title: Croatan

text: According to Thomas Harriot, the Native Americans living in coastal North Carolina believed there was "one only chief and great God, which has been from all eternity" and made petty gods, "to be used in the creation and government to follow." They believed in the immortality of the soul. Upon death, the soul either enters heaven to live with the gods or goes to a place near the setting sun called Popogusso, to burn for eternity in a huge pit of fire. The concept of heaven and hell was used on the common people to respect leaders and live a life that would be beneficial to them in the afterlife. Conjurors and priests were distinctive spiritual leaders. Priests were chosen for their knowledge and wisdom and were leaders of the organized religion. Conjurors, on the other hand, were chosen for their magical abilities. Conjurors were thought to have powers from a personal connection with a supernatural being (mostly spirits from the animal world).


title: Croatan

text: It is known that the arrival of English Settlers upset some pre-existing tribal relationships. The Algonquian people advocated cooperation while others (the Yamasee, Cherokee and Chickasaw, for example) resisted. Later, this conflict between tribes and settlers would lead to the Yamasee War. Tribes that maintained mutually beneficial contact with the settlers gained power through their access to and control of European trade goods. While the English may have held great military superiority over the Carolina Algonquians, the Native Americans' control over food and natural resources was a much more decisive factor in the conflict with early settlers. Despite the varying relationships among tribes, the Roanoke and Croatan were believed to have been on very good terms with English Settlers of the Roanoke Colony. Wanchese, the last leader of the Roanoke, accompanied the English on a trip to England.


title: Croatan

text: Some of the survivors of the Lost Colony of Roanoke may have joined the Croatan. Governor White finally reached Roanoke Island on August 18, 1590, three years after he had last seen them there, but he found his colony had been long deserted. The buildings had collapsed and "the houses [were] taken down." The few clues about the colonists' whereabouts included the letters "CROATOAN" carved into a tree. Croatoan was the name of a nearby island (likely modern-day Hatteras Island) in addition to the local tribe of Native Americans. Roanoke Island was not originally the planned location for the colony and the idea of moving elsewhere had been discussed. Before the Governor's departure, he and the colonists had agreed that a message would be carved into a tree if they had moved and would include an image of a Maltese Cross if the decision was made by force. White found no such cross and was hopeful that his family was still alive.


title: Croatan

text: The Croatan, like other Carolina Algonquians, suffered from epidemics of infectious disease such as smallpox in 1598. These greatly reduced the tribe's numbers and left them subject to colonial pressure. They are believed to have become extinct as a tribe by the early seventeenth century.


title: Croatan

text: Based on legend, some people said that the Lumbee tribe, based in North Carolina, were descendants of the Croatan and survivors of the Lost Colony of Roanoke Island. For over a hundred years, historians and other scholars have been examining the question of Lumbee origin. Although there have been many explanations and conjectures, two theories persist. In 1885, Hamilton McMillan, a local historian and state legislator, proposed the "Lost Colony" theory. Based upon oral tradition among the Lumbees and what he deemed as strong circumstantial evidence, McMillan posited a connection between the Lumbees and the early English colonists who settled on Roanoke Island in 1587 and the Algonquian tribes (Croatan included) who inhabited coastal North Carolina at the same time. According to historical accounts, the colonists mysteriously disappeared soon after they settled, leaving little evidence of their destination or fate. McMillan's hypothesis, which was also supported by the historian Stephen Weeks, contends that the colonists migrated with the Indians toward the interior of North Carolina's and by 1650 had settled along the banks of the Lumber River. It is suggested the present-day Lumbees are the descendants of these two groups.


title: Croatan

text: Other scholars believe the Lumbees to be descended from an eastern Siouan group called the Cheraws. During the seventeenth and eighteenth centuries, several Siouan-speaking tribes occupied southeastern North Carolina. John R. Swanton, a pioneering ethnologist at the Smithsonian Institution, wrote in 1938 that the Lumbees were probably of Cheraw descent, but were also genealogically influenced by other Siouan tribes in the area. Contemporary historians such as James Merrell and William Sturtevant confirm this theory by suggesting that the Cheraws, along with survivors of other tribes whose populations had been devastated by warfare and disease, found refuge from both aggressive settlers and hostile tribes in the Robeson County swamps in eastern North Carolina.


title: Croatan

text: In 1914, when Special Indian Agent O.M. McPherson was reporting on the rights of various Indian groups, he published a list of names of the Lost Colony. Numerous names on the list were typical Indian names in the North Carolina counties of Robeson and Sampson, at the time of his report. Many of the surnames included were that of surviving Croatan Indians. Late twentieth-century research has demonstrated that among surnames established as Lumbee ancestors were numerous mixed-race African Americans free in Virginia before the American Revolution and their descendants who migrated to Virginia and North Carolina frontiers in the late eighteenth and early nineteenth centuries. These "free people of color" were mostly descendants of European men and African women who worked and lived together in colonial Virginia. These connections have been traced for numerous individuals and families through court records, land deeds, and other existing historical documents. In Robeson County, they may have intermarried with Native American survivors and acculturated as Native Americans.


title: Croatan

text: The Lost Colony Center for Science and Research has excavated English artifacts within the territory of the former Croatan tribe. The artifacts may also be evidence of trade with the tribe or of natives finding them at the former colony site. The Center is conducting a DNA study to try to determine if there are European lines among Croatan descendants.


title: Croatan

text: Researchers from the University of Bristol, UK, have also been excavating on Hatteras Island in conjunction with the Croatoan Archaeological Society. Hatteras Island is the main locus for the settlement of the Croatoan tribe and to date, they have discovered a large contact/pre-contact period settlement, midden deposits, and European trade items.


title: Croatan

text: Historian Malinda Maynor (Lumbee) wrote that, in 1890, a group of about 100 people who identified as Croatan descendants, or Lumbees, left Robeson County, North Carolina, for southern Georgia. By building a church and a school for their people outside of the influence of publicly-funded or pre-existing buildings in the area, they established an identity for themselves that subverted the racial barriers of the time which, prior to 1890, had operated under a very clear distinction between "black" and "white." This group, instead, considered themselves to be "Indians." They headed back to Bulloch County where they could keep their people together as "Indians." They used the segregation of Jim Crow South to develop themselves as an entire community. In 1910, the North Carolina state legislature renamed the Croatan Indians in North Carolina to "Cherokee."


title: Croatan

text: A historical marker placed by the state of Georgia states: "In 1870 a group of Croatan Indians migrated from their homes in Robeson County North Carolina, following the turpentine industry to southeast Georgia. Eventually many of the Croatans became tenant farmers for the Adabelle Trading Company, growing cotton and tobacco. The Croatan community established the Mt. Zion Baptist Church in Adabelle, as well as a school and a nearby cemetery. After the collapse of the Adabelle Trading Company, the Croatans faced both economic hardship and social injustice. As a result, most members of the community returned to North Carolina by 1920."


title: Croatan

text: The North Carolina state legislature recognized the Croatan Indians of Robeson County and the Croatan Indians of Sampson County in 1911. They were also granted the right of "Indians and their descendants shall have separate school for their children, school committees of their own race, and shall also have the right to choose their own teachers based upon the general assembly of North Carolina. Today, these two groups are state-recognized tribes, known as the Lumbee Tribe of North Carolina and the Coharie Intra-tribal Council, Inc., respectively.


title: Croatan

text: The Croatan Indian Tribe of South Carolina, an unrecognized organization, claims to descend from Croatan people.


title: Point Pleasant, West Virginia

text: Point Pleasant is a city in and the county seat of Mason County, West Virginia, United States, at the confluence of the Ohio and Kanawha Rivers. The population was 4,101 at the 2020 census. It is the principal city of the Point Pleasant, WV-OH Micropolitan Statistical Area.


title: Point Pleasant, West Virginia

text: According to the United States Census Bureau, the city has a total area of , of which is land and is water.


title: Point Pleasant, West Virginia

text: As of the census of 2010, there were 4,350 people, 2,014 households, and 1,162 families residing in the city. The population density was . There were 2,244 housing units at an average density of . The racial makeup of the city was 95.9% White, 1.3% African American, 0.3% Native American, 0.6% Asian, 0.3% Pacific Islander, and 1.7% from two or more races. Hispanic or Latino of any race were 0.6% of the population.


title: Point Pleasant, West Virginia

text: There were 2,014 households, of which 25.7% had children under the age of 18 living with them, 37.9% were married couples living together, 16.0% had a female householder with no husband present, 3.8% had a male householder with no wife present, and 42.3% were non-families. 38.5% of all households were made up of individuals, and 18.7% had someone living alone who was 65 years of age or older. The average household size was 2.15 and the average family size was 2.82.


title: Point Pleasant, West Virginia

text: The median age in the city was 44 years. 21.5% of residents were under the age of 18; 7.8% were between the ages of 18 and 24; 21.6% were from 25 to 44; 27.4% were from 45 to 64; and 21.6% were 65 years of age or older. The gender makeup of the city was 44.9% male and 55.1% female.


title: Point Pleasant, West Virginia

text: As of the census of 2000, there were 4,637 people, 2,107 households, and 1,310 families residing in the city. The population density was 1,945.6 people per square mile (752.3/km). There were 2,313 housing units at an average density of 970.5 per square mile (375.2/km). The racial makeup of the city was 96.57% White, 1.90% African American, 0.15% Native American, 0.60% Asian, 0.09% from other races, and 0.69% from two or more races. Hispanic or Latino of any race were 0.54% of the population.


title: Point Pleasant, West Virginia

text: There were 2,107 households, out of which 26.3% had children under the age of 18 living with them, 44.7% were married couples living together, 14.4% had a female householder with no husband present, and 37.8% were non-families. 34.8% of all households were made up of individuals, and 17.8% had someone living alone who was 65 years of age or older. The average household size was 2.18 and the average family size was 2.80.


title: Point Pleasant, West Virginia

text: In the city, the population was spread out, with 21.3% under the age of 18, 8.4% from 18 to 24, 23.7% from 25 to 44, 26.2% from 45 to 64, and 20.4% who were 65 years of age or older. The median age was 43 years. For every 100 females, there were 83.6 males. For every 100 females age 18 and over, there were 75.3 males.


title: Point Pleasant, West Virginia

text: The median income for a household in the city was $27,022, and the median income for a family was $33,527. Males had a median income of $31,657 versus $16,607 for females. The per capita income for the city was $16,692. About 22.2% of families and 24.2% of the population were below the poverty line, including 37.9% of those under age 18 and 13.3% of those age 65 or over.


title: Point Pleasant, West Virginia

text: A Shawnee village known as Upper Shawneetown was established in this area before 1749, which the Shawnees called "Chinoudaista" or "Chinodahichetha."


title: Point Pleasant, West Virginia

text: In the second half of 1749, the French explorer Pierre Joseph Céloron de Blainville (1693-1759) claimed French sovereignty over the Ohio Valley, burying a lead plaque at the meeting point of the Ohio and Kanawha Rivers.


title: Point Pleasant, West Virginia

text: Céloron's expedition was a diplomatic failure since the local tribes remained pro-British, and British representatives in the region refused to leave. This incident was the prelude to conflicts between the French and British in North America that would lead to the outbreak of the French and Indian War in 1754 (as part of the Seven Years' War) that would lead to the cessation of New France to the British and the ultimate expulsion of France from most of its possessions in North America.


title: Point Pleasant, West Virginia

text: The expedition can nevertheless be seen in more positive terms as a geographical project, since the Céloron expedition was the starting point for the first map of the Ohio Valley. The map was the work of the Jesuit Joseph Pierre de Bonnecamps.


title: Point Pleasant, West Virginia

text: In 1770, Colonel George Washington visited the confluence that would become Point Pleasant, then proceeded 14 miles up the "Great Kanawha" and later reported that "This Country abounds in Buffalo and Wild game of all kinds as also in all kinds of wild fowl, there being in the Bottoms a great many small grassy Ponds or Lakes which are full of Swans, Geese, and Ducks of different kinds."


title: Point Pleasant, West Virginia

text: In the Battle of Point Pleasant (October 10, 1774), fought on the future site of the town, over one thousand Virginia militiamen, led by Colonel Andrew Lewis (1720–1781), defeated a roughly equal force of an Algonquin confederation of Shawnee and Mingo warriors led by Shawnee Chief Cornstalk (c. 1720–1777). The event is celebrated locally as the "First Battle of the American Revolutionary War" and in 1908 the U.S. Senate authorized erection of a local monument to commemorate it as such. Most historians, however, regard it not as a battle of the Revolution (1775–1783), but as a part of Lord Dunmore's War (1774).


title: Point Pleasant, West Virginia

text: "Camp Point Pleasant" was established by Col. Lewis at the time of the Battle and the settlement that followed also took that name. Although not certain, Point Pleasant may have been permanently settled by whites as early as 1774. A permanent stockade known as Fort Blair was erected there at about that time. Prior to that, hostilities between whites and Indians all along the Ohio River Valley probably precluded the possibility of settlement in the absence of a substantial stockade. In 1776, a new fort was built on the site of the earlier fort and named for the recently deceased Virginia official Peyton Randolph (1721–1775). Fort Randolph is best remembered as the place where Chief Cornstalk was murdered in 1777. It withstood attack by Indians the following year, but was abandoned in 1779.


title: Point Pleasant, West Virginia

text: George Washington's 1770 journey to the Ohio River Valley had been occasioned by military grants that had been awarded by proclamation in 1754 by Governor Dinwiddie to officers and soldiers who had served in the French and Indian War. The resulting survey encompassed 52,302 acres (or 80 square miles) and was subdivided in the 1780s as follows: 9,876 acres — including the present side of Point Pleasant — to Andrew Lewis, 5,000 acres for George Muse, 5,000 acres for Peter Hogg, 8,000 acres for Andrew Stephens, another 3,000 acres for Peter Hogg, another 5,026 acres for George Muse, 3,400 acres for Andrew Waggener, 6,000 acres for John Poulson, 6,000 acres for John West. On the lower side of the Kanawha River, 13,532 acres for Hugh Mercer (see Mercers Bottom) and, finally, 10,990 acres for Washington himself.


title: Point Pleasant, West Virginia

text: Fort Randolph was rebuilt nearby in 1785 after the renewal of hostilities between the United States government and the Indians, but saw little action and was eventually abandoned once again. The settlement at Point Pleasant did not receive an official charter until 1794.


title: Point Pleasant, West Virginia

text: Mason County was carved out of Kanawha County in 1804 and Point Pleasant was designated the county seat at that time. According to historian Virgil A. Lewis, "Point Pleasant did not flourish for many years [after the turn of the century]. There was no church for more than fifty years and society was at a low ebb. There was a popular superstition that because of the fiendish murder of Cornstalk there in 1777, the place was laid under a curse for a hundred years". Lewis also relates that a visitor to Point Pleasant in 1810 observed that ... Point Pleasant is pleasantly situated immediately above the mouth of the Great Kanawha, on an extensive and fertile bottom of the Ohio, of which it has a fine prospect up and down that river. It is the seat of justice of Mason county Virginia, and contains about 15 or 20 families, a log courthouse, a log jail and as usual (but unfortunately) in the Virginia towns, a pillory and whipping post. Point Pleasant seems rather on the stand in point of improvement, arising, it is said, from the difficulty in establishing the land titles. It is, however, a considerable place of embarkation for those descending the Ohio from the back and western parts of Virginia. There is one merchant. Mr. William Langtry.


title: Point Pleasant, West Virginia

text: During the American Civil War, the Virginia Secession Convention of 1861, Mason County's delegate, lawyer James H. Couch (1821-1899), although a slaveholder, voted against secession. Mason County then sent no delegates to the Virginia House of Delegates until West Virginia's statehood, which Virginia's House of Delegates refused to recognize, thus seating James Hutcheson who had been elected by Confederate soldiers in their camp. Meanwhile, William W. Newman claimed to represent Mason as well as nearby Jackson, Cabell, Wayne and Wirt counties throughout the war. Mason County sent more than 1000 men to the Union army and one company of 61 men to the Confederate Army (the 37th Virginia Infantry). In March 1863, in the only wartime skirmish in Point Pleasant, during the Jones-Imboden Raid, the 6th Virginia Cavalry and 8th Virginia Cavalry attacked the Mason County Courthouse, where they believed munitions stored, leaving bullet holes in the walls until a replacement was built in 1954.


title: Point Pleasant, West Virginia

text: On October 10, 1974, Point Pleasant celebrated the 200th anniversary of the Battle of Point Pleasant. A replica of Fort Randolph was built in 1973-74 and dedicated as part of the festivities. The town of Point Pleasant was situated over the site of the fort and so the replica is located at Krodel Park, about one mile away.


title: Point Pleasant, West Virginia

text: The Eastham House, Lewis-Capehart-Roseberry House, and Point Pleasant Battleground are listed on the National Register of Historic Places. The central business district and surrounding residential areas are included in the Point Pleasant Historic District.


title: Point Pleasant, West Virginia

text: Paranormal enthusiasts flock to Point Pleasant in search of Mothman, a creature said to be a harbinger of imminent disaster that inhabits an abandoned TNT factory from World War II. John Keel published a book in 1975 entitled "The Mothman Prophecies", and a film inspired by the novel was released in January 2002. Later, another film, loosely based on the legend, was also released. The town is host to a Mothman Museum, and every year it holds a Mothman Festival that features tours, pageants, balls, films, music, and other events to celebrate what they consider "one of Point Pleasant's largest tourist attractions."


title: Point Pleasant, West Virginia

text: The climate in this area is characterized by evenly distributed precipitation throughout the year. According to the Köppen Climate Classification system, Point Pleasant has a humid subtropical climate, abbreviated "Cfa" on climate maps.


title: Gus Johnson (sportscaster)

text: Augustus Cornelius Johnson Jr. (born ) is an American sportscaster. He is the lead play-by-play announcer for Fox Sports calling college football and college basketball. Prior to working with Fox, he was with CBS Sports.


title: Gus Johnson (sportscaster)

text: Johnson was born in Detroit, Michigan. He graduated in 1985 from the University of Detroit Jesuit High School and Academy. He was an all-league quarterback and co-captain of the school's football team, an all-league shooting guard, co-captain and MVP of the basketball team and a first baseman and catcher on the baseball team.


title: Gus Johnson (sportscaster)

text: Johnson graduated from Howard University with a degree in political science in 1990 and was a four-year letter winner on the baseball team.


title: Gus Johnson (sportscaster)

text: Johnson called play-by-play for the NBA's Minnesota Timberwolves (1996–97), Big East basketball on the Big East Network, college hockey and college basketball on ESPN and Canadian Football League games for ESPN2, and NFL games for CBS from 1998 to 2010.


title: Gus Johnson (sportscaster)

text: Johnson hosted ESPN's "Black College Sports Today" in 1991. After brief stints as an on-air personality with KXXV-TV in Waco, Texas, WAAY-TV in Huntsville, Alabama, and WXII-TV in Winston-Salem, North Carolina, he served as the weekend anchor for WTTG in Washington, D.C. from 1991 to 1992. He also had a small cameo as an announcer in the 1998 film "He Got Game".


title: Gus Johnson (sportscaster)

text: Johnson called play-by-play for numerous sports for CBS Sports, including the network's coverage of March Madness from 1996 to 2011. Among the memorable games that Johnson has called are UCLA's 17-point comeback over Gonzaga in 2006, the double-overtime Xavier vs. Kansas State game on March 25, 2010 and George Mason's upset of Villanova in 2011. He also announced the Big Ten Network's Sunday-night basketball games.


title: Gus Johnson (sportscaster)

text: Johnson worked for the Madison Square Garden Network (MSG) from 1994 to 2010, where he was the radio and backup television play-by-play announcer for the NBA's New York Knicks and the television play-by-play announcer for the WNBA's New York Liberty. Johnson has also hosted MSG studio shows focused on the Yankees, Rangers and Knicks. He called 20 Milwaukee Bucks games during the 2015–16 season on Fox Sports Wisconsin. Johnson also handled play-by-play duties for the inaugural season of BIG3 basketball.


title: Gus Johnson (sportscaster)

text: He has announced preseason television games for the NFL's Baltimore Ravens, Buffalo Bills, Philadelphia Eagles and Detroit Lions as well as the Arena Football League's New York Dragons.


title: Gus Johnson (sportscaster)

text: Johnson has called MSG's coverage of the Golden Gloves as well as "Showtime Championship Boxing" on Showtime, replacing longtime voice Steve Albert. Johnson was also a mixed martial arts commentator for both EliteXC and Strikeforce through until 2011. Johnson drew scorn for his commentary during the Kimbo Slice vs. Seth Petruzelli fight, in which he announced that the fight was "the most incredible victory in the history of mixed martial arts."


title: Gus Johnson (sportscaster)

text: Johnson has lent his voice for the play-by-play commentary in the video games "NCAA Basketball 10," "Madden NFL 11" and "Madden NFL 12". He was also heard as the play-by-play announcer for the fictional football games seen in commercials for Buffalo Wild Wings.


title: Gus Johnson (sportscaster)

text: Before the 2010–11 NBA season, Johnson left MSG Network to spend more time with his son. CBS released him on May 5, 2011 following a contract dispute. On May 9, 2011, he finalized a deal to call college football and NFL telecasts for Fox Sports.


title: Gus Johnson (sportscaster)

text: In 2012, Johnson served as radio play-by-play announcer of Major League Soccer's San Jose Earthquakes. He called his first UEFA Champions League match on February 13, 2013 but stepped down as Fox's lead soccer announcer in 2014.


title: Gus Johnson (sportscaster)

text: In August 2021, Fox Sports announced that Johnson would announce "select" NFL games for the 2021 season with former NFL player Aqib Talib.


title: Gus Johnson (sportscaster)

text: Gus Johnson worked as a Play by play man for the First Round of the 2022 NBA Playoffs for TNT and NBATV.


title: Gus Johnson (sportscaster)

text: In September 2021, Johnson was challenged by comedian Gus Johnson to an athletic competition for the Twitter handle @GusJohnson, as the sportscaster has not tweeted since 2012.


title: Gus Johnson (sportscaster)

text: Johnson's high-energy style has resulted in a polarized response from sports fans. He often uses signature phrases like "Hurt My Feelings!", "Oh my goodness!", "Rise and fire... Count it!", "Here comes the pain!", "He's got 'get away from the cops' speed!", "From the parking lot!", "And the runner... bang!", "Pure!", "BAM!", "Hot Sauce!", "Cold-Blooded!", "What a game!", "Down the Sideline!" and "HA-HAAA". Despite being known for his catchphrases, Johnson also utilizes silence at opportune times to let television viewers absorb the moment, such as during a 2015 college football matchup between Notre Dame and Stanford when Stanford kicked the game-winning field goal at the end of a high-scoring game.


title: Gus Johnson (sportscaster)

text: As Knicks announcer – With the Knicks, Johnson was well-known for calls such as "My name is Al Harrington... and I get buckets!" Perhaps Johnson's most famous Knicks call was his enthusiastic description of Allan Houston's last-second shot to defeat the top-seeded Miami Heat in the first round of the 1998–1999 NBA playoffs.


title: Gus Johnson (sportscaster)

text: March 23, 2006 – During the 2006 NCAA Division I men's basketball tournament, Johnson was calling the Sweet 16 matchup between UCLA and Gonzaga. Gonzaga held a 71–70 lead with just 19.7 seconds left in the game, needing to wind the clock down while passing the ball in from its own side of the court:


title: Gus Johnson (sportscaster)

text: Analyst Len Elmore: You don't want to foul Morrison. You make them get it over half court, you know you gotta foul- "[UCLA guard Jordan Farmar steals the ball from Gonzaga forward J. P. Batista]" Woah!


title: Gus Johnson (sportscaster)

text: Johnson: And a steal! Farmar! Inside... the freshman up- "[nearly inaudible over the crowd cheering as UCLA forward Luc Mbah a Moute scores a layup]" Oh and they go in front! Raivio! Last chance to dance! "[inaudible as Mbah a Moute steals the ball via a jump ball before Gonzaga commits a foul, leaving just over two seconds left]" Mbah a Moute!


title: Gus Johnson (sportscaster)

text: Following this sequence, Gonzaga had one last chance to score a game-winning basket, once again throwing the ball in from its side of the court.


title: Gus Johnson (sportscaster)

text: Johnson: In the frontcourt, Batista with THE CAATCH! "[Batista shoots before the buzzer, but misses]" And that's it! WHAT A COMEBACK! UCLA defeats Gonzaga 73–71 after being down by 17!


title: Gus Johnson (sportscaster)

text: As the game wound up having a tight finish, Johnson received praise for his enthusiastic announcing, earning the nickname "Screaming Gus Johnson". The next day, CBS Sports host Greg Gumbel later joked that Johnson would be "out of the hospital" by the next game.


title: Gus Johnson (sportscaster)

text: September 13, 2009 – Johnson was calling an NFL regular season opening game between the Cincinnati Bengals and Denver Broncos. During the waning seconds of the game, Denver, down 6–7, needed to drive down the field to get into field goal range or score a touchdown. Quarterback Kyle Orton threw a pass to receiver Brandon Marshall near the sideline. Though the ball was tipped by Bengals defender Leon Hall, it landed into the hands of Broncos receiver Brandon Stokley, who ran it in for an improbable game-winning touchdown. Johnson's call of the play is as follows:


title: Gus Johnson (sportscaster)

text: Johnson: Orton in the gun, Buckhalter right next to him. Orton... pumps again to the sideline... batted up- OH, CAUGHT! STOKLEY! DOWN THE SIDELINE! CAN HE CATCH HIM!? STOKLEY! WOW! "[Pause]" Touchdown Denver! Unbelievable! "[pause]" Oh my goodness! What a play! 87 yards! "[pause]" "Woah!""


title: Gus Johnson (sportscaster)

text: In a later interview on "The Dan Patrick Show", Johnson later explained of the play: "I thought I was gonna have a heart attack. It was the most incredible thing. I’ve seen a lot of great things in sports. I started doing this in 1990, but I’ve never seen anything; not like in that in football. I mean wow."


title: Gus Johnson (sportscaster)

text: November 1, 2009 – Johnson was calling another regular season NFL game, this time between the Jacksonville Jaguars and Tennessee Titans when Titans running back Chris Johnson broke away for a 52-yard touchdown. This was Gus Johnson's call:


title: Gus Johnson (sportscaster)

text: First down and 10... Johnson... gets a shoulder he's- WOW! Watch out! He's got "gettin' away from the cops speed!" Touchdown! "[pause]" 52 yards!


title: Gus Johnson (sportscaster)

text: Though Gus Johnson received some criticism for this call, it has nonetheless become one of his most famous, as Complex magazine named it his top call in 2013.


title: Gus Johnson (sportscaster)

text: November 14, 2010 – Johnson was announcing another Jacksonville Jaguars game, this time against their AFC South rivals the Houston Texans. With 0:03 left in regulation, the score tied at 24, and the ball at midfield, the Jaguars and quarterback David Garrard had a chance to win the game and avoid a potential overtime loss. The ball was snapped, Garrard stepped into the pocket, and launched the ball 50 yards downfield into the endzone to his target, receiver Mike Sims-Walker. Texans safety Glover Quin batted the ball down, but the ball miraculously landed in the hands of Jaguars receiver Mike Thomas, resulting in a touchdown, a win for the Jaguars, and one of Gus Johnson’s most memorable calls:


title: Gus Johnson (sportscaster)

text: Johnson: Garrard… steps up… fires, Mike Sims-Walker…! ["Ball is batted down"] Knocked down- ["Ball lands in the hands of Thomas"]


title: Gus Johnson (sportscaster)

text: October 7, 2017 – As the play-by-play announcer of a college football game between Ohio State and Maryland, Johnson added some playful commentary after Ohio State cornerback Denzel Ward laid a vicious hit on Maryland receiver Taivon Jacobs. Though the play ultimately resulted in Ward's ejection from the game, Johnson's enthusiasm was noted:


title: Gus Johnson (sportscaster)

text: Second down after the 7-yard gain... [Maryland quarterback] Bortenschlager to the sideline, caught, first down. "[Ward levels Jacobs, causing a fumble] Whoo!" What a hit! Denzel Ward! You've got barbecue back there, and you didn't invite me? Hurt! My! Feelings!


title: Gus Johnson (sportscaster)

text: December 8, 2018 – Johnson called the 2018 Citi Hoops Classic match-up between the Seton Hall Pirates and the 9th ranked Kentucky Wildcats at Madison Square Garden, where Keldon Johnson took a pass from P. J. Washington and made a half-court shot at the buzzer to tie the game at 70. Johnson's call of the final seconds of regulation:


title: Gus Johnson (sportscaster)

text: Here's P.J. Washington, he can run the baseline. Throws it, midcourt, Keldon Johnson! "[buzzer sounds]" OHH! HE BURIED IT! WOW! AND WE'RE – LEVEL AT 70! Whoo! Unbelieveable. And we're going to overtime... at the Garden!


title: Gus Johnson (sportscaster)

text: September 18, 2021 – On the 50th anniversary of the "Game of the Century" between Oklahoma and Nebraska, Johnson was the play-by-play announcer when the two teams faced each other again. During the fourth quarter, Oklahoma DB D.J. Graham made a one-handed interception on fourth down, leading to a notable call by Johnson, who referenced a similar one-handed touchdown catch made by Odell Beckham Jr. in 2014:


title: Gus Johnson (sportscaster)

text: Martinez, steps up, throws ... OHH, WHAT AN INTERCEPTION! OH MY GOSH! D.J. Graham! "Gimme that Odell!"


title: Gus Johnson (sportscaster)

text: September 19, 2021 – After returning to NFL duties for Fox, Johnson called the Week 2 NFL matchup between the Vikings and Cardinals, which came down to the Vikings attempting a game-winning field goal at the end of regulation, behind 34–33. The kick from Greg Joseph sailed to the right of the goalposts, leaving Johnson flabbergasted:


title: Gus Johnson (sportscaster)

text: Good snap, clean hold, for the winnnn...OHHHHH MY GOODNESS, HE MISSED IT! (pause) UNBELIEVABLE! And the Cardinals survive...34...33! You're watching the NFL, folks! On "F-O-X!""


title: Gus Johnson (sportscaster)

text: September 26, 2021 – Merely a week later in Week 3, Johnson was assigned again to a Cardinals game, this time against the Jaguars. Cardinal placekicker Matt Prater attempted a 68-yard field goal before halftime to top his previous league record 64-yarder in 2013, with the Jaguars readying Jamal Agnew for a possible return of a miss from the end zone. With Prater's kick trajectory short (by coincidence, Justin Tucker would hit a 66-yard winner in Detroit the same day, winning the game for Baltimore and earning the record), Agnew caught the ball 109 yards away in the Jaguars end zone, setting up Johnson for an enthusiastic call of his 'kick-six' runback:


title: Gus Johnson (sportscaster)

text: So here we go, Matt Prater, ready to attempt a 68-yarder, for NFL history. Got it up...it's short! Agnew, brings it out of the end zone. Agnew...still running. AGNEW...DOWN THE SIDELINE! AGNEW! TOUCHDOWN, JACKSONVILLE! A hundred...and...nine...yards. INCREDIBLE! "[pause]" Oh my goodness, watch this! (cuts to replay with Aqib Talib's analysis of the play)


title: Gus Johnson (sportscaster)

text: Johnson's call, which had him screaming at the top of his lungs, was well received by several fans and commentators.


title: Jason Narvy

text: Jason Andrew Narvy (born March 27, 1974) is an American actor known for playing the role of Eugene "Skull" Skullovitch on the various iterations of "Power Rangers" and film franchise from 1993 to 2012, beginning with "Mighty Morphin Power Rangers" in 1993.


title: Jason Narvy

text: Narvy grew up in Los Angeles. He studied at the Lee Strasberg Theater Institute. He is best known for playing Skull, one half of the bullying rival duo on Fox Television's children's TV series "Mighty Morphin Power Rangers", a role he reprised on its spin-offs, "Power Rangers Zeo", "Power Rangers Turbo", and "Power Rangers in Space", before leaving the franchise to continue college. He made a cameo appearance in the last episode of "Power Rangers Super Samurai". He also appeared in the feature film adaptations, "" in 1995 and the "" in 1997.


title: Jason Narvy

text: Narvy appeared in a lead role in a Fox Family pilot, "Men in White". He also appeared numerous commercials, public service announcements and voiced numerous toys, tie-ins, and video games for Fox, ABC, and Disney.


title: Jason Narvy

text: He received a Bachelor of Arts degree from Franklin and Marshall College, and got his master's degree from Mary Baldwin College, where he studied with the American Shakespeare Center, performing in the title role in "Henry V", "Pericles", and "Hamlet". He also appeared as Richard of Gloucester and Suffolk in a conflation of the Henry VI trilogy. Jason also worked with the Legitimate Theater Company of New York, a Lower East Side company that emphasizes new plays and experimental works.


title: Jason Narvy

text: Narvy is a certified actor/combatant with the British Academy of Stage and Screen Combat, a member of the Screen Actors Guild, and holds a PhD in Theater Studies from the University of California, Santa Barbara. He is currently an associate professor and chair in the Theater Department at Concordia University in Chicago.


title: Jason Narvy

text: To this date, Narvy remains very good friends with his co-star Paul Schrier, and was close to Jason David Frank before his death.


title: Fashion Sakala

text: Junior Fashion Sakala (born 14 March 1997) is a Zambian professional footballer who plays as a forward for Scottish Premiership club Rangers and the Zambia national team.


title: Fashion Sakala

text: Sakala played for Zambian clubs Nchanga Rangers and Zanaco, winning the Zambia Super League in 2016 with the latter. He signed for Spartak Moscow in February 2017. Sakala made no first-team appearances for the club, instead appearing for Spartak-2 Moscow in the second tier of Russian football. He joined Belgian club KV Oostende in July 2018, where he scored 31 goals in 102 appearances over three seasons. He joined Rangers on a free transfer in 2021.


title: Fashion Sakala

text: Sakala was a member of the Zambia under-20 team that won the 2017 Africa U-20 Cup of Nations. He made his senior international debut in September 2017.


title: Fashion Sakala

text: Sakala began his senior career in Zambia with Nchanga Rangers and Zanaco. He helped Zanaco win the Zambia Super League in 2016. In February 2017, he signed a three-year contract with Russian Premier League club FC Spartak Moscow, after being invited for a trial at their training camp in Cyprus. He made his debut in the Russian Football National League for FC Spartak-2 Moscow on 23 March 2017, in a game against FC Baltika Kaliningrad.


title: Fashion Sakala

text: On 4 May 2021, with his Oostende contract due to expire in the summer, Sakala signed a pre-contract agreement with Scottish Premiership club Rangers on a four-year deal. On 31 July, he made his official debut in a 3–0 win over Livingston in the league. On 31 October, he scored his first hat-trick for Rangers in a 6–1 league victory over Motherwell. On 4 October 2022, Sakala made his UEFA Champions League debut as a substitute in a 2–0 away loss against Liverpool.


title: Fashion Sakala

text: Sakala played youth international football for Zambia at under-20 and under-23 levels. He featured for the Zambia under-20 team that won the 2017 Africa U-20 Cup of Nations, scoring three goals at the tournament. He also played for the under-20 team that reached the quarter-finals of the 2017 FIFA U-20 World Cup, scoring four goals in the tournament. He scored seven goals in ten appearances in total at under-20 level. Sakala played one game for the Zambia under-23 team, against Nigeria at the 2019 Africa U-23 Cup of Nations.


title: Fashion Sakala

text: Sakala made his debut for the senior Zambia national team on 2 September 2017, in a 2018 FIFA World Cup qualifier against Algeria, and was sent off for two bookings in the 56th minute.


title: William Grant Still

text: William Grant Still Jr. (May 11, 1895 – December 3, 1978) was an American composer of nearly two hundred works, including five symphonies, four ballets, nine operas, over thirty choral works, plus art songs, chamber music and works for solo instruments. Born in Mississippi, he grew up in Little Rock, Arkansas, attended Wilberforce University and Oberlin Conservatory of Music, and was a student of George Whitefield Chadwick and later, Edgard Varèse. Because of his close association and collaboration with prominent African-American literary and cultural figures, Still is considered to have been part of the Harlem Renaissance.


title: William Grant Still

text: Often referred to as the "Dean of Afro-American Composers," Still was the first American composer to have an opera produced by the New York City Opera. Still is known primarily for his first symphony, "Afro-American Symphony" (1930), which was, until 1950, the most widely performed symphony composed by an American. Also of note, Still was the first African-American to conduct a major American symphony orchestra, the first to have a symphony (which was, in fact, the first one he composed) performed by a leading orchestra, the first to have an opera performed by a major opera company, and the first to have an opera performed on national television.


title: William Grant Still

text: William Grant Still Jr. was born on May 11, 1895, in Woodville, Mississippi. He was the son of two teachers, Carrie Lena Fambro (1872–1927) and William Grant Still Sr. (1871–1895). His father was a partner in a grocery store and performed as a local bandleader. William Grant Still Sr. died when his infant son was three months old.


title: William Grant Still

text: Still's mother moved with him to Little Rock, Arkansas, where she taught high school English. She met and in 1904 married Charles B. Shepperson, who nurtured his stepson William's musical interests by taking him to operettas and buying Red Seal recordings of classical music, which the boy greatly enjoyed. The two attended a number of performances by musicians on tour. His maternal grandmother Anne Fambro sang African-American spirituals to him.


title: William Grant Still

text: Still started violin lessons in Little Rock at the age of 15. He taught himself to play the clarinet, saxophone, oboe, double bass, cello and viola, and showed a great interest in music. At 16 years old, he graduated as class valedictorian from M. W. Gibbs High School in Little Rock in 1911.


title: William Grant Still

text: His mother wanted him to go to medical school, so Still pursued a Bachelor of Science degree program at Wilberforce University, a historically black college in Ohio. Still became a member of Kappa Alpha Psi fraternity. He conducted the university band, learned to play various instruments, and started to compose and to do orchestrations. He left Wilberforce without graduating.


title: William Grant Still

text: Upon receiving a small amount of money left to him by his father, he began studying at the Oberlin Conservatory of Music. Still worked for the school assisting the janitor, along with a few other small jobs outside of the school, yet still struggled financially. When Professor Lehmann asked Still why he wasn't studying composition, Still told him honestly that he couldn't afford to, leading to George Andrews agreeing to teach him composition without charge. He also studied privately with the modern French composer Edgard Varèse and the American composer George Whitefield Chadwick.


title: William Grant Still

text: On October 4, 1915, Still married Grace Bundy, whom he had met while they were both at Wilberforce. They had a son, William III, and three daughters, Gail, June, and Caroline. They separated in 1932 and divorced February 6, 1939. On February 8, 1939, he married pianist Verna Arvey, driving to Tijuana for the ceremony because interracial marriage was illegal in California. They had a daughter, Judith Anne, and a son, Duncan. Still's granddaughter is journalist Celeste Headlee, a daughter of Judith Anne.


title: William Grant Still

text: On December 1, 1976, his home was designated Los Angeles Historic-Cultural Monument #169. It is located at 1262 Victoria Avenue in Oxford Square, Los Angeles.


title: William Grant Still

text: In 1916, Still worked in Memphis for W.C. Handy's band. In 1918 Still joined the United States Navy to serve in World War I. After the war he went to Harlem, where he continued to work for Handy. During his time in Harlem Still was involved with other important cultural figures of the Harlem Renaissance such as Langston Hughes, Alain Locke, Arna Bontemps, and Countee Cullen, and is considered to be part of that movement.


title: William Grant Still

text: He recorded with Fletcher Henderson's Dance Orchestra in 1921, and later played in the pit orchestra for Noble Sissle and Eubie Blake's musical, "Shuffle Along" and in other pit orchestras for Sophie Tucker, Artie Shaw, and Paul Whiteman. With Henderson, he joined Henry Pace's Pace Phonograph Company (Black Swan). Later in the 1920s, Still served as the arranger of ""Yamekraw"", a "Negro Rhapsody" (1930), composed by the Harlem stride pianist James P. Johnson.


title: William Grant Still

text: In the 1930s, Still worked as an arranger of popular music, writing for Willard Robison's "Deep River Hour" and Paul Whiteman's "Old Gold Show", both popular NBC Radio broadcasts.


title: William Grant Still

text: Still's first major orchestral composition, "Symphony No. 1 "Afro-American"," was performed in 1931 by the Rochester Philharmonic, conducted by Howard Hanson. It was the first time the complete score of a work by an African American was performed by a major orchestra. By the end of World War II the piece had been performed in New York, Chicago, Los Angeles, Berlin, Paris, and London. Until 1950 the symphony was the most popular of any composed by an American. Still developed a close professional relationship with Hanson; many of Still's compositions were performed for the first time in Rochester.


title: William Grant Still

text: In 1934, Still moved to Los Angeles. He received his first Guggenheim Fellowship and started work on the first of his nine operas, "Blue Steel".


title: William Grant Still

text: In 1936, Still conducted the Los Angeles Philharmonic Orchestra at the Hollywood Bowl; he was the first African American to conduct a major American orchestra in a performance of his own works.


title: William Grant Still

text: Still arranged music for films. These included "Pennies from Heaven" (the 1936 film starring Bing Crosby and Madge Evans) and "Lost Horizon" (the 1937 film starring Ronald Colman, Jane Wyatt and Sam Jaffe). For "Lost Horizon", he arranged the music of Dimitri Tiomkin. Still was also hired to arrange the music for the 1943 film "Stormy Weather", but left the assignment because "Twentieth-Century Fox 'degraded colored people.'"


title: William Grant Still

text: Still composed "Song of a City" for the 1939 World's Fair in New York City. The song played continuously during the fair by the exhibit "Democracity." According to Still's granddaughter, he couldn't attend the fair except on "Negro Day" without police protection.


title: William Grant Still

text: In 1949, his opera "Troubled Island", originally completed in 1939, about Jean-Jacques Dessalines and Haiti, was performed by the New York City Opera. It was the first opera by an American to be performed by that company and the first by an African American to be performed by a major company. Still was upset by the negative reviews it received.


title: William Grant Still

text: In 1955, he conducted the New Orleans Philharmonic Orchestra; he was the first African American to conduct a major orchestra in the Deep South. Still's works were performed internationally by the Berlin Philharmonic Orchestra, the London Symphony Orchestra, the Tokyo Philharmonic Orchestra, and the BBC Orchestra.


title: William Grant Still

text: In 1981, the opera "A Bayou Legend" was the first by an African-American composer to be performed on national television.


title: William Grant Still

text: Still was known as the "Dean of Afro-American Composers". Still and Arvey's papers are held by the University of Arkansas.


title: William Grant Still

text: Still composed almost 200 works, including nine operas, five symphonies, four ballets, plus art songs, chamber music, and works for solo instruments. He composed more than thirty choral works. Many of his works are believed to be lost.


title: PG: Psycho Goreman

text: PG: Psycho Goreman, or simply Psycho Goreman, is a 2020 Canadian science fantasy action horror-comedy film written and directed by Steven Kostanski. It stars Nita-Josee Hanna and Owen Myre as a young sister and brother who unwittingly resurrect an ancient extraterrestrial overlord (voiced by Steven Vlahos and played by Matt Ninaber).


title: PG: Psycho Goreman

text: "Psycho Goreman" was originally scheduled to premiere at the South by Southwest film festival in March 2020, but the festival was cancelled due to the COVID-19 pandemic. It screened later that year as part of Beyond Fest, the Sitges Film Festival and Monster Fest. Having been acquired by RLJE Films and Shudder, "Psycho Goreman" was released in theaters and on video on demand on January 22, 2021.


title: PG: Psycho Goreman

text: Siblings Mimi and Luke discover a strange, glowing gem while digging in their garden. That night, an alien monster emerges from the hole. The monster enters an old shoe factory and brutally kills a group of thieves hiding out there. The next day, Mimi and Luke follow a trail to the shoe factory and discover the monster. The monster identifies himself as "Arch-Duke of Nightmares", a deadly alien warrior imprisoned on earth after attempting to destroy the galaxy in a rampage. Before he can kill them, he realises Mimi has the gem, which allows her to command him. Mimi dubs the alien "Psycho Goreman" (or "PG" for short) and begins commanding PG around despite Luke's concerns. A group of aliens called the "Planetary Alliance" discover PG has escaped imprisonment, and send the warrior Pandora to Earth in the form of a human woman to kill him.


title: PG: Psycho Goreman

text: PG tells the children he was a slave to the Templars, Pandora's religious order on his home planet Gigax until he discovered the gem which bonded with him, giving immense power. He assembled an army called "The Paladins Obsidian" and battled the Templars, and began a rampage across the galaxy until the Planetary Alliance defeated him and imprisoned him on Earth. When the children leave, PG broadcasts a call for help to the Paladins Obsidian. Mimi and Luke's parents Susan and Greg see PG and Mimi introduces him to them, showing how she can control him. Mimi forces PG to accompany the family on activities and become a reluctant friend to the family.


title: PG: Psycho Goreman

text: While out with PG, the group is approached by two police officers who attack PG. PG mutates one of them into a deformed slave while the other officer escapes. Pandora arrives at the police station and interrogates the officer that escaped PG for information. In the woods, the Paladins Obsidian arrive in front of the group. PG orders them to kill Mimi and Luke only for the Paladins to reveal they are now allied with the Templars. PG is injured by them when Mimi keeps him from fighting back until he apologises, but kills them easily when he is released. He then collapses from his injuries.


title: PG: Psycho Goreman

text: PG comes to Greg in a vision demanding he collects him and the children from the woods. Greg does so and they drive back to the house where Pandora is waiting with Susan. Susan suggests they hand over PG to Pandora, and Luke agrees. Greg sides with Mimi and drives away with PG, hiding in the shoe factory. Pandora reveals her true form before transforming Susan into an armored warrior to help take down PG. PG states giving him the gem is the only way to heal him, and Mimi agrees on the promise he will spare her and her family in his crusade against the galaxy, but realises Luke has stolen it.


title: PG: Psycho Goreman

text: Pandora, Susan, and Luke arrive and battle Mimi, Greg, and PG. Luke convinces Mimi that the power of the gem and PG have corrupted her. Before Pandora can kill PG, he challenges her to a battle of Mimi's choosing. She chooses Crazy Ball, a game she and Luke made up with extremely complex rules. Mimi's team wins but Pandora moves in to attack Mimi and PG anyway. Susan uses her powers to save Mimi but is reverted to her human form by Pandora. Luke and Mimi reconcile and hand the gem to PG, healing him. PG defeats Pandora and devours her. PG returns the now powerless gem to Mimi, stating that after witnessing the family's affection for each other, he is now powered by love. He will use that love to destroy the galaxy, but promises to spare the family. The family bids farewell to PG and watches as he begins to destroy their town. The news shows PG in giant form devastating the Earth, and in deep space the Planetary Alliance debates killing themselves before he can reach them.


title: PG: Psycho Goreman

text: "Psycho Goreman" was initially scheduled to premiere at the South by Southwest film festival in March 2020, prior to the festival's cancellation due to the COVID-19 pandemic. It screened later that year as part of Beyond Fest on October 7, 2020, and also screened as part of the Sitges Film Festival and Australia's Monster Fest. The film's distribution rights were acquired by RLJE Films and Shudder, and it was simultaneously released in theaters and on video on demand on January 22, 2021. A limited edition DVD/Blu-ray was released on March 16, 2021.


title: PG: Psycho Goreman

text: On the review aggregator website Rotten Tomatoes, the film holds an approval rating of based on reviews, with an average rating of . The site's consensus reads, "Over the top and enthusiastically strange, "PG: Psycho Goreman" delivers all the cheesy midnight-movie goodness promised by its title."


title: PG: Psycho Goreman

text: Barry Hertz of "The Globe and Mail" praised the film, writing that "if you happen to be operating on Kostanski's very particular and peculiar wavelength, the movie is an absolute riot. Working with little resources, the director creates a wildly colourful, surprisingly epic universe full of alien landscapes, energetic set-pieces and a fantastical creature design that strikes just the right balance between inventive and derivative." Owen Gleiberman, in his review of the film for "Variety", concluded that "As satire, "Psycho Goreman" is no "Planet Terror", but it's a droll enough schlock-in-quote-marks diversion, and part of its appeal is just how damn cheap it is. In the omni-tech era, it's fun to see a filmmaker build an FX fantasy out of scraps, from the ground up."


title: PG: Psycho Goreman

text: Bloody Disgusting's Meagan Navarro wrote that "We may not care about the human protagonists by the time the end credits roll and the '90s-style end credit rap kicks in, but ["Psycho Goreman"] does leave you hoping to see more of P.G. and his continued quest for domination of the cosmos." Richard Whittaker of "The Austin Chronicle" gave the film a score of three out of five stars, writing that it "channels Saturday mornings loaded with "Power Rangers" reruns, just with the added realization that the creatures were supercool." Chris Aitkens of Nightmare on Film Street praised the film, saying it was " a vehicle for over-the-top violence". Mary Beth McAndrews of "Paste" called the film "a necessary explosion of ridiculous fun in a time when it's needed most. [...] The extreme tonal shifts from hard sci-fi to family comedy will be weird for some, but Kostanski never hides what this film is: Ridiculous."


title: PG: Psycho Goreman

text: Conversely, Simon Abrams of RogerEbert.com gave the film one-and-a-half stars out of four, writing that it "isn't clever or lively enough to be more than fitfully fun, especially given how much time is spent mocking generic, but painstakingly recreated plot contrivances." "Slant Magazine"s Pat Brown gave it two out of four stars, calling it a "tongue-in-cheek gorefest" but also "a somewhat empty film."


title: Waikato

text: Waikato () is a local government region of the upper North Island of New Zealand. It covers the Waikato District, Waipa District, Matamata-Piako District, South Waikato District and Hamilton City, as well as Hauraki, Coromandel Peninsula, the northern King Country, much of the Taupō District, and parts of Rotorua District. It is governed by the Waikato Regional Council.


title: Waikato

text: The region stretches from Coromandel Peninsula in the north, to the north-eastern slopes of Mount Ruapehu in the south, and spans the North Island from the west coast, through the Waikato and Hauraki to Coromandel Peninsula on the east coast. Broadly, the extent of the region is the Waikato River catchment. Other major catchments are those of the Waihou, Piako, Awakino and Mokau rivers. The region is bounded by Auckland on the north, Bay of Plenty on the east, Hawke's Bay on the south-east, and Manawatū-Whanganui and Taranaki on the south. Waikato Region is the fourth largest region in the country in area and population: It has a land area of and a population of


title: Waikato

text: The region encompasses all or part of eleven territorial authorities, the most of any region of New Zealand. It is centred on the Waikato which consists of Waikato District, Matamata-Piako District, Waipa District, South Waikato District and Hamilton City. In descending order of land area the eleven territorial authorities are Taupō District (part), Waikato District, Waitomo District (part), Thames-Coromandel District, Ōtorohanga District, South Waikato District, Matamata-Piako District, Waipa District, Hauraki District, Rotorua District (part), and Hamilton City.


title: Waikato

text: The name for the region is taken from the Waikato River; "waikato" is a Māori word traditionally translated as "flowing water" (specifically, "wai" = "water" and "kato" = "the pull of the river current in the sea").


title: Waikato

text: When Waikato is used in spoken language it takes the definite article: the Waikato. But this usually refers to a smaller region than the Waikato local government region. Two definitions that would meet with wide acceptance are those of the Waikato rugby football union and of Hamilton Waikato tourism. The former takes in the local government areas of Hamilton City, the southern part of Waikato district, Waipa district, most of Matamata-Piako district and the South Waikato district. Hamilton Waikato tourism takes in additionally the northern part of Waikato district (Tuakau and other centres), the northern King Country (Waitomo and Ōtorohanga districts), and the Te Aroha district.


title: Waikato

text: The parts of Waikato region beyond these limits are usually identified as Thames Valley and/or Hauraki/Coromandel (for the north-eastern part of Waikato region) and Taupō, on the Volcanic or Central Plateau (for the south-eastern part of the region).


title: Waikato

text: To the west, the region is bounded by the Tasman Sea. The coastal region is largely rough hill country, known locally as the Hakarimata Range, though it is more gently undulating in the north, closer to the mouth of the Waikato River. The coast is punctured by three large natural harbours: Raglan Harbour, Aotea Harbour, and Kawhia Harbour. The area around Raglan is noted for its volcanic black sand beaches and for its fine surfing conditions at Manu Bay and Ruapuke beach.


title: Waikato

text: To the east of the coastal hills lies the broad alluvial plain of the Waikato River. This region has a wet temperate climate, and the land is largely pastoral farmland created by European settlers draining the extensive natural swamps, although it also contains undrained peat swamp such as the peat dome south of Ngatea. It is in the broad undulating Waikato Plains that most of the region's population resides, and the land is intensively farmed with both livestock, mainly dairy cattle but with sheep farming on the hillier west margins, and crops such as maize. The area around Cambridge has many thoroughbred stables.


title: Waikato

text: The north of the region around Te Kauwhata produces some of New Zealand's best wines. Dozens of small shallow lakes lie in this area, the largest of which is Lake Waikare.


title: Waikato

text: To the east, the land rises towards the forested slopes of the Kaimai and Mamaku Ranges. The upper reaches of the Waikato River are used for hydroelectricity, helped by several large artificial lakes in the region's south-east. The lowest and earliest-created such lake is Lake Karapiro, now developed as a world-class rowing centre, where the world championships were held in 2010. The river flows out of the country's largest lake, Lake Taupō, which is served by several important fishing rivers such as the Tongariro, on the Central Plateau, draining the eastern side of Mount Ruapehu and its neighbours.


title: Waikato

text: The climate is mild and temperate with moderate rainfall of 1200–1600mm per annum, with the higher western hills having the most rain. Summers are drier with typical maximum temperatures of 22–28 degrees Celsius and overnight lows of 12-16 degrees. Summer droughts occur one year in ten. Typical winter maxima are 10–16 degrees Celsius, with lows generally ranging from 0-8 degrees. Depressions experience regular morning fog, under anticyclonic conditions, which burns off by late morning to produce many still, clear sunny days. Morning frosts are also common during winter anticyclones. Another distinctive feature is the low average wind speed in the interior basin due to the sheltering influence of the hills and mountains to the west and south-west. The prevailing winter wind is from the south-west. The Waikato has very high sunshine hours by world standards, averaging 2200 hours per year or about 40% higher than in the UK. This results in rapid growth of grass, crops and ornamental plants.


title: Waikato

text: Waikato Region covers and had an estimated population of as of with a population density of people per km.


title: Waikato

text: Waikato Region had a population of 458,202 at the 2018 New Zealand census, an increase of 54,561 people (13.5%) since the 2013 census, and an increase of 77,379 people (20.3%) since the 2006 census. There were 162,927 households. There were 226,386 males and 231,816 females, giving a sex ratio of 0.98 males per female. The median age was 37.4 years (compared with 37.4 years nationally), with 96,765 people (21.1%) aged under 15 years, 90,342 (19.7%) aged 15 to 29, 198,063 (43.2%) aged 30 to 64, and 73,032 (15.9%) aged 65 or older.


title: Waikato

text: Ethnicities were 74.4% European/Pākehā, 23.9% Māori, 4.5% Pacific peoples, 9.5% Asian, and 2.3% other ethnicities (totals add to more than 100% since people could identify with multiple ethnicities).


title: Waikato

text: Although some people objected to giving their religion, 50.6% had no religion, 34.8% were Christian, 1.7% were Hindu, 0.9% were Muslim, 0.8% were Buddhist and 4.1% had other religions.


title: Waikato

text: Of those at least 15 years old, 67,560 (18.7%) people had a bachelor or higher degree, and 71,901 (19.9%) people had no formal qualifications. The median income was $30,400, compared with $31,800 nationally. 55,953 people (15.5%) earned over $70,000 compared to 17.2% nationally. The employment status of those at least 15 was that 176,901 (48.9%) people were employed full-time, 53,970 (14.9%) were part-time, and 15,660 (4.3%) were unemployed.


title: Waikato

text: The largest city in the Waikato Region is Hamilton, with an urban population of . It is home to the University of Waikato and the Waikato Institute of Technology (Wintec).


title: Waikato

text: Other major towns in the region are Tokoroa, Te Awamutu, Cambridge and Taupō with respective populations of , , and . (These populations include the urban and peri-urban areas). The region also includes the smaller towns of Huntly, Matamata, Morrinsville, Ngāruawāhia, Otorohanga, Paeroa, Putāruru, Raglan, Te Aroha, Te Kauwhata, Te Kuiti, Thames, Tīrau, Tuakau, Turangi, Whangamatā and Whitianga.


title: Waikato

text: The subnational gross domestic product (GDP) of the Waikato region was estimated at NZ$25.84 billion in the year to March 2019, 8.5% of New Zealand's national GDP. The subnational GDP per capita was estimated at $54,128 in the same period. In the year to March 2018, primary industries contributed $3.14 billion (13.0%) to the regional GDP, goods-producing industries contributed $5.70 billion (23.5%), service industries contributed $13.35 billion (55.0%), and taxes and duties contributed $2.08 billion (8.6%).


title: Waikato

text: Between 2000 and 2004, Waikato economic growth was lower than the national average. But from 2004 to 2007, real gross regional product for the Waikato Region increased by 5 per cent per year compared with 3.2 per cent for the national average. This faster growth can be attributed to rapidly growing dairy and business services industries, facilitated by proximity to the Auckland city, the main international gateway for New Zealand.


title: Waikato

text: Given the suitable geography and climate, the Waikato economy is strongly based on agriculture, especially dairy. Dairy farming has been the main agricultural activity since the late nineteenth century. Within the Waikato region, small co-operative dairy companies were widespread during the 20th century. Towards the end of the 20th century, frequent mergers of co-operative dairy companies occurred, which ultimately ended in the formation of New Zealand wide dairy co-operative Fonterra in 2001. In 2007, dairy farming and dairy processing combined contributed $2 billion (13%) to GRP, which had risen to $2.4bn by 2014, but only 13,683 (7.6%) of jobs in 2016.


title: Waikato

text: Dairy farms are mainly family owned (2,608 of 4,020 farms in 2016) with owners employing sharemilkers in many cases (1,412 sharemilkers). The size of the average dairy herd in the Waikato has progressively increased. It was about 320 cows in 2012 and in 2016 was about 351 (total Waikato herd 1.41m cows), milked in either a herringbone or automated rotary cowshed so a large herd can be milked in under two hours. The cows are kept on grassland pasture all year due to the mild climate. In the Waikato the original English grasses used by earlier settlers – browntop, fescue and Yorkshire Fog – have been replaced with higher producing Italian ryegrass and nitrogen-fixing white clover. Farmers use a variety of supplementary feeds in winter or during the infrequent summer droughts. Main feeds are hay, grass silage and chopped corn feed. The later is often fed out on a concrete pad to save transportation and wastage by trampling.


title: Waikato

text: The manufacturing sector in Waikato contributed $2,688 million in GDP in the year to March 2018, 11.1% of the regional GDP. According to the 2013 New Zealand census, the sector employed 18,519 people, or 9.9% of the region's employed population.


title: Waikato

text: With a large dairy farming industry, the Waikato also has a large dairy processing industry. Fonterra operates dairy processing plants at Te Rapa, Te Awamutu, Hautapu, Waitoa, Tīrau and Lichfield. Other dairy processing plants include Tatua Dairy Company's plant at Tatuanui, and Open Country Dairy's plant at Horotiu and Waharoa.


title: Waikato

text: The Waikato region has eight major freezing works: AFFCO at Horotiu, Greenlea at Hamilton and Morrinsville, Silver Fern Farms at Te Aroha and Waitoa, Te Kuiti Meat Processors and Universal Beef Packers at Te Kuiti, and Crusader Meats at Benneydale.


title: Waikato

text: Before the arrival of Europeans, the Waikato contained the third most densely populated part of New Zealand, after Northland/Auckland and the Bay of Plenty. The Waikato "rohe" (area) was inhabited by "iwi" (tribes) such as those of the Tainui confederation, including Waikato and Ngāti Toa who conquered the native inhabitants about 1450 according to Tainui historians, finally destroying them at a battle at Aratiatia. Between about 1750 and 1842 the area was subject to a large number of invasions by other Māori iwi and hapu confederations and large scale population migrations took place by a number of "hapu" and "iwi". The largest battle ever fought in New Zealand took place near Ohaupo about 1790–1805, between two competing alliances of "hapu". During the latter stages of this volatile period, known as the Musket Wars (1807–1845), conflict led to a migration south to Taranaki and eventually Kapiti Island.


title: Waikato

text: In 1840 44 Waikato chiefs travelled north to the Manukau Heads and Manukau Harbour to sign the Treaty of Waitangi, officially making the Waikato area part of New Zealand. Three Ngati Maniapoto chiefs signed, as did three Ngati Haua chiefs but most signatories were Waikato. Chief Te Whero whero did not sign, "probably due to the lack of dignity compared to the Waitangi event". Unusually, the copy signed was in English. Between 1840 and 1860 the CMS missionaries of the Anglican church assisted Waikato Maori in revolutionizing their economy in the Kihikihi area by the introduction of such crops as peaches, maize and wheat.


title: Waikato

text: Missionaries brought in millers and helped Maori establish eight flour mills. These flourished until 1857, as they provided flour for the growing Auckland market in the 1850s and for a brief while were exporting to Australia. There were mills at Aotea, Kaitotehe, Karakariki, Kihikihi, Kirikiriroa, Kohanga, Kopatauaki, Mahoe, Mangaharakeke, Mangapapa, Mangarewarewa, Mangatawhiri, Matamata pā, Maungakawa, Maungatautari, Mohoaonui, Otawhao, Patetere, Rangataiki, Rangiaowhia, Taupō, Te Kopua, Te Rore, Tireke, Tuakau, Waitetuna, Whaingaroa and Whatawhata.


title: Waikato

text: The route used to travel to and from Auckland was by dray to the Puniu stream, along the Waipā River to its junction with the Waikato. Near the Waikato Heads travellers entered the small Awaroa River. During summer it was necessary to push or pull the waka through to the Manukau Harbour at Waiuku. By the 1850s a small bullock track had been established to Auckland via the settlements of Mauku, Drury, Papakura and Otahuhu, or waka could take the sea route across the Manukau to Ihumatao (where Auckland International Airport is now). The main tribe to use this route and the main traders were the Maniapoto tribe. They occupied an area of fertile land south of Te Awamutu at Kihikihi and Rangiaowhia. Maniapoto sold wheat, peaches, potatoes and other food to Auckland and bought back shirts, sugar, tobacco and rum. The boom time ended in 1856–1857 with the end of the Australian gold rush, allowing importing of cheaper food, especially flour, from Australia. Even in the boom time of 1854–55, food grown by Waikato Maori, such as Ngati Maniapoto, was taken to the Auckland market in very small amounts compared to food from the Waiheke Island -Thames area. In early 1855 Ngati Maniapoto took only 3 canoes of potatoes to Auckland compared to 279 canoes containing a much wider variety of food from the Thames area. Missionaries had also established schools for Maori. Benjamin and Harriet Ashwell ran a school for 50 Maori girls aged 6–17 at Taupiri in 1853. The girls had been at the school for up to 3 years and could read and write in English and do mental arithmetic.


title: Waikato

text: At the time of the Waikato campaign of 1863 against the rebel Māori King Movement forces, the population was estimated by the government at about 3,500 Māori.


title: Waikato

text: During the late 1850s Maniapoto in particular become disgruntled in their dealings with Pakeha. They complained about the way they were treated in Auckland by traders but their chief complaint was that the government was underpaying them for land they were selling. The average price paid by government was 6d per acre but it was sold to settlers for 10/- per acre. The government argued that it had to pay for surveying and administration costs but to Maori it seemed unfair. Before the elevation of the first Maori king there was a wide range of opinions among influential Maori with some such as Wirimu Tamihana's father advocating supporting the Crown while Te Heuheu of Tuwharetoa advocated all out war against the government. This view was initially unpopular as the king movement hoped to work alongside the crown. Maori were upset at the number of children that had been fathered by Pakeha, who had then disappeared. The children were left to be raised by their mothers with general hapu support. John Gorst, a well-educated government agent, reported significant numbers of half-caste children in the Waikato in the late 1850s. However, in the Ngati Maniapoto iwi at least 7 Pakeha integrated successfully with the tribe from 1842, marrying Maori women. The best known are William Searancke, who became an important government agent, and Frenchman Louis Hetet, who became a successful trader. Their half-caste children lived with the iwi, and some became leading figures.


title: Waikato

text: What tipped the balance was conflict and criminal activity within the Waikato region. Influential chiefs said the treaty had promised the government would help maintain peace. They asked for government magistrates and courts. The government attempted to fulfill these requests but many of the young men who put themselves forward for the positions simply saw that they had an opportunity to get wealthy at the government's expense. This upset the older chiefs, who wanted the strong Maori leader Te Wherowhero to return from Mangere to his lands at Tamahere (South Hamilton) to rein in the out-of-control young chief magistrates.


title: Waikato

text: The Waikato has a prominent history, particularly regarding relationships between Māori and European in early colonial New Zealand. The Waikato was within the defined boundaries of the colonial provinces of New Ulster (1841–1853) and Auckland (1853–1876) but was principally Māori. During the land wars of the 1860s, the Waikato was the scene of five battles in what is referred to as the Invasion of the Waikato. In retaliation for the help Waikato Māori (mainly Ngāti Maniapoto) gave Taranaki Māori in their conflict over land in the earlier First Taranaki War, and the decision by some Waikato "hapu" to form a separate kingdom – the King Movement or "Kingitanga" – in opposition to the government, the colonial government, with the help of troops brought from Britain and Queenite Māori loyal to the Crown, pushed south from the main settlement of Auckland, fighting against Waikato raiders in Auckland before venturing into the Waikato to attack the combined "hapu" of the King Movement. During 1863 and 1864 fighting occurred at Pukekohe East, Titi hill, Burtts Farm, Galloway Redoubt, Kiri Kiri, Martyn's Farm, Patumahoe, Rhodes Clearing, Williamson's Clearing, Otau, Camerontown, Kakaramea and Wairoa ranges (all Auckland), Meremere, Rangiriri, Ngāruawāhia, Rangiaowhia (southwest of Cambridge), Hairini Ridge and Ōrākau (near Kihikihi), all resulting in defeat for the "Kingitanga" forces. Eventually the rebel King Movement forces pulled back to positions in the area to the south of the Punui River in South Waikato, still known as the King Country, after 19 defeats by the British. "Rewi's Last Stand", one of New Zealand's first motion pictures, in 1925, portrayed an entertaining, fictionalized version of the Ōrākau siege.


title: Waikato

text: After the end of the war and the withdrawal of British and Australian troops, the region experienced a long period of economic recession after 1866. Most Maori had moved to the King Country and European settlers were more attracted to the South Island with its large gold discovery in Otago and the more easily farmed Canterbury Plains. The Waikato had poor land access and was not suitable for sheep farming which dominated livestock production in New Zealand until the 1890s invention of refrigeration. Dairying and the completion of the main trunk railway line at the turn of the century lead to a small, steady increase in population. After 1900, dairy production in the Waikato continued to grow, exporting butter and cheese mainly to Britain.


title: Waikato

text: Following major floods in 1907, a Waikato River Board was formed in 1911. However, it was reported as ineffective in 1921 and ceased to operate, though the need for a replacement was considered in 1933.


title: Waikato

text: Major floods also occurred in 1953 and 1956. Waikato Valley Authority was established by the Waikato Valley Authority Act on 26 October 1956. The Water and Soil Conservation Act 1967 extended it to become a Catchment/Regional Water Board. The Ministry of Works and Development Abolition Act 1988, left WVA with that work and it became the Waikato Catchment Board.


title: Waikato

text: The Waikato United Council, was formulated under the Local Government Act 1974, but due to objections excluded Thames/Coromandel district, though otherwise covered the present extent of the region. It was set up under the Town and Country Planning Act 1977 and the Waikato Region Constitution Order 1980. WUC covered Hamilton City, Huntly, Ngāruawāhia, Cambridge, Te Awamutu, Matamata, Putāruru and Tokoroa boroughs, Matamata, Raglan, Waikato, and Waipa counties, Ōtorohanga and Waitomo districts. It took over the Hamilton Regional Planning Authority and mainly dealt with regional planning and civil defence. By 1989, WUC had committees for regional planning, civil defence, regional government, and the Waikato Regional Development Board. From 1987 it also included Thames-Coromandel District, Great Barrier Island, Hauraki Plains, Ohinemuri and Piako counties, and Morrinsville, Paeroa, Te Aroha and Waihi boroughs.


title: Waikato

text: On 1 November 1989, Waikato Regional Council was established by the Local Government (Waikato Region) Reorganisation Order 1989. from 40 former authorities:- 2 catchment boards (Hauraki and Waikato), 3 united councils (Waikato, Thames Valley and part of Tongariro), 12 noxious plants authorities, 11 pest destruction boards and 12 drainage boards. The Land Transport Act 1998 added transport to WRC's responsibilities. From 1 November 2010 Environment Waikato took over the southern parts of Franklin District. That seems to be the only legislation naming it 'Environment Waikato', which had been its operating name until 2011, shortly after the 'Rates Control Team' won about half the seats in the 2010 election.


title: Waikato

text: In the 2010 local government elections, the Waikato Region had the country's lowest rate of returned votes. Since then the percentage turnout has declined further.


title: Waikato

text: The people of the Waikato use the nickname Mooloo to apply to themselves or to their region, particularly in relation to sporting endeavours. The word was likely first applied to the Waikato provincial rugby team. Its origin is related to the mascot of a pantomime-like milking cow used in parades, public events and sports matches — particularly rugby, reflecting the importance of the dairy industry to the region. Waikato hosts the Chiefs Super Rugby team and Waikato Mitre 10 Cup rugby team at Waikato Stadium and the Northern Districts Knights in domestic cricket at Seddon Park, both in Hamilton.


title: Drug design

text: Drug design, often referred to as rational drug design or simply rational design, is the inventive process of finding new medications based on the knowledge of a biological target. The drug is most commonly an organic small molecule that activates or inhibits the function of a biomolecule such as a protein, which in turn results in a therapeutic benefit to the patient. In the most basic sense, drug design involves the design of molecules that are complementary in shape and charge to the biomolecular target with which they interact and therefore will bind to it. Drug design frequently but not necessarily relies on computer modeling techniques. This type of modeling is sometimes referred to as computer-aided drug design. Finally, drug design that relies on the knowledge of the three-dimensional structure of the biomolecular target is known as structure-based drug design. In addition to small molecules, biopharmaceuticals including peptides and especially therapeutic antibodies are an increasingly important class of drugs and computational methods for improving the affinity, selectivity, and stability of these protein-based therapeutics have also been developed.


title: Drug design

text: The phrase "drug design" is to some extent a misnomer. A more accurate term is ligand design (i.e., design of a molecule that will bind tightly to its target). Although design techniques for prediction of binding affinity are reasonably successful, there are many other properties, such as bioavailability, metabolic half-life, side effects, etc., that first must be optimized before a ligand can become a safe and efficacious drug. These other characteristics are often difficult to predict with rational design techniques. Nevertheless, due to high attrition rates, especially during clinical phases of drug development, more attention is being focused early in the drug design process on selecting candidate drugs whose physicochemical properties are predicted to result in fewer complications during development and hence more likely to lead to an approved, marketed drug. Furthermore, in vitro experiments complemented with computation methods are increasingly used in early drug discovery to select compounds with more favorable ADME (absorption, distribution, metabolism, and excretion) and toxicological profiles.


title: Drug design

text: A biomolecular target (most commonly a protein or a nucleic acid) is a key molecule involved in a particular metabolic or signaling pathway that is associated with a specific disease condition or pathology or to the infectivity or survival of a microbial pathogen. Potential drug targets are not necessarily disease causing but must by definition be disease modifying. In some cases, small molecules will be designed to enhance or inhibit the target function in the specific disease modifying pathway. Small molecules (for example receptor agonists, antagonists, inverse agonists, or modulators; enzyme activators or inhibitors; or ion channel openers or blockers) will be designed that are complementary to the binding site of target. Small molecules (drugs) can be designed so as not to affect any other important "off-target" molecules (often referred to as antitargets) since drug interactions with off-target molecules may lead to undesirable side effects. Due to similarities in binding sites, closely related targets identified through sequence homology have the highest chance of cross reactivity and hence highest side effect potential.


title: Drug design

text: Most commonly, drugs are organic small molecules produced through chemical synthesis, but biopolymer-based drugs (also known as biopharmaceuticals) produced through biological processes are becoming increasingly more common. In addition, mRNA-based gene silencing technologies may have therapeutic applications.


title: Drug design

text: In contrast to traditional methods of drug discovery (known as forward pharmacology), which rely on trial-and-error testing of chemical substances on cultured cells or animals, and matching the apparent effects to treatments, rational drug design (also called reverse pharmacology) begins with a hypothesis that modulation of a specific biological target may have therapeutic value. In order for a biomolecule to be selected as a drug target, two essential pieces of information are required. The first is evidence that modulation of the target will be disease modifying. This knowledge may come from, for example, disease linkage studies that show an association between mutations in the biological target and certain disease states. The second is that the target is "druggable". This means that it is capable of binding to a small molecule and that its activity can be modulated by the small molecule.


title: Drug design

text: Once a suitable target has been identified, the target is normally cloned and produced and purified. The purified protein is then used to establish a screening assay. In addition, the three-dimensional structure of the target may be determined.


title: Drug design

text: The search for small molecules that bind to the target is begun by screening libraries of potential drug compounds. This may be done by using the screening assay (a "wet screen"). In addition, if the structure of the target is available, a virtual screen may be performed of candidate drugs. Ideally the candidate drug compounds should be "drug-like", that is they should possess properties that are predicted to lead to oral bioavailability, adequate chemical and metabolic stability, and minimal toxic effects. Several methods are available to estimate druglikeness such as Lipinski's Rule of Five and a range of scoring methods such as lipophilic efficiency. Several methods for predicting drug metabolism have also been proposed in the scientific literature.


title: Drug design

text: Due to the large number of drug properties that must be simultaneously optimized during the design process, multi-objective optimization techniques are sometimes employed. Finally because of the limitations in the current methods for prediction of activity, drug design is still very much reliant on serendipity and bounded rationality.


title: Drug design

text: The most fundamental goal in drug design is to predict whether a given molecule will bind to a target and if so how strongly. Molecular mechanics or molecular dynamics is most often used to estimate the strength of the intermolecular interaction between the small molecule and its biological target. These methods are also used to predict the conformation of the small molecule and to model conformational changes in the target that may occur when the small molecule binds to it. Semi-empirical, ab initio quantum chemistry methods, or density functional theory are often used to provide optimized parameters for the molecular mechanics calculations and also provide an estimate of the electronic properties (electrostatic potential, polarizability, etc.) of the drug candidate that will influence binding affinity.


title: Drug design

text: Molecular mechanics methods may also be used to provide semi-quantitative prediction of the binding affinity. Also, knowledge-based scoring function may be used to provide binding affinity estimates. These methods use linear regression, machine learning, neural nets or other statistical techniques to derive predictive binding affinity equations by fitting experimental affinities to computationally derived interaction energies between the small molecule and the target.


title: Drug design

text: Ideally, the computational method will be able to predict affinity before a compound is synthesized and hence in theory only one compound needs to be synthesized, saving enormous time and cost. The reality is that present computational methods are imperfect and provide, at best, only qualitatively accurate estimates of affinity. In practice it still takes several iterations of design, synthesis, and testing before an optimal drug is discovered. Computational methods have accelerated discovery by reducing the number of iterations required and have often provided novel structures.


title: Drug design

text: In order to overcome the insufficient prediction of binding affinity calculated by recent scoring functions, the protein-ligand interaction and compound 3D structure information are used for analysis. For structure-based drug design, several post-screening analyses focusing on protein-ligand interaction have been developed for improving enrichment and effectively mining potential candidates:


title: Drug design

text: There are two major types of drug design. The first is referred to as ligand-based drug design and the second, structure-based drug design.


title: Drug design

text: Ligand-based drug design (or indirect drug design) relies on knowledge of other molecules that bind to the biological target of interest. These other molecules may be used to derive a pharmacophore model that defines the minimum necessary structural characteristics a molecule must possess in order to bind to the target. In other words, a model of the biological target may be built based on the knowledge of what binds to it, and this model in turn may be used to design new molecular entities that interact with the target. Alternatively, a quantitative structure-activity relationship (QSAR), in which a correlation between calculated properties of molecules and their experimentally determined biological activity, may be derived. These QSAR relationships in turn may be used to predict the activity of new analogs.


title: Drug design

text: Structure-based drug design (or direct drug design) relies on knowledge of the three dimensional structure of the biological target obtained through methods such as x-ray crystallography or NMR spectroscopy. If an experimental structure of a target is not available, it may be possible to create a homology model of the target based on the experimental structure of a related protein. Using the structure of the biological target, candidate drugs that are predicted to bind with high affinity and selectivity to the target may be designed using interactive graphics and the intuition of a medicinal chemist. Alternatively various automated computational procedures may be used to suggest new drug candidates.


title: Drug design

text: Current methods for structure-based drug design can be divided roughly into three main categories. The first method is identification of new ligands for a given receptor by searching large databases of 3D structures of small molecules to find those fitting the binding pocket of the receptor using fast approximate docking programs. This method is known as virtual screening. A second category is de novo design of new ligands. In this method, ligand molecules are built up within the constraints of the binding pocket by assembling small pieces in a stepwise manner. These pieces can be either individual atoms or molecular fragments. The key advantage of such a method is that novel structures, not contained in any database, can be suggested. A third method is the optimization of known ligands by evaluating proposed analogs within the binding cavity.


title: Drug design

text: Binding site identification is the first step in structure based design. If the structure of the target or a sufficiently similar homolog is determined in the presence of a bound ligand, then the ligand should be observable in the structure in which case location of the binding site is trivial. However, there may be unoccupied allosteric binding sites that may be of interest. Furthermore, it may be that only apoprotein (protein without ligand) structures are available and the reliable identification of unoccupied sites that have the potential to bind ligands with high affinity is non-trivial. In brief, binding site identification usually relies on identification of concave surfaces on the protein that can accommodate drug sized molecules that also possess appropriate "hot spots" (hydrophobic surfaces, hydrogen bonding sites, etc.) that drive ligand binding.


title: Drug design

text: Structure-based drug design attempts to use the structure of proteins as a basis for designing new ligands by applying the principles of molecular recognition. Selective high affinity binding to the target is generally desirable since it leads to more efficacious drugs with fewer side effects. Thus, one of the most important principles for designing or obtaining potential new ligands is to predict the binding affinity of a certain ligand to its target (and known antitargets) and use the predicted affinity as a criterion for selection.


title: Drug design

text: One early general-purposed empirical scoring function to describe the binding energy of ligands to receptors was developed by Böhm. This empirical scoring function took the form:


title: Drug design

text: The basic idea is that the overall binding free energy can be decomposed into independent components that are known to be important for the binding process. Each component reflects a certain kind of free energy alteration during the binding process between a ligand and its target receptor. The Master Equation is the linear combination of these components. According to Gibbs free energy equation, the relation between dissociation equilibrium constant, K, and the components of free energy was built.


title: Drug design

text: Various computational methods are used to estimate each of the components of the master equation. For example, the change in polar surface area upon ligand binding can be used to estimate the desolvation energy. The number of rotatable bonds frozen upon ligand binding is proportional to the motion term. The configurational or strain energy can be estimated using molecular mechanics calculations. Finally the interaction energy can be estimated using methods such as the change in non polar surface, statistically derived potentials of mean force, the number of hydrogen bonds formed, etc. In practice, the components of the master equation are fit to experimental data using multiple linear regression. This can be done with a diverse training set including many types of ligands and receptors to produce a less accurate but more general "global" model or a more restricted set of ligands and receptors to produce a more accurate but less general "local" model.


title: Drug design

text: A particular example of rational drug design involves the use of three-dimensional information about biomolecules obtained from such techniques as X-ray crystallography and NMR spectroscopy. Computer-aided drug design in particular becomes much more tractable when there is a high-resolution structure of a target protein bound to a potent ligand. This approach to drug discovery is sometimes referred to as structure-based drug design. The first unequivocal example of the application of structure-based drug design leading to an approved drug is the carbonic anhydrase inhibitor dorzolamide, which was approved in 1995.


title: Drug design

text: Another important case study in rational drug design is imatinib, a tyrosine kinase inhibitor designed specifically for the "bcr-abl" fusion protein that is characteristic for Philadelphia chromosome-positive leukemias (chronic myelogenous leukemia and occasionally acute lymphocytic leukemia). Imatinib is substantially different from previous drugs for cancer, as most agents of chemotherapy simply target rapidly dividing cells, not differentiating between cancer cells and other tissues.


title: Drug design

text: It has been argued that the highly rigid and focused nature of rational drug design suppresses serendipity in drug discovery.


title: Choo Young-woo

text: Choo Young-woo (born June 5, 1999) is a South Korean actor. He made his acting debut in the boys' love web series "You Make Me Dance" (2021).


title: Opportunistic infection

text: An opportunistic infection is an infection caused by pathogens (bacteria, fungi, parasites or viruses) that take advantage of an opportunity not normally available. These opportunities can stem from a variety of sources, such as a weakened immune system (as can occur in acquired immunodeficiency syndrome or when being treated with immunosuppressive drugs, as in cancer treatment), an altered microbiome (such as a disruption in gut microbiota), or breached integumentary barriers (as in penetrating trauma). Many of these pathogens do not necessarily cause disease in a healthy host that has a non-compromised immune system, and can, in some cases, act as commensals until the balance of the immune system is disrupted. Opportunistic infections can also be attributed to pathogens which cause mild illness in healthy individuals but lead to more serious illness when given the opportunity to take advantage of an immunocompromised host.


title: Opportunistic infection

text: A wide variety of pathogens are involved in opportunistic infection and can cause a similarly wide range in pathologies. A partial list of opportunistic pathogens and their associated presentations includes:


title: Opportunistic infection

text: Immunodeficiency or immunosuppression are characterized by the absence of or disruption in components of the immune system, leading to lower-than-normal levels of immune function and immunity against pathogens. They can be caused by a variety of factors, including:


title: Opportunistic infection

text: The lack of or the disruption of normal vaginal microbiota allows the proliferation of opportunistic microorganisms and will cause the opportunistic infection bacterial vaginosis.


title: Opportunistic infection

text: HIV is a virus that targets T cells of the immune system and, as a result, HIV infection can lead to progressively worsening immunodeficiency, a condition ideal for the development of opportunistic infection. Because of this, respiratory and central nervous system opportunistic infections, including tuberculosis and meningitis, respectively, are associated with later-stage HIV infection, as are numerous other infectious pathologies. Kaposi’s sarcoma, a virally-associated cancer, has higher incidence rates in HIV-positive patients than in the general population. As immune function declines and HIV-infection progresses to AIDS, individuals are at an increased risk of opportunistic infections that their immune systems are no longer capable of responding properly to. Because of this, opportunistic infections are a leading cause of HIV/AIDS-related deaths.


title: Opportunistic infection

text: Since opportunistic infections can cause severe disease, much emphasis is placed on measures to prevent infection. Such a strategy usually includes restoration of the immune system as soon as possible, avoiding exposures to infectious agents, and using antimicrobial medications ("prophylactic medications") directed against specific infections.


title: Opportunistic infection

text: Individuals at higher risk are often prescribed prophylactic medication to prevent an infection from occurring. A patient's risk level for developing an opportunistic infection is approximated using the patient's CD4 T-cell count and sometimes other markers of susceptibility. Common prophylaxis treatments include the following:


title: Opportunistic infection

text: Treatment depends on the type of opportunistic infection, but usually involves different antibiotics.


title: Opportunistic infection

text: Opportunistic infections caused by feline leukemia virus and feline immunodeficiency virus retroviral infections can be treated with lymphocyte T-cell immunomodulator.