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Composition of electronic cigarette aerosol	Aldehydes in e-cigarette aerosol	∗Abbreviations: <LOQ, below the limit of quantitation but above the limit of detection; N.D., not detected; N.T., not tested.
Composition of electronic cigarette aerosol	Tobacco-specific nitrosamines in nicotine-containing products	∗ng/g, but not for gum and patch. ng/gum piece is for gum and ng/patch is for patch.
Composition of electronic cigarette aerosol	Comparison of levels of toxicants in e-cigarette aerosol	Abbreviations: μg, microgram; ng, nanogram; ND, not detected.
Composition of electronic cigarette aerosol	Comparison of levels of toxicants in e-cigarette aerosol	∗Fifteen puffs were chosen to estimate the nicotine delivery of one traditional cigarette.Each e-cigarette cartridge, which varies across manufacturers, and each cartridge produces 10 to 250 puffs of vapor. This correlates to 5 to 30 traditional cigarettes. A puff usually lasts for 3 to 4 seconds. A 2014 study found there is wide differences in daily puffs in experienced vapers, which typically varies from 120 to 225 puffs per day. From puff-to-puff e-cigarettes do not provide as much nicotine as traditional cigarettes. A 2016 review found "The nicotine contained in the aerosol from 13 puffs of an e-cigarette in which the nicotine concentration of the liquid is 18 mg per milliliter has been estimated to be similar to the amount in the smoke of a typical tobacco cigarette, which contains approximately 0.5 mg of nicotine."
Leap year starting on Tuesday	Leap year starting on Tuesday	A leap year starting on Tuesday is any year with 366 days (i.e. it includes 29 February) that begins on Tuesday, 1 January, and ends on Wednesday, 31 December. Its dominical letters hence are FE. The most recent year of such kind was 2008 and the next one will be 2036 in the Gregorian calendar or, likewise 2020 and 2048 in the obsolete Julian calendar.
Leap year starting on Tuesday	Leap year starting on Tuesday	Any leap year that starts on Tuesday, Friday or Saturday has only one Friday the 13th; the only one in this leap year occurs in June. Common years starting on Wednesday share this characteristic.
Leap year starting on Tuesday	Applicable years	Gregorian Calendar Leap years that begin on Tuesday, along with those starting on Wednesday, occur at a rate of approximately 14.43% (14 out of 97) of all total leap years in a 400-year cycle of the Gregorian calendar. Thus, their overall occurrence is 3.5% (14 out of 400).
Leap year starting on Tuesday	Applicable years	400 year cycle century 1: 8, 36, 64, 92 century 2: 104, 132, 160, 188 century 3: 228, 256, 284 century 4: 324, 352, 380 Julian Calendar Like all leap year types, the one starting with 1 January on a Tuesday occurs exactly once in a 28-year cycle in the Julian calendar, i.e. in 3.57% of years. As the Julian calendar repeats after 28 years that means it will also repeat after 700 years, i.e. 25 cycles. The year's position in the cycle is given by the formula ((year + 8) mod 28) + 1).
Leap year starting on Tuesday	Holidays	International Valentine's Day falls on a Thursday The leap day (February 29) falls on a Friday World Day for Grandparents and the Elderly falls on July 27 Halloween falls on a Friday Christmas Day falls on a Thursday Roman Catholic Solemnities Epiphany falls on a Sunday Candlemas falls on a Saturday Saint Joseph's Day falls on a Wednesday The Annunciation of Jesus falls on a Tuesday The Nativity of John the Baptist falls on a Tuesday The Solemnity of Saints Peter and Paul falls on a Sunday The Transfiguration of Jesus falls on a Wednesday The Assumption of Mary falls on a Friday The Exaltation of the Holy Cross falls on a Sunday All Saints' Day falls on a Saturday All Souls' Day falls on a Sunday The Feast of Christ the King falls on November 23 (or on October 26 in versions of the calendar between 1925 and 1962) The First Sunday of Advent falls on November 30 The Immaculate Conception falls on a Monday Gaudete Sunday falls on December 14 Rorate Sunday falls on December 21 Australia and New Zealand Australia Day falls on a Saturday Waitangi Day falls on a Wednesday Daylight saving ends on April 6 ANZAC Day falls on a Friday Mother's Day falls on May 11 Father's Day falls on its latest possible date, September 7 Daylight saving begins on September 28 in New Zealand and October 5 in Australia British Isles Saint David's Day falls on a Saturday Mother's Day falls on March 2, March 9, March 16, March 23 or March 30 Saint Patrick's Day falls on a Monday Daylight saving begins on March 30 Saint George's Day falls on a Wednesday Father's Day falls on its earliest possible date, June 15 Orangeman's Day falls on a Saturday Daylight saving ends on October 26 Guy Fawkes Night falls on a Wednesday Saint Andrew's Day falls on a Sunday Canada Daylight saving begins on March 9 Mother's Day falls on May 11 Victoria Day falls on May 19 Father's Day falls on its earliest possible date, June 15 Canada Day falls on a Tuesday Labour Day falls on its earliest possible date, September 1 Thanksgiving Day falls on October 13 Daylight saving ends on November 2 United States Martin Luther King Jr. Day falls on its latest possible date, January 21 President's Day falls on February 18 Daylight saving begins on March 9 Mother's Day falls on May 11 Memorial Day falls on May 26 Father's Day falls on its earliest possible date, June 15 Juneteenth falls on a Thursday Independence Day falls on a Friday Labor Day falls on its earliest possible date, September 1 Grandparents' Day falls on its earliest possible date, September 7 Columbus Day falls on October 13 Daylight saving ends on November 2 Election Day falls on November 4 Thanksgiving Day falls on November 27
XAP044	XAP044	XAP044 is a drug which acts as a potent and selective antagonist of the metabotropic glutamate receptor 7 (mGluR7). It inhibits long-term potentiation in the amygdala and inhibits responses associated with stress and anxiety in animal models, as well as being used to study the role of mGluR7 in various other processes.
Prochlorperazine	Prochlorperazine	Prochlorperazine, formerly sold under the brand name Compazine among others, is a medication used to treat nausea, migraines, schizophrenia, psychosis and anxiety. It is a less preferred medication for anxiety. It may be taken by mouth, rectally, injection into a vein, or injection into a muscle.Common side effects include sleepiness, blurry vision, low blood pressure, and dizziness. Serious side effects may include movement disorders including tardive dyskinesia and neuroleptic malignant syndrome. Use in pregnancy and breastfeeding is generally not recommended. It is a typical antipsychotic which is believed to work by reducing the action of dopamine in the brain.Prochlorperazine was approved for medical use in the United States in 1956. It is available as a generic medication. In 2020, it was the 355th most commonly prescribed medication in the United States, with more than 600 thousand prescriptions.
Prochlorperazine	Medical uses	Vomiting Prochlorperazine is used to prevent vomiting caused by chemotherapy, radiation therapy and in the pre- and postoperative setting. A 2015 Cochrane review found no differences in efficacy among drugs commonly used for this purpose in emergency rooms. Migraine Prochlorperazine, generally by intravenous, is used to treat migraine. Such use is recommended by The American Headache Society. A 2019 systematic review found prochlorperazine was nearly three times as likely as metoclopramide to relieve headache within 60 minutes of administration. Labyrinthitis In the UK prochlorperazine maleate has been used for labyrinthitis, which include not only nausea and vertigo, but spatial and temporal 'jerking' and distortion.
Prochlorperazine	Side effects	Sedation is very common, and extrapyramidal side effects are common and include restlessness, dystonic reactions, pseudoparkinsonism, and akathisia; the extrapyramidal symptoms can affect 2% of people at low doses, whereas higher doses may affect as many as 40% of people.Prochlorperazine can also cause a life-threatening condition called neuroleptic malignant syndrome (NMS). Some symptoms of NMS include high fever, stiff muscles, neck muscle spasm, confusion, irregular pulse or blood pressure, fast heart rate (tachycardia), sweating, abnormal heart rhythms (arrhythmias). Research from the Veterans Administration and United States Food and Drug Administration show injection site reactions. Adverse effects are similar in children.
Prochlorperazine	Side effects	Warning The FDA approved label for prochlorperazine includes a warning for increased risk of mortality in elderly patients with dementia related psychosis.
Prochlorperazine	Side effects	Discontinuation The British National Formulary recommends a gradual withdrawal when discontinuing antipsychotics to avoid acute withdrawal syndrome or rapid relapse. Symptoms of withdrawal commonly include nausea, vomiting, and loss of appetite. Other symptoms may include restlessness, increased sweating, and trouble sleeping. Less commonly there may be a feeling of the world spinning, numbness, or muscle pains. Symptoms generally resolve after a short period of time.There is tentative evidence that discontinuation of antipsychotics can result in psychosis. It may also result in reoccurrence of the condition that is being treated. Rarely tardive dyskinesia can occur when the medication is stopped.
Prochlorperazine	Pharmacology	Prochlorperazine is thought to exert its antipsychotic effects by blocking dopamine receptors.Prochlorperazine is analogous to chlorpromazine; both of these agents antagonize dopaminergic D2 receptors in various pathways of the central nervous system. This D2 blockade results in antipsychotic, antiemetic and other effects. Hyperprolactinemia is a side effect of dopamine antagonists as blockade of D2 receptors within the tuberoinfundibular pathway results in increased plasma levels of prolactin due to increased secretion by lactotrophs in the anterior pituitary.
Prochlorperazine	Pharmacology	Following intramuscular injection, the antiemetic action is evident within 5 to 10 minutes and lasts for 3 to 4 hours. Rapid action is also noted after buccal treatment. With oral dosing, the start of action is delayed but the duration somewhat longer (approximately 6 hours).
Prochlorperazine	Society and culture	In the United Kingdom, prochlorperazine is available for the treatment of nausea caused by migraine as a tablet dissolved in the mouth, and in Australia as a tablet swallowed whole. In the UK, it is available via a prescription and as a pharmacy medicine, meaning it does not require a prescription but is only available after talking with a pharmacist.
Prochlorperazine	Society and culture	Marketing Prochlorperazine is available as tablets, suppositories, and in an injectable form.As of September 2017 it was marketed under the trade names Ametil, Antinaus, Buccastem, Bukatel, Chlormeprazine, Chloropernazine, Compazine, Compro, Daolin, Dhaperazine, Emedrotec, Emetiral, Eminorm, Lotamin, Mitil, Mormal, Nautisol, Novamin, Novomit, Proazine, Procalm, Prochlorperazin, Prochlorperazine, Prochlorpérazine, Prochlorperazinum, Prochlozine, Proclorperazina, Promat, Promin, Promtil, Roumin, Scripto-metic, Seratil, Stemetil, Steremal, Vergon, Vestil, and Volimin.It was also marketed at that time as a combination drug for humans with paracetamol as Vestil-A, as a combination drug for veterinary use, with isopropamide as Darbazine.
Prochlorperazine	Research	Alexza Pharmaceuticals studied an inhaled form of prochlorperazine for the treatment of migraine through Phase II trials under the development name AT-001; development was discontinued in 2011.
Prochlorperazine	Synthesis	The alkylation of 2-chlorophenothiazine (1) and 1-(3-Chloropropyl)-4-methylpiperazine [104-16-5] (2) in the presence of sodamide gives Prochlorperazine (3); or by alkylation of 2-Chloro-10-(3-chloropropyl)phenothiazine [2765-59-5] (4) and 1-methylpiperazine (5).
Gojūshiho	Gojūshiho	Gojūshiho (五十四歩, lit. 54 steps) is a kata practiced in karate. Gojushiho was developed by Sokon Matsumura, one of the key founders of Okinawan martial arts and named it "Uesheishi", which literally means 54 methods in Chinese. In some styles of karate, there are two versions of this kata - Gojūshiho Shō and Gojūshiho Dai. An advantage of the two versions of the kata is to better master the difficult techniques presented therein, but not without facing some confusion, for many sequences are the same and others only slightly different. The embusen of both Gojūshiho Shō and Gojūshiho Dai are nearly identical. Gojūshiho Shō begins straight off with a wide variety of advanced techniques and, as such, is highly recommended for study. Gojūshiho Dai consists of many advanced open-handed techniques and attacks to the collar-bone.
Gojūshiho	Gojūshiho	Gojushiho movement is quite similar with Aikido grappling technique in terms of flowing knife hand or "tate-shuto-uke" or vertical knife hand block. "Tate-shuto-uke" does not resemble other shuto uke which resemble as "block technique". Rather it was throwing technique in "aiki-jujutsu". Another "shuto" technique as "shuto-nagashi-uke" or "knife-hand-flowing-block" has become the unique characteristic of Gojushiho because of flowing movement which is not merely interpreted as "block", but "throw".
Gojūshiho	Gojūshiho	Gojūshiho Shō and Gojūshiho Dai are two versions in Shotokan of the Shōrin-ryū kata called Useishi (54) or Gojūshiho. The oft-repeated story about the JKA having to rename the Gojushiho kata due to a tournament mix-up; and Kanazawa Hirokazu, because of his seniority, keeping the original names in his SKIF organisation is without foundation. In fact, Kanazawa is on record as saying that when he formed SKIF he changed the names of the two kata as he felt that the “sho” designation suited the smaller, more difficult, kata better. Kanazawa also mentioned that this kata was introduced into the JKA before its sibling, and this explained why the JKA decided to call it “dai” when they introduced the second Gojushiho into the syllabus.
Gojūshiho	Gojūshiho	This kata is also practiced in Tang Soo Do and is called O Sip Sa Bo in Korean. And it is said that it also has some influences of Ng Ying Kungfu (Chinese: 五形功夫). Due to its difficulty, this kata is often reserved for advanced students, usually for those who are 6th degree black belts and above. Gojushiho is also practiced in Goshin Kagen Goju Karate, a modified style of Goju founded by Hanshi Gerald Thomson
Muck (gambling)	Muck (gambling)	Mucking is the discarding of cards in card games. Depending on the game, it may be a regular part of play or it may be considered cheating.
Muck (gambling)	Poker	In poker, it most often refers to the discard pile into which players may throw their folded hands, and into which the dealer places burned cards. It also refers to when a player is folding his hand (face down) without saying anything. In fact, the hand is not folded until it reaches the muck (it can be taken back and used if the dealer did not take the hand yet). The practice of mucking cards when discarding helps to ensure that no other player can reliably determine which cards were in the folded hand.
Muck (gambling)	Poker	In poker, the term may also refer to the action that a player who has not folded may take; he can have his hand "mucked" if another player attempts to discard but one or more cards end up in the live players hand. This is why many players will place a chip or other object on their cards: it helps to prevent errant cards from entering their hand. Sometimes they are referred to as card covers, card guards or card protector.
Muck (gambling)	Poker	Mucking as a strategy In some variations of poker a player may "muck" their cards in order to reinforce a bluff while preserving their image on the table.
Muck (gambling)	Other card games	Mucking or hand mucking may also refer to a form of sleight of hand, and, if used in a card game, is cheating. A player conceals a card through sleight of hand, removing it from play so that it may later be inserted back into the game to the cheater's advantage. For example, in blackjack a cheating player might remove an ace from the table to use the next time he is dealt a ten to make a blackjack.
Nine oils	Nine oils	In the 19th century, the nine oils was a preparation, or liniment, which was rubbed into the skin to relieve aches, such as over bruises. "Nine oils" was apparently developed in veterinary medicine, for treating horses, but later was adopted for human medical use.
Nine oils	Nine oils	According to one 19th-century druggists' book, oils used in the preparation included: train oil; that is, whale oil or the oil of the blubber of another marine mammal oil of turpentine oil of bricks, the oil obtained by the distillation of pieces of brick saturated with rapeseed oil or olive oil oil of amber spirit of camphor Barbados tar, a kind of greenish petroleum found in Barbados oil of vitriol; that is, sulfuric acidHowever, it is certain that many "nine oils" preparations did not contain these ingredients, and in fact it is possible that the name "nine oils" never referred to any specific combination of compounds. The writer James Greenwood, in 1883, put these words in the mouth of the street-doctor "Dr. Quackinbosh", in his series of articles Toilers in London, by One of the Crowd, originally serialized in the Daily Telegraph: When I first started I worked Woolwich with my "miraculous Nine Oils." Men who work at heavy lifting and hauling, and are likely to get strains and ricks of the back, have a superstitious belief in the "Nine Oils." It is the same wherever you go. What are they? what, the original Nine? Blessed if I know, nor they don't know either. But that don't make any difference. I used to give 'em one – sperm oil – and call it the Nine.
Kiskatom Formation	Kiskatom Formation	The Kiskatom Formation is a geologic formation in New York. It preserves fossils dating back to the Devonian period.
Mosquito-borne disease	Mosquito-borne disease	Mosquito-borne diseases or mosquito-borne illnesses are diseases caused by bacteria, viruses or parasites transmitted by mosquitoes. Nearly 700 million people get a mosquito-borne illness each year resulting in over 725,000 deaths.Diseases transmitted by mosquitoes include malaria, dengue, West Nile virus, chikungunya, yellow fever, filariasis, tularemia, dirofilariasis, Japanese encephalitis, Saint Louis encephalitis, Western equine encephalitis, Eastern equine encephalitis, Venezuelan equine encephalitis, Ross River fever, Barmah Forest fever, La Crosse encephalitis, and Zika fever, as well as newly detected Keystone virus and Rift Valley fever. There is no evidence as of April 2020 that COVID-19 can be transmitted by mosquitoes, and it is extremely unlikely this could occur.
Mosquito-borne disease	Types	Protozoa The female mosquito of the genus Anopheles may carry the malaria parasite. Four different species of protozoa cause malaria: Plasmodium falciparum, Plasmodium malariae, Plasmodium ovale and Plasmodium vivax (see Plasmodium). Worldwide, malaria is a leading cause of premature mortality, particularly in children under the age of five, with an estimated 207 million cases and more than half a million deaths in 2012, according to the World Malaria Report 2013 published by WHO. The death toll increased to one million as of 2018 according to the American Mosquito Control Association.
Mosquito-borne disease	Types	Myiasis Botflies are known to parasitize humans or other mammalians, causing myiasis, and to use mosquitoes as intermediate vector agents to deposit eggs on a host. The human botfly Dermatobia hominis attaches its eggs to the underside of a mosquito, and when the mosquito takes a blood meal from a human or an animal, the body heat of the mammalian host induces hatching of the larvae.
Mosquito-borne disease	Types	Helminthiasis Some species of mosquito can carry the filariasis worm, a parasite that causes a disfiguring condition (often referred to as elephantiasis) characterized by a great swelling of several parts of the body; worldwide, around 40 million people are living with a filariasis disability.
Mosquito-borne disease	Types	Virus The viral diseases yellow fever, dengue fever, Zika fever and chikungunya are transmitted mostly by Aedes aegypti mosquitoes.Other viral diseases like epidemic polyarthritis, Rift Valley fever, Ross River fever, St. Louis encephalitis, West Nile fever, Japanese encephalitis, La Crosse encephalitis and several other encephalitic diseases are carried by several different mosquitoes. Eastern equine encephalitis (EEE) and Western equine encephalitis (WEE) occur in the United States where they cause disease in humans, horses, and some bird species. Because of the high mortality rate, EEE and WEE are regarded as two of the most serious mosquito-borne diseases in the United States. Symptoms range from mild flu-like illness to encephalitis, coma, and death.Viruses carried by arthropods such as mosquitoes or ticks are known collectively as arboviruses. West Nile virus was accidentally introduced into the United States in 1999 and by 2003 had spread to almost every state with over 3,000 cases in 2006.
Mosquito-borne disease	Types	Other species of Aedes as well as Culex and Culiseta are also involved in the transmission of disease.Myxomatosis is spread by biting insects, including mosquitoes.
Mosquito-borne disease	Transmission	A mosquito's period of feeding is often undetected; the bite only becomes apparent because of the immune reaction it provokes. When a mosquito bites a human, it injects saliva and anti-coagulants. For any given individual, with the initial bite there is no reaction but with subsequent bites the body's immune system develops antibodies and a bite becomes inflamed and itchy within 24 hours. This is the usual reaction in young children. With more bites, the sensitivity of the human immune system increases, and an itchy red hive appears in minutes where the immune response has broken capillary blood vessels and fluid has collected under the skin. This type of reaction is common in older children and adults. Some adults can become desensitized to mosquitoes and have little or no reaction to their bites, while others can become hyper-sensitive with bites causing blistering, bruising, and large inflammatory reactions, a response known as skeeter syndrome.One study found Dengue virus and Zika virus altered the skin bacteria of rats in a way that caused their body odor to be more attractive to mosquitoes.
Mosquito-borne disease	Signs and symptoms	Symptoms of illness are specific to the type of viral infection and vary in severity, based on the individuals infected. Zika virus Symptoms vary in severity, from mild unnoticeable symptoms to more common symptoms like fever, rash, headache, achy muscle and joints, and conjunctivitis. Symptoms can last several days to weeks, but death resulting from this infection is rare.
Mosquito-borne disease	Signs and symptoms	West Nile virus, dengue fever Most people infected with the West Nile virus usually do not develop symptoms. However, some individuals can develop cases of severe fatigue, weakness, headaches, body aches, joint and muscle pain, vomiting, diarrhea, and rash, which can last for weeks or months. More serious symptoms have a greater risk of appearing in people over 60 years of age, or those with cancer, diabetes, hypertension, and kidney disease.Dengue fever is mostly characterized by high fever, headaches, joint pain, and rash. However, more severe instances can lead to hemorrhagic fever, internal bleeding, and breathing difficulty, which can be fatal.
Mosquito-borne disease	Signs and symptoms	Chikungunya People infected with this virus can develop sudden onset fever along with debilitating joint and muscle pain, rash, headache, nausea, and fatigue. Symptoms can last a few days or be prolonged to weeks and months. Although patients can recover completely, there have been cases in which joint pain has persisted for several months and can extend beyond that for years. Other people can develop heart complications, eye problems, and even neurological complications.
Mosquito-borne disease	Mechanism	Mosquitoes carrying such arboviruses stay healthy because their immune systems recognizes the virions as foreign particles and "chop off" the virus' genetic coding, rendering it inert. Human infection with a mosquito-borne virus occurs when a female mosquito bites someone while its immune system is still in the process of destroying the virus's harmful coding. It is not completely known how mosquitoes handle eukaryotic parasites to carry them without being harmed. Data has shown that the malaria parasite Plasmodium falciparum alters the mosquito vector's feeding behavior by increasing frequency of biting in infected mosquitoes, thus increasing the chance of transmitting the parasite.The mechanism of transmission of this disease starts with the injection of the parasite into the victim's blood when malaria-infected female Anopheles mosquitoes bite into a human being. The parasite uses human liver cells as hosts for maturation where it will continue to replicate and grow, moving into other areas of the body via the bloodstream. The spread of this infection cycle then continues when other mosquitoes bite the same individual. The result will cause that mosquito to ingest the parasite and allow it to transmit the Malaria disease into another person through the same mode of bite injection. Flaviviridae viruses transmissible via vectors like mosquitoes include West Nile virus and yellow fever virus, which are single stranded, positive-sense RNA viruses enveloped in a protein coat.
Mosquito-borne disease	Mechanism	Once inside the host's body, the virus will attach itself to a cell's surface through receptor-mediated endocytosis. This essentially means that the proteins and DNA material of the virus are ingested into the host cell. The viral RNA material will undergo several changes and processes inside the host's cell so that it can release more viral RNA that can then be replicated and assembled to infect neighboring host cells. Mosquito-borne flaviviruses also encode viral antagonists to the innate immune system in order to cause persistent infection in mosquitoes and a broad spectrum of diseases in humans. The data on transmissibility via insect vectors of hepatitis C virus, also belonging to family Flaviviridae (as well as for hepatitis B virus, belonging to family Hepadnaviridae) are inconclusive. WHO states that "There is no insect vector or animal reservoir for HCV.", while there are experimental data supporting at least the presence of [PCR]-detectable hepatitis C viral RNA in Culex mosquitoes for up to 13 days.Currently, there are no specific vaccine therapies for West Nile virus approved for humans; however, vaccines are available and some show promise for animals, as a means to intervene with the mechanism of spreading such pathogens.
Mosquito-borne disease	Diagnosis	Doctors can typically identify a mosquito bite by sight.A doctor will perform a physical examination and ask about medical history as well as any travel history. Be ready to give details on any international trips, including the dates you were traveling, the countries you visited and any contact you had with mosquitoes. Dengue fever Diagnosing dengue fever can be difficult, as its symptoms often overlap with many other diseases such as malaria and typhoid fever. Laboratory tests can detect evidence of the dengue viruses, however the results often come back too late to assist in directing treatment.
Mosquito-borne disease	Diagnosis	West Nile virus Medical testing can confirm the presence of West Nile fever or a West Nile-related illness, such as meningitis or encephalitis. If infected, a blood test may show a rising level of antibodies to the West Nile virus. A lumbar puncture (spinal tap) is the most common way to diagnose meningitis, by analyzing the cerebrospinal fluid surrounding your brain and spinal cord. The fluid sample may show an elevated white cell count and antibodies to the West Nile virus if you were exposed. In some cases, an electroencephalography (EEG) or magnetic resonance imaging (MRI) scan can help detect brain inflammation.
Mosquito-borne disease	Diagnosis	Zika virus A Zika virus infection might be suspected if symptoms are present and an individual has traveled to an area with known Zika virus transmission. Zika virus can only be confirmed by a laboratory test of body fluids, such as urine or saliva, or by blood test. Chikungunya Laboratory blood tests can identify evidence of chikungunya or other similar viruses such as dengue and Zika. Blood test may confirm the presence of IgM and IgG anti-chikungunya antibodies. IgM antibodies are highest 3 to 5 weeks after the beginning of symptoms and will continue be present for about 2 months.
Mosquito-borne disease	Prevention	There is a re-emergence of mosquito vectored viruses (arthropod-borne viruses) called arboviruses carried by the Aedes aegypti mosquito. Examples are the Zika virus, chikungunya virus, yellow fever and dengue fever. The re-emergence of the viruses has been at a faster rate, and over a wider geographic area, than in the past. The rapid re-emergence is due to expanding global transportation networks, the mosquito's increasing ability to adapt to urban settings, the disruption of traditional land use and the inability to control expanding mosquito populations. Like malaria, arboviruses do not have a vaccine. (The only exception is yellow fever.) Prevention is focused on reducing the adult mosquito populations, controlling mosquito larvae and protecting individuals from mosquito bites. Depending on the mosquito vector, and the affected community, a variety of prevention methods may be deployed at one time.
Mosquito-borne disease	Prevention	Insecticidal nets and indoor residual spraying The use of insecticide treated mosquito nets (ITNs) are at the forefront of preventing mosquito bites that cause malaria. The prevalence of ITNs in sub-Saharan Africa has grown from 3% of households to 50% of households from 2000 to 2010 with over 254 million insecticide treated nets distributed throughout sub-Saharan Africa for use against the mosquito vectors Anopheles gambiae and Anopheles funestus which carry malaria. Because the Anopheles gambiae feeds indoors (endophagic) and rests indoors after feeding (endophilic), insecticide treated nets (ITNs) interrupt the mosquito's feeding pattern. The ITNs continue to offer protection, even after there are holes in the nets, because of their excito-repellency properties which reduce the number of mosquitoes that enter the home. The World Health Organization (WHO) recommends treating ITNs with the pyrethroid class of insecticides. There is an emerging concern of mosquito resistance to insecticides used in ITNs. Twenty-seven (27) sub-Saharan African countries have reported Anopheles vector resistance to pyrethroid insecticides.Indoor spraying of insecticides is another prevention method widely used to control mosquito vectors. To help control the Aedes aegypti mosquito, homes are sprayed indoors with residual insecticide applications. Indoor residual spraying (IRS) reduces the female mosquito population and mitigates the risk of dengue virus transmission. Indoor residual spraying is completed usually once or twice a year. Mosquitoes rest on walls and ceilings after feeding and are killed by the insecticide. Indoor spraying can be combined with spraying the exterior of the building to help reduce the number of mosquito larvae and subsequently, the number of adult mosquitoes.
Mosquito-borne disease	Prevention	Personal protection methods There are other methods that an individual can use to protect themselves from mosquito bites. Limiting exposure to mosquitoes from dusk to dawn when the majority of mosquitoes are active and wearing long sleeves and long pants during the period mosquitoes are most active. Placing screens on windows and doors is a simple and effective means of reducing the number of mosquitoes indoors. Anticipating mosquito contact and using a topical mosquito repellant with icaridin or DEET is also recommended. Draining or covering water receptacles, both indoor and outdoors, is also a simple but effective prevention method. Removing debris and tires, cleaning drains, and cleaning gutters help larval control and reduce the number of adult mosquitoes.
Mosquito-borne disease	Prevention	Vaccines There is a vaccine for yellow fever which was developed in the 1930s, the yellow 17D vaccine, and it is still in use today. The initial yellow fever vaccination provides lifelong protection for most people and provides immunity within 30 days of the vaccine. Reactions to the yellow fever vaccine have included mild headache and fever, and muscle aches. There are rare cases of individuals presenting with symptoms that mirror the disease itself. The risk of complications from the vaccine are greater for individuals over 60 years of age. In addition, the vaccine is not usually administered to babies under nine months of age, pregnant women, people with allergies to egg protein, and individuals living with AIDS/HIV. The World Health Organization (WHO) reports that 105 million people have been vaccinated for yellow fever in West Africa from 2000 to 2015.To date, there are relatively few vaccines against mosquito-borne diseases, this is due to the fact that most viruses and bacteria caused by mosquitos are highly mutatable. The National Institute of Allergy and Infectious Disease (NIAID) began Phase 1 clinical trials of a new vaccine that would be nearly universal in protecting against the majority of mosquito-borne diseases.
Mosquito-borne disease	Prevention	Education and community involvement The arboviruses have expanded their geographic range and infected populations that had no recent community knowledge of the diseases carried by the Aedes aegypti mosquito. Education and community awareness campaigns are necessary for prevention to be effective. Communities are educated on how the disease is spread, how they can protect themselves from infection and the symptoms of infection. Community health education programs can identify and address the social/economic and cultural issues that can hinder preventative measures. Community outreach and education programs can identify which preventative measures a community is most likely to employ. Leading to a targeted prevention method that has a higher chance of success in that particular community. Community outreach and education includes engaging community health workers and local healthcare providers, local schools and community organizations to educate the public on mosquito vector control and disease prevention.
Mosquito-borne disease	Treatments	Yellow fever Numerous drugs have been used to treat yellow fever disease with minimal satisfaction to date. Patients with multisystem organ involvement will require critical care support such as possible hemodialysis or mechanical ventilation. Rest, fluids, and acetaminophen are also known to relieve milder symptoms of fever and muscle pain. Due to hemorrhagic complications, aspirin should be avoided. Infected individuals should avoid mosquito exposure by staying indoors or using a mosquito net.
Mosquito-borne disease	Treatments	Dengue fever Dengue infection's therapeutic management is simple, cost effective and successful in saving lives by adequately performing timely institutionalized interventions. Treatment options are restricted, while no effective antiviral drugs for this infection have been accessible to date. Patients in the early phase of the dengue virus may recover without hospitalization. However, ongoing clinical research is in the works to find specific anti-dengue drugs.
Mosquito-borne disease	Treatments	Dengue fever occurs via aedes aegypti mosquito( it acts as a vector) Zika virus Zika virus vaccine clinical trials are to be conducted and established. There are efforts being put toward advancing antiviral therapeutics against zika virus for swift control. Present day Zika virus treatment is symptomatic through antipyretics and analgesics. Currently there are no publications regarding viral drug screening. Nevertheless, therapeutics for this infection have been used.
Mosquito-borne disease	Treatments	Chikungunya There are no treatment modalities for acute and chronic chikungunya that currently exist. Most treatment plans use supportive and symptomatic care like analgesics for pain and anti-inflammatories for inflammation caused by arthritis. In acute stages of this virus, rest, antipyretics and analgesics are used to subside symptoms. Most use non-steroidal anti-inflammatory drugs (NSAIDs). In some cases, joint pain may resolve from treatment but stiffness remains.
Mosquito-borne disease	Treatments	Latest treatment The sterile insect technique (SIT) uses irradiation to sterilize insect pests before releasing them in large numbers to mate with wild females. Since they do not produce any offspring, the population, and consequently the disease incidence, is reduced over time. Used successfully for decades to combat fruit flies and livestock pests such as screwworm and tsetse flies, the technique can be adapted also for some disease-transmitting mosquito species. Pilot projects are being initiated or are under way in different parts of the world.
Mosquito-borne disease	Epidemiology	Mosquito-borne diseases, such as dengue fever and malaria, typically affect developing countries and areas with tropical climates. Mosquito vectors are sensitive to climate changes and tend to follow seasonal patterns. Between years there are often dramatic shifts in incidence rates. The occurrence of this phenomenon in endemic areas makes mosquito-borne viruses difficult to treat.Dengue fever is caused by infection through viruses of the family Flaviviridae. The illness is most commonly transmitted by Aedes aegypti mosquitoes in tropical and subtropical regions. Dengue virus has four different serotypes, each of which are antigenically related but have limited cross-immunity to reinfection.Although dengue fever has a global incidence of 50-100 million cases, only several hundreds of thousands of these cases are life-threatening. The geographic prevalence of the disease can be examined by the spread of Aedes aegypti. Over the last twenty years, there has been a geographic spread of the disease. Dengue incidence rates have risen sharply within urban areas which have recently become endemic hot spots for the disease. The recent spread of Dengue can also be attributed to rapid population growth, increased coagulation in urban areas, and global travel. Without sufficient vector control, the dengue virus has evolved rapidly over time, posing challenges to both government and public health officials.Malaria is caused by a protozoan called Plasmodium falciparum. P. falciparum parasites are transmitted mainly by the Anopheles gambiae complex in rural Africa. In just this area, P. falciparum infections comprise an estimated 200 million clinical cases and 1 million annual deaths. 75% of individuals affected in this region are children. As with dengue, changing environmental conditions have led to novel disease characteristics. Due to increased illness severity, treatment complications, and mortality rates, many public health officials concede that malaria patterns are rapidly transforming in Africa. Scarcity of health services, rising instances of drug resistance, and changing vector migration patterns are factors that public health officials believe contribute to malaria's dissemination.
Mosquito-borne disease	Epidemiology	Climate heavily affects mosquito vectors of malaria and dengue. Climate patterns influence the lifespan of mosquitos as well as the rate and frequency of reproduction. Climate change impacts have been of great interest to those studying these diseases and their vectors. Additionally, climate impacts mosquito blood feeding patterns as well as extrinsic incubation periods. Climate consistency gives researchers an ability to accurately predict annual cycling of the disease but recent climate unpredictability has eroded researchers' ability to track the disease with such precision.
Mosquito-borne disease	Advances in biological control of arboviruses	In many insect species, such as Drosophila melanogaster, researchers found that a natural infection with the bacteria strain Wolbachia pipientis increases the fitness of the host by increasing resistance to RNA viral infections. Robert L. Glaser and Mark A. Meola investigated Wolbachia-induced resistance to West Nile virus (WNV) in Drosophila melanogaster (fruit flies). Two groups of fruit flies were naturally infected with Wolbachia. Glaser and Meola then cured one group of fruit flies of Wolbachia using tetracycline. Both the infected group and the cured groups were then infected with WNV. Flies infected with Wolbachia were found to have a changed phenotype that caused resistance to WNV. The phenotype was found to be caused by a “dominant, maternally transmitted, cytoplasmic factor”. The WNV-resistance phenotype was then reversed by curing the fruit flies of Wolbachia. Since Wolbachia is also maternally transmitted, it was found that the WNV-resistant phenotype is directly related to the Wolbachia infection. West Nile virus is transmitted to humans and animals through the Southern house mosquito, Culex quinquefasciatus. Glaser and Meola knew vector compatibility could be reduced through Wolbachia infection due to studies done with other species of mosquitoes, mainly, Aedes aegypti. Their goal was to transfer WNV resistance to Cx. quinquefasciatus by inoculating the embryos of the mosquito with the same strain of Wolbachia that naturally occurred in the fruit flies. Upon infection, Cx. quinquefasciatus showed an increased resistance to WNV that was transferable to offspring. The ability to genetically modify mosquitoes in the lab and then have the infected mosquitoes transmit it to their offspring showed that it was possible to transmit the bacteria to wild populations to decrease human infections.In 2011, Ary Hoffmann and associates produced the first case of Wolbachia-induced arbovirus resistance in wild populations of Aedes aegypti through a small project called Eliminate Dengue: Our Challenge. This was made possible by an engineered strain of Wolbachia termed wMel that came from D. melanogaster. The transfer of wMel from D. melanogaster into field-caged populations of the mosquito Aedes aegypti induced resistance to dengue, yellow fever, and chikungunya viruses. Although other strains of Wolbachia also reduced susceptibility to dengue infection, they also put a greater demand on the fitness of Ae. aegypti. wMel was different in that it was thought to only cost the organism a small portion of its fitness. wMel-infected Ae. aegypti were released into two residential areas in the city of Cairns, Australia over a 14-week period. Hoffmann and associates, released a total of 141,600 infected adult mosquitoes in Yorkeys Knob suburb and 157,300 in Gordonvale suburb. After release, the populations were monitored for three years to record the spread of wMel. Population monitoring was gauged by measuring larvae laid in traps. At the beginning of the monitoring period but still within the release period, it was found that wMel-infected Ae. aegypti had doubled in Yorkeys Knob and increased 1.5-fold in Gordonvale. Uninfected Ae. aegypti populations were in decline. By the end of the three years, wMel-infected Ae. aegypti had stable populations of about 90%. However, these populations were isolated to the Yorkeys Knob and Gordonvale suburbs due to unsuitable habitat surrounding the neighborhoods.Although populations flourished in these areas with nearly 100% transmission, no signs of spread were noted, proving disappointing for some. Following this experiment, Tom L. Schmidt and his colleagues conducted an experiment releasing Wolbachia-infected Aedes aegypti using different site selection methods occurred in different areas of Cairns during 2013. The release sites were monitored over two years. This time the release was done in urban areas that were adjacent to adequate habitat to encourage mosquito dispersal. Over the two years, the population doubled, and spatial spread was also increased, unlike the first release, giving ample satisfactory results. By increasing the spread of the Wolbachia-infected mosquitoes, the researchers were able to establish that population of a large city was possible if the mosquitoes were given adequate habitat to spread into upon release in different local locations throughout the city. An important detail in both of these studies is that no adverse effects on public health or the natural ecosystem occurred. This made it an extremely attractive alternative to traditional insecticide methods given the increased pesticide resistance occurring from heavy use.
Mosquito-borne disease	Advances in biological control of arboviruses	From the success seen in Australia, the researchers were able to begin operating in more threatened portions of the world. The Eliminate Dengue program spread to 10 countries throughout Asia, Latin America, and the Western Pacific blooming into the non-profit organization, World Mosquito Program, as of September 2017. They still use the same technique of infecting wild populations of Ae. aegypti as they did in Australia, but their target diseases now include Zika, chikungunya and yellow fever as well as dengue. Although not alone in their efforts to use Wolbachia-infected mosquitoes to reduce mosquito-borne disease, the World Mosquito Program method is praised for being self-sustaining in that it causes permanent phenotype change rather than reducing mosquito populations through cytoplasmic incompatibility through male-only dispersal.
Ytterbium(III) bromide	Ytterbium(III) bromide	Ytterbium(III) bromide (YbBr3) is an inorganic chemical compound. Refer to the adjacent table for the main properties of Ytterbium(III) bromide.
Ytterbium(III) bromide	Preparation	Dissolving ytterbium oxide into 40% hydrobromic acid forms YbBr3·6H2O crystals. After mixing the hydrate with ammonium bromide and heating it in a vacuum, anhydrous YbBr3 can be obtained. Yb2O3 + 6 HBr → 2 YbBr3 + 3 H2OYtterbium(III) bromide can also be prepared by directly heating ytterbium oxide and ammonium bromide.
Linearizer	Linearizer	In signal processing, linearizers are electronic circuits which improve the non-linear behaviour of amplifiers to increase efficiency and maximum output power.
Linearizer	Linearizer	Creating circuits with the inverted behaviour to the amplifier is one way to implement this concept. These circuits counteract the non-linearities of the amplifier and minimize the distortion of the signal. This increases linear operating range up to the saturation (maximum output power) of the amplifier. Linearized amplifiers have a significantly higher efficiency with improved signal quality. There are different concepts to linearize an amplifier, including pre- and post-distortion and feedback linearization. Most commonly used is pre-distortion linearization.
Linearizer	Linearizer	The function performed by the linearizer in relation to the amplifier is very similar to that of eyeglasses in relation to the eye. The eye distorts the image seen; the glasses pre-distort the image. When these two distortions are combined, the result is a clear image. For the nearsighted, the glasses must pre-distort the image one way. For the farsighted, the image must be pre-distorted in the opposite way.
Linearizer	Functionality of Pre-distortion Linearizers	Non-linearities occur in amplifiers due to decreasing amplification and changing phase when operated near saturation. This behavior is commonly referred to as gain or phase compression. The pre-distortion linearizer is designed to compensate these changes. The resulting behavior is commonly referred to as gain or phase expansion.
Linearizer	Functionality of Pre-distortion Linearizers	A pre-distortion linearizer works by creating signal distortion (amplitude and phase) that is the complement of the signal distortion inherent in the High-Powered Amplifier. The signal to be amplified is first passed through the linearizer, distorting the signal, with no loss in gain. The distorted signal is then fed to the High-Powered Amplifier to be amplified. The distortion inherent in the High-Powered Amplifier negates the distortion introduced by the linearizer producing a near linear transfer characteristic.
Linearizer	Functionality of Pre-distortion Linearizers	Figure 1 shows the amplification (gain) contingent upon input power. The gain compression of the amplifier starts above a certain input power level (red curve).
Linearizer	Functionality of Pre-distortion Linearizers	By adding a pre-distortion linearizer (blue curve) in front of the amplifier, the gain compression effect is compensated up to a certain power level (green curve). The point where the gain of the total system is starting to drop off is pushed to a higher power level thereby increasing the linear operating range. In practice, the linear output power level of an amplifier increases significantly (up to four times).
Linearizer	Functionality of Pre-distortion Linearizers	The increased linear operating range is also illustrated in Figure 2 (light blue area). The chart shows the relationship between input and output power of an amplifier with and without pre-distortion linearizer. The dotted line shows the output power of the amplifier as a function of the input power on a logarithmic scale. In this illustration the compression is shown as the deviation from the ideal 45° line. The amplifier with pre-distortion linearizer (solid line) deviates from the ideal line at a much higher power level. The light blue area illustrates the improved linear operating power range gained by adding a pre-distortion linearizer.
Linearizer	Advantages of Pre-distortion Linearizers	Pre-distortion linearizers operate in the small signal area and increase the DC power consumption of the system only marginally. Additional advantages can be deduced including: Small foot print, low weight. Low cost solution compared to use of higher power amplifier in similar linear operating range. Lower environmental impact through improved efficiency. Retrofit possible Adjustment to different amplifier types possible Highly reliable
Linearizer	Typical Properties of a Pre-distortion Linearizer	Dimensions: Dependent on design in the range of a few cm Weight: 20g to 200g depending on features Frequencies: 1 to 50 GHz with different bandwidths Expansion levels: Gain: up to 10 dB, dependent on amplifier data Phase: up to 60°
Linearizer	Applications	The preferred application of linearizers is in high power amplifiers using electron tubes (traveling wave tubes, Klystron tubes, magnetron tubes) or solid state amplifiers (GaN, GaAs, Si). These systems are used in broadband voice and data transfer applications including Satellite Communication, Broadband Internet, or HD/3D television. These applications require high signal quality. The optimization of the amplifier characteristics enables the ideal use of available power and leads to energy savings of up to 50%.
Brickfielder	Brickfielder	The Brickfielder is a hot and dry wind in Southern Australia that develops in the country's deserts in late spring and summer, which heavily raises temperatures in the southeast coast.
Brickfielder	Etymology	The term name was recorded in early 19th century, which emanated from the name of Brickfield Hill, a site which was a former brickworks in the centre of Sydney CBD. The area was associated with dusty wind that conveyed clouds of reddish dust from the brickworks over the emerging city. A more frequently used term for the winds is a "burster".
Brickfielder	Development	The brickfielder precedes the passage of a frontal zone of a low pressure system passing by, and causes severe dust storms that often last for days and led to its naming as the winds blow up red brick dust. It blows to the coastal regions in the south from the outback, reaching the capitals of Adelaide and Melbourne to south, and Sydney to the east. The dry northwesterly desert air from the interior of Australia transports dusty clouds alongside sudden hot spells that usually surpass 38C (100F) to places that feature a relatively mild climate. The temperature might rise up by 15 to 20°C within hours.
Brickfielder	Effects	The northern brickfielder is almost invariably followed by a strong "southerly buster," cloudy and cool from the ocean. The two winds are due to the same cause, viz. a cyclonic system over the Australian Bight. These systems frequently extend inland as a narrow V-shaped depression (the apex northward), bringing the winds from the north on their eastern sides and from the south on their western. Hence as the narrow system passes eastward the wind suddenly changes from north to south, and the thermometer has been known to fall 15 °F (−9 °C) in twenty minutes.On the coastal plains of New South Wales, such as in Western Sydney, the Brickfielder may be exacerbated by the southeast Australian foehn.
Complex lamellar vector field	Complex lamellar vector field	In vector calculus, a complex lamellar vector field is a vector field which is orthogonal to a family of surfaces. In the broader context of differential geometry, complex lamellar vector fields are more often called hypersurface-orthogonal vector fields. They can be characterized in a number of different ways, many of which involve the curl. A lamellar vector field is a special case given by vector fields with zero curl.
Complex lamellar vector field	Complex lamellar vector field	The adjective "lamellar" derives from the noun "lamella", which means a thin layer. The lamellae to which "lamellar vector field" refers are the surfaces of constant potential, or in the complex case, the surfaces orthogonal to the vector field. This language is particularly popular with authors in rational mechanics.
Complex lamellar vector field	Complex lamellar vector fields	In vector calculus, a complex lamellar vector field is a vector field in three dimensions which is orthogonal to its own curl. That is, 0. The term lamellar vector field is sometimes used as a synonym for the special case of an irrotational vector field, meaning that ∇×F=0. Complex lamellar vector fields are precisely those that are normal to a family of surfaces. An irrotational vector field is locally the gradient of a function, and is therefore orthogonal to the family of level surfaces (the equipotential surfaces). Any vector field can be decomposed as the sum of an irrotational vector field and a complex lamellar field.
Complex lamellar vector field	Hypersurface-orthogonal vector fields	In greater generality, a vector field F on a pseudo-Riemannian manifold is said to be hypersurface-orthogonal if through an arbitrary point there is a smoothly embedded hypersurface which, at all of its points, is orthogonal to the vector field. By the Frobenius theorem this is equivalent to requiring that the Lie bracket of any smooth vector fields orthogonal to F is still orthogonal to F.The condition of hypersurface-orthogonality can be rephrased in terms of the differential 1-form ω which is dual to F. The previously given Lie bracket condition can be reworked to require that the exterior derivative dω, when evaluated on any two tangent vectors which are orthogonal to F, is zero. This may also be phrased as the requirement that there is a smooth 1-form whose wedge product with ω equals dω.Alternatively, this may be written as the condition that the differential 3-form ω ∧ dω is zero. This can also be phrased, in terms of the Levi-Civita connection defined by the metric, as requiring that the totally anti-symmetric part of the 3-tensor field ωi∇j ωk is zero. Using a different formulation of the Frobenius theorem, it is also equivalent to require that ω is locally expressible as λ du for some functions λ and u.In the special case of vector fields on three-dimensional Euclidean space, the hypersurface-orthogonal condition is equivalent to the complex lamellar condition, as seen by rewriting ω ∧ dω in terms of the Hodge star operator as ∗⟨ω, ∗dω⟩, with ∗dω being the 1-form dual to the curl vector field.Hypersurface-orthogonal vector fields are particularly important in general relativity, where (among other reasons) the existence of a Killing vector field which is hypersurface-orthogonal is one of the requirements of a static spacetime. In this context, hypersurface-orthogonality is sometimes called irrotationality, although this is in conflict with the standard usage in three dimensions. Another name is rotation-freeness.An even more general notion, in the language of Pfaffian systems, is that of a completely integrable 1-form ω, which amounts to the condition ω ∧ dω = 0 as given above. In this context, there is no metric and so there is no notion of "orthogonality".
Duocarmycin	Duocarmycin	The duocarmycins are members of a series of related natural products first isolated from Streptomyces bacteria in 1978. They are notable for their extreme cytotoxicity and thus represent a class of exceptionally potent antitumour antibiotics.
Duocarmycin	Biological activity	As small-molecule, synthetic, DNA minor groove binding alkylating agents, duocarmycins are suitable to target solid tumors. They bind to the minor groove of DNA and alkylate the nucleobase adenine at the N3 position. The irreversible alkylation of DNA disrupts the nucleic acid architecture, which eventually leads to tumor cell death. Analogues of naturally occurring antitumour agents, such as duocarmycins, represent a new class of highly potent antineoplastic compounds.The work of Dale L. Boger and others created a better understanding of the pharmacophore and mechanism of action of the duocarmycins. This research has led to synthetic analogs including adozelesin, bizelesin, and carzelesin which progressed into clinical trials for the treatment of cancer. Similar research that Boger utilized for comparison to his results involving elimination of cancerous tumors and antigens was centered around the use of similar immunoconjugates that were introduced to cancerous colon cells. These studies related to Boger's research involving antigen-specificity that is necessary to the success of the duocarmycins as antitumor treatments.
Duocarmycin	Duocarmycin analogues vs tubulin binders	The duocarmycin have shown activity in a variety of multi-drug resistant (MDR) models. Agents that are part of this class of duocarmycins have the potency in the low picomolar range. This makes them suitable for maximizing the cell-killing potency of antibody-drug conjugates to which they are attached.
Duocarmycin	Antibody-drug conjugates	The DNA modifying agents such as duocarmycin are being used in the development of antibody-drug conjugate or ADCs. Scientists at The Netherlands-based Synthon (formerly Syntarga) have combined a unique linkers with duocarmycin derivatives that have a hydroxyl group which is crucial for biological activity. Using this technology scientists aim to create ADCs having an optimal therapeutic window, balancing the effect of potent cell-killing agents on tumor cells versus healthy cells.
Duocarmycin	Synthetic analogs	The synthetic analogs of duocarmycins include adozelesin, bizelesin, and carzelesin. As members of the cyclopropylpyrroloindole family, these investigational drugs have progressed into clinical trials for the treatment of cancer. Bizelesin Bizelesin is antineoplastic antibiotic which binds to the minor groove of DNA and induces interstrand cross-linking of DNA, thereby inhibiting DNA replication and RNA synthesis. Bizelesin also enhances p53 and p21 induction and triggers G2/M cell-cycle arrest, resulting in cell senescence without apoptosis.
Amortized analysis	Amortized analysis	In computer science, amortized analysis is a method for analyzing a given algorithm's complexity, or how much of a resource, especially time or memory, it takes to execute. The motivation for amortized analysis is that looking at the worst-case run time can be too pessimistic. Instead, amortized analysis averages the running times of operations in a sequence over that sequence.: 306 As a conclusion: "Amortized analysis is a useful tool that complements other techniques such as worst-case and average-case analysis.": 14 For a given operation of an algorithm, certain situations (e.g., input parametrizations or data structure contents) may imply a significant cost in resources, whereas other situations may not be as costly. The amortized analysis considers both the costly and less costly operations together over the whole sequence of operations. This may include accounting for different types of input, length of the input, and other factors that affect its performance.
Amortized analysis	History	Amortized analysis initially emerged from a method called aggregate analysis, which is now subsumed by amortized analysis. The technique was first formally introduced by Robert Tarjan in his 1985 paper Amortized Computational Complexity, which addressed the need for a more useful form of analysis than the common probabilistic methods used. Amortization was initially used for very specific types of algorithms, particularly those involving binary trees and union operations. However, it is now ubiquitous and comes into play when analyzing many other algorithms as well.
Amortized analysis	Method	Amortized analysis requires knowledge of which series of operations are possible. This is most commonly the case with data structures, which have state that persists between operations. The basic idea is that a worst-case operation can alter the state in such a way that the worst case cannot occur again for a long time, thus "amortizing" its cost. There are generally three methods for performing amortized analysis: the aggregate method, the accounting method, and the potential method. All of these give correct answers; the choice of which to use depends on which is most convenient for a particular situation. Aggregate analysis determines the upper bound T(n) on the total cost of a sequence of n operations, then calculates the amortized cost to be T(n) / n.
Amortized analysis	Method	The accounting method is a form of aggregate analysis which assigns to each operation an amortized cost which may differ from its actual cost. Early operations have an amortized cost higher than their actual cost, which accumulates a saved "credit" that pays for later operations having an amortized cost lower than their actual cost. Because the credit begins at zero, the actual cost of a sequence of operations equals the amortized cost minus the accumulated credit. Because the credit is required to be non-negative, the amortized cost is an upper bound on the actual cost. Usually, many short-running operations accumulate such credit in small increments, while rare long-running operations decrease it drastically.
Amortized analysis	Method	The potential method is a form of the accounting method where the saved credit is computed as a function (the "potential") of the state of the data structure. The amortized cost is the immediate cost plus the change in potential.
Amortized analysis	Examples	Dynamic array Consider a dynamic array that grows in size as more elements are added to it, such as ArrayList in Java or std::vector in C++. If we started out with a dynamic array of size 4, we could push 4 elements onto it, and each operation would take constant time. Yet pushing a fifth element onto that array would take longer as the array would have to create a new array of double the current size (8), copy the old elements onto the new array, and then add the new element. The next three push operations would similarly take constant time, and then the subsequent addition would require another slow doubling of the array size.
Amortized analysis	Examples	In general if we consider an arbitrary number of pushes n + 1 to an array of size n, we notice that push operations take constant time except for the last one which takes Θ(n) time to perform the size doubling operation. Since there were n + 1 operations total we can take the average of this and find that pushing elements onto the dynamic array takes: nΘ(1)+Θ(n)n+1=Θ(1) , constant time.
Amortized analysis	Examples	Queue Shown is a Ruby implementation of a Queue, a FIFO data structure: The enqueue operation just pushes an element onto the input array; this operation does not depend on the lengths of either input or output and therefore runs in constant time.
Amortized analysis	Examples	However the dequeue operation is more complicated. If the output array already has some elements in it, then dequeue runs in constant time; otherwise, dequeue takes O(n) time to add all the elements onto the output array from the input array, where n is the current length of the input array. After copying n elements from input, we can perform n dequeue operations, each taking constant time, before the output array is empty again. Thus, we can perform a sequence of n dequeue operations in only O(n) time, which implies that the amortized time of each dequeue operation is O(1) .Alternatively, we can charge the cost of copying any item from the input array to the output array to the earlier enqueue operation for that item. This charging scheme doubles the amortized time for enqueue but reduces the amortized time for dequeue to O(1)
Amortized analysis	Common use	In common usage, an "amortized algorithm" is one that an amortized analysis has shown to perform well. Online algorithms commonly use amortized analysis.
Amortized analysis	Literature	"Lecture 7: Amortized Analysis" (PDF). Carnegie Mellon University. Retrieved 14 March 2015. Allan Borodin and Ran El-Yaniv (1998). Online Computation and Competitive Analysis. pp. 20, 141.
Bristle	Bristle	A bristle is a stiff hair or feather (natural or artificial), either on an animal, such as a pig, a plant, or on a tool such as a brush or broom.

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