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NRs share a common architecture of an N-terminal ligand-independent activation domain followed by a DNA-binding domain (DBD), a flexible hinge region and a ligand-binding domain composed of twelve α-helices (α1-α12). Especially the C-terminal α12, the so-called activation function 2 (AF-2) of the LBD, has been identified as crucial for NR activation since stabilisation of α12 and concomitant binding to the core of the LBD provides a surface for co-activator binding12.
Other forms of poetry, including such ancient collections of religious hymns as the Indian Sanskrit-language Rigveda, the Avestan Gathas, the Hurrian songs, and the Hebrew Psalms, possibly developed directly from folk songs. The earliest entries in the oldest extant collection of Chinese poetry, the Classic of Poetry (Shijing), were initially lyrics.[17] The Shijing, with its collection of poems and folk songs, was heavily valued by the philosopher Confucius and is considered to be one of the official Confucian classics. His remarks on the subject have become an invaluable source in ancient music theory.[18]
Some 20th-century literary theorists rely less on the ostensible opposition of prose and poetry, instead focusing on the poet as simply one who creates using language, and poetry as what the poet creates.[34] The underlying concept of the poet as creator is not uncommon, and some modernist poets essentially do not distinguish between the creation of a poem with words, and creative acts in other media. Yet other modernists challenge the very attempt to define poetry as misguided.[35]
Postmodernism goes beyond modernism's emphasis on the creative role of the poet, to emphasize the role of the reader of a text (hermeneutics), and to highlight the complex cultural web within which a poem is read.[37] Today, throughout the world, poetry often incorporates poetic form and diction from other cultures and from the past, further confounding attempts at definition and classification that once made sense within a tradition such as the Western canon.[38]
Lines of poems are often organized into stanzas, which are denominated by the number of lines included. Thus a collection of two lines is a couplet (or distich), three lines a triplet (or tercet), four lines a quatrain, and so on. These lines may or may not relate to each other by rhyme or rhythm. For example, a couplet may be two lines with identical meters which rhyme or two lines held together by a common meter alone.[89]
Other poems may be organized into verse paragraphs, in which regular rhymes with established rhythms are not used, but the poetic tone is instead established by a collection of rhythms, alliterations, and rhymes established in paragraph form.[90] Many medieval poems were written in verse paragraphs, even where regular rhymes and rhythms were used.[91]
Among the most common forms of poetry, popular from the Late Middle Ages on, is the sonnet, which by the 13th century had become standardized as fourteen lines following a set rhyme scheme and logical structure. By the 14th century and the Italian Renaissance, the form had further crystallized under the pen of Petrarch, whose sonnets were translated in the 16th century by Sir Thomas Wyatt, who is credited with introducing the sonnet form into English literature.[111] A traditional Italian or Petrarchan sonnet follows the rhyme scheme ABBA, ABBA, CDECDE, though some variation, perhaps the most common being CDCDCD, especially within the final six lines (or sestet), is common.[112] The English (or Shakespearean) sonnet follows the rhyme scheme ABAB, CDCD, EFEF, GG, introducing a third quatrain (grouping of four lines), a final couplet, and a greater amount of variety in rhyme than is usually found in its Italian predecessors. By convention, sonnets in English typically use iambic pentameter, while in the Romance languages, the hendecasyllable and Alexandrine are the most widely used meters.
As with other forms with a long history in many languages, many variations have been developed, including forms with a quasi-musical poetic diction in Urdu.[137] Ghazals have a classical affinity with Sufism, and a number of major Sufi religious works are written in ghazal form. The relatively steady meter and the use of the refrain produce an incantatory effect, which complements Sufi mystical themes well.[138] Among the masters of the form is Rumi, a 13th-century Persian poet.[139]One of the most famous poet in this type of poetry is Hafez, whose poems often include the theme of exposing hypocrisy. His life and poems have been the subject of much analysis, commentary and interpretation, influencing post-fourteenth century Persian writing more than any other author.[140][141] The West-östlicher Diwan of Johann Wolfgang von Goethe, a collection of lyrical poems, is inspired by the Persian poet Hafez.[142][143][144]
The same is true of the English satirical tradition. John Dryden (a Tory), the first Poet Laureate, produced in 1682 Mac Flecknoe, subtitled "A Satire on the True Blue Protestant Poet, T.S." (a reference to Thomas Shadwell).[152] Satirical poets outside England include Poland's Ignacy Krasicki, Azerbaijan's Sabir, Portugal's Manuel Maria Barbosa du Bocage, and Korea's Kim Kirim, especially noted for his Gisangdo.
An elegy is a mournful, melancholy or plaintive poem, especially a lament for the dead or a funeral song. The term "elegy," which originally denoted a type of poetic meter (elegiac meter), commonly describes a poem of mourning. An elegy may also reflect something that seems to the author to be strange or mysterious. The elegy, as a reflection on a death, on a sorrow more generally, or on something mysterious, may be classified as a form of lyric poetry.[153][154]
Prose poetry is a hybrid genre that shows attributes of both prose and poetry. It may be indistinguishable from the micro-story (a.k.a. the "short short story", "flash fiction"). While some examples of earlier prose strike modern readers as poetic, prose poetry is commonly regarded as having originated in 19th-century France, where its practitioners included Aloysius Bertrand, Charles Baudelaire, Stéphane Mallarmé, and Arthur Rimbaud.[164] Since the late 1980s especially, prose poetry has gained increasing popularity, with entire journals, such as The Prose Poem: An International Journal,[165] Contemporary Haibun Online,[166] and Haibun Today[167] devoted to that genre and its hybrids. Latin American poets of the 20th century who wrote prose poems include Octavio Paz and Alejandra Pizarnik.
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The most commonly used method for conducting dose-escalation studies in oncology is the 3+3 design [16, 17]. It is a simple, rule-based approach under which patients are dosed in cohorts of three. Based on the number of DLTs observed in the current cohort of patients, recommendations are made to dose the next three patients at either the next escalating dose or the current dose. Upon observing a pre-specified number of toxic outcomes at a dose level (say DLTs in more than 2 in 6 patients), the trial is terminated and the dose level below is considered to be the MTD. The 3+3 design is a special case of the more general A+B design [18]; when a new dose is introduced, a cohort of A patients are dosed, and if further observations are required on the same dose, a cohort of B further patients are then dosed.
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