Premise.

Dr. Mary Harris works at the emergency department of the Eden General Hospital and has a side business as an end of life counselor—she and her partner Des provide assisted suicide. Their lives get complicated when the police start investigating them.

Production.

The series, which was to comprise six episodes, was commissioned by TV network Global on January 28, 2016. Production began in summer 2016, and the first episode aired January 25, 2017. In the United States, the series was picked up by Lifetime on October 13, 2016. "Mary Kills People" premiered in the US on Lifetime on April 23, 2017.  As of January 23, 2017, there were talks to produce a second season according to Metro News and Caroline Dhavernas. On June 5, 2017, the series was renewed for a six-episode followup season. Production occurred over summer 2017 in Toronto. Lifetime announced their pickup of the second season in the United States on July 28, 2017; it premiered on March 12, 2018.  On December 3, 2018, it was announced that Lifetime would not air the final season. The series is slated to conclude production at the end of the third season.

Reception.

Critical response.

The first season has received a score of 66 on Metacritic, indicating generally favourable reviews, based on eight reviews, and a rating of 100% on review aggregate website Rotten Tomatoes based on eleven reviews for an average rating of 7.5/10, the site's critical consensus stating: ""Mary Kills People" is more than its unique premise, with a layered lead performance and consistently entertaining narrative keeping the show's dark comedy grounded in relatable reality." The second season also received 100% based on five reviews, for an average rating of 9.4/10.  John Doyle of "The Globe and Mail" called the first episode of the show "remarkably assured, droll and adult. It’s very smart and utterly intriguing." He praises Mary Harris as "one of the most compelling, original female characters in years" and Caroline Dhavernas as "exceptional" in her portrayal: "Perhaps the best thing about it is the crazy sparkle in Mary’s eyes. There is something anarchic bubbling inside her."  "Variety"'s Maureen Ryan said the show "pulls off a melding of tones — comedic, dramatic, and philosophical — that seems next to impossible," but criticized the first season's romance subplots.

Mary Kills People is a Canadian drama television series starring Caroline Dhavernas. It premiered on Global on January 25, 2017.

Mary Kills People je kanadský televizní seriál, který má dvě série po šesti dílech. Seriál měl premiéru v televizi Global 25. ledna 2017. Hlavní roli ztvárnila Caroline Dhavernas.


Māori arrival and settlement.

New Zealand was first settled by Polynesians from Eastern Polynesia. Genetic and archaeological evidence suggests that humans emigrated from Taiwan via southeast Asia to Melanesia and then radiated eastwards into the Pacific in pulses and waves of discovery which gradually colonised islands from Samoa and Tonga all the way to Hawaii, the Marquesas, Easter Island, the Society Islands and, finally, New Zealand.  In New Zealand, there are no human artifacts or remains dating earlier than the Kaharoa Tephra, a layer of volcanic debris deposited by the Mt Tarawera eruption around 1314 CE. The 1999 dating of some kiore (Polynesian rat) bones to as early as 100 CE was later found to be an error; new samples of rat bone (and also of rat-gnawed shells and woody seed cases) mostly gave dates later than the Tarawera eruption with only three samples giving slightly earlier dates.  Pollen evidence of widespread forest fires a decade or two before the eruptions has been interpreted by some scientists as a possible sign of human presence, leading to a suggested first settlement period of 1280–1320 CE. However, the most recent synthesis of archaeological and genetic evidence, concludes that, whether or not some settlers arrived before the Tarawera eruption, the main settlement period was in the decades after it, somewhere between 1320 and 1350 CE, possibly involving a coordinated mass migration. This scenario is also supported by a much debated, and now largely ignored, third line of evidence – traditional genealogies which point to 1350 AD as a probable arrival date for the main founding canoes from which most Māori trace

Early contact periods.

Early European exploration.

The first Europeans known to reach New Zealand were the crew of Dutch explorer Abel Tasman who arrived in his ships "Heemskerck" and "Zeehaen". Tasman anchored at the northern end of the South Island in Golden Bay (he named it Murderers' Bay) in December 1642 and sailed northward to Tonga following an attack by local Māori. Tasman sketched sections of the two main islands' west coasts. Tasman called them "Staten Landt", after the "States General of the Netherlands", and that name appeared on his first maps of the country. In 1645 Dutch cartographers changed the name to "Nova Zeelandia" in Latin, from "Nieuw Zeeland", after the Dutch province of "Zeeland".  Over 100 years elapsed before Europeans returned to New Zealand; in 1769, British naval captain James Cook of HM Bark "Endeavour" visited New Zealand, and coincidentally, only two months later, Frenchman Jean-François-Marie de Surville, in command of his own expedition, reached the country. When Cook left on his first voyage,

Early European settlement.

European (Pākehā) settlement increased through the early decades of the 19th century, with numerous trading stations established, especially in the North Island. Christianity was introduced to New Zealand in 1814 by Samuel Marsden, who travelled to the Bay of Islands where he founded a mission station on behalf of the Church of England's Church Missionary Society. By 1840 over 20 stations had been established. From missionaries, the Māori learnt not just about Christianity but also about European farming practices and trades, and how to read and write. Building on the work

Māori response.

The effect of contact on Māori varied. In some inland areas life went on more or less unchanged, although a European metal tool such as a fish-hook or hand axe might be acquired through trade with other tribes. At the other end of the scale, tribes that frequently encountered Europeans, such as Ngāpuhi in Northland, underwent major changes.  Pre-European Māori had no distance weapons except for tao (spears) and the introduction of the musket had an enormous impact on Māori warfare. Tribes with muskets would attack tribes without them, killing or enslaving many. As a result,

Colonial period.

In 1788 the Colony of New South Wales had been founded. According to the future Governor, Captain Arthur Phillip's amended Commission, dated 25 April 1787 the colony of New South Wales included "all the islands adjacent in the Pacific Ocean within the latitudes of 10°37'S and 43°39'S" which included most of New Zealand except for the southern half of the South Island. In 1825 with Van Diemen's Land becoming a separate colony, the southern boundary of New South Wales was altered to the islands adjacent in the Pacific Ocean with a southern boundary of 39°12'S which included only the northern half of the North Island. However, these boundaries had no real impact as the New South Wales administration had little interest in New Zealand.  New Zealand was first mentioned in British statute in the Murders Abroad Act 1817. It made it easier for a court to punish "murders or manslaughters committed in places not within His Majesty's dominions", and the Governor of New South Wales was given increased legal authority over New Zealand. The jurisdiction of the Supreme Court of New South Wales over New Zealand was initiated in the New South Wales Act 1823, and lesser offences were included at that time. In response to complaints from missionaries, and a petition from Māori chiefs calling for King William IV to be a "friend and guardian" of New Zealand about lawless sailors and adventurers in New Zealand, the British Government appointed James Busby as British Resident in 1832. In 1834 he encouraged Māori chiefs to assert their sovereignty with the signing of the Declaration of Independence ("") in 1835. The declaration was sent to King William IV and was recognised by Britain. Busby was provided with neither legal authority nor military support and was thus ineffective in controlling the European population.

Treaty of Waitangi.

In 1839 the New Zealand Company announced plans to buy large tracts of land and to establish colonies in New Zealand. This and the increased commercial interests of merchants in Sydney and London spurred the British Government to take stronger action. Captain William Hobson was sent to New Zealand by the British government with instructions to persuade Māori to cede their sovereignty to the British Crown. In reaction to the New Zealand Company's moves, on 15 June 1839 the issue of new Letters Patent expanded the territory of New South Wales to include all of New Zealand. Governor of New South Wales George Gipps was appointed Governor over New Zealand. This represented the first clear expression of British intent to annex New Zealand.  On 6 February 1840, Hobson and about forty Māori chiefs signed the Treaty of Waitangi at Waitangi in the Bay of Islands. The British subsequently took copies of the Treaty around the islands of New Zealand for signature by other chiefs. A significant number refused to sign or were not

Establishing the colony.

At first New Zealand was administered from Australia as part of the colony of New South Wales, and from 16 June 1840 New South Wales laws were deemed to operate in New Zealand. However, this was a transitional arrangement and on 1 July 1841 New Zealand became a colony in its own right.  Settlement continued under British plans, inspired by a vision of New Zealand as a new land of opportunity. In 1846, the British Parliament passed the New Zealand Constitution Act 1846 for self-government for the 13,000 settlers in New

New Zealand Company.

The New Zealand Company was responsible for 15,500 settlers coming to New Zealand. Company prospectuses did not always tell the truth, and often colonists would only find out the reality once they had arrived in New Zealand. This private colonisation project was part of the reason that the British Colonial Office decided to speed up its plans for the annexation of New Zealand.

New Zealand Wars.

Māori had welcomed Pākehā for the trading opportunities and guns they brought. However it soon became clear that they had underestimated the number of settlers that would arrive in their lands. "Iwi" (tribes) whose land was the base of the main settlements quickly lost much of their land and autonomy through government acts. Others prospered – until about 1860 the city of Auckland bought most of its food from Māori who grew and sold it themselves. Many "iwi" owned flour mills, ships and other items of European technology, some exported food to Australia

Self-government, 1850s.

In response to increased petitioning for self-governance from the growing number of British settlers, the British Parliament passed the New Zealand Constitution Act 1852, setting up a central government with an elected General Assembly (Parliament) and six provincial governments. The General Assembly did not meet until 24 May

Farming and mining.

The Māori tribes at first sold the land to the settlers, but the government voided the sales in 1840. Now only the government was allowed to purchase land from Māori, who received cash. The government bought practically all the useful land, then resold it to the New Zealand Company, which promoted immigration, or leased it for sheep runs. The Company resold the best tracts to British settlers; its profits were used to pay the travel of the immigrants from Britain.  Because of the vast distances involved, the first settlers were self-sufficient farmers. By the 1840s, however, large scale sheep stations were exporting large quantities of wool to the textile mills of England. Most of the early settlers were brought over by a programme operated by the New Zealand Company and were located in the central region on either side of Cook Strait, and at Wellington, Wanganui, New Plymouth and Nelson. These settlements had access to some of the richest plains in the country and after refrigerated ships appeared in 1882, they developed into closely settled regions of small-scale farming. Outside these compact settlements

Vogel era.

In 1870 Julius Vogel introduced his "grand go-ahead policy" to dispel the slump with increased immigration and overseas borrowing to fund new railways, roads and telegraph lines. Local banks – notably the Bank of New Zealand and the Colonial Bank of New Zealand — were "reckless" and permitted

Women.

Although norms of masculinity were dominant, strong minded women originated a feminist movement starting in the 1860s, well before women gained the right to vote in 1893. Middle-class women employed the media (especially newspapers) to communicate with each other and define their priorities. Prominent feminist writers included Mary Taylor, Mary Colclough (pseud. Polly Plum), and Ellen Ellis. The first signs of a politicised collective female identity came in crusades to pass the Contagious Diseases Prevention Act.  Feminists by the 1880s were using the rhetoric of "white slavery" to reveal men's sexual and social oppression of women. By demanding that men take responsibility for the right of women to walk the streets in safety, New Zealand feminists deployed

Schools.

Prior to 1877 schools were operated by the provincial government, churches, or by private subscription. Education was not a requirement and many children did not attend any school, especially farm children whose

Immigration.

From 1840 there was considerable European settlement, primarily from England and Wales, Scotland and Ireland; and to a lesser extent the United States, India, China, and various parts of continental Europe, including the province of Dalmatia in what is now Croatia, and Bohemia in what is now the Czech Republic. Already a majority

Gold Rush and South Island growth.

In 1861 gold was discovered at Gabriel's Gully in Central Otago, sparking a gold rush. Dunedin became the wealthiest city in the country and many in the South Island resented financing the North Island's wars. In 1865 Parliament defeated a proposal to make the South Island independent by 17 to 31.  The South Island was home to most of the Pākehā population until around 1911 when the North

1890–1914.

Politics.

The pre-war era saw the advent of party politics, with the establishment of the Liberal Government. The landed gentry and aristocracy ruled Britain at this time. New Zealand never had an aristocracy but it did have wealthy landowners who largely controlled politics before 1891. The Liberal Party set out to change that by a policy it called "populism". Richard Seddon had proclaimed the goal as early as 1884: "It is the rich and the poor; it is the wealthy and the landowners against the middle and labouring classes. That, Sir, shows the real political position of New Zealand." The Liberal strategy was to create a large class of small land-owning farmers who supported Liberal ideals.  To obtain land for farmers the Liberal government from 1891 to 1911 purchased 3.1 million acres of Māori land. The government also purchased 1.3 million acres from large estate holders for subdivision and closer settlement by small farmers. The Advances to Settlers

Economic developments.

In the 1870s Julius Vogel's "grand go-ahead policy" of borrowing overseas had increased the public debt from £7.8 million in 1870 to £18.6 million in 1876, but had constructed many miles of railways, roads and telegraph lines and attracted many new migrants.  In the 1880s, New Zealand's economy grew from one based on wool and local trade to the export of wool, cheese, butter and frozen beef and mutton to Britain. The change was enabled by the invention of refrigerated steamships in 1882 and a result of the large market demands overseas. In order to increase production, alongside a more intensive use

Dominion and Realm.

New Zealand initially expressed interest in joining the proposed Federation of the Australian colonies, attending the 1891 National Australia Convention in Sydney. Interest in the proposed Australian Federation faded and New Zealand decided against joining the Commonwealth of Australia in 1901. New Zealand instead changed from being a colony to a separate "Dominion" in 1907, equal in status to Australia and Canada. Dominion status was a public mark of the self-governance that had evolved over half a century through responsible government. Just under one million people lived in New Zealand in 1907 and cities such as Auckland and Wellington were growing rapidly.

Temperance and prohibition.

In New Zealand, prohibition was a moralistic reform movement begun in the mid-1880s by the Protestant evangelical and Nonconformist churches and the Woman's Christian Temperance Union and after 1890 by the Prohibition League. It never achieved its goal of national prohibition. It was a middle-class movement which accepted the existing economic and social order; the effort to legislate morality assumed that individual redemption was all that was needed to carry the colony forward from a pioneering society to a more mature one. However, both

First World War.

The country remained an enthusiastic member of the British Empire. 4 August is the date the outbreak of World War I is marked in New Zealand. During the war, more than 120,000 New Zealanders enlisted to the New Zealand Expeditionary Force, and around 100,000 served overseas; 18,000 died and about 41,000 men were listed as wounded. Conscription had been in force since 1909, and while it was opposed in peacetime there was less opposition during the war. The labour movement was pacifistic, opposed the war, and alleged that the rich were

Imperial loyalties.

After the war New Zealand signed the Treaty of Versailles (1919), joined the League of Nations and pursued an independent foreign policy, while its defence was still controlled by Britain. New Zealand depended on Britain's Royal Navy for its military security during the 1920s and 1930s. Officials in Wellington trusted Conservative Party governments in London, but not Labour. When the British Labour Party took power in 1924 and 1929, the New Zealand government felt threatened by Labour's foreign policy because of

Labour movement.

The Labour Party emerged as a force in 1919 with a socialist platform. It won about 25% of the vote. However its appeals to working class solidarity were not effective because a large fraction of the working class voted for conservative candidates of the Liberal and Reform parties. (They merged in 1936 to form

Great Depression.

Like many other countries, New Zealand suffered in the Great Depression of the 1930s, which affected the country via its international trade, with steep decreases in farm exports subsequently affecting the money supply and in turn consumption, investment and imports. The country was most affected around 1930–1932, when average farm incomes for a short time dipped below zero, and the unemployment rate peaked. Though actual unemployment numbers were not officially counted, the country was affected especially strongly in the North Island.  Unlike in later years, there were

Building the welfare state.

Attempts by the United-Reform Coalition to deal with the situation with spending cuts and relief work were ineffective and unpopular. In 1935, the First Labour Government was elected, and the post-depression decade showed that average Labour support in New Zealand had roughly doubled comparable to pre-depression times. By 1935 economic conditions had improved somewhat, and the new government had more positive financial conditions. Prime Minister Michael Joseph Savage proclaimed that: "Social Justice must be the guiding principle and economic organization must adapt itself to social needs."  The new government quickly set about implementing a number of

1930s foreign policy.

In foreign policy, the Labour Party in power after 1935 disliked the Versailles Treaty of 1919 as too harsh on Germany, opposed militarism and arms build-ups, distrusted the political conservatism of the National Government in Britain, sympathized with the Soviet Union, and increasingly worried about threats from Japan. It denounced Italy's role in Ethiopia and sympathized with the republican forces

Second World War.

When war broke out in 1939, New Zealanders saw their proper role as defending their proud place in the British Empire. It contributed some 120,000 troops. They mostly fought in North Africa, Greece/Crete, and Italy, relying on the Royal Navy and later the United States to protect New Zealand from the Japanese forces. Japan had no interest in New Zealand in the first place; it had already over-reached when it invaded New Guinea in 1942. (There were a few highly publicised but ineffective Japanese scouting incursions.) The 3rd New Zealand Division fought in the Solomons in 1943–44, but New Zealand's limited manpower meant 2 Divisions could not be maintained, and it was disbanded and its men returned to civilian life or used to reinforce the 2nd Division in Italy. The armed forces peaked at 157,000 in September 1942;

Post-war era.

Labour to National.

Labour remained in power after the Second World War and in 1945, Labour Prime Minister Peter Fraser played an important role in the establishment of the United Nations, of which New Zealand was a founding member. However, domestically Labour had lost the reforming zeal of the 1930s and its electoral support ebbed after the war. After Labour lost power

The British connection.

Fedorowich and Bridge argue that the demands of the Second World War produced long-term consequences for New Zealand's relationship with the government in London. The key component was the office of the high commissioner. By 1950 it was the main line of communications between the British and New Zealand governments.  1950s New Zealand culture was deeply British and conservative, with the concept of "fairness" holding a central role. New immigrants, still mainly British, flooded in while New Zealand remained prosperous by exporting farm products to Britain. In 1953 New Zealanders took pride that a countryman, Edmund Hillary, gave Queen Elizabeth II a

Māori urbanisation.

Māori always had a high birth rate; that was neutralised by a high death rate until modern public health measures became effective in the 20th century when tuberculosis deaths and infant mortality declined sharply. Life expectancy grew from 49 years in 1926 to 60 years in 1961 and the total numbers grew rapidly. Many Māori served in the Second World War and learned how to cope in the modern urban world; others moved from their rural homes to the cities to take up jobs vacated by Pākehā servicemen. The shift to the cities was also caused by their strong birth rates in the early 20th century, with the existing rural farms

The Muldoon years, 1975–1984.

The country's economy suffered in the aftermath of the 1973 global energy crisis, the loss of New Zealand's biggest export market upon Britain's entry to the European Economic Community, and rampant inflation. Robert Muldoon, Prime Minister from 1975 to 1984, and his Third National Government responded to the crises of the 1970s by attempting to preserve the New Zealand of the 1950s. He attempted to maintain New Zealand's "cradle to the grave" welfare state, which dated to 1935. His government sought to give retirees 80% of the

The radical 1980s reforms.

In 1984, the Fourth Labour Government, led by David Lange, was elected amid a constitutional and economic crisis. The crisis led the incoming government to review New Zealand's constitutional structures, which resulted in the Constitution Act 1986. In power from 1984 to 1990, the Labour government launched a major policy of restructuring the economy, radically reducing the role of government. A political scientist reports: "Between 1984 and 1993, New Zealand underwent radical economic reform, moving from what had probably been the most protected, regulated and state-dominated system of any capitalist democracy to an extreme position at the open, competitive, free-market end of the spectrum." The economic reforms were led by finance minister Roger Douglas (1984–1988). Dubbed Rogernomics, it was a rapid programme of deregulation and public-asset sales. Subsidies were phased out to farmers and consumers. High finance was partly deregulated. Restrictions on foreign exchange were relaxed and the dollar was allowed to float and seek its natural level on the world market. The tax on high incomes was cut in

Continuing reform under National.

Voters unhappy with the rapid speed and far-reaching extent of reforms elected a National government in 1990, led by Jim Bolger. However the new government continued the economic reforms of the previous Labour government, in what was known as Ruthanasia. Unhappy with what seemed to be a pattern of governments failing to reflect the mood of the electorate, New Zealanders

21st century.

In the 21st century, international tourism is a major contributor to the New Zealand economy, and the service sector more generally has grown. Meanwhile, the traditional agricultural exports of meat, dairy and wool have been supplemented by other products such as fruit, wine and timber as the economy has diversified.

2000s and 2010s.

The Fifth Labour Government led by Helen Clark was formed following the December 1999 election. In power for nine years, it maintained most of the previous governments' economic reforms – restricting government intervention in the economy much more so than previous governments – while putting more of an emphasis on social policy and outcomes. For example, employment law was modified to give more protection to workers, and the student loan system was changed to eliminate interest payments for New Zealand resident students and graduates.  New Zealand retains strong but informal links to Britain, with many young New Zealanders travelling to Britain for their "OE" (overseas experience) due to favourable working visa arrangements with Britain. Despite New Zealand's immigration liberalisation in the 1980s, Britons are still the largest group of migrants to New Zealand, due in part to recent immigration law changes which privilege fluent speakers of English. One constitutional link to Britain remains – New Zealand's head of state, the Queen in Right of New Zealand, is a British resident. However, British imperial honours were discontinued in 1996, the governor-general has taken a more active role in representing New Zealand overseas, and appeals from

2020s.

The COVID-19 pandemic, which had originated in Wuhan, China, sometime late 2019, has seriously affected New Zealand. In March 2020, borders and entry ports of New Zealand were closed to all

The history of New Zealand dates back approximately 700 years to when it was discovered and settled by Polynesians, who developed a distinct Māori culture. Like other Pacific cultures, Māori society was centred on kinship links and connection with the land but, unlike them, it was adapted to a cool, temperate environment rather than a warm, tropical one.

Dějiny Nového Zélandu jsou dějinami státu Nový Zéland, který vznikl roku 1907, a dějinami území tohoto státu před jeho vznikem. Nový Zéland je geograficky souostrovím především dvou velkých ostrovů, Severního a Jižního, plus asi 600 malých ostrůvků.


Career.

Frans Zimmer was raised in Berlin's Kreuzberg district, where he lives and works today. After high school, Zimmer wanted to study art, but was not admitted to university. In the following years, he worked various odd jobs, including work as a confectioner in a Berlin café. In 2010, he began DJing in Berlin nightclubs and bars. Inspired by the artist Friedensreich Hundertwasser, he took the alias "Hundert Farben" (meaning Hundred Colours), which he later changed to his current stage name "Alle Farben" (meaning All Colours)  On May 9, 2012, he played for 30,000 people at the former Tempelhof Airport in Berlin. Since then, Zimmer DJs almost every weekend throughout Europe; he also played several shows in Tel Aviv.  In September 2013, Zimmer announced through his Facebook page that he had begun work on his debut album and in January 2014 in an interview with the German newspaper "Die Tageszeitung" he confirmed the album would be ready in a few months. On April 15, 2014, Alle Farben released "She Moves (Far Away)" featuring the vocals of Graham Candy as a prerelease and the album's debut single. The album, entitled "Synesthesia – I Think in Colours" as per the official cover and the iTunes download page (with some media outlets opting to use the shorter term "Synesthesia" album in their coverage of the release), was released on 25 May 2014 in Europe through Kallias record label and Sony Music. Its 15 tracks include collaborations with Graham Candy and Lydmor (on two songs apiece) and Sway Clarke II (on one). It also includes two bonus remixes "She Moves" by Bakermat and Goldfish. In 2019, Farben collaborated with James Blunt on the single and music video "Walk Away".

Discography.

Singles.

As featured artist.

Others

Frans Zimmer (born June 5, 1985), better known by his stage name Alle Farben (meaning "All Colours" in German) is a German DJ and producer. Since 2014 Zimmer is signed to the record label Guesstimate/b1 Recordings and the publishing house Budde Music.

Alle Farben (* 5. června 1985), vlastním jménem Frans Zimmer, lépe známý pod svým pseudonymem Alle Farben (německy "všechny barvy") je německý DJ. Od roku 2014 má smlouvu s náhravací společností Guesstimate/b1 Recordings.


Structure and mechanism.

Many membrane receptors are transmembrane proteins. There are various kinds, including glycoproteins and lipoproteins. Hundreds of different receptors are known and many more have yet to be studied. Transmembrane receptors are typically classified based on their tertiary (three-dimensional) structure. If the three-dimensional structure is unknown, they can be classified based on membrane topology. In the simplest receptors, polypeptide chains cross the lipid bilayer once, while others, such as the G-protein coupled receptors, cross as many as seven times. Each cell membrane can have several kinds of membrane receptors, with varying surface distributions. A single receptor may also be differently distributed at different membrane positions, depending on the sort of membrane and cellular function. Receptors are often clustered on the membrane surface, rather than evenly distributed.

Mechanism.

Two models have been proposed to explain transmembrane receptors' mechanism of action.

Domains.

Transmembrane receptors in plasma membrane can usually be divided into three parts.

Extracellular domains.

The extracellular domain just externally from the cell or organelle. If the polypeptide chain crosses the bilayer several times, the external domain comprises loops entwined through the membrane. By definition, a receptor's main function is to recognize and respond to a type of ligand. For example, a neurotransmitter, hormone, or atomic ions may each bind to the extracellular domain as a ligand coupled to receptor. Klotho is an enzyme which effects a receptor to recognize the ligand (FGF23).

Transmembrane domains.

Two most abundant classes of transmembrane receptors are GPCR and single-pass transmembrane proteins. In some receptors, such as the nicotinic acetylcholine receptor, the transmembrane domain forms a protein pore through the membrane, or around the ion channel. Upon activation of an extracellular domain by binding of the appropriate ligand, the pore becomes accessible to ions, which then diffuse. In other receptors, the transmembrane domains undergo a conformational change upon binding, which effects intracellular conditions. In some receptors, such as members of the 7TM superfamily, the transmembrane domain includes a ligand binding pocket.

Intracellular domains.

The intracellular (or cytoplasmic) domain of the receptor interacts with the interior of the cell or organelle, relaying the signal. There are two fundamental paths for this interaction:

Signal transduction.

Signal transduction processes through membrane receptors involve the external reactions, in which the ligand binds to a membrane receptor, and the internal reactions, in which intracellular response is triggered.  Signal transduction through membrane receptors requires four parts:  Membrane receptors are mainly divided by structure and function into 3 classes: The ion channel linked receptor; The enzyme-linked receptor; and The G protein-coupled receptor.

Ion channel-linked receptor.

During the signal transduction event in a neuron, the neurotransmitter binds to the receptor and alters the conformation of the protein. This opens the ion channel, allowing extracellular ions into the cell. Ion permeability of the plasma membrane is altered, and this transforms the extracellular chemical signal into an intracellular electric signal which alters the cell excitability.  Acetylcholine receptor is a receptor linked to a cation channel. The protein consists of 4 subunits: α, β, γ, and δ subunits. There are two α subunits, with one acetylcholine binding site each. This receptor can exist in three conformations. The closed and unoccupied state is the native protein conformation. As two molecules of acetylcholine both bind to the binding sites on α subunits, the conformation of the receptor is altered and the gate is opened, allowing for the entry of many ions and small molecules. However, this open and occupied state only lasts for a minor duration and then the gate is closed, becoming the closed and occupied state. The two molecules of acetylcholine will soon dissociate from the receptor, returning it to the native closed and unoccupied state.

Enzyme-linked receptors.

As of 2009, there are 6 known types of enzyme-linked receptors: Receptor tyrosine kinases; Tyrosine kinase associated receptors; Receptor-like tyrosine phosphatases; Receptor serine/threonine kinases; Receptor guanylyl cyclases and histidine kinase associated receptors. Receptor tyrosine kinases have the largest population and widest application. The majority of these molecules are receptors for growth factors such as epidermal growth factor (EGF), platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), hepatocyte growth factor (HGF), nerve growth factor (NGF) and hormones such as insulin. Most of these receptors will dimerize after binding with their ligands, in order to activate further signal transductions. For example, after the epidermal growth factor (EGF) receptor binds with its ligand EGF, the two receptors dimerize and then undergo phosphorylation of the tyrosine residues in the enzyme portion of each receptor molecule. This will activate the tyrosine kinase and catalyze further intracellular reactions.

G protein-coupled receptors.

G protein-coupled receptors comprise a large protein family of transmembrane receptors. They are found only in eukaryotes. The ligands which bind and activate these receptors include: photosensitive compounds, odors, pheromones, hormones, and neurotransmitters. These vary in size from small molecules to peptides and large proteins. G protein-coupled receptors are involved in many diseases, and thus are the targets of many modern medicinal drugs.  There are two principal signal transduction pathways involving the G-protein coupled receptors: the cAMP signaling pathway and the phosphatidylinositol signaling pathway. Both are mediated via G protein activation. The G-protein is a trimeric protein, with three subunits designated as α, β, and γ. In response to receptor activation, the α subunit releases bound guanosine diphosphate (GDP), which is displaced by guanosine triphosphate (GTP), thus activating the α subunit, which then dissociates from the β and γ subunits. The activated α subunit can further affect intracellular signaling proteins or target functional proteins directly.

Membrane receptor-related disease.

If the membrane receptors are denatured or deficient, the signal transduction can be hindered and cause diseases. Some diseases are caused by disorders of membrane receptor function. This is due to deficiency or degradation of the receptor via changes in the genes that encode and regulate the receptor protein. The membrane receptor TM4SF5 influences the migration of hepatic cells and hepatoma. Also, the cortical NMDA receptor influences membrane fluidity, and is altered in Alzheimer's disease. When the cell is infected by a non-enveloped virus, the virus first binds to specific membrane receptors and then passes itself or a subviral component to the cytoplasmic side of the cellular membrane. In the case of poliovirus, it is known in vitro that interactions with receptors cause conformational rearrangements which release a virion protein called VP4.The N terminus of VP4 is myristylated and thus hydrophobic【myristic acid=CH(CH)COOH】. It is proposed that the conformational changes induced by receptor binding result in the attachment of myristic acid on VP4 and the formation of a channel for RNA.

Structure-based drug design.

Through methods such as X-ray crystallography and NMR spectroscopy, the information about 3D structures of target molecules has increased dramatically, and so has structural information about the ligands. This drives rapid development of structure-based drug design. Some of these new drugs target membrane receptors. Current approaches to structure-based drug design can be divided into two categories. The first category is about determining ligands for a given receptor. This is usually accomplished through database queries, biophysical simulations, and the construction of chemical libraries. In each case, a large number of potential ligand molecules are screened to find those fitting the binding pocket of the receptor. This approach is usually referred to as ligand-based drug design. The key advantage of searching a database is that it saves time and power to obtain new effective compounds. Another approach of structure-based drug design is about combinatorially mapping ligands, which is referred to as receptor-based drug design. In this case, ligand molecules are engineered within the constraints of a binding pocket by assembling small pieces in a stepwise manner. These pieces can be either atoms or molecules. The key advantage of such a method is that novel structures can be discovered.

Cell surface receptors (membrane receptors, transmembrane receptors) are receptors that are embedded in the plasma membrane of cells. They act in cell signaling by receiving (binding to) extracellular molecules. They are specialized integral membrane proteins that allow communication between the cell and the extracellular space. The extracellular molecules may be hormones, neurotransmitters, cytokines, growth factors, cell adhesion molecules, or nutrients; they react with the receptor to induce changes in the metabolism and activity of a cell. In the process of signal transduction, ligand binding affects a cascading chemical change through the cell membrane.

Transmembránový receptor, nebo také buněčný povrchový receptor nebo membránový receptor je receptor v membránách buněk umožňující buněčnou signalizaci tím, že se něj naváže extracelulární molekula (ligand) a způsobí tím nějakou změnu uvnitř buňky. Mezi extracelulární molekuly patří mohou být hormony, neurotransmitery, cytokiny, růstové faktory, buněčné adhezní molekuly, nebo živiny. Reakce s transmembránovým receptorem vyvolá změny v metabolismu a činnosti buněk.


Premise.

The series centers on Sam (Rachel Bilson), fresh out of rehab and former star of a hit cop series, and Eddie (Eddie Cibrian), a private investigator. They team up to solve crimes, with Sam doing the job as research for a potential comeback role. To get a P.I. movie lead, she has to shadow Eddie, an ex-LAPD detective-turned-private-eye. After solving a case, Sam decides to become Eddie's partner and learn more about being a P.I.

Production.

Development.

The series, which was in development since late March 2016, was ordered straight-to-series by ABC on November 16, 2017, with German RTL Group's channel VOX and French France 2 instantly joining them.

Casting.

On November 16, 2017, Rachel Bilson and Eddie Cibrian were cast as Sam and Eddie, the female and male leads, respectively. Xavier de Guzman joined the cast as Berto on February 15, 2018, and afterwards on March 13, 2018, Aliyah O'Brien and Alice Lee were cast as Detective Christine Rollins and Monica, respectively.

Filming.

Production of the series started shooting at Crossing Riverbend Studios in Burnaby, British Columbia, on February 26, 2018, and concluded on July 23, 2018.

Reception.

Critical response.

On the review aggregator website Rotten Tomatoes, the series has an approval rating of 67% based on 15 reviews, with an average rating of 5.96/10. The website's critical consensus reads, "While "Take Two" is more entertaining than expected – with a desirable chemistry between the stars – the writing is too shaky to break its cookie-cutter mold." Metacritic, which uses a weighted average, scores the series 53 out of 100 based on 10 reviews, indicating "mixed or average reviews".

Take Two is an American crime comedy-drama television series. Created by Andrew W. Marlowe and Terri Edda Miller, the creator and executive producer of "Castle" respectively, it stars Rachel Bilson and Eddie Cibrian. It premiered on ABC in the United States on June 21, 2018.

Take Two je německo-francouzsko-americký komediálně-dramatický televizní seriál, jehož tvůrci jsou Andrew W. Marlowe a Terrie Edda Miller, tvůrce a výkonný producent seriálu "Castle na zabití". Hlavní role hrají Rachel Bilson a Eddie Cibrian. První řada měla premiéru na stanici ABC dne 21. června 2018.


Premise.

Set in Boston, a tight-knit circle of friends is shocked after a member of the group dies from suicide unexpectedly. The friends realize that they need to finally start living life as they cope with their loss. The title is a reference to the saying "Friendship isn't a big thing – it's a million little things."

Production.

Development.

On August 18, 2017, ABC landed a series titled "A Million Little Things" with a put pilot commitment, to be written by DJ Nash, who would serve as executive producer alongside Aaron Kaplan and Dana Honor. The series was described as "being in the tone of "The Big Chill"," with the title stemming from the popular adage, "Friendship isn't a big thing – it's a million little things." Nash came up with the idea for the series following his single-camera comedy pilot "Losing It". He said that "Sometimes in comedy, you have to apologize for adding drama, which is why I was so thrilled to see ABC's passion for a drama that has comedy". ABC officially ordered the series to pilot in January 2018, and the show was officially picked up to series on May 9, 2018. The series is produced by ABC Studios and Kapital Entertainment. On February 5, 2019, during the TCA press tour, "A Million Little Things" was renewed for a second season. On August 8, 2019, it was announced that ABC had ordered a full season for the second season.  On May 21, 2020, ABC renewed the series for a third season.

Casting.

On February 6, 2018, David Giuntoli was cast as Eddie. A week later, Romany Malco was cast as Rome. By the end of the month, Christina Ochoa had joined the cast as Ashley, along with Anne Son as Katherine, Christina Moses as Regina Howard, and James Roday as Gary. In early March 2018, Stéphanie Szostak was cast as Delilah, while Lizzy Greene was cast as Sophie Dixon. That month, it was also revealed that Ron Livingston had joined the series in an unspecified role, which was revealed with the series order in May to be the character Jon. On June 27, 2018, Grace Park was cast as Katherine, replacing Anne Son who was in the original pilot.

Filming.

Production on the pilot took place from March 12 to 29, 2018, in Vancouver, British Columbia. Principal photography for the first season began on July 24, 2018, and concluded on February 4, 2019. Filming for the second season began on June 19, 2019 and ended on February 19, 2020.

Music.

The soundtrack for the first season was released digitally on March 1, 2019, by Hollywood Records.

Release.

The series premiered on September 26, 2018 on ABC in the United States. In Turkey, the series broadcast through pay broadcaster Digiturk. The second season is set to premiere on September 26, 2019.

Reception.

Critical response.

On review aggregation Rotten Tomatoes, the series holds an approval rating of 53% with an average rating of 6.34/10, based on 32 reviews. The website's critical consensus reads, "Despite a decent ensemble and a few intriguing elements, "A MillIon Little Things" breaks under the weight of its own emotionally lofty ambitions." Metacritic, which uses a weighted average, assigned the series a score of 51 out of 100 based on 15 critics, indicating "mixed or average reviews."

A Million Little Things is an American family drama television series created by DJ Nash for ABC. Nash, Aaron Kaplan, Dana Honor, and James Griffiths serve as executive producers on the series. The series is produced by ABC Studios and Kapital Entertainment. The series features an ensemble cast including David Giuntoli, Romany Malco, Allison Miller, Christina Moses, Christina Ochoa, Grace Park, James Roday, Stéphanie Szostak, Tristan Byon and Lizzy Greene. The series received a put pilot commitment at ABC in August 2017; "A Million Little Things" was ordered to series in May 2018 and premiered on September 26, 2018. In October 2018, the show was picked for a full season of 17 episodes. In February 2019, ABC renewed the series for a second season which premiered on September 26, 2019. In May 2020, ABC renewed the series for a third season.

A Million Little Things je americký dramatický televizní seriál stanice ABC, jehož tvůrcem je DJ Nash. Seriál je produkován společnostmi ABC Studios a Kapital Entertainment. Hlavní role hrají David Giuntoli, Ron Livingston, Romany Malco, Allison Miller, Christina Moses, Christina Ochoa, James Roday, Stéphanie Szostak, Lizzy Greene a Chance Hurstfield.


History.

The first attempt to bring professional hockey to Georgia was made in 1968, by the Eastern Hockey League. The Macon Coliseum was completed in 1968, and was the first facility in the state with an ice surface, and the seating capacity to host professional hockey. The EHL considered an expansion team for the 1968–69 season, but opted instead to have the Jacksonville Rockets play six home games at the coliseum to gauge interest.  In 1973, the Southern Hockey League was created when the four southernmost teams in the EHL broke away to form their own league, partially due to travel costs of going to northern arenas. The new league searched for other Southeastern United States cities to host hockey teams. Macon was targeted due to the new arena, and its location adjacent to Interstate 75, which was on a direct route travelling to the Suncoast Suns arena, from the other teams in North Carolina and Virginia. The league chose Jerry Pinkerton, a stockbroker from Atlanta, as the franchise owner. The SHL and Pinkerton believed the timing was right for Macon. The population had grown rapidly, surpassing 120,000 residents as of the 1970 United States Census. The Omni Coliseum had just opened up in 1972, and the National Hockey League came to Georgia with the Atlanta Flames. The SHL and its commissioner Tedd Munchak, were desperate enough for a sixth team, that Munchak himself put up the $25,000 expansion fee, and appointed a league businessman to help raise the $300,000 in expected operating expenses.  The choice of name arose from Pinkerton's favorite song being the Doris Day version of "Makin' Whoopee", and the euphemism being popularized on "The Newlywed Game" by Bob Eubanks. The Macon Whoopees were officially announced at press conference on July 4, 1973, as one of the six teams in the inaugural season of the Southern Hockey League. The Whoopees made affiliation agreements with the Houston Aeros, and Cleveland Crusaders in the World Hockey Association. Keke Mortson from the Aeros was hired as general manager and player-coach, and Bill Buckley was named his assistant, and the club's business manager. Pinkerton was able to secure investors from Atlanta, New York City, and Macon in September.  People in Georgia knew little about hockey, but the fighting was similar to professional wrestling. In promoting the team, management mentioned similarities to football, and held information sessions with civic groups, schools, and churches. Pamphlets for season tickets included explanations of hockey, as did the team's pocket schedule. Radio stations in central Georgia played the Doris Day song frequently, local press and television stories were used to promote the team, "Sports Illustrated," and "The Wall Street Journal" ran items on the team, and 5,000 t‐shirts were sold in advance.  When the team hit the ice in October, jerseys resembled the colors and patterns of the Montreal Canadiens. The Whoopees debuted at home on October 12, 1973, versus the Suncoast Suns. Macon won 5–4 in overtime, in a game that included seven fights, but many fans left after the second period, not knowing it was three periods. Doris Day was invited to sing the national anthem on opening night, but declined. The Whoopees sat in second place for the early part of the season, and Mortson led the team in scoring, with 24 goals, 51 assists, and 75 points.  Despite the good start, the Whoopees could not make payroll in November, and resorted to giving players free rent and television sets to stay with the team. The Whoopees averaged only 1,100 spectators for home games, as Wednesdays and Sundays were church nights in Macon. The team forfeited a game against the Charlotte Checkers on January 17, 1974, when players refused to play due to not being paid. The team was eventually shut down by the Internal Revenue Service on February 15, 1974, for taxes in arrears. The Macon Whoopees won 22 games, lost 38 games, and had 2 ties, in 62 games played.

Players.

Twelve Whoopees players also played in the National Hockey League or World Hockey Association:

Results.

Season-by-season results:

The Macon Whoopees were a minor league professional ice hockey team based in Macon, Georgia, and played home games at the Macon Coliseum. The Whoopees played in the Southern Hockey League, and were the second professional hockey team in Georgia. The attempt in Macon to expand hockey southward failed, as the team ceased operations before completion of the 1973–74 season. Hockey did not return to Macon until 1996, when the name was revived by the Macon Whoopee in the Central Hockey League. The original Whoopees team was named after the song "Makin' Whoopee" by Gus Kahn, and is the subject of the book "Once Upon A Whoopee: A Town, A Team, A Song, A Dream," by Ed Grisamore and Bill Buckley.

Macon Whoopees byl profesionální americký klub ledního hokeje, který sídlil v Maconu ve státě Georgie. V letech 1973–1974 působil v profesionální soutěži Southern Hockey League. Whoopees ve své poslední sezóně v SHL skončily v základní části. Klub byl během své existence farmami celků WHA. Jmenovitě se jedná o Cleveland Crusaders a Houston Aeros. Své domácí zápasy odehrával v hale Macon Coliseum s kapacitou 7 182 diváků. Klubové barvy byly červená, bílá a modrá.


Early life and popularity.

Koko was born on July 4, 1971, at the San Francisco Zoo to her biological mother Jacqueline and father Bwana. Koko was the 50th gorilla born in captivity and one of the first gorillas accepted by her mother in captivity. Koko remained with her mother until the age of one when she was taken to the zoo's hospital to be treated for a life-threatening illness. Patterson along with Charles Pasternak originally cared for Koko at the San Francisco Zoo as part of their doctoral research at Stanford University after Koko came to the zoo's hospital. Koko was loaned to Patterson and Pasternak under the condition that they would spend at least four years with her. Eventually, Koko remained with Patterson, supported by The Gorilla Foundation, which Patterson founded to support gorilla research and conservation.  In 1978, Koko gained worldwide attention as she was pictured on the cover of "National Geographic" magazine. The cover picture was an image of Koko taking her own picture in the mirror. Koko was later featured on the cover of National Geographic in 1985 with a picture of her and her kitten, All-Ball. At the preserve, Koko also met and interacted with a variety of celebrities including Robin Williams, Fred Rogers, Betty White, William Shatner, Flea, Leonardo DiCaprio, Peter Gabriel, and Sting.

Characteristics.

Use of language.

Patterson reported that Koko's use of signs indicated that she mastered the use of sign language. Koko's training began at the age of 1 and she had a working vocabulary of more than 1,000 signs, which she was able to combine in complex ways.  Patterson reported that Koko made several complex uses of signs that suggested a more developed degree of cognition than is usually attributed to non-human primates and their use of communication. For example, Koko was reported to use displacement (the ability to communicate about objects that are not currently present). At age 19, Koko was able to pass the mirror test of self-recognition, which most other gorillas fail. She had been reported to relay personal memories. Koko was reported to use meta-language, being able to use language reflexively to speak about language itself, signing "good sign" to another gorilla who successfully used signing. Koko was reported to use language deceptively, and to use counterfactual statements for humorous effects, suggesting an underlying theory of other minds.  Patterson reported that she documented Koko inventing new signs to communicate novel thoughts. For example, she said that nobody taught Koko the word for "ring", but to refer to it, Koko combined the words "finger" and "bracelet", hence "finger-bracelet".  Criticism from some scientists centered on the fact that while publications often appeared in the popular press about Koko, scientific publications with substantial data were fewer in number. Other researchers argued that Koko did not understand the meaning behind what she was doing and learned to complete the signs simply because the researchers rewarded her for doing so (indicating that her actions were the product of operant conditioning). Another concern that has been raised about Koko's ability to express coherent thoughts through signs is that interpretation of the gorilla's conversation was left to the handler, who may have seen improbable concatenations of signs as meaningful. For example, when Koko signed "sad" there was no way to tell whether she meant it with the connotation of "How sad". Following Patterson's initial publications in 1978, a series of critical evaluations of her reports of signing behavior in great apes argued that video evidence suggested that Koko was simply being prompted by her trainers' unconscious cues to display specific signs, in what is commonly called the Clever Hans effect.

Intelligence.

Between 1972 and 1977, Koko was administered several infant IQ tests, including the Cattell Infant Intelligence Scale and form B of the Peabody Picture Vocabulary Test. She achieved scores in the 70–90 range, which is comparable to a human infant that is slow but not intellectually impaired. According to Francine Patterson, however, it is specious to compare her IQ directly with that of a human infant because gorillas develop locomotor abilities earlier than humans and many IQ tests for infants require mostly motor responses. Gorillas and humans also mature at different rates, so using a gorilla's chronological age to compute their IQ results in a score that is not very useful for comparative purposes.

Pets.

Researchers at The Gorilla Foundation said that Koko asked for a cat for Christmas in 1983. Ron Cohn, a biologist with the foundation, explained to the "Los Angeles Times" that when she was given a lifelike stuffed animal, she was less than satisfied. She did not play with it and continued to sign "sad". So on her birthday in July 1984, she was able to choose a kitten from a litter of abandoned kittens. Koko selected a gray male Manx and named him "All Ball". Penny Patterson, who had custody of Koko and who had organized The Gorilla Foundation, wrote that Koko cared for the kitten as if it were a baby gorilla. Researchers said that she tried to nurse All Ball and was very gentle and loving. They believed that Koko's nurturing of the kitten and the skills she gained through playing with dolls would be helpful in Koko's learning how to nurture an offspring.  In December 1984, All Ball escaped from Koko's cage and was hit and killed by a car. Later, Patterson said that when she signed to Koko that All Ball had been killed, Koko signed "Bad, sad, bad" and "Frown, cry, frown, sad, trouble". Patterson also reported later hearing Koko making a sound similar to human weeping.  In 1985, Koko was allowed to pick out two new kittens from a litter to be her companions. The animals she chose, which she named "Lipstick" and "Smoky", were also Manxes. Koko picked the name after seeing the tiny orange Manx for the first time. When her trainer asked the meaning of the name, Koko answered, "Lips lipstick".  To celebrate her birthday in July 2015, Koko was presented another litter of kittens. Picking two, she named them Miss Black and Miss Grey.

Nipple fixation.

Koko was reported to have a preoccupation with both male and female human nipples, with several people saying that Koko requested to see their nipples. In 2005, three staff at The Gorilla Foundation, where Koko resided, filed lawsuits against the organization, alleging that they were pressured to reveal their nipples to Koko by the organization's executive director, among other violations of labor law. The lawsuits were settled out of court. Gorilla expert Kristen Lukas has said that other gorillas are not known to have had a similar nipple fixation.

Later life and death.

After Patterson's research with Koko was completed, the gorilla moved to a reserve in Woodside, California. At the reserve, Koko lived with another gorilla, Michael, who also learned sign language, but he died in 2000. She then lived with another male gorilla, Ndume, until her death. Koko's weight of was higher than would be normal for a gorilla in the wild, where the average weight is approximately, but the foundation stated that Koko "is, like her mother, a larger frame Gorilla".  Koko died in her sleep during the morning of June 19, 2018, at the Gorilla Foundation's preserve in Woodside, California, at the age of 46. The Gorilla Foundation released a statement that "The impact has been profound and what she has taught us about emotional capacity of gorillas and their cognitive abilities will continue to shape the world." Even though Koko was 46 years old when she died, her death took staff members of the Gorilla Foundation by surprise.

In media.

Koko and Patterson's work with her have been the subject of several books and documentaries.

Hanabiko "Koko" (July 4, 1971 – June 19, 2018) was a female western lowland gorilla known for having learned many hand signs from a modified version of American Sign Language (ASL). Koko was born at the San Francisco Zoo and lived most of her life in Woodside, California, at The Gorilla Foundation's preserve in the Santa Cruz Mountains. The name,, is of Japanese origin and is a reference to her date of birth, the Fourth of July. Koko gained public attention upon a report of her having adopted a kitten as a pet and creating a name for him.

Koko (4. července 1971, San Francisco, Kalifornie – 19. června 2018, Woodside, Kalifornie) byla nadprůměrně inteligentní samice gorily nížinné západní s IQ mezi 75 a 95, která byla známá tím, že se v rámci výzkumu zvířecí psycholožky Francine Pettersonové naučila více než tisíc znaků americké znakové řeči, jež používala v komplikovanějších formách. Rozuměla 2000 mluvených slov v angličtině a uměla znakovat o svých myšlenkách a pocitech. Oproti jiným gorilám se dokázala poznat v zrcadle nebo mluvit i o věcech, které nebyly zrovna v jejím dohledu. Kromě toho používala znakovou řeč také k projevení smyslu pro humor a vymýšlela nové znaky. Milovala kočky, které si sama pojmenovávala.


Description.

As sauropods, the Saltasauridae are herbivorous saurischians with the characteristic body plan of a small head, long neck, four erect legs, and a counterbalancing tail. Most sauropods are from the clade Neosauropoda, which is further split into the narrow-toothed Diplodocoidea and the broad-toothed Macronaria. The Macronarians emerged in the Jurassic and a subclade, the Titanosauria, survived into the Cretaceous and spread across the continents. Because of their diversity, wide distribution, and the fragmentary or incomplete nature of most specimens, little is known about the titanosaurs beyond their size and tendency to have scutes.  The saltasaurids, one of the several titanosaur families, are recognized by the convexities in certain caudal vertebrae and the markings on their coracoid bones. All saltasaurids have thirty-five or fewer caudal vertebrae, each of which is convex on both sides of its centrum, and the one closest to the tail is shorter than the others. Their coracoid bones have rectangular margins on the anteroventral side, as well as a lip where they meet the infraglenoid. The Opisthocoelicaudiinae, a subfamily of the saltasaurids, are unique in that they lack phalanges in their forelimbs. Although "Saltasaurus" is known to possess dorsal osteoderms, scutes have not been discovered in all saltasaurids, and it is unclear when and where the evolution of osteoderms occurred in saltasaurids and titanosaurs in general.

History of study.

The first saltasaurid to be discovered was "Alamosaurus", found by paleontologist Charles Gilmore in Utah in 1922. The next species would not be described until "Opisthocoelicaudia" was named by Magdalena Borsuk-Bialynicka from a postcranial material in Mongolia in 1977. In 1980, Jose Bonaparte and Jaime Powell discovered "Saltasaurus" in Argentina. This was the first sauropod to be discovered with armor and proved that sauropods had thrived in Cretaceous South America. Paul Sereno eventually recognized a cladistic relationship between "Opisthocoelicauda" and "Saltasaurus" to create the family Saltasauridae.

Classification.

The group is defined by the characteristics shared by all with the two best-known members, "Saltasaurus" and "Opisthocoelicaudia". Paleontologists J Wilson and P Upchurch defined the Saltasauridae in 2003 as the least inclusive clade containing "Opisthocoelicaudia skarzynskii", and "Saltasaurus loricatus", their most recent common ancestor, and all that species’ descendants.

Taxonomy.

This taxonomy is based on those of González Riga "et al." (2009) and Curry Rogers & Wilson (2005).

Phylogeny.

The family is then further divided into two subfamilies. Wilson and Upchurch defined Saltasaurinae in 2003 as the least-inclusive clade containing "Saltasaurus" but not "Opisthocoelicaudia". The same paleontologists defined Opisthocoelicaudiinae as the inverse: the least-inclusive clade containing "Opisthocoelicaudia" but not "Saltasaurus". Some species, due to the incompleteness of their skeletons, cannot yet be placed in either subfamily.

Paleobiology.

Geographic range.

Many fragmentary saltasaurids have been discovered since 1980, placing members of the family in territories as widely dispersed as today's Australia, Madagascar, and France, in addition to their earlier-known residencies in North and South America. Like the other titanosaurs, the saltasaurids where a widespread, successful group that colonized all continents in the Cretaceous.

Feeding habits.

Like all titanosaurs, the saltasaurids possessed small, peg-like teeth that were not usable for chewing. Coproliths from an unidentified titanosaur found in India suggest a diet of conifers, cycads, and early species of grasses. Unable to chew and probably lacking gastroliths, sauropods survived by retaining plant matter in their stomachs for long periods of time, fermenting it to extract as many resources as possible. Their long necks allowed them to graze over a large area while standing, reducing energy use.

Osteoderms.

The osteoderms of "Saltasaurus" consisted of numerous, large bony plates embedded in the dorsal skin, each surrounded by a pattern of smaller plates. The large osteoderms contained some hollow spaces for blood vessels and spongy trabecular bone, while the small ones were solid. Patches of skin from unidentified Cretaceous titanosaurs have revealed similar scale patterns in embryos (a large scale surrounded by ten smaller ones) but no bone or mineralized structure, suggesting that, like crocodiles, those saltasaurids that possessed armor only developed it some time after hatching. Analysis of the osteoderms of the titanosaur "Rapetosaurus" (not a member of Saltasauridae) revealed that the bones were hollow in adults, while those of juveniles were solid pieces similar to those in crocodiles. Paleontologist Kristina Curry Rogers, who made this discovery, theorized that the adult animals used their hollow osteoderms to store minerals during lean times. It is unknown whether any of the Saltasauridae used their osteoderms in a similar manner.

Reproduction and development.

The same Argentine dig site, Auca Mahuevo, that provided information on embryonic skin, has also yielded information on the nesting habits of titanosaurs, but not saltasaurids specifically. The nests were constructed on the surface by piling debris in a ring around the eggs, with the eggs themselves left uncovered. Each egg was porous and spherical, about 14 cm in diameter, and they were laid in clutches. The embryos show smaller rostrum and nares close to the anterior portion of the face compared to adult titanosaurs, suggesting that the nostrils may have moved towards the back of the head as the animal grew.

Saltasauridae (named after the Salta region of Argentina where they were first found) — a family of armored herbivorous sauropods from the Upper Cretaceous. They are known from fossils found in South America, Asia, North America, and Europe. They are characterized by their vertebrae and feet, which are similar to those of "Saltasaurus", the first of the group to be discovered and the source of the name. The last and largest of the group and only one found in North America, "Alamosaurus", was in length and the last sauropod to go extinct.

Saltasauridae („saltasauridi“) byla čeleď titanosaurních sauropodních dinosaurů, žijících v období pozdní svrchní křídy (geologický stupeň santon až maastricht, asi před 86 až 66 miliony let).


Design and construction.

The M1916 Type minesweeper was an improved and slightly enlarged derivative of the M1914 and M1915 Type minesweepers which Germany had built since 1914. They were fleet minesweepers, seaworthy enough to operate in the open sea, and proved to be successful and reliable in service.  "M68" was long overall and at the waterline, with a beam of and a draught of. The ship had a design displacement of and a deep load displacement of. Two coal-fired water-tube boilers fed steam to two sets of 3-cylinder triple expansion steam engines, rated at, which in turn drove two propeller shafts. Speed was. 120 tons of coal was carried, sufficient for a range of at.  As built, "M68" had a main gun armament of two 8.8 cm (3.5 in) SK L/45 naval guns, while 30 mines could be carried. Armament in Latvian service was listed as two Canet guns and one 2-pounder (40 mm) gun in 1931. In Soviet service, the ship was armed with two 76.2 mm (3 inch) guns and two 45 mm guns, backed up by four 7.62 mm machine guns, and was rearmed in September 1941 with three 102 mm (4 inch) and two 37 mm guns, backed up with two 12.7 mm machine guns. The ship had a crew of 40 in German service, with a crew of 69 in Latvia service, and 66 in Soviet service.  "M68" was laid down early in 1917 at A. G. Neptun's shipyard in Rostock as yard number 382, was launched on 25 July 1917 and was commissioned on 6 October 1917.

Service.

Germany.

"M68" joined the 3rd Minesweeping half-flotilla of the 2nd Minesweeping Flotilla, operating in the Baltic. Her service with the Imperial German Navy was short, however, as she was sunk after striking a mine off Riga on 29 October 1917.

Latvia.

In 1918, "M68" was raised and taken to Riga for repair, but in January 1919 was seized by the forces of the Latvian Socialist Soviet Republic as they gained control of most of the country during the Latvian War of Independence. In May 1919, "M68" changed hands again when Riga was captured by German Freikorps, and in July control of Riga passed back to the forces of the Latvian Provisional Government. With repairs complete, the ship was commissioned into the Latvian Navy as "Virsaitis" on 10 November 1921, serving as a guardship.  In October 1939, Latvia was pressured into signing a Mutual Assistance Treaty with the Soviet Union, permitting the Soviets to base troops on Latvian territory, and in June 1940 the Soviet Union occupied Latvia, with Latvia formally being incorporated into the Soviet Union on 3 August 1940. As a result, the Latvian armed forces, including its Navy, became part of the Soviet armed forces.

Soviet Navy.

As part of this process, "Virsaitis" joined the Soviet Baltic Fleet on 19 August 1940 as a minesweeper, and was renamed "T-297". Germany invaded the Soviet Union on 22 June 1941. "T-297", which was redesignated as an escort vessel on 25 July 1941 (returning to the name "Virsaitis"), was used to defend naval bases and communication routes. From 31 October 1941, the Baltic Fleet carried out a series of convoy operations to evacuate the garrison of the Hanko Peninsula, which the Finns had been forced to lease to the Soviets for use as a naval base following the Winter War between Finland and the Soviet Union, but was now besieged. "Virsaitis" took part in the fourth evacuation convoy on 24 November 1941 and the final operation, which left Hanko on the evening of 2 December. "Virsaitis" struck a mine later that day and sunk.

Wreck site.

In 2011, the wreck of "Virsaitis" was found off the coast of Finland near Hanko.

SMS "M68 was a M1916 type minesweeper built for the Imperial German Navy during the First World War. She entered service on 6 October 1917, but was mined and sunk off Latvia on 29 October 1917. The ship was salvaged by Latvia and entered service with the Latvian Navy on 10 November 1921 under the name Virsatis. She was taken over by the Soviet Navy in August 1940 when the Soviet Union occupied Latvia in August 1940, serving as T-297" and was sunk by a mine on 2 December 1941.

Virsaitis byla minolovka a hlídková loď lotyšského námořnictva. Původně byla postavena jako německá minolovka M68. Německé císařské námořnictvo ji nasadilo do první světové války. Ve válce poškozené plavidlo opravilo a roku 1919 zařadilo lotyšské námořnictvo. Po okupaci země Sovětským svazem roku 1940 byla zařazena do sovětského námořnictva. Byla potopena za druhé světové války.


Henry Pelham-Clinton, 5th Duke of Newcastle

Background.

Newcastle was the son of Henry Pelham-Clinton, 4th Duke of Newcastle-under-Lyne, by his wife Georgina Elizabeth, daughter of Edward Miller-Mundy. He was educated at Eton and Christ Church, Oxford, where he took his B.A. degree in 1832, and was created a D.C.L. in 1863.

Political career.

Newcastle was returned to Parliament for South Nottinghamshire in 1832, a seat he held until 1846, and then represented Falkirk Burghs until 1851, when he succeeded his father in the dukedom. Initially a Tory, he served under Sir Robert Peel as First Commissioner of Woods and Forests from 1841 to 1846 and as Chief Secretary for Ireland in 1846, as the effects of the Great Irish Famine began to take hold. He was admitted to the British Privy Council in 1841, and to the Irish Privy Council on 14 February 1846.  Newcastle joined the Peelites in 1846, and held office in Lord Aberdeen's coalition government as Secretary of State for War and the Colonies between 1852 and 1854, and as Secretary of State for War and Secretary at War between 12 June 1854 and 1 February 1855, when he resigned over the Crimean War.  From 18 June 1859 to April 1864, he served as Secretary of State for the Colonies in Lord Palmerston's Liberal administration. In 1860, while holding this office, he went to Canada and the United States, in company with the Prince of Wales. Apart from his political career he also held the honorary posts of Lord Lieutenant of Nottinghamshire from 1857 to 1864 and Lord Warden of the Stannaries from 1862 to 1864. He was made a Knight of the Garter on 17 December 1860.  Lord Lincoln was a member of the Canterbury Association from 27 March 1848. Upon succeeding to the dukedom, he joined the association's management committee on 29 January 1851. In 1849, the chief surveyor of the Canterbury Association, Joseph Thomas, named the future town of Lincoln in New Zealand after him. The town's university was in turn also named after Lord Lincoln.

Family.

Newcastle married Lady Susan Hamilton (9 June 181428 November 1889), daughter of Alexander Hamilton, 10th Duke of Hamilton, on 27 November 1832. They had five children:  The marriage was unhappy and the Duke and Duchess were divorced in 1850, after a considerable scandal in which the Duchess eloped with Horatio Walpole, Lord Walpole, and had an illegitimate child by him. Newcastle died in October 1864, aged 53, and was succeeded in the dukedom by his eldest son, Henry.  His papers are now held at Manuscripts and Special Collections, The University of Nottingham.

References.

Attribution:

Henry Pelham Fiennes Pelham-Clinton, 5th Duke of Newcastle-under-Lyne, (22 May 181118 October 1864), styled Earl of Lincoln before 1851, was a British politician.

Henry Pelham-Clinton, 5. vévoda z Newcastle ("Henry Pelham Fiennes Pelham-Clinton, 5th Duke of Newcastle, 12th Earl of Lincoln") (22. května 1811 – 18. října 1864) byl britský státník ze šlechtického rodu Pelhamů. Politicky patřil k liberálům a v několika britských vládách zastával funkce ministra, v době krymské války byl ministrem války a kolonií. Byl též rytířem Podvazkového řádu.


Definition.

Following the original definition by Agrawal, Imieliński, Swami the problem of association rule mining is defined as:  Let formula_2 be a set of formula_3 binary attributes called "items".  Let formula_4 be a set of transactions called the "database".  Each "transaction" in formula_5 has a unique transaction ID and contains a subset of the items in formula_6.  A "rule" is defined as an implication of the form:  formula_7, where formula_8.  In Agrawal, Imieliński, Swami a "rule" is defined only between a set and a single item, formula_9 for formula_10.  Every rule is composed by two different sets of items, also known as "itemsets", formula_11 and formula_12, where formula_11 is called "antecedent" or left-hand-side (LHS) and formula_12 "consequent" or right-hand-side (RHS).  To illustrate the concepts, we use a small example from the supermarket domain. The set of items is formula_15 and in the table is shown a small database containing the items, where, in each entry, the value 1 means the presence of the item in the corresponding transaction, and the value 0 represents the absence of an item in that transaction.  An example rule for the supermarket could be formula_16 meaning that if butter and bread are bought, customers also buy milk.  Note: this example is extremely small. In practical applications, a rule needs a support of several hundred transactions before it can be considered statistically significant, and datasets often contain thousands or millions of transactions.

Useful Concepts.

In order to select interesting rules from the set of all possible rules, constraints on various measures of significance and interest are used. The best-known constraints are minimum thresholds on support and confidence.  Let formula_17 be itemsets, formula_7 an association rule and formula_19 a set of transactions of a given database.

Support.

Support is an indication of how frequently the itemset appears in the dataset.  The support of formula_11 with respect to formula_19 is defined as the proportion of transactions formula_22 in the dataset which contains the itemset formula_11.  formula_24  In the example dataset, the itemset formula_25 has a support of formula_26 since it occurs in 20% of all transactions (1 out of 5 transactions). The argument of formula_27 is a set of preconditions, and thus becomes more restrictive as it grows (instead of more inclusive).

Confidence.

Confidence is an indication of how often the rule has been found to be true.  The "confidence" value of a rule, formula_7, with respect to a set of transactions formula_19, is the proportion of the transactions that contains formula_11 which also contains formula_12.  Confidence is defined as:  formula_32  For example, the rule formula_16 has a confidence of formula_34 in the database, which means that for 100% of the transactions containing butter and bread the rule is correct (100% of the times a customer buys butter and bread, milk is bought as well).  Note that formula_35 means the support of the union of the items in X and Y. This is somewhat confusing since we normally think in terms of probabilities of events and not sets of items. We can rewrite formula_35 as the probability formula_37, where formula_38 and formula_39 are the events that a transaction contains itemset formula_11 and formula_12, respectively.  Thus confidence can be interpreted as an estimate of the conditional probability formula_42, the probability of finding the RHS of the rule in transactions under the condition that these transactions also contain the LHS.

Lift.

The "lift" of a rule is defined as:  formula_43  or the ratio of the observed support to that expected if X and Y were independent.  For example, the rule formula_44 has a lift of formula_45.  If the rule had a lift of 1, it would imply that the probability of occurrence of the antecedent and that of the consequent are independent of each other. When two events are independent of each other, no rule can be drawn involving those two events.  If the lift is > 1, that lets us know the degree to which those two occurrences are dependent on one another, and makes those rules potentially useful for predicting the consequent in future data sets.  If the lift is < 1, that lets us know the items are substitute to each other. This means that presence of one item has negative effect on presence of other item and vice versa.  The value of lift is that it considers both the support of the rule and the overall data set.

Conviction.

The "conviction" of a rule is defined as formula_46.  For example, the rule formula_44 has a conviction of formula_48, and can be interpreted as the ratio of the expected frequency that X occurs without Y (that is to say, the frequency that the rule makes an incorrect prediction) if X and Y were independent divided by the observed frequency of incorrect predictions. In this example, the conviction value of 1.2 shows that the rule formula_44 would be incorrect 20% more often (1.2 times as often) if the association between X and Y was purely random chance.

Alternative measures of interestingness.

In addition to confidence, other measures of "interestingness" for rules have been proposed. Some popular measures are:  Several more measures are presented and compared by Tan et al. and by Hahsler. Looking for techniques that can model what the user has known (and using these models as interestingness measures) is currently an active research trend under the name of "Subjective Interestingness."

Process.

Association rules are usually required to satisfy a user-specified minimum support and a user-specified minimum confidence at the same time. Association rule generation is usually split up into two separate steps: While the second step is straightforward, the first step needs more attention.  Finding all frequent itemsets in a database is difficult since it involves searching all possible itemsets (item combinations). The set of possible itemsets is the power set over formula_6 and has size formula_51 (excluding the empty set which is not a valid itemset). Although the size of the power-set grows exponentially in the number of items formula_3 in formula_6, efficient search is possible using the downward-closure property of support (also called "anti-monotonicity") which guarantees that for a frequent itemset, all its subsets are also frequent and thus no infrequent itemset can be a subset of a frequent itemset. Exploiting this property, efficient algorithms (e.g., Apriori and Eclat) can find all frequent itemsets.

History.

The concept of association rules was popularised particularly due to the 1993 article of Agrawal et al., which has acquired more than 18,000 citations according to Google Scholar, as of August 2015, and is thus one of the most cited papers in the Data Mining field. However, what is now called "association rules" is introduced already in the 1966 paper on GUHA, a general data mining method developed by Petr Hájek et al.  An early (circa 1989) use of minimum support and confidence to find all association rules is the Feature Based Modeling framework, which found all rules with formula_54 and formula_55 greater than user defined constraints.

Statistically sound associations.

One limitation of the standard approach to discovering associations is that by searching massive numbers of possible associations to look for collections of items that appear to be associated, there is a large risk of finding many spurious associations. These are collections of items that co-occur with unexpected frequency in the data, but only do so by chance. For example, suppose we are considering a collection of 10,000 items and looking for rules containing two items in the left-hand-side and 1 item in the right-hand-side. There are approximately 1,000,000,000,000 such rules. If we apply a statistical test for independence with a significance level of 0.05 it means there is only a 5% chance of accepting a rule if there is no association. If we assume there are no associations, we should nonetheless expect to find 50,000,000,000 rules. Statistically sound association discovery controls this risk, in most cases reducing the risk of finding "any" spurious associations to a user-specified significance level.

Algorithms.

Many algorithms for generating association rules have been proposed.  Some well-known algorithms are Apriori, Eclat and FP-Growth, but they only do half the job, since they are algorithms for mining frequent itemsets. Another step needs to be done after to generate rules from frequent itemsets found in a database.

Apriori algorithm.

Apriori uses a breadth-first search strategy to count the support of itemsets and uses a candidate generation function which exploits the downward closure property of support.

Eclat algorithm.

Eclat (alt. ECLAT, stands for Equivalence Class Transformation) is a depth-first search algorithm based on set intersection. It is suitable for both sequential as well as parallel execution with locality-enhancing properties.

FP-growth algorithm.

FP stands for frequent pattern.  In the first pass, the algorithm counts the occurrences of items (attribute-value pairs) in the dataset of transactions, and stores these counts in a 'header table'. In the second pass, it builds the FP-tree structure by inserting transactions into a trie.  Items in each transaction have to be sorted by descending order of their frequency in the dataset before being inserted so that the tree can be processed quickly. Items in each transaction that do not meet the minimum support requirement are discarded. If many transactions share most frequent items, the FP-tree provides high compression close to tree root.  Recursive processing of this compressed version of the main dataset grows frequent item sets directly, instead of generating candidate items and testing them against the entire database (as in the apriori algorithm).  Growth begins from the bottom of the header table i.e. the item with the smallest support by finding all sorted transactions that end in that item. Call this item formula_6.  A new conditional tree is created which is the original FP-tree projected onto formula_6. The supports of all nodes in the projected tree are re-counted with each node getting the sum of its children counts. Nodes (and hence subtrees) that do not meet the minimum support are pruned. Recursive growth ends when no individual items conditional on formula_6 meet the minimum support threshold. The resulting paths from root to formula_6 will be frequent itemsets. After this step, processing continues with the next least-supported header item of the original FP-tree.  Once the recursive process has completed, all frequent item sets will have been found, and association rule creation begins.

Others.

ASSOC.

The ASSOC procedure is a GUHA method which mines for generalized association rules using fast bitstrings operations. The association rules mined by this method are more general than those output by apriori, for example "items" can be connected both with conjunction and disjunctions and the relation between antecedent and consequent of the rule is not restricted to setting minimum support and confidence as in apriori: an arbitrary combination of supported interest measures can be used.

OPUS search.

OPUS is an efficient algorithm for rule discovery that, in contrast to most alternatives, does not require either monotone or anti-monotone constraints such as minimum support. Initially used to find rules for a fixed consequent it has subsequently been extended to find rules with any item as a consequent. OPUS search is the core technology in the popular Magnum Opus association discovery system.

Lore.

A famous story about association rule mining is the "beer and diaper" story. A purported survey of behavior of supermarket shoppers discovered that customers (presumably young men) who buy diapers tend also to buy beer. This anecdote became popular as an example of how unexpected association rules might be found from everyday data. There are varying opinions as to how much of the story is true. Daniel Powers says:  In 1992, Thomas Blischok, manager of a retail consulting group at Teradata, and his staff prepared an analysis of 1.2 million market baskets from about 25 Osco Drug stores. Database queries were developed to identify affinities. The analysis "did discover that between 5:00 and 7:00 p.m. that consumers bought beer and diapers". Osco managers did NOT exploit the beer and diapers relationship by moving the products closer together on the shelves.

Other types of association rule mining.

Multi-Relation Association Rules: Multi-Relation Association Rules (MRAR) are association rules where each item may have several relations. These relations indicate indirect relationship between the entities. Consider the following MRAR where the first item consists of three relations "live in", "nearby" and "humid": “Those who "live in" a place which is "nearby" a city with "humid" climate type and also are "younger" than 20 -> their "health condition" is good”. Such association rules are extractable from RDBMS data or semantic web data.  Contrast set learning is a form of associative learning. Contrast set learners use rules that differ meaningfully in their distribution across subsets.  Weighted class learning is another form of associative learning in which weight may be assigned to classes to give focus to a particular issue of concern for the consumer of the data mining results.  High-order pattern discovery facilitate the capture of high-order (polythetic) patterns or event associations that are intrinsic to complex real-world data. K-optimal pattern discovery provides an alternative to the standard approach to association rule learning that requires that each pattern appear frequently in the data.  Approximate Frequent Itemset mining is a relaxed version of Frequent Itemset mining that allows some of the items in some of the rows to be 0.  Generalized Association Rules hierarchical taxonomy (concept hierarchy)  Quantitative Association Rules categorical and quantitative data  Interval Data Association Rules e.g. partition the age into 5-year-increment ranged  Sequential pattern mining discovers subsequences that are common to more than minsup sequences in a sequence database, where minsup is set by the user. A sequence is an ordered list of transactions.  Subspace Clustering, a specific type of Clustering high-dimensional data, is in many variants also based on the downward-closure property for specific clustering models.  Warmr is shipped as part of the ACE data mining suite. It allows association rule learning for first order relational rules.

Association rule learning is a rule-based machine learning method for discovering interesting relations between variables in large databases. It is intended to identify strong rules discovered in databases using some measures of interestingness.

Asociační analýza v oblasti dobývání znalostí z databází je metoda nalézání "asociačních pravidel" spojujících zároveň se vyskytující atributy (události, položky...) u zkoumaných objektů. Častým použitím je analýza nákupního košíku: jestliže objektem je nákup jednoho zákazníka v obchodě a atributy tohoto nákupu jsou názvy položek, jež zákazník zakoupil, tak příkladem jednoho pravidla může být


Architecture.

The Laurentian Library was commissioned in 1523 and construction began in 1525; however, when Michelangelo left Florence in 1534, only the walls of the reading room were complete. It was then continued by Tribolo, Vasari, and Ammannati based on plans and verbal instructions from Michelangelo. The library opened by 1571. In this way, the library integrates parts executed by Michelangelo with others built much later in an interpretation of his instructions. The Laurentian Library is one of Michelangelo's most important architectural achievements. Even Michelangelo's contemporaries realized that the innovations and use of space in the Laurentian Library were revolutionary. The admirable distribution of the windows, the construction of the ceiling, and the fine entrance of the Vestibule can never be sufficiently extolled. Boldness and grace are equally conspicuous in the work as a whole, and in every part; in the cornices, corbels, the niches for statues, the commodious staircase, and its fanciful division, in all the building, as a word, which is so unlike the common fashion of treatment, that every one stands amazed at the sight thereof. – Giorgio Vasari. The two-story quattrocento cloister remained unchanged by the addition of the library. Because of this, certain features of Michelangelo’s plan, such as length and width, were already determined. Therefore, new walls were built on pre-existing walls and cloisters. Because the walls were built on pre-existing walls, recessing the columns into the walls was a structural necessity. This led to a unique style and pattern that Michelangelo took advantage of.

Vestibule.

The vestibule, also known as the "ricetto", is 10.50 m long, 10.50 m wide, and 14.6 m tall (34.5 by 34.5 by 48 feet). It was built above existing monastic quarters on the east range of the cloister, with an entrance from the upper level of the cloisters. Originally, Michelangelo planned for a skylight, but Clement VII believed that it would cause the roof to leak, so clerestory windows were incorporated into the west wall. Blank tapering windows––framed in pietra serena, surmounted by either triangular or segmental pediments, and separated by paired columns set into the wall––circumscribe the interior of the vestibule.  Lit by windows in bays that are articulated by pilasters corresponding to the beams of the ceiling, with a tall constricted vestibule (executed to Michelangelo's design in 1559 by Bartolomeo Ammannati) that is filled with a stair that flows up to (and down from) the entrance to the reading room, the library is often mentioned as a prototype of Mannerism in architecture.

Staircase.

The plan of the stairs changed dramatically in the design phase. Originally in the first design in 1524, two flights of stairs were placed against the side walls and formed a bridge in front of the reading room door. A year later the stairway was moved to the middle of the vestibule. Tribolo attempted to carry out this plan in 1550 but nothing was built. Ammannati took on the challenge of interpreting Michelangelo’s ideas to the best of his abilities using a small clay model, scanty material, and Michelangelo’s instructions.  The staircase leads up to the reading room and takes up half of the floor of the vestibule. The treads of the centre flights are convex and vary in width, while the outer flights are straight. The three lowest steps of the central flight are wider and higher than the others, almost like concentric oval slabs. As the stairway descends, it divides into three flights.

Reading room.

The reading room is 46.20 m. long, 10.50 m. wide, and 8.4 m. high (152 by 35 by 28 feet). There are two blocks of seats separated by a centre aisle with the backs of each serving as desks for the benches behind them. The desks are lit by the evenly spaced windows along the wall. The windows are framed by pilasters, forming a system of bays which articulate the layout of the ceiling and floor.  Because the reading room was built upon an existing story, Michelangelo had to reduce the weight of the reading-room walls. The system of frames and layers in the walls’ articulation reduced the volume and weight of the bays between the pilasters.  Beneath the current wooden floor of the library in the Reading Room is a series of 15 rectangular red and white "terra cotta" floor panels. These panels, measuring on a side, when viewed in sequence demonstrate basic principles of geometry. It is believed that these tiles were arranged so as to be visible under the original furniture; but this furniture was later changed to increase the number of reading desks in the room.

Interpretation.

In the "ricetto", critics have noted that the recessed columns in the vestibule make the walls look like taut skin stretched between vertical supports. This caused the room to appear as if it mimics the human body, which at the time of the Italian Renaissance was believed to be the ideal form. The columns of the building also appear to be supported on corbels so that the weight seems to be carried on weak elements. Because of the seeming instability of the structure, the viewer cannot discern whether the roof is supported by the columns or the walls. This sense of ambiguity is heightened by the unorthodox forms of the windows and, especially, by the compressed quality of all architectural elements, which creates a sense of tension and constrained energy.  The use of the classical orders in the space is particularly significant. The recessed columns superficially appear to be of the austere and undecorated Doric order, typically considered to have a more masculine character. The Doric order would be placed at the base in a hierarchy of orders such as found in Roman buildings like the Colosseum, with the Ionic, Composite and Corinthian being progressively lighter and more decorative and feminine. However, closer examination establishes that the Composite order is used, but with the characteristic decorative acanthus leaves and diagonal volutes of the capitals stripped off, leaving the top of the column denuded. In architectural terms, it is an act of violence that is unprecedented in mannerism, and a sophistication that would not have escaped contemporary observers.  The dynamic sculpture of the staircase appears to pour forth like lava from the upper level and reduces the floor space of the vestibule in a highly unusual way. In the central flight, the convex treads vary in width which makes the entire arrangement disquieting.  In sharp contrast to the vestibule and staircase, the reading room’s evenly spaced windows set between pilasters in the side walls let in copious amounts of natural light and create a serene, quiet, and restful appearance.  Mark Rothko stated that the vestibule and the walls in the staircase of the library influenced his 1959 Seagram Murals.

Collection.

In 1571, Cosimo I, Grand Duke of Tuscany, opened the still-incomplete library to scholars. Notable additions to the collection were made by its most famous librarian, Angelo Maria Bandini, who was appointed in 1757 and oversaw its printed catalogues.  The Laurentian Library houses about 11,000 manuscripts, 2,500 papyri, 43 ostraca, 566 incunabula, 1,681 16th-century prints, and 126,527 prints of the 17th to 20th centuries. The core collection consists of about 3,000 manuscripts, indexed by Giovanni Rondinelli and Baccio Valori in 1589, which were placed on parapets ("plutei") at the library's opening in 1571. These manuscripts have the signature "Pluteus" or "Pluteo" ("Plut."). These manuscripts include the library Medici family collected during the 15th century and re-acquired by Giovanni di Medici (Pope Leo X) in 1508 and moved to Florence in the 1520s by Giulio di Giuliano de' Medici (Pope Clement VII). The Medici library was joined by collections by Francesco Sassetti and Francesco Filelfo and manuscripts acquired by Leo X and by the library of the Dominican convent of San Marco.  The library conserves the Nahuatl Florentine Codex, the major source of pre-Conquest Aztec life. Among other well-known manuscripts in the Laurentian Library are the sixth-century Syriac Rabula Gospels; the Codex Amiatinus, which contains the earliest surviving manuscript of the Latin Vulgate Bible; the Squarcialupi Codex, an important early musical manuscript; and the fragmentary Erinna papyrus containing poems of the friend of Sappho.

The Laurentian Library (Biblioteca Medicea Laurenziana or BML) is a historic library in Florence, Italy, containing more than 11,000 manuscripts and 4,500 early printed books. Built in a cloister of the Medicean Basilica di San Lorenzo di Firenze under the patronage of the Medici pope Clement VII, the library was built to emphasize that the Medici were no longer merchants but members of intelligent and ecclesiastical society. It contains the manuscripts and books belonging to the private library of the Medici family. The library is renowned for its architecture, designed by Michelangelo, and is an example of Mannerism.

Medicejská knihovna sv. Vavřince ve Florencii ( "Biblioteca Medicea Laurenziana", zkr. též "Laurenziana") je slavná knihovna v italské Florencii, známá díky svým rukopisům. Knihovna je přístupná veřejnosti jako "Biblioteca pubblica statale" a spadá pod správu italského ministerstva kultury a turismu.