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The United States purchased Louisiana from the French First Republic in 1803 as part of the Louisiana Purchase. The United States nominally acquired 828,000 sq mi in Middle America for fifteen million dollars, or roughly eighteen dollars per square mile.

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The Monroe Doctrine is the best known U.S. policy toward the Western Hemisphere. Buried in a routine annual message delivered to Congress by President James Monroe in December 1823, the doctrine warns European nations that the United States would not tolerate further colonization or puppet monarchs.

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The Mexican-American War, often referred to as the Mexican War in the United States and the Intervención estadounidense en México in Mexico, was a military confrontation that lasted from 1846 to 1848 between the two countries. It came after the annexation of Texas by the United States in 1845, when Mexico still regarded it as its domain.

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Between the Hudson River and Lake Erie, the Erie Canal is a historic canal in upstate New York. The canal, which was the first navigable waterway between the Atlantic Ocean and the Great Lakes when it was finished in 1825, significantly decreased the cost of moving people and commodities across the Appalachians.

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On May 28, 1830, President Andrew Jackson signed the Indian Removal Act into law, giving him the power to exchange Indian territories inside current state boundaries for uninhabited territory west of the Mississippi. While some tribes left quietly, many opposed the policy of removal.

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The Lewis and Clark National Historic Trail travels the length of the United States to honor the 1804–1806 Lewis and Clark Expedition. It is a piece of the American National Trails System. From Pittsburgh, Pennsylvania, to the mouth of the Columbia River in Oregon, it travels for around 4,900 miles.

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The United States had various statutes known as the "Homestead Acts" that allowed applicants to obtain ownership of public or government land, often known as a "homestead."

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A 19th-century American cultural idea known as "manifest destiny" held that American immigrants were destined to colonize all of North America.