title: Nizari Isma'ilism

text: Followers of the young Imam Hadi who wished to be fighters were trained as Fidai (Fedayeen), whose bravery and self-sacrificing spirituality was due to their belief that the Nizari "Imam-ul-waqt" ("Imam of the time") had the "noor" (light) of God within him. As such it became a religious duty for the Fidai to obey every dictate of their "Imam-ul-waqt" and to protect him and their community of believers without compromise even to the extent of dying for their cause.


title: Nizari Isma'ilism

text: Under Hassan-i Sabbah in Iran, and Rashid ad-Din Sinan in Syria, the Nizari Fidai targeted the most powerful enemy leaders faced by these new Nizari Ismaili communities in the Elburz Mountains of northern Iran and in the mountains of the Levantine coast, the Jabal Bahra, overlooking the eastern Mediterranean Sea.


title: Nizari Isma'ilism

text: The Fidai were feared as the Assassins, but did not assassinate for payment. Although they were trained in the art of spying and combat, they also practiced Islamic mysticism at the highest level. This religious ardor turned them into formidable foes, as in the anecdote of Count Henry of Champagne. Returning from Armenia, Henry spoke with Grand Master Rashid ad-Din Sinan (known to the West as "The Old Man of the Mountain") at one of his castles, al-Kahf, in Syria. Henry pointed out that since his army was bigger by far than Sinan's, Sinan should pay him an annual tribute.


title: Nizari Isma'ilism

text: Sinan refused, asserting that his army was far stronger, in spirit and unquestioning obedience if not in numbers. He invited Henry to witness this obedience and sacrificial spirit of his Fidai. Sinan signalled to a Fidai standing on the parapet of a high wall of his castle, to jump. The Fidai called out "God is Great" and unhesitatingly took a headlong death dive into the rocks far below.


title: Nizari Isma'ilism

text: The bewildered Henry asked Sinan the cause for the suicidal jump. Sinan pointed once again to the Fidai who had taken the place of the now dead Fidai. Again Sinan gave a signal to the Fidai to jump and the second Fidai also called out "God is Great" and jumped to his death. Henry was visibly shaken by the experience of witnessing the two Fidais' total disregard for their own lives. He accepted Sinan's terms of peace on a non-tribute-paying basis. The Nizaris thus averted debilitating wars against them because of their Fidais' feats of self-sacrifice and assassinations of powerful enemy leaders to demonstrate the will and commitment of the community to live free from being a vassal to any Levantine power.


title: Nizari Isma'ilism

text: The Fidai were some of the most feared assassins in the then known world. Sinan ordered assassinations against politicians and generals such as the great Kurdish general and founder of the Ayyubid dynasty, Saladin. A sleeping Saladin had a note from Sinan delivered to him by a Fidai planted in his entourage. The note was pinned to his pillow with a dagger, and it informed Saladin that he had been spared this once and should give up his anti-Nizari militancy. A shaken Saladin quickly made a truce with Sinan.


title: Nizari Isma'ilism

text: Subsequently, the Fidai aided the Muslim cause against the Christian Crusaders of the Third Crusade which included Richard the Lionheart of England. Saladin having by now established a friendly relationship with Sinan, the Nizari Fidai themselves joined Saladin's forces to defeat the Crusaders in the last great battle between the two forces. Later on, when "the Nizaris faced renewed Frankish hostilities, they received timely assistance from the Ayyubids".


title: Nizari Isma'ilism

text: The Fidais' apparent lack of fear of personal injury or even death could not be understood by the Crusaders, who propagated the black legends of the so-called Assassins. According to Daftary, these were "fictions ... meant to provide satisfactory explanations for behavior that would otherwise seem strange to the medieval Western mind". These black legends were then further popularized in the Western world by Marco Polo, the Venetian storyteller who had, in fact, never investigated Sinan, in contradiction to his claim that he had. Polo asserted that Sinan fed hashish to his drugged followers, the so-called "Hashishins" (Assassins), so as to fortify them with the type of courage to commit the assassinations of the most intrepid kind.


title: Nizari Isma'ilism

text: This tale of the "Old Man of the Mountain" was assembled by Marco Polo and accepted by Joseph von Hammer-Purgstall, a 19th-century Austrian orientalist responsible for much of the spread of this legend. Until the 1930s, Hammer-Purgstall's retelling of Marco Polo's fiction served as the standard description of the Nizari Ismailis across Europe. "The Russian orientalist Vladimir Alexeyevich Ivanov ... gained access also to Nizari literature preserved in Central Asia, Persia, Afghanistan and elsewhere ... compiled the first detailed catalogue of (Nizari and Fatimid) Ismaili works, citing some 700 separate titles attesting to the hitherto unknown richness and diversity of (Nizari and Fatimid) Ismaili literature and literary traditions".


title: Nizari Isma'ilism

text: As with all Shia Muslims, the succession of leadership following the death of the prophet Muhammed is of major importance to Nizaris. Nizaris believe that at al-Ghadir Khumm, by God's direct command, Muhammad designated his cousin and son-in-law Ali—the husband of his daughter Fatimah—as his successor. As such, Ali became the spiritual successor and the first Imam in the continuing line of hereditary Imams that leads up to the present 49th imam Prince Shah Karim Al Hussaini.


title: Nizari Isma'ilism

text: The Nizari Ismaili tradition is unique in that it is the only tradition that has this continuity of hereditary divine authority vested in the Imamim-Mubeen. In all the Sunni traditions, the Imamim-Mubeen is interpreted as the Quran itself; and in all the Shia traditions, except the Shia Nizari, the Imamim-Mubeen is the last Imam of a dynasty that went into occultation. However, in Nizari Ismailism, the Imamim-Mubeen is a living human Imam who is never in occultation, who will never ever be absent from this world but will always be perpetually present and physically alive, and who is designated as the inheritor of an Imamate passed down from father to son. This tradition has continued for almost 1400 years.


title: Nizari Isma'ilism

text: The Ismailis and the Twelvers split over the succession to Imam Ja'far al-Sadiq. Ismailis contend that Jafar had designated his son Isma'il ibn Jafar as his heir and the next Imam in the hereditary line, and thus the Isma'ilis follow the Imamate of Isma'il and his progeny. Although Imam Ismail predeceased his father, Isma'il supposedly had designated his own son Muhammad ibn Ismail as the next hereditary Imam to follow. In opposition to this belief, the Twelvers believe that Imam Ismail's younger brother Musa al Kadhim was, from the beginning, the rightful successor to Imam Jafar and that Ismail was never a contender.


title: Nizari Isma'ilism

text: The Nizari Ismailis have since split from others, initially from the Qarmatians, Druze, Musta'li Ismailis, Muhammad Shahi Nizari Ismailis, and Satpanthis, the last two splitting from the Nizari branch of Ismailism in the 14th and 15th centuries.


title: Nizari Isma'ilism

text: The "Nizari Ismailis" have always maintained that the Imamah (also known as 'Imamat') can only be inherited from the current Imam to a direct descendant in a father-to-son (or grandson) "hereditary lineage" starting with Imam Ali and then to Imam Hussain and so on until their present and living 49th Imam, Prince Karim al-Husayni Aga Khan IV.


title: Nizari Isma'ilism

text: The Nizaris regard Hassan bin (son of) Ali as a Trustee Imam (imam al-mustawda) as opposed to a Hereditary Imam (imam al-mustaqarr). This fact is clearly demonstrated in the recitation of the Nizari Ismailis’ daily prayers three times a day in which although Hassan bin Ali is revered as part of the Prophet's personal family (Ahl al-Bayt), his name is not included in the hereditary lineage from their first Imam, Imam Ali, to their 49th Imam Prince Karim al Hussaini. If Hassan bin Ali's name were to be included as one of the Ismaili Imams in their prayer recitation then the present Imam Prince Karim of the Nizari Ismailis would have to be the 50th Imam and not the 49th Imam - the way he has identified himself and is known to the world.


title: Nizari Isma'ilism

text: All Nizārī Ismā'īlīs now accept Prince Shah Karim Al-Husayni, the Aga Khan IV, as their Imām-i-Zaman (Imam of the Time). He is referred to in Persian as "Khudawand" (Lord of the Time), in Arabic as "Maulana" (Master) or "Hāzar Imām" (Present Imam). Karim succeeded his grandfather Sir Sultan Muhammad Shah Aga Khan III as Imām in 1957, when he was just 20 and still an undergraduate at Harvard University. He was referred to as "the Imam of the Atomic Age". The period following his accession can be characterized as one of rapid political and economic change. Planning of programs and institutions became increasingly difficult due to the rapid changes in the newly emerging post-colonial nations where many of his followers resided. Upon becoming Imām, Karim's immediate concern was the preparation of his followers, wherever they lived, for the changes that lay ahead. This rapidly evolving situation called for bold initiatives and new programs to reflect developing national aspirations in the newly independent nations.


title: Nizari Isma'ilism

text: In Africa, Asia, and the Middle East, a major objective of the community's social welfare and economic programs, until the mid-1950s, had been to create a broad base of businessmen, agriculturists, and professionals. The educational facilities of the community tended to emphasize secondary-level education. With the coming of independence, each nation's economic aspirations took on new dimensions, focusing on industrialization and the modernization of agriculture. The community's educational priorities had to be reassessed in the context of new national goals, and new institutions had to be created to respond to the growing complexity of the development process.


title: Nizari Isma'ilism

text: In 1972, under the regime of the then President Idi Amin, Ismā'īlīs and Asians were expelled from Uganda, despite being citizens of the country and having lived there for generations. The Imam took urgent steps to facilitate the resettlement of Ismāʿīlīs displaced from Uganda, but also Tanzania, Kenya, and from Burma. Owing to his personal efforts, most found homes, not only in Asia, but also in Europe and North America. Most of the basic resettlement problems were overcome remarkably rapidly. This was due to the adaptability of the Ismāʿīlīs themselves—helped in particular by their education—their linguistic abilities, the efforts of the host countries, and the moral and material support from Ismāʿīlī community programs.


title: Nizari Isma'ilism

text: In view of the importance that Islām places on maintaining a balance between the spiritual well-being of the individual and the quality of his life, the Imām's guidance deals with both aspects of the life of his followers. The Aga Khan has encouraged Ismā'īlī Muslims settled in the industrialized world to contribute towards the progress of communities in the developing world through various development programs. "The Economist" noted that Isma'ili immigrant communities integrated seamlessly as immigrant communities, and did better at attaining graduate and post-graduate degrees, "far surpassing their native, Hindu, Sikh, fellow Muslims, and Chinese communities".


title: Nizari Isma'ilism

text: From July 1982 to July 1983, to celebrate the present Aga Khan's Silver Jubilee marking the 25th anniversary of his accession to the Imamate, many new social and economic development projects were launched. These ranged from the establishment of the US$450 million international Aga Khan University with its Faculty of Health Sciences and teaching hospital based in Karachi; the expansion of schools for girls and medical centers in the Hunza region, one of the remote parts of Northern Pakistan bordering on China and Afghanistan; the establishment of the Aga Khan Rural Support Program in Gujarat, India; and the extension of existing urban hospitals and primary health care centers in Tanzania and Kenya. These initiatives form part of an international network of institutions involved in fields that range from education, health, and rural development, to architecture and the promotion of private sector enterprise and together make up the Aga Khan Development Network.


title: Nizari Isma'ilism

text: From 2007 to 2008, during the Golden Jubilee marking 50 years of his Imamate, the Aga Khan commissioned a number of projects: renowned Pritzker Prize winning Japanese architect Fumihiko Maki was commissioned to design a new kind of community structure, resembling an embassy, in Ottawa, Canada; and the Delegation of the Ismaili Imamat, to be composed of two large interconnected spaces an atrium and a courtyard, opened on 8 December 2008. The atrium is an interior space, to be used all year round. It is protected by a unique glass dome made of multi-faceted, angular planes assembled to create the effect of rock crystal; the Aga Khan asked Maki to consider the qualities of "rock crystal", which was valued by the Imams of the Fatimid Empire, in his design. Within the glass dome is an inner layer of woven glass-fibre fabric which will appear to float and hover over the atrium. The delegation building is located on Sussex Drive near the Canadian parliament. Future delegation buildings are planned for other capitals, beginning with Lisbon, Portugal.


title: Nizari Isma'ilism

text: In addition to primary and secondary schools, the Aga Khan academies, were set up to educate future leaders in the developing world. The Aga Khan Museum, in Toronto, Canada, is the first museum in the West dedicated to Islamic civilization. Completed in 2013, it is dedicated to the "acquisition, preservation and display of artefacts – from various periods and geographies – relating to the intellectual, cultural, artistic and religious heritage of Islamic communities". A series of new Isma'ili centres are underway: including in Toronto, Ontario; Houston, Texas; Dushanbe and the Pamir, Tajikistan.


title: Nizari Isma'ilism

text: During 2017–2018 the Ismaili Muslim community commemorated 60 years since the Aga Khan became the 49th hereditary Imam on 11 July 1957.


title: Nizari Isma'ilism

text: Following an agreement with the Republic of Portugal in 2015, on 11 July 2018, the Aga Khan officially designated the Henrique de Mendonça Palace, located on Rua Marquês de Fronteira in Lisbon, as the "Diwan (seat) of the Ismaili Imamat" ().


title: Nizari Isma'ilism

text: Nizari Ismaili theology is the pre-eminent negative or apophatic theology of Islam because it affirms the absolute Oneness of God ("tawhid") through negating all names, descriptions, conceptions, and limitations from God. The Ismaili theology of tawhid goes back to the teachings of the early Shi‘a Imams, especially Imam Ali ibn Abi Talib (d. 661), Imam Muhammad al-Baqir (d. 743), and Imam Ja‘far al-Sadiq (d. 765). Additionally, a number of eminent Ismaili Muslim philosophers—Abu Ya‘qub al-Sjistani (d. 971), Ja‘far ibn Mansur al-Yaman (d. 960), Hamid al-Din al-Kirmani (d. 1021), al-Mu’ayyad al-Din Shirazi (d. 1077), Nasir-i Khusraw (d. 1088), Abd al-Karim al-Shahrastani (d. 1153), Nasir al-Din al-Tusi (d. 1273)—consolidated and refined the Ismaili theology of tawhid using the strongest philosophical arguments of their time. Even in the present age, Imam Shah Karim al-Husayni Aga Khan IV, the present and 49th hereditary Imam of the Shi‘a Ismaili Muslims, continues to stress the absolute and utter transcendence of God. At the 1975 All-Ismailia Paris Conference, the Ismaili Imam endorsed and approved the following resolution concerning the contemporary Ismaili position on the concept of God:


title: Nizari Isma'ilism

text: The absolute transcendence of God to be emphasized, and the Ismaili belief in God to be expounded in association with the general stress on the transcendence of God in the Qur’an, as exemplified particularly in the Surat al-Ikhlas.


title: Nizari Isma'ilism

text: The full recognition of tawhid, in a mode beyond human rational discourse, is a spiritual and mystical realization in the human soul and intellect called "ma'rifah". In the Ismaili "tariqah" of Islam, the "ma‘rifah" of the "tawhid" of God is attained through the Imam of the Time. The perfect soul of the Imam of the Time always experiences the fullness of the "ma‘rifah" of God and his "murids" reach that recognition through the recognition of the Imam. This is the essential role of the Imam of the time and embodied in the Ismaili Muslim daily prayer called "du'a'". The Aga Khan III also alluded to this when he said that the "real miracle of "Hazrat" Ali is that he brought people to the Truth".


title: Nizari Isma'ilism

text: Nizaris, like all Muslims, consider the Quran, the central religious text of Islam, to be the word of God. Nizaris employ "tafsir" (the science of Quranic commentary) for "zahir", or exoteric understanding, and "tawil" (the Quranic poetic metre), for "batin", or esoteric understanding.


title: Nizari Isma'ilism

text: Tawil stems from the Quranic root word "to return to" the original meaning of the Quran. While acknowledging the importance of both, the "zahir" and the "batin" in religion, the "batin" informs on how the "zahir" is to be practiced. More importantly, the "batin" guides the believer on a spiritual journey of discovery of the intangible truth ("haqiqa") that engages both the intellect (''aql") and the spirit ("ruh") with the ultimate destination being that of gnostic enlightenment ("marifa" or "fana-fillah").


title: Nizari Isma'ilism

text: The word "Quran" means "recitation". When Muslims speak of "the Quran" in the abstract, they usually mean the scripture as recited rather than the printed work or any translation of it. For the Nizari Ismaili, the "tafsir" and "tawil" of the Quran are embodied most perfectly in the being of the "Imam-i-Zaman" (the Imam of the Time), due to his divinity as "the Imam from God Himself" as expressed in the third part of their Shahada.


title: Nizari Isma'ilism

text: Isma'ilism holds that there are seven pillars in Islam, each of which possesses both an exoteric ("outer" or "zahir") expression and an esoteric ("inner" or "batin") one.


title: Nizari Isma'ilism

text: Ismailis believe in the basic principle of One God, and Prophet Muhammed is the final messenger. However, they believe that Muhammed's progeny are the rightful successors of Islam, hence, they seek guidance from "the living imam", who is a living descendant of Muhammed's family.


title: Nizari Isma'ilism

text: Various rival approaches to the challenge that Greek rationalism posed to Quranic revelation permeated early Islamic society. The Athʿaris considered "Kalam" (reason) as contradictory to Islam, and "falsafa" (philosophy) as antagonistic to faith, which asserts the absolute supremacy of revelation, and the abandonment of reason in the spiritual and secular space (which are interconnected within orthodox Islam). The Mu'tazilis took a less absolutist approach, allowing for a limited role of reason (Kalam). Isma'ilis adopted an altogether more philosophical approach, in which only through reasoned discourse could one attain understanding of revelation, social structure, and individualism, as well as the functioning of the natural world. For this reason Isma'ilis produced a relatively scant collection of theological discourse in comparison to other Shia, and the Sunni. Yet they had a leading place in the development of philosophical discourse within the Islamic world.


title: Nizari Isma'ilism

text: While Nizaris subscribe to the Imami jurisprudence, they also follow in part the "Ja'fāriyya" "Madhhab" (school of Jurisprudence), which is believed by Shias to have been founded by Imam Ja'far as-Sadiq. Nizaris adhere to supremacy of "Kalam" in the interpretation of scripture, and in the temporal relativism of understanding, as opposed to "fiqh" (traditional legalism), which adheres to an absolutist approach to revelation.


title: Nizari Isma'ilism

text: For Nizaris, there exists a dialectic between revelation and human reasoning, based on a synergy of Islamic scripture and classical Greek philosophy, in particular Aristotelian reasoning and neoplatonic metaphysics. It seeks to extend an understanding of religion and revelation to identify the outwardly apparent ("zahir"), and also to penetrate to the roots, to retrieve and disclose that which is the inner underlying ("batin"). This process of discovery engages both the intellect ("'aql") and the spirit ("ruh"), generating an integral synergy to illuminate and disclose truths ("haqi'qat") culminating in "gnosis" ("ma'rifat"). Parallels have also been noted between the Nizari version of "Imamah" and the Platonic idea of a philosopher king.


title: Nizari Isma'ilism

text: Over the many phases of Nizārī Ismāʿīlī history – pre-Fāṭimid, Fāṭimid, Alamūt, Post-Alamūt, Anjudan, etc., there has never been a single unified view of eschatology. While there are certainly eschatological ideas from the Pre-Fāṭimid period that have been carried unto the present day, particularly those of Abū Ya’qūb al-Sijistānī and his intellectual disciples, each phase has brought in original ideas and renewed those of the past. The academic field of Ismāʿīlī eschatology is one that has been rarely studied in western secondary literature, and the little work that has been done on Ismāʿīlī eschatology primarily surrounds the event of the proclamation of a qiyāmah during the Alamūt period. Otherwise, there have been zero studies published on the eschatologies of pre-Fāṭimid Ismāʿīlī thinkers and post-Alamūt Ismaili thinkers. Furthermore, no work done has been done on the eschatology of the South Asian traditions of Nizārī Ismāʿīlism.


title: Nizari Isma'ilism

text: The Ismāʿīlīs, like the "falāsifa" (Islamic Neoplatonic-Aristotelian philosophers), have understood resurrection, paradise, and hell through "taʾwīl" (esoteric interpretation) and, thus, have all argued that these are spiritual realties and not physical, material realities. On the rewards of Paradise, al-Sijistānī writes in the "Kitāb al-Yanābīʿ":لما كان قصارى الثواب انما هي اللذة ، وكانت اللذة الحسية منقطعة زائلة ، وجب ان تكون التي ينالها المثاب ازلية غير فانية ، باقية غير منقطعة . وليست لذة بسيطة باقية على حالاتها غير لذة العلم . كان من هذا القول وجوب لذه العلم للمثاب  في دار البقاء ، كما قال الله عز وجل : اكلها دائم وظلها تلك عقبى الذين اتقوا


title: Nizari Isma'ilism

text: “"Because the limit of reward is pleasure, and sensual pleasure is ephemeral, and it is necessary that the reward which is obtained be eternal and not ephemeral, everlasting and not discontinuous. And there is no simple, everlasting pleasure except the pleasure of knowledge. From this statement, it necessarily follows that the pleasure of knowledge is the reward in the hereafter, as God, glorified and sublime, said: “Its fruit is everlasting and its shade, that is the destination of those who are righteous" (Qurʾān 13:35)”According to al-Sijistānī, the most important piece of knowledge to acquire is the recognition of the one who initiates the resurrection, whom he calls "Ṣāḥib al-Qiyāmah" (Lord of Resurrection). Al-Sijistānī writes in the "Kitāb al-Yanābīʿ":فترى الناس على طبقتين : طبقة ممن آمنوا به وصدقوه وانتظروا ظهور، فهم بذلك النور مقتبسون، متنعمون ، مستبشرون . وطبقة ممن كذبوا به وغفلوا عن حده ۲ ، فهم بذلك النور ايضاً متحرقون ، معاقبون


title: Nizari Isma'ilism

text: “"So you will see people divided into two classes: One class consists of those who believe in the Lord of Resurrection, pronounce his Truth, and await his appearance. They are in that Light, acquiring knowledge, blessed, and rejoicing. The other class consists of those who deny him and ignore his rank. They are in the Light also, but are burned and punished"”Paradise and Hellfire in the Nizārī Ismāʿīlī tradition, thus, are not characterized by material forms, sensual pleasures, and physical burning, rather Paradise is understood to be the presence of knowledge of real truths while Hellfire is understood to be ignorance. The Nizārī Ismāʿīlī philosopher-theologians, as can be seen in the passage quoted above, did not believe that Paradise and Hellfire were “places” that souls inhabit, rather – because the rewards and punishments are spiritual – they are something the soul directly experiences in itself. Al-Sijistānī explicitly says in the passage above that both classes of people are exposed to same Light (فهم بذلك النور ايضاً), however one class experiences this Light as blessings whilst the other experiences it as burning. These states correspond not to location, but to the level of knowledge in the soul. Additionally, the most famous intellectual disciple of al- Sijistānī – Nāṣir-i Khusraw – writes in the "Shish Fasl":“"[I]t is inevitable that the human soul should return to the Universal Soul. The question only concerns the manner in which it will return...If, however, the return of the individual soul to its source is not in harmony, it will meet with suffering hardships whose painfulness is described by being placed in the midst of fire, the position which will never come to an end"”Thus, for Nāṣir-i Khusraw, all souls return to the same spiritual abode but those souls which are ignorant will experience pain, as if “"being placed in the midst of fire"”. While Nāṣir-i Khusraw suggests here the suffering is eternal, he has in another text – specifically the "Wajh-i Dīn" – indicated that the pains of Hell are temporary and that the Prophet will come on the Day of Resurrection to blow out the fires of Hell and rescue its inhabitants. While both infernalist and universalist positions have existed as legitimate views in the community, annihilationist views have existed as well, specifically being introduced by Naṣīr al-Dīn al-Ṭūsī. Like both al-Sijistānī and Nāṣir-i Khusraw, Naṣīr al-Dīn al-Ṭūsī believed that paradise and hell were spiritual and mental states that the soul experiences and not physical places or sensual pains and desires. While Naṣīr al-Dīn al-Ṭūsī believed that the punishment of ignorant, damned souls was eternal, he believed this eternal punishment took the form of annihilation, i.e. permanent non-existence. He writes:“"There is also only one real Hell, and that is eternal punishment, everlasting disappointment and eternal non-existence; the meaning of all this is being outcast from God in every sense of the word"” The last most public eschatological view espoused by any Ismāʿīlī was written by the 48th Ismāʿīlī Imām – Sulṭān Muḥammad Shāh Āgā Khān III – who endorses a universalist position in regards to salvation and specifically states in his Memoirs that he prays “"that all may be reconciled in Heaven in a final total absolution"”. The position of Āgā Khān III can be said to be generally in line with classical Ismāʿīlī views, as well as the views of the "falāsifa" and Sunnī-Sufīs like Ibn ʿArabi (such as in his "Futūḥāt al-Makkiyya") and those of the Shīʿī ʿIrfān tradition, like Mullā Ṣadra (such as in his "Tafsīr Sūrat al-Fātiḥa").


title: Nizari Isma'ilism

text: The present Aga Khan continued the practice of his predecessor and gave constitutions to Ismā'īlī communities in the US, Canada, several European countries, the Persian Gulf, Syria, and Iran, following a process of consultation within each constituency. In 1986, he promulgated a World Constitution that, for the first time, brought the social governance of the worldwide Ismā'īlī community into a single structure with built-in flexibility to account for diverse circumstances of different regions. Served by volunteers appointed by and accountable to the Imam, the Constitution functions to enable individual creativity in an ethos of group responsibility to promote the common well-being.


title: Nizari Isma'ilism

text: Like its predecessors, the present constitution is founded on adherence to the basic principles of Islam, belief in one God and Muhammad as the seal of the prophets, and on each Ismā'īlī's spiritual allegiance to the Imām of the Time, which is separate from the secular allegiance that all Ismā'īlīs owe as citizens to their national entities. The present Imam and his predecessor emphasized every Ismāʿīlī's allegiance to his or her country as a fundamental obligation. These obligations are discharged not by passive affirmation but through responsible engagement and active commitment to uphold national integrity and contribute to peaceful development.


title: Nizari Isma'ilism

text: Jama'at Khana (, from the Arabic "Jamaat" (congregation) and the Persian "Khaneh" (house)) are Isma'ili houses of prayer, study, and community. They usually contain separate spaces for prayer and a social hall for community gatherings.


title: Nizari Isma'ilism

text: There are no principle architectural guidelines for Jama'at Khana, although inspiration is drawn from Islamic architecture and local architectural traditions to seamlessly and discreetly blend them with the local architectural environment, informed by a minimalist design aesthetic.


title: Nizari Isma'ilism

text: Larger Jama'at Khana are referred to as "Darkhanas", or "Isma'ili Centers" in the West, and have been referred to as "Isma'ili Cathedrals" by observers. While containing prayer and social infrastructure albeit on a larger scale, they may also contain auditoriums and lecture spaces, libraries, offices, and council chambers, as they act as the regional or national governing centers for community administration.


title: Nizari Isma'ilism

text: Jama'at Khana, particularly the larger centers, offer their spaces to the community at large, and arrange guided tours. However, during the obligatory prayer ("Holy Du'a") only Isma'ili are allowed to enter the prayer hall ("masjid").


title: Nizari Isma'ilism

text: In the Ismaili tariqah, the guardian of each Jamatkhana is called mukhi (in the South-Asian tradition) or Sheikh (in the Arab tradition) there are also other names that are applied based on the cultural context of the Jamat, mukhi is a word derived from mukhiya means foremost. Since the Imam physically is not present all the times in the Jamatkhana, the Mukhi acts [as the] tangible symbol of the Imam's authority. In the big jamat, the Mukhi was assisted by a caretaker called tha'nak. Later, the office of kamadia (from kamdar [meaning] accountant) was created. The Mukhi and Kamadia are the traditional titles going back to the pre-Aga Khan period when they enjoyed considerable local power. Their responsibilities include officiating over the daily rituals in the Jamatkhana, but they are primarily lay officials. Since the wholesale reorganizations undertaken by the Imams, the local committees are now tied into an elaborately hierarchical administrative structure of boards and councils.


title: Nizari Isma'ilism

text: The Fatimids adopted Green ("akhdar") as the colour of their standard, which symbolized their allegiance to Ali, who, in order to thwart an assassination attempt on Muhammad, once wrapped himself in a green coverlet to appear to be Muhammad. When Hassan I Sabbah captured Alamut, it is said he hoisted the green standard over the fortress, it was later reported that Hassan I Sabbah prophesied that when the Hidden Imam made himself known he would hoist a red flag, which Hasan II did during his appearance. Following the destruction of Alamut, Isma'ili hoisted both green and red flags above the tombs of their Imams. Green and Red were combined in the 19th century Isma'ili flag known as "My Flag".


title: Nizari Isma'ilism

text: The Fatimids also used a white standard with gold inlays, and the Caliph Imams often wore white with gold, as Isma'ili Imams do today. Isma'ili use a gold crest on white standard to symbolize the authority of Imamate, and often wear white in the presence of their Imam.


title: Nizari Isma'ilism

text: Marriage ("urs", عرس) is a legal wedding contract ("Nikah", النكاح) between a consenting adult man and a woman. As a contract, it allows both parties to add certain conditions. Nizari ideals of marriage envision a long-term union.


title: Nizari Isma'ilism

text: Since marriage is not considered a sacrament, Nizari Isma'ili consider secular court marriages in the West as valid legal contracts. However many Isma'ili couples opt to have both a court marriage to secure legal recognition as well as a "Nikah" ceremony performed at a Jama'at Khana.


title: Nizari Isma'ilism

text: Unlike many other groups, inter-faith marriages are recognized by the community. In addition to the other Abrahamic faiths, the prevalence of Nizari Ismailis of South Asian descent has resulted in growing numbers married to those of Dharmic faiths, such as Hinduism, Buddhism, and Jainism, as well as other Indian religions, such as Sikhism and Zoroastrianism. The Aga Khan IV has said that he has no objection to increasingly-common mixed marriages, and has met non-Ismaili spouses and children during his various "deedars" throughout the world. In fact, many members of his family, including his daughter Princess Zahra Aga Khan, have married non-Ismailis in inter-faith ceremonies. Child marriages are strictly prohibited. The Aga Khan IV also condemned polygamy, except in certain circumstances.


title: Nizari Isma'ilism

text: "Nāndi" is a ceremony in which food is symbolically offered to the Imām-e Zamān, and is subsequently auctioned to the congregation. Money obtained is used for the expenses incurred in JammatKhana. The ceremony is conducted by volunteers from the community. The food is prepared at home and is brought to the Jama'at Khana; the Mukhi (congregation head) blesses the food offering, known as "Mehmāni", at the end of prayers, informing the congregation that it has been offered to the Imam and the benefits of it are for the whole Jamat. If no physical food offering has been brought to the Jama'at Khana, then a symbolic plate called the "Mehmāni plate", which serves as a substitute, can be touched during the "Du'a Karavi" ceremony.


title: Nizari Isma'ilism

text: The origins of "Nāndi" are said to be in the Prophet Muhammad's time when a similar practice occurred.


title: Nizari Isma'ilism

text: Nizari use an arithmetically based lunar calendar to calculate the year, unlike most Muslim communities, which rely on visual sightings. The Isma'ili calendar was developed in the Middle Ages during the Faitmid Caliphate of Imam Al-Hakim.


title: Nizari Isma'ilism

text: A lunar year contains about 354 11/30 days, Nizari Isma'ili employ a cycle of 11 leap years ("kasibah") with 355 days in a 30-year cycle. The odd-numbered months contain 30 days and the even numbered months 29 days; the 12th and final month in a leap year contains 30 days.


title: Nizari Isma'ilism

text: Unlike the other branches of Islam, Nizari Isma'ilis divide the Ramadan fast into two separate, but closely related, kinds: "ẓāhirī ṣawm" (exoteric fasting) and "bāṭinī ṣawm" (esoteric fasting). The former refers to the abstention food, drink and sensual pleasure. The latter refers to the abstention from communicating the esoteric knowledge of revelation ("tanzīl") and interpretation ("ta’wīl") to those who are not ready to receive it.


title: Nizari Isma'ilism

text: A third kind of fasting known as "ḥaqīqī ṣawm" (real fasting) is the abstention from anything (in thought, word, or deed) which is contrary to the Command of God. This kind is observed year-round.


title: Nizari Isma'ilism

text: The Aga Khan Development Network (AKDN) was set up by the Imamate and the Ismaili community as a group of private, non-denominational development agencies that seek to empower communities and individuals, regardless of ethnicity or religious affiliation, and seek to improve living conditions and opportunities within the developing world. It has active working relationships with international organizations such as the United Nations (UN) and the European Union (EU), and private organizations such as the Bill & Melinda Gates Foundation. Governmental bodies the AKDN works with include the United States Agency for International Development, the Canadian International Development Agency, the United Kingdom's Department for International Development, and Germany's Federal Ministry of Economic Cooperation and Development.


title: Nizari Isma'ilism

text: It's also known that the Aga Khan Development Network is funded by donations and offerings given by the followers of the Aga Khan.


title: Nizari Isma'ilism

text: For a list of Ismaili Imams: Daftary, Farhad (1990). "The Ismailis: Their history and doctrines". Cambridge, England: Cambridge University Press. pp. 551–553. .


title: Toll-like receptor

text: Toll-like receptors (TLRs) are a class of proteins that play a key role in the innate immune system. They are single-pass membrane-spanning receptors usually expressed on sentinel cells such as macrophages and dendritic cells, that recognize structurally conserved molecules derived from microbes. Once these microbes have reached physical barriers such as the skin or intestinal tract mucosa, they are recognized by TLRs, which activate immune cell responses. The TLRs include TLR1, TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR8, TLR9, TLR10, TLR11, TLR12, and TLR13. Humans lack genes for TLR11, TLR12 and TLR13 and mice lack a functional gene for TLR10. TLR1, TLR2, TLR4, TLR5, TLR6, and TLR10 are located on the cell membrane, whereas TLR3, TLR7, TLR8, and TLR9 are located in intracellular vesicles (because they are sensors of nucleic acids).


title: Toll-like receptor

text: The ability of the immune system to recognize molecules that are broadly shared by pathogens is, in part, due to the presence of immune receptors called toll-like receptors (TLRs) that are expressed on the membranes of leukocytes including dendritic cells, macrophages, natural killer cells, cells of the adaptive immunity T cells, and B cells, and non-immune cells (epithelial and endothelial cells, and fibroblasts).


title: Toll-like receptor

text: The binding of ligands - either in the form of adjuvant used in vaccinations or in the form of invasive moieties during times of natural infection - to the TLR marks the key molecular events that ultimately lead to innate immune responses and the development of antigen-specific acquired immunity.


title: Toll-like receptor

text: Upon activation, TLRs recruit adaptor proteins (proteins that mediate other protein-protein interactions) within the cytosol of the immune cell to propagate the antigen-induced signal transduction pathway. These recruited proteins are then responsible for the subsequent activation of other downstream proteins, including protein kinases (IKKi, IRAK1, IRAK4, and TBK1) that further amplify the signal and ultimately lead to the upregulation or suppression of genes that orchestrate inflammatory responses and other transcriptional events. Some of these events lead to cytokine production, proliferation, and survival, while others lead to greater adaptive immunity. If the ligand is a bacterial factor, the pathogen might be phagocytosed and digested, and its antigens presented to CD4+ T cells.


title: Toll-like receptor

text: In the case of a viral factor, the infected cell may shut off its protein synthesis and may undergo programmed cell death (apoptosis). Immune cells that have detected a virus may also release anti-viral factors such as interferons.


title: Toll-like receptor

text: Toll-like receptors have also been shown to be an important link between innate and adaptive immunity through their presence in dendritic cells. Flagellin, a TLR5 ligand, induces cytokine secretion on interacting with TLR5 on human T cells.


title: Toll-like receptor

text: TLRs are a type of pattern recognition receptor (PRR) and recognize molecules that are broadly shared by pathogens but distinguishable from host molecules, collectively referred to as pathogen-associated molecular patterns (PAMPs). In addition to the recognition of exogenous PAMPs, TLRs can also bind to endogenous damage-associated molecular patterns (DAMPs) such as heat shock proteins (HSPs) or plasma membrane constituents. TLRs together with the Interleukin-1 receptors form a receptor superfamily, known as the "interleukin-1 receptor / toll-like receptor superfamily"; all members of this family have in common a so-called TIR (toll-IL-1 receptor) domain.


title: Toll-like receptor

text: Three subgroups of TIR domains exist. Proteins with subgroup 1 TIR domains are receptors for interleukins that are produced by macrophages, monocytes, and dendritic cells and all have extracellular Immunoglobulin (Ig) domains. Proteins with subgroup 2 TIR domains are classical TLRs, and bind directly or indirectly to molecules of microbial origin. A third subgroup of proteins containing TIR domains consists of adaptor proteins that are exclusively cytosolic and mediate signaling from proteins of subgroups 1 and 2.


title: Toll-like receptor

text: TLRs are present in vertebrates as well as invertebrates. Molecular building blocks of the TLRs are represented in bacteria and in plants, and plant pattern recognition receptors are well known to be required for host defence against infection. The TLRs thus appear to be one of the most ancient, conserved components of the immune system.


title: Toll-like receptor

text: In recent years TLRs were identified also in the mammalian nervous system. Members of the TLR family were detected on glia, neurons and on neural progenitor cells in which they regulate cell-fate decision.


title: Toll-like receptor

text: It has been estimated that most mammalian species have between ten and fifteen types of toll-like receptors. Thirteen TLRs (named simply TLR1 to TLR13) have been identified in humans and mice together, and equivalent forms of many of these have been found in other mammalian species. However, equivalents of certain TLR found in humans are not present in all mammals. For example, a gene coding for a protein analogous to TLR10 in humans is present in mice, but appears to have been damaged at some point in the past by a retrovirus. On the other hand, mice express TLRs 11, 12, and 13, none of which is represented in humans. Other mammals may express TLRs that are not found in humans. Other non-mammalian species may have TLRs distinct from mammals, as demonstrated by the anti-cell-wall TLR14, which is found in the Takifugu pufferfish. This may complicate the process of using experimental animals as models of human innate immunity.


title: Toll-like receptor

text: Vertebrate TLRs are divided by similarity into the families of TLR 1/2/6/10/14/15, TLR 3, TLR 4, TLR 5, TLR 7/8/9, and TLR 11/12/13/16/21/22/23.


title: Toll-like receptor

text: The involvement of toll signalling in immunity was first demonstrated in the fruit fly, "Drosophila melanogaster". Fruit flies have only innate immune responses allowing studies to avoid interference of adaptive immune mechanisms on signal transduction. The fly response to fungal or bacterial infection occurs through two distinct signalling cascades, one of which is the toll pathway and the other is the immune deficiency pathway. The toll pathway is similar to mammalian TLR signalling, but unlike mammalian TLRs, toll is not activated directly by pathogen-associated molecular patterns (PAMPs). Its receptor ectodomain recognizes the cleaved form of the cytokine spätzle, which is secreted in the haemolymph as an inactive dimeric precursor. The toll receptor shares the cytoplasmatic TIR domain with mammalian TLRs, but the ectodomain and intracytoplasmatic tail are different. This difference might reflect a function of these receptors as cytokine receptors rather than PRRs.


title: Toll-like receptor

text: The toll pathway is activated by different stimuli, such as Gram positive bacteria, fungi and virulence factors. First, the Spätzle processing enzyme (SPE) is activated in response to infection and cleaves spätzle ("spz"). Cleaved spätzle then binds to the toll receptor and crosslinks its ectodomains. This triggers conformational changes in the receptor resulting in signalling through toll. From this point forward, the signalling cascade is very similar to mammalian signalling through TLRs. The toll-induced signalling complex (TICS) is composed of MyD88, Tube, and Pelle (the orthologue of mammalian IRAK). Signal from TICS is then transduced to Cactus (homologue of mammalian IκB), phosphorylated Cactus is polyubiquitylated and degraded, allowing nuclear translocation of DIF (dorsal-related immunity factor; a homologue of mammalian NF-κB) and induction of transcription of genes for antimicrobial peptides (AMPs) such as drosomycin.


title: Toll-like receptor

text: "Drosophila" have a total of 9 "toll" family and 6 "spz" family genes that interact with each other to differing degrees.


title: Toll-like receptor

text: TLR3 does not use the MyD88 dependent pathway. Its ligand is retroviral double-stranded RNA (dsRNA), which activates the TRIF dependent signalling pathway. To explore the role of this pathway in retroviral reprograming, knock down techniques of TLR3 or TRIF were prepared, and results showed that only the TLR3 pathway is required for full induction of target gene expression by the retrovirus expression vector. This retroviral expression of four transcriptional factors (Oct4, Sox2, Klf4 and c-Myc; OSKM) induces pluripotency in somatic cells. This is supported by study, which shows, that efficiency and amount of human iPSC generation, using retroviral vectors, is reduced by knockdown of the pathway with peptide inhibitors or shRNA knockdown of TLR3 or its adaptor protein TRIF. Taken together, stimulation of TLR3 causes great changes in chromatin remodeling and nuclear reprogramming, and activation of inflammatory pathways is required for these changes, induction of pluripotency genes and generation of human induced pluripotent stem cells (iPSC) colonies.


title: Toll-like receptor

text: As noted above, human cells do not express TLR11, but mice cells do. Mouse-specific TLR11 recognizes uropathogenic "E.coli" and the apicomplexan parasite "Toxoplasma gondii". With "Toxoplasma" its ligand is the protein profilin and the ligand for "E. coli" is flagellin. The flagellin from the enteropathogen "Salmonella" is also recognized by TLR11.


title: Toll-like receptor

text: As mouse TLR11 is able to recognize "Salmonella" effectively, normal mice do not get infected by oral "Salmonella" Typhi, which causes food- and waterborne gastroenteritis and typhoid fever in humans. TLR11 deficient knockout mice, on the other hand, are efficiently infected. As a result, this knockout mouse can act as a disease model of human typhoid fever.


title: Toll-like receptor

text: Toll-like receptors bind and become activated by different ligands, which, in turn, are located on different types of organisms or structures. They also have different adapters to respond to activation and are located sometimes at the cell surface and sometimes to internal cell compartments. Furthermore, they are expressed by different types of leucocytes or other cell types:


title: Toll-like receptor

text: Because of the specificity of toll-like receptors (and other innate immune receptors) they cannot easily be changed in the course of evolution, these receptors recognize molecules that are constantly associated with threats (i.e., pathogen or cell stress) and are highly specific to these threats (i.e., cannot be mistaken for self molecules that are normally expressed under physiological conditions). Pathogen-associated molecules that meet this requirement are thought to be critical to the pathogen's function and difficult to change through mutation; they are said to be evolutionarily conserved. Somewhat conserved features in pathogens include bacterial cell-surface lipopolysaccharides (LPS), lipoproteins, lipopeptides, and lipoarabinomannan; proteins such as flagellin from bacterial flagella; double-stranded RNA of viruses; or the unmethylated CpG islands of bacterial and viral DNA; and also of the CpG islands found in the promoters of eukaryotic DNA; as well as certain other RNA and DNA molecules. For most of the TLRs, ligand recognition specificity has now been established by gene targeting (also known as "gene knockout"): a technique by which individual genes may be selectively deleted in mice. See the table above for a summary of known TLR ligands.


title: Toll-like receptor

text: The stereotypic inflammatory response provoked by toll-like receptor activation has prompted speculation that endogenous activators of toll-like receptors might participate in autoimmune diseases. TLRs have been suspected of binding to host molecules including fibrinogen (involved in blood clotting), heat shock proteins (HSPs), HMGB1, extracellular matrix components and self DNA (it is normally degraded by nucleases, but under inflammatory and autoimmune conditions it can form a complex with endogenous proteins, become resistant to these nucleases and gain access to endosomal TLRs as TLR7 or TLR9). These endogenous ligands are usually produced as a result of non-physiological cell death.


title: Toll-like receptor

text: TLRs are believed to function as dimers. Though most TLRs appear to function as homodimers, TLR2 forms heterodimers with TLR1 or TLR6, each dimer having a different ligand specificity. TLRs may also depend on other co-receptors for full ligand sensitivity, such as in the case of TLR4's recognition of LPS, which requires MD-2. CD14 and LPS-Binding Protein (LBP) are known to facilitate the presentation of LPS to MD-2.


title: Toll-like receptor

text: A set of endosomal TLRs comprising TLR3, TLR7, TLR8 and TLR9 recognize nucleic acid derived from viruses as well as endogenous nucleic acids in context of pathogenic events. Activation of these receptor leads to production of inflammatory cytokines as well as type I interferons (interferon type I) to help fight viral infection.


title: Toll-like receptor

text: The adapter proteins and kinases that mediate TLR signaling have also been targeted. In addition, random germline mutagenesis with ENU has been used to decipher the TLR signaling pathways. When activated, TLRs recruit adapter molecules within the cytoplasm of cells to propagate a signal. Four adapter molecules are known to be involved in signaling. These proteins are known as MyD88, TIRAP (also called Mal), TRIF, and TRAM (TRIF-related adaptor molecule).


title: Toll-like receptor

text: TLR signaling is divided into two distinct signaling pathways, the MyD88-dependent and TRIF-dependent pathway.


title: Toll-like receptor

text: The MyD88-dependent response occurs on dimerization of TLRs, and is used by every TLR except TLR3. Its primary effect is activation of NFκB and Mitogen-activated protein kinase. Ligand binding and conformational change that occurs in the receptor recruits the adaptor protein MyD88, a member of the TIR family. MyD88 then recruits IRAK4, IRAK1 and IRAK2. IRAK kinases then phosphorylate and activate the protein TRAF6, which in turn polyubiquinates the protein TAK1, as well as itself to facilitate binding to IKK-β. On binding, TAK1 phosphorylates IKK-β, which then phosphorylates IκB causing its degradation and allowing NFκB to diffuse into the cell nucleus and activate transcription and consequent induction of inflammatory cytokines.


title: Toll-like receptor

text: Both TLR3 and TLR4 use the TRIF-dependent pathway, which is triggered by dsRNA and LPS, respectively. For TLR3, dsRNA leads to activation of the receptor, recruiting the adaptor TRIF. TRIF activates the kinases TBK1 and RIPK1, which creates a branch in the signaling pathway. The TRIF/TBK1 signaling complex phosphorylates IRF3 allowing its translocation into the nucleus and production of Interferon type I. Meanwhile, activation of RIPK1 causes the polyubiquitination and activation of TAK1 and NFκB transcription in the same manner as the MyD88-dependent pathway.


title: Toll-like receptor

text: TLR signaling ultimately leads to the induction or suppression of genes that orchestrate the inflammatory response. In all, thousands of genes are activated by TLR signaling, and collectively, the TLRs constitute one of the most pleiotropic yet tightly regulated gateways for gene modulation.


title: Toll-like receptor

text: TLR4 is the only TLR that uses all four adaptors. Complex consisting of TLR4, MD2 and LPS recruits TIR domain-containing adaptors TIRAP and MyD88 and thus initiates activation of NFκB (early phase) and MAPK. TLR4-MD2-LPS complex then undergoes endocytosis and in endosome it forms a signalling complex with TRAM and TRIF adaptors. This TRIF-dependent pathway again leads to IRF3 activation and production of type I interferons, but it also activates late-phase NFκB activation. Both late and early phase activation of NFκB is required for production of inflammatory cytokines.


title: Toll-like receptor

text: Imiquimod (cardinally used in dermatology) is a TLR7 agonist, and its successor resiquimod, is a TLR7 and TLR8 agonist. Recently, resiquimod has been explored as an agent for cancer immunotherapy, acting through stimulation of tumor-associated macrophages.


title: Toll-like receptor

text: Several TLR ligands are in clinical development or being tested in animal models as vaccine adjuvants, with the first clinical use in humans in a recombinant herpes zoster vaccine in 2017, which contains a monophosphoryl lipid A component.


title: Toll-like receptor

text: TLR7 messenger RNA expression levels in dairy animals in a natural outbreak of foot-and-mouth disease have been reported.


title: Toll-like receptor

text: TLR4 has been shown to be important for the long-term side-effects of opioids. Its activation leads to downstream release of inflammatory modulators including TNF-α and IL-1β, and constant low-level release of these modulators is thought to reduce the efficacy of opioid drug treatment with time, and is involved in opioid tolerance, hyperalgesia and allodynia. Morphine induced TLR4 activation attenuates pain suppression by opioids and enhances the development of opioid tolerance and addiction, drug abuse, and other negative side effects such as respiratory depression and hyperalgesia. Drugs that block the action of TNF-α or IL-1β have been shown to increase the analgesic effects of opioids and reduce the development of tolerance and other side-effects, and this has also been demonstrated with drugs that block TLR4 itself.


title: Toll-like receptor

text: The "unnatural" enantiomers of opioid drugs such as (+)-morphine and (+)-naloxone lack affinity for opioid receptors, still produce the same activity at TLR4 as their "normal" enantiomers. So, "unnatural" entianomers of opioids such as (+)-naloxone, can be used to block the TLR4 activity of opioid analgesic drugs without having any affinity for μ-opioid receptor


title: Toll-like receptor

text: When microbes were first recognized as the cause of infectious diseases, it was immediately clear that multicellular organisms must be capable of recognizing them when infected and, hence, capable of recognizing molecules unique to microbes. A large body of literature, spanning most of the last century, attests to the search for the key molecules and their receptors. More than 100 years ago, Richard Pfeiffer, a student of Robert Koch, coined the term "endotoxin" to describe a substance produced by Gram-negative bacteria that could provoke fever and shock in experimental animals. In the decades that followed, endotoxin was chemically characterized and identified as a lipopolysaccharide (LPS) produced by most Gram-negative bacteria. This lipopolysaccharide is an integral part of the gram-negative membrane and is released upon destruction of the bacterium. Other molecules (bacterial lipopeptides, flagellin, and unmethylated DNA) were shown in turn to provoke host responses that are normally protective. However, these responses can be detrimental if they are excessively prolonged or intense. It followed logically that there must be receptors for such molecules, capable of alerting the host to the presence of infection, but these remained elusive for many years. Toll-like receptors are now counted among the key molecules that alert the immune system to the presence of microbial infections.


title: Toll-like receptor

text: The prototypic member of the family, the "toll" receptor (; Tl) in the fruit fly "Drosophila melanogaster", was discovered in 1985 by 1995 Nobel Laureates Christiane Nüsslein-Volhard and Eric Wieschaus and colleagues. It was known for its developmental function in embryogenesis by establishing the dorsal-ventral axis. It was named after Christiane Nüsslein-Volhard's 1985 exclamation, "" ("That's amazing!"), in reference to the underdeveloped ventral portion of a fruit fly larva. It was cloned by the laboratory of Kathryn Anderson in 1988. In 1996, "toll" was found by Jules A. Hoffmann and his colleagues to have an essential role in the fly's immunity to fungal infection, which it achieved by activating the synthesis of antimicrobial peptides.


title: Toll-like receptor

text: The first reported human toll-like receptor was described by Nomura and colleagues in 1994, mapped to a chromosome by Taguchi and colleagues in 1996. Because the immune function of toll in "Drosophila" was not then known, it was assumed that TIL (now known as TLR1) might participate in mammalian development. However, in 1991 (prior to the discovery of TIL) it was observed that a molecule with a clear role in immune function in mammals, the interleukin-1 (IL-1) receptor, also had homology to drosophila toll; the cytoplasmic portions of both molecules were similar.


title: Toll-like receptor

text: In 1997, Charles Janeway and Ruslan Medzhitov showed that a toll-like receptor now known as TLR4 could, when artificially ligated using antibodies, induce the activation of certain genes necessary for initiating an adaptive immune response. TLR 4 function as an LPS sensing receptor was discovered by Bruce A. Beutler and colleagues. These workers used positional cloning to prove that mice that could not respond to LPS had mutations that abolished the function of TLR4. This identified TLR4 as one of the key components of the receptor for LPS.


title: Toll-like receptor

text: In turn, the other TLR genes were ablated in mice by gene targeting, largely in the laboratory of Shizuo Akira and colleagues. Each TLR is now believed to detect a discrete collection of molecules – some of microbial origin, and some products of cell damage – and to signal the presence of infections.


title: Toll-like receptor

text: Plant homologs of "toll" were discovered by Pamela Ronald in 1995 (rice XA21) and Thomas Boller in 2000 ("Arabidopsis" FLS2).


title: Toll-like receptor

text: In 2011, Beutler and Hoffmann were awarded the Nobel Prize in Medicine or Physiology for their work. Hoffmann and Akira received the Canada Gairdner International Award in 2011.


The Basilica of the National Shrine of the Immaculate Conception is a large minor Catholic basilica and national shrine in the United States in Washington, D.C., located at 400 Michigan Avenue Northeast, adjacent to Catholic University.


title: Basilica of the National Shrine of the Immaculate Conception

text: The shrine is the largest Catholic church building in North America, and one of the largest in the world; the basilica is also the tallest habitable building in Washington, D.C. Its construction of Byzantine Revival and Romanesque Revival architecture began on September 23, 1920, with renowned contractor John McShain and was completed on December 8, 2017, with the dedication and solemn blessing of the "Trinity Dome" mosaic.


text: The basilica is the national and patronal Catholic church of the United States, honoring the Immaculate Conception as Patroness, accorded by Pope Pius IX on February 7, 1847. Pope Pius XI donated a mosaic rendition of the image in 1923. The shrine has merited several papal visits, namely the following:


text: Although the basilica is situated within the geographical boundaries of the Archdiocese of Washington, the basilica is not a parish of the archdiocese, does not have its own parish community, and the shrine’s administration does not fall under the direct authority of the Archbishop, but it serves adjacent Catholic University, which donated the land for its construction, and the United States Conference of Catholic Bishops. It also hosts numerous Masses for various organizations of the Church from across the United States. The basilica is not the cathedral of the archdiocese, as that title and honor belongs to the Cathedral of St. Matthew the Apostle, although numerous archdiocesan events are held at the basilica. As of 2022, the rector of the basilica is the Reverend Monsignor Walter R. Rossi, who holds a Licentiate of Canon Law.


text: The basilica houses 82 Marian chapels (including the Our Mother of Africa Chapel), as well as other sacred images, flanking the sides of the Great Upper Church and the Crypt Church. They were designed to reflect the origins of Catholic Americans and the religious orders whose generosity erected them.


text: Its Greek-styled interior is crowned with numerous domes decorated in mosaics, similar to the Basilica of St. Mark in Venice, Italy, but much larger. The mosaics feature American renditions of traditional Catholic images. Artist Jan Henryk De Rosen, who presided over the shrine's iconography committee was also responsible for much of its decor, including composing the large mosaic over the northern apse.


text: The exterior of the basilica is long, wide, and tall to the top of the cross on the dome. The exterior area of the basilica is . The diameter of the main dome (the "Trinity Dome") of the basilica is only smaller than that of the dome of the U.S. Capitol. The interior area of the basilica is for the Upper Level and Great Upper Church, and for the Lower Level and Crypt Church, for a grand total of .


text: The shrine was built in the style of medieval churches, relying on thick masonry walls and columns in place of structural steel and reinforced concrete. It was designed to hold 10,000 worshipers and includes modern amenities such as a basement cafeteria, hidden public address speakers to carry speech at the altar to the rear of the building, air conditioning and what was the largest radiant heating slab in the world (in 1959).


text: There are arches outlined with iridescent Pewabic Pottery tile, large ceramic medallions set in the ceiling, and fourteen Stations of the Cross in the Crypt Church.


text: In 1792 John Carroll, the bishop of Baltimore and the United States's first Catholic bishop, consecrated the newly created United States under the protection of the Blessed Virgin Mary under the title of the Immaculate Conception. In 1846, the 6th Provincial Councils of Baltimore reiterated this episcopal choice to name the title "Virgin Mary, conceived without sin" as the principal patroness of the land. Pope Pius IX formalized the decision on February 7, 1847, and it was published on July 2, 1847.


text: Bishop Thomas Joseph Shahan, the fourth rector of The Catholic University of America in Washington, proposed the construction of a national shrine to commemorate the Immaculate Conception in the country's capital. Bishop Shahan took his appeal to Pope Pius X on August 15, 1913.


text: Shahan received the pope's enthusiastic support and personal contribution of US$400 (US$11,681 in 2022, adjusted for inflation). Shahan returned to the United States and persuaded the board of trustees of The Catholic University of America to donate land at the southwest corner of the campus for his shrine.


text: In January 1914, Shahan published the first issue of "Salve Regina", a newsletter meant to stir enthusiasm for his project. He wrote that the shrine would be a "monument of love and gratitude, a great hymn in stone as perfect as the art of man can make it and as holy as the intentions of its builders could wish it to be." His newsletter was circulated to dioceses throughout the country and financial donations began to pour into Washington. In 1915, Shahan appointed Father Bernard McKenna of Philadelphia as first director of the national shrine. Shahan oversaw the construction of the shrine until his death on March 9, 1932. His are the only remains interred at the basilica/national shrine.


text: By 1919, Shahan and McKenna chose architectural drawings by the Boston firm of Maginnis & Walsh for construction of the national shrine. Initially, they considered a traditional Neo-Gothic architectural style, but Shahan opted instead for a Byzantine Revival–Romanesque Revival design. On May 16, 1920, Archbishop Giovanni Bonzano, Apostolic Nuncio to the United States of America, celebrated Mass and blessed the site of the future National Shrine. On September 23, 1920, Cardinal James Gibbons, archbishop of Baltimore, blessed the foundation stone. More than 10,000 people attended the Mass, including ambassadors, government officials, and military officers. On April 20, 1924, the first public mass ever offered at the shrine was held in the unfinished Crypt Church. In 1932, the death of Bishop Shahan and the Great Depression halted the construction above the completed Crypt Church level. The beginning of American involvement in World War II stalled plans even further, and construction was not resumed until 1954.


text: After the war, in 1953, American bishops under the leadership of John Noll, archbishop "ad personam" of Fort Wayne, and Patrick O'Boyle, archbishop of Washington, pledged to raise the funds necessary to complete the Great Upper Church of the national shrine. On November 15, 1954, work was resumed on building the shrine, and on November 20, 1959, thousands of Catholics gathered with the bishops for the dedication of the Great Upper Church.


text: On October 12, 1990, Pope John Paul II raised the national shrine to the status of a minor basilica. The papal bull was signed and notarized by Cardinal Agostino Casaroli. It is the 36th designated basilica within the United States.


text: In August 2006, work was completed on a mosaic covering the Redemption Dome in the Great Upper Church. Following its completion in the summer of 2007, the Incarnation Dome was blessed on November 17, 2007. A small chapel on the Crypt Church level honoring Our Lady of La Vang (Vietnam) was completed in 2006.


text: In 2008, during his trip to the United States, Pope Benedict XVI bestowed the Golden Rose upon the Basilica of the National Shrine of the Immaculate Conception.


text: In June 2011, a new chapel dedicated to Our Lady of Lebanon was erected within the basilica, commemorating the fidelity of the Maronite Church and its faithful. A mosaic of Saint Maroun and the Crucifixion was copied from the 6th-century "Rabboula" Maronite manuscript, and was donated by Cardinal Donald Wuerl. The chapel was formally consecrated by Maronite Bishop Gregory J. Mansour on September 23, 2011.


text: On January 26, 2013, the basilica held a televised thanksgiving Mass and enshrined two first class relics of Americans Kateri Tekakwitha and Marianne Cope, who were both canonized October 20, 2012.


text: Pope Francis visited the shrine on September 23, 2015, and celebrated a Mass for the canonization of Saint Junípero Serra, O.F.M., on the mall of the Catholic University of America. The altar, ambo, and chair used for this Mass match the existing marble in the basilica. After the Mass, the papal altar was placed in front of the High Altar, and is now used as the altar in the Great Upper Church.


text: On February 20, 2016, the basilica was the site of the funeral Mass of US Supreme Court Justice Antonin Scalia at which his son Fr. Paul Scalia was the celebrant.


text: The final architectural element was completed with the installation of the 24 tons of Venetian glass in the central "Trinity Dome", one of the largest mosaics of its kind in the world. On December 8, 2017, the Feast of the Immaculate Conception, the dome was dedicated and solemnly blessed by Cardinal Donald Wuerl.


title: 2018–19 FC Barcelona season

text: The 2018–19 season was Futbol Club Barcelona's 119th season in existence and the club's 88th consecutive season in the top flight of Spanish football. Barcelona was involved in four competitions after winning the double of La Liga and the Copa del Rey in the previous season.


title: 2018–19 FC Barcelona season

text: Contrary to the expectations and primarily due to stellar Lionel Messi performances, Barcelona was en route to its third continental treble until May 7 when it infamously lost to Liverpool 0–4 in the second leg of the Champions League semi-finals, having been up 3–0 after the first game. The league title was secured earlier on April 27 and Barça advanced to its sixth consecutive Copa del Rey final on February 27. The loss at Anfield derailed the team and they went on to lose the Copa final as well. Barça's league title was its eighth in eleven seasons; they have since won none, only securing the 2020–21 Copa del Rey in the three years since. Head coach Ernesto Valverde was sacked midway next season.


title: 2018–19 FC Barcelona season

text: The season was the first since 2001–02 season without former captain Andrés Iniesta, who departed to join Vissel Kobe.


title: 2018–19 FC Barcelona season

text: On 3 June, Barcelona and defender Samuel Umtiti reached an agreement to extend the player's contract for a further five seasons through to 2022–23 with a release clause of €500 million.


title: 2018–19 FC Barcelona season

text: On 11 June, Barcelona reached an agreement with Watford for the transfer of Gerard Deulofeu for €13 million plus €4 million in variables. Barcelona will also receive a percentage of any future transfer fee.


title: 2018–19 FC Barcelona season

text: On 8 July, Barcelona announced that they had reached an agreement with Guangzhou Evergrande for the loan transfer of Paulinho for one season, with a subsequent purchase option for the Chinese club.


title: 2018–19 FC Barcelona season

text: On 9 July, Barcelona and Grêmio finalized the transfer of Arthur following the agreement the two clubs reached in March for a transfer fee of €31 million plus €9 million in variables. The player will sign a contract for the next six seasons and the buyout clause is set at €400 million.


title: 2018–19 FC Barcelona season

text: On 12 July, Barcelona announced that they had paid the buyout clause for Clément Lenglet which stood at €35.9 million. The player, who joined from Sevilla, signed a contract with the club for the next five seasons and the buyout clause is set at €300 million.


title: 2018–19 FC Barcelona season

text: On 23 July, Barcelona announced that they had reached an agreement with Sivasspor for the loan transfer of Douglas for one season.


title: 2018–19 FC Barcelona season

text: On 23 July, Barcelona announced that they had reached an agreement with Deportivo La Coruña for the loan transfer of Adrián Ortolá for one season, with a subsequent purchase option for the A Coruña club.


title: 2018–19 FC Barcelona season

text: On 24 July, Barcelona announced that they had reached an agreement with Bordeaux for the transfer of Malcom for a transfer fee of €41 million plus €1 million in variables. The player signed a contract for the next five seasons until the end of 2022–23.


title: 2018–19 FC Barcelona season

text: On 1 August, Barcelona and Everton reached an agreement for the transfer of Lucas Digne to the English club for an initial fee of €20.2 million and €1.5 million in variables.


title: 2018–19 FC Barcelona season

text: On 3 August, Barcelona announced that they had reached an agreement with Bayern Munich for the transfer of Arturo Vidal to the Catalan club for the next three seasons for a fee of €18 million.


title: 2018–19 FC Barcelona season

text: On 4 August, Barcelona and Sevilla reached an agreement for the transfer of Aleix Vidal to the Andalusian club for a transfer fee of €8.5 million, plus €2 million in variables.


title: 2018–19 FC Barcelona season

text: On 9 August, Barcelona and Everton reached an agreement for the transfer of Yerry Mina for a fee of €30.25 million with an additional €1.5 million in variables. Barcelona also negotiated a buy-back clause in the transfer. Additionally, André Gomes was loaned to Everton for the 2018–19 season. The English club agreed to pay a fee of €2.25 million for the single season.


title: 2018–19 FC Barcelona season

text: On 12 August, Barcelona defeated Sevilla 1–2 in the Spanish Super Cup at the Stade Ibn Batouta in Morocco; goals from Gerard Piqué and Ousmane Dembélé handed the Catalans their 13th Supercopa de España title. The trophy was the first won under the captaincy of Lionel Messi, who also claimed his record-breaking 33rd trophy with the club. Additionally, the match saw official debuts from Arthur, Lenglet, and Arturo Vidal.


title: 2018–19 FC Barcelona season

text: On 16 August, Barcelona announced that they had reached an agreement for the transfer of Marlon to the Italian club Sassuolo for an initial fee of €6 million, including a buy-back clause for the Catalans. Barcelona will receive additional €6 million if Marlon makes 50 appearances for Sassuolo. If he would be sold before that, Barcelona will receive 50% of the future transfer fee.


title: 2018–19 FC Barcelona season

text: On 18 August, Barcelona defeated Alavés 3–0 with two goals from Messi, including the 6,000th La Liga goal in the club's history, and one from Coutinho to secure Barça an opening day victory for a tenth successive season.


title: 2018–19 FC Barcelona season

text: On 25 August, Barcelona defeated Real Valladolid 0–1, Barça made it two wins out of two thanks to a goal from Dembélé. The match also saw an official debut from Malcom.


title: 2018–19 FC Barcelona season

text: On 2 September, Barcelona demolished newly promoted Huesca 8–2. A sensational Messi who scored 2 goals had the chance to get his hat-trick with a final minute penalty, but chose to be generous and gave the chance to Suárez who scored his 2nd goal of the game. Dembélé, Ivan Rakitić, Jordi Alba were also on the scoresheet, along with an own goal from Jorge Pulido.


title: 2018–19 FC Barcelona season

text: On 15 September, Barcelona defeated Real Sociedad 1–2. Despite trailing at half time, goals from Suárez and Dembélé turned things around to make it four wins out of four in La Liga.


title: 2018–19 FC Barcelona season

text: On 18 September, Barcelona beat PSV Eindhoven 4–0 in their first Champions League game of the season. Another great performance of Messi as he managed his record-breaking 8th Champions League hat-trick and Dembélé notched the remaining goal from a solo effort to complete another victory for the "Blaugrana" side.


title: 2018–19 FC Barcelona season

text: On 23 September, Barcelona draw Girona 2–2. Sending off for Lenglet hinders home side, Messi and Piqué found the net for the Blaugrana.


title: 2018–19 FC Barcelona season

text: On 26 September, Barcelona lost to Leganés 2–1. Coutinho's opener counts for nothing as top against bottom clash took unexpected twist with two goals in a minute.


title: 2018–19 FC Barcelona season

text: On 29 September, Barcelona draw Athletic Bilbao 1–1. Substitutes Messi and Munir came to the rescue to salvage a draw at Camp Nou after Basques had taken 41st-minute lead


title: 2018–19 FC Barcelona season

text: On 3 October, Barcelona defeated Tottenham 2–4, with some major changes in the starting eleven introducing Arthur as a starter for the first time in midfield, the benching of Dembele and putting Coutinho back in attack with Messi and Suarez. Valverde's men secured an important victory in a classic, end-to-end match in London to maintain their perfect start in the Champions League group stage.


title: 2018–19 FC Barcelona season

text: On 7 October, Barcelona drew with Valencia CF 1-1. Messi scored a beautiful equaliser after an early opener from Garay to earn the blaugranes a share of the spoils at Mestalla.


title: 2018–19 FC Barcelona season

text: On 20 October, Barcelona defeated Sevilla 4-2. Four goals and a sensational performance by Ter Stegen allowed Barça to snatch first place back from the leaders on a night that Leo Messi went off injured.


title: 2018–19 FC Barcelona season

text: On 24 October, Barcelona defeated Inter Milan 2-0. Rafinha and Jordi Alba's superb goals left the Catalans flying high in Champions League Group B with the maximum points at the halfway stage.


title: 2018–19 FC Barcelona season

text: On 28 October, in the first "El Clásico" of the season, and the first since 2007 not to feature Messi or Cristiano Ronaldo, Barcelona thrashed Real Madrid 5–1 at the Camp Nou, with Luis Suárez scoring a hat-trick.


title: 2018–19 FC Barcelona season

text: On 3 November, Barca defeated Rayo Vallecano 2-3, two goals from Suárez and another from Ousmane Dembélé earned the Blaugranes a late win at Vallecas.


title: 2018–19 FC Barcelona season

text: On 6 November, Barca draw Inter Milan 1-1, Malcom's 1st goal was not enough at the Giuseppe Meazza after the equalizing goal of Icardi, but Barça still made the knockout stages with two games in hand.


title: 2018–19 FC Barcelona season

text: On 11 November, Barca lost 3-4 to Betis, The Andalusians spoiled Messi's return to action who scored 2 goals, with a shock victory in a dramatic encounter at the Camp Nou seeing Rakitic being sent off after picking his 2nd yellow card .


title: 2018–19 FC Barcelona season

text: On 24 November, Barca draw Atlético Madrid 1-1, Diego Costa's late header at the Wanda Metropolitano was cancelled out by Ousmane Dembélé after a brilliant pass of Messi in the final minute of normal time.in addition both Sergi Roberto and rafinha got injured after the game against Atlético


title: 2018–19 FC Barcelona season

text: On 28 November, Barca defeated PSV Eindhoven 1-2, Goals from a sensational Messi and Piqué clinched the points that ensure top spot in Champions League Group B with a game in hand.


title: 2018–19 FC Barcelona season

text: On 2 December, Barcelona defeated Villarreal 2-0 with goals from Gerard Piqué and Carles Aleñá, as well as a great all-round team performance which ensured the win and a clean sheet against worthy opponents.


title: 2018–19 FC Barcelona season

text: On 8 December, Barcelona defeated Espanyol 0-4 with two sensational free kicks from Leo Messi, plus goals from Dembélé and Luis Suárez which brought derby delight and another week at the top of the table.


title: 2018–19 FC Barcelona season

text: On 11 December, Barcelona drew 1-1 with Tottenham producing a magnificent performance as Dembélé scored Barça's only goal.


title: 2018–19 FC Barcelona season

text: On 16 December, Barcelona defeated Levante 0-5 playing sensational football which saw them power their way to victory in Valencia. Leo Messi scored yet another hat-trick with Luis Suárez and Gerard Piqué scoring the other goals.


title: 2018–19 FC Barcelona season

text: On 20 December, Barcelona announced that they had reached an agreement with Valencia for the transfer of Jeison Murillo on loan for the remainder of the 2018/19 season. The agreement includes a purchase option worth €25m.


title: 2018–19 FC Barcelona season

text: On 22 December, Barcelona defeated Celta Vigo 2-0 with goals from Leo Messi and Ousmane Dembele. The win ensured Barca remained on top of the table, three points ahead of Atletico Madrid, heading into the winter break.


title: 2018–19 FC Barcelona season

text: On 6 January, Barcelona defeated Getafe 1-2, goals from a sensational Leo Messi and a volley from Luis Suárez overcame a tough opponent and put the Barcelona five points clear at the top of the Liga table.


title: 2018–19 FC Barcelona season

text: On 10 January, Barcelona lost to Levante 2-1 in Copa del Rey round of 16, Philippe Coutinho converted a penalty five minutes from the end.


title: 2018–19 FC Barcelona season

text: On 13 January, Barcelona defeated Eibar 3-0, by 2 goals of Luis Suarez who was on fire with the first goal coming from a brilliant combination with a reborn Philipe Coutinho, the other goal being scored by none other than a sensational Leo Messi, which made it his record 400th La Liga goal.


title: 2018–19 FC Barcelona season

text: On 17 January, Barcelona defeated Levante 3-0 in Copa del Rey round of 16 return game, by 2 goals of Ousmane Dembele and a goal of Leo Messi, this win made sure Barcelona qualified for the Copa del Rey quarter finals.


title: 2018–19 FC Barcelona season

text: On 20 January, Barcelona defeated Leganés 3-1, as the first-place Catalans chew up the 'Cucumber Growers' at Camp Nou.


title: 2018–19 FC Barcelona season

text: On 23 January, Barcelona lost to Sevilla 2-0 in the Copa del Rey quarterfinals. Juan Sarabia and Ben Yedder scored the goals for Sevilla.


title: 2018–19 FC Barcelona season

text: On 23 January, Barcelona announced that they had reached an agreement with Ajax for the transfer of Frankie De Jong who will be joining the Catalan club from 1 July 2019. The transfer fee is 75 million euros, plus a further 11 million in variables. The player will be signing a contract for the next five seasons, through to 2023/24.


title: 2018–19 FC Barcelona season

text: On 27 January, Barcelona won Girona 0-2. Nelson Semedo's first League goal and another Leo Messi special handed Barça all three points.


title: 2018–19 FC Barcelona season

text: On 30 January, Barcelona won Sevilla 6-1 in the Copa del Rey quarterfinals 2nd leg. Phil Coutinho nets a brace, while Ivan Rakitic, Sergi Roberto, Luis Suárez and Leo Messi notch a goal each. the victory made sure Barcelona qualified for the semifinals of the Copa del Rey


title: 2018–19 FC Barcelona season

text: On 1 February, the announcement was made that Barcelona would face Real Madrid in the semifinals of the Copa del Rey,


title: 2018–19 FC Barcelona season

text: On 2 February, Barça draw Valencia 2-2, Leo Messi scored twice as first-place Barça battle back from 2-0, first-half deficit to earn a tie and provisionally extend their lead at the top of the table.


title: 2018–19 FC Barcelona season

text: On 6 February, Barça draw Real Madrid 1-1, The Catalans and the Madrileños finished all square at Camp Nou in the first leg of the Copa del Rey semifinals; Malcom pulled Barça even after Lucas Vásquez put Los Blancos up early. Making the second leg game at the Bernabeu even more exciting


title: 2018–19 FC Barcelona season

text: On 10 February, Barça draw Athletic 0-0, Barça had the possession but without doing too much with it.


title: 2018–19 FC Barcelona season

text: On 16 February, Barça won Valladolid 1-0, Barça picked up three vital points in La Liga thanks to a Leo Messi first half penalty. Messi could have doubled the lead with a second penalty given near the end, but the keeper stopped the penalty


title: 2018–19 FC Barcelona season

text: On 23 February, Barça won Sevilla 2-4, Lionel Messi's stunning hat-trick against his favourite opponent, and Luis Suarez's late goal secured the points for the Blaugrana who twice went behind.


title: 2018–19 FC Barcelona season

text: On 27 February, Barça won Real Madrid 0-3 (1-4 agg), Luis Suárez was the hero as his two goals plus an own goal send a rampant Barça flying into yet another cup final, the 6th Copa Del Rey final in a row for Barca and they are looking to make it their 5th straight victory in a row


title: 2018–19 FC Barcelona season

text: On 2 March, Barça won Real Madrid 0-1, Ivan Rakitic goal secured second win of the week at the Bernabéu. It was four seasons in a row now that Barça have won at Real Madrid in the league, a feat that no other team has ever achieved. FC Barcelona have claimed their 96th win the fixture overtaking Real Madrid for the first time in 87 years.


title: 2018–19 FC Barcelona season

text: On 9 March, Barça won Rayo Vallecano 3-1. Raúl de Tomás scored for the visitors in the 25th minute with an outside of the box shot, Gerard Piqué equalised with a header in the 39th minute, Lionel Messi put Barcelona in the lead with a 51st-minute penalty and Luis Suárez finished off the game with an 82nd minute tap-in.


title: 2018–19 FC Barcelona season

text: On 13 March, Barça won Lyon 5-1 (5-1 agg), a magnificent performance from Lionel Messi saw the Argentine grab two of Barça's five goals, and assist in two more for Gerard Piqué and Ousmane Dembélé, Philippe Coutinho completing the scoring. FC Barcelona hold the record in the Champions League for 12 consecutive appearances in the last eight of Europe's top club competition.


title: 2018–19 FC Barcelona season

text: On 15 March, it was announced that Barça would face Manchester United in the quarter-finals of the UEFA Champions League.


title: 2018–19 FC Barcelona season

text: On 17 March, Barça won Real Betis 1-4. Leo Messi posted yet another legendary hat-trick performance, Luis Suárez added the other, and Barça fly into a ten-point lead in La Liga. Unfortunately the Uruguayan sustained an injury keeping him out of play for 10–15 days.


title: 2018–19 FC Barcelona season

text: On the 30th, Barcelona got back to winning ways after the international break, with a 2-0 victory over Espanyol in Derbi barceloní with both goals from Messi.


title: 2018–19 FC Barcelona season

text: A thriller of an encounter against Villarreal on 2 April found Barça grab a point in a 4-4 draw after two late goals from Messi and Suárez.


title: 2018–19 FC Barcelona season

text: On 6 April, Barça won against Atlético de Madrid at the Camp Nou 2-0, goals scored by Luis Suarez and Lionel Messi, a thriller of a match that saw Spanish centre forward Diego Costa being sent off the field after receiving a red card. With that win, Messi became the player with the most wins in La Liga with 335.


title: 2018–19 FC Barcelona season

text: On 10 April, Barça won Manchester United 0-1, that was the first victory at Old Trafford via a Luke Shaw own goal.


title: 2018–19 FC Barcelona season

text: On 13 April, Barça drew with Huesca 0-0, a much-changed Barcelona gave first team debuts to Jean-Clair Todibo and Moussa Wague.


title: 2018–19 FC Barcelona season

text: incredible performance by Messi who scored two first-half goals with Coutinho adding a second-half rocket to qualify Barça for their eighth Champions League semi-final in the last 12 seasons.


title: 2018–19 FC Barcelona season

text: On 20 April, Barça won against Real Sociedad 2-1, Lenglet's towering first-half header and Alba's second were enough for Barça to take all three points.


title: 2018–19 FC Barcelona season

text: On 23 April, Barça won against Alavés 0-2, Aleñá's opener and Suárez's spot-kick were enough to earn all three points against Alavés.


title: 2018–19 FC Barcelona season

text: On 27 April, Barça won against Levante 1-0, Substitute Messi fired in the only goal of the game to secure a 26th Liga title with three games in hand, which made it Barça's 8th La Liga title in 11 years.


title: 2018–19 FC Barcelona season

text: On 1 May, Barça won 3–0 against Liverpool in the first leg of the Champions League semi-final. Suarez scored the first goal, followed by two goals by Messi, the third a superb freekick from over 30 yards, providing them with a clear advantage going into the away leg on 7 May at Anfield. Messi's second goal saw him reach 600 goals for Barça in 683 matches. On 4 May, Barça lost 2–0 to Celta Vigo in La Liga, with much of the team rested for the second game with Liverpool.


title: 2018–19 FC Barcelona season

text: On 7 May, Barça lost 4–0 against Liverpool via goals from Divock Origi (2) and Georginio Wijnaldum (2), crashing out of the Champions League.


title: 2018–19 FC Barcelona season

text: On 19 May, in Barcelona's final La Liga match of the season, Messi scored twice in a 2–2 away draw against Eibar (his 49th and 50th goals of the season in all competitions), which saw him capture his sixth Pichichi Trophy as the league's top scorer, with 36 goals in 34 appearances; with six titles, he equalled Zarra as the player with the most top-scorer awards in La Liga.


title: 2018–19 FC Barcelona season

text: On 25 May, Barça lost the Copa Del Rey final to Valencia 1–2. Lionel Messi scored the only Barcelona goal that night. This loss marked the end of the season for FC Barcelona who won two trophies (La liga and Supercopa de España) out of the possible four, despite having been close to winning them all up until 7 May.


title: 2018–19 FC Barcelona season

text: Barcelona began their 2018–19 pre-season with a tour of the United States in the 2018 International Champions Cup. "Barça" played against Tottenham Hotspur at the Rose Bowl in Pasadena, Roma at the AT&T Stadium in Arlington and Milan at the Levi's Stadium in Santa Clara.


title: 2018–19 FC Barcelona season

text: The "Blaugrana" finished their pre-season preparations with the annual Joan Gamper Trophy match against Boca Juniors of Argentina at the Camp Nou on 15 August.


title: 2018–19 FC Barcelona season

text: Barcelona were the defending champions. On 24 July 2018, the La Liga fixtures for the forthcoming season were announced.


title: 2018–19 FC Barcelona season

text: Barcelona entered the competition as the four-time defending champions, having won consecutive editions in 2014–15, 2015–16, 2016–17 and 2017–18.


title: 2018–19 FC Barcelona season

text: As the winners of the 2017–18 Copa del Rey and 2017–18 La Liga, Barcelona faced the Copa del Rey runners-up, Sevilla, for the season opening Supercopa de España. For the first time in the tournament history, it was a single match hosted in a neutral venue at the Stade Ibn Batouta in Tangier, Morocco.


title: 2018–19 FC Barcelona season

text: On 30 August, Barcelona were drawn in Group B of the UEFA Champions League alongside Tottenham Hotspur from Premier League, PSV Eindhoven from Eredivise and Internazionale from Serie A. After topping Group B, Barcelona advanced to knockout phase as a seeded team, and were drawn against Lyon from Ligue 1 in the round of 16. In the draw for the quarter-finals, Barcelona were drawn against Premier League side Manchester United, and in the draw for the semi-finals, against the winner of the tie between Liverpool and Porto, if Barcelona advance to a further round. Originally, the quarter-finals match was scheduled to be played with the first leg at Camp Nou and the second leg at Old Trafford, but the order of the two legs was reversed to avoid Manchester United and Manchester City from playing home on the same night or on consecutive nights.


title: 2018–19 FC Barcelona season

text: ! colspan=14 style=background:#dcdcdc; text-align:center|Players who have made an appearance this season but have left the club


title: Frank (Amy Winehouse album)

text: Frank is the debut studio album by English singer and songwriter Amy Winehouse. It was released on 20 October 2003 by Island Records. Production for the album took place during 2002 to 2003 and was handled by Winehouse, Salaam Remi, Commissioner Gordon, Jimmy Hogarth and Matt Rowe. Its title alludes to the nature and tone of Winehouse's lyrics on the album, as well as one of her influences, Frank Sinatra.


title: Frank (Amy Winehouse album)

text: Upon its release, "Frank" received generally positive reviews from most music critics and earned Winehouse several accolades, including an Ivor Novello Award. The album has sold over one million copies in the United Kingdom and has been certified triple platinum by the British Phonographic Industry (BPI).


title: Frank (Amy Winehouse album)

text: After playing around with her brother's guitar, Winehouse bought her own when she was 15 and began writing music a year later. Soon after, she began working for a living, including, at one time, as an entertainment journalist for the World Entertainment News Network, in addition to singing with local group the Bolsha Band. In July 2000, she became the featured female vocalist with the National Youth Jazz Orchestra; her influences were to include Sarah Vaughan and Dinah Washington, the latter whom she was already listening to at home.


title: Frank (Amy Winehouse album)

text: Winehouse's best friend, soul singer Tyler James, sent her demo tape to an artists and repertoire (A&R) executive. Winehouse signed to Simon Fuller's 19 Management in 2002 and was paid £250 a week against future earnings. While being developed by the management company, she was kept as a recording industry secret, although she was a regular jazz standards singer at the Cobden Club. Her soon-to-be A&R representative at Island Records, Darcus Beese, heard of her by accident when the manager of The Lewinson Brothers showed him some productions of his clients, which featured Winehouse as key vocalist. When he asked who the singer was, the manager told him he was not allowed to say. Having decided that he wanted to sign her, it took several months of asking around for Beese to eventually discover who the singer was. However, Winehouse had already recorded a number of songs and signed a publishing deal with EMI by this time. She formed a working relationship with producer Salaam Remi through these record publishers.


title: Frank (Amy Winehouse album)

text: Beese introduced Winehouse to his boss, Nick Gatfield, and the Island head shared his enthusiasm in signing her. Winehouse was signed to Island, as rival interest in Winehouse had started to build to include representatives of EMI and Virgin starting to make moves. Beese told HitQuarters that he felt the reason behind the excitement, over an artist who was an atypical pop star for the time, was due to a backlash against reality TV music shows, which included audiences starved for fresh, genuine young talent.


title: Frank (Amy Winehouse album)

text: In a 2004 interview with "The Observer", Winehouse expressed dissatisfaction with the album, stating:


title: Frank (Amy Winehouse album)

text: Some things on this album make me go to a little place that's fucking bitter. I've never heard the album from start to finish. I don't have it in my house. Well, the marketing was fucked, the promotion was terrible. Everything was a shambles. It's frustrating, because you work with so many idiots—but they're nice idiots. So you can't be like, "You're an idiot." They know that they're idiots.


title: Frank (Amy Winehouse album)

text: In the liner notes for Winehouse's 2011 album "", producer Salaam Remi wrote about the track "Half Time", an outtake from the recording sessions for "Frank", and revealed that "Frank"s title refers partly to Frank Sinatra, an early influence on Winehouse.


title: Frank (Amy Winehouse album)

text: "Frank" was first released in the United Kingdom on 20 October 2003 through Island Records. In 2004, the album was released to European countries, including Poland and Germany, as well as being released in Canada through Universal Music Group.


title: Frank (Amy Winehouse album)

text: In 2007 the album was released once again to Australia in March and the United States in November, with the latter being released via Universal Republic Records.


title: Frank (Amy Winehouse album)

text: In 2008, the album was re-released as a deluxe edition, including an 18-track bonus disc of rare tracks, remixes, B-sides and live performances. It was first released in Germany on 9 May 2008, followed by its release in the United Kingdom on 12 May 2008 through Island Records. Over May, June and July the album was released in Australia, Canada, United States and Japan.


title: Frank (Amy Winehouse album)

text: Following the release of the critically acclaimed documentary film about Winehouse, "Amy" (2015), "Frank" was reissued on vinyl on 31 July 2015 by Republic Records.


title: Frank (Amy Winehouse album)

text: "Frank" received mostly positive reviews from contemporary music critics. At Metacritic, which assigns a normalised rating out of 100 to reviews from mainstream publications, the album received an average score of 78, based on 11 reviews. AllMusic's John Bush called Winehouse "an excellent vocalist possessing both power and subtlety". Nate Chinen of "The New York Times" complimented her original lyrics and called the music a "glossy admixture of breezy funk, dub and jazz-inflected soul". "The A.V. Club"s Nathan Rabin commended its loose, organic songcraft and wrote that it "features languid, wide-open neo-soul grooves and jazzy vamping". Beccy Lindon of "The Guardian" described Winehouse's sound as "somewhere between Nina Simone and Erykah Badu ... at once innocent and sleazy". "Entertainment Weekly"s Chris Willman found its musical style reminiscent of Sade. "MusicOMH"s John Murphy said that her lyrics are "commendably feisty and, as the album title suggests, frank". Dan Cairns of "The Times" called "Frank" "a staggeringly assured, sit-up-and-listen debut, both commercial and eclectic, accessible and uncompromising". Robert Christgau, writing for MSN Music, was less enthusiastic and graded the album a "dud", indicating "a bad record whose details rarely merit further thought."


title: Frank (Amy Winehouse album)

text: Winehouse was nominated for British Female Solo Artist and British Urban Act at the 2004 BRIT Awards, while "Frank" was shortlisted for the Mercury Music Prize that same year. The album earned Winehouse an Ivor Novello Award. In retrospective reviews for both "Pitchfork" and "Rolling Stone", critic Douglas Wolk was ambivalent towards Winehouse's themes and felt that they are relevant to her public image at the time, writing in the former review, "in the light of her subsequent career, "Frank" comes off as the first chapter in the Romantic myth of the poet who feels too deeply and ends up killing herself for her audience's entertainment". By contrast, "PopMatters" writer Mike Joseph felt that the album shows that Winehouse's success is "based on pure talent rather than good producers or gimmicks". "The Washington Post"s Bill Friskics-Warren noted most of its content as "sultry ballads and shambling neo-soul jams", while writing that it "more than confirms what the fuss over Winehouse – then just 19 and with a lot fewer tattoos – was originally all about... her attitude and command were already there. And then some". The album was also included in the book "1001 Albums You Must Hear Before You Die". In 2019, the album was ranked 57th on "The Guardian"'s 100 Best Albums of the 21st Century list.