of the Russian Romanian Front.

References

See also
 List of Russian armies in World War I

Armies of the Russian Empire
Military units and formations established in 1916
1916 establishments in the Russian Empire


title: Healthcare in Utah

text:
This article summarizes healthcare in Utah.

Utah Department of Health

The Utah Department of Health manages state government projects in Utah.

The health insurance marketplace for Utah is Avenue H.

Hospitals in Utah

Utah has hospitals serving every part of the state.

Health campaigns in Utah
HealthInsight, a regional nonprofit organization, organizes the Choosing Wisely campaign in Utah.

References

External links
Utah Department of Health


title: John Junkin (Northern Ireland politician)

text:
John Junkin (born 1949) is a former unionist politician in Northern Ireland.

Long active in the Ulster Unionist Party (UUP), Junkin was elected to Magherafelt District Council at the 1981 Northern Ireland local elections, and held a seat in Moyola in 1985, 1989 and 1993.  By the start of the 1990s, he was a Vice-President of the UUP, serving alongside Ken Maginnis, Martin Smyth and Hazel Bradford.

Junkin was elected to the Northern Ireland Forum in 1996, representing Mid Ulster, and held his council seat in 1997, but lost out in the 1998 Northern Ireland Assembly election, to fellow party member Billy Armstrong.

Although Junkin was re-elected to Magherafelt Council in 2001, he then resigned from the UUP and stood as an independent in 2005.  He lost his seat, defeated by new UUP candidate Jackie Crawford.  He subsequently left politics, but hit the local news in 2007 after a boat which he had fitted out for the use of an autistic child was destroyed by arson.

References

1949 births
Living people
Members of Magherafelt District Council
Independent politicians in Northern Ireland
Members of the Northern Ireland Forum
Politicians from County Londonderry
Ulster Unionist Party councillors


title: Diedra calocedrana

text:
Diedra calocedrana is a species of moth of the family Tortricidae. It is found in the United States, where it has been recorded from California.

The moth is about 20 mm. Adults have been recorded on wing in July and August.

References

Moths described in 1999
Archipini


title: Diedra intermontana

text:
Diedra intermontana is a species of moth of the family Tortricidae. It is found in the United States, where it has been recorded from California, Nevada and New Mexico.

The moth is about 19–20 mm. Adults have been recorded on wing from June to August.

References

Moths described in 1999
Archipini


title: Mieczysław Kapiak

text:
Mieczysław Kapiak (15 August 1911 – 20 September 1975) was a Polish cyclist. He competed in the individual and team road race events at the 1936 Summer Olympics.

References

1911 births
1975 deaths
Polish male cyclists
Olympic cyclists for Poland
Cyclists at the 1936 Summer Olympics
Cyclists from Warsaw
20th-century Polish people


title: Diedra leuschneri

text:
Diedra leuschneri is a species of moth of the family Tortricidae. It is found in the United States, where it has been recorded from California.

The moth is about 16 mm. Adults have been recorded on wing in May, September and October.

References

Moths described in 1999
Archipini


Staten Island Economic Development Corporation (SIEDC) is a 501(c)(3) non-profit organization that serves as a lead advocate for the economic development of Staten Island's economy. The organization is responsible for over $900 million in new investments, the creation of over 12,500 jobs, the development of over 6,000 acres of vacant industrial land by providing assistance to developers and companies implementing projects in the borough, while at the same time serving the smallest entrepreneurs and small business owners with tailored financing, procurement, and real estate assistance. Every year, approximately 3,000 businesses and individuals are assisted by the SIEDC through financial assistance, tax incentives, job training, and technical assistance. Since its establishment, the SIEDC has organized and planned yearly community events to benefit the public at no cost, such as the SIEDC Business Conference and the SIEDC Health and Wellness Expo. Cesar J. Claro serves as the President & CEO of the organization.

Mission

Established in 1993, the SIEDC's mission is to enhance Staten Island's economy by promoting public and private investment, and encouraging responsible and sustainable development, all of which improve the quality of life and provide broad and diverse employment opportunities in the borough.

Projects and programs

West Shore Light Rail - In 2005, the SIEDC recognized the unlimited potential of the hundreds of acres between the Goethals Bridge and the Outerbridge Crossing in the south. Numerous programs have been launched to assist in growing the area including the West Shore Industrial Business Improvement District (BID), the West Shore Brownfield Opportunity Area (BOA), various infrastructure and storm water studies and the effort to connect the West Shore via mass transit.

Today, nearly 20 major projects are now under development on the West Shore including the Matrix Development/Amazon/Ikea site, Freshkills Park, Staten Island Stages and other large scale development projects throughout the corridor. With over 7,000 new potential employees along the West Shore, the borough must supply effective internal mass transit as well as connections to Manhattan, New Jersey and the rest of the region via mass transit.

In 2004 and 2009, the SIEDC conducted studies to determine the need and feasibility of a light rail system that would travel along the median of the West Shore Expressway and connect the South and West Shores with the Hudson-Bergen Light Rail on the Bayonne side of the bridge.

This project would create a new route for Staten Island commuters while alleviating traffic congestion related to the thousands of new jobs along the transit corridor. Thanks to funding secured by State Senator Andrew Lanza and Assemblyman Michael Cusick, in May 2017, the Metropolitan Transportation Authority (MTA) announced that it would undertake an Alternatives Analysis (AA) for the project. This occurred as the SIEDC was actively pursuing additional funding for the Environmental Impact Statement (EIS) which would follow the AA.

SI Skyway - The abandoned North Shore Rail Right-Of-Way (ROW) stretches over five miles from St. George neighborhood to Arlington neighborhood on Staten Island.

Drawing inspiration from the highly successful Manhattan High Line, the SIEDC envisioned a similar project being implemented in the residential and commercial neighborhood of Port Richmond. Based on the enormous economic development in the Chelsea and Meatpacking districts resulting from the Manhattan High Line, the SIEDC believes this project will spur unique recreational and commercial activity for Port Richmond Avenue.

The proposed Skyway project will occupy a half-mile elevated portion of the rail line along the Richmond Terrace between Heberton Avenue and Nicholas Avenue.

The Port Richmond neighborhood suffered a severe economic decline in the latter half of the 20th century, largely as a result of the shift of development and commercial activity to the center of the island, following the construction of the Verrazano Narrows Bridge. Port Richmond Avenue was once a unique center of commercial activity serving thousands of residents on the north shore. The lack of activated park space, transportation connectivity and the shift of commercial centers all led to the decline of local commercial activity.

SI Gondola - Over 10 years ago, the SIEDC began the discussion on the West Shore Light Rail and now the SIEDC is looking to the skies for the next endeavor – the SI Gondola. In 2015, the SIEDC proposed an aerial gondola system to connect Staten Island to the rest of the region and in 2016 hosted a global design competition for concepts and proposals. As a result of this work, and the selection of Leitner-Poma of America and their route between Staten Island and Bayonne, SIEDC is working with local elected officials and agencies to bring the project to fruition.

Healthy Housing - SIEDC’s approach to “Healthy Housing” addresses numerous obstacles to housing development including limited local political support, cost of construction, prohibitive zoning, a limited history of affordable development and the need for more strategic partnerships with developers.

Healthy housing is critical for the growth of the community and involves a variety of housing strategies including new building stock, access to transit opportunities, environmental resiliency, and housing for young professionals and seniors who are significantly represented on Staten Island.

Local Needs Assessment - LOCAL NEEDS ASSESSMENT Staten Island has seen significant development over the past five years. Planning efforts have not kept pace with development, and local leaders are concerned with a variety of economic development issues. In response, the Staten Island Economic Development Corporation (SIEDC) has received grants from New York State Senator Diane Savino and National Grid to conduct a Local Needs Assessment for the borough of Staten Island.

Neighborhood development

The SIEDC manages several business improvement districts throughout the borough along with a merchant’s associations. SIEDC has been able to assist with town cleanups, restaurant crawls, holiday tree lighting, and other fun events for the public to enjoy. Each town has its own sights and activities to enjoy. Read about them all below.

New Dorp BID - The mission of the New Dorp Local Development Corporation is to enhance the New Dorp economy by promoting public and private investment, providing services and events, and encouraging responsible and sustainable development, all of which improve the quality of life and provide broad and diverse employment opportunities in the New Dorp area.

West Shore BID - In May 2012, Staten Island Economic Development Corporation (SIEDC) was selected by the New York City Economic Development Corporation (NYCEDC) to assist in developing a new industrial business improvement district on the West Shore of Staten Island. Since its inception in July 2015, the West Shore Business Improvement District (WS-IBID) has provided much-needed services including private maintenance, private security, signage and wayfinding, advocacy on behalf of property owners and important infrastructure improvements. The ultimate goal of the WS-IBID is to transform the West Shore into a premier industrial corridor for Staten Island and the City.

Victory Boulevard Merchants Group - Victory Blvd. Merchants Association has been created to benefit the local community. The SIEDC is helping to grow and improve the Victory Boulevard shopping experience. It started with Holiday lights, new trash receptacles, a cleaning crew, and some beautification.

Huguenot Merchants Association - The SIEDC provides marketing and economic development opportunities to small businesses in Huguenot, Staten Island.

Richmond Road Merchants Association - The SIEDC provides marketing and economic development opportunities to small businesses on Richmond Road in Staten Island.

Richmond Valley Merchants Association - The SIEDC provides marketing and economic development opportunities to small businesses on Richmond Valley in Staten Island.

Membership

To achieve SIEDC's mission, the organization relies on the support of small businesses and corporations. SIEDC offers 5 different levels of membership and has over 200 members.

References

Non-profit organizations based in New York City
Economy of Staten Island
Economic development organizations in the United States


title: Seattle Impact

text:
Seattle Impact FC was an American professional indoor soccer team that began play as a member of the Major Arena Soccer League with its 2014-15 season. Based in Seattle, Washington, the Impact played its home games at the ShoWare Center in nearby Kent. After struggles on and off the field, the team's assets were sold mid-season to Lane Smith whose Tacoma Stars completed Seattle's scheduled 2015 regular season games.

History
Originally, the team was going to be named the Tacoma Stars, in honor of the original Stars which played in the original Major Indoor Soccer League from 1983 until the league folded in 1992.  However, because of a legal dispute with the Tacoma Soccer Center over ownership of said name, owner Dion Earl abandoned these plans, choosing instead to name the team Seattle Impact FC (Seattle to represent the greater metropolitan area which also included Tacoma and Kent, and Impact at his wife's suggestion).

Jason Dunn, an Olympia native who played college soccer for Washington and Seattle Pacific and later for the American Professional Soccer League's Seattle Sounders and the indoor Seattle SeaDogs, was set to serve as the Impact's inaugural head coach. Just before the regular season started, Dunn and assistant coach Todd Haley left the team after the Impact failed to make contractual payments due on October 25. Impact owner Dion Earl announced that he will serve as head coach as well as continue his role as a player.

The planned "Ladies with Impact" dance team disbanded when several members resigned after alleging that Impact owner Dion Earl made sexual advances towards them. The dancers also claimed that the team had not paid them for their work. The dance team's former co-captain obtained a sexual harassment protection order against Earl from King County Superior Court Judge Chad Allred on October 22. A large number of the players contracted to Impact quit in protest. Earl denied the claims. Although no criminal charges were filed, Earl subsequently lost a civil suit brought by four former employees in a default judgment after he refused to attend the trial.

On January 12, 2015, The Seattle Times revealed that Impact owner Dion Earl was negotiating to sell the struggling franchise to Lane Smith, owner of the Tacoma Stars of the semi-pro Western Indoor Soccer League. The Impact sold the rights to its top players for cash during the negotiation period. The sale was completed on January 14, with Smith acquiring the team's assets but not the staff or player roster. The Tacoma Stars took over the Impact's remaining schedule and played their MASL home games at the ShoWare Center while continuing to also compete in the Western Indoor Soccer League.

Year-by-year

References

External links
Seattle Impact official website

Association football clubs established in 2014
Association football clubs disestablished in 2015
Indoor soccer clubs in the United States
Defunct Major Arena Soccer League teams
Defunct indoor soccer clubs in the United States
Soccer clubs in Seattle
Sports in Kent, Washington
2014 establishments in Washington (state)
2015 disestablishments in Washington (state)
Defunct soccer clubs in Washington (state)


title: César Peñaranda

text:
César Augusto Peñaranda Murguira (14 May 1915 – 22 March 2007) was a Peruvian cyclist. He competed in the individual and team road race events at the 1936 Summer Olympics.

References

External links

1915 births
2007 deaths
Peruvian male cyclists
Olympic cyclists for Peru
Cyclists at the 1936 Summer Olympics
Sportspeople from Lima
20th-century Peruvian people


title: At the Sign of the Swingin' Cymbal

text:
"At the Sign of the Swingin' Cymbal" (alternatively titled "At the Sign of the Swinging Cymbal") is an instrumental piece written by Brian Fahey. The piece was first released in September 1960 under the name Brian Fahey and His Orchestra.

It is best known as Alan Freeman's signature song, having been used as the theme tune to his BBC Light Programme Pick of the Pops from 1961 to 1966.  The original version was proposed to Alan by the BBC producer Derek Chinnery. By April 1966 it was replaced as the main theme by "Quite Beside the Point" by the Harry Roberts Sound and written by Cliff Adams. But bits of the original "Swinging Cymbal" theme were used occasionally by Alan as jingles in the show. From 5 April 1970, the show used a new version of "At The Sign of the Swinging Cymbal" arranged by former Ladybirds singer Barbara Moore and recorded by Brass Incorporated. This version is still used by the BBC today.

The Propellerheads modernised the song in their 1998 re-imagining "Crash!" which was included on the second soundtrack of the film Austin Powers: The Spy Who Shagged Me. It was also used for several years as the music for the Radio 1 Top 40, following a brief outing of an alternative remix by Norman Cook.

Background
After joining BBC Light Programme from Radio Luxembourg in 1961, Alan Freeman used the piece as his theme music for Records Around Five and a year later as the theme to Pick of the Pops.

References

1960s songs
Instrumentals
Radio theme songs
Songs about musical instruments


title: Diedra cockerellana

text:
Diedra cockerellana, Cockerell's moth, is a species of moth of the family Tortricidae. It is found in North America, where it has been recorded from California, Colorado, Illinois, Indiana, Iowa, New Mexico, Ontario, Utah and Wisconsin.

The moth is about 18–22 mm. The forewings are yellowish-brown, covered by series of connected loops. Two of these have a black margin and white filling. Adults have been recorded on wing from July to October.

References

Moths described in 1907
Archipini


title: PharmGKB

text:
The Pharmacogenomics Knowledgebase (PharmGKB) is a publicly available, online knowledge base responsible for the aggregation, curation, integration and dissemination of knowledge regarding the impact of human genetic variation on drug response. It is funded by the National Institutes of Health (NIH) National Institute of General Medical Sciences (NIGMS), and is a partner of the NIH Pharmacogenomics Research Network (PGRN). It has been managed at Stanford University since its inception in 2000.

Purpose
The main goal of PharmGKB is to aid researchers in understanding how variation in a person’s genetic makeup affects how he or she responds to a drug, a field known as pharmacogenomics or pharmacogenetics (PGx). In order to achieve this goal, PharmGKB manually curates PGx information from the primary literature, and then stores it in the knowledge base. This information can be aggregated, allowing PharmGKB to identify consistent genetic variant-drug response interactions. Variant-drug interactions with a large amount of supporting evidence may then be considered for potential clinical implementation. In order to capitalize on cases where strong PGx literature evidence exists, PharmGKB cofounded the Clinical Pharmacogenetic Implementation Consortium (CPIC), an organization responsible for the creation and dissemination of peer-reviewed, freely available genotype-based drug-dosing guidelines for clinicians. PharmGKB also works with various international consortia groups, such as the International Warfarin Pharmacogenetics Consortium (IWPC) and the International Clopidogrel Pharmacogenomics Consortium (ICPC), facilitating collaboration and analysis of large PGx datasets.

Content
PharmGKB has many different types of PGx-related information available through the website, discussed in the sections below. PharmGKB has PGx content on genetic variants (including single-nucleotide polymorphisms (SNPs) and haplotypes, as well as some copy number variations (CNVs) and indels), genes, drugs, phenotypes (including diseases and side effects) and PubMed IDs (PMIDs).

Variant Annotations
Variant annotations are summaries describing how a particular genetic polymophism is associated with a drug response, as reported in a single publication. Examples of drug responses include adverse drug reactions, changes in drug efficacy and alterations in how quickly or slowly a drug is metabolized. Curators review past and present literature and add any studies containing PGx-relevant results to the knowledge base through these variant annotations. The variant-drug associations may be negative or positive, and they come from a wide variety of study types, including genome-wide association studies, clinical trials, and functional in vitro studies. All variant annotations contain a standardized sentence, which allows results to be easily compared and contrasted between studies throughout the knowledge base. In addition to recording the genetic variant-drug phenotype association, key study parameters such as study size, population ethnicity, p-values and allele frequencies are also noted in the annotation

Clinical Annotations
Clinical annotations combine all variant annotations that discuss the same variant-drug phenotype association and bring them together into a single written summary of the association. Clinical annotations consist of summary text, which is written as the association for each genotype as compared to other genotypes. Below this summary text, clinical annotations contain a list of all the variant annotations that support this particular variant-drug phenotype association. Each clinical annotation is also given a level of evidence, providing a measure of confidence in the association. The level of evidence for a clinical annotation is manually assessed, and is based on criteria such as the number of studies finding positive versus negative results, p-values and study sizes:
 Level 1A: Clinical annotation for a variant-drug combination in a CPIC or medical society-endorsed PGx guideline, or implemented at a Pharmacogenomics Research Network (PGRN) site or in another major health system.
 Level 1B: Clinical annotation for a variant-drug combination where the preponderance of evidence shows an association. The association must be replicated in more than one cohort with significant p-values, and preferably will have a strong effect size.
 Level 2A: Clinical annotation for a variant-drug combination that qualifies for level 2B where the variant is within a Very Important Pharmacogene (VIP) as defined by PharmGKB. The variants in level 2A are in known pharmacogenes, so functional significance is more likely.
 Level 2B: Clinical annotation for a variant-drug combination with moderate evidence of an association. The association must be replicated but there may be some studies that do not show statistical significance, and/or the effect size may be small.
 Level 3: Annotation for a variant-drug combination based on a single significant (not yet replicated) or annotation for a variant-drug combination evaluated in multiple studies but lacking clear evidence of an association.
 Level 4: Annotation based on a case report, non-significant study or in vitro, molecular or functional assay evidence only.

Very Important Pharmacogene (VIP) summaries
VIPs are overviews of important genes involved in drug response. They are intended to provide users a better understanding of a particular PGx-relevant gene, and consist of background information on the gene, including any disease associations, and an in-depth review of its pharmacogenetics. Though VIPs are available on the PharmGKB website in an interactive format, they are also typically published in the journal Pharmacogenetics and Genomics. VIPs also provide links to summaries for particularly important variants within that gene – these are known as VIP Variant summaries.

Pathways
PharmGKB pathways are evidence-based diagrams detailing the pharmacokinetics (PK) or pharmacodynamics (PD) of a PGx-relevant drug, accompanied by text providing background on the drug and a discussion of its PK, PD and PGx. Pathways are typically published in the journal Pharmacogenetics and Genomics. Pathways are manually created after an extensive literature review, and the connections on the pathway diagrams are supported by literature citations; these supporting citations can be viewed in the online versions of the pathways. Additionally, the information contained within each pathway diagram is available for download in TSV, BioPAX and GPML formats.

Dosing guidelines
PharmGKB provides PGx-based drug dosing guidelines from CPIC, as well as The Royal Dutch Association for the Advancement of Pharmacy Pharmacogenetics Working Group (DWPG) and professional societies such as The American College of Rheumatology. More information about the DPWG and their objectives and methods can be found at the PharmGKB  website.

CPIC
CPIC consists of members of NIH Pharmacogenomics Research Network (PGRN), PharmGKB staff, and experts in PGx and medicine. The goal of CPIC is to create freely-available, peer-reviewed drug-dosing guidelines for clinicians who have access to pre-emptive genetic testing results. CPIC guidelines are written for PGx associations that have substantial supporting evidence, such as the associations between HLA-B*58:01 and Stevens–Johnson syndrome/toxic epidermal necrolysis in patients taking allopurinol, and SLCO1B1 rs4149056 and myopathy in patients taking simvastatin CPIC guidelines are published in the journal Clinical Pharmacology & Therapeutics, and are also available through PharmGKB in an interactive format. CPIC dosing guidelines on PharmGKB include an excerpt from the published guideline, the therapeutic dosing recommendations in a table format, and PDF versions of the guideline and supplement. PharmGKB also provides a dosing guideline tool, where users can enter in a genotype of interest and receive the relevant dosing recommendation. Downloadable, computable versions of the guidelines in JSON format are also available on PharmGKB.

FDA and EMA drug labels
PharmGKB curates and annotates drug labels containing PGx information from both the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA). FDA-approved drug labels with PGx information are sourced from the FDA’s Table of Pharmacogenomic Biomarkers in Drug Labels page, or identified by curators. EMA-approved drug labels (known as European Public Assessment Reports (EPARs)) are manually searched for using the drugs in the FDA Biomarker table. PharmGKB tags each FDA or EMA label with a PGx level based on internally created guidelines:
Genetic testing required: The label states or implies that some sort of gene, protein or chromosomal testing, including genetic testing, functional protein assays, cytogenetic studies, etc., should be conducted before using this drug. This requirement may only be for a particular subset of patients. PharmGKB considers labels that state the variant is an indication for the drug, as implying a test requirement. If the label states a test "should be" performed, this is also interpreted as a requirement.
Genetic testing recommended: The label states or implies that some sort of gene, protein or chromosomal testing, including genetic testing, functional protein assays, cytogenetic studies, etc., is recommended before using this drug. This recommendation may only be for a particular subset of patients. PharmGKB considers labels that say testing "should be considered" to be recommending testing.
Actionable PGx: The label does not discuss genetic or other testing for gene/protein/chromosomal variants, but does contain information about changes in efficacy, dosage or toxicity due to such variants. The label may mention contraindication of the drug in a particular subset of patients but does not require or recommend gene, protein or chromosomal testing.
Informative PGx: The label mentions a gene or protein is involved in the metabolism or pharmacodynamics of the drug, but there is no information to suggest that variation in these genes/proteins leads to different response.

See also
pharmacogenetics
pharmacogenomics
pharmacokinetics
pharmacodynamics
 Pharmacogene Variation Consortium
 Clinical Pharmacogenetics Implementation Consortium

References

Biological databases


title: Tylomelania centaurus

text:
Tylomelania centaurus is a species of freshwater snail with an operculum, an aquatic gastropod mollusk in the family Pachychilidae.

Distribution
This species occurs in Lake Poso, Sulawesi, Indonesia.

Description
The shell has 7.5 whorls. The height of the shell is . The width of an aperture is . The height of an aperture is .

Ecology
Tylomelania centaurus is a lacustrine species.

References

centaurus
Gastropods described in 1898


title: 2001 1000 Guineas

text:
The 2001 1000 Guineas Stakes was a horse race held at Newmarket Racecourse on Sunday 6 May 2001. It was the 188th running of the 1000 Guineas.

The winner was Ahmed Al Maktoum's Ameerat, a British-bred bay filly trained at Newmarket, Suffolk by Michael Jarvis and ridden by Philip Robinson. Ameerat's victory was the first in the race for her owner and trainer and the second for Robinson who had won on Pebbles in 1985.

The contenders
The race attracted a field of fifteen runners: thirteen trained in the United Kingdom, one in Ireland and one in France. The favourite was the Michael Stoute-trained Karasta who had won the May Hill Stakes and finished second in the Prix Marcel Boussac in 2000. She was accompanied by her stable companion Enthused, winner of the Princess Margaret Stakes and Lowther Stakes. The Irish challenger was Toroca, trained by Aidan O'Brien at Ballydoyle who had won a maiden race at the Curragh two weeks earlier. The Godolphin Racing stable entered Muwakleh, a filly who had won both her races in Dubai including the UAE 1000 Guineas. France was represented by the Criquette Head-trained Stunning, winner of the Prix Imprudence. The other fancied runners included the undefeated Crystal Music, winner of the Fillies' Mile, and the Cherry Hinton Stakes winner Dora Carrington. Karasta headed the betting at odds of 9/2 ahead of Crystal Music (5/1), Enthused (6/1), Muwakleh (13/2), Stunning (9/1) and Toroca (10/1). Ameerat, whose only previous win had come in a maiden race at Goodwood Racecourse nine months earlier, was next in the betting at 11/1.

The race
The starting stalls were placed on the stands side (the left side from the jockeys' viewpoint) of the wide Newmarket straight and the field raced up that side of the course throughout the race. Muwakleh was sent to the front by Frankie Dettori soon after the start, and was followed by Sayedah with Ashlinn, Arhaaff, Ameerat and Autumnal as the fillies remained closely grouped until the final quarter-mile. Crystal Music made progress on the outside, but was unable to sustain her effort, leaving Ameerat as Muwakleh's only serious challenger. Ameerat gradually wore down the Godolphin filly, gaining the advantage 50 yards from the finish to win by a neck. Toroca stayed on well in the closing stages to take third place ahead of Crystal Music and Enthused. Stunning finished in seventh place whilst Karasta was thirteenth of the fifteen runners.

Ameerat's victory gave Jarvis his first British classic winner in a thirty-three-year training career. He described the moment as "a great thrill", while Robinson described the winner as a "remarkable filly".

Race details
 Sponsor: Sagitta
 First prize: £174,000
 Surface: Turf
 Going: Good
 Distance: 8 furlongs
 Number of runners: 15
 Winner's time: 1:38.36

Full result

 Abbreviations: nse = nose; nk = neck; shd = head; hd = head; dist = distance; UR = unseated rider; DSQ = disqualified; PU = pulled up

Winner's details
Further details of the winner, Ameerat
 Foaled: 4 April 1998
 Country: United Kingdom
 Sire: Mark of Esteem; Dam: Walimu (Darshaan)
 Owner: Ahmed Al Maktoum
 Breeder: Ahmed Al Maktoum

References

1000 Guineas
 2001
1000 Guineas
1000 Guineas
2000s in Suffolk


title: I Don't Dance (album)

text:
I Don't Dance is the third studio album by American country music artist Lee Brice. It was released on September 9, 2014 via Curb Records.

Content
The album's lead single is its title track, which became a number one single on Country Airplay in mid 2014. "Drinking Class" is the second single.

Brice produced the title track by himself; he co-produced with Jon Stone of American Young on tracks 2, 7–9, and 11–13, and Kyle Jacobs and Matt McClure on tracks 3–6, and 10. He also played every instrument on the track "Girls in Bikinis".

"Sirens" appears in the video game Madden NFL 16.

Critical reception

I Don't Dance received positive reviews from music critics. It has a score of 69 out of 100 on Metacritic indicating "generally favorable reviews", based on 4 critics reviews.
Jon Freeman of Country Weekly rated the album "B". He praised the songwriting of the title track, as well as "Drinkin' Class", "My Carolina", and "The Airport Song", and described Brice's voice as "spectacular, ranging from a gentle whisper to a right-from-the-gut, serrated-edge howl that elevates even the most forgettable material into high drama." Freeman also praised the sparseness of the album's production.

Commercial performance
The album debuted on the Billboard 200 at No. 5, and No. 1 on the Top Country Albums chart with 39,000 copies sold in the United States in its debut week. The album has sold 247,400 copies in the US as of March 2016. On October 18, 2017, the song received gold status by the RIAA.

Track listing

Personnel
Adapted from liner notes.

 Carolyn Wann Bailey - strings (tracks 5, 10)
 Hari Bernstein - strings (tracks 5, 10)
 Travis Bettis - electric guitar (tracks 1, 2, 12)
 Jessica Blackwell - strings (tracks 5, 10)
Lee Brice - acoustic guitar (tracks 1, 7-9, 12), banjo (tracks 8, 9) electric guitar (tracks 3-5, 7, 11), handclaps (track 9), horn arrangements (track 10), keyboards (track 8), string arrangements (tracks 5, 10), lead vocals (all tracks), background vocals (tracks 1, 2, 4, 6-8, 11), "Heys" (track 9), whistle (track 8)
 Sara Brice - talking girl (track 8)
 Tom Bukovac - electric guitar (tracks 2, 13)
 Perry Coleman - background vocals (tracks 2, 4, 5-7, 11, 13)
 Chad Cromwell - drums (tracks 7, 11)
 Eric Darken - percussion (track 1)
 Charles Kenneth Dixon - strings (tracks 5, 10), copyist (tracks 5, 10)
 Chip Esten - handclaps (track 9), "Heys" (track 9)
 Dan Frizsell - programming (track 12)
 Ben Glover - background vocals (track 3)
 Kevin "Swine" Grantt - bass guitar (track 7)
 Adrienne Harmon - strings (tracks 5, 10)
 Mark Hill - bass guitar (tracks 3, 5, 6, 10)
 June Iwasaki - strings (tracks 5, 10)
 Mike Johnson - steel guitar (tracks 3-6)
 Charlie Judge - B-3 organ (track 11), horn arrangements (track 10), keyboards (tracks 1, 3-8), piano (track 6), programming (tracks 1-8, 11), string arrangements (tracks 5, 10), strings (track 11)
 Jeff King - electric guitar (tracks 3-6, 9, 10)
 Jennifer Kummer - french horn (track 10)
 Phillip Lammonds - acoustic guitar (track 12)
 Tim Lauer - keyboards (track 2)
 Tony Lucido - bass guitar (track 8, 9)
 Donnie Marple - drums (tracks 1, 4, 12)
 Matt McClure - programming (tracks 3-6)
 Pat McGrath - acoustic guitar (tracks 3-6, 10)
 Jerry McPherson - e-bow (track 1), electric guitar (tracks 1, 3-6, 9, 10)
 Miles McPherson - drums (track 6)
 Greg Morrow - drums (track 2)
 Emily Nelson - strings (tracks 5, 10)
 Justin Niebank - programming (track 1)
 Kelly Norman - background noise (track 13)
 Kelly Norris - background vocals (track 2)
 Russ Pahl - steel guitar (tracks 1, 9)
 Sarighandi D. Reist - strings (tracks 5, 10)
 Paul Rippee - bass guitar (tracks 1, 2)
 Maggie Rose - background vocals (track 13)
 Bradley Smith - B-3 organ (track 12), piano (track 13), background vocals (track 12)
 Jimmie Lee Sloas - bass guitar (tracks 4, 11, 12)
 Jon Stone - acoustic guitar (tracks 8, 11), electric guitar (track 7), handclaps (track 9), background vocals (tracks 2, 9), "Heys" (track 9), "Woos" and "Yeas" (track 8)
 Russell Terrell - background vocals (track 10)
 Patrick Walle - french horn (track 10)
 Jason Webb - B-3 organ (tracks 3, 6), keyboards (tracks 3, 6), piano (track 4), programming (track 6)
 Derek Wells - electric guitar (tracks 3-5, 10)
 Nir Z. - drums (tracks 3, 5, 8, 9, 10)

Chart performance

Weekly charts

Year-end charts

Singles

Certifications

References

2014 albums
Lee Brice albums
Curb Records albums


title: Cavum Vergae

text:
The cavum Vergae is a posterior extension of the cavum septi pellucidi, an anomaly that is found in a small percentage of human brains. It was first described by Andrea Verga.

Brain
Ventricular system