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The 16th century begins with the Julian year 1501 and ends with either the Julian or the Gregorian year 1600 (depending on the reckoning used; the Gregorian calendar introduced a lapse of 10 days in October 1582). The term is often used to refer to the 1500s, the century between January 1, 1500 and December 31, 1599.

The 16th century is regarded by historians as the century in which the rise of Western civilization and the Age of the Islamic Gunpowders occurred. During the 16th century, Mauritius was introduced on maps, Spain and Portugal explored the Indian Ocean and opened worldwide oceanic trade routes, and Vasco da Gama was given permission by the Indian Sultans to settle in the wealthy Bengal Sultanate. Large parts of the New World became Spanish and Portuguese colonies, and while the Portuguese became the masters of Asia's and Africa's Indian Ocean trade, the Spanish opened trade across the Pacific Ocean, linking the Americas with India.

This era of colonialism established mercantilism as the leading school of economic thought, where the economic system was viewed as a zero-sum game in which any gain by one party required a loss by another. The mercantilist doctrine encouraged the many intra-European wars of the period and arguably fueled European expansion and imperialism throughout the world until the 19th century or early 20th century.

The Protestant Reformation gave a major blow to the authority of the papacy and the Catholic Church. European politics became dominated by religious conflicts, with the groundwork for the epochal Thirty Years' War being laid towards the end of the century. In Italy, various contributions made by renaissance leading figures led to the foundation of important subjects which include accounting and political science. Galileo Galilei invented the first thermometer and made substantial contributions in the field of Scientific Revolution. In England, the British-Italian Alberico Gentili wrote the first book on public international law and divided secularism from canon law and Catholic theology.

In the Middle East, the Ottoman Empire continued to expand, with the Sultan taking the title of Caliph, while dealing with a resurgent Persia. Iran and Iraq were caught by major popularity of the Shiite sect of Islam under the rule of the Safavid dynasty of warrior-mystics, providing grounds for a Persia independent of the majority-Sunni Muslim world.

In the Indian subcontinent, following the defeat of the Delhi Sultanate, new powers emerged, the Suri Empire founded by Sher Shah Suri and the Mughal Empire by Babur, a direct descendant of Timur and Genghis Khan. His successors Humayun and Akbar, enlarged the empire to include most of South Asia. The empire developed a strong and stable economy in the world, leading to commercial expansion and greater patronage of culture, which significantly influenced the course of Indian history.

China evacuated the coastal areas, because of Japanese piracy. Japan was suffering a severe civil war at the time, known as the Sengoku period.

Copernicus proposed the heliocentric universe, which was met with strong resistance, and Tycho Brahe refuted the theory of celestial spheres through observational measurement of the 1572 appearance of a Milky Way supernova. These events directly challenged the long-held notion of an immutable universe supported by Ptolemy and Aristotle, and led to major revolutions in astronomy and science.

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