Self-affinity.

In mathematics, self-affinity is a feature of a fractal whose pieces are scaled by different amounts in the x- and y-directions. This means that to appreciate the self similarity of these fractal objects, they have to be rescaled using an anisotropic affine transformation.

Definition.

A compact topological space "X" is self-similar if there exists a finite set "S" indexing a set of non-surjective homeomorphisms formula_4 for which  If formula_6, we call "X" self-similar if it is the only non-empty subset of "Y" such that the equation above holds for formula_7. We call  a "self-similar structure". The homeomorphisms may be iterated, resulting in an iterated function system. The composition of functions creates the algebraic structure of a monoid. When the set "S" has only two elements, the monoid is known as the dyadic monoid. The dyadic monoid can be visualized as an infinite binary tree; more generally, if the set "S" has "p" elements, then the monoid may be represented as a p-adic tree.  The automorphisms of the dyadic monoid is the modular group; the automorphisms can be pictured as hyperbolic rotations of the binary tree.  A more general notion than self-similarity is Self-affinity.

Examples.

The Mandelbrot set is also self-similar around Misiurewicz points.  Self-similarity has important consequences for the design of computer networks, as typical network traffic has self-similar properties. For example, in teletraffic engineering, packet switched data traffic patterns seem to be statistically self-similar. This property means that simple models using a Poisson distribution are inaccurate, and networks designed without taking self-similarity into account are likely to function in unexpected ways.  Similarly, stock market movements are described as displaying self-affinity, i.e. they appear self-similar when transformed via an appropriate affine transformation for the level of detail being shown. Andrew Lo describes stock market log return self-similarity in econometrics.  Finite subdivision rules are a powerful technique for building self-similar sets, including the Cantor set and the Sierpinski triangle.

In cybernetics.

The Viable System Model of Stafford Beer is an organizational model with an affine self-similar hierarchy, where a given viable system is one element of the System One of a viable system one recursive level higher up, and for whom the elements of its System One are viable systems one recursive level lower down.

In nature.

Self-similarity can be found in nature, as well. To the right is a mathematically generated, perfectly self-similar image of a fern, which bears a marked resemblance to natural ferns. Other plants, such as Romanesco broccoli, exhibit strong self-similarity.

In mathematics, a self-similar object is exactly or approximately similar to a part of itself (i.e., the whole has the same shape as one or more of the parts). Many objects in the real world, such as coastlines, are statistically self-similar: parts of them show the same statistical properties at many scales. Self-similarity is a typical property of fractals. Scale invariance is an exact form of self-similarity where at any magnification there is a smaller piece of the object that is similar to the whole. For instance, a side of the Koch snowflake is both symmetrical and scale-invariant; it can be continually magnified 3x without changing shape. The non-trivial similarity evident in fractals is distinguished by their fine structure, or detail on arbitrarily small scales. As a counterexample, whereas any portion of a straight line may resemble the whole, further detail is not revealed.

Soběpodobnost je charakteristika tvaru objektů. Libovolná část objektu má tvar, který je podobný tvaru téhož objektu při jiném rozlišení (zvětšení nebo zmenšení).


Origins.

The ancestors of the Indo-Scythians are thought to be Sakas (Scythian) tribes. "One group of Indo-European speakers that makes an early appearance on the Xinjiang stage is the Saka (Ch. Sai). Saka is more a generic term than a name for a specific state or ethnic group; Saka tribes were part of a cultural continuum of early nomads across Siberia and the Central Eurasian steppe lands from Xinjiang to the Black Sea. Like the Scythians whom Herodotus describes in book four of his "History" ("Saka" is an Iranian word equivalent to the Greek "Scythes", and many scholars refer to them together as Saka-Scythian), Sakas were Iranian-speaking horse nomads who deployed chariots in battle, sacrificed horses, and buried their dead in barrows or mound tombs called "kurgans"."

Achaemenid period (6th-4th century BCE).

During the Achaemenid conquest of the Indus Valley circa 515 BCE, the Achaemenid army was not uniquely Persian, and the Sakas probably participated in the invasion of northwestern India. The Achaemenid army was composed of many different ethnicities that were part of the vast Achaemenid Empire. The army included Bactrians, Sakas (Scythians), Parthians, Sogdians. Herodotus gives a full list of the ethnicities of the Achaemenid army, in which are included Sakas together with Ionians (Greeks), and even Ethiopians. These ethnicities are likely to have been included in the Achaemenid army which invaded India.  Some scholars, including Michael Witzel and Christopher I. Beckwith suggested that the Shakyas, the clan of the historical Gautama Buddha, were originally Scythians from Central Asia, and that the Indian ethnonym "Śākya" has the same origin as “Scythian”, called Sakas in India. This would also explain the strong support of the Sakas for the Buddhist faith in India.  The Persians, the Sakas and the Greeks, may have later participated in the campaigns of Chandragupta Maurya to gain the throne of Magadha circa 320 BCE. The "Mudrarakshasa" states that after Alexander's death, an alliance of ""Shaka-Yavana-Kamboja-Parasika-Bahlika"" was used by Chandragupta Maurya in his campaign to take the throne in Magadha and found the Mauryan Empire. The "Sakas" were the Scythians, the "Yavanas" were the Greeks, and the "Parasikas" were the Persians.

Yuezhi expansion (2nd century BCE).

In the 2nd century BC, a fresh nomadic movement started among the Central Asian tribes, producing lasting effects on the history of Rome in Europe, Parthia in Western Asia, and Bactria, Kabul, and India in the east in Southern Asia. Recorded in the annals of the Han dynasty and other Chinese records, this great tribal movement began after the Yuezhi tribe was defeated by the Xiongnu, fleeing westwards after their defeat and creating a domino effect as they displaced other central Asian tribes in their path. According to these ancient sources "Modu Shanyu" of the Xiongnu tribe of Mongolia attacked the Yuezhi (possibly related to the Tocharians who lived in eastern Tarim Basin area) and evicted them from their homeland between the Qilian Shan and Dunhuang around 175 BC. Leaving behind a remnant of their number, most of the population moved westwards into the Ili River area. There, they displaced the Sakas, who migrated south into Ferghana and Sogdiana. According to the Chinese historical chronicles (who call the Sakas, "Sai" 塞): "[The Yuezhi] attacked the king of the Sai who moved a considerable distance to the south and the Yuezhi then occupied his lands."  Sometime after 155 BC, the Yuezhi were again defeated by an alliance of the Wusun and the Xiongnu, and were forced to move south, again displacing the Scythians, who migrated south towards Bactria and present Afghanistan, and south-west closer towards Parthia.  The Sakas seem to have entered the territory of the Greco-Bactrian Kingdom around 145 BC, where they burnt to the ground the Greek city of Alexandria on the Oxus. The Yuezhi remained in Sogdiana on the northern bank of the Oxus, but they became suzerains of the Sakas in Bactrian territory, as described by the Chinese ambassador Zhang Qian who visited the region around 126 BC.  In Parthia, between 138–124 BC, a tribe known to ancient Greek scholars as the Sacaraucae (probably from the Old Persian "Sakaravaka" "nomadic Saka") and an allied, possibly non-Saka/Scythian people, the Massagetae came into conflict with the Parthian Empire. The Sacaraucae-Massagetae alliance won several battles and killed, in succession, the Parthian kings Phraates II and Artabanus I.  The Parthian king Mithridates II finally retook control of parts of Central Asia, first by defeating the Yuezhi in Sogdiana in 115 BC, and then defeating the Scythians in Parthia and Seistan around 100 BC.  After their defeat, the Yuezhi tribes migrated relatively far to the east into Bactria, which they were to control for several centuries, and from which they later conquered northern India to found the Kushan Empire.

Settlement in Sakastan.

The Sakas settled in Drangiana, an area of Southern Afghanistan, western Pakistan and south Iran, which was then called after them as Sakastan or Sistan. From there, they progressively expanded into present day Iran as well as northern India, where they established various kingdoms, and where they are known as "Saka".  The Arsacid emperor Mithridates II (c. 123–88/87 BCE) claimed many successes in battle and added many provinces to the Parthian Empire. Apparently the Scythian hordes that came from Bactria were conquered by him.  Following military pressure from the Yuezhi (precursors of the Kushana), a section of the Indo-Scythians moved from Bactria to Lake Helmond (or Hāmūn), and settled in or around Drangiana (Sigal), a region which later came to be called "Sakistana of the <br>Skythian Sakai ", towards the end of 1st century BC. The region is still known as Seistan. I The presence of the Sakas in Sakastan in the 1st century BC is mentioned by Isidore of Charax in his "Parthian stations". He explained that they were bordered at that time by Greek cities to the east (Alexandria of the Caucasus and Alexandria of the Arachosians), and the Parthian-controlled territory of Arachosia to the south:

Indo-Scythian kingdoms.

Pamirs to Taxila.

Ahmad Hassan Dani and professor Karl Jettmar, from the petroglyphs left by Saka soldiers at principle river crossings at Chilas and the Sacred Rock of Hunza, have established the route across the Karakoram mountains used by Maues, the first Indo-Scythian king, to capture Taxila from Indo-Greek King Apollodotus II.  The 1st century AD Periplus of the Erythraean Sea describes the Scythian territories there:  "Beyond this region (Gedrosia), the continent making a wide curve from the east across the depths of the bays, there follows the coast district of Scythia, which lies above toward the north; the whole marshy; from which flows down the river Sinthus, the greatest of all the rivers that flow into the Erythraean Sea, bringing down an enormous volume of water (...) This river has seven mouths, very shallow and marshy, so that they are not navigable, except the one in the middle; at which by the shore, is the market-town, Barbaricum. Before it there lies a small island, and inland behind it is the metropolis of Scythia, Minnagara; it is subject to Parthian princes who are constantly driving each other out.."  The Indo-Scythians ultimately established a kingdom in the northwest, based near Taxila, with two great Satraps, one in Mathura in the east, and one in Surastrene (Gujarat) in the southwest.  In the southeast, the Indo-Scythians invaded the area of Ujjain, but were subsequently repelled in 57 BC by the Malwa king Vikramaditya. To commemorate the event Vikramaditya established the Vikrama era, a specific Indian calendar starting in 57 BC. More than a century later, in AD 78, the Sakas would again invade Ujjain and establish the Saka era, marking the beginning of the long-lived Saka Western Satraps kingdom.

Gandhara and Punjab.

The presence of the Scythians in north-western India during the 1st century BCE was contemporary with that of the Indo-Greek Kingdoms there, and it seems they initially recognized the power of the local Greek rulers.  Maues first conquered Gandhara and Taxila around 80 BCE, but his kingdom disintegrated after his death. In the east, the Indian king Vikrama retook Ujjain from the Indo-Scythians, celebrating his victory by the creation of the Vikrama era (starting 58 BCE). Indo-Greek kings again ruled after Maues, and prospered, as indicated by the profusion of coins from Kings Apollodotus II and Hippostratos. Not until Azes I, in 55 BC, did the Indo-Scythians take final control of northwestern India, with his victory over Hippostratos.

Sculpture.

Several stone sculptures have been found in the Early Saka layer (Layer No4, corresponding to the period of Azes I, in which numerous coins of the latter were found) in the ruins of Sirkap, during the excavations organized by John Marshall. Several of them are toilet trays (also called Stone palettes) roughly imitative of earlier, and finer, Hellenistic ones found in the earlier layers. Marshall comments that "we have a praiseworthy effort to copy a Hellenistic original but obviously without the appreciation of form and skill which were necessary for the task". From the same layer, several statuettes in the round are also known, in very rigid and frontal style.

Bimaran casket.

Azes is connected to the Bimaran casket, one of the earliest representations of the Buddha. The casket was used for the dedication of a stupa in Bamiran, near Jalalabad in Afghanistan, and placed inside the stupa with several coins of Azes. This event may have happened during the reign of Azes (60–20 BCE), or slightly later. The Indo-Scythians are otherwise connected with Buddhism (see Mathura lion capital), and it is indeed possible they would have commended the work.

Mathura area ("Northern Satraps").

In northern India, the Indo-Scythians conquered the area of Mathura over Indian kings around 60 BCE. Some of their satraps were Hagamasha and Hagana, who were in turn followed by the Saca Great Satrap Rajuvula.  The Mathura lion capital, an Indo-Scythian sandstone capital in crude style, from Mathura in northern India, and dated to the 1st century CE, describes in kharoshthi the gift of a stupa with a relic of the Buddha, by Queen Nadasi Kasa, the wife of the Indo-Scythian ruler of Mathura, Rajuvula. The capital also mentions the genealogy of several Indo-Scythian satraps of Mathura.  Rajuvula apparently eliminated the last of the Indo-Greek kings Strato II around 10 CE, and took his capital city, Sagala.  The coinage of the period, such as that of Rajuvula, tends to become very crude and barbarized in style. It is also very much debased, the silver content becoming lower and lower, in exchange for a higher proportion of bronze, an alloying technique (billon) suggesting less than wealthy finances.  The Mathura lion capital inscriptions attest that Mathura fell under the control of the Sakas. The inscriptions contain references to Kharahostes and Queen Ayasia, the "chief queen of the Indo-Scythian ruler of Mathura, satrap Rajuvula." Kharahostes was the son of "Arta" as is attested by his own coins. Arta is stated to be brother of King Moga or Maues.  The Indo-Scythian satraps of Mathura are sometimes called the "Northern Satraps", in opposition to the "Western Satraps" ruling in Gujarat and Malwa. After Rajuvula, several successors are known to have ruled as vassals to the Kushans, such as the "Great Satrap" Kharapallana and the "Satrap" Vanaspara, who are known from an inscription discovered in Sarnath, and dated to the 3rd year of Kanishka (c. AD 130), in which they were paying allegiance to the Kushans.

Pataliputra.

The text of the Yuga Purana describes an invasion of Pataliputra by the Scythians sometimes during the 1st century BC, after seven great kings had ruled in succession in Saketa following the retreat of the Yavanas. The Yuga Purana explains that the king of the Sakas killed one fourth of the population, before he was himself slain by the Kalinga king Shata and a group of Sabalas (Sabaras or Bhillas).

Kushan and Indo-Parthian conquests.

After the death of Azes, the rule of the Indo-Scythians in northwestern India was shattered with the rise of the Indo-Parthian ruler Gondophares in the last years of the 1st century BC. For the following decades, a number of minor Scythian leaders maintained themselves in local strongholds on the fringes of the loosely assembled Indo-Parthian empire, some of them paying formal allegiance to Gondophares I and his successors.  During the latter part of the 1st century AD, the Indo-Parthian overlordship was gradually replaced with that of the Kushans, one of the five tribes of the Yuezhi who had lived in Bactria for more than a century, and were now expanding into India to create a Kushan Empire. The Kushans ultimately regained northwestern India from around AD 75, and the area of Mathura from around AD 100, where they were to prosper for several centuries.

Western Kshatrapas legacy.

Indo-Scythians continued to hold the area of Seistan until the reign of Bahram II (AD 276–293), and held several areas of India well into the 1st millennium: Kathiawar and Gujarat were under their rule until the 5th century under the designation of Western Kshatrapas, until they were eventually conquered by the Gupta emperor Chandragupta II (also called Vikramaditya).

Indo-Scythian coinage.

Indo-Scythian coinage is generally of a high artistic quality, although it clearly deteriorates towards the disintegration of Indo-Scythian rule around AD 20 (coins of Rajuvula). A fairly high-quality but rather stereotypical coinage would continue in the Western Satraps until the 4th century.  Indo-Scythian coinage is generally quite realistic, artistically somewhere between Indo-Greek and Kushan coinage. It is often suggested Indo-Scythian coinage benefited from the help of Greek celators (Boppearachchi).  Indo-Scythian coins essentially continue the Indo-Greek tradition, by using the Greek language on the obverse and the Kharoshthi language on the reverse. The portrait of the king is never shown however, and is replaced by depictions of the king on horse (and sometimes on camel), or sometimes sitting cross-legged on a cushion. The reverse of their coins typically show Greek divinities.  Buddhist symbolism is present throughout Indo-Scythian coinage. In particular, they adopted the Indo-Greek practice since Menander I of showing divinities forming the vitarka mudra with their right hand (as for the mudra-forming Zeus on the coins of Maues or Azes II), or the presence of the Buddhist lion on the coins of the same two kings, or the triratana symbol on the coins of Zeionises.

Depiction of Indo-Scythians.

Besides coinage, few works of art are known to indisputably represent Indo-Scythians. Indo-Scythian rulers are usually depicted on horseback in armour, but the coins of Azilises show the king in a simple, undecorated, tunic.  Several Gandharan sculptures also show foreigners in soft tunics, sometimes wearing the typical Scythian cap. They stand in contrast to representations of Kushan men, who seem to wear thick, rigid, tunics, and who are generally represented in a much more simplistic manner.

Buner reliefs.

Indo-Scythian soldiers in military attire are sometimes represented in Buddhist friezes in the art of Gandhara (particularly in Buner reliefs). They are depicted in ample tunics with trousers, and have heavy straight swords as weapons. They wear pointed hoods (the Scythian cap or bashlyk), which distinguishes them from the Indo-Parthians who only wore a simple fillet over their bushy hair, and which is also systematically worn by Indo-Scythian rulers on their coins. With the right hand, some of them are forming the Karana mudra against evil spirits. In Gandhara, such friezes were used as decorations on the pedestals of Buddhist stupas. They are contemporary with other friezes representing people in purely Greek attire, hinting at an intermixing of Indo-Scythians (holding military power) and Indo-Greeks (confined, under Indo-Scythian rule, to civilian life).  Another relief is known where the same type of soldiers are playing musical instruments and dancing, activities which are widely represented elsewhere in Gandharan art: Indo-Scythians are typically shown as reveling devotees.

Stone palettes.

Numerous stone palettes found in Gandhara are considered good representatives of Indo-Scythian art. These palettes combine Greek and Iranian influences, and are often realized in a simple, archaic style. Stone palettes have only been found in archaeological layers corresponding to Indo-Greek, Indo-Scythian and Indo-Parthian rule, and are essentially unknown in the preceding Mauryan layers or the succeeding Kushan layers.  Very often these palettes represent people in Greek dress in mythological scenes, a few in Parthian dress (head-bands over bushy hair, crossed-over jacket on a bare chest, jewelry, belt, baggy trousers), and even fewer in Indo-Scythian dress (Phrygian hat, tunic and comparatively straight trousers). A palette found in Sirkap and now in the New Delhi Museum shows a winged Indo-Scythian horseman riding winged deer, and being attacked by a lion.

The Indo-Scythians and Buddhism.

The Indo-Scythians seem to have been followers of Buddhism, and many of their practices apparently continued those of the Indo-Greeks.

Royal dedications.

Several Indo-Scythian kings after Azes are known for making Buddhist dedications in their name, on plaques or reliquaries:

Butkara Stupa.

Excavations at the Butkara Stupa in Swat by an Italian archaeological team have yielded various Buddhist sculptures thought to belong to the Indo-Scythian period. In particular, an Indo-Corinthian capital representing a Buddhist devotee within foliage has been found which had a reliquary and coins of Azes buried at its base, securely dating the sculpture to around 20 BC. A contemporary pilaster with the image of a Buddhist devotee in Greek dress has also been found at the same spot, again suggesting a mingling of the two populations. Various reliefs at the same location show Indo-Scythians with their characteristic tunics and pointed hoods within a Buddhist context, and side-by-side with reliefs of standing Buddhas.

Gandharan sculptures.

Other reliefs have been found, which show Indo-Scythian men with their characteristic pointed cap pushing a cart on which is reclining the Greek god Dionysos with his consort Ariadne.

Mathura lion capital.

The Mathura lion capital, which associates many of the Indo-Scythian rulers from Maues to Rajuvula, mentions a dedication of a relic of the Buddha in a stupa. It also bears centrally the Buddhist symbol of the triratana, and is also filled with mentions of the bhagavat Buddha Sakyamuni, and characteristically Buddhist phrases such as:

Indo-Scythians in Western sources.

The country of Scythia in the area of Pakistan, and especially around the mouth of the Indus with its capital at Minnagara (modern day Karachi) is mentioned extensively in Western maps and travel descriptions of the period. The Ptolemy world map, as well as the Periplus of the Erythraean Sea mention prominently, the country of Scythia on the Indus Valley, as well as Roman Tabula Peutingeriana. The Periplus states that Minnagara was the capital of Scythia, and that Parthian Princes from within it were fighting for its control during the 1st century AD. It also distinguishes Scythia with Ariaca further east (centred in Gujarat and Malwa), over which ruled the Western Satrap king Nahapana.

Indo-Scythians in Indian literature.

The Indo-Scythians were named "Shaka" in India, an extension on the name Saka used by the Persians to designate Scythians. From the time of the Mahabharata wars (3100 BC roughly, prior to Kaiyuga start ) Shakas receive numerous mentions in texts like the Puranas, the Manusmriti, the Ramayana, the Mahabharata, the Mahabhasiya of Patanjali, the Brhat Samhita of Vraha Mihira, the Kavyamimamsa, the Brihat-Katha-Manjari, the Katha-Saritsagara and several other old texts. They are described as part of an amalgam of other war-like tribes from the northwest.

Sai-Wang Scythian hordes of Chipin or Kipin.

A section of the Central Asian Scythians (under Sai-Wang) is said to have taken southerly direction and after passing through the Pamirs it entered the Chipin or Kipin after crossing the Hasuna-tu ("Hanging Pass") located above the valley of Kanda in Swat country. Chipin has been identified by Pelliot, Bagchi, Raychaudhury and some others with Kashmir while other scholars identify it with Kapisha (Kafirstan). The Sai-Wang had established his kingdom in Kipin. S. Konow interprets the Sai-Wang as Śaka Murunda of Indian literature, Murunda being equal to Wang i.e. king, master or lord, but Bagchi who takes the word Wang in the sense of the king of the Scythians but he distinguishes the Sai Sakas from the Murunda Sakas. There are reasons to believe that Sai Scythians were Kamboja Scythians and therefore "Sai-Wang" belonged to the "Scythianised Kambojas" (i.e. Parama-Kambojas) of the Transoxiana region and came back to settle among his own stock after being evicted from his ancestral land located in "Scythia" or "Shakadvipa". King Moga or Maues could have belonged to this group of Scythians who had migrated from the "Sai" country ("Central Asia") to Chipin.

Establishment of Mlechcha Kingdoms in Northern India.

The mixed Scythian hordes that migrated to Drangiana and surrounding regions later spread further into north and south-west India via the lower Indus valley. Their migration spread into Sovira, Gujarat, Rajasthan and northern India, including kingdoms in the Indian mainland.  There are important references to the warring "Mleccha" hordes of the Sakas, Yavanas, Kambojas and Pahlavas in the "Bala Kanda" of the Valmiki Ramayana. H. C. Raychadhury glimpses in these verses the struggles between the Hindus and the invading hordes of Mlechcha barbarians from the northwest. The time frame for these struggles is the 2nd century BC onwards. Raychadhury fixes the date of the present version of the Valmiki Ramayana around or after the 2nd century AD.  Mahabharata too furnishes a veiled hint about the invasion of the mixed hordes from the northwest. "Vanaparava" by Mahabharata contains verses in the form of prophecy deploring that "...the Mlechha (barbaric) kings of the Shakas, Yavanas, Kambojas, Bahlikas, etc. shall rule the earth un-righteously in Kaliyuga..."  According to H. C. Ray Chaudhury, this is too clear a statement to be ignored or explained away.

Evidence about joint invasions.

The Scythian groups that invaded India and set up various kingdoms included, besides the Sakas, other allied tribes, such as the Medii, Xanthii, and Massagetae. These peoples were all absorbed into the community of Kshatriyas of mainstream Indian society.  The Shakas were formerly a people of the "trans-Hemodos" region—the "Shakadvipa" of the Puranas or the Scythia of the classical writings. "Isidor of Charax" (beginning of 1st century AD) attests them in Sakastana (modern Seistan). The "Periplus of the Erythraean Sea" (c. AD 70–80) also attests a Scythian district in lower Indus with Minnagra as its capital. Ptolemy (c. AD 140) also attests to an Indo-Scythia in south-western India which comprised the Patalene and Surastrene (Saurashtra) territories.  The 2nd century BC Scythian invasion of India, was in all probability carried out jointly by the Sakas, Pahlavas, Kambojas, Paradas, Rishikas and other allied tribes from the northwest.

Descendants of the Indo-Scythians.

Tadeusz Sulimirski notes that the Sacae also invaded parts of Northern India. Weer Rajendra Rishi, an Indian linguist has identified linguistic affinities between Indian and Central Asian languages, which further lends credence to the possibility of historical Sacae influence in Northern India.

Indo-Scythians (also called Indo-Sakas) were a group of nomadic Iranian peoples of Saka and Scythian origin who migrated southward into western and northern South Asia (Sogdiana, Bactria, Arachosia, Gandhara, Sindh, Kashmir, Punjab, Haryana, Uttar Pradesh, Bihar, Rajasthan, Gujarat and Maharashtra) from the middle of the 2nd century BC to the 4th century AD.

Indoskythové jsou větví Šaků (Skythů), kteří zhruba od 2. století př. n. l. do 4. století migrovali z jižní Sibiře do Baktrie, Sogdiany, Arachósie, Gandháry, Kašmíru, Paňdžábu a do západních částí centrální Asie. Po vpádu do Gandháry se vůbec prvním králem Indoskythů stal Maues, který postupně vybudoval říši zabírající rozsáhlé území na severozápadě Indického subkontinentu. Vláda Indoskythů v Indii definitivně skončila se smrtí posledního krále Západních kšatrapů.


Background.

The initial location in the Prince-Bishopric of Basel reflected the desire among parties seeking reform to meet outside territories directly controlled by the Pope, the Emperor or the kings of Aragon and France, whose influences the council hoped to avoid. Ambrogio Traversari attended the Council of Basel as legate of Pope Eugene IV.  Under pressure for ecclesiastical reform, Pope Martin V sanctioned a decree of the Council of Constance (9 October 1417) obliging the papacy to summon general councils periodically. At the expiration of the first term fixed by this decree, Pope Martin V complied by calling a council at Pavia. Due to an epidemic the location transferred almost at once to Siena (see Council of Siena) and disbanded, in circumstances still imperfectly known, just as it had begun to discuss the subject of reform (1424). The next council fell due at the expiration of seven years in 1431; Martin V duly convoked it for this date to the town of Basel and selected to preside over it the cardinal Julian Cesarini, a well-respected prelate. Martin himself, however, died before the opening of the synod.  The Council was seated on 14 December 1431, at a period when the conciliar movement was strong and the authority of the papacy weak. The Council at Basel opened with only a few bishops and abbots attending, but it grew rapidly and to make its numbers greater gave the lower orders a majority over the bishops. It adopted an anti-papal attitude, proclaimed the superiority of the Council over the Pope and prescribed an oath to be taken by every Pope on his election. On 18 December Martin's successor, Pope Eugene IV, tried to dissolve it and open a new council on Italian soil at Bologna, but he was overruled.  Sigismund, King of Hungary and titular King of Bohemia, had been defeated at the Battle of Domažlice in the fifth crusade against the Hussites in August 1431. Under his sponsorship, the Council negotiated a peace with Calixtine faction of the Hussites in January 1433. Pope Eugene acknowledged the council in May and crowned Sigismund Holy Roman Emperor on 31 May 1433. The divided Hussites were defeated in May 1434. In June 1434, the pope had to flee a revolt in Rome and began a ten-year exile in Florence.  When the Council was moved from Basel to Ferrara in 1438, some remained at Basel, claiming to be the Council. They elected Amadeus VIII, Duke of Savoy, as Antipope. Driven out of Basel in 1448, they moved to Lausanne, where Felix V, the pope they had elected and the only claimant to the papal throne who ever took the oath that they had prescribed, resigned. The next year, they decreed the closure of what for them was still the Council of Basel.  The new council was transferred to Florence in 1439 because of the danger of plague at Ferrara and because Florence had agreed, against future payment, to finance the Council. The Council had meanwhile successfully negotiated reunification with several Eastern Churches, reaching agreements on such matters as the Western insertion of the phrase "Filioque" to the Nicene-Constantinopolitan Creed, the definition and number of the sacraments, and the doctrine of Purgatory. Another key issue was papal primacy, which involved the universal and supreme jurisdiction of the Bishop of Rome over the whole Church, including the national Churches of the East (Serbian, Greek, Moldo-Wallachian, Bulgarian, Russian, Georgian, Armenian etc.) and nonreligious matters such as the promise of military assistance against the Ottomans. The final decree of union was a signed document called the "Laetentur Caeli", "Let the Heavens Rejoice". Some bishops, perhaps feeling political pressure from the Byzantine Emperor, accepted the decrees of the Council and reluctantly signed. Others did so by sincere conviction, such as Isidore of Kiev, who subsequently suffered greatly for it. Only one Eastern Bishop, Mark of Ephesus, refused to accept the union and became the leader of opposition back in Byzantium, while the Serbian patriarch did not even attend the council. The Russians, upon learning of the union, angrily rejected it and ousted any prelate who was even remotely sympathetic to it, declaring the Russian Orthodox Church as autocephalus (i.e., as having its "own head"). Despite the religious union, Western military assistance to Byzantium was ultimately insufficient, and the fall of Constantinople occurred in May 1453. The Council declared the Basel group heretics and excommunicated them, and the superiority of the Pope over the Councils was affirmed in the bull "Etsi non dubitemus" of 20 April 1441.

Composition.

The democratic character of the assembly at Basel was a result of both its composition and its organization. Doctors of theology, masters and representatives of chapters, monks and clerks of inferior orders constantly outnumbered the prelates in it, and the influence of the superior clergy had less weight because instead of being separated into "nations", as at Constance, the fathers divided themselves according to their tastes or aptitudes into four large committees or "deputations" ("deputationes"). One was concerned with questions of faith ("fidei"), another with negotiations for peace ("pacis"), the third with reform ("reformatorii"), and the fourth with what they called "common concerns" ("pro communibus"). Every decision made by three "deputations" (the lower clergy formed the majority in each) received ratification for the sake of form in general congregation and, if necessary led to decrees promulgated in session. Papal critics thus termed the council "an assembly of copyists" or even "a set of grooms and scullions". However, some prelates, although absent, were represented by their proxies.  Nicholas of Cusa was a member of the delegation sent to Constantinople with the pope's approval to bring back the Byzantine emperor and his representatives to the Council of Florence of 1439. At the time of the council's conclusion in 1439, Cusa was thirty-eight years old and thus, compared to the other clergy at the council, a fairly young man though one of the more accomplished in terms of the body of his complete works.

Attempted dissolution.

From Italy, France and Germany, the fathers came late to Basel. Cesarini devoted all his energies to the war against the Hussites until the disaster of Taus forced him to evacuate Bohemia in haste. Pope Eugene IV, Martin V's successor, lost hope that the council could be useful owing to the progress of heresy, the reported troubles in Germany, the war that had lately broken out between the dukes of Austria and Burgundy, and finally, the small number of fathers who had responded to the summons of Martin V. That opinion and his desire to preside over the council in person, induced him to recall the fathers from Germany, as his poor health made it difficult for him to go. He commanded the council to disperse, and appointed Bologna as their meeting place in eighteen months' time, with the intention of making the session of the council coincide with some conferences with representatives of the Orthodox Church of the Greek East, scheduled to be held there with a view to ecumenical union (18 December 1431).  That order led to an outcry among the fathers and incurred the deep disapproval of the legate Cesarini. They argued that the Hussites would think the Church afraid to face them and that the laity would accuse the clergy of shirking reform, both with disastrous effects. The pope explained his reasons and yielded certain points, but the fathers were intransigent. Considerable powers had been decreed to Church councils by the Council of Constance, which amid the troubles of the Western Schism had proclaimed the superiority, in certain cases, of the council over the pope, and the fathers at Basel insisted upon their right of remaining assembled. They held sessions, promulgated decrees, interfered in the government of the papal countship of Venaissin, treated with the Hussites, and, as representatives of the universal Church, presumed to impose laws upon the sovereign pontiff himself.  Eugene IV resolved to resist the Council's claim of supremacy, but he did not dare openly to repudiate the conciliar doctrine considered by many to be the actual foundation of the authority of the popes before the schism. He soon realized the impossibility of treating the fathers of Basel as ordinary rebels, and tried a compromise; but as time went on, the fathers became more and more intractable, and between him and them gradually arose an impassable barrier.  Abandoned by a number of his cardinals, condemned by most of the powers, deprived of his dominions by "condottieri" who shamelessly invoked the authority of the council, the pope made concession after concession and ended on 15 December 1433 with a pitiable surrender of all the points at issue in a Papal bull, the terms of which were dictated by the fathers of Basel, that is, by declaring his bull of dissolution null and void and recognising that the synod as legitimately assembled throughout. However, Eugene IV did not ratify all the decrees coming from Basel, nor make a definite submission to the supremacy of the council. He declined to express any forced pronouncement on this subject, and his enforced silence concealed the secret design of safeguarding the principle of sovereignty. The fathers, filled with suspicion, would allow only the legates of the pope to preside over them on condition of their recognizing the superiority of the council. The legates submitted the humiliating formality but in their own names, it was asserted only after the fact, thus reserving the final judgment of the Holy See. Furthermore, the difficulties of all kinds against which Eugene had to contend, such as the insurrection at Rome, which forced him to escape by means of the Tiber, lying in the bottom of a boat, left him at first little chance of resisting the enterprises of the council.

Issues of reform.

Emboldened by their success, the fathers approached the subject of reform, their principal object being to further curtail the power and resources of the papacy. They took decisions on the disciplinary measures that regulated the elections, on the celebration of divine service and on the periodical holding of diocesan synods and provincial councils, which were usual topics in Catholic councils. They also made decrees aimed at some of the assumed rights by which the popes had extended their power and improved their finances at the expense of the local churches. Thus the council abolished annates, greatly limited the abuse of "reservation" of the patronage of benefices by the Pope and completely abolished the right claimed by the pope of "next presentation" to benefices not yet vacant (known as "gratiae expectativae"). Other conciliar decrees severely limited the jurisdiction of the court of Rome and even made rules for the election of popes and the constitution of the Sacred College. The fathers continued to devote themselves to the subjugation of the Hussites, and they also intervened, in rivalry with the pope, in the negotiations between France and England, which led to the treaty of Arras, concluded by Charles VII of France with the duke of Burgundy. Also, circumcision was deemed to be a mortal sin. Finally, they investigated and judged numbers of private cases, lawsuits between prelates, members of religious orders and holders of benefices, thus themselves committing one of the serious abuses for which they had criticized the court of Rome.

Papal supremacy.

The Council clarified the Latin dogma of papal supremacy:

Eugene IV's eastern strategy.

Eugene IV, however much he may have wished to keep on good terms with the fathers of Basel, found himself neither able nor willing to accept or observe all their decrees. The question of the union with the Greek church, especially, gave rise to a misunderstanding between them which soon led to a rupture. The Byzantine emperor John VIII Palaiologos, pressed hard by the Ottoman Turks, was keen to ally himself with the Catholics. He consented to come with the principal representatives of the Byzantine Church to some place in the West where the union could be concluded in the presence of the pope and of the Latin council. There arose a double negotiation between him and Eugene IV on the one hand and the fathers of Basel on the other. The council wished to fix the meeting-place at a place remote from the influence of the pope, and they persisted in suggesting Basel, Avignon or Savoy. On the other hand, the Byzantines wanted a coastal location in Italy for their ease of access by ship.

Council transferred to Ferrara and attempted reunion with Orthodox Churches.

As a result of negotiations with the East, Emperor John VIII Palaiologos accepted Pope Eugene IV's offer. By a bull dated 18 September 1437, Pope Eugene again pronounced the dissolution of the Council of Basel and summoned the fathers to Ferrara in the Po valley.  The first public session at Ferrara began on 10 January 1438. Its first act declared the Council of Basel transferred to Ferrara and nullified all further proceedings at Basel. In the second public session (15 February 1438), Pope Eugene IV excommunicated all who continued to assemble at Basel.  In early April 1438, the Greek contingent, over 700 strong, arrived at Ferrara. On 9 April 1438, the first solemn session at Ferrara began, with the Eastern Roman Emperor, the Patriarch of Constantinople and representatives of the Patriarchal Sees of Antioch, Alexandria and Jerusalem in attendance and Pope Eugene IV presiding. The early sessions lasted until 17 July 1438 with each theological issue of the Great Schism (1054) hotly debated, including the Processions of the Holy Spirit, the Filioque clause in the Nicene Creed, Purgatory and papal primacy. Resuming proceedings on 8 October 1438, the Council focused exclusively on the Filioque matter. Even as it became clear that the Greek Church would never consent to the Filioque clause, the Byzantine Emperor continued to press for a reconciliation.

Council transferred to Florence and the near East-West union.

With finances running thin and on the pretext that the plague was spreading in the area, both the Latins and the Greeks agreed to transfer the council to Florence. Continuing at Florence in January 1439, the Council made steady progress on a compromise formula, "ex filio".  In the following months, agreement was reached on the Western doctrine of Purgatory and a return to the pre-schism prerogatives of the Papacy. On 6 July 1439 an agreement ("Laetentur Caeli") was signed by all the Eastern bishops but one, Mark of Ephesus, who, contrary to the views of all others, held that Rome continued in both heresy and schism.  To complicate matters, Patriarch Joseph II of Constantinople had died the previous month. The Greek Patriarchs were unable to assert that ratification by the Eastern Church could be achieved without a clear agreement of the whole Church.  Upon their return, the Eastern bishops found their attempts toward agreement with the West broadly rejected by the monks, the populace, and by civil authorities (with the notable exception of the Emperors of the East who remained committed to union until the fall of the Byzantine Empire to the Turkish Ottoman Empire two decades later). Facing the imminent threat, the Union was officially proclaimed by Isidore of Kiev in Hagia Sophia on 12 December 1452.  The Emperor, bishops, and people of Constantinople accepted this act as a temporary provision until the removal of the Ottoman threat. Yet, it was too late: on 29 May 1453 Constantinople fell. The union signed at Florence, down to the present, has not been implemented by most Orthodox Churches.

Copts and Ethiopians.

The Council soon became even more international. The signature of this agreement for the union of the Latins and the Greeks encouraged Pope Eugenius to announce the good news to the Coptic Christians, and invite them to send a delegation to Florence. He wrote a letter on 7 July 1439, and to deliver it, sent Alberto da Sarteano as an apostolic delegate. On 26 August 1441, Sarteano returned with four Ethiopians from Emperor Zara Yaqob and Copts. According to a contemporary observer "They were black men and dry and very awkward in their bearing (...) really, to see them they appeared to be very weak". At that time, Rome had delegates from a multitude of nations, from Armenia to Russia, Greece and various parts of north and east Africa.

"Deposition of Eugene IV" and schism at Basel.

During this time the council of Basel, though nullified at Ferrara and abandoned by Cesarini and most of its members, persisted nonetheless, under the presidency of Cardinal Aleman. Affirming its ecumenical character on 24 January 1438, it suspended Eugene IV. The council went on (in spite of the intervention of most of the powers) to pronounce Eugene IV deposed (25 June 1439), giving rise to a new schism by electing (4 November 1439) duke Amadeus VIII of Savoy, as (anti)pope, who took the name of Felix V.

Effects of the schism.

This schism lasted fully ten years, although the antipope found few adherents outside of his own hereditary states, those of Alfonso V of Aragon, of the Swiss confederation and of certain universities. Germany remained neutral; Charles VII of France confined himself to securing to his kingdom (by the Pragmatic Sanction of Bourges, which became law on 13 July 1438) the benefit of a great number of the reforms decreed at Basel; England and Italy remained faithful to Eugene IV. Finally, in 1447, Frederick III, Holy Roman Emperor, after negotiations with Eugene, commanded the burgomaster of Basel not to allow the presence of the council any longer in the imperial city.

Schism reconciled at Lausanne.

In June 1448 the rump of the council migrated to Lausanne. The antipope, at the insistence of France, ended by abdicating (7 April 1449). Eugene IV died on 23 February 1447, and the council at Lausanne, to save appearances, gave their support to his successor, Pope Nicholas V, who had already been governing the Church for two years. Trustworthy evidence, they said, proved to them that this pontiff accepted the dogma of the superiority of the council as defined at Constance and at Basel.

Aftermath.

The struggle for East-West union at Ferrara and Florence, while promising, never bore fruit. While progress toward union in the East continued to be made in the following decades, all hopes for a proximate reconciliation were dashed with the fall of Constantinople in 1453. Following their conquest, the Ottomans encouraged hardline anti-unionist Orthodox clerics in order to divide European Christians.  Perhaps the council's most important historical legacy was the lectures on Greek classical literature given in Florence by many of the delegates from Constantinople, including the renowned Neoplatonist Gemistus Pletho. These greatly helped the progress of Renaissance humanism.

The Council of Florence is the seventeenth ecumenical council recognized by the Catholic Church, held between 1431 and 1449. It was convoked as the Council of Basel by Pope Martin V shortly before his death in February 1431 and took place in the context of the Hussite wars in Bohemia and the rise of the Ottoman Empire. At stake was the greater conflict between the Conciliar movement and the principle of papal supremacy.

Basilejský koncil, podle dalších měst jednání označovaný také jako basilejsko-ferrarsko-florentský koncil (přičemž termín basilejský koncil může pak úžeji označovat pouze jednání konaná v Basileji) byl podle počítání římskokatolické církve 17. ekumenický koncil, konaný v letech 1431–1445. Vedle jednání dodnes uznávaných katolíky za právoplatná došlo během koncilu také k vydělení skupiny církevních hodnostářů, jejíž rokování bylo později církví označeno za heretické. Koncil byl svolán papežem Evženem IV. do švýcarské Basileje, což odráželo přání řady účastníků jednat mimo území některé z tehdejších evropských velmocí či papežského státu. Jednání bylo roku 1438 papežem přeneseno do italské Ferrary a roku 1439 pro nebezpečí moru do Florencie. Někteří účastníci, odpůrci Evžena IV. a zastánci konciliarismu, ovšem zůstali v Basileji a považovali se za legitimní pokračování koncilu. Zde roku 1439 zvolili vzdoropapeže Felixe V., který ovšem rezignoval roku 1449, čímž ukončil poslední velké papežské schizma. Mezitím byla opoziční část koncilu vypuzena z Basileje do Lausanne, kde se po rezignaci Felixe V. sama rozpustila.


Early life and education.

Buckle, the son of Thomas Henry Buckle (1779–1840), a wealthy London merchant and shipowner, and his wife, Jane Middleton (d. 1859) of Yorkshire was born at Lee in London (Kent County) on November 24, 1821. He had two sisters. His father died in January 1840.

Education.

As a boy, Buckle's "delicate health" rendered him unsuited for the usual formal education or games of middle-class youth. However, he loved reading. This made him suitable to be "educated at home by his mother, to whom he was devoted until her death in 1859. She taught him to read the Bible, the "Arabian Nights", "The Pilgrim's Progress", and Shakespeare. His father read theology and literature and occasionally recited Shakespeare to the family in the evenings."  Buckle's one year of formal education was in Gordon House School at age fourteen. When his father offered him a reward for winning a prize in mathematics, Buckle asked "to be taken away from school". From then on he was self-taught. As such, Buckle said later, "I was never much tormented with what is called education, but allowed to pursue my own way undisturbed... Whatever I may now be supposed to know I taught myself."  At age nineteen, Buckle first gained distinction as a chess player. He was known as one of the best in the world. In matchplay he defeated Kieseritsky and Loewenthal.

Father's death.

Buckle's father died in 1840. Buckle inherited £20,000. This would be worth £1,613,000.00 in 2015. This inheritance allowed Buckle to live the rest of his life in reading, writing, and travel.

Writing "History of Civilization in England".

In July 1840 Buckle, his mother, and his sister Mary spent almost a year in Europe, with "extended stays in Germany, Italy, and France. Buckle studied the language, literature, and history of each place they visited." Buckle taught himself to read eighteen foreign languages.  By 1840, Buckle had decided "to direct all his reading and to devote all his energies to the preparation of some great historical work". During the next seventeen years he worked ten hours a day toward that purpose. By 1851 Buckle had decided that his "great historical work" would be "a history of civilization". During the next six years, he was engaged "in writing and rewriting, altering and revising the first volume". It was titled the "History of Civilization in England" and was published in June 1857.

Private life.

Because he was uneasy about his health, Buckle "rose, worked, walked, dined, and retired with remarkable regularity". His inheritance "enabled him to live comfortably", but he spent money prudently with two exceptions: fine cigars and his collection of 22,000 books. Buckle and his mother enjoyed giving dinners for friends and dining out. Buckle was mostly deemed to be "a good conversationalist" because of his "deep knowledge of a wide range of subjects". On the other hand, some thought him "tedious or egotistical" with a tendency "to dominate conversations". He won the first British chess tournament in 1849.

False accusation.

The pornographic publisher John Camden Hotten claimed that his series of flagellation reprints "The Library Illustrative of Social Progress" had been taken from Buckle's collection, but this was untrue, as reported by Henry Spencer Ashbee.

Death of his mother (1859).

On April 1, 1859, Buckle's mother died. Shortly after, under the influence of this "crushing and desolating affliction", he added an argument for immortality to a review he was writing of J. S. Mill's "Essay on Liberty". Buckle's argument was not based on theologians "with their books, their dogmas, their traditions, their rituals, their records, and their other perishable contrivances". Rather he based his argument on "the universality of the affections; the yearning of every mind to care for something out of itself". Buckle asserted "it is in the need of loving and of being loved, that the highest instincts of our nature are first revealed." As if reflecting on his mother's death, Buckle continued that "as long as we are with those whom we love..., we rejoice. But when "the enemy [death]" approaches, "when the very signs of life are mute... and there lies before us nought save the shell and husk of what we loved too well, then truly, if we believed the separation were final... the best of us would succumb, but for the deep conviction that all is not really over." We have "a forecast of another and a higher state". Thus, Buckle concludes, "it is, then, to that sense of immortality with which the affections inspire us, that I would appeal for the best proof of the reality of a future life". He also said, "If immortality be untrue it matters little if anything else be true or not."

Other women in Buckle's life.

Although love for his mother dominated his life, there were other instances of his love for women. At seventeen, he fell in love with a cousin and "challenged a man to whom she was engaged". He fell for another cousin, but his parents objected.  In 1861, when Buckle went to Egypt, he invited "one Elizabeth Faunch, the widow of a carpenter, to join him... Mrs. Faunch refused his invitation, but there is some evidence that the two had been engaged in a liaison for some time."  Last travels and death The death of his mother in 1859 combined with the exhausting work on the second volume of the "History of Civilization in England" and its publication in 1861 invoked a decision by Buckle to go to Egypt to recover from exhaustion. He toured Egypt. Then, feeling better, Buckle traveled to Palestine and Syria. He died of typhoid fever in Damascus, Syria, on 29 May 1862 and was buried there. A sister provided a gravestone with the epitaph "I know that he shall rise again". The sister of the British consul in Damascus added: "The written word remains long after the writer; The writer is resting under the earth, but his works endure".

"History of Civilization in England".

The description of "History of Civilization in England" is taken from "The Encyclopædia Britannica: A Dictionary of Arts, Sciences and General Literature, Volume 4" (1890).  Buckle's fame rests mainly on his "History of Civilization in England". It is a gigantic unfinished introduction, of which the plan was, first to state the general principles of the author's method and the general laws that govern the course of human progress—and secondly, to exemplify these principles and laws through the histories of certain nations characterized by prominent and peculiar features—Spain and Scotland, the United States and Germany. The completed work was to have extended to 14 volumes; its chief ideas are:

Assessments.

"The North American Review" (1861).

"The North American Review" characterized Buckle as a "self-styled historian of civilization". He "ransacks all history, history, literature, and science for proofs and illustrations of his preconceived opinion". Furthermore, "the absurdity of the conclusions to which he is led furnishes, perhaps, the best proof of the erroneousness of his method and the falsity of his premises." In conclusion, "under the guise of a history, [the book's] only aim is to teach the preconceived conclusions of a false and debasing philosophy."

"The New York Times" (1861).

There was a review of Buckle's "History of Civilization in England. Vol II" in "The New York Times". The review concluded, "notwithstanding these imperfections, we still regard the "History of Civilization" as perhaps the most important contribution to modern historical science... It is easy for one to make a great many very superficial objections to Mr. BUCKLE's mode of treating history..., but the more one comes up with the grandeur of his method, the less disposition there will be to make such objections... His influence on the thought of the present age cannot but be enormous; and if he gives us no more than we already have in the two volumes of the magnum opus, he will still be classed among the fathers and founders of the Science of History."

The "Encyclopædia Britannica" (1910).

Buckle did not define the general conceptions with which he worked, e.g., "civilization", "history", "science", "law". Therefore, "his arguments are often fallacies". Furthermore, "he sometimes altered and contorted the facts" and "he very often unduly simplified his problems." Nevertheless, "many of his ideas... have been more precisely elaborated by later writers on sociology and history" and his work was immensely valuable in provoking further research and speculation.

John William Cousin (1910).

Buckle is remembered for treating history as an exact science, which is why many of his ideas have passed into the common literary stock, and have been more precisely elaborated by later writers on sociology and history because of his careful scientific analyses. Nevertheless, his work is not free from one-sided views and generalisations resting on insufficient data.

Robert Bierstedt (1981).

In his "History of Civilization in England", "Buckle criticized historians on the ground that they were too much interested in biography and in military and political history and failed to seek universal principle or laws." In contrast, "Buckle was confident that it was possible to construct a science of society on the basic of inductions from history." His difficulty was the "sheer quantity of materials that would have to be mastered." Herbert Spencer said that Buckle 'took in' more than he was able to organize".

Works.

"The Influence of Women on the Progress of Knowledge"  "Mill on Liberty" (a review)  A Letter to a Gentleman respecting Pooley's Case  History of Civilization in England Three volumes edition  Fragment on the Reign of Elizabeth Unpublished fragments  The Miscellaneous and Posthumous Works of Henry Thomas Buckle Three volumes edition, edited by Helen Taylor  The Miscellaneous and Posthumous Works of Henry Thomas Buckle Two volumes new and abridged edition, edited by Grant Allen  Collected essays One volume, editor not named

Henry Thomas Buckle (24 November 1821 – 29 May 1862) was an English historian, the author of an unfinished "History of Civilization", and a strong amateur chess player. He is sometimes called "the Father of Scientific History".

Henry Thomas Buckle (24. listopadu 1821, Lee, Kent – 29. května 1862, Damašek, Sýrie) byl anglický historik a sociolog a také silný šachový hráč.


Osenberg List.

In the later part of World War II, Nazi Germany found itself at a logistical disadvantage, having failed to conquer the USSR with Operation Barbarossa (June–December 1941), the Siege of Leningrad (September 1941 – January 1944), Operation Nordlicht ("Northern Light", August–October 1942), and the Battle of Stalingrad (July 1942 – February 1943). The failed conquest had depleted German resources, and its military-industrial complex was unprepared to defend the "Großdeutsches Reich" (Greater German Reich) against the Red Army's westward counterattack. By early 1943, the German government began recalling from combat a number of scientists, engineers, and technicians; they returned to work in research and development to bolster German defense for a protracted war with the USSR. The recall from frontline combat included 4,000 rocketeers returned to Peenemünde, in northeast coastal Germany.  The Nazi government's recall of their now-useful intellectuals for scientific work first required identifying and locating the scientists, engineers, and technicians, then ascertaining their political and ideological reliability. Werner Osenberg, the engineer-scientist heading the "Wehrforschungsgemeinschaft" (Defense Research Association), recorded the names of the politically cleared men to the Osenberg List, thus reinstating them to scientific work.  In March 1945, at Bonn University, a Polish laboratory technician found pieces of the Osenberg List stuffed in a toilet; the list subsequently reached MI6, who transmitted it to U.S. Intelligence. Then U.S. Army Major Robert B. Staver, Chief of the Jet Propulsion Section of the Research and Intelligence Branch of the U.S. Army Ordnance Corps, used the Osenberg List to compile his list of German scientists to be captured and interrogated; Wernher von Braun, Germany's premier rocket scientist, headed Major Staver's list.

Identification.

In Operation Overcast, Major Staver's original intent was only to interview the scientists, but what he learned changed the operation's purpose. On May 22, 1945, he transmitted to the U.S. Pentagon headquarters Colonel Joel Holmes's telegram urging the evacuation of German scientists and their families, as most "important for [the] Pacific war" effort. Most of the Osenberg List engineers worked at the Baltic coast German Army Research Center Peenemünde, developing the V-2 rocket. After capturing them, the Allies initially housed them and their families in Landshut, Bavaria, in southern Germany.  Beginning on July 19, 1945, the U.S. JCS managed the captured ARC rocketeers under Operation Overcast. However, when the "Camp Overcast" name of the scientists' quarters became locally known, the program was renamed Operation Paperclip in November 1945. Despite these attempts at secrecy, later that year the press interviewed several of the scientists.

Capture and detention.

Early on, the United States created the Combined Intelligence Objectives Subcommittee (CIOS). This provided the information on targets for the T-Forces that went in and targeted scientific, military and industrial installations (and their employees) for their know-how. Initial priorities were advanced technology, such as infrared, that could be used in the war against Japan; finding out what technology had been passed on to Japan; and finally to halt the research.  A project to halt the research was codenamed "Project Safehaven", and it was not initially targeted against the Soviet Union; rather the concern was that German scientists might emigrate and continue their research in countries such as Spain, Argentina or Egypt, all of which had sympathized with Nazi Germany. In order to avoid the complications involved with the emigration of German scientists, the CIOS was responsible for scouting and kidnapping high-profile individuals for the deprivation of technological advancements in nations outside of the US.  Much U.S. effort was focused on Saxony and Thuringia, which by July 1, 1945, would become part of the Soviet Occupation zone. Many German research facilities and personnel had been evacuated to these states, particularly from the Berlin area. Fearing that the Soviet takeover would limit U.S. ability to exploit German scientific and technical expertise, and not wanting the Soviet Union to benefit from said expertise, the United States instigated an "evacuation operation" of scientific personnel from Saxony and Thuringia, issuing orders such as:  By 1947 this evacuation operation had netted an estimated 1,800 technicians and scientists, along with 3,700 family members. Those with special skills or knowledge were taken to detention and interrogation centers, such as one code-named DUSTBIN, to be held and interrogated, in some cases for months.  A few of the scientists were gathered up in Operation Overcast, but most were transported to villages in the countryside where there were neither research facilities nor work; they were provided stipends and forced to report twice weekly to police headquarters to prevent them from leaving. The Joint Chiefs of Staff directive on research and teaching stated that technicians and scientists should be released "only after all interested agencies were satisfied that all desired intelligence information had been obtained from them".  On November 5, 1947, the Office of Military Government of the United States (OMGUS), which had jurisdiction over the western part of occupied Germany, held a conference to consider the status of the evacuees, the monetary claims that the evacuees had filed against the United States, and the "possible violation by the US of laws of war or Rules of Land Warfare". The OMGUS director of Intelligence R. L. Walsh initiated a program to resettle the evacuees in the Third World, which the Germans referred to as General Walsh's "Urwald-Programm" (jungle program); however, this program never matured. In 1948, the evacuees received settlements of 69.5 million Reichsmarks from the U.S., a settlement that soon became severely devalued during the currency reform that introduced the Deutsche Mark as the official currency of western Germany.  John Gimbel concludes that the United States held some of Germany's best minds for three years, therefore depriving the German recovery of their expertise.

Arrivals.

In May 1945, the U.S. Navy "received in custody" Herbert A. Wagner, the inventor of the Hs 293 missile; for two years, he first worked at the Special Devices Center, at Castle Gould and at Hempstead House, Long Island, New York; in 1947, he moved to the Naval Air Station Point Mugu.  In August 1945, Colonel Holger Toftoy, head of the Rocket Branch of the Research and Development Division of the U.S. Army's Ordnance Corps, offered initial one-year contracts to the rocket scientists; 127 of them accepted. In September 1945, the first group of seven rocket scientists (aerospace engineers) arrived at Fort Strong, located on Long Island in Boston harbor: Wernher von Braun, Erich W. Neubert, Theodor A. Poppel, August Schulze, Eberhard Rees, Wilhelm Jungert, and Walter Schwidetzky.  Beginning in late 1945, three rocket-scientist groups arrived in the United States for duty at Fort Bliss, Texas, and at White Sands Proving Grounds, New Mexico, as "War Department Special Employees".  In 1946, the United States Bureau of Mines employed seven German synthetic fuel scientists at a Fischer-Tropsch chemical plant in Louisiana, Missouri.  On June 1, 1949, the Chief of Ordnance of the United States Army designated Redstone Arsenal in Huntsville, Alabama, as the Ordnance Rocket Center, its facility for rocket research and development. On April 1, 1950, the Fort Bliss missile development operation—including von Braun and his team of over 130 Paperclip members—was transferred to Redstone Arsenal.  In early 1950, legal U.S. residency for some of the Project Paperclip specialists was effected through the U.S. consulate in Ciudad Juárez, Chihuahua, Mexico; thus, German scientists legally entered the United States from Latin America.  Between 1945 and 1952, the United States Air Force sponsored the largest number of Paperclip scientists, importing 260 men, of whom 36 returned to Germany and one (Walter Schreiber) reemigrated to Argentina.  Eighty-six aeronautical engineers were transferred to Wright Field, Ohio, where the United States had Luftwaffe aircraft and equipment captured under Operation Lusty (Luftwaffe Secret Technology).  The United States Army Signal Corps employed 24 specialists – including the physicists Georg Goubau, Gunter Guttwein, Georg Hass, Horst Kedesdy, and Kurt Lehovec; the physical chemists Rudolf Brill, Ernst Baars, and Eberhard Both; the geophysicist Helmut Weickmann; the optician Gerhard Schwesinger; and the engineers Eduard Gerber, Richard Guenther, and Hans Ziegler.  In 1959, 94 Operation Paperclip men went to the United States, including Friedwardt Winterberg and Friedrich Wigand.  Overall, through its operations to 1990, Operation Paperclip imported 1,600 men, as part of the "intellectual reparations" owed to the US and the UK, valued at $10 billion in patents and industrial processes.

Major awards (in the United States).

The NASA Distinguished Service Medal is the highest award which may be bestowed by the National Aeronautics and Space Administration (NASA). After more than two decades of service and leadership in NASA, four Operation Paperclip members were awarded the NASA Distinguished Service Medal in 1969: Kurt Debus, Eberhard Rees, Arthur Rudolph, and Wernher von Braun. Ernst Geissler was awarded the medal in 1973.  The Department of Defense Distinguished Civilian Service Award is the highest civilian award given by the United States Department of Defense. After two decades of service, Operation Paperclip member Siegfried Knemeyer was awarded the Department of Defense Distinguished Civilian Service Award in 1966.  The Goddard Astronautics Award is the highest honor bestowed for notable achievements in the field of astronautics by the American Institute of Aeronautics and Astronautics (AIAA). For their service, three Operation Paperclip members were awarded the Goddard Astronautics Award: Wernher von Braun (1961), Hans von Ohain (1967), and Krafft Arnold Ehricke (1984).  The U.S. Space & Rocket Center in Huntsville, Alabama, owns and operates the U.S. Space Camp. Several Operation Paperclip members are members of the Space Camp Hall of Fame (which began in 2007): Wernher von Braun (2007), Georg von Tiesenhausen (2007), and Oscar Holderer (2008).  The New Mexico Museum of Space History includes the International Space Hall of Fame. Two Operation Paperclip members are members of the International Space Hall of Fame: Wernher von Braun (1976) and Ernst Steinhoff (1979). Hubertus Strughold was inducted in 1978 but removed as a member in 2006. Other closely related members include Willy Ley (1976), a German-American science writer, and Hermann Oberth (1976), a German scientist who advised von Braun's rocket team in the U.S. from 1955 to 1958.  Two lunar craters are named after Paperclip scientists: Debus after Kurt Debus, the first director of NASA's Kennedy Space Center, and von Braun.

Scientific accomplishments.

Wernher von Braun was chief architect of the Saturn V launch vehicle, the key instrument in getting humans to the moon.  Adolf Busemann was the mind behind the swept wing, which improved aircraft performance at high speeds.

Controversy and investigations.

Before his official approval of the program, President Truman, for sixteen months, was indecisive on the program. Years later in 1963, Truman recalled that he was not in the least reluctant to approve Paperclip; that because of relations with Russia "this had to be done and was done".  Several of the Paperclip scientists were later investigated because of their links with the Nazi Party during the war. Only one Paperclip scientist, Georg Rickhey, was formally tried for any crime, and no Paperclip scientist was found guilty of any crime, in America or Germany. Rickhey was returned to Germany in 1947 to stand trial at the Dora Trial, where he was acquitted.  In 1951, weeks after his U.S. arrival, Walter Schreiber was linked by the "Boston Globe" to human experiments conducted by Kurt Blome at Ravensbrück, and he emigrated to Argentina with the aid of the U.S. military.  In 1984, Arthur Rudolph, under perceived threat of prosecution relating to his connection—as operations director for V-2 missile production—to the use of forced labor from Mittelbau-Dora at the Mittelwerk, renounced his U.S. citizenship and moved to West Germany, which granted him citizenship.  For fifty years, from 1963 to 2013, the Strughold Award—named after Hubertus Strughold, "The Father of Space Medicine", for his central role in developing innovations like the space suit and space life support systems—was the most prestigious award from the Space Medicine Association, a member organization of the Aerospace Medical Association. On October 1, 2013, in the aftermath of a "Wall Street Journal" article published on December 1, 2012, which highlighted his connection to human experiments during WW2, the Space Medicine Association's Executive Committee announced that the Space Medicine Association Strughold Award had been retired.  (see List of German rocket scientists in the US).

Operation Paperclip was a secret program of the Joint Intelligence Objectives Agency (JIOA) largely carried out by special agents of Army CIC, in which more than 1,600 German scientists, engineers, and technicians, such as Wernher von Braun and his V-2 rocket team, were taken from Germany to the United States, for U.S. government employment, primarily between 1945 and 1959. Many were former members, and some were former leaders, of the Nazi Party.

Operace Paperclip (nebo také projekt Paperclip) bylo krycí jméno amerického projektu, který měl za úkol převézt po konci druhé světové války z nacistického Německa do Spojených států německé vědce. Pro tento účel byla vytvořena i tzv. Joint Intelligence Objectives Agency, která spravovala dokumenty a informace o této operaci.


Life and career.

He began a military career in Finland, but soon moved to Russia to teach rational mechanics in Petersburg (now Saint Petersburg). He dedicated his life to mathematics and chess, two subjects which he considered closely related. He tried to show their connections in his work "Découvertes sur le cavalier (aux échecs)", published in Petersburg in 1837.  In 1842–43 he published a book on the openings in two volumes: "Analyse Nouvelle des ouvertures". In 1862–63 he published his major work: "Traité des applications de l'analyse mathématique au jeu des échecs", in three volumes.  He wanted to take part in the London 1851 chess tournament, but arrived late and instead played a match with Howard Staunton, which he lost +2–7=1. Three years later he also lost to Ilya Shumov (+3–5=4).

Legacy.

Jaenisch is best remembered for having analysed and helped develop Petrov's Defence with Alexander Petrov, and for his work on the Schliemann–Jaenisch Gambit of the Ruy Lopez, which begins 1.e4 e5 2.Nf3 Nc6 3.Bb5 f5!? The dubious gambit 1.c4 b5 is sometimes referred to as the Jaenisch Gambit; Jaenisch mentioned this move but did not advocate it.  Staunton was most upset at his death in 1872, writing to Tassilo von Heydebrand und der Lasa in November of that year: I was sorry to lose Lewis and St. Amant, my dear friends Bolton and Sir T. Madden, and others of whom we have been deprived, but for Jaenisch I entertained a particular affection, and his loss was proportionately painful to me. He was truly an amiable and an upright man.  After Jaenisch's death a scholarship fund in his honor, which survives to this day, was established by his sister.

Carl Ferdinand von Jaenisch (; Vyborg, April 11, 1813 – Saint Petersburg, March 7, 1872) was a Finnish and Russian chess player and theorist. In the 1840s, he was among the top players in the world.

Karl Ferdinand Andrejevič Jänisch, rusky Карл Андреевич Яниш (11. dubna 1813, Vyborg - 7. března 1872, Petrohrad) byl ruský šachový mistr a šachový skladatel finského původu.


Signs and symptoms.

Untreated PKU can lead to intellectual disability, seizures, behavioral problems, and mental disorders. It may also result in a musty smell and lighter skin. A baby born to a mother who has poorly treated PKU may have heart problems, a small head, and low birth weight.  Because the mother's body is able to break down phenylalanine during pregnancy, infants with PKU are normal at birth. The disease is not detectable by physical examination at that time, because no damage has yet been done. Newborn screening is performed to detect the disease and initiate treatment before any damage is done. The blood sample is usually taken by a heel prick, typically performed 2–7 days after birth. This test can reveal elevated phenylalanine levels after one or two days of normal infant feeding.  If a child is not diagnosed during the routine newborn screening test and a phenylalanine restricted diet is not introduced, then phenylalanine levels in the blood will increase over time. Toxic levels of phenylalanine (and insufficient levels of tyrosine) can interfere with infant development in ways which have permanent effects. The disease may present clinically with seizures, hypopigmentation (excessively fair hair and skin), and a "musty odor" to the baby's sweat and urine (due to phenylacetate, a carboxylic acid produced by the oxidation of phenylketone). In most cases, a repeat test should be done at approximately two weeks of age to verify the initial test and uncover any phenylketonuria that was initially missed.  Untreated children often fail to attain early developmental milestones, develop microcephaly, and demonstrate progressive impairment of cerebral function. Hyperactivity, EEG abnormalities, and seizures, and severe learning disabilities are major clinical problems later in life. A characteristic "musty or mousy" odor on the skin, as well as a predisposition for eczema, persist throughout life in the absence of treatment.  The damage done to the brain if PKU is untreated during the first months of life is not reversible. It is critical to control the diet of infants with PKU very carefully so that the brain has an opportunity to develop normally. Affected children who are detected at birth and treated are much less likely to develop neurological problems or have seizures and intellectual disability (though such clinical disorders are still possible.)  In general, however, outcomes for people treated for PKU are good. Treated people may have no detectable physical, neurological, or developmental problems at all.

Genetics.

PKU is an autosomal recessive metabolic genetic disorder. As an autosomal recessive disorder, two PKU alleles are required for an individual to experience symptoms of the disease. For a child to inherit PKU, both the mother and father must have and pass on the defective gene. If both parents are carriers for PKU, there is a 25% chance any child they have will be born with the disorder, a 50% chance the child will be a carrier, and a 25% chance the child will neither develop nor be a carrier for the disease.  PKU is characterized by homozygous or compound heterozygous mutations in the gene for the hepatic enzyme phenylalanine hydroxylase (PAH), rendering it nonfunctional. This enzyme is necessary to metabolize the amino acid phenylalanine (Phe) to the amino acid tyrosine (Tyr). When PAH activity is reduced, phenylalanine accumulates and is converted into phenylpyruvate (also known as phenylketone), which can be detected in the urine.  Carriers of a single PKU allele do not exhibit symptoms of the disease but appear to be protected to some extent against the fungal toxin ochratoxin A. This accounts for the persistence of the allele in certain populations in that it confers a selective advantage—in other words, being a heterozygote is advantageous.  The PAH gene is located on chromosome 12 in the bands 12q22-q24.2. As of 2000, around 400 disease-causing mutations had been found in the PAH gene. This is an example of allelic genetic heterogeneity.

Pathophysiology.

When Phe cannot be metabolized by the body, a typical diet that would be healthy for people without PKU causes abnormally high levels of Phe to accumulate in the blood, which is toxic to the brain. If left untreated, complications of PKU include severe intellectual disability, brain function abnormalities, microcephaly, mood disorders, irregular motor functioning, and behavioral problems such as attention deficit hyperactivity disorder, as well as physical symptoms such as a "musty" odor, eczema, and unusually light skin and hair coloration.

Classical PKU.

Classical PKU, and its less severe forms "mild PKU" and "mild hyperphenylalaninemia" are caused by a mutated gene for the enzyme phenylalanine hydroxylase (PAH), which converts the amino acid phenylalanine ("Phe") to other essential compounds in the body, in particular tyrosine. Tyrosine is a conditionally essential amino acid for PKU patients because without PAH it cannot be produced in the body through the breakdown of phenylalanine. Tyrosine is necessary for the production of neurotransmitters like epinephrine, norepinephrine, and dopamine.  PAH deficiency causes a spectrum of disorders, including classic phenylketonuria (PKU) and mild hyperphenylalaninemia (also known as "hyperphe" or "mild HPA"), a less severe accumulation of phenylalanine. Compared to classic PKU patients, patients with "hyperphe" have greater PAH enzyme activity and are able to tolerate larger amounts of phenylalanine in their diets. Without dietary intervention, mild HPA patients have blood Phe levels higher than those with normal PAH activity. There is currently no international consensus on the definition of mild HPA, however it is most frequently diagnosed at blood Phe levels between 2-6 mg/dL.  Phenylalanine is a large, neutral amino acid (LNAA). LNAAs compete for transport across the blood–brain barrier (BBB) via the large neutral amino acid transporter (LNAAT). If phenylalanine is in excess in the blood, it will saturate the transporter. Excessive levels of phenylalanine tend to decrease the levels of other LNAAs in the brain. As these amino acids are necessary for protein and neurotransmitter synthesis, Phe buildup hinders the development of the brain, causing intellectual disability.  Recent research suggests that neurocognitive, psychosocial, quality of life, growth, nutrition, bone pathology are slightly suboptimal even for patients who are treated and maintain their Phe levels in the target range, if their diet is not supplemented with other amino acids.  Classic PKU affects myelination and white matter tracts in untreated infants; this may be one major causse of neurological problems associated with phenylketonuria. Differences in white matter development are observable with magnetic resonance imaging. Abnormalities in gray matter can also be detected, particularly in the motor and pre-motor cortex, thalamus and the hippocampus.  It was recently suggested that PKU may resemble amyloid diseases, such as Alzheimer's disease and Parkinson's disease, due to the formation of toxic amyloid-like assemblies of phenylalanine.  Other non-PAH mutations can also cause PKU.

Tetrahydrobiopterin-deficient hyperphenylalaninemia.

A rarer form of hyperphenylalaninemia is tetrahydrobiopterin deficiency, which occurs when the PAH enzyme is normal, and a defect is found in the biosynthesis or recycling of the cofactor tetrahydrobiopterin (BH). BH is necessary for proper activity of the enzyme PAH, and this coenzyme can be supplemented as treatment. Those who suffer from this form of hyperphenylalaninemia may have a deficiency of tyrosine (which is created from phenylalanine by PAH), in which case treatment is supplementation of tyrosine to account for this deficiency.  Levels of dopamine can be used to distinguish between these two types. Tetrahydrobiopterin is required to convert Phe to Tyr and is required to convert Tyr to L-DOPA via the enzyme tyrosine hydroxylase. L-DOPA, in turn, is converted to dopamine. Low levels of dopamine lead to high levels of prolactin. By contrast, in classical PKU (without dihydrobiopterin involvement), prolactin levels would be relatively normal.  Tetrahydrobiopterin deficiency can be caused by defects in four genes. They are known as HPABH4A, HPABH4B, HPABH4C, and HPABH4D.

Metabolic pathways.

The enzyme phenylalanine hydroxylase normally converts the amino acid phenylalanine into the amino acid tyrosine. If this reaction does not take place, phenylalanine accumulates and tyrosine is deficient. Excessive phenylalanine can be metabolized into phenylketones through the minor route, a transaminase pathway with glutamate. Metabolites include phenylacetate, phenylpyruvate and phenethylamine. Elevated levels of phenylalanine in the blood and detection of phenylketones in the urine is diagnostic, however most patients are diagnosed via newborn screening.

Screening.

PKU is commonly included in the newborn screening panel of many countries, with varied detection techniques. Most babies in developed countries are screened for PKU soon after birth. Screening for PKU is done with bacterial inhibition assay (Guthrie test), immunoassays using fluorometric or photometric detection, or amino acid measurement using tandem mass spectrometry (MS/MS). Measurements done using MS/MS determine the concentration of Phe and the ratio of Phe to tyrosine, the ratio will be elevated in PKU.

Treatment.

PKU is not curable. However, if PKU is diagnosed early enough, an affected newborn can grow up with normal brain development by managing and controlling phenylalanine ("Phe") levels through diet, or a combination of diet and medication.

Diet.

People who follow the prescribed dietary treatment from birth may have no symptoms. Their PKU would be detectable only by a blood test. People must adhere to a special diet low in Phe for optimal brain development. Since Phe is necessary for the synthesis of many proteins, it is required for appropriate growth, but levels must be strictly controlled.  For people who do not have phenylketonuria, the U.S. Institute of Medicine set recommended at least 33 mg/kg body weight/day phenylalanine plus tyrosine for adults 19 years and older. For people with PKU, a recommendation for children up to age 10 years is 200 to 500 mg/d; for older children and adults 220 to 1200 mg/day. Where in the range depends on body weight and age, and on monitoring blood concentration.  Optimal health ranges (or "target ranges") are between 120 and 360 μmol/L or equivalently 2 to 6 mg/dL, and aimed to be achieved during at least the first 10 years, to allow the brain to develop normally.  The age at which people with PKU may safely go off diet is subject to some debate. The diet should be maintained at least until the age of eight or ten. Some evidence supports discontinued after 10 years as a normal diet after that does not appear to have negative effects. One study however has shown temporarily detrimental effects when off the diet. There is no evidence for permanent brain damage in people who have gone off diet in adulthood. In case of mild neurocognitive impairment, the re-introduction of diet is indicated.  The diet requires restricting or eliminating foods high in Phe, such as soybeans, egg whites, shrimp, chicken breast, spirulina, watercress, fish, nuts, crayfish, lobster, tuna, turkey, legumes, and lowfat cottage cheese. Starchy foods, such as potatoes and corn are generally acceptable in controlled amounts, but the quantity of Phe consumed from these foods must be monitored. A food diary is usually kept to record the amount of Phe consumed with each meal, snack, or drink. An "exchange" system can be used to calculate the amount of Phe in a food from the protein content identified on a nutritional information label. Lower-protein "medical food" substitutes are often used in place of normal bread, pasta, and other grain-based foods, which contain a significant amount of Phe. Many fruits and vegetables are lower in Phe and can be eaten in larger quantities. Infants may still be breastfed to provide all of the benefits of breastmilk, but the quantity must also be monitored and supplementation for missing nutrients will be required. The sweetener aspartame, present in many diet foods and soft drinks, must also be avoided, as aspartame is metabolised into phenylalanine.  Different people can tolerate different amounts of Phe in their diet. Regular blood tests are used to determine the effects of dietary Phe intake on blood Phe level.

Nutritional supplements.

Supplementary "protein substitute" formulas are typically prescribed for people PKU (starting in infancy) to provide the amino acids and other necessary nutrients that would otherwise be lacking in a low-phenylalanine diet. Tyrosine, which is normally derived from phenylalanine and which is necessary for normal brain function, is usually supplemented. Consumption of the protein substitute formulas can actually reduce phenylalanine levels, probably because it stops the process of protein catabolism from releasing Phe stored in the muscles and other tissues into the blood. Many PKU patients have their highest Phe levels after a period of fasting (such as overnight), because fasting triggers catabolism. A diet that is low in phenylalanine but does not include protein substitutes may also fail to lower blood Phe levels, since a nutritionally insufficient diet may also trigger catabolism. For all these reasons, the prescription formula is an important part of the treatment for patients with classic PKU.  Tentative evidence supports dietary supplementation with large neutral amino acids (LNAAs). The LNAAs (e.g. leu, tyr, trp, met, his, ile, val, thr) may compete with phe for specific carrier proteins that transport LNAAs across the intestinal mucosa into the blood and across the blood–brain barrier into the brain. Its use is really only indicated in adults who will not follow an appropriate diet.  Another interesting treatment strategy is casein glycomacropeptide (CGMP), which is a milk peptide naturally free of Phe in its pure form CGMP can substitute for the main part of the free amino acids in the PKU diet and provides several beneficial nutritional effects compared to free amino acids. The fact that CGMP is a peptide ensures that the absorption rate of its amino acids is prolonged compared to free amino acids and thereby results in improved protein retention and increased satiety compared to free amino acids. Another important benefit of CGMP is that the taste is significantly improved when CGMP substitutes part of the free amino acids and this may help ensure improved compliance to the PKU diet.  Furthermore, CGMP contains a high amount of the Phe-lowering LNAAs, which constitutes about 41 g per 100 g protein and will therefore help maintain plasma phe levels in the target range.

Enzyme substitutes.

In 2018, the FDA approved an enzyme substitute called pegvaliase which metabolizes phenylalanine. It is for adults who are poorly managed on other treatments.  Tetrahydrobiopterin (BH4) (a cofactor for the oxidation of phenylalanine) when taken by mouth can reduce blood levels of this amino acid in some people. Most people, however, with the "classical" sequence of mutations, will have little or no benefit.

Mothers.

For women with PKU, it is important for the health of their children to maintain low Phe levels before and during pregnancy. Though the developing fetus may only be a carrier of the PKU gene, the intrauterine environment can have very high levels of phenylalanine, which can cross the placenta. The child may develop congenital heart disease, growth retardation, microcephaly and intellectual disability as a result. PKU-affected women themselves are not at risk of additional complications during pregnancy.  In most countries, women with PKU who wish to have children are advised to lower their blood Phe levels (typically to between 2 and 6 mg/dL) before they become pregnant, and carefully control their levels throughout the pregnancy. This is achieved by performing regular blood tests and adhering very strictly to a diet, in general monitored on a day-to-day basis by a specialist metabolic dietitian. In many cases, as the fetus' liver begins to develop and produce PAH normally, the mother's blood Phe levels will drop, requiring an increased intake to remain within the safe range of 2–6 mg/dL. The mother's daily Phe intake may double or even triple by the end of the pregnancy, as a result. When maternal blood Phe levels fall below 2 mg/dL, anecdotal reports indicate that the mothers may suffer adverse effects, including headaches, nausea, hair loss, and general malaise. When low phenylalanine levels are maintained for the duration of pregnancy, there are no elevated levels of risk of birth defects compared with a baby born to a non-PKU mother.

Epidemiology.

The average number of new cases of PKU varies in different human populations. United States Caucasians are affected at a rate of 1 in 10,000. Turkey has the highest documented rate in the world, with 1 in 2,600 births, while countries such as Finland and Japan have extremely low rates with fewer than one case of PKU in 100,000 births. A 1987 study from Slovakia reports a Roma population with an extremely high incidence of PKU (one case in 40 births) due to extensive inbreeding. It is the most common amino acid metabolic problem in the United Kingdom.

History.

Before the causes of PKU were understood, PKU caused severe disability in most people who inherited the relevant mutations. Nobel and Pulitzer Prize winning author Pearl S. Buck had a daughter named Carol who lived with PKU before treatment was available, and wrote an account of its effects in a book called "The Child Who Never Grew." Many untreated PKU patients born before widespread newborn screening are still alive, largely in dependent living homes/institutions.  Phenylketonuria was discovered by the Norwegian physician Ivar Asbjørn Følling in 1934 when he noticed hyperphenylalaninemia (HPA) was associated with intellectual disability. In Norway, this disorder is known as Følling's disease, named after its discoverer. Følling was one of the first physicians to apply detailed chemical analysis to the study of disease.  In 1934 at Rikshospitalet, Følling saw a young woman named Borgny Egeland. She had two children, Liv and Dag, who had been normal at birth but subsequently developed intellectual disability. When Dag was about a year old, the mother noticed a strong smell to his urine. Følling obtained urine samples from the children and, after many tests, he found that the substance causing the odor in the urine was phenylpyruvic acid. The children, he concluded, had excess phenylpyruvic acid in the urine, the condition which came to be called phenylketonuria (PKU).  His careful analysis of the urine of the two affected siblings led him to request many physicians near Oslo to test the urine of other affected patients. This led to the discovery of the same substance he had found in eight other patients. He conducted tests and found reactions that gave rise to benzaldehyde and benzoic acid, which led him to conclude that the compound contained a benzene ring. Further testing showed the melting point to be the same as phenylpyruvic acid, which indicated that the substance was in the urine.  In 1954, Horst Bickel, Evelyn Hickmans and John Gerrard published a paper that described how they created a diet that was low in phenylalanine and the patient recovered. Bickel, Gerrard and Hickmans were awarded the John Scott Medal in 1962 for their discovery.  PKU was the first disorder to be routinely diagnosed through widespread newborn screening. Robert Guthrie introduced the newborn screening test for PKU in the early 1960s. With the knowledge that PKU could be detected before symptoms were evident, and treatment initiated, screening was quickly adopted around the world. Ireland was the first country to introduce a national screening programme in February 1966, Austria also started screening in 1966 and England in 1968.  In 2017 the European Guidelines were published. They were called for by the patient organizations such as the European Society for Phenylketonuria and Allied Disorders Treated as Phenylketonuria. They have received some critical reception.

Etymology and pronunciation.

The word "phenylketonuria" uses combining forms of "phenyl" + "ketone" + "-uria"; it is pronounced.

Research.

Other therapies are currently under investigation, including gene therapy.  Biomarin is currently conducting clinical trials to investigate PEG-PAL (PEGylated recombinant phenylalanine ammonia lyase or ‘PAL’) is an enzyme substitution therapy in which the missing PAH enzyme is replaced with an analogous enzyme that also breaks down Phe. PEG-PAL is now in Phase 2 clinical development.

Phenylketonuria (PKU) is an inborn error of metabolism that results in decreased metabolism of the amino acid phenylalanine. Untreated, PKU can lead to intellectual disability, seizures, behavioral problems, and mental disorders. It may also result in a musty smell and lighter skin. A baby born to a mother who has poorly treated PKU may have heart problems, a small head, and low birth weight. Phenylketonuria is a genetic disorder inherited from a person's parents. It is due to mutations in the "PAH" gene, which results in low levels of the enzyme phenylalanine hydroxylase. This results in the buildup of dietary phenylalanine to potentially toxic levels. It is autosomal recessive, meaning that both copies of the gene must be mutated for the condition to develop. There are two main types, classic PKU and variant PKU, depending on whether any enzyme function remains. Those with one copy of a mutated gene typically do not have symptoms. Many countries have newborn screening programs for the disease. Treatment is with a diet low in foods that contain phenylalanine and special supplements. Babies should use a special formula with a small amount of breast milk. The diet should begin as soon as possible after birth and be continued for life. People who are diagnosed early and maintain a strict diet can have normal health and a normal life span. Effectiveness is monitored through periodic blood tests. The medication sapropterin dihydrochloride may be useful in some. Phenylketonuria affects about 1 in 12,000 babies. Males and females are affected equally. The disease was discovered in 1934 by Ivar Asbjørn Følling, with the importance of diet determined in 1953. Gene therapy, while promising, requires a great deal more study as of 2014.

Fenylketonurie (PKU) někdy nazývaná jako Føllingova nemoc je dědičné metabolické onemocnění spočívající v poruše přeměny aminokyseliny fenylalaninu na tyrosin, jenž u zdravých lidí katalyzuje jaterní enzym fenylalaninhydroxyláza (PAH). Právě mutaci genu kódujícího tento enzym má největší procento pacientů s fenylketonurií. V České republice populační frekvence výskytu fenylketonurie odpovídá 1: 9 000.