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Dewey Decimal Classification -- robin hasan, 06:31:16 02/10/16 Wed 
The Dewey Decimal Classification (DDC), or Dewey Decimal System, is a proprietary library classification system first published in the United States by Melvil Dewey in 1876. It has been revised and expanded through 23 major editions, the latest issued in 2011, and has grown from a four-page pamphlet in 1876 with fewer than 1,000 classes to a four volume set. It is also available in an abridged version suitable for smaller libraries. It is currently maintained by the Online Computer Library Center (OCLC), a non-profit cooperative that serves libraries. OCLC licenses access to an online version for catalogers called WebDewey.
The Decimal Classification introduced the concepts of relative location and relative index which allow new books to be added to a library in their appropriate location based on subject. Libraries previously had given books permanent shelf locations that were related to the order of acquisition rather than topic. The classification's notation makes use of three-digit Arabic numerals for main classes, with fractional decimals allowing expansion for further detail. A library assigns a classification number that unambiguously locates a particular volume in a position relative to other books in the library, on the basis of its subject. The number makes it possible to find any book and to return it to its proper place on the library shelves.[notes 1] The classification system is used in 200,000 libraries in at least 135 countries.
The major competing classification system to the Dewey Decimal system is the Library of Congress Classification system created by the U.S. Library of Congress.
Early development (1873–1885)
Melvil Dewey (1851–1931) was an American librarian and self-declared reformer. He is best known for the Decimal System that he created, but he also was a founding member of the American Library Association and can be credited with the promotion of card systems in libraries and business. He developed the ideas for his library classification system in 1873 while working at Amherst College library. He applied the classification to the books in that library, until in 1876 he had a first version of the classification. In 1876, he published the classification in pamphlet form with the title A Classification and Subject Index for Cataloguing and Arranging the Books and Pamphlets of a Library. He used the pamphlet, published in more than one version during the year, to solicit comments from other librarians. It is not known who received copies or how many commented as only one copy with comments has survived, that of Ernest Cushing Richardson. His classification system was mentioned in an article in the first issue of the Library Journal and in an article by Dewey in the Department of Education publication "Public Libraries in America" in 1876. In March 1876, he applied for, and received copyright on the first edition of the index. The edition was 44 pages in length, with 2,000 index entries, and was printed in 200 copies.
Period of adoption (1885–1942)
The second edition of the Dewey Decimal system, published in 1885 with the title Decimal Classification and Relativ Index for arranging, cataloging, and indexing public and private libraries and for pamflets, clippings, notes, scrap books, index rerums, etc.,[notes 2] comprised 314 pages, with 10,000 index entries. 500 copies were produced. Editions 3–14, published between 1888 and 1942, used a variant of this same title. Dewey modified and expanded his system considerably for the second edition. In an introduction to that edition Dewey states that "nearly 100 persons hav [sic] contributed criticisms and suggestions".
One of the innovations of the Dewey Decimal system was that of positioning books on the shelves in relation to other books on similar topics. When the system was first introduced, most libraries in the US used fixed positioning: each book was assigned a permanent shelf position based on the book's height and date of acquisition. Library stacks were generally closed to all but the most privileged patrons, so shelf browsing was not considered of importance. The use of the Dewey Decimal system increased during the early 20th century as librarians were convinced of the advantages of relative positioning and of open shelf access for patrons.
New editions were readied as supplies of previously published editions were exhausted, even though some editions provided little change from the previous, as they were primarily needed to fulfill demand. In the next decade, three editions followed closely on: the 3rd (1888), 4th (1891), and 5th (1894). Editions 6 through 11 were published from 1899 to 1922. The 6th edition was published in a record 7,600 copies, although subsequent editions were much lower. During this time, the size of the volume grew, and edition 12 swelled to 1243 pages, an increase of 25% over the previous edition.
In response to the needs of smaller libraries who were finding the expanded classification schedules difficult to use, in 1894, the first abridged edition of the Dewey Decimal system was produced. The abridged edition generally parallels the full edition, and has been developed for most full editions since that date. By popular request, in 1930, the Library of Congress began to print Dewey Classification numbers on nearly all of its cards, thus making the system immediately available to all libraries making use of the Library of Congress card sets.
Dewey's was not the only library classification available, although it was the most complete. Charles Ammi Cutter published the Expansive Classification in 1882, with initial encouragement from Melvil Dewey. Cutter's system was not adopted by many libraries, with one major exception: it was used as the basis for the Library of Congress Classification system.
In 1895, the International Institute of Bibliography, located in Belgium and led by Paul Otlet, contacted Dewey about the possibility of translating the classification into French, and using the classification system for bibliographies (as opposed to its use for books in libraries). This would have required some changes to the classification, which was under copyright. Dewey gave permission for the creation of a version intended for bibliographies, and also for its translation into French. Dewey did not agree, however, to allow the International Institute of Bibliography to later create an English version of the resulting classification, considering that a violation of their agreement, as well as a violation of Dewey's copyright. Shortly after Dewey's death in 1931, however, an agreement was reached between the committee overseeing the development of the Decimal Classification and the developers of the French Classification Decimal. The English version was published as the Universal Decimal Classification and is still in use today.
According to a study done in 1927, the Dewey system was used in the US in approximately 96% of responding public libraries and 89% of the college libraries. After the death of Melvil Dewey in 1931, administration of the classification was under the Decimal Classification Committee of the Lake Placid Club Education Foundation, and the editorial body was the Decimal Classification Editorial Policy Committee with participation of the American Library Association (ALA), Library of Congress, and Forest Press. By the 14th edition in 1942, the Dewey Decimal Classification index was over 1,900 pages in length and was published in two volumes.
Forging an identity (1942–present)
The growth of the classification to date had led to significant criticism from medium and large libraries which were too large to use the abridged edition but found the full classification overwhelming. Dewey had intended issuing the classification in three editions: the library edition, which would be the fullest edition; the bibliographic edition, in English and French, which was to be used for the organization of bibliographies rather than of books on the shelf; and the abridged edition. In 1933, the bibliographic edition became the Universal Decimal Classification, which left the library and abridged versions as the formal Dewey Decimal Classification editions. The 15th edition, edited by Milton Ferguson, implemented the growing concept of the "standard edition", designed for the majority of general libraries but not attempting to satisfy the needs of the very largest or of special libraries. It also reduced the size of the Dewey system by over half, from 1,900 to 700 pages, a revision so radical that Ferguson was removed[by whom?] from the editorship for the next edition. The 16th and 17th editions, under the editorship of the Library of Congress, grew again to two volumes. However, by now, the Dewey Decimal system had established itself as a classification for general libraries, with the Library of Congress Classification having gained acceptance for large research libraries.
The first electronic version of "Dewey" was created in 1993. Hard-copy editions continue to be issued at intervals; the online WebDewey and Abridged WebDewey are updated quarterly.
Administration and publication
Administratively, the very early editions were managed by Dewey and a small editorial staff. Beginning in 1922, administrative affairs were managed by the Lake Placid Club Educational Foundation, a not-for-profit organization founded by Melvil Dewey. The ALA created a Special Advisory Committee on the Decimal Classification as part of the Cataloging and Classification division of ALA, in 1952. The previous Decimal Classification Committee was changed to the Decimal Classification Editorial Policy Committee, with participation of the ALA Division of Cataloging and Classification, and the Library of Congress.
Melvil Dewey edited the first three editions of the classification system and oversaw the revisions of all editions until his death in 1931. May Seymour became editor in 1891, until her death in 1921. She was followed by Dorcas Fellows, who was editor until her death in 1938. Constantin J. Mazney edited the 14th edition. Milton Ferguson was editor from 1949 to 1951. The 16th edition in 1958 was edited under an agreement between the Library of Congress and Forest Press, with David Haykin as director. Editions 16-19 were edited by Benjamin A. Custer and the editor of edition 20 was John P. Comaromi. Joan Mitchell was editor until 2013, covering editions 21-23. The current Editor-in-Chief is Michael Panzer of OCLC.
Copyright in editions 1-6 (1876–1919) was held by Dewey himself. Copyright in editions 7–10 were held by the publisher, The Library Bureau. On the death of May Seymour, Dewey conveyed the "copyryts and control of all editions" to the Lake Placid Club Educational Foundation, a non-profit chartered in 1922. The Online Computer Library Center (OCLC) of Dublin, Ohio, US, acquired the trademark and copyrights associated with the Dewey Decimal Classification system when it bought Forest Press in 1988. In 2003, the Dewey Decimal Classification came to national attention when OCLC sued the Library Hotel for trademark infringement for using the classification system as the hotel theme. The case was settled shortly thereafter.
Since 1988, the classification has been maintained by the OCLC, which also publishes new editions of the system. The editorial staff responsible for updates is based partly at the Library of Congress and partly at OCLC. Their work is reviewed by the Decimal Classification Editorial Policy Committee, a ten-member international board which meets twice each year. The four-volume unabridged edition is published approximately every six years, the most recent edition (DDC 23) in mid-2011. The web edition is updated on an ongoing basis, with changes announced each month. An experimental version of Dewey in RDF is available at dewey.info. This includes access to the top three levels of the classification system in 14 languages.
In addition to the full version, a single volume abridged edition designed for libraries with 20,000 titles or fewer has been made available since 1895. "Abridged 15" was published in early 2012
The Dewey Decimal Classification organizes library materials by discipline or field of study. Main divisions include philosophy, social sciences, science, technology, and history. The scheme is made up of ten classes, each divided into ten divisions, each having ten sections. The system's notation uses Arabic numbers, with three whole numbers making up the main classes and sub-classes and decimals creating further divisions. The classification structure is hierarchical and the notation follows the same hierarchy. Libraries not needing the full level of detail of the classification can trim right-most decimal digits from the class number to obtain a more general classification. For example:
500 Natural sciences and mathematics
516.3 Analytic geometries
516.37 Metric differential geometries
516.375 Finsler Geometry
The classification was originally enumerative, meaning that it listed all of the classes explicitly in the schedules. Over time it added some aspects of a faceted classification scheme, allowing classifiers to construct a number by combining a class number for a topic with an entry from a separate table. Tables cover commonly used elements such as geographical and temporal aspects, language, and bibliographic forms. For example, a class number could be constructed using 330 for economics + .9 for geographic treatment + .04 for Europe to create the class 330.94 European economy. Or one could combine the class 973 for United States + .05 for periodical publications on the topic to arrive at the number 973.05 for periodicals concerning the United States generally. The classification also makes use of mnemonics in some areas, such that the number 5 represents the country Italy in classification numbers like 945 (history of Italy), 450 (Italian language), 195 (Italian philosophy). The combination of faceting and mnemonics makes the classification synthetic in nature, with meaning built into parts of the classification number.
The Dewey Decimal Classification has a number for all subjects, including fiction, although many libraries create a separate fiction section shelved by alphabetical order of the author's surname. Each assigned number consists of two parts: a class number (from the Dewey system) and a book number, which "prevents confusion of different books on the same subject."  A common form of the book number is called a Cutter number, which represents the author and distinguishes the book from other books on the same topic.
Main article: List of Dewey Decimal classes
(From DDC 23)
000 – General works, Computer science and Information
100 – Philosophy and psychology
200 – Religion
300 – Social sciences
400 – Language
500 – Pure Science
600 – Technology
700 – Arts & recreation
800 – Literature
900 – History & geography
(From DDC 23)
T1 Standard Subdivisions
T2 Geographic Areas, Historical Periods, Biography
T3 Subdivisions for the Arts, for Individual Literatures, for Specific Literary Forms
T3A Subdivisions for Works by or about Individual Authors
T3B Subdivisions for Works by or about More than One Author
T3C Notation to Be Added Where Instructed in Table 3B, 700.4, 791.4, 808–809
T4 Subdivisions of Individual Languages and Language Families
T5 Ethnic and National Groups
The "Relativ Index" [sic] is an alphabetical index to the classification, for use both by classifiers but also by library users when seeking books by topic. The index was "relative" because the index entries pointed to the class numbers, not to the page numbers of the printed classification schedule. In this way, the Dewey Decimal Classification itself had the same relative positioning as the library shelf and could be used either as an entry point to the classification, by catalogers, or as an index to the Dewey-classed library itself.
Dewey Decimal Classification numbers formed the basis of the Universal Decimal Classification (UDC), which combines the basic Dewey numbers with selected punctuation marks (comma, colon, parentheses, etc.). Adaptations of the system for specific regions outside the English-speaking world include the Korean Decimal Classification, the New Classification Scheme for Chinese Libraries, and the Nippon Decimal Classification (Japanese).
Despite its widespread usage, the classification has been criticized for its complexity and limited scope of scheme-adjustment. In particular, the arrangement of subheadings has been described as archaic and as being biased towards an Anglo-American world view. In 2007–08, the Maricopa County Library District in Arizona, abandoned the DDC in favor of the Book Industry Standards and Communications (BISAC) system, one that is commonly used by commercial bookstores, in an effort to make their libraries more accessible for patrons. Several other libraries across the United States, and other countries (including Canada and The Netherlands) followed suit. The classification has also been criticized as being a proprietary system licensed by a single entity (OCLC), making it expensive to adopt. However, book classification critic Justin Newlan stands by the Dewey Decimal System, stating newer, more advanced book classification systems "are too confusing to understand for newcomers".
It should be noted, however, that BISAC is also a proprietary classification system.
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Dengue fever -- robin hasan, 06:27:40 02/10/16 Wed 
Dengue fever is a mosquito-borne tropical disease caused by the dengue virus. Symptoms typically begin three to fourteen days after infection. This may include a high fever, headache, vomiting, muscle and joint pains, and a characteristic skin rash. Recovery generally takes less than two to seven days. In a small proportion of cases, the disease develops into the life-threatening dengue hemorrhagic fever, resulting in bleeding, low levels of blood platelets and blood plasma leakage, or into dengue shock syndrome, where dangerously low blood pressure occurs.
Dengue is spread by several species of mosquito of the Aedes type, principally A. aegypti. The virus has five different types; infection with one type usually gives lifelong immunity to that type, but only short-term immunity to the others. Subsequent infection with a different type increases the risk of severe complications. A number of tests are available to confirm the diagnosis including detecting antibodies to the virus or its RNA.
A novel vaccine for dengue fever has been approved in three countries, but it is not yet commercially available. Prevention is by reducing mosquito habitat and limiting exposure to bites. This may be done by getting rid of or covering standing water and wearing clothing that covers much of the body. Treatment of acute dengue is supportive and includes giving fluid either by mouth or intravenously for mild or moderate disease. For more severe cases blood transfusion may be required. About half a million people require admission to hospital a year. Nonsteroidal anti-inflammatory drug (NSAIDs) such as ibuprofen should not be used.
Dengue has become a global problem since the Second World War and is common in more than 110 countries. Each year between 50 and 528 million people are infected and approximately 20,000 die. The earliest descriptions of an outbreak date from 1779. Its viral cause and spread were understood by the early 20th century. Apart from eliminating the mosquitoes, work is ongoing for medication targeted directly at the virus.
Typically, people infected with dengue virus are asymptomatic (80%) or have only mild symptoms such as an uncomplicated fever. Others have more severe illness (5%), and in a small proportion it is life-threatening. The incubation period (time between exposure and onset of symptoms) ranges from 3 to 14 days, but most often it is 4 to 7 days. Therefore, travelers returning from endemic areas are unlikely to have dengue if fever or other symptoms start more than 14 days after arriving home. Children often experience symptoms similar to those of the common cold and gastroenteritis (vomiting and diarrhea) and have a greater risk of severe complications, though initial symptoms are generally mild but include high fever
Dengue fever virus (DENV) is an RNA virus of the family Flaviviridae; genus Flavivirus. Other members of the same genus include yellow fever virus, West Nile virus, St. Louis encephalitis virus, Japanese encephalitis virus, tick-borne encephalitis virus, Kyasanur forest disease virus, and Omsk hemorrhagic fever virus. Most are transmitted by arthropods (mosquitoes or ticks), and are therefore also referred to as arboviruses (arthropod-borne viruses).
The dengue virus genome (genetic material) contains about 11,000 nucleotide bases, which code for the three different types of protein molecules (C, prM and E) that form the virus particle and seven other types of protein molecules (NS1, NS2a, NS2b, NS3, NS4a, NS4b, NS5) that are found in infected host cells only and are required for replication of the virus. There are five strains of the virus, called serotypes, of which the first four are referred to as DENV-1, DENV-2, DENV-3 and DENV-4. The fifth type was announced in 2013. The distinctions between the serotypes are based on their antigenicity
Dengue virus is primarily transmitted by Aedes mosquitoes, particularly A. aegypti. These mosquitoes usually live between the latitudes of 35° North and 35° South below an elevation of 1,000 metres (3,300 ft). They typically bite during the early morning and in the evening, but they may bite and thus spread infection at any time of day. Other Aedes species that transmit the disease include A. albopictus, A. polynesiensis and A. scutellaris. Humans are the primary host of the virus, but it also circulates in nonhuman primates. An infection can be acquired via a single bite. A female mosquito that takes a blood meal from a person infected with dengue fever, during the initial 2–10 day febrile period, becomes itself infected with the virus in the cells lining its gut. About 8–10 days later, the virus spreads to other tissues including the mosquito's salivary glands and is subsequently released into its saliva. The virus seems to have no detrimental effect on the mosquito, which remains infected for life. Aedes aegypti is particularly involved, as it prefers to lay its eggs in artificial water containers, to live in close proximity to humans, and to feed on people rather than other vertebrates.
Dengue can also be transmitted via infected blood products and through organ donation. In countries such as Singapore, where dengue is endemic, the risk is estimated to be between 1.6 and 6 per 10,000 transfusions. Vertical transmission (from mother to child) during pregnancy or at birth has been reported. Other person-to-person modes of transmission have also been reported, but are very unusual. The genetic variation in dengue viruses is region specific, suggestive that establishment into new territories is relatively infrequent, despite dengue emerging in new regions in recent decades.
Severe disease is more common in babies and young children, and in contrast to many other infections, it is more common in children who are relatively well nourished. Other risk factors for severe disease include female sex, high body mass index, and viral load. While each serotype can cause the full spectrum of disease, virus strain is a risk factor. Infection with one serotype is thought to produce lifelong immunity to that type, but only short-term protection against the other three. The risk of severe disease from secondary infection increases if someone previously exposed to serotype DENV-1 contracts serotype DENV-2 or DENV-3, or if someone previously exposed to DENV-3 acquires DENV-2. Dengue can be life-threatening in people with chronic diseases such as diabetes and asthma.
Polymorphisms (normal variations) in particular genes have been linked with an increased risk of severe dengue complications. Examples include the genes coding for the proteins known as TNFα, mannan-binding lectin, CTLA4, TGFβ, DC-SIGN, PLCE1, and particular forms of human leukocyte antigen from gene variations of HLA-B. A common genetic abnormality, especially in Africans, known as glucose-6-phosphate dehydrogenase deficiency, appears to increase the risk. Polymorphisms in the genes for the vitamin D receptor and FcγR seem to offer protection against severe disease in secondary dengue infection.
When a mosquito carrying dengue virus bites a person, the virus enters the skin together with the mosquito's saliva. It binds to and enters white blood cells, and reproduces inside the cells while they move throughout the body. The white blood cells respond by producing a number of signaling proteins, such as cytokines and interferons, which are responsible for many of the symptoms, such as the fever, the flu-like symptoms and the severe pains. In severe infection, the virus production inside the body is greatly increased, and many more organs (such as the liver and the bone marrow) can be affected. Fluid from the bloodstream leaks through the wall of small blood vessels into body cavities due to capillary permeability. As a result, less blood circulates in the blood vessels, and the blood pressure becomes so low that it cannot supply sufficient blood to vital organs. Furthermore, dysfunction of the bone marrow due to infection of the stromal cells leads to reduced numbers of platelets, which are necessary for effective blood clotting; this increases the risk of bleeding, the other major complication of dengue fever.
Once inside the skin, dengue virus binds to Langerhans cells (a population of dendritic cells in the skin that identifies pathogens). The virus enters the cells through binding between viral proteins and membrane proteins on the Langerhans cell, specifically the C-type lectins called DC-SIGN, mannose receptor and CLEC5A. DC-SIGN, a non-specific receptor for foreign material on dendritic cells, seems to be the main point of entry. The dendritic cell moves to the nearest lymph node. Meanwhile, the virus genome is translated in membrane-bound vesicles on the cell's endoplasmic reticulum, where the cell's protein synthesis apparatus produces new viral proteins that replicate the viral RNA and begin to form viral particles. Immature virus particles are transported to the Golgi apparatus, the part of the cell where some of the proteins receive necessary sugar chains (glycoproteins). The now mature new viruses bud on the surface of the infected cell and are released by exocytosis. They are then able to enter other white blood cells, such as monocytes and macrophages.
The initial reaction of infected cells is to produce interferon, a cytokine that raises a number of defenses against viral infection through the innate immune system by augmenting the production of a large group of proteins mediated by the JAK-STAT pathway. Some serotypes of dengue virus appear to have mechanisms to slow down this process. Interferon also activates the adaptive immune system, which leads to the generation of antibodies against the virus as well as T cells that directly attack any cell infected with the virus. Various antibodies are generated; some bind closely to the viral proteins and target them for phagocytosis (ingestion by specialized cells and destruction), but some bind the virus less well and appear instead to deliver the virus into a part of the phagocytes where it is not destroyed but is able to replicate further.
It is not entirely clear why secondary infection with a different strain of dengue virus places people at risk of dengue hemorrhagic fever and dengue shock syndrome. The most widely accepted hypothesis is that of antibody-dependent enhancement (ADE). The exact mechanism behind ADE is unclear. It may be caused by poor binding of non-neutralizing antibodies and delivery into the wrong compartment of white blood cells that have ingested the virus for destruction. There is a suspicion that ADE is not the only mechanism underlying severe dengue-related complications, and various lines of research have implied a role for T cells and soluble factors such as cytokines and the complement system.
Severe disease is marked by the problems of capillary permeability (an allowance of fluid and protein normally contained within blood to pass) and disordered blood clotting. These changes appear associated with a disordered state of the endothelial glycocalyx, which acts as a molecular filter of blood components. Leaky capillaries (and the critical phase) are thought to be caused by an immune system response. Other processes of interest include infected cells that become necrotic—which affect both coagulation and fibrinolysis (the opposing systems of blood clotting and clot degradation)—and low platelets in the blood, also a factor in normal clotting.
The diagnosis of dengue is typically made clinically, on the basis of reported symptoms and physical examination; this applies especially in endemic areas. However, early disease can be difficult to differentiate from other viral infections. A probable diagnosis is based on the findings of fever plus two of the following: nausea and vomiting, rash, generalized pains, low white blood cell count, positive tourniquet test, or any warning sign (see table) in someone who lives in an endemic area. Warning signs typically occur before the onset of severe dengue. The tourniquet test, which is particularly useful in settings where no laboratory investigations are readily available, involves the application of a blood pressure cuff at between the diastolic and systolic pressure for five minutes, followed by the counting of any petechial hemorrhages; a higher number makes a diagnosis of dengue more likely with the cut off being more than 10 to 20 per 1 inch2 (6.25 cm2).
The diagnosis should be considered in anyone who develops a fever within two weeks of being in the tropics or subtropics. It can be difficult to distinguish dengue fever and chikungunya, a similar viral infection that shares many symptoms and occurs in similar parts of the world to dengue. Often, investigations are performed to exclude other conditions that cause similar symptoms, such as malaria, leptospirosis, viral hemorrhagic fever, typhoid fever, meningococcal disease, measles, and influenza. Zika fever also has similar symptoms as dengue.
The earliest change detectable on laboratory investigations is a low white blood cell count, which may then be followed by low platelets and metabolic acidosis. A moderately elevated level of aminotransferase (AST and ALT) from the liver is commonly associated with low platelets and white blood cells. In severe disease, plasma leakage results in hemoconcentration (as indicated by a rising hematocrit) and hypoalbuminemia. Pleural effusions or ascites can be detected by physical examination when large, but the demonstration of fluid on ultrasound may assist in the early identification of dengue shock syndrome. The use of ultrasound is limited by lack of availability in many settings. Dengue shock syndrome is present if pulse pressure drops to ≤ 20 mm Hg along with peripheral vascular collapse. Peripheral vascular collapse is determined in children via delayed capillary refill, rapid heart rate, or cold extremities. While warning signs are an important aspect for early detection of potential serious disease, the evidence for any specific clinical or laboratory marker is weak.
The World Health Organization's 2009 classification divides dengue fever into two groups: uncomplicated and severe. This replaces the 1997 WHO classification, which needed to be simplified as it had been found to be too restrictive, though the older classification is still widely used including by the World Health Organization's Regional Office for South-East Asia as of 2011. Severe dengue is defined as that associated with severe bleeding, severe organ dysfunction, or severe plasma leakage while all other cases are uncomplicated. The 1997 classification divided dengue into undifferentiated fever, dengue fever, and dengue hemorrhagic fever. Dengue hemorrhagic fever was subdivided further into grades I–IV. Grade I is the presence only of easy bruising or a positive tourniquet test in someone with fever, grade II is the presence of spontaneous bleeding into the skin and elsewhere, grade III is the clinical evidence of shock, and grade IV is shock so severe that blood pressure and pulse cannot be detected. Grades III and IV are referred to as "dengue shock syndrome".
The diagnosis of dengue fever may be confirmed by microbiological laboratory testing. This can be done by virus isolation in cell cultures, nucleic acid detection by PCR, viral antigen detection (such as for NS1) or specific antibodies (serology). Virus isolation and nucleic acid detection are more accurate than antigen detection, but these tests are not widely available due to their greater cost. Detection of NS1 during the febrile phase of a primary infection may be greater than 90% sensitive however is only 60–80% in subsequent infections. All tests may be negative in the early stages of the disease. PCR and viral antigen detection are more accurate in the first seven days. In 2012 a PCR test was introduced that can run on equipment used to diagnose influenza; this is likely to improve access to PCR-based diagnosis.
These laboratory tests are only of diagnostic value during the acute phase of the illness with the exception of serology. Tests for dengue virus-specific antibodies, types IgG and IgM, can be useful in confirming a diagnosis in the later stages of the infection. Both IgG and IgM are produced after 5–7 days. The highest levels (titres) of IgM are detected following a primary infection, but IgM is also produced in reinfection. IgM becomes undetectable 30–90 days after a primary infection, but earlier following re-infections. IgG, by contrast, remains detectable for over 60 years and, in the absence of symptoms, is a useful indicator of past infection. After a primary infection IgG reaches peak levels in the blood after 14–21 days. In subsequent re-infections, levels peak earlier and the titres are usually higher. Both IgG and IgM provide protective immunity to the infecting serotype of the virus. In testing for IgG and IgM antibodies there may be cross-reactivity with other flaviviruses which may result in a false positive after recent infections or vaccinations with yellow fever virus or Japanese encephalitis. The detection of IgG alone is not considered diagnostic unless blood samples are collected 14 days apart and a greater than fourfold increase in levels of specific IgG is detected. In a person with symptoms, the detection of IgM is considered diagnostic.
International Anti-Dengue Day is observed every year on June 15. The idea was first agreed upon in 2010 with the first event held in Jakarta, Indonesia in 2011. Further events were held in 2012 in Yangon, Myanmar and in 2013 in Vietnam. Goals are to increase public awareness about dengue, mobilize resources for its prevention and control and, to demonstrate the Asian region’s commitment in tackling the disease
There are no specific antiviral drugs for dengue, however maintaining proper fluid balance is important. Treatment depends on the symptoms. Those who are able to drink, are passing urine, have no "warning signs" and are otherwise healthy can be managed at home with daily follow up and oral rehydration therapy. Those who have other health problems, have "warning signs" or who cannot manage regular follow up should be cared for in hospital. In those with severe dengue care should be provided in an area where there is access to an intensive care unit.
Intravenous hydration, if required, is typically only needed for one or two days. In children with shock due to dengue a rapid dose of 20mL/kg is reasonable. The rate of fluid administration is than titrated to a urinary output of 0.5–1 mL/kg/h, stable vital signs and normalization of hematocrit. The smallest amount of fluid required to achieve this is recommended.
Invasive medical procedures such as nasogastric intubation, intramuscular injections and arterial punctures are avoided, in view of the bleeding risk. Paracetamol (acetaminophen) is used for fever and discomfort while NSAIDs such as ibuprofen and aspirin are avoided as they might aggravate the risk of bleeding. Blood transfusion is initiated early in people presenting with unstable vital signs in the face of a decreasing hematocrit, rather than waiting for the hemoglobin concentration to decrease to some predetermined "transfusion trigger" level. Packed red blood cells or whole blood are recommended, while platelets and fresh frozen plasma are usually not. There is not enough evidence to determine if corticosteroids have a positive or negative effect in dengue fever.
During the recovery phase intravenous fluids are discontinued to prevent a state of fluid overload. If fluid overload occurs and vital signs are stable, stopping further fluid may be all that is needed. If a person is outside of the critical phase, a loop diuretic such as furosemide may be used to eliminate excess fluid from the circulation.
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DNA-encoded chemical library -- robin hasan, 06:22:27 02/10/16 Wed 
DNA-encoded chemical libraries (DEL) is a technology for the synthesis and screening of collections of small molecule compounds of unprecedented size. DEL is used in medicinal chemistry to bridge the fields of combinatorial chemistry and molecular biology. The aim of DEL technology is to accelerate the drug discovery process and in particular early phase discovery activities such as target validation and hit identification.
DEL technology involves the conjugation of chemical compounds or building blocks to short DNA fragments that serve as identification bar codes and in some cases also direct and control the chemical synthesis. The technique enables the mass creation and interrogation of libraries via affinity selection, typically on an immobilized protein target. A homogeneous method for screening DNA-encoded libraries has recently been developed which uses water-in-oil emulsion technology to isolate, count and identify individual ligand-target complexes in a single-tube approach. In contrast to conventional screening procedures such as high-throughput screening, biochemical assays are not required for binder identification, in principle allowing the isolation of binders to a wide range of proteins historically difficult to tackle with conventional screening technologies. So, in addition to the general discovery of target specific molecular compounds, the availability of binders to pharmacologically important, but so-far “undruggable” target proteins opens new possibilities to develop novel drugs for diseases that could not be treated so far. In eliminating the requirement to initially assess the activity of hits it is hoped and expected that many of the high affinity binders identified will be shown to be active in independent analysis of selected hits, therefore offering an efficient method to identify high quality hits and pharmaceutical leads.
DNA-encoded chemical libraries and display technologies
Until recently, the application of molecular evolution in the laboratory had been limited to display technologies involving biological molecules, where small molecules lead discovery was considered beyond this biological approach. DEL has opened the field of display technology to include non-natural compounds such as small molecules, extending the application of molecular evolution and natural selection to the identification of small molecule compounds of desired activity and function. DNA encoded chemical libraries bear resemblance to biological display technologies such as antibody phage display technology, yeast display, mRNA display and aptamer SELEX. In antibody phage display, antibodies are physically linked to phage particles that bear the gene coding for the attached antibody, which is equivalent to a physical linkage of a “phenotype” (the protein) and a “genotype” (the gene encoding for the protein ). Phage-displayed antibodies can be isolated from large antibody libraries by mimicking molecular evolution: through rounds of selection (on an immobilized protein target), amplification and translation. In DEL the linkage of a small molecule to an identifier DNA code allows the facile identification of binding molecules. DEL libraries are subjected to affinity selection procedures on an immobilized target protein of choice, after which non-binders are removed by washing steps, and binders can subsequently be amplified by polymerase chain reaction (PCR) and identified by virtue of their DNA code (e.g.by DNA sequencing). In evolution-based DEL technologies (see below) hits can be further enriched by performing rounds of selection, PCR amplification and translation in analogy to biological display systems such as antibody phage display. This makes it possible to work with much larger libraries.
The concept of DNA-encoding was first described in a theoretical paper by Brenner and Lerner in 1992 in which was proposed to link each molecule of a chemically synthesized entity to a particular oligonucleotide sequence constructed in parallel and to use this encoding genetic tag to identify and enrich active compounds. In 1993 the first practical implementation of this approach was presented by S. Brenner and K. Janda and similarly by the group of M.A. Gallop. Brenner and Janda suggested to generate individual encoded library members by an alternating parallel combinatorial synthesis of the heteropolymeric chemical compound and the appropriate oligonucleotide sequence on the same bead in a “split-&-pool”-based fashion (see below).
Since unprotected DNA is restricted to a narrow window of conventional reaction conditions, until the end of the 1990s a number of alternative encoding strategies were envisaged (i.e. MS-based compound tagging, peptide encoding, haloaromatic tagging, encoding by secondary amines, semiconductor devices.), mainly to avoid inconvenient solid phase DNA synthesis and to create easily screenable combinatorial libraries in high-throughput fashion. However, the selective amplifiability of DNA greatly facilitates library screening and it becomes indispensable for the encoding of organic compounds libraries of this unprecedented size. Consequently, at the beginning of the 2000s DNA-combinatorial chemistry experienced a revival.
The beginning of the millennium saw the introduction of several independent developments in DEL technology. These technologies can be classified under two general categories: non-evolution-based and evolution-based DEL technologies capable of molecular evolution. The first category benefits from the ability to use off the shelf reagents and therefore enables rather straightforward library generation. Hits can be identified by DNA sequencing, however DNA translation and therefore molecular evolution is not feasible by these methods. The split and pool approaches developed by researchers at Praecis Pharmaceuticals (now owned by GlaxoSmithKline), Nuevolution (Copenhagen, Denmark) and ESAC technology developed in the laboratory of Prof D. Neri (Institute of Pharmaceutical Science, Zurich, Switzerland) fall under this category. ESAC technology sets itself apart being a combinatorial self-assembling approach which resembles fragment based hit discovery (Fig 1b). Here DNA annealing enables discrete building block combinations to be sampled, but no chemical reaction takes place between them. Examples of evolution-based DEL technologies are DNA-routing developed by Prof. D.R. Halpin and Prof. P.B. Harbury (Stanford University, Stanford, CA), DNA-templated synthesis developed by Prof. D. Liu (Harvard University, Cambridge, MA) and commercialized by Ensemble Therapeutics (Cambridge, MA) and YoctoReactor technology. developed and commercialized by Vipergen (Copenhagen, Denmark). These technologies are described in further detail below. DNA-templated synthesis and YoctoReactor technology require the prior conjugation of chemical building blocks (BB) to a DNA oligonucleotide tag before library assembly, therefore more upfront work is required before library assembly. Furthermore, the DNA tagged BBs enable the generation of a genetic code for synthesized compounds and artificial translation of the genetic code is possible: That is the BB’s can be recalled by the PCR-amplified genetic code, and the library compounds can be regenerated. This, in turn, enables the principle of Darwinian natural selection and evolution to be applied to small molecule selection in direct analogy to biological display systems; through rounds of selection, amplification and translation.
Non-evolution based technologies
Split-&-Pool DNA Encoding
In order to apply combinatorial chemistry for the synthesis of DNA-encoded chemical libraries, a Split-&-Pool approach was pursued. Initially a set of unique DNA-oligonucleotides (n) each containing a specific coding sequence is chemically conjugated to a corresponding set of small organic molecules.Consequently the oligonucleotide-conjugate compounds are mixed ("Pool") and divided ("Split") into a number of groups (m). In appropriate conditions a second set of building blocks (m) are coupled to the first one and a further oligonucleotide which is coding for the second modification is enzymatically introduced before mixing again. This “split-&-pool” steps can be iterated a number of times (r) increasing at each round the library size in a combinatorial manner (i.e. (n x m)r).
Stepwise coupling of coding DNA fragments to nascent organic molecules
A promising strategy for the construction of DNA-encoded libraries is represented by the use of multifunctional building blocks covalently conjugate to an oligonucleotide serving as a “core structure” for library synthesis. In a ‘pool-and-split’ fashion a set of multifunctional scaffolds undergo orthogonal reactions with series of suitable reactive partners. Following each reaction step, the identity of the modification is encoded by an enzymatic addition of DNA segment to the original DNA “core structure”. The use of N-protected amino acids covalently attached to a DNA fragment allow, after a suitable deprotection step, a further amide bond formation with a series of carboxylic acids or a reductive amination with aldehydes. Similarly, diene carboxylic acids used as scaffolds for library construction at the 5’-end of amino modified oligonucleotide, could be subjected to a Diels-Alder reaction with a variety of maleimide derivatives. After completion of the desired reaction step, the identity of the chemical moiety added to the oligonucleotide is established by the annealing of a partially complementary oligonucleotide and by a subsequent Klenow fill-in DNA-polymerization, yielding a double stranded DNA fragment. The synthetic and encoding strategies described above enable the facile construction of DNA-encoded libraries of a size up to 104 member compounds carrying two sets of “building blocks”. However the stepwise addition of at least three independent sets of chemical moieties to a tri-functional core building block for the construction and encoding of a very large DNA-encoded library (comprising up to 106 compounds) can also be envisaged
Encoded Self-Assembling Chemical (ESAC) libraries rely on the principle that two sublibraries of a size of x members (e.g. 103) containing a constant complementary hybridization domain can yield a combinatorial DNA-duplex library after hybridization with a complexity of x2 uniformly represented library members (e.g. 106). Each sub-library member would consist of an oligonucleotide containing a variable, coding region flanked by a constant DNA sequence, carrying a suitable chemical modification at the oligonucleotide extremity. The ESAC sublibraries can be used in at least four different embodiments.
A sub-library can be paired with a complementary oligonucleotide and used as a DNA encoded library displaying a single covalently linked compound for affinity-based selection experiments.
A sub-library can be paired with an oligonucleotide displaying a known binder to the target, thus enabling affinity maturation strategies.
Two individual sublibraries can be assembled combinatorially and used for the de novo identification of bindentate binding molecules.
Three different sublibraries can be assembled to form a combinatorial triplex library.
Preferential binders isolated from an affinity-based selection can be PCR-amplified and decoded on complementary oligonucleotide microarrays or by concatenation of the codes, subcloning and sequencing. The individual building blocks can eventually be conjugated using suitable linkers to yield a drug-like high-affinity compound. The characteristics of the linker (e.g. length, flexibility, geometry, chemical nature and solubility) influence the binding affinity and the chemical properties of the resulting binder.(Fig.3)
Bio-panning experiments on HSA of a 600-member ESAC library allowed the isolation of the 4-(p-iodophenyl)butanoic moiety. The compound represents the core structure of a series of portable albumin binding molecules and of AlbufluorTM a recently developed fluorescein angiographic contrast agent currently under clinical evaluation.
ESAC technology has been used for the isolation of potent inhibitors of bovine trypsin and for the identification of novel inhibitors of stromelysin-1 (MMP-3), a matrix metalloproteinase involved in both physiological and pathological tissue remodeling processes, as well as in disease processes, such as arthritis and metastasis.
In 2004, D.R. Halpin and P.B. Harbury presented a novel intriguing method for the construction of DNA-encoded libraries. For the first time the DNA-conjugated templates served for both encoding and programming the infrastructure of the “split-&-pool” synthesis of the library components. The design of Halpin and Harbury enabled alternating rounds of selection, PCR amplification and diversification with small organic molecules, in complete analogy to phage display technology. The DNA-routing machinery consists of a series of connected columns bearing resin-bound anticodons, which could sequence-specifically separate a population of DNA-templates into spatially distinct locations by hybridization. According to this split-and-pool protocol a peptide combinatorial library DNA-encoded of 106 members was generated.
In 2001 David Liu and co-workers showed that complementary DNA oligonucleotides can be used to assist certain synthetic reactions, which do not efficiently take place in solution at low concentration. A DNA-heteroduplex was used to accelerate the reaction between chemical moieties displayed at the extremities of the two DNA strands. Furthermore, the "proximity effect", which accelerates bimolecular reaction, was shown to be distance-independent (at least within a distance of 30 nucleotides). In a sequence-programmed fashion oligonucleotides carrying one chemical reactant group were hybridized to complementary oligonucleotide derivatives carrying a different reactive chemical group. The proximity conferred by the DNA hybridization drastically increases the effective molarity of the reaction reagents attached to the oligonucleotides, enabling the desired reaction to occur even in an aqueous environment at concentrations which are several orders of magnitude lower than those needed for the corresponding conventional organic reaction not DNA-templated. Using a DNA-templated set-up and sequence-programmed synthesis Liu and co-workers generated a 64 member compound DNA encoded library of macrocycles.
3-Dimensional proximity-based technology (YoctoReactor technology)
The YoctoReactor (yR) is a 3D proximity-driven approach which exploits the self-assembling nature of DNA oligonucleotides into 3, 4 or 5-way junctions to direct small molecule synthesis at the center of the junction. Figure 5 illustrates the basic concept with a 4-way DNA junction.
In summary, chemical building-blocks (BB) are attached via cleavable or non-cleavable linkers to three types of bispecific DNA oligonucleotides (oligo-BBs) representing each arm of the yR. To facilitate synthesis in a combinatorial manner, the oligo-BBs are designed such that the DNA contains (a) the code for an attached BB at the distal end of the oligo (colored lines) and (b) areas of constant DNA sequence (black lines) to bring about the self-assembly of the DNA into a 3-way junction (independently of the BB) and the subsequent chemical reaction. Chemical reactions are performed via a stepwise procedure and after each step the DNA is ligated and the product purified by polyacryamide gel electrophoresis. Cleavable linkers (BB-DNA) are used for all but one position yielding a library of small molecules with a single covalent link to the DNA code. Table 1 outlines how libraries of different sizes can be generated using yR technology.
Table 1. YoctoReactor library size. yR library size is a function of the number of different functionalized oligos used in each position and the number of positions in the DNA junction
The yR design approach provides an unvarying reaction site with regard to both (a) distance between reactants and (b) sequence environment surrounding the reaction site. Furthermore the intimate connection between the code and the BB on the oligo-BB moieties which are mixed combinatorially in a single pot confers a high fidelity to the encoding of the library. The code of the synthesized products, furthermore, is not preset, but rather is assembled combinatorially and synthesized in synchronicity with the innate product.
Homogeneous screening of yoctoreactor libraries
A homogeneous method for screening yoctoreactor libraries (yR) has recently been developed which uses water-in-oil emulsion technology to isolate individual ligand-target complexes. Called Binder Trap Enrichment (BTE), ligands to a protein target are identified by trapping binding pairs (DNA-labelled protein target and yR ligand) in emulsion droplets during dissociation dominated kinetics. Once trapped, the target and ligand DNA are joined by ligation, thus preserving the binding information.
Hereafter, identification of hits is essentially a counting exercise: information on binding events is deciphered by sequencing and counting the joined DNA - selective binders are counted with a much higher frequency than random binders. This is possible because random trapping of target and ligand is "diluted" by the high number of water droplets in the emulsion. The low noise and background signal characteristic of BTE is attributed to the "dilution" of the random signal, the lack of surface artifacts and the high fidelity of the yR library and screening method. Screening is performed in a single tube method. Biologically active hits are identified in a single round of BTE characterized by a low false positive rate.
BTE mimics the non-equilibrium nature of in vivo ligand-target interactions and offers the unique possibility to screen for target specific ligands based on ligand-target residence time because the emulsion, which traps the binding complex, is formed during a dynamic dissociation phase.
Following selection from DNA-encoded chemical libraries, the decoding strategy for the fast and efficient identification of the specific binding compounds is crucial for the further development of the DEL technology. So far, Sanger-sequencing-based decoding, microarray-based methodology and high-throughput sequencing techniques represented the main methodologies for the decoding of DNA-encoded library selections.
Sanger sequencing-based decoding
Although many authors implicitly envisaged a traditional Sanger sequencing-based decoding, the number of codes to sequence simply according to the complexity of the library is definitely an unrealistic task for a traditional Sanger sequencing approach. Nevertheless, the implementation of Sanger sequencing for decoding DNA-encoded chemical libraries in high-throughput fashion was the first to be described. After selection and PCR amplification of the DNA-tags of the library compounds, concatamers containing multiple coding sequences were generated and ligated into a vector. Following Sanger sequencing of a representative number of the resulting colonies revealed the frequencies of the codes present in the DNA-encoded library sample before and after selection.
A DNA microarray is a device for high-throughput investigations widely used in molecular biology and in medicine. It consists of an arrayed series of microscopic spots (‘features’ or ‘locations’) containing few picomoles of oligonucleotides carrying a specific DNA sequence. This can be a short section of a gene or other DNA element that are used as probes to hybridize a DNA or RNA sample under suitable conditions. Probe-target hybridization is usually detected and quantified by fluorescence-based detection of fluorophore-labeled targets to determine relative abundance of the target nucleic acid sequences. Microarray has been used for the successfully decoding of ESAC DNA-encoded libraries. The coding oligonucleotides representing the individual chemical compounds in the library, are spotted and chemically linked onto the microarray slides, using a BioChip Arrayer robot. Subsequently, the oligonucleotide tags of the binding compounds isolated from the selection are PCR amplified using a fluorescent primer and hybridized onto the DNA-microarray slide. Afterwards, microarrays are analyzed using a laser scan and spot intensities detected and quantified. The enrichment of the preferential binding compounds is revealed comparing the spots intensity of the DNA-microarray slide before and after selection.
Decoding by high throughput sequencing
According to the complexity of the DNA encoded chemical library (typically between 103 and 106 members), a conventional Sanger sequencing based decoding is unlikely to be usable in practice, due both to the high cost per base for the sequencing and to the tedious procedure involved. High throughput sequencing technologies exploited strategies that parallelize the sequencing process displacing the use of capillary electrophoresis and producing thousands or millions of sequences at once. In 2008 was described the first implementation of a high-throughput sequencing technique originally developed for genome sequencing (i.e. "454 technology") to the fast and efficient decoding of a DNA encoded chemical library comprising 4000 compounds. This study led to the identification of novel chemical compounds with submicromolar dissociation constants towards streptavidin and definitely shown the feasibility to construct, perform selections and decode DNA-encoded libraries containing millions of chemical compounds
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DNA -- robin hasan, 06:17:45 02/10/16 Wed 
Deoxyribonucleic acid (Listeni/diˈɒksiˌraɪboʊnjʊˌkliːɪk, -ˌkleɪɪk/; DNA) is a molecule that carries most of the genetic instructions used in the development, functioning and reproduction of all known living organisms and many viruses. DNA is a nucleic acid; alongside proteins and carbohydrates, nucleic acids compose the three major macromolecules essential for all known forms of life. Most DNA molecules consist of two biopolymer strands coiled around each other to form a double helix. The two DNA strands are known as polynucleotides since they are composed of simpler units called nucleotides. Each nucleotide is composed of a nitrogen-containing nucleobase—either cytosine (C), guanine (G), adenine (A), or thymine (T)—as well as a monosaccharide sugar called deoxyribose and a phosphate group. The nucleotides are joined to one another in a chain by covalent bonds between the sugar of one nucleotide and the phosphate of the next, resulting in an alternating sugar-phosphate backbone. According to base pairing rules (A with T, and C with G), hydrogen bonds bind the nitrogenous bases of the two separate polynucleotide strands to make double-stranded DNA. The total amount of related DNA base pairs on Earth is estimated at 5.0 x 1037, and weighs 50 billion tonnes. In comparison, the total mass of the biosphere has been estimated to be as much as 4 TtC (trillion tons of carbon).
DNA stores biological information. The DNA backbone is resistant to cleavage, and both strands of the double-stranded structure store the same biological information. Biological information is replicated as the two strands are separated. A significant portion of DNA (more than 98% for humans) is non-coding, meaning that these sections do not serve as patterns for protein sequences.
The two strands of DNA run in opposite directions to each other and are therefore anti-parallel. Attached to each sugar is one of four types of nucleobases (informally, bases). It is the sequence of these four nucleobases along the backbone that encodes biological information. Under the genetic code, RNA strands are translated to specify the sequence of amino acids within proteins. These RNA strands are initially created using DNA strands as a template in a process called transcription.
Within cells, DNA is organized into long structures called chromosomes. During cell division these chromosomes are duplicated in the process of DNA replication, providing each cell its own complete set of chromosomes. Eukaryotic organisms (animals, plants, fungi, and protists) store most of their DNA inside the cell nucleus and some of their DNA in organelles, such as mitochondria or chloroplasts. In contrast, prokaryotes (bacteria and archaea) store their DNA only in the cytoplasm. Within the chromosomes, chromatin proteins such as histones compact and organize DNA. These compact structures guide the interactions between DNA and other proteins, helping control which parts of the DNA are transcribed.
DNA was first isolated by Friedrich Miescher in 1869. Its molecular structure was identified by James Watson and Francis Crick in 1953, whose model-building efforts were guided by X-ray diffraction data acquired by Rosalind Franklin. DNA is used by researchers as a molecular tool to explore physical laws and theories, such as the ergodic theorem and the theory of elasticity. The unique material properties of DNA have made it an attractive molecule for material scientists and engineers interested in micro- and nano-fabrication. Among notable advances in this field are DNA origami and DNA-based hybrid materials.
DNA is a long polymer made from repeating units called nucleotides. DNA was first identified and isolated by Friedrich Miescher in 1869 at the University of Tübingen, a substance he called nuclein, and the double helix structure of DNA was first discovered in 1953 by Watson and Crick at the University of Cambridge, using experimental data collected by Rosalind Franklin and Maurice Wilkins. The structure of DNA is non-static, all species comprises two helical chains each coiled round the same axis, and each with a pitch of 34 ångströms (3.4 nanometres) and a radius of 10 ångströms (1.0 nanometre). According to another study, when measured in a particular solution, the DNA chain measured 22 to 26 ångströms wide (2.2 to 2.6 nanometres), and one nucleotide unit measured 3.3 Å (0.33 nm) long. Although each individual repeating unit is very small, DNA polymers can be very large molecules containing millions of nucleotides. For instance, the DNA in the largest human chromosome, chromosome number 1, consists of approximately 220 million base pairs and would be 85 mm long if straightened.
In living organisms DNA does not usually exist as a single molecule, but instead as a pair of molecules that are held tightly together. These two long strands entwine like vines, in the shape of a double helix. The nucleotide repeats contain both the segment of the backbone of the molecule, which holds the chain together, and a nucleobase, which interacts with the other DNA strand in the helix. A nucleobase linked to a sugar is called a nucleoside and a base linked to a sugar and one or more phosphate groups is called a nucleotide. A polymer comprising multiple linked nucleotides (as in DNA) is called a polynucleotide.
The backbone of the DNA strand is made from alternating phosphate and sugar residues. The sugar in DNA is 2-deoxyribose, which is a pentose (five-carbon) sugar. The sugars are joined together by phosphate groups that form phosphodiester bonds between the third and fifth carbon atoms of adjacent sugar rings. These asymmetric bonds mean a strand of DNA has a direction. In a double helix the direction of the nucleotides in one strand is opposite to their direction in the other strand: the strands are antiparallel. The asymmetric ends of DNA strands are called the 5′ (five prime) and 3′ (three prime) ends, with the 5′ end having a terminal phosphate group and the 3′ end a terminal hydroxyl group. One major difference between DNA and RNA is the sugar, with the 2-deoxyribose in DNA being replaced by the alternative pentose sugar ribose in RNA.
The DNA double helix is stabilized primarily by two forces: hydrogen bonds between nucleotides and base-stacking interactions among aromatic nucleobases. In the aqueous environment of the cell, the conjugated π bonds of nucleotide bases align perpendicular to the axis of the DNA molecule, minimizing their interaction with the solvation shell and therefore, the Gibbs free energy. The four bases found in DNA are adenine (abbreviated A), cytosine (C), guanine (G) and thymine (T). These four bases are attached to the sugar/phosphate to form the complete nucleotide, as shown for adenosine monophosphate. Adenine pairs with thymine and guanine pairs with cytosine. It was represented by A-T base pairs and G-C base pairs.
The nucleobases are classified into two types: the purines, A and G, being fused five- and six-membered heterocyclic compounds, and the pyrimidines, the six-membered rings C and T. A fifth pyrimidine nucleobase, uracil (U), usually takes the place of thymine in RNA and differs from thymine by lacking a methyl group on its ring. In addition to RNA and DNA a large number of artificial nucleic acid analogues have also been created to study the properties of nucleic acids, or for use in biotechnology.
Uracil is not usually found in DNA, occurring only as a breakdown product of cytosine. However, in a number of bacteriophages – Bacillus subtilis bacteriophages PBS1 and PBS2 and Yersinia bacteriophage piR1-37 – thymine has been replaced by uracil. Another phage - Staphylococcal phage S6 - has been identified with a genome where thymine has been replaced by uracil.
Base J (beta-d-glucopyranosyloxymethyluracil), a modified form of uracil, is also found in a number of organisms: the flagellates Diplonema and Euglena, and all the kinetoplastid genera. Biosynthesis of J occurs in two steps: in the first step a specific thymidine in DNA is converted into hydroxymethyldeoxyuridine; in the second HOMedU is glycosylated to form J. Proteins that bind specifically to this base have been identified. These proteins appear to be distant relatives of the Tet1 oncogene that is involved in the pathogenesis of acute myeloid leukemia. J appears to act as a termination signal for RNA polymerase II.
Twin helical strands form the DNA backbone. Another double helix may be found tracing the spaces, or grooves, between the strands. These voids are adjacent to the base pairs and may provide a binding site. As the strands are not symmetrically located with respect to each other, the grooves are unequally sized. One groove, the major groove, is 22 Å wide and the other, the minor groove, is 12 Å wide. The width of the major groove means that the edges of the bases are more accessible in the major groove than in the minor groove. As a result, proteins such as transcription factors that can bind to specific sequences in double-stranded DNA usually make contact with the sides of the bases exposed in the major groove. This situation varies in unusual conformations of DNA within the cell (see below), but the major and minor grooves are always named to reflect the differences in size that would be seen if the DNA is twisted back into the ordinary B form.
Further information: Base pair
In a DNA double helix, each type of nucleobase on one strand bonds with just one type of nucleobase on the other strand. This is called complementary base pairing. Here, purines form hydrogen bonds to pyrimidines, with adenine bonding only to thymine in two hydrogen bonds, and cytosine bonding only to guanine in three hydrogen bonds. This arrangement of two nucleotides binding together across the double helix is called a base pair. As hydrogen bonds are not covalent, they can be broken and rejoined relatively easily. The two strands of DNA in a double helix can therefore be pulled apart like a zipper, either by a mechanical force or high temperature. As a result of this complementarity, all the information in the double-stranded sequence of a DNA helix is duplicated on each strand, which is vital in DNA replication. Indeed, this reversible and specific interaction between complementary base pairs is critical for all the functions of DNA in living organisms.[
The two types of base pairs form different numbers of hydrogen bonds, AT forming two hydrogen bonds, and GC forming three hydrogen bonds (see figures, right). DNA with high GC-content is more stable than DNA with low GC-content.
As noted above, most DNA molecules are actually two polymer strands, bound together in a helical fashion by noncovalent bonds; this double stranded structure (dsDNA) is maintained largely by the intrastrand base stacking interactions, which are strongest for G,C stacks. The two strands can come apart – a process known as melting – to form two single-stranded DNA molecules (ssDNA) molecules. Melting occurs at high temperature, low salt and high pH (low pH also melts DNA, but since DNA is unstable due to acid depurination, low pH is rarely used).
The stability of the dsDNA form depends not only on the GC-content (% G,C basepairs) but also on sequence (since stacking is sequence specific) and also length (longer molecules are more stable). The stability can be measured in various ways; a common way is the "melting temperature", which is the temperature at which 50% of the ds molecules are converted to ss molecules; melting temperature is dependent on ionic strength and the concentration of DNA. As a result, it is both the percentage of GC base pairs and the overall length of a DNA double helix that determines the strength of the association between the two strands of DNA. Long DNA helices with a high GC-content have stronger-interacting strands, while short helices with high AT content have weaker-interacting strands. In biology, parts of the DNA double helix that need to separate easily, such as the TATAAT Pribnow box in some promoters, tend to have a high AT content, making the strands easier to pull apart.
In the laboratory, the strength of this interaction can be measured by finding the temperature necessary to break the hydrogen bonds, their melting temperature (also called Tm value). When all the base pairs in a DNA double helix melt, the strands separate and exist in solution as two entirely independent molecules. These single-stranded DNA molecules (ssDNA) have no single common shape, but some conformations are more stable than others.
Sense and antisense
Further information: Sense (molecular biology)
A DNA sequence is called "sense" if its sequence is the same as that of a messenger RNA copy that is translated into protein. The sequence on the opposite strand is called the "antisense" sequence. Both sense and antisense sequences can exist on different parts of the same strand of DNA (i.e. both strands can contain both sense and antisense sequences). In both prokaryotes and eukaryotes, antisense RNA sequences are produced, but the functions of these RNAs are not entirely clear. One proposal is that antisense RNAs are involved in regulating gene expression through RNA-RNA base pairing.
A few DNA sequences in prokaryotes and eukaryotes, and more in plasmids and viruses, blur the distinction between sense and antisense strands by having overlapping genes. In these cases, some DNA sequences do double duty, encoding one protein when read along one strand, and a second protein when read in the opposite direction along the other strand. In bacteria, this overlap may be involved in the regulation of gene transcription, while in viruses, overlapping genes increase the amount of information that can be encoded within the small viral genome.
Further information: DNA supercoil
DNA can be twisted like a rope in a process called DNA supercoiling. With DNA in its "relaxed" state, a strand usually circles the axis of the double helix once every 10.4 base pairs, but if the DNA is twisted the strands become more tightly or more loosely wound. If the DNA is twisted in the direction of the helix, this is positive supercoiling, and the bases are held more tightly together. If they are twisted in the opposite direction, this is negative supercoiling, and the bases come apart more easily. In nature, most DNA has slight negative supercoiling that is introduced by enzymes called topoisomerases. These enzymes are also needed to relieve the twisting stresses introduced into DNA strands during processes such as transcription and DNA replication.[
DNA exists in many possible conformations that include A-DNA, B-DNA, and Z-DNA forms, although, only B-DNA and Z-DNA have been directly observed in functional organisms. The conformation that DNA adopts depends on the hydration level, DNA sequence, the amount and direction of supercoiling, chemical modifications of the bases, the type and concentration of metal ions, as well as the presence of polyamines in solution.
The first published reports of A-DNA X-ray diffraction patterns—and also B-DNA—used analyses based on Patterson transforms that provided only a limited amount of structural information for oriented fibers of DNA. An alternate analysis was then proposed by Wilkins et al., in 1953, for the in vivo B-DNA X-ray diffraction/scattering patterns of highly hydrated DNA fibers in terms of squares of Bessel functions. In the same journal, James Watson and Francis Crick presented their molecular modeling analysis of the DNA X-ray diffraction patterns to suggest that the structure was a double-helix.
Although the "B-DNA form" is most common under the conditions found in cells, it is not a well-defined conformation but a family of related DNA conformations that occur at the high hydration levels present in living cells. Their corresponding X-ray diffraction and scattering patterns are characteristic of molecular paracrystals with a significant degree of disorder.
Compared to B-DNA, the A-DNA form is a wider right-handed spiral, with a shallow, wide minor groove and a narrower, deeper major groove. The A form occurs under non-physiological conditions in partially dehydrated samples of DNA, while in the cell it may be produced in hybrid pairings of DNA and RNA strands, as well as in enzyme-DNA complexes. Segments of DNA where the bases have been chemically modified by methylation may undergo a larger change in conformation and adopt the Z form. Here, the strands turn about the helical axis in a left-handed spiral, the opposite of the more common B form. These unusual structures can be recognized by specific Z-DNA binding proteins and may be involved in the regulation of transcription.
Alternative DNA chemistry
For a number of years exobiologists have proposed the existence of a shadow biosphere, a postulated microbial biosphere of Earth that uses radically different biochemical and molecular processes than currently known life. One of the proposals was the existence of lifeforms that use arsenic instead of phosphorus in DNA. A report in 2010 of the possibility in the bacterium GFAJ-1, was announced, though the research was disputed, and evidence suggests the bacterium actively prevents the incorporation of arsenic into the DNA backbone and other biomolecules.
Further information: G-quadruplex
At the ends of the linear chromosomes are specialized regions of DNA called telomeres. The main function of these regions is to allow the cell to replicate chromosome ends using the enzyme telomerase, as the enzymes that normally replicate DNA cannot copy the extreme 3′ ends of chromosomes. These specialized chromosome caps also help protect the DNA ends, and stop the DNA repair systems in the cell from treating them as damage to be corrected. In human cells, telomeres are usually lengths of single-stranded DNA containing several thousand repeats of a simple TTAGGG sequence
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Dragon Ball -- robin hasan, 06:14:00 02/10/16 Wed 
Dragon Ball (Japanese: ドラゴンボール Hepburn: Doragon Bōru?) is a Japanese manga series written and illustrated by Akira Toriyama. It was originally serialized in Weekly Shōnen Jump from 1984 to 1995, with the 519 individual chapters published into 42 tankōbon volumes by Shueisha. Dragon Ball was initially inspired by the classical Chinese novel Journey to the West. The series follows the adventures of the protagonist, Goku, from his childhood through adulthood as he trains in martial arts and explores the world in search of the seven orbs known as the Dragon Balls, which summon a wish-granting dragon when gathered. Along his journey, Goku makes several friends and battles a wide variety of villains, many of whom also seek the Dragon Balls.
The 42 tankōbon have been adapted into two anime series produced by Toei Animation: Dragon Ball and Dragon Ball Z, which together were broadcast in Japan from 1986 to 1996. Additionally, the studio has developed nineteen animated feature films and three television specials, as well as a third anime titled Dragon Ball GT. Between 2009 and 2015, a revised, faster-paced version of Dragon Ball Z was broadcast under the title Dragon Ball Kai, in which most of the original version's footage not featured in the manga is removed. A fifth television series titled Dragon Ball Super began on July 5, 2015. Several companies have developed various types of merchandising based on the series leading to a large media franchise that includes films, both animated and live-action, collectible trading card games, numerous action figures, along with several collections of soundtracks and a large number of video games.
The manga series was licensed for an English-language release in North America by Viz Media, in the United Kingdom by Gollancz Manga, and Australia and New Zealand by Madman Entertainment. The entire anime series was licensed by Funimation Entertainment for an English-language release in the United States, although the series has not always been dubbed by the same studio. There have been many films of the franchise including the first live-action film adaptation being produced in 1989 in Taiwan. In 2002, 20th Century Fox acquired the rights to produce an American-made live-action film titled Dragonball Evolution that was received negatively by critics and fans; the movie was released on April 10, 2009 in the United States.
Since its release, Dragon Ball has become one of the most successful manga and anime series of all time. The manga's 42 volumes have sold over 156 million copies in Japan and more than 230 million copies worldwide, making it the second best-selling manga series in history. Reviewers have praised the art, characterization, and humor of the story. It is widely regarded as one of the greatest manga series ever made, with many manga artists such as Eiichiro Oda (One Piece), Masashi Kishimoto (Naruto), Tite Kubo (Bleach), Hiro Mashima (Rave Master, Fairy Tail) and Kentaro Yabuki (Black Cat) citing Dragon Ball as a source of inspiration for their own now popular works. The anime, particularly Dragon Ball Z, is also highly popular in various countries and was arguably one of the most influential in boosting the popularity of Japanese animation in Western culture.
See also: List of Dragon Ball characters
The series begins with a monkey-tailed boy named Goku befriending a teenage girl named Bulma, whom he accompanies to find the seven Dragon Balls (ドラゴンボール Doragon Bōru?), which summon the dragon Shenlong to grant the user one wish. The journey leads them to the desert bandit Yamcha, who later becomes an ally; Chi-Chi, whom Goku unknowingly agrees to marry; and Pilaf, an impish man who seeks the Dragon Balls to fulfill his desire to rule the world. Goku then undergoes rigorous training regimes under the martial arts master Kame-Sen'nin in order to fight in the Tenkaichi Budōkai (天下一武道会?, "Strongest Under the Heavens Martial Arts Tournament"). A monk named Kuririn becomes his training partner and rival, but they soon become best friends. After the tournament, Goku searches for the Dragon Ball his grandfather left him and almost single-handedly defeats the Red Ribbon Army and their hired assassin Taopaipai. Thereafter Goku reunites with his friends to defeat the fortuneteller Baba Uranai's fighters and have her locate the last Dragon Ball to revive a friend killed by Taopaipai.
At the Tenkaichi Budōkai three years later Goku and his allies oppose Kame-Sen'nin's rival and Taopaipai's brother, Tsuru-Sen'nin, and his students Tenshinhan and Chaozu. Kuririn is killed after the tournament and Goku tracks down and is defeated by his killer, Piccolo Daimao. The samurai Yajirobe takes Goku to the hermit Karin, where he receives healing and a power boost. Meanwhile, Piccolo fights Kame-Sen'nin and Chaozu, leading to both their deaths, and uses the Dragon Balls to regain his youth before destroying Shenlong. Goku then kills Piccolo Daimao, who, just before dying, spawns his son/reincarnation Piccolo. Karin then directs Goku to Kami-sama, the original creator of the Dragon Balls, to restore Shenlong and revive his slain friends. Goku trains under Kami for the next three years, once again reuniting with his friends at the Tenkaichi Budōkai, where he narrowly wins against Piccolo before leaving with Chi-Chi to keep his promise to marry her.
Five years later, Goku is a young adult and father to his son Gohan, when Raditz arrives on Earth, identifies Goku as his younger brother 'Kakarrot' and reveals to him that they are members of a nearly extinct extraterrestrial race called the Saiyans (サイヤ人 Saiya-jin?), who sent Goku to conquer Earth for them, until he suffered a severe head injury and lost all memory of his mission. Goku refuses to continue the mission, sides with Piccolo, and sacrifices his life to defeat Raditz. In the afterlife Goku trains under the North Kaiō until he is revived by the Dragon Balls to save the Earth from the invading Nappa and Vegeta. In the battle Yamcha, Chaozu, Tenshinhan, and Piccolo are killed, and the Dragon Balls cease to exist. Kuririn and the galactic tyrant Freeza learn of another set of Dragon Balls on planet Namek (ナメック星 Namekku-sei?), whereupon Bulma, Gohan, and Kuririn search for them to revive their friends and subsequently the Earth's Dragon Balls, leading to several battles with Freeza's minions and Vegeta, the latter standing alongside the heroes to fight the Ginyu Force, a team of mercenaries. The long battle with Freeza himself comes to a close when Goku transforms into a Super Saiyan (超サイヤ人 Sūpā Saiya-jin?) of legends and defeats him.
A group of Androids (人造人間 Jinzōningen?, "Artificial Humans") created by a member of the former Red Ribbon Army, Doctor Gero, appear three years later, seeking revenge against Goku. During this time, an evil life form called Cell also emerges and, after absorbing two of the Androids to achieve his "perfect form," holds his own fighting tournament to challenge the protagonists. After Goku sacrifices his own life to no avail, Gohan avenges his father by defeating Cell. Seven years later, Goku, briefly revived for one day, and his allies are drawn into a fight against Majin Boo. After numerous battles, including destruction and re-creation of the Earth, Goku destroys Boo with a Genki-Dama (a sphere of pure energy drawn from all intelligent beings on Earth) and wishes for him to be reincarnated as a "good person." Ten years later, at another Tenkaichi Budōkai, Goku meets Boo's human reincarnation, Oob. Leaving their match unfinished, Goku departs with Oob to train him to be Earth's new guardian.
Akira Toriyama loosely modeled Dragon Ball on the classic Chinese novel Journey to the West; but also redeveloped it from his 1983 one-shot manga Dragon Boy. He has said that the fighting was influenced from movies by famous martial arts actor Jackie Chan, as he wanted to create a story with the basic theme of Journey to the West, but with "a little kung fu." Since it was serialized in a shōnen magazine, he added the idea of the Dragon Balls to give it a game-like activity of gathering something, without thinking of what the characters would wish for. With Goku being Sun Wukong, Bulma as Xuanzang, Oolong as Zhu Bajie and Yamcha being Sha Wujing, he originally thought it would last about a year or end once the Dragon Balls were collected. Toriyama stated that although the stories are purposefully easy to understand, he specifically aimed Dragon Ball at readers older than those of his previous serial Dr. Slump. He also wanted to break from the Western influences common in Dr. Slump, deliberately going for Chinese scenery, referencing Chinese buildings and photographs of China his wife had bought. The island where the Tenkaichi Budōkai (天下一武道会?, "Strongest Under the Heavens Martial Arts Tournament", renamed "World Martial Arts Tournament" in Funimation's dub) is held is modeled after Bali, which he, his wife and assistant visited in mid-1985, and for the area around Bobbidi's spaceship he consulted photos of Africa.
It was when the Tenkaichi Budōkai martial arts tournament began that Dragon Ball truly became popular, having recalled the races and tournaments in Dr. Slump. Anticipating that readers would expect Goku to win the tournaments, Toriyama had him lose the first two while planning an eventual victory. He said that Muscle Tower in the Red Ribbon Army storyline was inspired by the video game Spartan X, in which enemies tended to appear very fast. He then created Piccolo Daimao as a truly evil villain, and as a result called that arc the most interesting to draw. Once Goku and company had become the strongest on Earth, they turned to extraterrestrial opponents including the Saiyans. Freeza, who forcibly took over planets to resell them, was created around the time of the Japanese economic bubble and was inspired by real estate speculators, whom Toriyama called the "worst kind of people." Finding the escalating enemies difficult, he created the Ginyu Force to add more balance to the series. He added time travel next, but said he had a hard time with it, only thinking of what to do that week and having to discuss it with his second editor Yu Kondo. After Cell's death, Toriyama intended for Gohan to replace Goku as the series' protagonist, but felt the character was not suited for the role and changed his mind
Written and illustrated by Akira Toriyama, Dragon Ball was serialized in the manga anthology Weekly Shōnen Jump from November 20, 1984 to May 23, 1995, when Toriyama grew exhausted and felt he needed a break from drawing. The 519 individual chapters were published into 42 tankōbon volumes by Shueisha from September 10, 1985 through August 4, 1995. In 2002, the chapters were re-released in a collection of 34 kanzenban volumes, which included a slightly rewritten ending, new covers, and color artwork from its Weekly Shōnen Jump run. The February 2013 issue of V Jump, which was released in December 2012, announced that parts of the manga will be fully colored and re-released in 2013. Twenty volumes, beginning from chapter 195 and grouped by story arcs, were released between February 4, 2013 and July 4, 2014.
The Dragon Ball manga is licensed for release in English in North America by Viz Media. Viz originally released volumes 17 through 42 (chapters 195 through 519) under the title "Dragon Ball Z" to mimic the name of the anime series adapted from those volumes, feeling it would reduce the potential for confusion by its readers. They initially released both series chapter by chapter in a monthly comic book format starting in 1998, and later began collecting them in graphic novels in 2000. In 2000, while releasing Dragon Ball in the monthly format, Viz began to censor the series in response to complaints by parents. They argued that when there are parental complaints, major chain stores stop selling the series, so to keep wide distribution, they made some "concessions". They assured that all changes were done with approval by Toriyama and Shueisha, with Toriyama making suggestions himself: such as to obscure Goku's genitals with objects, rather than "neuter him". A fan petition that garnered over 10,000 signatures was created, and a year later, Viz announced they would stop censoring the series and instead increased its "rating" to 13 and up, and reprinted the first 3 graphic novels.
"Dragon Ball Z", from Trunk's appearance to chapter 226, was published in Viz's monthly magazine Shonen Jump from its debut issue in January 2003 to April 2005. Later, the first ten collected volumes of both series were re-released from March to May 2003 under their "Shonen Jump" imprint, with Dragon Ball being completed on August 3, 2004 and Dragon Ball Z finishing on June 6, 2006. However, when releasing the last few volumes of Dragon Ball Z, the company began to censor the series again; translating the sound effects of gunshots to "zap" and changing the few sexual references. In June 2008, Viz began re-releasing the two series in a wideban format called "Viz Big Edition," which collects three individual volumes into a single large volume. These editions are on higher quality paper and include some of the original Weekly Shōnen Jump color pages, however, they include new censorship not in the 2003 releases. On November 3, 2008, the first volumes of both series were released in hardcover "Collector's Editions." Viz began releasing new 3-in-1 volumes of Dragon Ball, similar to their "Viz Big Edition", with volume one released on June 4, 2013. This version uses the Japanese kanzenban covers and marks the first time in English that the entire series is being released under the Dragon Ball name. They serialized chapter 195 to 245 of the fully colored version of the manga in their digital anthology Weekly Shonen Jump from February 2013 to February 2014. They began publishing Dragon Ball Full Color Edition into large printed volumes on February 4, 2014.
The manga has also been licensed in other English-speaking countries, distributed in the same Viz format of separating it into Dragon Ball and Dragon Ball Z. The United Kingdom's release of the manga has been through different distributors. From August 2005 to November 2007, Gollancz Manga an imprint of the Orion Publishing Group released the 16 volumes of Dragon Ball and the first 4 of Dragon Ball Z. Viz would release the books after Gollancz and expand to digital sales on the Nook in August 2013. In Australia and New Zealand, Madman Entertainment has released all 16 volumes of the Dragon Ball manga and the 9 "Viz Big" volumes of Dragon Ball Z.
Spin-offs and crossovers
Toriyama also created a short series, Neko Majin, that became a self-parody of Dragon Ball. First appearing in August 1999, the eight chapter series was released sporadically in Weekly Shōnen Jump and Monthly Shōnen Jump until it was completed in 2005. These chapters were compiled into one kanzenban volume for release on April 4, 2005. In 2006, in celebration of the 30th anniversary of Kochira Katsushika-ku Kameari Kōen-mae Hashutsujo (or Kochikame), a special manga titled Super Kochikame (超こち亀 Chō Kochikame?) was released on September 15. It included characters from the series appearing in special crossover chapters of other well-known manga. The chapter "This is the Police Station in front of Dragon Park on Planet Namek" (こちらナメック星ドラゴン公園前派出所 Kochira Namekku-sei Dragon Kōen-mae Hashutsujo?) was a Dragon Ball crossover by Toriyama and Kochikame author Osamu Akimoto. That same year, Toriyama teamed up with Eiichiro Oda to create a single crossover chapter of Dragon Ball and One Piece. Entitled Cross Epoch, the chapter was published in the December 25, 2006 issue of Weekly Shōnen Jump and the April 2011 issue of English Shonen Jump. The final chapter of Toriyama's 2013 manga series Jaco the Galactic Patrolman revealed that it is set before Dragon Ball, with several characters making appearances. Jaco's collected volumes contain a bonus Dragon Ball chapter depicting Goku's mother. Jaco and the bonus chapter were both published in Viz's digital English Weekly Shonen Jump.
A colored spin-off manga titled Dragon Ball SD and written by Naho Ōishi has been published in Shueisha's Saikyō Jump magazine since its debut issue released in December 2010. The manga is a condensed retelling of Goku's various adventures as a child, with many details changed, in a super deformed art style, hence the title. It has been collected into three volumes, with the first being released on April 4, 2013, the second on April 4, 2014, and the third on December 4, 2014.
Dragon Ball: Episode of Bardock is a three-chapter manga, once again penned by Naho Ōishi, that was published in the monthly magazine V Jump from August and October 2011. This manga is a sequel to the 1990 TV special Bardock – The Father of Goku with some key details changed. As the title indicates the manga's story revolves around Bardock, Goku's father, who in this special is featured in a scenario in which he did not die at the hands of Freeza and gets to fight his enemy as a Super Saiyan.
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Daylight saving time -- robin hasan, 06:10:38 02/10/16 Wed 
Daylight saving time (DST) or summer time is the practice of advancing clocks during summer months by one hour so that in the evening daylight is experienced an hour longer, while sacrificing normal sunrise times. Typically, regions with summer time adjust clocks forward one hour close to the start of spring and adjust them backward in the autumn to standard time.
New Zealander George Hudson proposed the modern idea of daylight saving in 1895. Germany and Austria-Hungary organized the first nationwide implementation, starting on 30 April 1916. Many countries have used it at various times since then, particularly since the energy crisis of the 1970s.
The practice has received both advocacy and criticism. Putting clocks forward benefits retailing, sports, and other activities that exploit sunlight after working hours, but can cause problems for evening entertainment and for other activities tied to sunlight, such as farming. Although some early proponents of DST aimed to reduce evening use of incandescent lighting, which used to be a primary use of electricity, modern heating and cooling usage patterns differ greatly and research about how DST affects energy use is limited or contradictory.
DST clock shifts sometimes complicate timekeeping and can disrupt travel, billing, record keeping, medical devices, heavy equipment, and sleep patterns. Computer software can often adjust clocks automatically, but policy changes by various jurisdictions of the dates and timings of DST may be confusing
Industrialized societies generally follow a clock-based schedule for daily activities that do not change throughout the course of the year. The time of day that individuals begin and end work or school, and the coordination of mass transit, for example, usually remain constant year-round. In contrast, an agrarian society's daily routines for work and personal conduct are more likely governed by the length of daylight hours and by solar time, which change seasonally because of the Earth's axial tilt. North and south of the tropics daylight lasts longer in summer and shorter in winter, the effect becoming greater as one moves away from the tropics.
By synchronously resetting all clocks in a region to one hour ahead of Standard Time (one hour "fast"), individuals who follow such a year-round schedule will wake an hour earlier than they would have otherwise; they will begin and complete daily work routines an hour earlier, and they will have available to them an extra hour of daylight after their workday activities. However, they will have one less hour of daylight at the start of each day, making the policy less practical during winter.
While the times of sunrise and sunset change at roughly equal rates as the seasons change, proponents of Daylight Saving Time argue that most people prefer a greater increase in daylight hours after the typical "nine-to-five" workday. Supporters have also argued that DST decreases energy consumption by reducing the need for lighting and heating, but the actual effect on overall energy use is heavily disputed.
The manipulation of time at higher latitudes (for example Iceland, Nunavut or Alaska) has little impact on daily life, because the length of day and night changes more extremely throughout the seasons (in comparison to other latitudes), and thus sunrise and sunset times are significantly out of sync with standard working hours regardless of manipulations of the clock. DST is also of little use for locations near the equator, because these regions see only a small variation in daylight in the course of the year.
Daylight saving has caused controversy since it began. Winston Churchill argued that it enlarges "the opportunities for the pursuit of health and happiness among the millions of people who live in this country" and pundits have dubbed it "Daylight Slaving Time". Historically, retailing, sports, and tourism interests have favored daylight saving, while agricultural and evening entertainment interests have opposed it, and its initial adoption had been prompted by energy crisis and war.
The fate of Willett's 1907 proposal illustrates several political issues involved. The proposal attracted many supporters, including Balfour, Churchill, Lloyd George, MacDonald, Edward VII (who used half-hour DST at Sandringham), the managing director of Harrods, and the manager of the National Bank. However, the opposition was stronger: it included Prime Minister H. H. Asquith, Christie (the Astronomer Royal), George Darwin, Napier Shaw (director of the Meteorological Office), many agricultural organizations, and theater owners. After many hearings the proposal was narrowly defeated in a Parliament committee vote in 1909. Willett's allies introduced similar bills every year from 1911 through 1914, to no avail. The US was even more skeptical: Andrew Peters introduced a DST bill to the US House of Representatives in May 1909, but it soon died in committee.
After Germany led the way with starting DST (German: Sommerzeit) during World War I on 30 April 1916 together with its allies to alleviate hardships from wartime coal shortages and air raid blackouts, the political equation changed in other countries; the United Kingdom used DST first on 21 May 1916. US retailing and manufacturing interests led by Pittsburgh industrialist Robert Garland soon began lobbying for DST, but were opposed by railroads. The US's 1917 entry to the war overcame objections, and DST was established in 1918.
The war's end swung the pendulum back. Farmers continued to dislike DST, and many countries repealed it after the war. Britain was an exception: it retained DST nationwide but over the years adjusted transition dates for several reasons, including special rules during the 1920s and 1930s to avoid clock shifts on Easter mornings. The US was more typical: Congress repealed DST after 1919. President Woodrow Wilson, like Willett an avid golfer, vetoed the repeal twice but his second veto was overridden. Only a few US cities retained DST locally thereafter, including New York so that its financial exchanges could maintain an hour of arbitrage trading with London, and Chicago and Cleveland to keep pace with New York. Wilson's successor Warren G. Harding opposed DST as a "deception". Reasoning that people should instead get up and go to work earlier in the summer, he ordered District of Columbia federal employees to start work at 08:00 rather than 09:00 during summer 1922. Some businesses followed suit though many others did not; the experiment was not repeated.
Since Germany's adoption in 1916 the world has seen many enactments, adjustments, and repeals of DST, with similar politics involved.
The history of time in the United States includes DST during both world wars, but no standardization of peacetime DST until 1966. In May 1965, for two weeks, St. Paul, Minnesota and Minneapolis, Minnesota were on different times, when the capital city decided to join most of the nation by starting Daylight Saving Time while Minneapolis opted to follow the later date set by state law. In the mid-1980s, Clorox (parent of Kingsford Charcoal) and 7-Eleven provided the primary funding for the Daylight Saving Time Coalition behind the 1987 extension to US DST, and both Idaho senators voted for it based on the premise that during DST fast-food restaurants sell more French fries, which are made from Idaho potatoes.
In 1992 after a three-year trial of daylight saving in Queensland, Australia, a referendum on daylight saving was held and defeated with a 54.5% 'no' vote – with regional and rural areas strongly opposed, while those in the metropolitan south-east were in favor. In 2005, the Sporting Goods Manufacturers Association and the National Association of Convenience Stores successfully lobbied for the 2007 extension to US DST. In December 2008, the Daylight Saving for South East Queensland (DS4SEQ) political party was officially registered in Queensland, advocating the implementation of a dual-time zone arrangement for Daylight Saving in South East Queensland while the rest of the state maintains standard time. DS4SEQ contested the March 2009 Queensland State election with 32 candidates and received one percent of the statewide primary vote, equating to around 2.5% across the 32 electorates contested. After a three-year trial, more than 55% of Western Australians voted against DST in 2009, with rural areas strongly opposed. On 14 April 2010, after being approached by the DS4SEQ political party, Queensland Independent member Peter Wellington, introduced the Daylight Saving for South East Queensland Referendum Bill 2010 into Queensland Parliament, calling for a referendum to be held at the next State election on the introduction of daylight saving into South East Queensland under a dual-time zone arrangement. The Bill was defeated in Queensland Parliament on 15 June 2011.
In the UK the Royal Society for the Prevention of Accidents supports a proposal to observe SDST's additional hour year-round, but is opposed in some industries, such as postal workers and farmers, and particularly by those living in the northern regions of the UK.
In some Muslim countries DST is temporarily abandoned during Ramadan (the month when no food should be eaten between sunrise and sunset), since the DST would delay the evening dinner. Ramadan took place in July and August in 2012. This concerns at least Morocco and Palestine, although Iran keeps DST during Ramadan. Most Muslim countries do not use DST, partially for this reason.
The 2011 declaration by Russia that it would not turn its clocks back and stay in DST all year long was subsequently followed by a similar declaration from Belarus. The plan generated widespread complaints due to the dark of wintertime morning, and thus was abandoned in 2014. The country changed its clocks to Standard Time on 26 October 2014 - and intends to stay there permanently.
In 1975 the US DOT conservatively identified a 0.7% reduction in traffic fatalities during DST, and estimated the real reduction at 1.5% to 2%, but the 1976 NBS review of the DOT study found no differences in traffic fatalities. In 1995 the Insurance Institute for Highway Safety estimated a reduction of 1.2%, including a 5% reduction in crashes fatal to pedestrians. Others have found similar reductions. Single/Double Summer Time (SDST), a variant where clocks are one hour ahead of the sun in winter and two in summer, has been projected to reduce traffic fatalities by 3% to 4% in the UK, compared to ordinary DST. However, accidents do increase by as much as 11% during the two weeks that follow the end of British Summer Time. It is not clear whether sleep disruption contributes to fatal accidents immediately after the spring clock shifts. A correlation between clock shifts and traffic accidents has been observed in North America and the UK but not in Finland or Sweden. If this effect exists, it is far smaller than the overall reduction in traffic fatalities. A 2009 US study found that on Mondays after the switch to DST, workers sleep an average of 40 minutes less, and are injured at work more often and more severely.
In the 1970s the US Law Enforcement Assistance Administration (LEAA) found a reduction of 10% to 13% in Washington, D.C.'s violent crime rate during DST. However, the LEAA did not filter out other factors, and it examined only two cities and found crime reductions only in one and only in some crime categories; the DOT decided it was "impossible to conclude with any confidence that comparable benefits would be found nationwide". Outdoor lighting has a marginal and sometimes even contradictory influence on crime and fear of crime.
In several countries, fire safety officials encourage citizens to use the two annual clock shifts as reminders to replace batteries in smoke and carbon monoxide detectors, particularly in autumn, just before the heating and candle season causes an increase in home fires. Similar twice-yearly tasks include reviewing and practicing fire escape and family disaster plans, inspecting vehicle lights, checking storage areas for hazardous materials, reprogramming thermostats, and seasonal vaccinations. Locations without DST can instead use the first days of spring and autumn as reminders.
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Michael Jackson -- Hasanur Rahman, 06:58:00 02/09/16 Tue 
Michael Joseph Jackson (August 29, 1958 – June 25, 2009) was an American singer, songwriter, record producer, dancer, and actor. Called the King of Pop, his contributions to music and dance, along with his publicized personal life, made him a global figure in popular culture for over four decades.
The eighth child of the Jackson family, he debuted on the professional music scene along with his elder brothers Jackie, Tito, Jermaine, and Marlon as a member of the Jackson 5 in 1964, and began his solo career in 1971. In the early 1980s, Jackson became a dominant figure in popular music. The music videos for his songs, including those of "Beat It", "Billie Jean", and "Thriller" from his 1982 album Thriller, were credited with breaking down racial barriers and with transforming the medium into an art form and promotional tool. The popularity of these videos helped to bring the then-relatively-new television channel MTV to fame. His 1987 album Bad spawned the U.S. Billboard Hot 100 number-one singles "I Just Can't Stop Loving You", "Bad", "The Way You Make Me Feel", "Man in the Mirror", and "Dirty Diana", becoming the first album to have five number-one singles on the Billboard Hot 100. With videos such as "Black or White" and "Scream", he continued to innovate the medium throughout the 1990s, as well as forging a reputation as a touring solo artist. Through stage and video performances, Jackson popularized a number of complicated dance techniques, such as the robot and the moonwalk, to which he gave the name. His distinctive sound and style has influenced numerous artists of various music genres.
Thriller is the best-selling album of all time, with estimated sales of 65 million copies worldwide. His other albums, including Off the Wall (1979), Bad (1987), Dangerous (1991), and HIStory (1995), also rank among the world's best-selling albums. Jackson is one of the few artists to have been inducted into the Rock and Roll Hall of Fame twice. He was also inducted into the Songwriters Hall of Fame and the Dance Hall of Fame as the first and only dancer from pop and rock music. His other achievements include multiple Guinness World Records, 13 Grammy Awards, the Grammy Legend Award, the Grammy Lifetime Achievement Award, 26 American Music Awards—more than any other artist—including the "Artist of the Century" and "Artist of the 1980s", 13 number-one singles in the United States during his solo career,—more than any other male artist in the Hot 100 era—and estimated sales of over 400 million records worldwide.[Note 1] Jackson has won hundreds of awards, making him the most awarded recording artist in the history of popular music. He became the first artist in history to have a top ten single in the Billboard Hot 100 in five different decades when "Love Never Felt So Good" reached number nine on May 21, 2014. Jackson traveled the world attending events honoring his humanitarianism, and, in 2000, the Guinness World Records recognized him for supporting 39 charities, more than any other entertainer.
1958–75: Early life and the Jackson 5
The single-storey house has white walls, two windows, a central white door with a black door frame, and a black roof. In front of the house there is a walk way and multiple colored flowers and memorabilia.
Jackson's childhood home in Gary, Indiana, showing floral tributes after his death.
Michael Joseph Jackson was born on August 29, 1958. He was the eighth of ten children in an African-American working-class family who lived in a two-bedroom house on Jackson Street in Gary, Indiana, an industrial city and a part of the Chicago metropolitan area. His mother, Katherine Esther Scruse, was a devout Jehovah's Witness. She once aspired to be a country-and-western performer who played clarinet and piano, but worked part-time at Sears to help support the family. His father, Joseph Walter "Joe" Jackson, a former boxer, was a steelworker at U.S. Steel. Joe also performed on guitar with a local rhythm and blues band called the Falcons to supplement the family's household income. Michael grew up with three sisters (Rebbie, La Toya, and Janet) and five brothers (Jackie, Tito, Jermaine, Marlon, and Randy). A sixth brother, Marlon's elder twin Brandon, died shortly after birth.
Jackson had a troubled relationship with his father, Joe. In 2003, Joe acknowledged that he regularly whipped Jackson as a boy. Joe was also said to have verbally abused his son, often saying that he had a "fat nose". Jackson stated that he was physically and emotionally abused during incessant rehearsals, though he credited his father's strict discipline with playing a large role in his success. Speaking openly about his childhood in an interview with Oprah Winfrey, broadcast in February 1993, Jackson acknowledged that his youth had been lonely and isolating. Jackson's deep dissatisfaction with his appearance, his nightmares and chronic sleep problems, his tendency to remain hyper-compliant, especially with his father, and to remain childlike throughout his adult life, are consistent with the effects of the maltreatment he endured as a young child.
In an interview with Martin Bashir, later included in the 2003 broadcast of Living with Michael Jackson, Jackson acknowledged that his father hurt him when he was a child, recalling that Joseph often sat in a chair with a belt in his hand as he and his siblings rehearsed, and that "if you didn't do it the right way, he would tear you up, really get you." Both of Jackson's parents have disagreed with the longstanding allegations of abuse, with Katherine stating that while the whippings are considered abuse today, such action was a common way to discipline children back then. Jackie, Tito, Jermaine and Marlon have also said that their father is not abusive, but rather misunderstood.
The Jackson 5 recorded several songs, including "Big Boy" (1968), their first single, for Steeltown Records, a Gary, Indiana, record label, before signing with Motown in 1969. The Jackson 5 left Gary in 1969 and relocated to the Los Angeles area, where they continued to record music for Motown. The magazine Rolling Stone later described the young Michael as "a prodigy" with "overwhelming musical gifts," writing that he "quickly emerged as the main draw and lead singer." The group set a chart record when its first four singles—"I Want You Back" (1969), "ABC" (1970), "The Love You Save" (1970), and "I'll Be There" (1970)—peaked at number one on the Billboard Hot 100. In May 1971, the Jackson family moved into a large home on two-acre estate in Encino, California, where Michael evolved from child performer into a teen idol. As Jackson began to emerge as a solo performer in the early 1970s, he continued to maintain ties to the Jackson 5 and Motown. Between 1972, when his solo career began, and 1975, Michael released four solo studio albums with Motown: Got to Be There (1972), Ben (1972), Music & Me (1973), and Forever, Michael (1975). "Got to Be There" and "Ben", the title tracks from his first two solo albums, both became successful singles, as did a remake of Bobby Day's "Rockin' Robin".
The Jackson 5 were later described as "a cutting-edge example of black crossover artists." Although the group's sales began declining in 1973, and the band members chafed under Motown's refusal to allow them creative control or input, they continued to score several top 40 hits, including the top five single "Dancing Machine" (1974), before the group left Motown in 1975.
In June 1975, the Jackson 5 signed with Epic Records, a subsidiary of CBS Records, and renamed themselves the Jacksons. Younger brother Randy formally joined the band around this time, while Jermaine chose to stay with Motown and pursue a solo career. The Jacksons continued to tour internationally, and released six more albums between 1976 and 1984. Michael, the group's lead songwriter during this time, wrote hits such as "Shake Your Body (Down to the Ground)" (1979), "This Place Hotel" (1980), and "Can You Feel It" (1980). Jackson's work in film began in 1978, when he starred as the Scarecrow in The Wiz, a musical directed by Sidney Lumet that also starred Diana Ross, Nipsey Russell, and Ted Ross. The film was a box-office disaster. While working on the film Jackson met Quincy Jones, who was arranging the film's musical score, and Jones agreed to produce Jackson's next solo album, Off the Wall. In 1979, Jackson broke his nose during a complex dance routine. His subsequent rhinoplasty was not a complete success; he complained of breathing difficulties that would affect his career. He was referred to Dr. Steven Hoefflin, who performed Jackson's second rhinoplasty and subsequent operations.
Off the Wall (1979), which Jones and Jackson co-produced, established Jackson as a solo performer. The album helped Jackson transition from the "bubblegum pop" of his youth to the more complex sounds he would create as an adult. Songwriters for the album included Jackson, Rod Temperton, Stevie Wonder, and Paul McCartney. Off the Wall was the first solo album to generate four top 10 hits in the United States: "Off the Wall", "She's Out of My Life", and the chart-topping singles "Don't Stop 'Til You Get Enough" and "Rock with You". The album reached number three on the Billboard 200 and eventually sold over 20 million copies worldwide. In 1980, Jackson won three awards at the American Music Awards for his solo efforts: Favorite Soul/R&B Album, Favorite Soul/R&B Male Artist, and Favorite Soul/R&B Single for "Don't Stop 'Til You Get Enough". He also won Billboard Year-End awards for Top Black Artist and Top Black Album, and a Grammy Award for Best Male R&B Vocal Performance for 1979 with "Don't Stop 'Til You Get Enough". In 1981 Jackson was the American Music Awards winner for Favorite Soul/R&B Album and Favorite Soul/R&B Male Artist. Despite its commercial success, Jackson felt Off the Wall should have made a much bigger impact, and was determined to exceed expectations with his next release. In 1980, he secured the highest royalty rate in the music industry: 37 percent of wholesale album profit.
1982–83: Thriller and Motown 25: Yesterday, Today, Forever
In 1982, Jackson combined his interests in songwriting and film when he contributed the song "Someone in the Dark" to the storybook for the film E.T. the Extra-Terrestrial. The song, with Quincy Jones as its producer, won a Grammy for Best Recording for Children for 1983. Even more success came after the release of Thriller in late 1982. The album earned Jackson seven more Grammys and eight American Music Awards, including the Award of Merit, the youngest artist to win it.
Thriller was the best-selling album worldwide in 1983. It became the best-selling album of all time in the United States, and the best-selling album of all time worldwide, selling an estimated 65 million copies. The album topped the Billboard 200 chart for 37 weeks and was in the top 10 of the 200 for 80 consecutive weeks. It was the first album to have seven Billboard Hot 100 top 10 singles, including "Billie Jean", "Beat It", and "Wanna Be Startin' Somethin'". In December 2015, Thriller was certified for 30 million shipments by the RIAA, making it the only album to achieve that feat in the United States. Thriller won Jackson and Quincy Jones the Grammy award for Producer of the Year (Non-Classical) for 1983. It also won Album of the Year, with Jackson as the album's artist and Jones as its co-producer, and a Best Pop Vocal Performance, Male, award for Jackson. "Beat It" won Record of the Year, with Jackson as artist and Jones as co-producer, and a Best Rock Vocal Performance, Male, award for Jackson. "Billie Jean" won Jackson two Grammy awards, Best R&B Song, with Jackson as its songwriter, and Best R&B Vocal Performance, Male, as its artist. Thriller also won another Grammy for Best Engineered Recording – Non Classical in 1984, awarding Bruce Swedien for his work on the album. The AMA Awards for 1984 provided Jackson with an Award of Merit and AMAs for Favorite Male Artist, Soul/R&B, and Favorite Male Artist, Pop/Rock. "Beat It" won Jackson AMAs for Favorite Video, Soul/R&B, Favorite Video, Pop/Rock, and Favorite Single, Pop/Rock. Thriller won him AMAs for Favorite Album, Soul/R&B, and Favorite Album, Pop/Rock.
In addition to the award-winning album, Jackson released "Thriller", a fourteen-minute music video short directed by John Landis, in 1983. It "defined music videos and broke racial barriers" on the Music Television Channel (MTV), a fledgling entertainment television channel at the time. In December 2009, the Library of Congress selected the music video for "Thriller" for inclusion in the National Film Registry. It was one of twenty-five films named that year as "works of enduring importance to American culture" that would be "preserved for all time." The zombie-themed "Thriller" is the first and, as of 2009, the only music video to be inducted into the registry.
Jackson's attorney John Branca noted that Jackson had the highest royalty rate in the music industry at that point: approximately $2 for every album sold. He was also making record-breaking profits from sales of his recordings. The videocassette of the documentary The Making of Michael Jackson's Thriller sold over 350,000 copies in a few months. The era saw the arrival of novelties like dolls modeled after Michael Jackson, which appeared in stores in May 1984 at a price of $12. Biographer J. Randy Taraborrelli writes that, "Thriller stopped selling like a leisure item—like a magazine, a toy, tickets to a hit movie—and started selling like a household staple." In 1985, The Making of Michael Jackson's Thriller won a Grammy for Best Music Video, Longform. Time described Jackson's influence at that point as "Star of records, radio, rock video. A one-man rescue team for the music business. A songwriter who sets the beat for a decade. A dancer with the fanciest feet on the street. A singer who cuts across all boundaries of taste and style and color too". The New York Times wrote that, "in the world of pop music, there is Michael Jackson and there is everybody else".
A defining point in Jackson's career took place on March 25, 1983, when he reunited with his brothers for a legendary live performance, which was taped at the Pasadena Civic Auditorium, for Motown 25: Yesterday, Today, Forever, an NBC television special. The show aired on May 16, 1983, to an estimated audience of 47 million viewers, and featured the Jacksons and other Motown stars. The show is best remembered for Jackson's solo performance of "Billie Jean", which earned Jackson his first Emmy nomination. Wearing a distinctive black-sequined jacket and a golf glove decorated with rhinestones, he debuted his signature dance move, the moonwalk, which former Soul Train dancer and Shalamar member Jeffrey Daniel had taught him three years earlier. Jackson originally turned down the invitation to perform at the show, believing he had been doing too much television at the time; however at the request of Berry Gordy, Jackson relented and agreed to perform at the show in exchange for time to do a solo performance. According to Rolling Stone reporter Mikal Gilmore, "There are times when you know you are hearing or seeing something extraordinary...that came that night." Jackson's performance drew comparisons to Elvis Presley's and the Beatles' appearances on The Ed Sullivan Show. Anna Kisselgoff of The New York Times later wrote, "The moonwalk that he made famous is an apt metaphor for his dance style. How does he do it? As a technician, he is a great illusionist, a genuine mime. His ability to keep one leg straight as he glides while the other bends and seems to walk requires perfect timing." Berry Gordy said of the performance, "from the first beat of Billie Jean, I was mesmerized, and when he did his iconic moonwalk, I was shocked, it was magic, Michael Jackson went into orbit, and never came down."
1984–85: Pepsi, "We Are the World", and business career
By the mid-1980s, Jackson's award-winning musical career contributed to his commercial appeal, which proved to be substantial. In November 1983 he, along with his brothers, partnered with PepsiCo in a $5 million promotional deal that broke advertising industry records for a celebrity endorsement. The first Pepsi campaign, which ran in the United States from 1983 to 1984 and launched its "New Generation" theme, included advertising, tour sponsorship, public relations events, and in-store displays. Jackson, who was actively involved in creating the iconic Pepsi advertisement, suggested using his song, "Billie Jean", as its musical jingle with a revised chorus. According to a Billboard report in 2009, Brian J. Murphy, executive VP of branded management at TBA Global, commented, "You couldn't separate the tour from the endorsement from the licensing of the music, and then the integration of the music into the Pepsi fabric."
On January 27, 1984, Michael and other members of the Jacksons filmed a Pepsi Cola commercial that was overseen by executive Phil Dusenberry, a BBDO ad agency executive, and Alan Pottasch, Pepsi's Worldwide Creative Director, at the Shrine Auditorium in Los Angeles. In front of a full house of fans during a simulated concert, pyrotechnics accidentally set Jackson's hair on fire, causing second-degree burns to his scalp. Jackson underwent treatment to hide the scars on his scalp, and had his third rhinoplasty shortly thereafter. Pepsi settled out of court, and Jackson donated his $1.5 million settlement to the Brotman Medical Center in Culver City, California. Its Michael Jackson Burn Center is named in his honor. Dusenberry later recounted the episode in his memoir, Then We Set His Hair on Fire: Insights and Accidents from a Hall of Fame Career in Advertising. Jackson signed a second agreement with Pepsi in the late 1980s for a reported $10 million. The second campaign had a global reach to more than twenty countries and provided financial support for Jackson's Bad album and his world tour in 1987–88. Although Jackson had endorsements and advertising deals with other companies, such as LA Gear, Suzuki, and Sony, none were as significant as his deals with Pepsi, which later signed other music stars such as Britney Spears and Beyoncé to promote its products
Jackson's humanitarian work was recognized on May 14, 1984, when he was invited to the White House to receive an award from President Ronald Reagan for his support of charities that helped people overcome alcohol and drug abuse, and in recognition of his support for the Ad Council's and the National Highway Traffic Safety Administration's Drunk Driving Prevention campaign. Jackson donated the use of "Beat It" for the campaign's public service announcements.
Unlike later albums, Thriller did not have an official tour to promote it, but the Victory Tour of 1984 headlined the Jacksons and showcased much of Jackson's new solo material to more than two million Americans. It was the last tour he would do with his brothers. Following a controversy over the concert's ticket sales, Jackson held a press conference and announced that he would donate his share of the proceeds from the Victory Tour, an estimated $3 to 5 million, to charity. Jackson's charitable work and humanitarian awards continued with the release of "We Are the World" (1985), which he co-wrote with Lionel Richie. The song was recorded on January 28, 1985 and was released worldwide in March 1985 to aid the poor in the United States and Africa. The song earned $63 million for famine relief, and became one of the best-selling singles of all time, with 20 million copies sold. "We Are the World" won four Grammys for 1985, including Song of the Year going to Jackson and Richie as its co-songwriters. Although the American Music Award directors removed the charity song from the competition because they felt it would be inappropriate, the AMA show in 1986 concluded with a tribute to the song in honor of its first anniversary. The project's creators received two special AMA honors: one for the creation of the song and another for the USA for Africa idea. Jackson, Quincy Jones, and entertainment promoter Ken Kragan received special awards for their roles in creation of the song.
Jackson's financial interests in the music publishing business expanded after Jackson collaborated with Paul McCartney in the early 1980s. He subsequently learned that McCartney was making approximately $40 million a year from other people's songs. By 1983, Jackson had begun investing in publishing rights to songs that others had written, but he was careful with his acquisitions, only bidding on a few of the dozens that were offered to him. Jackson's early acquisitions of music catalogs and song copyrights such as the Sly Stone collection included "Everyday People" (1968), Len Barry's "1-2-3" (1965), and Dion DiMucci's "The Wanderer" (1961) and "Runaround Sue" (1961); however, Jackson's most significant purchase came in 1985, when he acquired the publishing rights to ATV Music Publishing after months of negotiation. ATV had acquired the publishing rights to nearly 4000 songs, including the Northern Songs catalog that contained the majority of the Lennon–McCartney compositions recorded by the Beatles.
In 1984 Robert Holmes à Court, the wealthy Australian investor who owned ATV Music Publishing, announced he was putting the ATV catalog up for sale. In 1981, McCartney was offered the ATV music catalog for £20 million ($40 million). According to McCartney, he contacted Yoko Ono about making a joint purchase by splitting the cost at £10 million each, but Ono thought they could buy it for £5 million each. When they were unable to make a joint purchase, McCartney, who did not want to be the sole owner of the Beatles' songs, did not pursue an offer on his own. According to a negotiator for Holmes à Court in the 1984 sale, "We had given Paul McCartney first right of refusal but Paul didn't want it at that time."
Jackson was first informed about the sale by his attorney, John Branca, in September 1984. An attorney for McCartney also assured Branca that McCartney was not interested in bidding. McCartney reportedly said "It's too pricey", but several other companies and investors were interested in bidding. Jackson submitted a bid of $46 million on November 20, 1984. His agents thought they had a deal several times, but encountered new bidders or new areas of debate. In May 1985, Jackson's team walked away from talks after having spent more than $1 million and four months of due diligence work on the negotiations. In June 1985, Jackson and Branca learned that Charles Koppelman's and Marty Bandier's The Entertainment Company had made a tentative agreement with Holmes à Court to buy ATV Music for $50 million; however, in early August, Holmes à Court's team contacted Jackson and talks resumed. Jackson raised his bid to $47.5 million, which was accepted because he could close the deal more quickly, having already completed due diligence of ATV Music. Jackson also agreed to visit Holmes à Court in Australia, where he would appear on the Channel Seven Perth Telethon. Jackson's purchase of ATV Music was finalized on August 10, 1985.
1986–90: Appearance, tabloids, Bad, films, autobiography, and Neverland
See also: Michael Jackson's health and appearance
Jackson's skin had been a medium-brown color for the duration of his youth, but starting in the mid-1980s it gradually grew paler. The change gained widespread media coverage, including rumors that he might have been bleaching his skin. According to J. Randy Taraborrelli's biography, in 1984, Jackson was diagnosed with vitiligo, which Taraborrelli noted may be a consequence of skin bleaching. He claimed Jackson was diagnosed with lupus. The vitiligo partially lightened his skin, and the lupus was in remission. Both illnesses made his skin sensitive to sunlight. The treatments Jackson used for his condition further lightened his skin tone, and with the application of pancake makeup to even out blotches he could appear very pale. Jackson was also diagnosed with vitiligo in his autopsy, though not lupus.
Jackson claimed he had only two rhinoplasties and no other surgery on his face, although at one point he mentioned having a dimple created in his chin. He lost weight in the early 1980s because of a change in diet and a desire for "a dancer's body". Witnesses reported that he was often dizzy, and speculated he was suffering from anorexia nervosa. Periods of weight loss would become a recurring problem later in life.
During the course of his treatment, Jackson made two close friends: his dermatologist, Dr. Arnold Klein, and Klein's nurse Debbie Rowe. Rowe eventually became Jackson's second wife and the mother of his two eldest children. He also relied heavily on Klein for medical and business advice.
Jackson became the subject of increasingly sensational reports. In 1986, the tabloids ran a story claiming that Jackson slept in a hyperbaric oxygen chamber to slow the aging process; he was pictured lying down in a glass box. Although the claim was untrue, according to tabloid reports that are widely cited, Jackson had disseminated the fabricated story himself. When Jackson bought a chimpanzee called Bubbles from a laboratory, he was reported to be increasingly detached from reality. It was reported that Jackson had offered to buy the bones of Joseph Merrick (the "Elephant Man") and, although untrue, Jackson did not deny the story. Although he initially saw these stories as opportunities for publicity, he stopped leaking untruths to the press as they became more sensational. Consequently, the media began making up their own stories. These reports became embedded in the public consciousness, inspiring the nickname "Wacko Jacko", which Jackson came to despise. Responding to the gossip, Jackson remarked to Taraborrelli:
Why not just tell people I'm an alien from Mars? Tell them I eat live chickens and do a voodoo dance at midnight. They'll believe anything you say, because you're a reporter. But if I, Michael Jackson, were to say, "I'm an alien from Mars and I eat live chickens and do a voodoo dance at midnight," people would say, "Oh, man, that Michael Jackson is nuts. He's cracked up. You can't believe a single word that comes out of his mouth.
In 1988, Jackson released his only autobiography, Moonwalk, which took four years to complete and sold 200,000 copies. Jackson wrote about his childhood, the Jackson 5, and the abuse he had suffered. He also wrote about his facial appearance. He attributed much of the change in the structure of his face to puberty, weight loss, a strict vegetarian diet, a change in hair style, and stage lighting. Moonwalk reached the top position on The New York Times best sellers' list. The musician then released a film called Moonwalker, which featured live footage and short films that starred Jackson and Joe Pesci. The film was originally intended to be released to theaters, but due to financial issues, the film was released direct-to-video. It saw a theatrical release in Germany, though. It debuted atop the Billboard Top Music Video Cassette chart, staying there for 22 weeks. It was eventually knocked off the top spot by Michael Jackson: The Legend Continues.
In March 1988, Jackson purchased land near Santa Ynez, California, to build Neverland Ranch at a cost of $17 million. He installed several carnival rides on the 2,700-acre (11 km2) property, including a Ferris wheel, a carousel, and a menagerie, as well as a movie theater and a zoo. A security staff of 40 patrolled the grounds. In 2003, it was valued at approximately $100 million. In 1989, his annual earnings from album sales, endorsements, and concerts were estimated at $125 million for that year alone. Shortly afterwards, he became the first Westerner to appear in a television ad in the Soviet Union.
His success resulted in him being dubbed the "King of Pop". The nickname was popularized by Elizabeth Taylor when she presented him with the Soul Train Heritage Award in 1989, proclaiming him "the true king of pop, rock and soul." President George H. W. Bush designated him the White House's "Artist of the Decade". From 1985 to 1990, he donated $455,000 to the United Negro College Fund, and all of the profits from his single "Man in the Mirror" went to charity. Jackson's live rendition of "You Were There" at Sammy Davis Jr.'s 60th birthday celebration allowed Jackson to receive his second Emmy nomination.
1991–93: Dangerous, Heal the World Foundation, and Super Bowl XXVII
In March 1991, Jackson renewed his contract with Sony for $65 million, a record-breaking deal at the time, displacing Neil Diamond's renewal contract with Columbia Records. In 1991, he released his eighth album, Dangerous, co-produced with Teddy Riley. Dangerous was certified seven times platinum in the U.S., and, as of 2008, has approximately sold 30 million copies worldwide. In the United States, the album's first single "Black or White" was its biggest hit, reaching number one on the Billboard Hot 100 and remaining there for seven weeks, with similar chart performances worldwide. The album's second single "Remember the Time" spent eight weeks in the top five in the United States, peaking at number three on the Billboard Hot 100 singles chart. At the end of 1992, Dangerous was awarded the best-selling album of the year worldwide and "Black or White" was awarded best-selling single of the year worldwide at the Billboard Music Awards. Additionally, he won an award as best-selling artist of the 1980s. In 1993, Jackson performed the song at the Soul Train Music Awards in a chair, saying he had suffered an injury in rehearsals. In the UK and other parts of Europe, "Heal the World" was the album's most successful song; it sold 450,000 copies in the UK and spent five weeks at number two in 1992.
Jackson founded the Heal the World Foundation in 1992. The charity organization brought underprivileged children to Jackson's ranch to enjoy theme park rides that Jackson had built on the property. The foundation also sent millions of dollars around the globe to help children threatened by war, poverty, and disease. In the same year, Jackson published his second book, the bestselling collection of poetry, Dancing the Dream. While it was a commercial success, and revealed a more intimate side to Jackson's nature, the collection was mostly critically unacclaimed at the time of its release. In 2009, the book was republished by Doubleday and was more positively received by some critics in the wake of Jackson's untimely death. The Dangerous World Tour grossed $100 million. The tour began on June 27, 1992, and finished on November 11, 1993. Jackson performed to 3.5 million people in 70 concerts. He sold the broadcast rights to his Dangerous world tour to HBO for $20 million, a record-breaking deal that still stands.
Following the illness and death of Ryan White, Jackson helped draw public attention to HIV/AIDS, something that was still controversial at the time. He publicly pleaded with the Clinton Administration at Bill Clinton's Inaugural Gala to give more money to HIV/AIDS charities and research. In a high-profile visit to Africa, Jackson visited several countries, among them Gabon and Egypt. His first stop to Gabon was greeted with a sizable and enthusiastic reception of more than 100,000 people, some of them carrying signs that read, "Welcome Home Michael." In his trip to Ivory Coast, Jackson was crowned "King Sani" by a tribal chief. He then thanked the dignitaries in French and English, signed official documents formalizing his kingship, and sat on a golden throne while presiding over ceremonial dances.
In January 1993, Jackson made an appearance at the Super Bowl XXVII halftime show in Pasadena, California. Because of dwindling interest during halftime in the years before, the NFL decided to seek big-name talent that would keep viewers and ratings high, with Jackson being selected because of his popularity and universal appeal. It was the first Super Bowl where the audience figures increased during the half-time show to more than the game itself. The performance began with Jackson catapulting onto the stage as fireworks went off behind him. As he landed on the canvas, he maintained a motionless "clenched fist, standing statue stance", dressed in a gold and black military outfit and sunglasses; he remained completely motionless for a minute and a half while the crowd cheered. He then slowly removed his sunglasses, threw them away and sang four songs: "Jam", "Billie Jean", "Black or White", and "Heal the World". Jackson's Dangerous album rose 90 places up the album chart soon after.
Jackson gave a 90-minute interview to Oprah Winfrey on February 10, 1993, his second television interview since 1979. He grimaced when speaking of his childhood abuse at the hands of his father; he believed he had missed out on much of his childhood years, admitting that he often cried from loneliness. He denied tabloid rumors that he had bought the bones of the Elephant Man, slept in a hyperbaric oxygen chamber, or bleached his skin, stating for the first time that he had vitiligo. Dangerous re-entered the album chart in the top 10, more than a year after its original release.
In February 1993, Jackson was given the "Living Legend Award" at the 35th Annual Grammy Awards in Los Angeles. "Black or White" was Grammy-nominated for best vocal performance. "Jam" gained two nominations: Best R&B Vocal Performance and Best R&B Song. The Dangerous album won a Grammy for Best Engineered – Non Classical, awarding the work of Bruce Swedien and Teddy Riley. In the same year, Michael Jackson won three American Music Awards for Favorite Pop/Rock Album (Dangerous), Favorite Soul/R&B Single ("Remember the Time"), and was the first to win the International Artist Award, for his global performances and humanitarian concerns. This award will bear his name in the future.
Also during this time, Jackson signed on to produce the soundtrack for Sega's 1994 video game, Sonic the Hedgehog 3. Jackson brought collaborators Brad Buxer, Bobby Brooks, Darryl Ross, Geoff Grace, Doug Grigsby, and Cirocco Jones with him to help. However, Jackson left the project before completion and was never officially credited with his work, with the official reason being given as him disliking the low quality synthesized audio chips inside the Sega Genesis, the console on which the game was played.
1993–94: First child sexual abuse allegations and first marriage
Main article: 1993 child sexual abuse accusations against Michael Jackson
In the summer of 1993, Jackson was accused of child sexual abuse by a 13-year-old boy named Jordan Chandler and his father, Evan Chandler, a dentist. The Chandler family demanded payment from Jackson, and the singer initially refused. Jordan Chandler eventually told the police that Jackson had sexually abused him. Evan Chandler was tape-recorded discussing his intention to pursue charges, saying, "If I go through with this, I win big-time. There's no way I lose. I will get everything I want and they will be destroyed forever..... Michael's career will be over". Jordan's mother was, however, adamant at the time that there had been no wrongdoing on Jackson's part. Jackson later used the recording to argue that he was the victim of a jealous father whose only goal was to extort money from the singer. In January 1994, however, after investigation on allegations of extortion against the singer by Chandler, deputy Los Angeles County district attorney Michael J. Montagna stated that Chandler would not be charged due to lack of cooperation from Jackson's camp and its willingness to negotiate with Chandler for several weeks among other reasons.
In August 1993, Jackson's home was raided by the police who, according to court documents, found books and photographs in his bedroom featuring young boys with little or no clothing. Since the books were legal to purchase and own, the jury decided not to indict Jackson. In December 1993, Jackson was strip searched. Jordan Chandler had reportedly given police a description of Jackson's intimate parts, and the strip search revealed that Jordan had correctly claimed Jackson had patchy-colored buttocks, short pubic hair, and pink and brown marked testicles. Reportedly, Jordan had also previously drawn accurate pictures of a dark spot on Jackson's penis only visible when his penis was lifted. Despite differing initial internal reports from prosecutors and investigators and later, with reports of jurors feeling otherwise that the photos did not match the description, the DA stated his belief in a sworn affidavit that the description was accurate, along with the sheriff's photographer stating the description was accurate. A 2004 motion filed by Jackson's defense asserted that Jackson was never criminally indicted by any grand jury and that his settlement admitted no wrongdoing and contained no evidence of criminal misconduct.
The investigation was inconclusive and no charges were ever filed. Jackson described the search in an emotional public statement, and proclaimed his innocence. On January 1, 1994, Jackson settled with the Chandlers out of court for $22 million. A Santa Barbara County grand jury and a Los Angeles County grand jury disbanded on May 2, 1994, without indicting Jackson, and the Chandlers stopped co-operating with the criminal investigation around July 6, 1994. The out-of-court settlement's documentation specifically stated Jackson admitted no wrongdoing and no liability; the Chandlers and their family lawyer Larry Feldman signed it without contest.
Feldman also explicitly stated "nobody bought anybody's silence". A decade after the fact, during the second round of child abuse allegations, Jackson's lawyers would file a memo stating that the 1994 settlement was done without his consent. A later disclosure by the FBI of investigation documents compiled over nearly 20 years led Jackson's attorney to suggest that no evidence of molestation or sexual impropriety from Jackson toward minors existed. According to reports the DCFS had investigated Jackson beginning in 1993 with the Chandler allegation and again in 2003. Reports show the LAPD and DCFS did not find credible evidence of abuse or sexual misconduct.
In May 1994, Jackson married Lisa Marie Presley, the daughter of Elvis and Priscilla Presley. They had first met in 1975, when a seven-year-old Presley attended one of Jackson's family engagements at the MGM Grand Hotel and Casino, and were reconnected through a mutual friend. According to a friend of Presley's, "their adult friendship began in November 1992 in L.A." They stayed in contact every day over the telephone. As the child molestation accusations became public, Jackson became dependent on Presley for emotional support; she was concerned about his faltering health and addiction to drugs. Presley explained, "I believed he didn't do anything wrong and that he was wrongly accused and yes I started falling for him. I wanted to save him. I felt that I could do it." She eventually persuaded him to settle the civil case out of court and go into rehabilitation to recover.
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