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Single-track road
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In mountains
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When practical, it is usually considered better for the vehicle going downhill to yield the right of way by stopping at a wide spot. The reason seems to be that it may be harder for the vehicle going up to get started again. At least in California, it is also the vehicle going downhill that must back up, if it is too late to stop at a wide spot.
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Single-track road
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Types
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Chicanes Chicanes are often placed on residential streets as a more aesthetic means to slow down cars.
One-lane passages Sometimes, for budget reasons, and where traffic is fairly low, bridges exist as single-track corridors. Tunnels in remote areas can also be one lane when the tunnel is short and traffic is low, when building a hill or blasting away the mountain is too cost-prohibitive.
One-way single-track roads Single-track roads also exist as one-way stretches. Exit and entrance ramps for freeways and motorways are among common examples of one-way single-track roads.
Private single-track roads The most common example of private single-track roads are long driveways of rural properties such as country houses and farm property.
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Single-track road
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Types
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Ice roads The mountain passes on the Dalton Highway in Alaska have a rule where goods-carrying northbound truck traffic has the right of way, while returning southbound traffic has to stop, as mentioned on Ice Road Truckers. The reason behind this procedure is that traffic going north is in somewhat of a hurry to deliver equipment to Deadhorse, Prudhoe Bay, and the drill site over the frozen Arctic Ocean.
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Single-track road
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Types
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Temporary one-lane restrictions When reconstruction is being done on two-lane highways where traffic is moderately heavy, a worker will often stand at each end of the construction zone, holding a sign with "SLOW" or "GO" written on one side and "STOP" on the reverse. The workers, who communicate through yelling, hand gestures, or radio, will periodically reverse their signs to allow time for traffic to flow in each direction. A modification of this for roadways that have heavier traffic volumes is to maintain one direction on the existing roadway, and detour the other, thus not requiring the use of flaggers. An example of this is the M-89 reconstruction project in Plainwell, Michigan, where westbound traffic is detoured via county roads around town.
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Single-track road
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User etiquette
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If lines of sight are long, and both drivers are familiar with the road, vehicles heading towards each other can adjust their speed so as to arrive at a wide spot at the same time and pass slowly, avoiding the need for either vehicle to stop.
When two vehicles meet head-on, generally the drivers confer to decide in which direction lies the closest wide spot, and together they travel there, the lead vehicle necessarily in reverse gear.
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Single-track road
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User etiquette
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In Scotland, and places like the Isle of Man most drivers are accustomed to single-track roads. When opposing traffic is encountered, the first driver to reach the nearest passing place pulls over, no matter which side, and flashes the headlights to signal the other car to proceed forward. It is customary for both drivers to then acknowledge each other with a wave as they pass. At night, both drivers acknowledge each other by flashing their off-side direction indicators headlights immediately before or as they pass. It is extremely dangerous to flash headlights at close proximity on narrow unlit country roads at night as this affects drivers' night vision.
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Single-track road
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User etiquette
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Usually when there is a brief one-lane bottleneck of a two-lane road, traffic will usually yield to oncoming traffic already in the bottleneck. One-lane single-track roads usually have no conflict.
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Single-track road
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User etiquette
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In the United States, if the situation permits, both vehicles will pull off the road slightly and pass in this manner. Although saving time, this process can cause ruts and erosion along the edge of the road. For this reason, single track roads are generally used in places with very low traffic volumes, though one-lane stop-gap measures will have a STOP and YIELD on a sign construction workers flip.
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Single-track road
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User etiquette
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If there are no passing places or wide parts of the road then the start of the road is considered as the passing place.
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WAY-163909
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WAY-163909
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WAY-163,909 is a drug which acts as a potent and reasonably selective agonist for the serotonin 5-HT2C receptor. It has antipsychotic-like effects in animal models, and has been used to study the role of the 5-HT2C receptor subtype in the action of addictive drugs such as nicotine and methamphetamine.
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Barrow's inequality
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Barrow's inequality
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In geometry, Barrow's inequality is an inequality relating the distances between an arbitrary point within a triangle, the vertices of the triangle, and certain points on the sides of the triangle. It is named after David Francis Barrow.
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Barrow's inequality
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Statement
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Let P be an arbitrary point inside the triangle ABC. From P and ABC, define U, V, and W as the points where the angle bisectors of BPC, CPA, and APB intersect the sides BC, CA, AB, respectively. Then Barrow's inequality states that PA+PB+PC≥2(PU+PV+PW), with equality holding only in the case of an equilateral triangle and P is the center of the triangle.
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Barrow's inequality
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Generalisation
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Barrow's inequality can be extended to convex polygons. For a convex polygon with vertices A1,A2,…,An let P be an inner point and Q1,Q2,…,Qn the intersections of the angle bisectors of ∠A1PA2,…,∠An−1PAn,∠AnPA1 with the associated polygon sides A1A2,…,An−1An,AnA1 , then the following inequality holds: sec (πn)∑k=1n|PQk| Here sec (x) denotes the secant function. For the triangle case n=3 the inequality becomes Barrow's inequality due to sec (π3)=2
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Barrow's inequality
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History
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Barrow's inequality strengthens the Erdős–Mordell inequality, which has identical form except with PU, PV, and PW replaced by the three distances of P from the triangle's sides. It is named after David Francis Barrow. Barrow's proof of this inequality was published in 1937, as his solution to a problem posed in the American Mathematical Monthly of proving the Erdős–Mordell inequality. This result was named "Barrow's inequality" as early as 1961.A simpler proof was later given by Louis J. Mordell.
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String quintet repertoire
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String quintet repertoire
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The string quintet normally comprises the four instruments of the standard string quartet (2 violins, viola, and cello), plus one additional instrument. This additional instrument may be a viola, cello or double bass. Of these three different combinations, the string quintet with a second viola has the widest repertoire and may be referred to as the standard string quintet. The other two combinations have far fewer important works, though the combination with two cellos includes the string quintet by Schubert, which is widely considered the greatest of all string quintets.
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String quintet repertoire
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String quintet repertoire
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Ordering in each section is by surname of composer. These lists should be complete for major composers and their string quintets. For secondary or minor composers, the lists are not exhaustive but those shown may be taken as representative examples. For recent or living composers, no attempt has been made at completeness.
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String quintet repertoire
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"Viola" quintets
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String quintets with 2 violins, 2 violas and cello Arnold Bax (1883-1953) String Quintet in G (1908) Lyrical Interlude (1922) Ludwig van Beethoven (1770-1827) String Quintet in E flat, Op. 4 (1792-3; 1795–6) String Quintet in C major, Op. 29 (1801) String Quintet in C minor, Op. 104 (1793-5; 1817) Luigi Boccherini (1743-1805) String Quintet Op. 60 No. 1 in C major, G 391 (1801) String Quintet Op. 60 No. 2 in B flat major, G 392 (1801) String Quintet Op. 60 No. 3 in A major, G 393 (1801) String Quintet Op. 60 No. 4 in E flat major, G 394 (1801; lost) String Quintet Op. 60 No. 5 in G major, G 395 (1801) String Quintet Op. 60 No. 6 in F major, G 396 (1801) String Quintet Op. 62 No. 1 in C major, G 397 (1802) String Quintet Op. 62 No. 2 in E flat major, G 398 (1802) String Quintet Op. 62 No. 3 in F major, G 399 (1802) String Quintet Op. 62 No. 4 in B flat major, G 400 (1802) String Quintet Op. 62 No. 5 in D major, G 401 (1802) String Quintet Op. 62 No. 6 in E major, G 402 (1802) Also 12 further quintets arranged from piano quintets Johannes Brahms (1833-1897) String Quintet No. 1 in F major, Op. 88 (1883) String Quintet No. 2 in G major, Op. 111 (1891) Frank Bridge (1879-1941) String Quintet in E minor, H 7 (1901) Benjamin Britten (1913-1976) Phantasy Quintet (1932) Max Bruch (1838-1920) String Quintet No. 1 in A minor (1918) String Quintet No. 2 in E flat major (1918) Anton Bruckner (1824-1896) String Quintet in F major, WAB 112 (1878-9) Intermezzo for String Quintet, WAB 113 (1879) Franz Danzi (1763-1826) String Quintet in E flat major, op. 66 no. 1 (1823-4) String Quintet in F minor, op. 66 no. 2 (1823-4) String Quintet in A major, op. 66 no. 3 (1823-4) Gaetano Donizetti (1797-1848) Allegro in C major Antonín Dvořák (1841-1904) String Quintet in A minor, Op. 1 (1861) String Quintet in E-flat major, Op. 97 (1893) François-Joseph Fétis (1784-1871) String Quintet no. 1 in A minor (1860) String Quintet no. 2 (1862) String Quintet no. 3 (1862) Niels Gade (1817-1890) String Quintet in E minor, op. 8 (1845) Joseph Haydn (1732-1809) Divertimento in G major, Hob.II:2 (c. 1753) Michael Haydn (1737-1806) Quintet in C major, MH 187 Quintet in B flat major, MH 412 Quintet in F major, MH 367 Quintet in F major, MH 411 Quintet in G major, MH 189 Heinrich von Herzogenberg (1843-1900) String Quintet in C minor, op. 77 (1892) Felix Mendelssohn (1809-1847) String Quintet No. 1 in A major, op. 18 (1826; 1832) Minuet in F sharp minor (1826) String Quintet No. 2 in B flat major, op. 87 (1845) Wolfgang Amadeus Mozart (1756-1791) String Quintet in B-flat, K. 174 (1773) String Quintet in C major, K. 515 (1787) String Quintet in G minor, K. 516 (1787) String Quintet in C minor, K. 406/516b (1782; c. 1788) String Quintet in D major, K. 593 (1790) String Quintet in E-flat major, K. 614 (1791) Carl Nielsen (1865-1931) String Quintet in G major, FS 5 (1888) George Onslow (1784-1853) Three string quintets Three further string quintets with two versions, either for 2 violins, 2 violas and cello or for 2 violins, viola and 2 cellos Sir Hubert Parry (1848-1918) String Quintet in E flat major (1883-4) Anton Reicha (1770-1836) Seven string quintets Ferdinand Ries (1784-1838) Five string quintets Franz Schubert (1797-1828) Overture in C minor, D. 8 (1811) Louis Spohr (1784-1859) Seven string quintets Sir Charles Villiers Stanford (1852-1924) String Quintet no. 1 in F major, op. 85 (1903) String Quintet no. 2 in C minor, op. 86 (1903; unpublished) Johan Svendsen (1840-1911) String Quintet in C major, Op. 5 (1867) Sergey Taneyev (1856-1915) String Quintet no. 2 in C major, Op. 16 (1903-4) Ralph Vaughan Williams (1872-1958) Phantasy Quintet (1912)
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String quintet repertoire
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"Cello" quintets
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String quintets with 2 violins, viola and 2 cellos David Baker (1931-2016) Two Cello String Quintet (1987) Violoncello and string quartet (Commissioned by Janos Starker) Ludwig van Beethoven Kreutzer Sonata arranged for String Quintet (Simrock, 1832) Luigi Boccherini (1743-1805) String Quintet Op. 10 No. 1 in A major, G 265 String Quintet Op. 10 No. 2 in E flat major, G 266 String Quintet Op. 10 No. 3 in C minor, G 267 String Quintet Op. 10 No. 4 in C major, G 268 String Quintet Op. 10 No. 5 in E flat major, G 269 String Quintet Op. 10 No. 6 in D major, G 270 String Quintet Op. 11 No. 1 in B flat major, G 271 String Quintet Op. 11 No. 2 in A major, G 272 String Quintet Op. 11 No. 3 in C major, G 273 String Quintet Op. 11 No. 4 in F minor, G 274 String Quintet Op. 11 No. 5 in E major, G 275 (This quintet includes the well-known "Boccherini's Minuet") String Quintet Op. 11 No. 6 in D major ("L'uccelliera" - "Bird Sanctuary"), G 276 String Quintet Op. 13 No. 1 in E flat major, G 277 String Quintet Op. 13 No. 2 in C major, G 278 String Quintet Op. 13 No. 3 in F major, G 279 String Quintet Op. 13 No. 4 in D minor, G 280 String Quintet Op. 13 No. 5 in A major, G 281 String Quintet Op. 13 No. 6 in E major, G 282 String Quintet Op. 18 No. 1 in C minor, G 283 String Quintet Op. 18 No. 2 in D major, G 284 String Quintet Op. 18 No. 3 in E flat major, G 285 String Quintet Op. 18 No. 4 in C major, G 286 String Quintet Op. 18 No. 5 in D minor, G 287 String Quintet Op. 18 No. 6 in E major, G 288 String Quintet Op. 20 No. 1 in E flat major, G 289 String Quintet Op. 20 No. 2 in B flat major, G 290 String Quintet Op. 20 No. 3 in F major, G 291 String Quintet Op. 20 No. 4 in G major, G 292 String Quintet Op. 20 No. 5 in D minor, G 293 String Quintet Op. 20 No. 6 in A minor, G 294 String Quintet Op. 25 No. 1 in D minor, G 295 String Quintet Op. 25 No. 2 in E flat major, G 296 String Quintet Op. 25 No. 3 in A major, G 297 String Quintet Op. 25 No. 4 in C major, G 298 String Quintet Op. 25 No. 5 in D major, G 299 String Quintet Op. 25 No. 6 in A minor, G 300 String Quintet Op. 27 No. 1 in A major, G 301 String Quintet Op. 27 No. 2 in G major, G 302 String Quintet Op. 27 No. 3 in E minor, G 303 String Quintet Op. 27 No. 4 in E flat major, G 304 String Quintet Op. 27 No. 5 in G minor, G 305 String Quintet Op. 27 No. 6 in B minor, G 306 String Quintet Op. 28 No. 1 in F major, G 307 String Quintet Op. 28 No. 2 in A major, G 308 String Quintet Op. 28 No. 3 in E flat major, G 309 String Quintet Op. 28 No. 4 in C major, G 310 String Quintet Op. 28 No. 5 in D minor, G 311 String Quintet Op. 28 No. 6 in B flat major, G 312 String Quintet Op. 29 No. 1 in D major, G 313 String Quintet Op. 29 No. 2 in C minor, G 314 String Quintet Op. 29 No. 3 in F major, G 315 String Quintet Op. 29 No. 4 in A major, G 316 String Quintet Op. 29 No. 5 in E flat major, G 317 String Quintet Op. 29 No. 6 in G minor, G 318 String Quintet Op. 30 No. 1 in B flat major, G 319 String Quintet Op. 30 No. 2 in A minor, G 320 String Quintet Op. 30 No. 3 in C major, G 321 String Quintet Op. 30 No. 4 in E flat major, G 322 String Quintet Op. 30 No. 5 in E minor, G 323 String Quintet Op. 30 No. 6 in C major ("Musica notturna delle strade di Madrid"), G 324 String Quintet Op. 31 No. 1 in E flat major, G 325 String Quintet Op. 31 No. 2 in G major, G 326 String Quintet Op. 31 No. 3 in B flat major, G 327 String Quintet Op. 31 No. 4 in C minor, G 328 String Quintet Op. 31 No. 5 in A major, G 329 String Quintet Op. 31 No. 6 in F major, G 330 String Quintet Op. 36 No. 1 in E flat major, G 331 String Quintet Op. 36 No. 2 in D major, G 332 String Quintet Op. 36 No. 3 in G major, G 333 String Quintet Op. 36 No. 4 in A minor, G 334 String Quintet Op. 36 No. 5 in G minor, G 335 String Quintet Op. 36 No. 6 in F major, G 336 String Quintet Op. 39 No. 1 in B flat major, G 337 String Quintet Op. 39 No. 2 in F major, G 338 String Quintet Op. 39 No. 3 in D major, G 339 String Quintet Op. 40 No. 1 in A major, G 340 String Quintet Op. 40 No. 2 in D major, G 341 String Quintet Op. 40 No. 3 in D major, G 342 String Quintet Op. 40 No. 4 in C major, G 343 String Quintet Op. 40 No. 5 in E minor, G 344 String Quintet Op. 40 No. 6 in B flat major, G 345 String Quintet Op. 41 No. 1 in E flat major, G 346 String Quintet Op. 41 No. 2 in F major, G 347 String Quintet Op. 42 No. 1 in F minor, G 348 String Quintet Op. 42 No. 2 in C major, G 349 String Quintet Op. 42 No. 3 in B minor, G 350 String Quintet Op. 42 No. 4 in G minor, G 351 String Quintet Op. 43 No. 1 in E flat major, G 352 String Quintet Op. 43 No. 2 in D major, G 353 String Quintet Op. 43 No. 3 in F major, G 354 String Quintet Op. 45 No. 1 in C minor, G 355 String Quintet Op. 45 No. 2 in A major, G 356 String Quintet Op. 45 No. 3 in B flat major, G 357 String Quintet Op. 45 No. 4 in C major, G 358 String Quintet Op. 46 No. 1 in B flat major, G 359 String Quintet Op. 46 No. 2 in D minor, G 360 String Quintet Op. 46 No. 3 in C major, G 361 String Quintet Op. 46 No. 4 in G minor, G 362 String Quintet Op. 46 No. 5 in F major, G 363 String Quintet Op. 46 No. 6 in E flat major, G 364 String Quintet Op. 49 No. 1 in D major, G 365 String Quintet Op. 49 No. 2 in B flat major, G 366 String Quintet Op. 49 No. 3 in E flat major, G 367 String Quintet Op. 49 No. 4 in D minor, G 368 String Quintet Op. 49 No. 5 in E flat major, G 369 String Quintet Op. 50 No. 1 in A major, G 370 String Quintet Op. 50 No. 2 in E flat major, G 371 String Quintet Op. 50 No. 3 in B flat major, G 372 String Quintet Op. 50 No. 4 in E major, G 373 String Quintet Op. 50 No. 5 in C major, G 374 String Quintet Op. 50 No. 6 in B flat major, G 375 String Quintet Op. 51 No. 1 in E flat major, G 376 String Quintet Op. 51 No. 2 in C minor, G 377 String Quintet in C major, G 378 String Quintet in E minor (from G 407), G 379 String Quintet in F major (from G 408), G 380 String Quintet in E flat major (from G 410), G 381 String Quintet in A minor (from G 412), G 382 String Quintet in D major (from G 411), G 383 String Quintet in C major (from G 409), G 384 String Quintet in D minor (from G 416), G 385 String Quintet in E minor (from G 417), G 386 String Quintet in B flat major (from G 414), G 387 String Quintet in A major (from G 413), G 388 String Quintet in E minor (from G 415), G 389 String Quintet in C major (from G 418), G 390 String Quintet Op. 60 No. 1 in C major, G 391 String Quintet Op. 60 No. 2 in B flat major, G 392 String Quintet Op. 60 No. 3 in A major, G 393 String Quintet Op. 60 No. 4 in E flat major (lost), G 394 String Quintet Op. 60 No. 5 in G major, G 395 String Quintet Op. 60 No. 6 in E major, G 396 String Quintet Op. 62 No. 1 in C major, G 397 String Quintet Op. 62 No. 2 in E flat major, G 398 String Quintet Op. 62 No. 3 in F major, G 399 String Quintet Op. 62 No. 4 in B flat major, G 400 String Quintet Op. 62 No. 5 in D major, G 401 String Quintet Op. 62 No. 6 in E major, G 402 String Quintet in E flat major (lost), G 406 Also: "String Quintet in C major" put together by Johann Lauterbach (1832-1918) from unrelated Boccherini string quintet movements Aleksandr Borodin (1833-87) String Quintet in F minor (1853-4: unfinished; completed by O. Evlakhov) Luigi Cherubini (1760-1842) String Quintet in E minor (1837) Carl Ditters von Dittersdorf (1739-99) Six string quintets Henry Eccles (1670-1742) Sonata in G minor for cello and strings (This is actually a sonata for viola da gamba and figured bass and not a string quintet. The version for cello and strings is a transcription. This sonata is also often played in a transcription for cello and piano.) Aleksandr Glazunov (1865-1936) String Quintet in A major, Op. 39 (1891-2) Karl Goldmark (1820-1915) String Quintet in A minor, Op. 9 (1862) Jay Greenberg (born 1991) String Quintet (2005) George Onslow (1784-1853) Twenty-two string quintets Three further string quintets with two versions, either for 2 violins, viola and 2 cellos or for 2 violins, 2 violas and cello Anton Reicha (1770-1836) Three string quintets Franz Schubert (1797-1828) Quintet in C major, D. 956, Op. 163 (1828) Peter Seabourne (born 1960) String Quintet Adrien-François Servais (1807-66) Souvenir de Spa for cello and strings Sergey Taneyev (1856-1915) String Quintet no. 1 in G major, Op. 14 (1900–01)
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String quintet repertoire
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"Double bass" quintets
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String quintets with two violins, viola, cello and double bass Luigi Boccherini (1743-1805) String Quintet Op. 39 No. 1 in B flat major, G 337 (1787) String Quintet Op. 39 No. 2 in F major, G 338 (1787) String Quintet Op. 39 No. 3 in D major, G 339 (1787) Carl Ditters von Dittersdorf (1739-99) Six string quintets (with non-obbligato horns) Antonín Dvořák (1841-1904) String Quintet in G major, Op. 77 (1875) Alistair Hinton (born 1950) String Quintet (1969–77) George Onslow (1784-1853) Six string quintets
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String quintet repertoire
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Sources
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Grove Music Online Jeffery, Paul 'A Player's Guide to Chamber Music' (Robert Hale, 2017)
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Low-g condition
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Low-g condition
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Low-g condition is a phase of aerodynamic flight where the airframe is temporarily unloaded. The pilot—and the airframe—feel temporarily "weightless" because the aircraft is in free-fall or decelerating vertically at the top of a climb. It may also occur during an excessively rapid entry into autorotation. This can have a disastrous effect on the aircraft, particularly in the case of helicopters, some of which need the rotor to constantly be under a non-zero amount of load.
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Low-g condition
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Effects
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In smaller airplanes Most smaller airplanes and gliders have no problems with 0g conditions. In fact, it can be enjoyable to have zero gravity in the cockpit. To produce 0g, the aircraft has to follow a ballistic flight path, which is essentially an upside down parabola.
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Low-g condition
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Effects
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This is the only method to simulate zero gravity for humans on earth. In helicopters In contrast, low-g conditions can be disastrous for helicopters. In such a situation their rotors may flap beyond normal limits. The excessive flapping can cause the root of the blades to exceed the limit of their hinges and this condition, known as mast bumping, can cause the separation of the blades from the hub or for the mast to shear, and hence detach the whole system from the aircraft, falling from the sky. This is especially true for helicopters with teetering rotors, such as the two-bladed design seen on Robinson helicopters.
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Low-g condition
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Effects
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This effect was first discovered when many accidents with Bell UH-1 and AH-1 helicopters occurred. These particular helicopters simply crashed without any obvious cause. Later, it was found that these accidents usually happened during low terrain flight after passing a ridge and initiating a dive from the previous climb.
Articulated and rigid rotor systems do not lose controlling forces up to 0g, but may encounter this depending on their flapping hinge offset from the mast. However, dangerous situations, as with a teetering rotor, may not occur.
On fixed-wing aircraft Low-g conditions can also affect fixed-wing aircraft in some instances, mainly by disrupting the airflow over the wings, making them difficult or impossible to control via the aerodynamic surfaces.
The controllability of an airplane by the control surfaces only depends on airspeed. So, if one keeps airspeed, control is retained. Usually the controllability is even increased, because there is no need to produce lift. 0g forces are a minimal problem for fixed wing aircraft, but there are exceptions, including, but not limited to, airplanes with gravity-fed fuel systems.
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Low-g condition
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Use in space agencies
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To simulate 0-g conditions some space agencies uses a modified passenger aircraft to simulate a low-g condition. The ESA uses an Airbus A300, for example. NASA has the Vomit Comet. One upside down parabola simulates 0g for about 25 s.
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Legacy system
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Legacy system
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In computing, a legacy system is an old method, technology, computer system, or application program, "of, relating to, or being a previous or outdated computer system", yet still in use. Often referencing a system as "legacy" means that it paved the way for the standards that would follow it. This can also imply that the system is out of date or in need of replacement.
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Legacy system
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Legacy system
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Legacy code is old computer source code that is no longer supported on the standard hardware and environments, and is a codebase that is in some respect obsolete or supporting something obsolete. Legacy code may be written in programming languages, use frameworks and external libraries, or use architecture and patterns that are no longer considered modern, increasing the mental burden and ramp-up time for software engineers who work on the codebase. Legacy code may have zero or insufficient automated tests, making refactoring dangerous and likely to introduce bugs. Long-lived code is susceptible to software rot, where changes to the runtime environment, or surrounding software or hardware may require maintenance or emulation of some kind to keep working. Legacy code may be present to support legacy hardware, a separate legacy system, or a legacy customer using an old feature or software version.
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Legacy system
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Legacy system
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While the term usually refers to source code, it can also apply to executable code that no longer runs on a later version of a system, or requires a compatibility layer to do so. An example would be a classic Macintosh application which will not run natively on macOS, but runs inside the Classic environment, or a Win16 application running on Windows XP using the Windows on Windows feature in XP.
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Legacy system
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Legacy system
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An example of legacy hardware are legacy ports like PS/2 and VGA ports, and CPUs with older, incompatible instruction sets (with e.g. newer operating systems). Examples in legacy software include legacy file formats like .swf for Adobe Flash or .123 for Lotus 1-2-3, and text files encoded with legacy character encodings like EBCDIC.
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Legacy system
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Overview
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The first use of the term legacy to describe computer systems probably occurred in the 1960s. By the 1980s it was commonly used to refer to existing computer systems to distinguish them from the design and implementation of new systems. Legacy was often heard during a conversion process, for example, when moving data from the legacy system to a new database.
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Legacy system
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Overview
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While this term may indicate that some engineers may feel that a system is out of date, a legacy system can continue to be used for a variety of reasons. It may simply be that the system still provides for the users' needs. In addition, the decision to keep an old system may be influenced by economic reasons such as return on investment challenges or vendor lock-in, the inherent challenges of change management, or a variety of other reasons other than functionality. Backward compatibility (such as the ability of newer systems to handle legacy file formats and character encodings) is a goal that software developers often include in their work.
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Legacy system
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Overview
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Even if it is no longer used, a legacy system may continue to impact the organization due to its historical role. Historic data may not have been converted into the new system format and may exist within the new system with the use of a customized schema crosswalk, or may exist only in a data warehouse. In either case, the effect on business intelligence and operational reporting can be significant. A legacy system may include procedures or terminology which are no longer relevant in the current context, and may hinder or confuse understanding of the methods or technologies used.
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Legacy system
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Overview
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Organizations can have compelling reasons for keeping a legacy system, such as: The system works satisfactorily, and the owner sees no reason to change it.
The costs of redesigning or replacing the system are prohibitive because it is large, monolithic, and/or complex.
Retraining on a new system would be costly in lost time and money, compared to the anticipated appreciable benefits of replacing it (which may be zero).
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Legacy system
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Overview
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The system requires near-constant availability, so it cannot be taken out of service, and the cost of designing a new system with a similar availability level is high. Examples include systems to handle customers' accounts in banks, computer reservations systems, air traffic control, energy distribution (power grids), nuclear power plants, military defense installations, and systems such as the TOPS database.
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Legacy system
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Overview
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The way that the system works is not well understood. Such a situation can occur when the designers of the system have left the organization, and the system has either not been fully documented or documentation has been lost.
The user expects that the system can easily be replaced when this becomes necessary.
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Legacy system
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Overview
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Newer systems perform undesirable (especially for individual or non-institutional users) secondary functions such as a) tracking and reporting of user activity and/or b) automatic updating that creates "back-door" security vulnerabilities and leaves end users dependent on the good faith and honesty of the vendor providing the updates. This problem is especially acute when these secondary functions of a newer system cannot be disabled.
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Legacy system
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Problems posed by legacy computing
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Legacy systems are considered to be potentially problematic by some software engineers for several reasons.
If legacy software runs on only antiquated hardware, the cost of maintaining the system may eventually outweigh the cost of replacing both the software and hardware unless some form of emulation or backward compatibility allows the software to run on new hardware.
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Legacy system
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Problems posed by legacy computing
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These systems can be hard to maintain, improve, and expand because there is a general lack of understanding of the system; the staff who were experts on it have retired or forgotten what they knew about it, and staff who entered the field after it became "legacy" never learned about it in the first place. This can be worsened by lack or loss of documentation. Comair airline company fired its CEO in 2004 due to the failure of an antiquated legacy crew scheduling system that ran into a limitation not known to anyone in the company.
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Legacy system
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Problems posed by legacy computing
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Legacy systems may have vulnerabilities in older operating systems or applications due to lack of security patches being available or applied. There can also be production configurations that cause security problems. These issues can put the legacy system at risk of being compromised by attackers or knowledgeable insiders.
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Legacy system
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Problems posed by legacy computing
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Integration with newer systems may also be difficult because new software may use completely different technologies. Integration across technology is quite common in computing, but integration between newer technologies and substantially older ones is not common. There may simply not be sufficient demand for integration technology to be developed. Some of this "glue" code is occasionally developed by vendors and enthusiasts of particular legacy technologies.
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Legacy system
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Problems posed by legacy computing
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Budgetary constraints often lead corporations to not address the need of replacement or migration of a legacy system. However, companies often don't consider the increasing supportability costs (people, software and hardware, all mentioned above) and do not take into consideration the enormous loss of capability or business continuity if the legacy system were to fail. Once these considerations are well understood, then based on the proven ROI of a new, more secure, updated technology stack platform is not as costly as the alternative—and the budget is found.
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Legacy system
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Problems posed by legacy computing
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Due to the fact that most legacy programmers are entering retirement age and the number of young engineers replacing them is very small, there is an alarming shortage of available workforce. This in turn results in difficulty in maintaining legacy systems, as well as an increase in costs of procuring experienced programmers.
Some legacy systems have a hard limit on their total capacity which may not be enough for today's needs, for example the 4 GB memory limit on many older x86 CPUs, or the 4 billion address limit in IPv4.
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Legacy system
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Improvements on legacy software systems
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Where it is impossible to replace legacy systems through the practice of application retirement, it is still possible to enhance (or "re-face") them. Most development often goes into adding new interfaces to a legacy system. The most prominent technique is to provide a Web-based interface to a terminal-based mainframe application. This may reduce staff productivity due to slower response times and slower mouse-based operator actions, yet it is often seen as an "upgrade", because the interface style is familiar to unskilled users and is easy for them to use. John McCormick discusses such strategies that involve middleware.Printing improvements are problematic because legacy software systems often add no formatting instructions, or they use protocols that are not usable in modern PC/Windows printers. A print server can be used to intercept the data and translate it to a more modern code. Rich Text Format (RTF) or PostScript documents may be created in the legacy application and then interpreted at a PC before being printed.
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Legacy system
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Improvements on legacy software systems
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Biometric security measures are difficult to implement on legacy systems. A workable solution is to use a Telnet or HTTP proxy server to sit between users and the mainframe to implement secure access to the legacy application.
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Legacy system
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Improvements on legacy software systems
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The change being undertaken in some organizations is to switch to automated business process (ABP) software which generates complete systems. These systems can then interface to the organizations' legacy systems and use them as data repositories. This approach can provide a number of significant benefits: the users are insulated from the inefficiencies of their legacy systems, and the changes can be incorporated quickly and easily in the ABP software.
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Legacy system
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Improvements on legacy software systems
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Model-driven reverse and forward engineering approaches can be also used for the improvement of legacy software.
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Legacy system
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NASA example
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Andreas M. Hein, from the Technical University of Munich, researched the use of legacy systems in space exploration. According to Hein, legacy systems are attractive for reuse if an organization has the capabilities for verification, validation, testing, and operational history. These capabilities must be integrated into various software life cycle phases such as development, implementation, usage, or maintenance. For software systems, the capability to use and maintain the system are crucial. Otherwise the system will become less and less understandable and maintainable.
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Legacy system
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NASA example
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According to Hein, verification, validation, testing, and operational history increases the confidence in a system's reliability and quality. However, accumulating this history is often expensive. NASA's now retired Space Shuttle program used a large amount of 1970s-era technology. Replacement was cost-prohibitive because of the expensive requirement for flight certification. The original hardware completed the expensive integration and certification requirement for flight, but any new equipment would have had to go through that entire process again. This long and detailed process required extensive tests of the new components in their new configurations before a single unit could be used in the Space Shuttle program. Thus any new system that started the certification process becomes a de facto legacy system by the time it is approved for flight.
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Legacy system
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NASA example
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Additionally, the entire Space Shuttle system, including ground and launch vehicle assets, was designed to work together as a closed system. Since the specifications did not change, all of the certified systems and components performed well in the roles for which they were designed. Even before the Shuttle was scheduled to be retired in 2010, NASA found it advantageous to keep using many pieces of 1970s technology rather than to upgrade those systems and recertify the new components.
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Legacy system
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Perspectives on legacy code
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Some in the software engineering prefer to describe "legacy code" without the connotation of being obsolete. Among the most prevalent neutral conceptions are source code inherited from someone else and source code inherited from an older version of the software. Eli Lopian, CEO of Typemock, has defined it as "code that developers are afraid to change". Michael Feathers introduced a definition of legacy code as code without tests, which reflects the perspective of legacy code being difficult to work with in part due to a lack of automated regression tests. He also defined characterization tests to start putting legacy code under test.
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Legacy system
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Perspectives on legacy code
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Ginny Hendry characterized creation of code as a `challenge` to current coders to create code that is "like other legacies in our lives—like the antiques, heirlooms, and stories that are cherished and lovingly passed down from one generation to the next. What if legacy code was something we took pride in?".
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Legacy system
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Additional uses of the term Legacy in computing
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The term legacy support is often used in conjunction with legacy systems. The term may refer to a feature of modern software. For example, Operating systems with "legacy support" can detect and use older hardware. The term may also be used to refer to a business function; e.g. a software or hardware vendor that is supporting, or providing software maintenance, for older products.
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Legacy system
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Additional uses of the term Legacy in computing
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A "legacy" product may be a product that is no longer sold, has lost substantial market share, or is a version of a product that is not current. A legacy product may have some advantage over a modern product making it appealing for customers to keep it around. A product is only truly "obsolete" if it has an advantage to nobody—if no person making a rational decision would choose to acquire it new.
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Legacy system
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Additional uses of the term Legacy in computing
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The term "legacy mode" often refers specifically to backward compatibility. A software product that is capable of performing as though it were a previous version of itself, is said to be "running in legacy mode". This kind of feature is common in operating systems and internet browsers, where many applications depend on these underlying components.
The computer mainframe era saw many applications running in legacy mode. In the modern business computing environment, n-tier, or 3-tier architectures are more difficult to place into legacy mode as they include many components making up a single system.
Virtualization technology is a recent innovation allowing legacy systems to continue to operate on modern hardware by running older operating systems and browsers on a software system that emulates legacy hardware.
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Legacy system
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Brownfield architecture
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Programmers have borrowed the term brownfield from the construction industry, where previously developed land (often polluted and abandoned) is described as brownfield.
Brownfield architecture is a type of software or network architecture that incorporates legacy systems.
Brownfield deployment is an upgrade or addition to an existing software or network architecture that retains legacy components.
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Legacy system
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Alternative view
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There is an alternate favorable opinion—growing since the end of the Dotcom bubble in 1999—that legacy systems are simply computer systems in working use: "Legacy code" often differs from its suggested alternative by actually working and scaling.
IT analysts estimate that the cost of replacing business logic is about five times that of reuse, even discounting the risk of system failures and security breaches. Ideally, businesses would never have to rewrite most core business logic: debits = credits is a perennial requirement.
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Legacy system
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Alternative view
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The IT industry is responding with "legacy modernization" and "legacy transformation": refurbishing existing business logic with new user interfaces, sometimes using screen scraping and service-enabled access through web services. These techniques allow organizations to understand their existing code assets (using discovery tools), provide new user and application interfaces to existing code, improve workflow, contain costs, minimize risk, and enjoy classic qualities of service (near 100% uptime, security, scalability, etc.).This trend also invites reflection on what makes legacy systems so durable. Technologists are relearning the importance of sound architecture from the start, to avoid costly and risky rewrites. The most common legacy systems tend to be those which embraced well-known IT architectural principles, with careful planning and strict methodology during implementation. Poorly designed systems often don't last, both because they wear out and because their inherent faults invite replacement. Thus, many organizations are rediscovering the value of both their legacy systems and the theoretical underpinnings of those systems.
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Citric acid/potassium-sodium citrate
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Citric acid/potassium-sodium citrate
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Citric acid/potassium-sodium citrate is a drug used in the treatment of metabolic acidosis (a disorder in which the blood is too acidic).
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Salpicon
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Salpicon
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Salpicon (or salpicón, meaning "hodgepodge" or "medley" in Spanish) is a dish of one or more ingredients diced or minced and bound with a sauce or liquid. There are different versions found in Spanish and the broader Latin American cuisine. A salpicon is sometimes used as stuffing.
In Mexican cuisine and Central American cuisine, the term refers to a salad mixture containing thinly sliced or chopped flank steak, onion, oregano, chile serrano, avocado, tomatoes, and vinegar. The mixture is commonly served on tostadas, tacos or as a filling of poblano peppers. In Honduras, rabbit meat is used.
In Colombian cuisine, salpicón is a fruit cocktail beverage made with a base of watermelon and/or orange juice, which gives it its bright red color, and soda water.
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Phred quality score
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Phred quality score
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A Phred quality score is a measure of the quality of the identification of the nucleobases generated by automated DNA sequencing. It was originally developed for the computer program Phred to help in the automation of DNA sequencing in the Human Genome Project. Phred quality scores are assigned to each nucleotide base call in automated sequencer traces. The FASTQ format encodes phred scores as ASCII characters alongside the read sequences. Phred quality scores have become widely accepted to characterize the quality of DNA sequences, and can be used to compare the efficacy of different sequencing methods. Perhaps the most important use of Phred quality scores is the automatic determination of accurate, quality-based consensus sequences.
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Phred quality score
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Definition
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Phred quality scores Q are logarithmically related to the base-calling error probabilities P and defined as 10 log 10 P This relation can be also be written as 10 10 For example, if Phred assigns a quality score of 30 to a base, the chances that this base is called incorrectly are 1 in 1000.
The phred quality score is the negative ratio of the error probability to the reference level of P=1 expressed in Decibel (dB).
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Phred quality score
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History
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The idea of sequence quality scores can be traced back to the original description of the SCF file format by Staden's group in 1992. In 1995, Bonfield and Staden proposed a method to use base-specific quality scores to improve the accuracy of consensus sequences in DNA sequencing projects.However, early attempts to develop base-specific quality scores had only limited success.
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Phred quality score
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History
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The first program to develop accurate and powerful base-specific quality scores was the program Phred. Phred was able to calculate highly accurate quality scores that were logarithmically linked to the error probabilities. Phred was quickly adopted by all the major genome sequencing centers as well as many other laboratories; the vast majority of the DNA sequences produced during the Human Genome Project were processed with Phred.
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Phred quality score
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History
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After Phred quality scores became the required standard in DNA sequencing, other manufacturers of DNA sequencing instruments, including Li-Cor and ABI, developed similar quality scoring metrics for their base calling software.
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Phred quality score
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Methods
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Phred's approach to base calling and calculating quality scores was outlined by Ewing et al.. To determine quality scores, Phred first calculates several parameters related to peak shape and peak resolution at each base. Phred then uses these parameters to look up a corresponding quality score in huge lookup tables. These lookup tables were generated from sequence traces where the correct sequence was known, and are hard coded in Phred; different lookup tables are used for different sequencing chemistries and machines. An evaluation of the accuracy of Phred quality scores for a number of variations in sequencing chemistry and instrumentation showed that Phred quality scores are highly accurate.Phred was originally developed for "slab gel" sequencing machines like the ABI373. When originally developed, Phred had a lower base calling error rate than the manufacturer's base calling software, which also did not provide quality scores. However, Phred was only partially adapted to the capillary DNA sequencers that became popular later. In contrast, instrument manufacturers like ABI continued to adapt their base calling software changes in sequencing chemistry, and have included the ability to create Phred-like quality scores. Therefore, the need to use Phred for base calling of DNA sequencing traces has diminished, and using the manufacturer's current software versions can often give more accurate results.
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Phred quality score
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Applications
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Phred quality scores are used for assessment of sequence quality, recognition and removal of low-quality sequence (end clipping), and determination of accurate consensus sequences.
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Phred quality score
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Applications
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Originally, Phred quality scores were primarily used by the sequence assembly program Phrap. Phrap was routinely used in some of the largest sequencing projects in the Human Genome Sequencing Project and is currently one of the most widely used DNA sequence assembly programs in the biotech industry. Phrap uses Phred quality scores to determine highly accurate consensus sequences and to estimate the quality of the consensus sequences. Phrap also uses Phred quality scores to estimate whether discrepancies between two overlapping sequences are more likely to arise from random errors, or from different copies of a repeated sequence.
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Phred quality score
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Applications
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Within the Human Genome Project, the most important use of Phred quality scores was for automatic determination of consensus sequences. Before Phred and Phrap, scientists had to carefully look at discrepancies between overlapping DNA fragments; often, this involved manual determination of the highest-quality sequence, and manual editing of any errors. Phrap's use of Phred quality scores effectively automated finding the highest-quality consensus sequence; in most cases, this completely circumvents the need for any manual editing. As a result, the estimated error rate in assemblies that were created automatically with Phred and Phrap is typically substantially lower than the error rate of manually edited sequence.
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Phred quality score
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Applications
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In 2009, many commonly used software packages make use of Phred quality scores, albeit to a different extent. Programs like Sequencher use quality scores for display, end clipping, and consensus determination; other programs like CodonCode Aligner also implement quality-based consensus methods.
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Phred quality score
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Compression
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Quality scores are normally stored together with the nucleotide sequence in the widely accepted FASTQ format. They account for about half of the required disk space in the FASTQ format (before compression), and therefore the compression of the quality values can significantly reduce storage requirements and speed up analysis and transmission of sequencing data. Both lossless and lossy compression are recently being considered in the literature. For example, the algorithm QualComp performs lossy compression with a rate (number of bits per quality value) specified by the user. Based on rate-distortion theory results, it allocates the number of bits so as to minimize the MSE (mean squared error) between the original (uncompressed) and the reconstructed (after compression) quality values. Other algorithms for compression of quality values include SCALCE, Fastqz and more recently QVZ, AQUa and the MPEG-G standard, that is currently under development by the MPEG standardisation working group. Both are lossless compression algorithms that provide an optional controlled lossy transformation approach. For example, SCALCE reduces the alphabet size based on the observation that “neighboring” quality values are similar in general.
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Macrophomic acid
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Macrophomic acid
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Macrophomic acid is a fungal metabolite isolated from the fungus Macrophoma commelinae. The enzyme macrophomate synthase converts 5-acetyl-4-methoxy-6-methyl-2-pyrone to 4-acetyl-3-methoxy-5-methyl-benzoic acid (macrophomic acid) through an unusual intermolecular Diels-Alder reaction (Scheme 1). The pathway to formation of macrophomic acid suggests that the enzyme is a natural Diels-Alderase. Formation of this type of aromatic ring compound normally proceeds via the shikimate and polyketide pathways; however, the production of macrophomic acid by macrophomate synthase proceeds totally differently. Learning about the production of macrophomic acid by a possible natural Diels-Alderase enzyme is important in understanding enzyme catalytic mechanisms. This knowledge can then be applied to organic synthesis.
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Macrophomic acid
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Biosynthesis
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The biosynthesis of macrophomic acid is catalyzed by the enzyme macrophomate synthase. The unusual multistep conversion of 5-acetyl-4-methoxy-6-methyl-2-pyrone (3) to macrophomic acid is thought to proceed by either a concerted Diels-Alder reaction or a recently proposed 2-step Michael-aldol sequence. The Michael-aldol sequence involves a Michael addition reaction and an aldol condensation. The actual pathway is not yet understood completely. In the conversion of the 2-pyrone (3), oxaloacetate (1) is decarboxylated to form an enolate that coordinates to a Mg2+ metal center (2) found in the active site of the enzyme. Then, the coordinated enolate can either add to the 2-pyrone (3) through a Michael-aldol or Diels-Alder pathway. Both pathways include a bicyclic intermediate (4).
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Macrophomic acid
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Biosynthesis
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In the Michael-aldol pathway (Scheme 2), The coordinated oxaloacetate enolate performs a Michael addition to the ring of the pyrone to form intermediate 4. Next, this intermediate undergoes an aldol condensation to form the proposed bicyclic intermediate (5). Finally, this bicyclic compound undergoes a decarboxylation to form intermediate 6 and dehydration to form macrophomic acid (7).
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Macrophomic acid
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Biosynthesis
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In the Diels-Alder mechanism for the biosynthesis of macrophomic acid (Scheme 3), oxaloacetate is decarboxylated to form the enolate complex with Mg2+. Next, the enolate complex adds to the pyrone through a Diels-Alder concerted reaction to form a bicyclic intermediate (8). Then, just as in the Michael-aldol sequence, the bicyclic intermediate gets decarboxylated and dehydrated to form macrophomic acid (9). This pathway is thought to be the actual mechanism; however, according to QM/MM calculations, it seems that the Michael-aldol sequence is more energetically favored. There has also been difficulty in isolating the key intermediates for either proposed pathway.
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Fricative
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Fricative
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A fricative is a consonant produced by forcing air through a narrow channel made by placing two articulators close together. These may be the lower lip against the upper teeth, in the case of [f]; the back of the tongue against the soft palate in the case of German [x] (the final consonant of Bach); or the side of the tongue against the molars, in the case of Welsh [ɬ] (appearing twice in the name Llanelli). This turbulent airflow is called frication.A particular subset of fricatives are the sibilants. When forming a sibilant, one still is forcing air through a narrow channel, but in addition, the tongue is curled lengthwise to direct the air over the edge of the teeth. English [s], [z], [ʃ], and [ʒ] are examples of sibilants.
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Fricative
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Fricative
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The usage of two other terms is less standardized: "Spirant" is an older term for fricatives used by some American and European phoneticians and phonologists. "Strident" could mean just "sibilant", but some authors include also labiodental and uvular fricatives in the class.
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Fricative
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Types
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The airflow is not completely stopped in the production of fricative consonants. In other words, the airflow experiences friction.
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Fricative
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Types
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Sibilants [s] voiceless coronal sibilant, as in English sip [z] voiced coronal sibilant, as in English zip [s̪] voiceless dental sibilant [z̪] voiced dental sibilant [s̺] voiceless apical sibilant [z̺] voiced apical sibilant [s̟] voiceless predorsal sibilant (laminal, with tongue tip at lower teeth) [z̟] voiced predorsal sibilant (laminal) [s̠] voiceless postalveolar sibilant (laminal) [z̠] voiced postalveolar sibilant (laminal) [ʃ] voiceless palato-alveolar sibilant (domed, partially palatalized), as in English ship [ʒ] voiced palato-alveolar sibilant (domed, partially palatalized), as the si in English vision [ɕ] voiceless alveolo-palatal sibilant (laminal, palatalized) [ʑ] voiced alveolo-palatal sibilant (laminal, palatalized) [ʂ] voiceless retroflex sibilant (apical or subapical) [ʐ] voiced retroflex sibilant (apical or subapical)All sibilants are coronal, but may be dental, alveolar, postalveolar, or palatal (retroflex) within that range. However, at the postalveolar place of articulation, the tongue may take several shapes: domed, laminal, or apical, and each of these is given a separate symbol and a separate name. Prototypical retroflexes are subapical and palatal, but they are usually written with the same symbol as the apical postalveolars. The alveolars and dentals may also be either apical or laminal, but this difference is indicated with diacritics rather than with separate symbols.
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Fricative
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Types
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Central non-sibilant fricatives [ɸ] voiceless bilabial fricative [β] voiced bilabial fricative [f] voiceless labiodental fricative, as in English fine [v] voiced labiodental fricative, as in English vine [θ̼] voiceless linguolabial fricative [ð̼] voiced linguolabial fricative [θ], [θ̟] voiceless dental non-sibilant fricative, as in English thing [ð], [ð̟] voiced dental non-sibilant fricative, as in English that [θ̠], [ɹ̝̊] voiceless alveolar non-sibilant fricative [ð̠], [ɹ̝] voiced alveolar non-sibilant fricative [r̝̊] voiceless trilled fricative [r̝] voiced trilled fricative [ç] voiceless palatal fricative [ʝ] voiced palatal fricative [x] voiceless velar fricative [ɣ] voiced velar fricative [ɧ] voiceless palatal-velar fricative (articulation disputed)The IPA also has letters for epiglottal fricatives, [ʜ] voiceless epiglottal fricative [ʢ] voiced epiglottal fricativewith allophonic trilling, but these might be better analyzed as pharyngeal trills.
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Fricative
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Types
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[ʩ] voiceless velopharyngeal fricative (often occurs with a cleft palate) [ʩ̬] voiced velopharyngeal fricative Lateral fricatives [ɬ̪] voiceless dental lateral fricative [ɮ̪] voiced dental lateral fricative [ɬ] voiceless alveolar lateral fricative [ɮ] voiced alveolar lateral fricative [ɬ̠] voiceless postalveolar lateral fricative (Mehri) [ɮ̠] voiced postalveolar lateral fricative [ɭ˔̥] or extIPA [ꞎ] voiceless retroflex lateral fricative [ɭ˔] or extIPA [𝼅] Voiced retroflex lateral fricative (in Ao) [ʎ̥˔] or [ʎ̝̥] or extIPA [𝼆] voiceless palatal lateral fricative [ʎ̝] or extIPA [𝼆̬] voiced palatal lateral fricative (allophonic in Jebero) [ʟ̝̊] or extIPA [𝼄] voiceless velar lateral fricative [ʟ̝] or extIPA [𝼄̬] voiced velar lateral fricativeThe lateral fricative occurs as the ll of Welsh, as in Lloyd, Llewelyn, and Machynlleth ([maˈxənɬɛθ], a town), as the unvoiced 'hl' and voiced 'dl' or 'dhl' in the several languages of Southern Africa (such as Xhosa and Zulu), and in Mongolian.
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Fricative
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Types
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ʪ or [ɬ͜s] and [θ͜ɬ] voiceless grooved lateral alveolar fricative (a laterally lisped [s] or [θ]) (Modern South Arabian) ʫ or [ɮ͜z] and [ð͜ɮ] voiced grooved lateral alveolar fricative (a laterally lisped [z] or [ð]) (Modern South Arabian) IPA letters used for both fricatives and approximants [χ] voiceless uvular fricative [ʁ] voiced uvular fricative [ħ] voiceless pharyngeal fricative [ʕ] voiced pharyngeal fricativeNo language distinguishes fricatives from approximants at these places, so the same symbol is used for both. For the pharyngeal, approximants are more numerous than fricatives. A fricative realization may be specified by adding the uptack to the letters, [χ̝, ʁ̝, ħ̝, ʕ̝]. Likewise, the downtack may be added to specify an approximant realization, [χ̞, ʁ̞, ħ̞, ʕ̞].
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Fricative
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Types
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(The bilabial approximant and dental approximant do not have dedicated symbols either and are transcribed in a similar fashion: [β̞, ð̞]. However, the base letters are understood to specifically refer to the fricatives.) Pseudo-fricatives [h] voiceless glottal transition, as in English hat [ɦ] breathy-voiced glottal transitionIn many languages, such as English, the glottal "fricatives" are unaccompanied phonation states of the glottis, without any accompanying manner, fricative or otherwise. However, in languages such as Arabic, they are true fricatives.In addition, [ʍ] is usually called a "voiceless labial-velar fricative", but it is actually an approximant. True doubly articulated fricatives may not occur in any language; but see voiceless palatal-velar fricative for a putative (and rather controversial) example.
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Fricative
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Types
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Aspirated fricatives Fricatives are very commonly voiced, though cross-linguistically voiced fricatives are not nearly as common as tenuis ("plain") fricatives. Other phonations are common in languages that have those phonations in their stop consonants. However, phonemically aspirated fricatives are rare. /s~sʰ/ contrasts with a tense, unaspirated /s͈/ in Korean; aspirated fricatives are also found in a few Sino-Tibetan languages, in some Oto-Manguean languages, in the Siouan language Ofo (/sʰ/ and /fʰ/), and in the (central?) Chumash languages (/sʰ/ and /ʃʰ/). The record may be Cone Tibetan, which has four contrastive aspirated fricatives: /sʰ/ /ɕʰ/, /ʂʰ/, and /xʰ/.
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Fricative
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Types
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Nasalized fricatives Phonemically nasalized fricatives are rare. Umbundu has /ṽ/ and Kwangali and Souletin Basque have /h̃/. In Coatzospan Mixtec, [β̃, ð̃, s̃, ʃ̃] appear allophonically before a nasal vowel, and in Igbo nasality is a feature of the syllable; when /f v s z ʃ ʒ/ occur in nasal syllables they are themselves nasalized.
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Fricative
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Occurrence
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Until its extinction, Ubykh may have been the language with the most fricatives (29 not including /h/), some of which did not have dedicated symbols or diacritics in the IPA. This number actually outstrips the number of all consonants in English (which has 24 consonants). By contrast, approximately 8.7% of the world's languages have no phonemic fricatives at all. This is a typical feature of Australian Aboriginal languages, where the few fricatives that exist result from changes to plosives or approximants, but also occurs in some indigenous languages of New Guinea and South America that have especially small numbers of consonants. However, whereas [h] is entirely unknown in indigenous Australian languages, most of the other languages without true fricatives do have [h] in their consonant inventory.
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Fricative
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Occurrence
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Voicing contrasts in fricatives are largely confined to Europe, Africa, and Western Asia. Languages of South and East Asia, such as Mandarin Chinese, Korean, and the Austronesian languages, typically do not have such voiced fricatives as [z] and [v], which are familiar to many European speakers. In some Dravidian languages they occur as allophones. These voiced fricatives are also relatively rare in indigenous languages of the Americas. Overall, voicing contrasts in fricatives are much rarer than in plosives, being found only in about a third of the world's languages as compared to 60 percent for plosive voicing contrasts.About 15 percent of the world's languages, however, have unpaired voiced fricatives, i.e. a voiced fricative without a voiceless counterpart. Two-thirds of these, or 10 percent of all languages, have unpaired voiced fricatives but no voicing contrast between any fricative pair.This phenomenon occurs because voiced fricatives have developed from lenition of plosives or fortition of approximants. This phenomenon of unpaired voiced fricatives is scattered throughout the world, but is confined to nonsibilant fricatives with the exception of a couple of languages that have [ʒ] but lack [ʃ]. (Relatedly, several languages have the voiced affricate [dʒ] but lack [tʃ], and vice versa.) The fricatives that occur most often without a voiceless counterpart are – in order of ratio of unpaired occurrences to total occurrences – [ʝ], [β], [ð], [ʁ] and [ɣ].
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Fricative
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Acoustics
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Fricatives appear in waveforms as somewhat random noise caused by the turbulent airflow, upon which a periodic pattern is overlaid if voiced. Fricatives produced in the front of the mouth tend to have energy concentration at higher frequencies than ones produced in the back. The centre of gravity (CoG), i.e. the average frequency in a spectrum weighted by the amplitude (also known as spectral mean), may be used to determine the place of articulation of a fricative relative to that of another.
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SARS conspiracy theory
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SARS conspiracy theory
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The SARS conspiracy theory began to emerge during the severe acute respiratory syndrome (SARS) outbreak in China in the spring of 2003, when Sergei Kolesnikov, a Russian scientist and a member of the Russian Academy of Medical Sciences, first publicized his claim that the SARS coronavirus is a synthesis of measles and mumps. According to Kolesnikov, this combination cannot be formed in the natural world and thus the SARS virus must have been produced under laboratory conditions. Another Russian scientist, Nikolai Filatov, head of Moscow's epidemiological services, had earlier commented that the SARS virus was probably man-made.However, independent labs concluded these claims to be premature since the SARS virus is a coronavirus, whereas measles and mumps are paramyxoviruses. The primary differences between a coronavirus and a paramyxovirus are in their structures and method of infection, thus making it implausible for a coronavirus to have been created from two paramyxoviruses.
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SARS conspiracy theory
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SARS conspiracy theory
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The widespread reporting of claims by Kolesnokov and Filatov caused controversy in many Chinese internet discussion boards and chat rooms. Many Chinese believed that the SARS virus could be a biological weapon manufactured by the United States, which perceived China as a potential threat.
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SARS conspiracy theory
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SARS conspiracy theory
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The failure to find the source of the SARS virus further convinced these people and many more that SARS was artificially synthesised and spread by some individuals and even governments. Circumstantial evidence suggests that the SARS virus crossed over to humans from Asian palm civets ("civet cats"), a type of animal that is often killed and eaten in Guangdong, where SARS was first discovered.Supporters of the conspiracy theory suggest that SARS caused the most serious harm in mainland China, Hong Kong, Taiwan and Singapore, regions where most Chinese reside, while the United States, Europe and Japan were not affected as much. However, the highest mortality from SARS outside of China occurred in Canada where 43 died. Conspiracists further take as evidence the idea that, although SARS has an average mortality rate of around 10% around the world, no one died in the United States from SARS. However, there were only 8 confirmed cases out of 27 probable cases in the US (10% of 8 people is less than 1 person). Regarding reasons why SARS patients in the United States experienced a relatively mild illness, the U.S. Centers for Disease Control has explained that anybody with fever and a respiratory symptom who had traveled to an affected area was included as a SARS patient in the U.S., even though many of these were found to have had other respiratory illnesses.Tong Zeng, an activist with no medical background, authored the book The Last Defense Line: Concerns About the Loss of Chinese Genes, published in 2003. In the book, Zeng suggested researchers from the United States may have created SARS as an anti-Chinese bioweapon after taking blood samples in China for a longevity study in the 1990s. The book's hypothesis was a front-page report in the Guangzhou newspaper Southern Metropolis Daily.Coronaviruses similar to SARS have been found in bats in China, suggesting they may be their natural reservoir.
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Solithromycin
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Solithromycin
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Solithromycin (trade name Solithera) is a ketolide antibiotic undergoing clinical development for the treatment of community-acquired pneumonia and other infections.Solithromycin exhibits excellent in vitro activity against a broad spectrum of Gram-positive respiratory tract pathogens, including macrolide-resistant strains. Solithromycin has activity against most common respiratory Gram-positive and fastidious Gram-negative pathogens, and is being evaluated for its utility in treating gonorrhea.
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Solithromycin
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Pre-clinical studies
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An in vivo pre-clinical study performed by Jeffrey Keelan done in sheep may provide a prophylactic approach for intrauterine infections during pregnancy. This study was carried out by administering solithromycin to pregnant sheep, resulting in effective concentrations greater than 30 ng/ml in the fetal plasma, maternal plasma and amniotic fluid. A single maternal dose maintained these concentrations for over 12 hours.
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Solithromycin
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Clinical trials
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May 2011: solithromycin is in a Phase 2 clinical trial for serious community-acquired bacterial pneumonia and in a Phase 1 clinical trial with an intravenous formulation.
September 2011: solithromycin demonstrated comparable efficacy to levofloxacin with reduced adverse events in Phase 2 trial in people with community-acquired pneumonia January 2015: in a Phase 3 clinical trial for community-acquired bacterial pneumonia, solithromycin administered orally demonstrated statistical non-inferiority to the fluoroquinolone moxifloxacin.
July 2015: patient enrollment for the second Phase 3 clinical trial (Solitaire IV) for community-acquired bacterial pneumonia was completed with results expected in Q4 2015.
Oct 2015: IV to oral solithromycin demonstrated statistical non-inferiority to IV to oral moxifloxacin in adults with community-acquired bacterial pneumonia.
July 2016: Cempra announced FDA acceptance of IV and oral formulations of Solithera (solithromycin) new drug applications for the treatment of community-acquired bacterial pneumonia.
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Solithromycin
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Structure
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X-ray crystallography studies have shown solithromycin, the first fluoroketolide in clinical development, has a third region of interactions with the bacterial ribosome, as compared with two binding sites for other ketolides.
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Solithromycin
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Structure
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The only previously marketed ketolide, telithromycin, suffers from rare but serious side effects. Recent studies have shown this to be likely due to the presence of the pyridine-imidazole group of the telithromycin side chain acting as an antagonist towards various nicotinic acetylcholine receptors. Solithromycin differs from telithromycin because the side chain does not significantly antagonize nicotinic acetylcholine receptors. Instead of the pyridine-imidazole group used on telithromycin, this molecule has a triazole-phenylamine moiety.
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Solithromycin
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Mechanism of action
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Solithromycin inhibits bacterial translation by binding to the 23S ribosomal RNA, preventing the offending bacteria from synthesizing proteins.
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Solithromycin
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Side effects
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During a clinical study some patients presented with elevated liver enzyme which may or may not be indicative of hepatotoxicity. This prompted the FDA Antimicrobial Drugs Advisory Committee to vote that the risk to the liver has not been adequately characterized and that further studies need to be conducted. To this extent, the FDA requests a 9,000 patient safety trial as well as restricting the drug.
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Solithromycin
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Development
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In 2008, investigational new drug applications for solithromycin capsules and an intravenous formulation were submitted. From studies of pharmacokinetics, safety, and efficacy several issues were found. There is variable absorption which can result in subtherapeutic drug concentrations and even therapy failure. Additionally, there are significant drug-drug interactions affecting solithromycin concentrations as well the concentrations of the offending drugs. There is also a narrow therapeutic margin which can make this drug challenging to dose.
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Solithromycin
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Commercial aspects
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Cempra's general plan is to develop solithromycin develop products through late stage clinical trials and sell them to their hospital based sales force or through partnerships, which would need negotiations with larger pharmaceutical companies. There are several manufacturing plants used such as Wockhardt Limited and Hospira Incorporated manufacturing facilities as well as Uquifa Laboratories, an alternative GMP facility.
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Solithromycin
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Intellectual property
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Due to the fact that bringing new products to the market takes a significant investment of time and money, companies place considerable importance on patent protection for new products. Solithromycin is a new chemical entity from the macrolide library of compounds that were licensed by Optimer. It is covered by a series of patents and patent applications which claim the composition of matter of solithromycin. There are also patents surrounding the synthesis and purification of this substance. For example, patent EP3190122 A1 presents a novel, efficient route of synthesis that bypasses the need for chromatographic purification which saves time.
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