document_title: Pleurisy

question_text: pain on right side of back when breathing

text: Pleurisy

text: Signs and symptoms[edit]

text: The defining symptom of pleurisy is a sudden sharp, stabbing, burning or dull pain in the right or left side of the chest during breathing, especially when one inhales and exhales.[9] It feels worse with deep breathing, coughing, sneezing, or laughing. The pain may stay in one place, or it may spread to the shoulder or back.[10] Sometimes, it becomes a fairly constant dull ache.[11]

text: Depending on its cause, pleuritic chest pain may be accompanied by other symptoms:[12]

text:
Dry cough
Fever and chills
Rapid, shallow breathing
Shortness of breath
Fast heart rate
Sore throat followed by pain and swelling in the joints

text: Causes[edit]

text: The pleural space can be invaded by fluid, air, and particles from other parts of the body, which fairly complicates diagnosis.[12][13] Viral infection (coxsackie B virus, HRSV, CMV, adenovirus, EBV, parainfluenza, influenza) is the most common cause of pleurisy. However, many other different conditions can cause pleuritic chest pain:[11]

text:
Aortic dissections
Autoimmune disorders such as systemic lupus erythematosus (or drug-induced lupus erythematosus), Autoimmune hepatitis (AIH), rheumatoid arthritis and Behçet's disease.
Bacterial infections associated with pneumonia and tuberculosis
Chest injuries (blunt or penetrating)
Familial Mediterranean fever, an inherited condition that often causes fever and swelling in the abdomen or the lungs
Fungal or parasitic infections
Heart surgery, especially coronary-artery bypass grafting
Cardiac problems (ischemia, pericarditis)
Inflammatory bowel disease
Lung cancer and lymphoma
Other lung diseases like cystic fibrosis, sarcoidosis, asbestosis, lymphangioleiomyomatosis, and mesothelioma
Pneumothorax
Pulmonary embolisms, which are blood clots that enter the lungs

text: When the space between the pleurae starts to fill with fluid, as in pleural effusion, the chest pain can be eased but a shortness of breath can result, since the lungs need room to expand during breathing. Some cases of pleuritic chest pain are idiopathic, which means that the exact cause cannot be determined.

text: Diagnosis[edit]

text: A diagnosis of pleurisy or another pleural condition is based on a medical history, physical examinations, and diagnostic tests.[12] The goals are to rule out other sources of the symptoms and to find the cause of the pleurisy so that the underlying disorder can be treated.

text: Physical examination[edit]

text: A doctor uses a stethoscope to listen to the breathing. This method detects any unusual sounds in the lungs. A person with pleurisy may have inflamed layers of the pleurae that make a rough, scratchy sound as they rub against each other during breathing. This is called pleural friction rub.

text: Diagnostic tests[edit]

text: Depending on the results of the physical examination, diagnostic tests are sometimes performed.

text: Chest x-ray[edit]

text: A chest x-ray takes a picture of the heart and lungs. It may show air or fluid in the pleural space. It also may show the cause (e.g., pneumonia, a fractured rib, or a lung tumor) of the pleurisy.

text: Sometimes an x-ray is taken while lying on the painful side. This may show fluid, as well as changes in fluid position, that did not appear in the vertical x-ray.

text: Blood test[edit]

text: Blood tests can detect bacterial or viral infections, pneumonia, rheumatic fever, a pulmonary embolism, or lupus.

text: ECG[edit]

text: Electrocardiography test can determine if a heart condition contributes to the symptoms.

text: Ultrasound[edit]

text: Ultrasonography uses sound waves to create an image. It may show where fluid is located in the chest. It also can show some tumors. Although ultrasound may detect fluid around the lungs, also known as a pleural effusion, sound waves are scattered by air. Therefore, an actual picture of the lungs cannot be obtained with ultrasonography.

text: Computed tomography (CT) scan[edit]

text: A CT scan provides a computer-generated picture of the lungs that can show pockets of fluid. It also may show signs of pneumonia, a lung abscess, or a tumor.

text: Magnetic resonance imaging (MRI)[edit]

text: Magnetic resonance imaging (MRI), also called nuclear magnetic resonance (NMR) scanning, uses powerful magnets to show pleural effusions and tumors.

text: Arterial blood gas[edit]

text: In arterial blood-gas sampling, a small amount of blood is taken from an artery, usually in the wrist. The blood is then checked for oxygen and carbon-dioxide levels. This test shows how well the lungs are taking in oxygen.

text: Thoracentesis[edit]

text: Once the presence of an excess fluid in the pleural cavity, or pleural effusion, is suspected and location of fluid is confirmed, a sample of fluid can be removed for testing.[14] The procedure to remove fluid in the chest is called a diagnostic thoracentesis.[15] The doctor inserts a small needle or a thin, hollow, plastic tube in the chest wall and withdraws fluid.[16]

text: Thoracentesis can be done in the doctor's office or at the hospital. Ultrasound is used to guide the needle to the fluid that is trapped in small pockets around the lungs.

text: Thoracentesis usually does not cause serious complications. Generally, a chest x-ray is done after the procedure to evaluate the lungs. Possible complications of thoracentesis include the following:

text:
Bleeding and bruising where the needle went in. In rare cases, bleeding may occur in or around the lung. The doctor can use a chest tube to drain the blood. In some cases, surgery is needed.
Infection where the needle went in
Injury to the liver or spleen (in rare cases)
Pain.
Pneumothorax, or buildup of air in the pleural space, with a collapsed or partially collapsed lung. Sometimes air comes in through the needle or the needle makes a hole in the lung. Usually, a hole seals itself—but sometimes air builds up around the lung and makes it collapse. A chest tube removes the air and lets the lung expand again.

text: The lung fluid is examined under a microscope and is evaluated for the presence of chemicals and for its color and texture. The degree of clarity is an indicator of infection, cancer, or other conditions that may be causing the buildup of fluid or blood in the pleural space.

text: Biopsy[edit]

text: If tuberculosis or cancer is suspected, a small piece of the pleura may be examined under a microscope to make a definitive diagnosis. This is called a biopsy.

text: Several approaches to taking tissue samples are available

text:
Insertion of a needle through the skin on the chest to remove a small sample of the outer layer of the pleura
Insertion of a small tube with a light on the end (endoscope) into tiny cuts in the chest wall to visualize the pleura, and biopsy of small pieces of tissue through the endoscope
Removal of a sample of the pleura through a small cut in the chest wall (open pleural biopsy), usually done if the sample from the needle biopsy is too small for accurate diagnosis

text: Treatment[edit]

text: Treatment has several goals:[12]

text:
Relief of symptoms
Removal of the fluid, air, or blood from the pleural space
Treatment of the underlying condition

text: Procedures[edit]

text: If large amounts of fluid, air, or blood are not removed from the pleural space, they may cause the lung to collapse.

text: The surgical procedures used to drain fluid, air, or blood from the pleural space are as follows:

text:
During thoracentesis, a needle or a thin, hollow, plastic tube is inserted through the ribs in the back of the chest into the chest wall. A syringe is attached to draw fluid out of the chest. This procedure can remove more than 6 cups (1.5 litres) of fluid at a time.
When larger amounts of fluid must be removed, a chest tube may be inserted through the chest wall. The doctor injects a local painkiller into the area of the chest wall outside where the fluid is. A plastic tube is then inserted into the chest between two ribs. The tube is connected to a box that suctions the fluid out. A chest x-ray is taken to check the tube's position.
A chest tube is also used to drain blood and air from the pleural space. This can take several days. The tube is left in place, and the patient usually stays in the hospital during this time.
Sometimes the fluid contains thick pus or blood clots, or it may have formed a hard skin or peel. This makes it harder to drain the fluid. To help break up the pus or blood clots, the doctor may use the chest tube to put certain medicines into the pleural space. These medicines are called fibrinolytics. If the pus or blood clots still do not drain out, surgery may be necessary.

text: Medications[edit]

text: A couple of medications are used to relieve pleurisy symptoms:

text:
Paracetamol (acetaminophen) or anti-inflammatory agents to control pain and decrease inflammation. Only indomethacin (brand name Indocin) has been studied with respect to relief of pleurisy.[17]
Codeine-based cough syrups to control the cough

text: There may be a role for the use of corticosteroids (for tuberculous pleurisy), tacrolimus (Prograf) and methotrexate (Trexall, Rheumatrex) in the treatment of pleurisy. Further studies are needed.

text: Lifestyle changes[edit]

text: The following may be helpful in the management of pleurisy:

text:
Lying on the painful side may be more comfortable
Breathing deeply and coughing to clear mucus as the pain eases. Otherwise, pneumonia may develop.
Getting rest

text: Treating the cause[edit]

text: Ideally, the treatment of pleurisy is aimed at eliminating the underlying cause of the disease.

text:
If the pleural fluid is infected, treatment involves antibiotics and draining the fluid. If the infection is tuberculosis or from a fungus, treatment involves long-term use of antibiotics or antifungal medicines.
If the fluid is caused by tumors of the pleura, it may build up again quickly after it is drained. Sometimes anti-tumor medicines prevent further fluid buildup. If they don't, the doctor may seal the pleural space. This is called pleurodesis. Pleurodesis involves the drainage of all the fluid out of the chest through a chest tube. A substance is inserted through the chest tube into the pleural space. This substance irritates the surface of the pleura. This causes the two layers of the pleurae to squeeze shut so there is no room for more fluid to build up.
Chemotherapy or radiation treatment also may be used to reduce the size of the tumors.
If congestive heart failure is causing the fluid buildup, treatment usually includes diuretics and other medicines.

text: The treatment for pleurisy depends on its origin and is prescribed by a physician on a base of an individual assessment.[18] Paracetamol (acetaminophen) and amoxicillin, or other antibiotics in case of bacterial infections, are common remedies dispensed by doctors to relieve the initial symptoms and pain in the chest, while viral infections are self-limited. Non-steroidal anti-inflammatory drugs (NSAIDs), preferably indometacin, are usually employed as pain control agents.[12]

text: Alternative treatments[edit]

text: A number of alternative or complementary medicines are being investigated for their anti-inflammatory properties, and their use in pleurisy. At this time, clinical trials of these compounds have not been performed.

text: Extracts from the Brazilian folk remedy Wilbrandia ebracteata ("Taiuia") have been shown to reduce inflammation in the pleural cavity of mice.[19][20] The extract is thought to inhibit the same enzyme, cyclooxygenase-2 (COX-2), as the non-steroidal anti-inflammatory drugs.[20]

text: Related problems[edit]

text: Pleurisy is often associated with complications that affect the pleural space.

text: Pleural effusion[edit]

text: In some cases of pleurisy, excess fluid builds up in the pleural space. This is called a pleural effusion. The buildup of fluid usually forces the two layers of the pleura apart so they don't rub against each other when breathing. This can relieve the pain of pleurisy. A large amount of extra fluid can push the pleura against the lung until the lung, or a part of it, collapses. This can make it hard to breathe.

text: In some cases of pleural effusion, the extra fluid gets infected and turns into an abscess. This is called an empyema.

text: Pleural effusion involving fibrinous exudates in the fluid may be called fibrinous pleurisy. It sometimes occurs as a later stage of pleurisy.

text: A person can develop a pleural effusion in the absence of pleurisy. For example, pneumonia, heart failure, cancer, or a pulmonary embolism can lead to a pleural effusion.

text: Pneumothorax[edit]

text: Air or gas also can build up in the pleural space. This is called a pneumothorax. It can result from acute lung injury or a lung disease like emphysema. Lung procedures, like surgery, drainage of fluid with a needle, examination of the lung from the inside with a light and a camera, or mechanical ventilation, also can cause a pneumothorax.

text: The most common symptom is sudden pain in one side of the lung and shortness of breath. A pneumothorax also can put pressure on the lung and cause it to collapse.

text: If the pneumothorax is small, it may go away on its own. If large, a chest tube is placed through the skin and chest wall into the pleural space to remove the air.

text: Hemothorax[edit]

text: Blood also can collect in the pleural space. This is called hemothorax. The most common cause is injury to the chest from blunt force or surgery on the heart or chest. Hemothorax also can occur in people with lung or pleural cancer.

text: Hemothorax can put pressure on the lung and force it to collapse. It also can cause shock, a state of hypoperfusion in which an insufficient amount of blood is able to reach the organs.

text: Prognosis[edit]

text: Pleurisy and other disorders of the pleurae can be serious, depending on what caused them. Generally, pleurisy treatment has an excellent prognosis, but if left untreated it can cause severe complications. For example, a resulting pulmonary heart disease cor pulmonale, which manifests itself with an inflammation of the arms and legs, can lead to heart failure. If the conditions that caused the pleurisy or other pleural disorders were adequately diagnosed and treated early, one can expect a full recovery. Help of a pulmonologist (respiratory physician in the U.K. and Australia) may be enlisted to address the underlying cause and chart post-illness rehabilitation.


document_title: Centuries (song)

question_text: who sings in the beginning of centuries by fall out boy

root

text: Centuries (song)

text: Background[edit]

text: "Centuries" was written by Pete Wentz, Patrick Stump, Joe Trohman, Andy Hurley, J.R. Rotem, Justin Tranter, Raja Kumari and Michael Fonseca in mid-2014 and was produced by Omega and Rotem. Stump originally came forward with the song while Fall Out Boy were on the Monumentour tour with fellow American band Paramore.[5] In an interview with Kerrang!, Wentz described the idea of the song as a "David vs. Goliath story", stating "We wanted to write a song that empowered people who are a little weird."[6]

tag: p

text: "Centuries" contains part of the melody from the song "Tom's Diner" by Suzanne Vega. The segment is not a sample, but was actually re-recorded by American singer Lolo for the track.[7] Stump described the inclusion as "a tip of the hat" to "Tom's Diner", a song which the band wanted to "re-inject" into popular culture.

text: Release[edit]

text: Days after the ending of co-headlining the Monumentour tour with Paramore, on September 4, 2014, Fall Out Boy released a teaser video depicting the title of the song in Morse code.[8] "Centuries" received its worldwide premiere on BBC Radio 1 on September 8, 2014 before being released worldwide the next day.[9] The song is featured as the second track of Now! 54 (2015).[10]

text: Critical reception[edit]

text:
"Centuries"

A 23-second sample of "Centuries" by Fall Out Boy, where the chorus is heard.

Problems playing this file? See media help.

tag: table

text: "Centuries" has received favorable reviews from music critics. MTV described as the song as "The ultimate battle cry of a track".[11]

text: Music video[edit]

text: The official music video, which features the band members in a gladiator-style battle, and a cameo from rapper Rick Ross, was released on October 17, 2014.[12] The video features strong Christian imagery and thematic elements, including a scene of a crucified figure, a cross in place of the "T" in the song title, the use of a sling against a "giant" (in reference to the Hebrew story of David and Goliath), and an angelic figure depicted as a human with white wings. The "giant" is portrayed by Canadian actor Jon Ambrose,[13] and the band's gladiator doubles were Simu Liu,[14] Ben Devries,[15] Sebastian Deery [16] and Paul Ebejer.[17] "Centuries" was shot on-site at Fort Henry National Historic Site in Kingston, Ontario, Canada.[18] Prior to the release of an official music video, Fall Out Boy released a video for "Centuries" filmed in Chicago featuring the use of the mobile app Hyperlapse on September 8, 2014.[19][20]

text: The official video features four gladiators doomed for some unknown reason prior to entering the Colosseum in Rome for the entertainment of the crowds. They are given two lengths of rope, a stone, and a cloth by a mysterious figure. This is followed by scenes of a woman styled as the Virgin Mary opening her arms to a crowd, a lady with two lions behind her, a "Christ" figure, and a decadent pope spreading his arms showing several ladies sitting at his feet. The viewers are then introduced to the ostensibly "crowd favourite", a large, muscular man who destroys the four without much ado, cheered on by the crowd and a laughing emperor. In desperation, the four use their items to create a sling, which is then used to slay the warrior. The video ends as another, unknown challenger enters the ring while the emperor laughs.

text: Commercial performance[edit]

text: "Centuries" debuted at No. 22 on the US Billboard Hot 100 and No. 4 on Digital Songs with 133,000 first week sales.[21] It also opened at No. 2 on Hot Rock Songs and No. 14 on Alternative Songs.[22] "Centuries" peaked at No. 4 on Alternative in December on strong airplay, the band's third highest position on that chart behind "Dance, Dance" and "Sugar, We're Goin Down". As a cross-over radio success it reached No. 16 on mainstream Pop Songs by January 2015. In its nineteenth week on the Hot 100, it reached No. 12, selling 111,000 downloads that week, and propelling the band to No. 10 on the Artist 100.[23] It eventually peaked at No. 10 on the Billboard Hot 100 in its 20th week (week ending February 7, 2015; the same as American Beauty/American Psycho's debut), becoming the band's first top 10 in almost eight years after "This Ain't A Scene, It's An Arms Race" peaked at No. 2 in February 2007;[24] "Centuries" also reached a new high of No. 15 on Pop Songs. In its 21st week, it held at No. 10 on the Hot 100 and reached No. 13 on both Pop and Adult Pop with heavy airplay.

text: "Centuries" has spent twelve consecutive weeks in the top 20 of the Hot 100 and twenty-two consecutive frames at No. 2 on Hot Rock Songs.[25][26] It was certified 2x Platinum by the RIAA in December 2014 and was upgraded to 4x Platinum in October 2015. In Australia the song debuted at No. 59 but rose to No. 55 in the following week. "Centuries" debuted at No. 36 on the Canadian Hot 100 and peaked at No. 26 in its fifteenth week.[26] In the UK, "Centuries" made its appearance in the UK Top 40 singles chart at No. 22 scoring the band another top 40 hit. On the singles sales format of the chart the song reached No. 12. As of June 2015, the song has spent 21 weeks in the UK Top 100 and has been certified Silver by the BPI, denoting 200,000 copies.

text: Media usage and live performances[edit]

text: On September 10, 2014, ESPN announced that "Centuries" would serve as a promotional song for its coverage of the inaugural College Football Playoff. The song was featured across promotions for the event throughout the 2014 college football season, and during coverage of the semi-final and national championship games.[11][27] In a January 2015 interview with FoxSports.com, the band apologized for ESPN's overexposure of the song; it was estimated that across its coverage of the two semi-final bowls, along with the National Championship game, that "Centuries" had been played a total of 45 times.[28]

text: Fall Out Boy performed "Centuries" live for the first time on Jimmy Kimmel Live! on September 17, 2014.[29] They next played on The Ellen DeGeneres Show with Suzanne Vega as a special guest on October 29, 2014.[30]

text: "Centuries" was used by WWE as the official theme song for Friday Night SmackDown's 15th anniversary show.[31][32][33] "Centuries" was also performed at the 2015 NHL All-Star game at Nationwide Arena, Columbus, Ohio in between periods.[34] On April 5, 2015, the band performed "Centuries" as part of pre-game festivities at Wrigley Field in their hometown of Chicago for the opening game of the 2015 Major League Baseball season; the performance was, ironically, televised by ESPN2 as part of its coverage.[28][35][36] "Centuries" was performed at the 2015 MTV Movie Awards on April 12, 2015.[37][38] "Centuries" was also used for an intro video of the 2015 Chicago White Sox season home games and Calgary Flames playoff home games.

text: "Centuries" was used by Apple during the pre-keynote for WWDC 2015.[39]

text: "Centuries" is frequently played at A-League team Adelaide United home games.

text: "Centuries" is featured in Rock Band 4.[40]

text: "Centuries" also used in the trailer for Nickelodeon's original movie inspired by mid-90s game show Legends of the Hidden Temple.

text: Track listing[edit]

text:
"Centuries" – 3:48
"Centuries" (Remix) (featuring Juicy J) – 3:28

tag: ol

text: Charts[edit]

text: Weekly charts[edit]

text:
Chart (2014–15)
Peak
position

Australia (ARIA)[42]
55

Austria (Ö3 Austria Top 40)[43]
62

Belgium (Ultratip Flanders)[44]
68

Brazilian Singles Chart (ABPD)[45]
33

Canada (Canadian Hot 100)[46]
26

Canada CHR/Top 40 (Billboard)[47]
48

Canada Hot AC (Billboard)[48]
48

Colombia (National-Report Top Rock)[49]
4

Czech Republic (Rádio Top 100)[50]
19

Czech Republic (Singles Digitál Top 100)[51]
13

Germany (Official German Charts)[52]
71

Ireland (IRMA)[53]
59

New Zealand (Recorded Music NZ)[54]
32

Slovakia (Rádio Top 100)[55]
44

Slovakia (Singles Digitál Top 100)[56]
15

Sweden (Sverigetopplistan)[57]
60

UK Singles (Official Charts Company)[58]
22

UK Rock and Metal (Official Charts Company)[59]
1

US Billboard Hot 100[60]
10

US Hot Rock Songs (Billboard)[61]
2

US Rock Airplay (Billboard)[62]
8

US Adult Contemporary (Billboard)[63]
26

US Adult Top 40 (Billboard)[64]
9

US Mainstream Top 40 (Billboard)[65]
13

text: Year-end charts[edit]

text:
Chart (2014)
Position

US Hot Rock Songs (Billboard)[66]
19

US Alternative Songs (Billboard)[67]
38

text:
Chart (2015)
Position

US Billboard Adult Pop Songs[68]
34

US Billboard Digital Songs[69]
27

US Billboard Hot 100
43

US Billboard Hot Rock Songs[70]
3

US Billboard Radio Songs[71]
54

US Billboard Rock Airplay Songs[72]
33

US Billboard Rock Digital Songs[73]
3

US Billboard Rock Streaming Songs[74]
3

US Billboard Streaming Songs[75]
49

text: Certifications[edit]

text:
Region
Certification
Certified units/Sales

United Kingdom (BPI)[76]
Silver
200,000^

United States (RIAA)[77]
4× Platinum
4,000,000^

^shipments figures based on certification alone

text: Release history[edit]

text:
Region
Date
Format
Label

United Kingdom[9]
September 8, 2014
Contemporary hit radio
Island

United States[78]
September 9, 2014
Modern rock radio

Island
Republic

Worldwide[41]
Digital download
Island

United States[79]
October 6, 2014
Hot adult contemporary radio

Island
Republic


document_title: List of NCAA Division I men's basketball players with 12 or more 3-point field goals in a game

question_text: what is the most 3 pointers made in a ncaa game

text: A three-point field goal (also known as a "three-pointer" or "3-pointer") is a field goal in a basketball game, made from beyond the three-point line, a designated arc radiating from the basket. A successful attempt is worth three points, in contrast to the two points awarded for shots made inside the three-point line. The National Collegiate Athletic Association (NCAA) keeps records of the Division I 3-point field made in a game leaders. The statistic was first recognized in the 1986–87 season when 3-point field goals were officially instituted by the NCAA. From the 1986–87 season through the 2007–08 season, the three-point perimeter was marked at 19 ft 9 in (6.02 m) for both men's and women's college basketball.[1] On May 3, 2007, the NCAA men's basketball rules committee passed a measure to extend the distance of the men's three-point line back to 20 ft 9 in (6.32 m), while the women's line would remain the same.[1]

text: Through January 6, 2017, only 17 players have made at least 12 three-point field goals in a single game.[2][3] The all-time record is 15, which has only occurred one time and it was by Marshall's Keith Veney.[4] On December 14, 1996, he set the record against Morehead State.[2] Only three other players have made 14 three-pointers: Ronald Blackshear, Dave Jamerson and Askia Jones.[2] The most recent player to make 12 threes in a game is Darius Dawkins of Jacksonville, who made 13 three-pointers against Middle Georgia State on January 3, 2017.[5]

text: Key[edit]

text:
Pos.
G
F
C
Ref.

Position
Guard
Forward
Center
Reference(s)

Class (Cl.) key

Fr
Freshman
So
Sophomore
Jr
Junior
Sr
Senior

Team (X)
Denotes the number of times a player from that school appears on the list

^
Player still active in NCAA Division I

text: Dates of 12+ three-pointers[edit]

text:
3-pointers
made
Player
Pos.
Cl.
Team
Opponent
Date
Ref.

15
Veney, KeithKeith Veney
G
4 !Sr
Marshall
Morehead State
19961214 !December 14, 1996
[4]

14
Blackshear, RonaldRonald Blackshear
G
3 !Jr
Marshall (2)
Akron
20020301 !March 1, 2002
[6]

14
Jones, AskiaAskia Jones
G
4 !Sr
Kansas State
Fresno State
19940324 !March 24, 1994
[7]

14
Jamerson, DaveDave Jamerson
G
4 !Sr
Ohio
Charleston (WV)
19891221 !December 21, 1989
[7]

13
Dawkins, DariusDarius Dawkins
G
4 !Sr
Jacksonville
Middle Georgia State
20170103 !January 3, 2017
[5]

13
English, A. J.A. J. English
G
4 !Sr
Iona
Fairfield
20151201 !December 1, 2015
[8]

13
Clarke, RotneiRotnei Clarke
G
2 !So
Arkansas
Alcorn State
20091113 !November 13, 2009
[3]

12
Hunter, R. J.R. J. Hunter
G
2 !So
Georgia State
UTSA
20131222 !December 22, 2013
[9]

12
Jackson, JamelJamel Jackson
G
3 !Jr
Seton Hall
VMI
20091212 !December 12, 2009
[10]

12
Jenkins, MichaelMichael Jenkins
G
3 !Jr
Winthrop
North Greenville
20061111 !November 11, 2006
[11]

12
Woods, TerrenceTerrence Woods
G
3 !Jr
Florida A&M
Coppin State
20030301 !March 1, 2003
[12]

12
Gilbert, ClarenceClarence Gilbert
G
4 !Sr
Missouri
Colorado
20020223 !February 23, 2002
[13]

12
McMahan, DavidDavid McMahan
G
4 !Sr
Winthrop (2)
Coastal Carolina
19960115 !January 15, 1996
[14]

12
Taylor, MitchMitch Taylor
G
3 !Jr
Southern
Louisiana Christian
19941201 !December 1, 1994
[2]

12
Dillard, AlAl Dillard
G
3 !Jr
Arkansas (2)
Delaware State
19931211 !December 11, 1993
[15]

12
Fitzgerald, DarrinDarrin Fitzgerald
G
4 !Sr
Butler
Detroit
19870209 !February 9, 1987
[16]

12
Bossert, GaryGary Bossert
G
4 !Sr
Niagara
Siena
19870107 !January 7, 1987
[17]


document_title: World Tamil Conference

question_text: where was the first world classical tamil conference held

text: World Tamil Conference

text: The World Tamil Conference (Tamil: உலகத் தமிழ் மாநாடு) is a series of occasional conferences to discuss the social growth of the Tamil language. Each conference is attended by thousands of Tamil enthusiasts around the world. Conferences are hosted in various cities in India, as well as world cities with a significant Tamil population. The conference aims in promoting the heritage of Tamil language.

text: A similar conference called World Classical Tamil Conference 2010, unapproved by the International Association for Tamil Research, was held in Tamil Nadu conducted by the Dravida Munnetra Kazhagam under the leadership of M. Karunanidhi. Not all agreed with the academic and intellectual rigour of the latter event. Despite these criticisms upholding such a huge event portraying the value of Tamil language and culture is being appreciated vastly and credited to the DMK supremo as commonly believed by the people in the state of Tamil Nadu. [1][2][3]

text: The next conference will be held on July 3-4, 2019 in Chicago. The 10th conference will be jointly hosted by Federation of Tamil Sangams in North America (FeTNA) and Chicago Tamil Sangam (CTS). [4]

text: List of conferences held[edit]

text:
List of conferences[5]

Official title
Host city
Host country
Year
Arranged by

1st World Tamil Conference
Kuala Lumpur
 Malaysia
1966
Thani Nayagam Adigalar

2nd World Tamil Conference
Chennai
 India
1968
M. Bhaktavatsalam and C. N. Annadurai

3rd World Tamil Conference
Paris
 France
1970

4th World Tamil Conference
Jaffna
 Sri Lanka
1974

5th World Tamil Conference
Madurai
 India
1981
M. G. Ramachandran

6th World Tamil Conference
Kuala Lumpur
 Malaysia
1987

7th World Tamil Conference
Port Louis
 Mauritius
1989

8th World Tamil Conference
Thanjavur
 India
1995
J. Jayalalithaa

9th World Tamil Conference
Kuala Lumpur
 Malaysia
2015

10th World Tamil Conference
Chicago
 USA
2019
FeTNA & Chicago Tamil Sangam


document_title: Miracles from Heaven (film)

question_text: who plays the mom in miracles from heaven

text: Miracles from Heaven (film)

text: Plot[edit]

text: Set in Burleson, Texas, between 2008 and 2012, the film centers on a 10-year-old girl named Annabel Beam, daughter of Christy Beam. One day, Anna starts to vomit, and when examined by her doctor, he does not find anything abnormal. On March 20, 2008, Anna wakes up her family at midnight because of an intense stomach pain severe enough that her parents decide to take her to the hospital. Doctors find no signs of illness, except to say it could be either acid reflux, or lactose intolerance, but Christy is not convinced by this. The following morning, Christy finally finds a pediatrician in the hospital that is able to diagnose Anna with an abdominal obstruction, and he tells them he must operate immediately or she will die. After the emergency surgery is performed, the doctor explains that Anna has been left with pseudo-obstruction motility disorder and she is unable to eat, so feeding tubes are needed for her nutrition. The doctor then tells the Beams' about America's foremost pediatric gastroenterologist, Dr. Nurko, who practices in Boston, but explains it could take months for them to be seen. In January 2009, Christy and Anna travel to Boston despite not having an appointment with the doctor.

text: Dr. Nurko has a last minute opening, and when Anna is subsequently examined at Boston Children's Hospital, the extent of her chronic illness is found. She then goes through extensive treatment. During this ordeal, Anna and her mother befriend a local Massachusetts resident named Angela, as well as Ben and his sick daughter, Haley.

text: On December 29, 2011, Anna, along with her bigger sister Abbie, climb up to a very high branch of an old cotton tree. While they are on that branch, it begins to break. Anna goes to the trunk for safety, whereupon stepping on it, she falls in a hole to the base of the tree. When Christy finds out what has happened, she desperately calls her husband, as well as the fire department. Anna is then rescued by the firefighters, who warn Christy to expect the worst by saying that nobody could fall 30 feet without sustaining a serious injury; broken bones or paralysis. Once out, Anna is airlifted to a hospital, where a battery of tests are run on her, and all of the tests come back negative. Other than a minor concussion, Anna is uninjured.

text: Sometime after the fall, Anna seems to no longer be affected by her illness. When Christy and Anna go to an appointment with Dr. Nurko, he tells Christy that Anna is miraculously cured. Anna then recounts with her parents the experience she had during the fall. She describes how her soul left her body during the fall, and God promised that she would be cured of her illness upon her return to Earth. At church, Christy shares the story of how God miraculously healed her daughter with His love. As Christy finishes her speech, one of the congregation protests, stating that she does not believe Christy. Ben, who has traveled from Boston upon hearing the story about Anna, believes her and tells her that his daughter Haley died peacefully because Anna gave her faith when in the hospital.

text: Cast[edit]

text:
Jennifer Garner as Christy Beam, Anna's mother[4]
Kylie Rogers as Anna Beam[5]
Martin Henderson as Dr. Kevin Beam, Christy's husband and Anna's father[6]
Eugenio Derbez as Dr. Nurko, a pediatric gastroenterologist who is Anna's doctor at the Boston Children's Hospital.[7]
Queen Latifah as Angela, a waitress who befriends Anna and her mother in a restaurant in Boston[8]
Brighton Sharbino as Abbie Beam, the oldest Beam daughter
Courtney Fansler as Adelynn Beam, the youngest Beam daughter
Zach Sale as Dr. Blyth, the first doctor to listen to Christy about her sick daughter
Kelly Collins Lintz as Emmy, a family friend of the Beams
John Carroll Lynch as Reverend Scott, the Senior Pastor of the Beam family's church
Brandon Spink as Billy Snyder, a friend of Anna
Hannah Alligood as Haley, a sick cancer patient who becomes friends with Anna
Wayne Pere as Ben, Haley's father
Bruce Altman as Dr. Burgi, Anna's doctor who is the head of the pediatric division at the hospital in Texas
Suehyla El-Attar as a receptionist at the Boston Children's hospital
The Beam family makes a cameo at the end of the film before the credits.

tag: ul

text: Production[edit]

text: On November 10, 2014, The Hollywood Reporter reported that Sony Pictures Entertainment had acquired the film adaptation rights to a faith-based memoir, Miracles From Heaven: A Little Girl, Her Journey to Heaven, and Her Amazing Story of Healing, written by Christy Beam, and hired Randy Brown to write the script.[9] The team behind the studios' 2014 Christian film Heaven Is for Real, T. D. Jakes and Joe Roth, were retained to produce the film along with DeVon Franklin.[9]

text: On April 8, 2015, the studio hired Patricia Riggen to direct the film.[10] On April 30, 2015, Jennifer Garner was cast to star in the film as Christy Beam.[4] On June 22, 2015, The Hollywood Reporter reported that Queen Latifah was cast as a waitress who befriends Anna and Beam at the Boston Children's Hospital.[8] On the same day, Variety confirmed the casting of Martin Henderson to play the girl's father and Beam's husband.[6]

text: On June 29, 2015, Kylie Rogers was cast as Beam's sick daughter Anna.[5] On July 17, 2015, Eugenio Derbez was cast to play a character inspired by Children's Hospital specialist Dr. Samuel Nurko, an American-based Mexican pediatric gastroenterologist who eases his young patients' treatment by playing games with them.[7] John Carroll Lynch was also cast in the film for an unspecified role.[11]

text: Filming[edit]

text: Principal photography on the film began in Atlanta, Georgia, in July 2015, as Garner was spotted filming on July 8.[12] Filming was subsequently confirmed by various sources, together with announcements that David R. Sandefur and Emma E. Hickox had been appointed as production designer and editor, respectively.[11][13] On August 2, 2015, Latifah and Garner were spotted on the set of film in Atlanta.[14]

text: Soundtrack[edit]

text: The Miracles from Heaven soundtrack features songs from Howie Day, George Harrison, Clayton Anderson, Third Day and others.[15] The southern Christian rock band Third Day made a cameo as the church worship band.[16]

text:
No.
Title
Music
Length

1.
"Soul on Fire"
Third Day

2.
"Right Where I Belong"
Clayton Anderson

3.
"Collide"
Howie Day

4.
"Your Words"
Third Day

5.
"Here Comes the Sun"
Cam

text: Release[edit]

text: On May 11, 2015, the film was scheduled for a March 18, 2016 release by Columbia Pictures. On January 10, it was moved up to March 16.[17] The film held its world premiere on February 21, 2016 in Dallas, Texas.[18]

text: Home media[edit]

text: Miracles from Heaven was released on Digital Media on June 21, 2016, and was followed by a DVD, Blu-ray, and 4K Ultra HD release on July 12, 2016, from AFFIRM Films and Sony Pictures Home Entertainment.[19][20] The film debuted in second place on the home video sales chart behind The Divergent Series: Allegiant for the week ending on July 17, 2016.[21]

text: Reception[edit]

text: Box office[edit]

text: Miracles from Heaven grossed $61.7 million in North America and $12.2 million in other territories for a worldwide total of $73.9 million, against a budget of $13 million.[3]

text: The film grossed $1.9 million on its first day, finishing second at the box office behind Zootopia ($4.6 million).[22] The film had an $18 million Wednesday-to-Sunday gross, including $14.8 million in its opening weekend, finishing third at the box office behind Zootopia ($37.2 million) and The Divergent Series: Allegiant ($29 million).[23]

text: On its opening weekend in the United Kingdom, Miracles from Heaven grossed $29 thousand, dropping to $231 by week four.[24]

text: Critical response[edit]

text: Miracles from Heaven received generally mixed reviews from critics, with Garner's performance receiving praise. On Rotten Tomatoes, the film has a rating of 43%, based on 87 reviews, with an average rating of 5/10. The site's consensus reads, "Miracles from Heaven makes the most out of an outstanding performance from Jennifer Garner, but it isn't quite enough to keep this faith-based drama from preaching to the choir."[25] On Metacritic the film has a score of 44 out of 100, based on 20 critics, indicating "mixed or average reviews".[26] Audiences polled by CinemaScore gave the film an average grade of "A+" on an A+ to F scale.[22]

text: Accolades[edit]

text:
Association
Category
Nominee
Result
Ref.

People's Choice Awards
Favorite Dramatic Movie
Miracles from Heaven
Nominated
[27]

Teen Choice Awards
Choice Movie: Drama
Miracles from Heaven
Won
[28]

Choice Movie Actress: Drama
Jennifer Garner
Nominated


document_title: Cell cycle

question_text: in which phase of cell cycle are chromosomes replicated

text: Cell cycle

text: Phases[edit]

text: The cell cycle consists of four distinct phases: G1 phase, S phase (synthesis), G2 phase (collectively known as interphase) and M phase (mitosis). M phase is itself composed of two tightly coupled processes: karyokinesis, in which the cell's chromosomes are divided, and cytokinesis, in which the cell's cytoplasm divides forming two daughter cells. Activation of each phase is dependent on the proper progression and completion of the previous one. Cells that have temporarily or reversibly stopped dividing are said to have entered a state of quiescence called G0 phase.

text:
State
Phase
Abbreviation
Description

Resting
Gap 0
G0
A phase where the cell has left the cycle and has stopped dividing.

Interphase
Gap 1
G1
Cells increase in size in Gap 1. The G1 checkpoint control mechanism ensures that everything is ready for DNA synthesis.

Synthesis
S
DNA replication occurs during this phase.

Gap 2
G2
During the gap between DNA synthesis and mitosis, the cell will continue to grow. The G2 checkpoint control mechanism ensures that everything is ready to enter the M (mitosis) phase and divide.

Cell division
Mitosis
M
Cell growth stops at this stage and cellular energy is focused on the orderly division into two daughter cells. A checkpoint in the middle of mitosis (Metaphase Checkpoint) ensures that the cell is ready to complete cell division.

text: After cell division, each of the daughter cells begin the interphase of a new cycle. Although the various stages of interphase are not usually morphologically distinguishable, each phase of the cell cycle has a distinct set of specialized biochemical processes that prepare the cell for initiation of cell division.

text: G0 phase (quiescence)[edit]

text: G0 is a resting phase where the cell has left the cycle and has stopped dividing. The cell cycle starts with this phase. The word "post-mitotic" is sometimes used to refer to both quiescent and senescent cells. Non-proliferative (non-dividing) cells in multicellular eukaryotes generally enter the quiescent G0 state from G1 and may remain quiescent for long periods of time, possibly indefinitely (as is often the case for neurons). This is very common for cells that are fully differentiated. Cellular senescence occurs in response to DNA damage and external stress and usually constitutes an arrest in G1. Some cells enter the G0 phase semi-permanently and are considered post-mitotic, e.g., some liver, kidney, and stomach cells. Many cells do not enter G0 and continue to divide throughout an organism's life, e.g., epithelial cells.

text: Cellular senescence is also a state that occurs in response to DNA damage or degradation that would make a cell's progeny nonviable; it is often a biochemical alternative to the self-destruction of such a damaged cell by apoptosis.

text: Interphase (intermitosis)[edit]

text: Before a cell can enter cell division, it needs to take in nutrients. All of the preparations are done during interphase. Interphase is a series of changes that takes place in a newly formed cell and its nucleus, before it becomes capable of division again. It is also called preparatory phase or intermitosis. Previously it was called resting stage because there is no apparent activity related to cell division.Typically interphase lasts for at least 91% of the total time required for the cell cycle.

text: Interphase proceeds in three stages, G1, S, and G2, followed by the cycle of mitosis and cytokinesis. The cell's nuclear DNA contents are duplicated during S phase but may continue till G2 in case of heterochromatin.

text: G1 phase (First growth phase or Post mitotic gap phase)[edit]

text: The first phase within interphase, from the end of the previous M phase until the beginning of DNA synthesis, is called G1 (G indicating gap). It is also called the growth phase. During this phase, the biosynthetic activities of the cell, which are considerably slowed down during M phase, resume at a high rate. The duration of G1 is highly variable, even among different cells of the same species.[3] In this phase, the cell increases its supply of proteins, increases the number of organelles (such as mitochondria, ribosomes), and grows in size. In G1 phase, a cell has three options. (1) To continue cell cycle and enter S phase (2) Stop cell cycle and enter G0 phase for undergoing differentiation. (3) Get arrested in G1 phase hence it may enter G0 phase or re-enter cell cycle. The deciding factor is availability of nitrogens and storage of energy rich compounds at the deciding point called check point. This check point is called G1 cyclin or CG1. It causes transition of G1 to S phase. Once the check point of G1 phase is crossed, cell cycle will go uninterrupted till it is completed.

text: S phase (DNA replication)[edit]

text: The ensuing S phase starts when DNA synthesis commences; when it is complete, all of the chromosomes have been replicated, i.e., each chromosome has two (sister) chromatids. Thus, during this phase, the amount of DNA in the cell has effectively doubled, though the ploidy of the cell remains the same. Rates of RNA transcription and protein synthesis are very low during this phase. An exception to this is histone production, most of which occurs during the S phase.[4][5][6]

text: G2 phase (growth)[edit]

text: G2 phase occurs after DNA replication and is a period of protein synthesis and rapid cell growth to prepare the cell for mitosis. During this phase microtubules begin to reorganize to form a spindle.

text: Mitotic phase (chromosome separation)[edit]

text: The relatively brief M phase consists of nuclear division (karyokinesis). It is a relatively short period of the cell cycle. M phase is complex and highly regulated. The sequence of events is divided into phases, corresponding to the completion of one set of activities and the start of the next. These phases are sequentially known as:

text:
prophase,
metaphase,
anaphase,
telophase

text: Mitosis is the process by which a eukaryotic cell separates the chromosomes in its cell nucleus into two identical sets in two nuclei.[7] During the process of mitosis the pairs of chromosomes condense and attach to fibers that pull the sister chromatids to opposite sides of the cell.[8]

text: Mitosis occurs exclusively in eukaryotic cells, but occurs in different ways in different species. For example, animals undergo an "open" mitosis, where the nuclear envelope breaks down before the chromosomes separate, while fungi such as Aspergillus nidulans and Saccharomyces cerevisiae (yeast) undergo a "closed" mitosis, where chromosomes divide within an intact cell nucleus.[9] Prokaryotic cells, which lack a nucleus, divide by a process called binary fission.

text: Cytokinesis phase (separation of all cell components)[edit]

text: Mitosis is immediately followed by cytokinesis, which divides the nuclei, cytoplasm, organelles and cell membrane into two cells containing roughly equal shares of these cellular components. Mitosis and cytokinesis together define the division of the mother cell into two daughter cells, genetically identical to each other and to their parent cell. This accounts for approximately 10% of the cell cycle.

text: Because cytokinesis usually occurs in conjunction with mitosis, "mitosis" is often used interchangeably with "M phase". However, there are many cells where mitosis and cytokinesis occur separately, forming single cells with multiple nuclei in a process called endoreplication. This occurs most notably among the fungi and slime moulds, but is found in various groups. Even in animals, cytokinesis and mitosis may occur independently, for instance during certain stages of fruit fly embryonic development.[10] Errors in mitosis can either kill a cell through apoptosis or cause mutations that may lead to cancer.

text: The process of mitosis is complex and highly regulated. The sequence of events is divided into phases, corresponding to the completion of one set of activities and the start of the next. These stages are prophase, prometaphase, metaphase, anaphase and telophase. During the process of mitosis the pairs of chromosomes condense and attach to fibers that pull the sister chromatids to opposite sides of the cell. The cell then divides in cytokinesis, to produce two identical daughter cells.[8]

text: Regulation of eukaryotic cell cycle[edit]

text: Regulation of the cell cycle involves processes crucial to the survival of a cell, including the detection and repair of genetic damage as well as the prevention of uncontrolled cell division. The molecular events that control the cell cycle are ordered and directional; that is, each process occurs in a sequential fashion and it is impossible to "reverse" the cycle.

text: Role of cyclins and CDKs[edit]

text:
Nobel Laureate
Paul Nurse

Nobel Laureate
Tim Hunt

text: Two key classes of regulatory molecules, cyclins and cyclin-dependent kinases (CDKs), determine a cell's progress through the cell cycle.[11] Leland H. Hartwell, R. Timothy Hunt, and Paul M. Nurse won the 2001 Nobel Prize in Physiology or Medicine for their discovery of these central molecules.[12] Many of the genes encoding cyclins and CDKs are conserved among all eukaryotes, but in general more complex organisms have more elaborate cell cycle control systems that incorporate more individual components. Many of the relevant genes were first identified by studying yeast, especially Saccharomyces cerevisiae;[13] genetic nomenclature in yeast dubs many of these genes cdc (for "cell division cycle") followed by an identifying number, e.g. cdc25 or cdc20.

text: Cyclins form the regulatory subunits and CDKs the catalytic subunits of an activated heterodimer; cyclins have no catalytic activity and CDKs are inactive in the absence of a partner cyclin. When activated by a bound cyclin, CDKs perform a common biochemical reaction called phosphorylation that activates or inactivates target proteins to orchestrate coordinated entry into the next phase of the cell cycle. Different cyclin-CDK combinations determine the downstream proteins targeted. CDKs are constitutively expressed in cells whereas cyclins are synthesised at specific stages of the cell cycle, in response to various molecular signals.[14]

text: General mechanism of cyclin-CDK interaction[edit]

text: Upon receiving a pro-mitotic extracellular signal, G1 cyclin-CDK complexes become active to prepare the cell for S phase, promoting the expression of transcription factors that in turn promote the expression of S cyclins and of enzymes required for DNA replication. The G1 cyclin-CDK complexes also promote the degradation of molecules that function as S phase inhibitors by targeting them for ubiquitination. Once a protein has been ubiquitinated, it is targeted for proteolytic degradation by the proteasome. However, results from a recent study of E2F transcriptional dynamics at the single-cell level argue that the role of G1 cyclin-CDK activities, in particular cyclin D-CDK4/6, is to tune the timing rather than the commitment of cell cycle entry.[15]

text: Active S cyclin-CDK complexes phosphorylate proteins that make up the pre-replication complexes assembled during G1 phase on DNA replication origins. The phosphorylation serves two purposes: to activate each already-assembled pre-replication complex, and to prevent new complexes from forming. This ensures that every portion of the cell's genome will be replicated once and only once. The reason for prevention of gaps in replication is fairly clear, because daughter cells that are missing all or part of crucial genes will die. However, for reasons related to gene copy number effects, possession of extra copies of certain genes is also deleterious to the daughter cells.

text: Mitotic cyclin-CDK complexes, which are synthesized but inactivated during S and G2 phases, promote the initiation of mitosis by stimulating downstream proteins involved in chromosome condensation and mitotic spindle assembly. A critical complex activated during this process is a ubiquitin ligase known as the anaphase-promoting complex (APC), which promotes degradation of structural proteins associated with the chromosomal kinetochore. APC also targets the mitotic cyclins for degradation, ensuring that telophase and cytokinesis can proceed.[16]

text: Specific action of cyclin-CDK complexes[edit]

text: Cyclin D is the first cyclin produced in the cell cycle, in response to extracellular signals (e.g. growth factors). Cyclin D binds to existing CDK4, forming the active cyclin D-CDK4 complex. Cyclin D-CDK4 complex in turn phosphorylates the retinoblastoma susceptibility protein (Rb). The hyperphosphorylated Rb dissociates from the E2F/DP1/Rb complex (which was bound to the E2F responsive genes, effectively "blocking" them from transcription), activating E2F. Activation of E2F results in transcription of various genes like cyclin E, cyclin A, DNA polymerase, thymidine kinase, etc. Cyclin E thus produced binds to CDK2, forming the cyclin E-CDK2 complex, which pushes the cell from G1 to S phase (G1/S, which initiates the G2/M transition).[17] Cyclin B-cdk1 complex activation causes breakdown of nuclear envelope and initiation of prophase, and subsequently, its deactivation causes the cell to exit mitosis.[14] A quantitative study of E2F transcriptional dynamics at the single-cell level by using engineered fluorescent reporter cells provided a quantitative framework for understanding the control logic of cell cycle entry, challenging the canonical textbook model. Genes that regulate the amplitude of E2F accumulation, such as Myc, determine the commitment in cell cycle and S phase entry. G1 cyclin-CDK activities are not the driver of cell cycle entry. Instead, they primarily tune the timing of E2F increase, thereby modulating the pace of cell cycle progression.[15]

text: Inhibitors[edit]

text: Two families of genes, the cip/kip (CDK interacting protein/Kinase inhibitory protein) family and the INK4a/ARF (Inhibitor of Kinase 4/Alternative Reading Frame) family, prevent the progression of the cell cycle. Because these genes are instrumental in prevention of tumor formation, they are known as tumor suppressors.

text: The cip/kip family includes the genes p21, p27 and p57. They halt cell cycle in G1 phase, by binding to, and inactivating, cyclin-CDK complexes. p21 is activated by p53 (which, in turn, is triggered by DNA damage e.g. due to radiation). p27 is activated by Transforming Growth Factor of β (TGF β), a growth inhibitor.

text: The INK4a/ARF family includes p16INK4a, which binds to CDK4 and arrests the cell cycle in G1 phase, and p14ARF which prevents p53 degradation.

text: Synthetic inhibitors of Cdc25 could also be useful for the arrest of cell cycle and therefore be useful as antineoplastic and anticancer agents.[18]

text: Transcriptional regulatory network[edit]

text: Current evidence suggests that a semi-autonomous transcriptional network acts in concert with the CDK-cyclin machinery to regulate the cell cycle. Several gene expression studies in Saccharomyces cerevisiae have identified 800–1200 genes that change expression over the course of the cell cycle.[13][19][20] They are transcribed at high levels at specific points in the cell cycle, and remain at lower levels throughout the rest of the cycle. While the set of identified genes differs between studies due to the computational methods and criteria used to identify them, each study indicates that a large portion of yeast genes are temporally regulated.[21]

text: Many periodically expressed genes are driven by transcription factors that are also periodically expressed. One screen of single-gene knockouts identified 48 transcription factors (about 20% of all non-essential transcription factors) that show cell cycle progression defects.[22] Genome-wide studies using high throughput technologies have identified the transcription factors that bind to the promoters of yeast genes, and correlating these findings with temporal expression patterns have allowed the identification of transcription factors that drive phase-specific gene expression.[19][23] The expression profiles of these transcription factors are driven by the transcription factors that peak in the prior phase, and computational models have shown that a CDK-autonomous network of these transcription factors is sufficient to produce steady-state oscillations in gene expression).[20][24]

text: Experimental evidence also suggests that gene expression can oscillate with the period seen in dividing wild-type cells independently of the CDK machinery. Orlando et al. used microarrays to measure the expression of a set of 1,271 genes that they identified as periodic in both wild type cells and cells lacking all S-phase and mitotic cyclins (clb1,2,3,4,5,6). Of the 1,271 genes assayed, 882 continued to be expressed in the cyclin-deficient cells at the same time as in the wild type cells, despite the fact that the cyclin-deficient cells arrest at the border between G1 and S phase. However, 833 of the genes assayed changed behavior between the wild type and mutant cells, indicating that these genes are likely directly or indirectly regulated by the CDK-cyclin machinery. Some genes that continued to be expressed on time in the mutant cells were also expressed at different levels in the mutant and wild type cells. These findings suggest that while the transcriptional network may oscillate independently of the CDK-cyclin oscillator, they are coupled in a manner that requires both to ensure the proper timing of cell cycle events.[20] Other work indicates that phosphorylation, a post-translational modification, of cell cycle transcription factors by Cdk1 may alter the localization or activity of the transcription factors in order to tightly control timing of target genes.[22][25][26]

text: While oscillatory transcription plays a key role in the progression of the yeast cell cycle, the CDK-cyclin machinery operates independently in the early embryonic cell cycle. Before the midblastula transition, zygotic transcription does not occur and all needed proteins, such as the B-type cyclins, are translated from maternally loaded mRNA.[27]

text: DNA replication and DNA replication origin activity[edit]

text: Analyses of synchronized cultures of Saccharomyces cerevisiae under conditions that prevent DNA replication initiation without delaying cell cycle progression showed that origin licensing decreases the expression of genes with origins near their 3' ends, revealing that downstream origins can regulate the expression of upstream genes.[28] This confirms previous predictions from mathematical modeling of a global causal coordination between DNA replication origin activity and mRNA expression,[29][30][31] and shows that mathematical modeling of DNA microarray data can be used to correctly predict previously unknown biological modes of regulation.

text: Checkpoints[edit]

text: Cell cycle checkpoints are used by the cell to monitor and regulate the progress of the cell cycle.[32] Checkpoints prevent cell cycle progression at specific points, allowing verification of necessary phase processes and repair of DNA damage. The cell cannot proceed to the next phase until checkpoint requirements have been met. Checkpoints typically consist of a network of regulatory proteins that monitor and dictate the progression of the cell through the different stages of the cell cycle.

text: There are several checkpoints to ensure that damaged or incomplete DNA is not passed on to daughter cells. Three main checkpoints exist: the G1/S checkpoint, the G2/M checkpoint and the metaphase (mitotic) checkpoint.

text: G1/S transition is a rate-limiting step in the cell cycle and is also known as restriction point.[14] This is where the cell checks whether it has enough raw materials to fully replicate its DNA (nucleotide bases, DNA synthase, chromatin, etc.). An unhealthy or malnourished cell will get stuck at this checkpoint.

text: The G2/M checkpoint is where the cell ensures that it has enough cytoplasm and phospholipids for two daughter cells. But sometimes more importantly, it checks to see if it is the right time to replicate. There are some situations where many cells need to all replicate simultaneously (for example, a growing embryo should have a symmetric cell distribution until it reaches the mid-blastula transition). This is done by controlling the G2/M checkpoint.

text: The metaphase checkpoint is a fairly minor checkpoint, in that once a cell is in metaphase, it has committed to undergoing mitosis. However that's not to say it isn't important. In this checkpoint, the cell checks to ensure that the spindle has formed and that all of the chromosomes are aligned at the spindle equator before anaphase begins.[33]

text: While these are the three "main" checkpoints, not all cells have to pass through each of these checkpoints in this order to replicate. Many types of cancer are caused by mutations that allow the cells to speed through the various checkpoints or even skip them altogether. Going from S to M to S phase almost consecutively. Because these cells have lost their checkpoints, any DNA mutations that may have occurred are disregarded and passed on to the daughter cells. This is one reason why cancer cells have a tendency to exponentially accrue mutations. Aside from cancer cells, many fully differentiated cell types no longer replicate so they leave the cell cycle and stay in G0 until their death. Thus removing the need for cellular checkpoints. An alternative model of the cell cycle response to DNA damage has also been proposed, known as the postreplication checkpoint.

text: Checkpoint regulation plays an important role in an organism's development. In sexual reproduction, when egg fertilization occurs, when the sperm binds to the egg, it releases signalling factors that notify the egg that it has been fertilized. Among other things, this induces the now fertilized oocyte to return from its previously dormant, G0, state back into the cell cycle and on to mitotic replication and division.

text: p53 plays an important role in triggering the control mechanisms at both G1/S and G2/M checkpoints. In addition to p53, checkpoint regulators are being heavily researched for their roles in cancer growth and proliferation.

text: Fluorescence imaging of the cell cycle[edit]

text: Pioneering work by Atsushi Miyawaki and coworkers developed the fluorescent ubiquitination-based cell cycle indicator (FUCCI), which enables fluorescence imaging of the cell cycle. Originally, a green fluorescent protein, mAG, was fused to hGem(1/110) and an orange fluorescent protein (mKO2) was fused to hCdt1(30/120). Note, these fusions are fragments that contain a nuclear localization signal and ubiquitination sites for degradation, but are not functional proteins. The green fluorescent protein is made during the S, G2, or M phase and degraded during the G0 or G1 phase, while the orange fluorescent protein is made during the G0 or G1 phase and destroyed during the S, G2, or M phase.[34] A far-red and near-infrared FUCCI was developed using a cyanobacteria-derived fluorescent protein (smURFP) and a bacteriophytochrome-derived fluorescent protein (movie found at this link).[35]

text: Role in tumor formation[edit]

text: A disregulation of the cell cycle components may lead to tumor formation.[36] As mentioned above, when some genes like the cell cycle inhibitors, RB, p53 etc. mutate, they may cause the cell to multiply uncontrollably, forming a tumor. Although the duration of cell cycle in tumor cells is equal to or longer than that of normal cell cycle, the proportion of cells that are in active cell division (versus quiescent cells in G0 phase) in tumors is much higher than that in normal tissue[citation needed]. Thus there is a net increase in cell number as the number of cells that die by apoptosis or senescence remains the same.

text: The cells which are actively undergoing cell cycle are targeted in cancer therapy as the DNA is relatively exposed during cell division and hence susceptible to damage by drugs or radiation. This fact is made use of in cancer treatment; by a process known as debulking, a significant mass of the tumor is removed which pushes a significant number of the remaining tumor cells from G0 to G1 phase (due to increased availability of nutrients, oxygen, growth factors etc.). Radiation or chemotherapy following the debulking procedure kills these cells which have newly entered the cell cycle.[14]

text: The fastest cycling mammalian cells in culture, crypt cells in the intestinal epithelium, have a cycle time as short as 9 to 10 hours. Stem cells in resting mouse skin may have a cycle time of more than 200 hours. Most of this difference is due to the varying length of G1, the most variable phase of the cycle. M and S do not vary much.

text: In general, cells are most radiosensitive in late M and G2 phases and most resistant in late S phase.

text: For cells with a longer cell cycle time and a significantly long G1 phase, there is a second peak of resistance late in G1.

text: The pattern of resistance and sensitivity correlates with the level of sulfhydryl compounds in the cell. Sulfhydryls are natural substances that protect cells from radiation damage and tend to be at their highest levels in S and at their lowest near mitosis.


document_title: Empiricism

question_text: who is the thinker that unified the divide between empiricism and rationalism

text: Empiricism

text: Etymology[edit]

text: The English term empirical derives from the Ancient Greek word ἐμπειρία, empeiria, which is cognate with and translates to the Latin experientia, from which are derived the word experience and the related experiment.

text: History[edit]

text: Background[edit]

text: A central concept in science and the scientific method is that it must be empirically based on the evidence of the senses. Both natural and social sciences use working hypotheses that are testable by observation and experiment. The term semi-empirical is sometimes used to describe theoretical methods that make use of basic axioms, established scientific laws, and previous experimental results in order to engage in reasoned model building and theoretical inquiry.

text: Philosophical empiricists hold no knowledge to be properly inferred or deduced unless it is derived from one's sense-based experience.[5] This view is commonly contrasted with rationalism, which states that knowledge may be derived from reason independently of the senses. For example, John Locke held that some knowledge (e.g. knowledge of God's existence) could be arrived at through intuition and reasoning alone. Similarly Robert Boyle, a prominent advocate of the experimental method, held that we have innate ideas.[6][7] The main continental rationalists (Descartes, Spinoza, and Leibniz) were also advocates of the empirical "scientific method".[8][9]

text: Early empiricism[edit]

text: Vaisheshika darsana, founded by the ancient Indian philosopher Kanada, accepted perception and inference as the only two reliable sources of knowledge. This is enumerated in his work Vaiśeṣika Sūtra.

text: The earliest Western proto-empiricists were the Empiric school of ancient Greek medical practitioners, who rejected the three doctrines of the Dogmatic school, preferring to rely on the observation of "phenomena".[10]

text: The notion of tabula rasa ("clean slate" or "blank tablet") connotes a view of mind as an originally blank or empty recorder (Locke used the words "white paper") on which experience leaves marks. This denies that humans have innate ideas. The image dates back to Aristotle:

text: What the mind (nous) thinks must be in it in the same sense as letters are on a tablet (grammateion) which bears no actual writing (grammenon); this is just what happens in the case of the mind. (Aristotle, On the Soul, 3.4.430a1).

text: Aristotle's explanation of how this was possible was not strictly empiricist in a modern sense, but rather based on his theory of potentiality and actuality, and experience of sense perceptions still requires the help of the active nous. These notions contrasted with Platonic notions of the human mind as an entity that pre-existed somewhere in the heavens, before being sent down to join a body on Earth (see Plato's Phaedo and Apology, as well as others). Aristotle was considered to give a more important position to sense perception than Plato, and commentators in the Middle Ages summarized one of his positions as "nihil in intellectu nisi prius fuerit in sensu" (Latin for "nothing in the intellect without first being in the senses").

text: This idea was later developed in ancient philosophy by the Stoic school. Stoic epistemology generally emphasized that the mind starts blank, but acquires knowledge as the outside world is impressed upon it.[11] The doxographer Aetius summarizes this view as "When a man is born, the Stoics say, he has the commanding part of his soul like a sheet of paper ready for writing upon."[12]

text: During the Middle Ages Aristotle's theory of tabula rasa was developed by Islamic philosophers starting with Al Farabi, developing into an elaborate theory by Avicenna[13] and demonstrated as a thought experiment by Ibn Tufail.[14] For Avicenna (Ibn Sina), for example, the tabula rasa is a pure potentiality that is actualized through education, and knowledge is attained through "empirical familiarity with objects in this world from which one abstracts universal concepts" developed through a "syllogistic method of reasoning in which observations lead to propositional statements which when compounded lead to further abstract concepts". The intellect itself develops from a material intellect (al-'aql al-hayulani), which is a potentiality "that can acquire knowledge to the active intellect (al-'aql al-fa'il), the state of the human intellect in conjunction with the perfect source of knowledge".[13] So the immaterial "active intellect", separate from any individual person, is still essential for understanding to occur.

text: In the 12th century CE the Andalusian Muslim philosopher and novelist Abu Bakr Ibn Tufail (known as "Abubacer" or "Ebn Tophail" in the West) included the theory of tabula rasa as a thought experiment in his Arabic philosophical novel, Hayy ibn Yaqdhan in which he depicted the development of the mind of a feral child "from a tabula rasa to that of an adult, in complete isolation from society" on a desert island, through experience alone. The Latin translation of his philosophical novel, entitled Philosophus Autodidactus, published by Edward Pococke the Younger in 1671, had an influence on John Locke's formulation of tabula rasa in An Essay Concerning Human Understanding.[14]

text: A similar Islamic theological novel, Theologus Autodidactus, was written by the Arab theologian and physician Ibn al-Nafis in the 13th century. It also dealt with the theme of empiricism through the story of a feral child on a desert island, but departed from its predecessor by depicting the development of the protagonist's mind through contact with society rather than in isolation from society.[15]

text: During the 13th century Thomas Aquinas adopted the Aristotelian position that the senses are essential to mind into scholasticism. Bonaventure (1221–1274), one of Aquinas' strongest intellectual opponents, offered some of the strongest arguments in favour of the Platonic idea of the mind.

text: Renaissance Italy[edit]

text: In the late renaissance various writers began to question the medieval and classical understanding of knowledge acquisition in a more fundamental way. In political and historical writing Niccolò Machiavelli and his friend Francesco Guicciardini initiated a new realistic style of writing. Machiavelli in particular was scornful of writers on politics who judged everything in comparison to mental ideals and demanded that people should study the "effectual truth" instead. Their contemporary, Leonardo da Vinci (1452–1519) said, "If you find from your own experience that something is a fact and it contradicts what some authority has written down, then you must abandon the authority and base your reasoning on your own findings."[16]

text: The decidedly anti-Aristotelian and anti-clerical music theorist Vincenzo Galilei (c. 1520 – 1591), father of Galileo and the inventor of monody, made use of the method in successfully solving musical problems, firstly, of tuning such as the relationship of pitch to string tension and mass in stringed instruments, and to volume of air in wind instruments; and secondly to composition, by his various suggestions to composers in his Dialogo della musica antica e moderna (Florence, 1581). The Italian word he used for "experiment" was esperienza. It is known that he was the essential pedagogical influence upon the young Galileo, his eldest son (cf. Coelho, ed. Music and Science in the Age of Galileo Galilei), arguably one of the most influential empiricists in history. Vincenzo, through his tuning research, found the underlying truth at the heart of the misunderstood myth of 'Pythagoras' hammers' (the square of the numbers concerned yielded those musical intervals, not the actual numbers, as believed), and through this and other discoveries that demonstrated the fallibility of traditional authorities, a radically empirical attitude developed, passed on to Galileo, which regarded "experience and demonstration" as the sine qua non of valid rational enquiry.

text: British empiricism[edit]

text: British empiricism, though it was not a term used at the time, derives from the 17th century period of early modern philosophy and modern science. The term became useful in order to describe differences perceived between two of its founders Francis Bacon, described as empiricist, and René Descartes, who is described as a rationalist. Thomas Hobbes and Baruch Spinoza, in the next generation, are often also described as an empiricist and a rationalist respectively. John Locke, George Berkeley, and David Hume were the primary exponents of empiricism in the 18th century Enlightenment, with Locke being the person who is normally known as the founder of empiricism as such.

text: In response to the early-to-mid-17th century "continental rationalism" John Locke (1632–1704) proposed in An Essay Concerning Human Understanding (1689) a very influential view wherein the only knowledge humans can have is a posteriori, i.e., based upon experience. Locke is famously attributed with holding the proposition that the human mind is a tabula rasa, a "blank tablet", in Locke's words "white paper", on which the experiences derived from sense impressions as a person's life proceeds are written. There are two sources of our ideas: sensation and reflection. In both cases, a distinction is made between simple and complex ideas. The former are unanalysable, and are broken down into primary and secondary qualities. Primary qualities are essential for the object in question to be what it is. Without specific primary qualities, an object would not be what it is. For example, an apple is an apple because of the arrangement of its atomic structure. If an apple was structured differently, it would cease to be an apple. Secondary qualities are the sensory information we can perceive from its primary qualities. For example, an apple can be perceived in various colours, sizes, and textures but it is still identified as an apple. Therefore, its primary qualities dictate what the object essentially is, while its secondary qualities define its attributes. Complex ideas combine simple ones, and divide into substances, modes, and relations. According to Locke, our knowledge of things is a perception of ideas that are in accordance or discordance with each other, which is very different from the quest for certainty of Descartes.

text: A generation later, the Irish Anglican bishop, George Berkeley (1685–1753), determined that Locke's view immediately opened a door that would lead to eventual atheism. In response to Locke, he put forth in his Treatise Concerning the Principles of Human Knowledge (1710) an important challenge to empiricism in which things only exist either as a result of their being perceived, or by virtue of the fact that they are an entity doing the perceiving. (For Berkeley, God fills in for humans by doing the perceiving whenever humans are not around to do it.) In his text Alciphron, Berkeley maintained that any order humans may see in nature is the language or handwriting of God.[17] Berkeley's approach to empiricism would later come to be called subjective idealism.[18][19]

text: The Scottish philosopher David Hume (1711–1776) responded to Berkeley's criticisms of Locke, as well as other differences between early modern philosophers, and moved empiricism to a new level of skepticism. Hume argued in keeping with the empiricist view that all knowledge derives from sense experience, but he accepted that this has implications not normally acceptable to philosophers. He wrote for example, "Locke divides all arguments into demonstrative and probable. On this view, we must say that it is only probable that all men must die or that the sun will rise to-morrow, because neither of these can be demonstrated. But to conform our language more to common use, we ought to divide arguments into demonstrations, proofs, and probabilities—by ‘proofs’ meaning arguments from experience that leave no room for doubt or opposition."[20] And,[21]

text: "I believe the most general and most popular explication of this matter, is to say [See Mr. Locke, chapter of power.], that finding from experience, that there are several new productions in matter, such as the motions and variations of body, and concluding that there must somewhere be a power capable of producing them, we arrive at last by this reasoning at the idea of power and efficacy. But to be convinced that this explication is more popular than philosophical, we need but reflect on two very obvious principles. First, That reason alone can never give rise to any original idea, and secondly, that reason, as distinguished from experience, can never make us conclude, that a cause or productive quality is absolutely requisite to every beginning of existence. Both these considerations have been sufficiently explained: and therefore shall not at present be any farther insisted on."

text: Hume divided all of human knowledge into two categories: relations of ideas and matters of fact (see also Kant's analytic-synthetic distinction). Mathematical and logical propositions (e.g. "that the square of the hypotenuse is equal to the sum of the squares of the two sides") are examples of the first, while propositions involving some contingent observation of the world (e.g. "the sun rises in the East") are examples of the second. All of people's "ideas", in turn, are derived from their "impressions". For Hume, an "impression" corresponds roughly with what we call a sensation. To remember or to imagine such impressions is to have an "idea". Ideas are therefore the faint copies of sensations.[22]

text: Hume maintained that no knowledge, even the most basic beliefs about the natural world, can be conclusively established by reason. Rather, he maintained, our beliefs are more a result of accumulated habits, developed in response to accumulated sense experiences. Among his many arguments Hume also added another important slant to the debate about scientific method—that of the problem of induction. Hume argued that it requires inductive reasoning to arrive at the premises for the principle of inductive reasoning, and therefore the justification for inductive reasoning is a circular argument.[22] Among Hume's conclusions regarding the problem of induction is that there is no certainty that the future will resemble the past. Thus, as a simple instance posed by Hume, we cannot know with certainty by inductive reasoning that the sun will continue to rise in the East, but instead come to expect it to do so because it has repeatedly done so in the past.[22]

text: Hume concluded that such things as belief in an external world and belief in the existence of the self were not rationally justifiable. According to Hume these beliefs were to be accepted nonetheless because of their profound basis in instinct and custom. Hume's lasting legacy, however, was the doubt that his skeptical arguments cast on the legitimacy of inductive reasoning, allowing many skeptics who followed to cast similar doubt.

text: Phenomenalism[edit]

text: Most of Hume's followers have disagreed with his conclusion that belief in an external world is rationally unjustifiable, contending that Hume's own principles implicitly contained the rational justification for such a belief, that is, beyond being content to let the issue rest on human instinct, custom and habit.[23] According to an extreme empiricist theory known as phenomenalism, anticipated by the arguments of both Hume and George Berkeley, a physical object is a kind of construction out of our experiences.[24] Phenomenalism is the view that physical objects, properties, events (whatever is physical) are reducible to mental objects, properties, events. Ultimately, only mental objects, properties, events, exist—hence the closely related term subjective idealism. By the phenomenalistic line of thinking, to have a visual experience of a real physical thing is to have an experience of a certain kind of group of experiences. This type of set of experiences possesses a constancy and coherence that is lacking in the set of experiences of which hallucinations, for example, are a part. As John Stuart Mill put it in the mid-19th century, matter is the "permanent possibility of sensation".[25] Mill's empiricism went a significant step beyond Hume in still another respect: in maintaining that induction is necessary for all meaningful knowledge including mathematics. As summarized by D.W. Hamlin:

text: [Mill] claimed that mathematical truths were merely very highly confirmed generalizations from experience; mathematical inference, generally conceived as deductive [and a priori] in nature, Mill set down as founded on induction. Thus, in Mill's philosophy there was no real place for knowledge based on relations of ideas. In his view logical and mathematical necessity is psychological; we are merely unable to conceive any other possibilities than those that logical and mathematical propositions assert. This is perhaps the most extreme version of empiricism known, but it has not found many defenders.[19]

text: Mill's empiricism thus held that knowledge of any kind is not from direct experience but an inductive inference from direct experience.[26] The problems other philosophers have had with Mill's position center around the following issues: Firstly, Mill's formulation encounters difficulty when it describes what direct experience is by differentiating only between actual and possible sensations. This misses some key discussion concerning conditions under which such "groups of permanent possibilities of sensation" might exist in the first place. Berkeley put God in that gap; the phenomenalists, including Mill, essentially left the question unanswered. In the end, lacking an acknowledgement of an aspect of "reality" that goes beyond mere "possibilities of sensation", such a position leads to a version of subjective idealism. Questions of how floor beams continue to support a floor while unobserved, how trees continue to grow while unobserved and untouched by human hands, etc., remain unanswered, and perhaps unanswerable in these terms.[19][27] Secondly, Mill's formulation leaves open the unsettling possibility that the "gap-filling entities are purely possibilities and not actualities at all".[27] Thirdly, Mill's position, by calling mathematics merely another species of inductive inference, misapprehends mathematics. It fails to fully consider the structure and method of mathematical science, the products of which are arrived at through an internally consistent deductive set of procedures which do not, either today or at the time Mill wrote, fall under the agreed meaning of induction.[19][27][28]

text: The phenomenalist phase of post-Humean empiricism ended by the 1940s, for by that time it had become obvious that statements about physical things could not be translated into statements about actual and possible sense data.[29] If a physical object statement is to be translatable into a sense-data statement, the former must be at least deducible from the latter. But it came to be realized that there is no finite set of statements about actual and possible sense-data from which we can deduce even a single physical-object statement. The translating or paraphrasing statement must be couched in terms of normal observers in normal conditions of observation. There is, however, no finite set of statements that are couched in purely sensory terms and can express the satisfaction of the condition of the presence of a normal observer. According to phenomenalism, to say that a normal observer is present is to make the hypothetical statement that were a doctor to inspect the observer, the observer would appear to the doctor to be normal. But, of course, the doctor himself must be a normal observer. If we are to specify this doctor's normality in sensory terms, we must make reference to a second doctor who, when inspecting the sense organs of the first doctor, would himself have to have the sense data a normal observer has when inspecting the sense organs of a subject who is a normal observer. And if we are to specify in sensory terms that the second doctor is a normal observer, we must refer to a third doctor, and so on (also see the third man).[30][31]

text: Logical empiricism[edit]

text: Logical empiricism (also logical positivism or neopositivism) was an early 20th-century attempt to synthesize the essential ideas of British empiricism (e.g. a strong emphasis on sensory experience as the basis for knowledge) with certain insights from mathematical logic that had been developed by Gottlob Frege and Ludwig Wittgenstein. Some of the key figures in this movement were Otto Neurath, Moritz Schlick and the rest of the Vienna Circle, along with A.J. Ayer, Rudolf Carnap and Hans Reichenbach.

text: The neopositivists subscribed to a notion of philosophy as the conceptual clarification of the methods, insights and discoveries of the sciences. They saw in the logical symbolism elaborated by Frege (1848–1925) and Bertrand Russell (1872–1970) a powerful instrument that could rationally reconstruct all scientific discourse into an ideal, logically perfect, language that would be free of the ambiguities and deformations of natural language. This gave rise to what they saw as metaphysical pseudoproblems and other conceptual confusions. By combining Frege's thesis that all mathematical truths are logical with the early Wittgenstein's idea that all logical truths are mere linguistic tautologies, they arrived at a twofold classification of all propositions: the analytic (a priori) and the synthetic (a posteriori).[32] On this basis, they formulated a strong principle of demarcation between sentences that have sense and those that do not: the so-called verification principle. Any sentence that is not purely logical, or is unverifiable is devoid of meaning. As a result, most metaphysical, ethical, aesthetic and other traditional philosophical problems came to be considered pseudoproblems.[33]

text: In the extreme empiricism of the neopositivists—at least before the 1930s—any genuinely synthetic assertion must be reducible to an ultimate assertion (or set of ultimate assertions) that expresses direct observations or perceptions. In later years, Carnap and Neurath abandoned this sort of phenomenalism in favor of a rational reconstruction of knowledge into the language of an objective spatio-temporal physics. That is, instead of translating sentences about physical objects into sense-data, such sentences were to be translated into so-called protocol sentences, for example, "X at location Y and at time T observes such and such."[34] The central theses of logical positivism (verificationism, the analytic–synthetic distinction, reductionism, etc.) came under sharp attack after World War II by thinkers such as Nelson Goodman, W.V. Quine, Hilary Putnam, Karl Popper, and Richard Rorty. By the late 1960s, it had become evident to most philosophers that the movement had pretty much run its course, though its influence is still significant among contemporary analytic philosophers such as Michael Dummett and other anti-realists.

text: Pragmatism[edit]

text: In the late 19th and early 20th century several forms of pragmatic philosophy arose. The ideas of pragmatism, in its various forms, developed mainly from discussions between Charles Sanders Peirce and William James when both men were at Harvard in the 1870s. James popularized the term "pragmatism", giving Peirce full credit for its patrimony, but Peirce later demurred from the tangents that the movement was taking, and redubbed what he regarded as the original idea with the name of "pragmaticism". Along with its pragmatic theory of truth, this perspective integrates the basic insights of empirical (experience-based) and rational (concept-based) thinking.

text: Charles Peirce (1839–1914) was highly influential in laying the groundwork for today's empirical scientific method.[35] Although Peirce severely criticized many elements of Descartes' peculiar brand of rationalism, he did not reject rationalism outright. Indeed, he concurred with the main ideas of rationalism, most importantly the idea that rational concepts can be meaningful and the idea that rational concepts necessarily go beyond the data given by empirical observation. In later years he even emphasized the concept-driven side of the then ongoing debate between strict empiricism and strict rationalism, in part to counterbalance the excesses to which some of his cohorts had taken pragmatism under the "data-driven" strict-empiricist view.

text: Among Peirce's major contributions was to place inductive reasoning and deductive reasoning in a complementary rather than competitive mode, the latter of which had been the primary trend among the educated since David Hume wrote a century before. To this, Peirce added the concept of abductive reasoning. The combined three forms of reasoning serve as a primary conceptual foundation for the empirically based scientific method today. Peirce's approach "presupposes that (1) the objects of knowledge are real things, (2) the characters (properties) of real things do not depend on our perceptions of them, and (3) everyone who has sufficient experience of real things will agree on the truth about them. According to Peirce's doctrine of fallibilism, the conclusions of science are always tentative. The rationality of the scientific method does not depend on the certainty of its conclusions, but on its self-corrective character: by continued application of the method science can detect and correct its own mistakes, and thus eventually lead to the discovery of truth".[36]

text: In his Harvard "Lectures on Pragmatism" (1903), Peirce enumerated what he called the "three cotary propositions of pragmatism" (L: cos, cotis whetstone), saying that they "put the edge on the maxim of pragmatism". First among these he listed the peripatetic-thomist observation mentioned above, but he further observed that this link between sensory perception and intellectual conception is a two-way street. That is, it can be taken to say that whatever we find in the intellect is also incipiently in the senses. Hence, if theories are theory-laden then so are the senses, and perception itself can be seen as a species of abductive inference, its difference being that it is beyond control and hence beyond critique—in a word, incorrigible. This in no way conflicts with the fallibility and revisability of scientific concepts, since it is only the immediate percept in its unique individuality or "thisness"—what the Scholastics called its haecceity—that stands beyond control and correction. Scientific concepts, on the other hand, are general in nature, and transient sensations do in another sense find correction within them. This notion of perception as abduction has received periodic revivals in artificial intelligence and cognitive science research, most recently for instance with the work of Irvin Rock on indirect perception.[37][38]

text: Around the beginning of the 20th century, William James (1842–1910) coined the term "radical empiricism" to describe an offshoot of his form of pragmatism, which he argued could be dealt with separately from his pragmatism—though in fact the two concepts are intertwined in James's published lectures. James maintained that the empirically observed "directly apprehended universe needs ... no extraneous trans-empirical connective support",[39] by which he meant to rule out the perception that there can be any value added by seeking supernatural explanations for natural phenomena. James' "radical empiricism" is thus not radical in the context of the term "empiricism", but is instead fairly consistent with the modern use of the term "empirical". His method of argument in arriving at this view, however, still readily encounters debate within philosophy even today.

text: John Dewey (1859–1952) modified James' pragmatism to form a theory known as instrumentalism. The role of sense experience in Dewey's theory is crucial, in that he saw experience as unified totality of things through which everything else is interrelated. Dewey's basic thought, in accordance with empiricism was that reality is determined by past experience. Therefore, humans adapt their past experiences of things to perform experiments upon and test the pragmatic values of such experience. The value of such experience is measured experientially and scientifically, and the results of such tests generate ideas that serve as instruments for future experimentation,[40] in physical sciences as in ethics.[41] Thus, ideas in Dewey's system retain their empiricist flavour in that they are only known a posteriori.


document_title: Meeting at Night

question_text: what is the rhyme scheme of meeting at night

text: Meeting at Night

text: Background[edit]

text: John Kenyon, a distant cousin of Elizabeth Barrett, presented a copy of Barrett's 1844 poems to Sarianna Browning, sister of Robert Browning. Browning, discovering his name in print in the poem volume, wrote a letter to Barrett on January 10, 1845. Upon getting a reply he sent her the manuscripts of poems and plays of the Dramatic Romances and Lyrics for proofreading.[2]

text: The poems in Dramatic Romances and Lyrics were arranged in groups of two or three with the two love poems "Night" and "Morning" as complementary. They are described by Kennedy and Hair as "a compact dramatic narrative reflecting a decidedly masculine attitude toward love."[1]

text: Themes[edit]

text: The poem is written in two stanzas of six lines each. The first stanza describes the excitement of a secret journey by a boat on the sea. The second stanza describes the joy of the meeting of the two lovers.

text: Like its sister poem "Parting at Morning" which uses pronominal reference to attribute the gender of the person in the boat (as male), the poem never reveals the identity of the two lovers.[3] It follows the rhyme scheme abccba and deffed.[4]

text: Reception[edit]

text: There are two published accounts of this poem: one by F. R. Leavis[5] and another by Ronald Carter and Walter Nash.[6] Kennedy and Hair explain that Browning's urgent love for Elizabeth Barrett had led him to write "the most sensual poem he had yet created."[1]