title: Coyote vs. Acme

text: In August 2018, Warner Bros. announced the development of a Wile E. Coyote project, titled "Coyote vs. Acme", with "The Lego Batman Movie" director Chris McKay as producer and Jon and Josh Silberman writing the screenplay. In mid-December 2019, Dave Green signed on to direct the live-action animated hybrid film, while Jon and Josh Silberman were replaced as screenwriters, though they remained as producers. In December 2020, McKay left the project, while Jon and Josh Silberman left their producing roles and returned to screenwriting duties alongside Samy Burch, Jeremy Slater, and James Gunn. Along with the departure of McKay, it was reported that the film would draw inspiration from the fictional "New Yorker" article of the same name by Ian Frazier.


title: Coyote vs. Acme

text: In February 2022, John Cena was announced to have been cast as the film's main antagonist, described as the lawyer in defense of ACME and the former boss to Wile E.'s lawyer; he previously collaborated with Gunn on the DC Extended Universe projects "The Suicide Squad" (2021) and "Peacemaker" (2022). The following month, Will Forte and Lana Condor would be added to the cast, with Forte starring as Coyote's lawyer.


title: Coyote vs. Acme

text: In October 2022, Eric Bauza was confirmed to voice Wile E. Coyote. In November 2022, Foghorn Leghorn, Granny, Sylvester the Cat and Tweety were confirmed to be in the film. In December 2022, Bugs Bunny, Daffy Duck, Elmer Fudd and Yosemite Sam were also confirmed to be in the film.


title: Coyote vs. Acme

text: Principal photography commenced on April 1, 2022, with cinematographer Brandon Trost. Filming took place in Albuquerque, New Mexico, as the location was known to be an iconic location in numerous "Looney Tunes" cartoons. Filming wrapped on May 28, 2022.


title: Coyote vs. Acme

text: "Coyote vs. Acme" was originally scheduled to be theatrically released in the United States on July 21, 2023, by Warner Bros. Pictures. On April 26, 2022, it was taken off the release schedule, with "Barbie" taking over its original release date. The film had a screening on October 23, 2022.


title: Auto rickshaw

text: An auto rickshaw is a motorized version of the pulled rickshaw or cycle rickshaw. Most have three wheels and do not tilt. They are known by many terms in various countries including auto, auto rickshaw, baby taxi, mototaxi, pigeon, jonnybee, bajaj, chand gari, lapa, tuk-tuk, tum-tum, Keke-napep, Maruwa, 3wheel, pragya, bao-bao, easy bike, cng and tukxi.


title: Auto rickshaw

text: The auto rickshaw is a common form of urban transport, both as a vehicle for hire and for private use, in many countries around the world. They are especially common in countries with tropical or subtropical climates, since they usually are not fully enclosed, and in many developing countries because they are relatively inexpensive to own and operate. As of 2019, Bajaj Auto of India is the world's largest auto rickshaw manufacturer, selling 780,000 during the 2019 fiscal year.


title: Auto rickshaw

text: There are many different auto rickshaw designs. The most common type is characterized by a sheet-metal body or open frame resting on three wheels; a canvas roof with drop-down side curtains; a small cabin at the front for the driver operating handlebar controls; and a cargo, passenger, or dual purpose space at the rear. Another common type is a motorcycle that has an expanded sidecar or, less often, is pushing or pulling a passenger compartment.


title: Auto rickshaw

text: In the 1930s Japan, which was the most industrialized country in Asia at the time, encouraged the development of motorized vehicles including less expensive three-wheeled vehicles based on motorcycles. The Mazda-Go, a 3-wheel open "truck" released in 1931, is often considered the first of what became auto rickshaws. Later that decade the Japanese Ministry of Posts and Telecommunications of Japan distributed about 20,000 used three-wheelers to Southeast Asia as part of efforts to expand its influence in the region. They became popular in some areas, especially Thailand, which developed local manufacturing and design after the Japanese government abolished the three-wheeler license in Japan in 1965 .


title: Auto rickshaw

text: Production in Southeast Asia started from the knockdown production of the Daihatsu Midget, which was introduced in 1959. An exception is the indigenously-modified Philippine tricycle, which originates from the Rikuo Type 97 motorcycle with a sidecar, introduced to the islands in 1941 by the Imperial Japanese Army during World War II.


title: Auto rickshaw

text: In Europe, Corradino D'Ascanio, aircraft designer at Piaggio and inventor of the Vespa, came up with the idea of building a light three-wheeled commercial vehicle to power Italy's post-war economic reconstruction. The Piaggio Ape followed suit in 1947.


title: Auto rickshaw

text: Locally named the "tuktuk," the rickshaw is used for transportation in most parts of Egypt. It is generally rare to find in suburban areas and newer parts of cities such as New Cairo and on highways due to police control.


title: Auto rickshaw

text: Together with the recent boom of recreational facilities in Gaza for the local residents, donkey carts have all but been displaced by tuk-tuks in 2010. Due to the ban by Egypt and Israel on the import of most motorised vehicles, the tuk-tuks have had to be smuggled in parts through the tunnel network connecting Gaza with Egypt.


title: Auto rickshaw

text: In Madagascar, man-powered rickshaws are a common form of transportation in a number of cities, especially Antsirabe. They are known as "posy" from "pousse-pousse", meaning "push-push". Cycle rickshaws took off since 2006 in a number of flat cities like Toamasina and replaced the major part of the posy, and are now threatened by the auto rickshaws, introduced in 2009. Provincial capitals like Toamasina, Mahajanga, Toliara, and Antsiranana are taking to them rapidly. They are known as "bajaji" in the north and "tuk-tuk" or "tik-tik" in the east, and are now licensed to operate as taxis. They are not yet allowed an operating licence in the congested, and more polluted national capital, Antananarivo.


title: Auto rickshaw

text: The auto rickshaw is used to provide transportation in cities all over Nigeria. Popularity and use varies across the country however. In Lagos, for example, the "keke" (Yoruba for bicycle) is regulated and transportation around the state's highways is prohibited.


title: Auto rickshaw

text: Tuk-tuks, introduced in Durban in the late 1980s enjoyed growing popularity in recent years, particularly in Gauteng. In Cape Town they are used to deliver groceries and, more recently, transport tourists.


title: Auto rickshaw

text: Rickshaws, known as "Raksha" in Sudan, is the most common mean of transportation followed by the bus in the capital Khartoum.


title: Auto rickshaw

text: Locally known as "bajaji", they are a common mode of transportation in Dar es Salaam, and many other cities and villages.


title: Auto rickshaw

text: A local delivery company called as Sokowatch in 2020 began a pilot project using electric tuk-tuks, to cut pollution.


title: Auto rickshaw

text: Hende Moto EV & Taxi company was founded in 2019 by Devine Mafa, an American-Zimbabwean businessman. Hende Moto taxi's were first introduced in Zimbabwe as the first car, manufactured by a Zimbabwean three wheeler manufacturing company Hende Moto Pvt Ltd. Hende Moto Engine in a Safari fiberglass body. The first Hende Moto Taxi was introduced in Kwekwe August 2019, Zimbabwe and thereafter, Victoria Falls City came second and lastly Harare 2019. Hende Moto is also the manufacturer of the first Zimbabwean made electric passenger three wheeled vehicle. It operates on a lithium ion battery that has a range of 70 miles on a 6-hour charge.


title: Auto rickshaw

text: Auto rickshaws are very common in the eastern Afghan city of Jalalabad, where they are popularly decorated in art and colors. They are also popular in the northern city of Kunduz.


title: Auto rickshaw

text: Auto rickshaws (locally called "baby taxis" and more recently "CNGs" due to their fuel source, compressed natural gas) are one of the more popular modes of transport in Bangladesh mainly due to their size and speed. They are best suited to narrow, crowded streets, and are thus the principal means of covering longer distances within urban areas.


title: Auto rickshaw

text: Two-stroke engines had been identified as one of the leading sources of air pollution in Dhaka. Thus, since January 2003, traditional auto rickshaws were banned from the capital; only the new natural gas-powered models (CNG) were permitted to operate within the city limits. All CNGs are painted green to signify that the vehicles are eco-friendly and that each one has a meter built-in.


title: Auto rickshaw

text: Most cities offer auto rickshaw service, although cycle rickshaws are also common and even hand-pulled rickshaws exist in certain areas such as Kolkata. Many state governments have launched an initiative of women friendly rickshaw service called the Pink Rickshaws driven by women. The drivers are known as the Rickshaw-wallah, "auto-wallah" or "tuktuk-wallah".


title: Auto rickshaw

text: Auto rickshaws are used in cities and towns for short distances; they are less suited to long distances because they are slow and the carriages are open to air pollution. Auto rickshaws (often called "autos") provide cheap and efficient transportation. Modern auto rickshaws run on electricity as government pushes for e mobility through its FAME-II scheme, compressed natural gas (CNG) and liquified petroleum gas (LPG) due to government regulations and are environmentally friendly compared to full-sized cars.


title: Auto rickshaw

text: To augment speedy movement of traffic, auto rickshaws are not allowed in the southern part of Mumbai.


title: Auto rickshaw

text: There are two types of auto rickshaws in India. In older versions the engines were below the driver's seat, while in newer versions engines are in the rear. They normally run on petrol, CNG, or diesel. The seating capacity of a normal rickshaw is four, including the driver's seat. Six-seater rickshaws exist in different parts of the country, but the model was officially banned in the city of Pune on 10 January 2003 by the Regional Transport Authority (RTA).


title: Auto rickshaw

text: Apart from this, modern electric auto rickshaws which runs on electric motor have high torque and loading capacity with better speed is also gaining popularity in India. Many auto drivers moved to electric three wheeler as the prices of CNG or Diesel is very high and that type of auto rickshaws are much costlier compared to the electric auto rickshaw. Government is also taking actions to convert current CNG and Diesel rickshaws to Electric Rickshaws.


title: Auto rickshaw

text: CNG autos in many cities (e.g. Delhi, Agra) are distinguishable from the earlier petrol-powered autos by a green and yellow livery, as opposed to the earlier black and yellow appearance. In other cities (such as Mumbai) the only distinguishing feature is the 'CNG' print found on the back or side of the auto. Some local governments are considering four-stroke engines instead of two-stroke versions.


title: Auto rickshaw

text: Auto rickshaw manufacturers in India include Bajaj Auto, Atul Auto Limited, Oculus Auto, Kerala Automobiles Limited, Force Motors, Mahindra & Mahindra, Piaggio Ape, TVS Motors and Fleek Motors.


title: Auto rickshaw

text: In Delhi there also used to be a variant powered by a Harley-Davidson engine called the "phat-phati", because of the sound it made. The story goes that shortly after Independence a stock of Harley-Davidson motorbikes were found that had been used by British troops during World War II and left behind in a military storage house in Delhi. Some enterprising drivers purchased these bikes, added on a gear box (probably from a Willys jeep), welded on a passenger compartment that was good for four to six passengers, and put the unconventional vehicles onto the roads. A 1998 ruling of the Supreme Court against the use of polluting vehicles finally signed the death warrant of Delhi's phat-phatis.


title: Auto rickshaw

text: Generally rickshaw fares are controlled by the government, however auto (and taxi) driver unions frequently go on strike demanding fare hikes. They have also gone on strike multiple times in Delhi to protest against the government and High Court's 2012 order to install GPS systems, and even though GPS installation in public transport was made mandatory in 2015, as of 2017 compliance remains very low.


title: Auto rickshaw

text: The 200cc variant of the Bajaj Auto auto rickshaw was used in the 2022 Rickshaw Run to set the record for the worlds highest auto rickshaw, over the Umling La Pass, at 5800meters/19024feet.


title: Auto rickshaw

text: Auto rickshaws were a popular mode of transport in Nepal during the 1980s and 1990s, until the government banned the movement of 600 such vehicles in the early 2000s. The earliest auto rickshaws running in Kathmandu were manufactured by Bajaj Auto.


title: Auto rickshaw

text: Nepal has been a popular destination for the Rickshaw Run. The 2009 Fall Run took place in Goa, India and ended in Pokhara, Nepal.


title: Auto rickshaw

text: Auto rickshaws are a popular mode of transport in Pakistani towns and are mainly used for travelling short distances within cities. One of the major manufacturers of auto rickshaws is Piaggio. The government is taking measures to convert all gasoline powered auto rickshaws to cleaner CNG rickshaws by 2015 in all the major cities of Pakistan by issuing easy loans through commercial banks. Environment Canada is implementing pilot projects in Lahore, Karachi, and Quetta with engine technology developed in Mississauga, Ontario, Canada that uses CNG instead of gasoline in the two-stroke engines, in an effort to combat environmental pollution and noise levels.


title: Auto rickshaw

text: In many cities in Pakistan, there are also motorcycle rickshaws, usually called "chand gari" (moon car) or "chingchi", after the Chinese company Jinan Qingqi Motorcycle Co. Ltd who first introduced these to the market.


title: Auto rickshaw

text: There are many rickshaw manufacturers in Pakistan. Lahore is the hub of CNG auto rickshaw manufacturing. Manufacturers include: New Asia automobile Pvt, Ltd; AECO Export Company; STAHLCO Motors; Global Sources; Parhiyar Automobiles; Global Ledsys Technologies; Siwa Industries; Prime Punjab Automobiles; Murshid Farm Industries; Sazgar Automobiles; NTN Enterprises; and Imperial Engineering Company.


title: Auto rickshaw

text: Auto rickshaws, commonly known as Three-wheelers, tuk-tuks () or trishaws can be found on all roads in Sri Lanka transporting people or freight . Sri Lankan three-wheelers are of the style of the light Phnom Penh-type. Most of the three-wheelers in Sri Lanka are a slightly modified Indian Bajaj model, imported from India though there are few manufactured locally and increasingly imports from other countries in the region and other brands of three-wheelers such as Piaggio Ape. a new gasoline powered tuk-tuk typically costs around , while a newly introduced Chinese electric model cost around . Since 2008, the Sri Lankan government has banned the import of all 2-stroke gasoline engines due to environmental concerns. Ones imported to the island now are four-stroke engines. Most three-wheelers are available as hired vehicles, with few being used to haul goods or as private company or advertising vehicles. Bajaj enjoys a virtual monopoly in the island, with its agent being David Pieries Motor Co, Ltd. A few three-wheelers in Sri Lanka have distance meters. In the capital city it is becoming more and more common. The vast majority of fares are negotiated between the passenger and driver. There are 1.2 million trishaw's in Sri Lanka and most are on financial loans.


title: Auto rickshaw

text: In Sri Lanka, tourists are able to drive a tuktuk. Through the Automobile Association of Ceylon, tourists are able to get a temporary Recognition Permit which allows them to drive a three-wheeler legally.


title: Auto rickshaw

text: In Cambodia, a passenger-carrying three-wheeled vehicle is known as "lemorque" from the French "remorque." It is a widely used form of transportation in the capital of Phnom Penh and for visitors touring the Angkor temples in Siem Reap. Some have four wheels and is composed of a motorcycle (which leans) and trailer (which does not). Cambodian cities have a much lower volume of automobile traffic than Thai cities, and tuk-tuks are still the most common form of urban transport. There are more than 6,000 tuk-tuks in Phnom Penh, according to the Independent Democracy of Informal Economy Association (IDEA), a union that represents tuk-tuk drivers among other members.


title: Auto rickshaw

text: In Indonesia, auto rickshaws are popular in Jakarta as "Bajay", Java, Medan and Gorontalo as "Bentor", and some parts of Sulawesi and other places in the country. In Jakarta, the auto rickshaws are called "Bajay" or "Bajaj" and they are the same to as the ones in India but are colored blue (for the ones which use Compressed natural gas) and orange (for the ones which use normal gasoline fuel). The blue ones are imported from India with the brand of Bajaj and TVS and the orange ones are the old design from 1990 and are not powered by gas like the blue ones, yet the government is increasing units of the blue Bajays and is step by step decreasing the orange bajays. The Bajaj is one of the most popular modes of transportation in the city. Outside of Jakarta, the "bentor"-style auto rickshaw is ubiquitous, with the passenger cabin mounted as a sidecar (like in Medan) or in-front (like the ones in some parts of Sulawesi) to a motorcycle.


title: Auto rickshaw

text: In the Philippines, a similar mode of public transport is the "tricycle" (Filipino: "traysikel"; Cebuano: "traysikol"). Unlike auto rickshaws, however, it has a motorcycle with a sidecar configuration and a different origin. The exact date of its appearance in the Philippines is unknown, but it started appearing after World War 2, roughly at the same time as the appearance of the jeepney. It is most likely derived from the Rikuo Type 97 military motorcycle used by the Imperial Japanese Army in the Philippines starting at 1941. The motorcycle was essentially a licensed copy of a Harley-Davidson with a sidecar. However, there is also another hypothesis which places the origin of the tricycle to the similarly built "trisikad", a human-powered cycle rickshaw built in the same configuration as the tricycle. However, the provenance of the trisikad is also unknown. Prior to the tricycles and trisikad, the most common means of mass public transport in the Philippines is a carriage pulled by horses or carabaos known as the kalesa ("calesa" or "carromata" in Philippine Spanish). The pulled rickshaw never gained acceptance in the Philippines. Americans tried to introduce it in the early 20th century, but it was strongly opposed by local Filipinos who viewed it as an undignified mode of transport that turned humans into "beasts".


title: Auto rickshaw

text: The design and configuration of tricycles vary widely from place to place, but tends towards rough standardization within each municipality. The usual design is a passenger or cargo sidecar fitted to a motorbike, usually on the right of the motorbike. It is rare to find one with a left sidecar. A larger variant of the tricycle with the motorcycle in the center enclosed by a passenger cab with two side benches is known as a "motorela." It is found in the islands of Mindanao, Camiguin, and Bohol. Another notable variant are the tricycles of the Batanes Islands which have cabs made from wood and roofed with thatched cogon grass. In Pagadian City, tricycles are also uniquely built with the passenger cab slanting upwards, due to the city's streets that run along steep hills.


title: Auto rickshaw

text: Tricycles can carry three passengers or more in the sidecar, one or two pillion passengers behind the driver, and even a few on the roof of the sidecar. Tricycles are one of the main contributors to air pollution in the Philippines, which account for 45% of all volatile organic compound emissions since majority of them employ two-stroke engines. However, some local governments are working towards phasing out two-stroke tricycles for ones with cleaner four-stroke engines.


title: Auto rickshaw

text: Tuk-Tuks have now been accepted as Three-Wheeled Vehicles by the Land Transportation Office (Philippines) as distinct from tricycles and are now seen in Philippine streets. Electric versions are now seen especially in the city of Manila where they are called e-trikes. Combustion engine tuktuks are locally distributed by TVS Motors and Bajaj Auto through dealerships


title: Auto rickshaw

text: The auto rickshaw, called tuk-tuk (, ) in Thailand, is a widely used form of urban transport in Bangkok and other Thai cities. The name is onomatopoeic, mimicking the sound of a small (often two-cycle) engine. It is particularly popular where traffic congestion is a major problem, such as in Bangkok and Nakhon Ratchasima. In Bangkok in the 1960s, these were called samlaws.


title: Auto rickshaw

text: Bangkok and other cities in Thailand have many tuk-tuks which are a more open variation on the Indian auto rickshaw. About 20,000 tuk-tuks were registered as taxis in Thailand in 2017. Bangkok alone is reported to have 9,000 tuk-tuks.


title: Auto rickshaw

text: Tuk-tuk hua kob (ตุ๊ก ๆ หัวกบ; literally: frog-headed tuk tuk) is a unique tuk tuk with a cab looking like a frog's head. Only Phra Nakhon Si Ayutthaya and Trang have vehicles like this.


title: Auto rickshaw

text: Various types of auto rickshaw are used around China, where they are called sān lún chē (三轮车) and sometimes sān bèng zǐ (三蹦子), meaning three wheeler or tricycle. They may be used to transport cargo or passengers in the more rural areas. However, in many urban areas the auto rickshaws for passengers are often operated illegally as they are considered unsafe and an eyesore. They are permitted in some towns and cities, however. The Southeast Asian word tuk tuk is transliterated as dū dū chē (嘟嘟车, or beep beep car) in Chinese.


title: Auto rickshaw

text: A number of tuk-tuks (250 in 2013 according to the Paris Prefecture) are used as an alternative tourist transport system in Paris, some of them being pedal-operated with electric motor assist. They are not yet fully licensed to operate and await customers on the streets. Vélotaxis were common during the Occupation years in Paris due to fuel restrictions.


title: Auto rickshaw

text: Auto rickshaws have been commonly used in Italy since the late 1940s, providing a low-cost means of transportation in the post–World War II years when the country was short of economic resources. The Piaggio Ape (Tukxi), designed by Vespa creator Corradino D'Ascanio and first manufactured in 1948 by the Italian company Piaggio, though primarily designed for carrying freight has also been widely used as an auto rickshaw. It is still extremely popular throughout the country, being particularly useful in the narrow streets found in the center of many little towns in central and southern Italy. Though it no longer has a key role in transportation, Piaggio Ape is still used as a minitaxi in some areas such as the islands of Ischia and Stromboli (on Stromboli no cars are allowed). It has recently been re-launched as a trendy-ecological means of transportation, or, relying on the role the Ape played in the history of Italian design, as a promotional tool.


title: Auto rickshaw

text: Tuk Tuks are used in the resort city of Albufeira in the Algarve as a novel form of transport for visitors during the tourist season.


title: Auto rickshaw

text: In 2006 a British travel writer Antonia Bolingbroke-Kent and her friend Jo Huxster travelled 12,561 miles (20,215 km) with an auto rickshaw from Bangkok to Brighton. With this 98 days'


title: Auto rickshaw

text: The "mototaxi" or "moto" is the El Salvadoran version of the auto rickshaw. These are most commonly made from the front end and engine of a motorcycle attached to a two-wheeled passenger area in back. Commercially produced models, such as the Indian Bajaj brand, are also employed.


title: Auto rickshaw

text: In Guatemala tuk-tuks operate, both as taxis and private vehicles, in Guatemala City, around the island town of Flores, Peten, in the mountain city of Antigua Guatemala, and in many small towns in the mountains. In 2005 the tuk-tuks were prevalent in the Lago de Atitlán towns of Panajachel and Santiago Atitlán.


title: Auto rickshaw

text: In the 1950s and 1960s, the United States Post Office (replaced in 1971 by the United States Postal Service) used the WestCoaster Mailster, a close relative of the tuk-tuk. Similar vehicles remain in limited use for parking enforcement, mall security, and other niche applications.


title: Auto rickshaw

text: In July 1998, the Supreme Court of India ordered the Government of Delhi to implement CNG or LPG (Autogas) fuel for all autos and for the entire bus fleet in and around the city. Delhi's air quality has improved with the switch to CNG. Initially, auto rickshaw drivers in Delhi had to wait in long queues for CNG refueling, but the situation improved following an increase in the number of CNG stations. Gradually, many state governments passed similar laws, thus shifting to CNG or LPG vehicles in most large cities to improve air quality and reduce pollution. Certain local governments are pushing for four-stroke engines instead of two-stroke ones. Typical mileage for an Indian-made auto rickshaw is around of petrol. Pakistan has passed a similar law prohibiting auto rickshaws in certain areas. CNG auto rickshaws have started to appear in huge numbers in many Pakistani cities.


title: Auto rickshaw

text: In January 2007 the Sri Lankan government also banned two-stroke trishaws to reduce air pollution. In the Philippines there are projects to convert carburated two-stroke engines to direct-injected via Envirofit technology. Research has shown LPG or CNG gas direct-injection can be retrofitted to existing engines, in similar fashion to the Envirofit system. In Vigan City majority of tricycles-for-hire as of 2008 are powered by motorcycles with four-stroke engines, as tricycles with two-stroke motorcycles are prevented from receiving operating permits. Direct injection is standard equipment on new machines in India.


title: Auto rickshaw

text: In March 2009 an international consortium coordinated by the International Centre for Hydrogen Energy Technologies initiated a two-year public-private partnership of local and international stakeholders aiming at operating a fleet of 15 hydrogen-fueled three-wheeled vehicles in New Delhi's Pragati Maidan complex. As of January 2011, the project was nearing completion.


title: Auto rickshaw

text: Hydrogen internal combustion (HICV) use in three-wheelers has only recently being started to be looked into, mainly by developing countries, to decrease local pollution at an affordable cost. At some point, Bajaj Auto made a HICV auto rickshaw together with the company "Energy Conversion Devices". They made a report on it called "Clean Hydrogen Technology for 3-Wheel Transportation in India" and it stated that the performance was comparable with CNG autos. In 2012, Mahindra & Mahindra showcased their first HICV auto rickshaw, called the Mahindra HyAlfa. The development of the hydrogen-powered rickshaw happened with support from the International Centre for Hydrogen Energy Technologies.


title: Auto rickshaw

text: On September 16, 2022 at 11:04 a.m. (Indian Standard Time), a Canadian team (Greg Harris and Priya Singh) and a Swiss team (Michele Daryanani & Nevena Lazarevic) set the world record for the highest altitude at which an auto rickshaw has ever been driven. The two teams set the record by driving to the summit of Umling La Pass at an altitude of 19,024 feet/5,798 meters.


title: Auto rickshaw

text: The two teams were participating in the Rickshaw Run (Himalayan Edition), an event promoted by The Adventurists, where teams drive auto rickshaws from the Thar desert town of Jaisalmer in Rajasthan the Himalayan town of Leh in Ladakh. Rickshaw Run teams are given the start and finish lines, but are otherwise unsupported and left to their own navigational choices in completing the approximately 2,300 km journey.


title: Auto rickshaw

text: The road at Umling La Pass was constructed by India’s Border Roads Organization and completed in 2017. Guinness World Records certified the road as the highest motorable road in the world.


title: Balsamic vinegar

text: Balsamic vinegar () is a very dark, concentrated and intensely flavoured vinegar originating in Modena, Italy, made wholly or partially from grape must: freshly crushed grape juice with all the skins, seeds and stems.


title: Balsamic vinegar

text: The term "aceto balsamico" is unregulated, but there are three protected balsamic vinegars: "Aceto Balsamico Tradizionale di Modena DOP" (Traditional Balsamic Vinegar of Modena), "Aceto Balsamico Tradizionale di Reggio Emilia DOP" (Traditional Balsamic Vinegar of Reggio Emilia), and "Aceto Balsamico di Modena IGP" (Balsamic Vinegar of Modena). The two traditional balsamic vinegars are made the same way from reduced grape must aged for several years in a series of wooden barrels, and are produced exclusively in either the province of Modena or Reggio Emilia. The names of these two vinegars are protected by the European Union's Protected Designation of Origin, while the usually less expensive Balsamic Vinegar of Modena ("Aceto Balsamico di Modena") is made from grape must blended with wine vinegar, and produced exclusively in either Modena or Reggio Emilia, with a Protected Geographical Indication status.


title: Balsamic vinegar

text: The Italian word "balsamico" (from Latin "balsamum", from Greek , "bálsamon") means "balsam-like" in the sense of "restorative" or "curative"; cf. English "balm".


title: Balsamic vinegar

text: Ultimately from Ancient Hebrew-Phoenician "בשׂם" (bāśām/besem, IPA [baːˈɬaːm]), the name means "perfume/spice", with the consonant sequence of letter 'λ' and 'σ' deriving from Ancient Greek to pronounce the שׂ (ś) sound, sounding back then as [ɬ].


title: Balsamic vinegar

text: There are also many products that contain "Aceto Balsamico di Modena IGP" as an ingredient, such as glazes and other condiments.


title: Balsamic vinegar

text: Only two consortia produce true traditional balsamic vinegar, Modena and neighboring Reggio Emilia. True balsamic vinegar is made from a reduction of pressed Trebbiano and Lambrusco grapes. The resulting thick syrup, called "mosto cotto" in Italian, is subsequently aged for a minimum of 12 years in a battery of several barrels of successively smaller sizes. The casks are made of different woods such as chestnut, cherry, oak, mulberry, ash and juniper. True balsamic vinegar is rich, glossy, deep brown in colour, and has a complex flavour that balances the natural sweet and sour elements of the cooked grape juice with hints of wood from the casks.


title: Balsamic vinegar

text: Reggio Emilia designates the different ages of their balsamic vinegar ("Aceto Balsamico Tradizionale di Reggio Emilia") by label colour. A red label means the vinegar has been aged for at least 12 years, a silver label that the vinegar has aged for at least 18 years, and a gold label designates that the vinegar has aged for 25 years or more.


title: Balsamic vinegar

text: Modena uses a different system to indicate the age of its balsamic vinegars ("Aceto Balsamico Tradizionale di Modena"). A white-coloured cap means the vinegar has aged for at least 12 years and a gold cap bearing the designation "extravecchio" (extra-old) shows the vinegar has aged for 25 years or more.


title: Balsamic vinegar

text: These commercial-grade products imitate the traditional product. They are made of as little as 20% grape must (and not necessarily from Modena or Reggio Emilia), with the addition of wine vinegar, colouring, caramel, and sometimes thickeners like guar gum or cornflour to artificially simulate the sweetness and thickness of the aged Aceto Balsamico Tradizionale di Modena. IGP status requires a minimum aging period of two months, not necessarily in wooden barrels, rising to three years when labeled as invecchiato (aged). As the manufacturing process is highly industrialized, the output of a medium-sized producer may be hundreds of litres per day.


title: Balsamic vinegar

text: In 2009, the European Commission inserted the Balsamic Vinegar of Modena (Aceto Balsamico di Modena) designation in the register of IGP productions.


title: Balsamic vinegar

text: "Condimento" (dressing) balsamic vinegars may be labeled as "condimento balsamico", "salsa balsamica" or "salsa di mosto cotto".


title: Balsamic vinegar

text: For those products, there is a risk of creating confusion among consumers looking for the original Balsamic Vinegar of Modena PGI, the two different Traditional Balsamic Vinegar of Modena PDO, and Traditional Balsamic Vinegar of Reggio Emilia PDO.


title: Balsamic vinegar

text: As there are no official standards or labeling systems to designate "condimento" balsamic vinegar, it can be hard to tell their quality based on the packaging alone.


title: Balsamic vinegar

text: Traditional balsamic vinegar is produced from the juice of just-harvested white grapes (typically, Trebbiano grapes) boiled down to reach a minimum sugar concentration of 30% (brix) or more in the must, which is then fermented with a slow aging process which further concentrates the flavours. The flavour intensifies over the years, with the vinegar being stored in wooden casks, becoming sweet, viscous and very concentrated. During this period, a portion evaporates: it is said that this is the "angels' share", a term also used in the production of bourbon whiskey, Scotch whisky, wine and other alcoholic beverages.


title: Balsamic vinegar

text: None of the product may be withdrawn until the end of the minimum aging period of 12 years. At the end of the aging period (12, 18 or 25 years) a small portion is drawn from the smallest cask and each cask is then topped up with the contents of the preceding (next larger) cask. Freshly reduced cooked must is added to the largest cask and in every subsequent year the drawing and topping up process is repeated. This process where the product is distributed from the oldest cask and then refilled from the next oldest vintage cask is called solera or "in perpetuum".


title: Balsamic vinegar

text: In Emilia-Romagna, "tradizionale" vinegar is most often served in drops on top of chunks of Parmigiano Reggiano and mortadella as an antipasto. It is also used sparingly to enhance steaks, eggs, or grilled fish, as well as on fresh fruit such as strawberries and pears and on plain crema (custard) gelato. "Tradizionale" vinegar may be sipped from a tiny glass to conclude a meal.


title: Balsamic vinegar

text: Contemporary chefs use both "Traditional Balsamic Vinegar of Modena PDO" and "Balsamic Vinegar of Modena PGI" sparingly in simple dishes where the balsamic vinegar's complex tastes are highlighted, using it to enhance dishes like scallops or shrimp, or on simple pastas and risottos.


title: Mycobacterium tuberculosis

text: Mycobacterium tuberculosis (M. tb) is a species of pathogenic bacteria in the family Mycobacteriaceae and the causative agent of tuberculosis. First discovered in 1882 by Robert Koch, "M. tuberculosis" has an unusual, waxy coating on its cell surface primarily due to the presence of mycolic acid. This coating makes the cells impervious to Gram staining, and as a result, "M. tuberculosis" can appear weakly Gram-positive. Acid-fast stains such as Ziehl–Neelsen, or fluorescent stains such as auramine are used instead to identify "M. tuberculosis" with a microscope. The physiology of "M. tuberculosis" is highly aerobic and requires high levels of oxygen. Primarily a pathogen of the mammalian respiratory system, it infects the lungs. The most frequently used diagnostic methods for tuberculosis are the tuberculin skin test, acid-fast stain, culture, and polymerase chain reaction.


title: Mycobacterium tuberculosis

text: In 2019, M. tuberculosis was found in a genetically related complex group of Mycobacterium species called Mycobacterium tuberculosis complex that has at least 9 members:


title: Mycobacterium tuberculosis

text: It requires oxygen to grow, and is nonmotile. "M. tuberculosis" divides every 18–24 hours. This is extremely slow compared with other bacteria, which tend to have division times measured in minutes ("Escherichia coli" can divide roughly every 20 minutes). It is a small bacillus that can withstand weak disinfectants and can survive in a dry state for weeks. Its unusual cell wall is rich in lipids such as mycolic acid and cord factor glycolipid, is likely responsible for its resistance to desiccation and is a key virulence factor.


title: Mycobacterium tuberculosis

text: Other bacteria are commonly identified with a microscope by staining them with Gram stain. However, the mycolic acid in the cell wall of "M. tuberculosis" does not absorb the stain. Instead, acid-fast stains such as Ziehl–Neelsen stain, or fluorescent stains such as auramine are used. Cells are curved rod-shaped and are often seen wrapped together, due to the presence of fatty acids in the cell wall that stick together. This appearance is referred to as cording, like strands of cord that make up a rope. "M. tuberculosis" is characterized in tissue by caseating granulomas containing Langhans giant cells, which have a "horseshoe" pattern of nuclei.


title: Mycobacterium tuberculosis

text: "M. tuberculosis" can be grown in the laboratory. Compared to other commonly studied bacteria, "M. tuberculosis" has a remarkably slow growth rate, doubling roughly once per day. Commonly used media include liquids such as Middlebrook 7H9 or 7H12, egg-based solid media such as Lowenstein-Jensen, and solid agar-based such as Middlebrook 7H11 or 7H10. Visible colonies require several weeks to grow on agar plates. It is distinguished from other mycobacteria by its production of catalase and niacin. Other tests to confirm its identity include gene probes and MALDI-TOF.


title: Mycobacterium tuberculosis

text: The slices of the "Mycobacterium tuberculosis" analyzed under a scanning electron microscope by a Japan-based research group has revealed that bacteria is about 2.71 ± 1.05μm in length with an average diameter of the cell approximately 0.345 ± 0.029 μm. The outer membrane and plasma membrane surface areas were measured to be 3.04 ± 1.33 μm and 2.67 ± 1.19 μm, respectively. The cell, outer membrane, periplasm, plasma membrane, and cytoplasm volumes were 0.293 ± 0.113 fl (= μm), 0.006 ± 0.003 fl, 0.060 ± 0.021 fl, 0.019 ± 0.008 fl, and 0.210 ± 0.091 fl, respectively. The average total ribosome number was 1,672 ± 568 with ribosome density about 716.5 ± 171.4/0.1 fl.


title: Mycobacterium tuberculosis

text: Humans are the only known reservoirs of "M. tuberculosis". A misconception is that "M. tuberculosis" can be spread by shaking hands, making contact with toilet seats, sharing food or drink, or sharing toothbrushes. However, major spread is through air droplets originating from a person who has the disease either coughing, sneezing, speaking, or singing.


title: Mycobacterium tuberculosis

text: When in the lungs, "M. tuberculosis" is phagocytosed by alveolar macrophages, but they are unable to kill and digest the bacterium. Its cell wall that is made of a cord factor glycoplipds that inhibit the fusion of the phagosome with the lysosome, which contains a host of antibacterial factors.


title: Mycobacterium tuberculosis

text: Specifically, "M. tuberculosis" blocks the bridging molecule, early endosomal autoantigen 1 (EEA1); however, this blockade does not prevent fusion of vesicles filled with nutrients. In addition, production of the diterpene isotuberculosinol prevents maturation of the phagosome. The bacteria also evades macrophage-killing by neutralizing reactive nitrogen intermediates. More recently, "M. tuberculosis" has been shown to secrete and cover itself in 1-tuberculosinyladenosine (1-TbAd), a special nucleoside that acts as an antacid, allowing it to neutralize pH and induce swelling in lysosomes.


title: Mycobacterium tuberculosis

text: In "M. tuberculosis" infections, PPM1A levels were found to be upregulated, and this, in turn, would impact the normal apoptotic response of macrophages to clear pathogens, as PPM1A is involved in the intrinsic and extrinsic apoptotic pathways. Hence, when PPM1A levels were increased, the expression of it inhibits the two apoptotic pathways. With kinome analysis, the JNK/AP-1 signalling pathway was found to be a downstream effector that PPM1A has a part to play in, and the apoptotic pathway in macrophages are controlled in this manner. As a result of having apoptosis being suppressed, it provides "M. tuberculosis" with a safe replicative niche, and so the bacteria are able to maintain a latent state for a prolonged time.


title: Mycobacterium tuberculosis

text: Granulomas, organized aggregates of immune cells, are a hallmark feature of tuberculosis infection. Granulomas play dual roles during infection: they regulate the immune response and minimize tissue damage, but also can aid in the expansion of infection.


title: Mycobacterium tuberculosis

text: The ability to construct "M. tuberculosis" mutants and test individual gene products for specific functions has significantly advanced the understanding of its pathogenesis and virulence factors. Many secreted and exported proteins are known to be important in pathogenesis. For example, one such virulence factor is cord factor (trehalose dimycolate), which serves to increase survival within its host. Resistant strains of "M. tuberculosis" have developed resistance to more than one TB drug, due to mutations in their genes. In addition, pre-existing first-line TB drugs such as rifampicin and streptomycin have decreased efficiency in clearing intracellular "M. tuberculosis" due not being able to effectively penetrate the macrophage niche.


title: Mycobacterium tuberculosis

text: JNK plays a key role in the control of apoptotic pathways—intrinsic and extrinsic. In addition, it is also found to be a substrate of PPM1A activity, hence the phosphorylation of JNK would cause apoptosis to occur. Since PPM1A levels are elevated during "M. tuberculosis" infections, by inhibiting the PPM1A signalling pathways, it could potentially be a therapeutic method to kill "M. tuberculosis"-infected macrophages by restoring its normal apoptotic function in defence of pathogens. By targeting the PPM1A-JNK signalling axis pathway, then, it could eliminate "M. tuberculosis"-infected macrophages.


title: Mycobacterium tuberculosis

text: The ability to restore macrophage apoptosis to "M. tuberculosis"-infected ones could improve the current tuberculosis chemotherapy treatment, as TB drugs can gain better access to the bacteria in the niche. thus decreasing the treatment times for "M. tuberculosis" infections.


title: Mycobacterium tuberculosis

text: Symptoms of "M. tuberculosis" include coughing that lasts for more than three weeks, hemoptysis, chest pain when breathing or coughing, weight loss, fatigue, fever, night sweats, chills, and loss of appetite. "M. tuberculosis" also has the potential of spreading to other parts of the body. This can cause blood in urine if the kidneys are affected, and back pain if the spine is affected.


title: Mycobacterium tuberculosis

text: Typing of strains is useful in the investigation of tuberculosis outbreaks, because it gives the investigator evidence for or against transmission from person to person. Consider the situation where person A has tuberculosis and believes he acquired it from person B. If the bacteria isolated from each person belong to different types, then transmission from B to A is definitively disproven; however, if the bacteria are the same strain, then this supports (but does not definitively prove) the hypothesis that B infected A.


title: Mycobacterium tuberculosis

text: Until the early 2000s, "M. tuberculosis" strains were typed by pulsed field gel electrophoresis. This has now been superseded by variable numbers of tandem repeats (VNTR), which is technically easier to perform and allows better discrimination between strains. This method makes use of the presence of repeated DNA sequences within the "M. tuberculosis" genome.


title: Mycobacterium tuberculosis

text: Three generations of VNTR typing for "M. tuberculosis" are noted. The first scheme, called exact tandem repeat, used only five loci, but the resolution afforded by these five loci was not as good as PFGE. The second scheme, called mycobacterial interspersed repetitive unit, had discrimination as good as PFGE. The third generation (mycobacterial interspersed repetitive unit – 2) added a further nine loci to bring the total to 24. This provides a degree of resolution greater than PFGE and is currently the standard for typing "M. tuberculosis". However, with regard to archaeological remains, additional evidence may be required because of possible contamination from related soil bacteria.


title: Mycobacterium tuberculosis

text: Antibiotic resistance in "M. tuberculosis" typically occurs due to either the accumulation of mutations in the genes targeted by the antibiotic or a change in titration of the drug. "M. tuberculosis" is considered to be multidrug-resistant (MDR TB) if it has developed drug resistance to both rifampicin and isoniazid, which are the most important antibiotics used in treatment. Additionally, extensively drug-resistant "M. tuberculosis" (XDR TB) is characterized by resistance to both isoniazid and rifampin, plus any fluoroquinolone and at least one of three injectable second-line drugs (i.e., amikacin, kanamycin, or capreomycin).


title: Mycobacterium tuberculosis

text: The genome of the H37Rv strain was published in 1998. Its size is 4 million base pairs, with 3,959 genes; 40% of these genes have had their function characterized, with possible function postulated for another 44%. Within the genome are also six pseudogenes.


title: Mycobacterium tuberculosis

text: The genome contains 250 genes involved in fatty acid metabolism, with 39 of these involved in the polyketide metabolism generating the waxy coat. Such large numbers of conserved genes show the evolutionary importance of the waxy coat to pathogen survival. Furthermore, experimental studies have since validated the importance of a lipid metabolism for" M. tuberculosis", consisting entirely of host-derived lipids such as fats and cholesterol. Bacteria isolated from the lungs of infected mice were shown to preferentially use fatty acids over carbohydrate substrates. "M. tuberculosis" can also grow on the lipid cholesterol as a sole source of carbon, and genes involved in the cholesterol use pathway(s) have been validated as important during various stages of the infection lifecycle of "M. tuberculosis", especially during the chronic phase of infection when other nutrients are likely not available.


title: Mycobacterium tuberculosis

text: About 10% of the coding capacity is taken up by the "PE"/"PPE" gene families that encode acidic, glycine-rich proteins. These proteins have a conserved N-terminal motif, deletion of which impairs growth in macrophages and granulomas.


title: Mycobacterium tuberculosis

text: Nine noncoding sRNAs have been characterised in "M. tuberculosis", with a further 56 predicted in a bioinformatics screen.


title: Mycobacterium tuberculosis

text: In 2013, a study on the genome of several sensitive, ultraresistant, and multiresistant "M. tuberculosis" strains was made to study antibiotic resistance mechanisms. Results reveal new relationships and drug resistance genes not previously associated and suggest some genes and intergenic regions associated with drug resistance may be involved in the resistance to more than one drug. Noteworthy is the role of the intergenic regions in the development of this resistance, and most of the genes proposed in this study to be responsible for drug resistance have an essential role in the development of "M. tuberculosis".


title: Mycobacterium tuberculosis

text: The "M. tuberculosis" complex evolved in Africa and most probably in the Horn of Africa. In addition to "M. tuberculosis", the "M. tuberculosis" complex (MTBC) has a number of members infecting various animal species, these include "M. africanum", "M. bovis" (Dassie's bacillus), "M. caprae", "M. microti", "M. mungi, M. orygis", and "M. pinnipedii". This group may also include the "M. canettii" clade. These animal strains of MTBC do not strictly deserve species status, as they are all closely related and embedded in the "M. tuberculosis" phylogeny, but for historic reasons, they currently hold species status.


title: Mycobacterium tuberculosis

text: The "M. canettii" clade – which includes "M. prototuberculosis" – is a group of smooth-colony "Mycobacterium" species. Unlike the established members of the "M. tuberculosis" group, they undergo recombination with other species. The majority of the known strains of this group have been isolated from the Horn of Africa. The ancestor of "M. tuberculosis" appears to be "M. canettii", first described in 1969.


title: Mycobacterium tuberculosis

text: The established members of the "M. tuberculosis" complex are all clonal in their spread. The main human-infecting species have been classified into seven lineages. Translating these lineages into the terminology used for spoligotyping, a very crude genotyping methodology, lineage 1 contains the East African-Indian (EAI), the Manila family of strains and some Manu (Indian) strains; lineage 2 is the Beijing group; lineage 3 includes the Central Asian (CAS) strains; lineage 4 includes the Ghana and Haarlem (H/T), Latin America-Mediterranean (LAM) and X strains; types 5 and 6 correspond to "M. africanum" and are observed predominantly and at high frequencies in West Africa. A seventh type has been isolated from the Horn of Africa. The other species of this complex belong to a number of spoligotypes and do not normally infect humans.


title: Mycobacterium tuberculosis

text: Lineages 2, 3 and 4 all share a unique deletion event (tbD1) and thus form a monophyletic group. Types 5 and 6 are closely related to the animal strains of MTBC, which do not normally infect humans. Lineage 3 has been divided into two clades: CAS-Kili (found in Tanzania) and CAS-Delhi (found in India and Saudi Arabia).


title: Mycobacterium tuberculosis

text: Lineage 4 is also known as the Euro-American lineage. Subtypes within this type include Latin American Mediterranean, Uganda I, Uganda II, Haarlem, X, and Congo.


title: Mycobacterium tuberculosis

text: A much cited study reported that "M. tuberculosis" has co-evolved with human populations, and that the most recent common ancestor of the "M. tuberculosis" complex evolved between 40,000 and 70,000 years ago. However, a later study that included genome sequences from "M. tuberculosis" complex members extracted from three 1,000-year-old Peruvian mummies, came to quite different conclusions. If the most recent common ancestor of the "M. tuberculosis" complex were 40,000 to 70,000 years old, this would necessitate an evolutionary rate much lower than any estimates produced by genomic analyses of heterochronous samples, suggesting a far more recent common ancestor of the "M. tuberculosis" complex as little as 6000 years ago.


title: Mycobacterium tuberculosis

text: An analysis of over 3000 strains of "M. bovis" from 35 countries suggested an Africa origin for this species.


title: Mycobacterium tuberculosis

text: There are currently two narratives existing in parallel regarding the age of MTBC and how it has spread and co-evolved with humans through time. One study compared the "M. tuberculosis" phylogeny to a human mitochondrial genome phylogeny and interpreted these as being highly similar. Based on this, the study suggested that "M. tuberculosis", like humans, evolved in Africa and subsequently spread with anatomically modern humans out of Africa across the world. By calibrating the mutation rate of M. tuberculosis to match this narrative, the study suggested that MTBC evolved 40,000–70,000 years ago. Applying this time scale, the study found that the "M. tuberculosis" effective population size expanded during the Neolithic Demographic Transition (around 10,000 years ago) and suggested that "M. tuberculosis" was able to adapt to changing human populations and that the historical success of this pathogen was driven at least in part by dramatic increases in human host population density. It has also been demonstrated that after emigrating from one continent to another, a human host's region of origin is predictive of which TB lineage they carry, which could reflect either a stable association between host populations and specific "M. tuberculosis" lineages and/or social interactions that are shaped by shared cultural and geographic histories.


title: Mycobacterium tuberculosis

text: Regarding the congruence between human and "M. tuberculosis" phylogenies, a study relying on "M. tuberculosis" and human Y chromosome DNA sequences to formally assess the correlation between them, concluded that they are not congruent. Also, a more recent study which included genome sequences from "M. tuberculosis" complex members extracted from three 1,000-year-old Peruvian mummies, estimated that the most recent common ancestor of the "M. tuberculosis" complex lived only 4,000 – 6,000 years ago. The "M. tuberculosis" evolutionary rate estimated by the Bos et al. study is also supported by a study on Lineage 4 relying on genomic aDNA sequences from Hungarian mummies more than 200 years old. In total, the evidence thus favors this more recent estimate of the age of the MTBC most recent common ancestor, and thus that the global evolution and dispersal of "M. tuberculosis" has occurred over the last 4,000–6,000 years.


title: Mycobacterium tuberculosis

text: Among the seven recognized lineages of "M. tuberculosis", only two are truly global in their distribution: Lineages 2 and 4. Among these, Lineage 4 is the most well dispersed, and almost totally dominates in the Americas. Lineage 4 was shown to have evolved in or in the vicinity of Europe, and to have spread globally with Europeans starting around the 13th century. This study also found that Lineage 4 tuberculosis spread to the Americas shortly after the European discovery of the continent in 1492, and suggests that this represented the first introduction of human TB on the continent (although animal strains have been found in human remains predating Columbus. Similarly, Lineage 4 was found to have spread from Europe to Africa during the Age of Discovery, starting in the early 15th century.


title: Mycobacterium tuberculosis

text: It has been suggested that ancestral mycobacteria may have infected early hominids in East Africa as early as three million years ago.


title: Mycobacterium tuberculosis

text: DNA fragments from "M. tuberculosis" and tuberculosis disease indications were present in human bodies dating from 9250 to 8160 years ago found at Atlit-Yam in the Levant.


title: Mycobacterium tuberculosis

text: "M. tuberculosis" is a clonal organism and does not exchange DNA via horizontal gene transfer. Despite an additionally slow evolution rate, the emergence and spread of antibiotic resistance in "M. tuberculosis" poses an increasing threat to global public health. In 2019, the WHO reported the estimated incidence of antibiotic resistant TB to be 3.4% in new cases, and 18% in previously treated cases. Geographical discrepancies exist in the incidence rates of drug-resistant TB. Countries facing the highest rates of ABR TB China, India, Russia, and South Africa. Recent trends reveal an increase in drug-resistant cases in a number of regions, with Papua New Guinea, Singapore, and Australia undergoing significant increases.


title: Mycobacterium tuberculosis

text: Multidrug-resistant Tuberculosis (MDR-TB) is characterised by resistance to at least the two front-line drugs isoniazid and rifampin. MDR is associated with a relatively poor treatment success rate of 52%. Isoniazid and rifampin resistance are tightly linked, with 78% of the reported rifampin-resistant TB cases in 2019 being resistant to isoniazid as well. Rifampin-resistance is primarily due to resistance-conferring mutations in the rifampin-resistance determining region (RRDR) within the rpoB gene. The most frequently observed mutations of the codons in RRDR are 531, 526 and 516. However, alternative more elusive resistance-conferring mutations have been detected. Isoniazid function occurs through the inhibition of mycolic acid synthesis through the NADH-dependent enoyl-acyl carrier protein (ACP)-reductase. This is encoded by the "inhA" gene. As a result, isoniazid resistance is primarily due to mutations within inhA and the KatG gene or its promoter region - a catalase peroxidase which is required to activate Isoniazid. As MDR in "M. tuberculosis" becomes increasingly common, the emergence of pre-extensively drug resistant (pre-XDR) and extensively drug resistant (XDR-) TB threatens to exasperate the public health crisis. XDR-TB is characterised by resistance to both rifampin and Isoniazid, as well second-line fluoroquinolones and at least one additional front-line drug. Thus, the development of alternative therapeutic measures is of utmost priority.


title: Mycobacterium tuberculosis

text: An intrinsic contributor to the antibiotic resistant nature of "M. tuberculosis" is its unique cell wall. Saturated with long-chain fatty acids or mycolic acids, the mycobacterial cell presents a robust, relatively insoluble barrier. This has led to its synthesis being the target of many antibiotics - such as Isoniazid. However, resistance has emerged to the majority of them. A novel, promising therapeutic target is mycobacterial membrane protein large 3 (MmpL3). The mycobacterial membrane protein large (MmpL) proteins are transmembrane proteins which play a key role in the synthesis of the cell wall and the transport of the associated lipids. Of these, MmpL3 is essential; knock-out of which has been shown to be bactericidal. Due to its essential nature, MmpL3 inhibitors show promise as alternative therapeutic measures in the age of antibiotic resistance. Inhibition of MmpL3 function showed an inability to transport trehalose monomycolate - an essential cell wall lipid - across the plasma membrane. The recently reported structure of MmpL3 revealed resistance-conferring mutations to associate primarily with the transmembrane domain. Although resistance to pre-clinical MmpL3 inhibitors has been detected, analysis of the widespread mutational landscape revealed a low level of environmental resistance. This suggests that MmpL3 inhibitors currently undergoing clinical trials would face little resistance if made available. Additionally, the ability of many MmpL3 inhibitors to work synergistically with other antitubercular drugs presents a ray of hope in combatting the TB crisis.


title: Mycobacterium tuberculosis

text: The nature of the host-pathogen interaction between humans and "M. tuberculosis" is considered to have a genetic component. A group of rare disorders called Mendelian susceptibility to mycobacterial diseases was observed in a subset of individuals with a genetic defect that results in increased susceptibility to mycobacterial infection.


title: Mycobacterium tuberculosis

text: Early case and twin studies have indicated that genetic components are important in host susceptibility to "M. tuberculosis". Recent genome-wide association studies (GWAS) have identified three genetic risk loci, including at positions 11p13 and 18q11. As is common in GWAS, the variants discovered have moderate effect sizes.


title: Mycobacterium tuberculosis

text: As an intracellular pathogen, "M. tuberculosis" is exposed to a variety of DNA-damaging assaults, primarily from host-generated antimicrobial toxic radicals. Exposure to reactive oxygen species and/or reactive nitrogen species causes different types of DNA damage including oxidation, depurination, methylation, and deamination that can give rise to single- and double-strand breaks (DSBs).


title: Mycobacterium tuberculosis

text: DnaE2 polymerase is upregulated in "M. tuberculosis" by several DNA-damaging agents, as well as during infection of mice. Loss of this DNA polymerase reduces the virulence of "M. tuberculosis" in mice. DnaE2 is an error-prone DNA repair polymerase that appears to contribute to "M. tuberculosis" survival during infection.


title: Mycobacterium tuberculosis

text: The two major pathways employed in repair of DSBs are homologous recombinational repair (HR) and nonhomologous end joining (NHEJ). Macrophage-internalized "M. tuberculosis" is able to persist if either of these pathways is defective, but is attenuated when both pathways are defective. This indicates that intracellular exposure of "M. tuberculosis" to reactive oxygen and/or reactive nitrogen species results in the formation of DSBs that are repaired by HR or NHEJ. However deficiency of DSB repair does not appear to impair "M. tuberculosis" virulence in animal models.


title: Mycobacterium tuberculosis

text: "M. tuberculosis", then known as the "tubercle bacillus", was first described on 24 March 1882 by Robert Koch, who subsequently received the Nobel Prize in Physiology or Medicine for this discovery in 1905; the bacterium is also known as "Koch's bacillus".


title: Mycobacterium tuberculosis

text: "M. tuberculosis" has existed throughout history, but the name has changed frequently over time. In 1720, though, the history of tuberculosis started to take shape into what is known of it today; as the physician Benjamin Marten described in his "A Theory of Consumption", tuberculosis may be caused by small living creatures transmitted through the air to other patients.


title: Mycobacterium tuberculosis

text: The BCG vaccine (bacille Calmette-Guerin), which was derived from "M. bovis," while effective against childhood and severe forms of tuberculosis, has limited success in preventing the most common form of the disease today, adult pulmonary tuberculosis. Because of this, it is primarily used in high tuberculosis incidence regions, and is not a recommended vaccine in the United States due to the low risk of infection. To receive this vaccine in the United States, an individual is required to go through a consultation process with an expert in M. tuberculosis and is only given to those who meet the specific criteria.


title: Mycobacterium tuberculosis

text: The BCG, according to an article of the Kyodo News (April 14, 2020) titled "Tuberculosis vaccine drawing attention in fight against coronavirus" indicates a possible correlation between BCG vaccination, and better immune response to the COVID-19.


title: The Tale of Genji

text: The work is a unique depiction of the lifestyles of high courtiers during the Heian period. It is written in archaic language and a poetic and complex style that make it unreadable to the average Japanese speaker without specialized study. It was not until the early 20th century that "Genji" was translated into modern Japanese by the poet Akiko Yosano. The first English translation was attempted in 1882 by Suematsu Kencho, but was of poor quality and incomplete.


title: The Tale of Genji

text: The work recounts the life of Hikaru Genji, or "Shining Genji", who is the son of an ancient Japanese emperor (known to readers as Emperor Kiritsubo) and a low-ranking concubine called Kiritsubo Consort. For political reasons, the emperor removes Genji from the line of succession, demoting him to a commoner by giving him the surname Minamoto, and he pursues a career as an imperial officer. The tale concentrates on Genji's romantic life and describes the customs of the aristocratic society of the time. It may be the world's first novel, the first psychological novel, and the first novel still to be considered a classic particularly in the context of Japanese literature.


title: The Tale of Genji

text: Murasaki was writing at the height of the Fujiwara clan's power—Fujiwara no Michinaga was the Regent in all but name, and the most significant political figure of his day. Consequently, Murasaki is believed to have partially informed the character of Genji through her experience of Michinaga.


title: The Tale of Genji

text: "The Tale of Genji" may have been written chapter by chapter in installments, as Murasaki delivered the tale to aristocratic women (ladies-in-waiting). It has many elements found in a modern novel: a central character and a very large number of major and minor characters, well-developed characterization of all the major players, a sequence of events covering the central character's lifetime and beyond. There is no specified plot, but events happen and characters simply grow older. Despite a "dramatis personæ" of some four hundred characters, it maintains internal consistency; for instance, all characters age in step, and both family and feudal relationships stay intact throughout.


title: The Tale of Genji

text: One complication for readers and translators of the "Genji" is that almost none of the characters in the original text is given an explicit name. The characters are instead referred to by their function or role (e.g. Minister of the Left), an honorific (e.g. His Excellency), or their relation to other characters (e.g. Heir Apparent), which changes as the novel progresses. This lack of names stems from Heian-era court manners that would have made it unacceptably familiar and blunt to freely mention a person's given name. Modern readers and translators have used various nicknames to keep track of the many characters.


title: The Tale of Genji

text: There is debate over how much of "Genji" was actually written by Murasaki Shikibu. Debates over the novel's authorship have gone on for centuries, and are unlikely to ever be settled unless some major archival discovery is made.


title: The Tale of Genji

text: It is generally accepted that the tale was finished in its present form by 1021, when the author of the wrote a diary entry about her joy at acquiring a complete copy of the tale. She writes that there are over 50 chapters and mentions a character introduced at the end of the work, so if other authors besides Murasaki did work on the tale, the work was finished very near to the time of her writing. Murasaki's own diary includes a reference to the tale, and indeed the application to herself of the name 'Murasaki' in an allusion to the main female character. That entry confirms that some if not all of the diary was available in 1008 when internal evidence convincingly suggests that the entry was written.


title: The Tale of Genji

text: Murasaki is said to have written the character of Genji based on the Minister on the Left at the time she was at court. Other translators, such as Tyler, believe the character Murasaki no Ue, whom Genji marries, is based on Murasaki Shikibu herself.


title: The Tale of Genji

text: Yosano Akiko, the first author to make a modern Japanese translation of "Genji", believed that Murasaki had written only chapters 1 to 33, and that chapters 35 to 54 were written by her daughter, Daini no Sanmi. Other scholars have also doubted the authorship of chapters 42 to 54 (particularly 44, which contains rare examples of continuity mistakes). According to Royall Tyler's introduction to his English translation of the work, recent computer analysis has turned up "statistically significant" discrepancies of style between chapters 45–54 and the rest, and also among the early chapters.


title: The Tale of Genji

text: Genji's mother dies when he is three years old, and the Emperor cannot forget her. The Emperor Kiritsubo then hears of a woman (Lady Fujitsubo), formerly a princess of the preceding emperor, who resembles his deceased concubine, and later she becomes one of his wives. Genji loves her first as a stepmother, but later as a woman, and they fall in love with each other. Genji is frustrated by his forbidden love for the Lady Fujitsubo and is on bad terms with his own wife (Aoi no Ue, the Lady Aoi). He engages in a series of love affairs with other women. These are however unfulfilling, as in most cases his advances are rebuffed, or his lover dies suddenly, or he becomes bored.


title: The Tale of Genji

text: Genji visits Kitayama, a rural hilly area north of Kyoto, where he finds a beautiful ten-year-old girl. He is fascinated by this little girl (Murasaki), and discovers that she is a niece of the Lady Fujitsubo. Finally he kidnaps her, brings her to his own palace and educates her to be like the Lady Fujitsubo, who is his womanly ideal. During this time Genji also meets Lady Fujitsubo secretly, and she bears his son, Reizei. Everyone except the two lovers believes the father of the child is the Emperor Kiritsubo. Later the boy becomes the Crown Prince and Lady Fujitsubo becomes the Empress, but Genji and Lady Fujitsubo swear to keep the child's true parentage secret.


title: The Tale of Genji

text: Genji and his wife, Lady Aoi, reconcile. She gives birth to a son but dies soon after. Genji is sorrowful but finds consolation in Murasaki, whom he marries. Genji's father, the Emperor Kiritsubo, dies. He is succeeded by his son Suzaku, whose mother (Kokiden), together with Kiritsubo's political enemies, take power in the court. Then another of Genji's secret love affairs is exposed: Genji and a concubine of the Emperor Suzaku are discovered while meeting in secret. The Emperor Suzaku confides his personal amusement at Genji's exploits with the woman (Oborozukiyo), but is duty-bound to punish Genji even though he is his half-brother. He exiles Genji to the town of Suma in rural Harima Province (now part of Kobe in Hyōgo Prefecture). There, a prosperous man known as the Akashi Novice (because he is from Akashi in Settsu Province) entertains Genji, and Genji has an affair with Akashi's daughter. She gives birth to Genji's only daughter, who will later become the Empress.


title: The Tale of Genji

text: In the capital the Emperor Suzaku is troubled by dreams of his late father, Kiritsubo, and something begins to affect his eyes. Meanwhile, his mother, Kokiden, grows ill, which weakens her influence over the throne, and leads to the Emperor ordering Genji to be pardoned. Genji returns to Kyoto. His son by Lady Fujitsubo, Reizei, becomes the emperor. The new Emperor Reizei knows Genji is his real father, and raises Genji's rank to the highest possible.


title: The Tale of Genji

text: However, when Genji turns 40 years old, his life begins to decline. His political status does not change, but his love and emotional life begin to incrementally diminish as middle age takes hold. He marries another wife, the Third Princess (known as Onna san no miya in the Seidensticker version, or Nyōsan in Waley's). Genji's nephew, Kashiwagi, later forces himself on the Third Princess, and she bears Kaoru (who, in a similar situation to that of Reizei, is legally known as the son of Genji). Genji's new marriage changes his relationship with Murasaki, who had expressed her wish of becoming a nun () though the wish was rejected by Genji.


title: The Tale of Genji

text: Genji's beloved Murasaki dies. In the following chapter, ("Illusion"), Genji contemplates how fleeting life is. Immediately after the chapter titled , there is a chapter titled ("Vanished into the Clouds"), which is left blank, but implies the death of Genji.


title: The Tale of Genji

text: Chapter 45–54 are known as the "Uji Chapters". These chapters follow Kaoru and his best friend, Niou. Niou is an imperial prince, the son of Genji's daughter, the current Empress now that Reizei has abdicated the throne, while Kaoru is known to the world as Genji's son but is in fact fathered by Genji's nephew. The chapters involve Kaoru and Niou's rivalry over several daughters of an imperial prince who lives in Uji, a place some distance away from the capital. The tale ends abruptly, with Kaoru wondering if Niou is hiding Kaoru's former lover away from him. Kaoru has sometimes been called the first anti-hero in literature.


title: The Tale of Genji

text: The tale has an abrupt ending. Opinions vary on whether this was intended by the author. Arthur Waley, who made the first English translation of the whole of "The Tale of Genji", believed that the work as we have it was finished. Ivan Morris, however, author of "The World of the Shining Prince", believed that it was not complete and that later chapters were missing. Edward Seidensticker, who made the second translation of the "Genji", believed that Murasaki Shikibu had not had a planned story structure with an ending as such but would simply have continued writing as long as she could.


title: The Tale of Genji

text: Because it was written to entertain the Japanese court of the 11th century, the work presents many difficulties to modern readers. First and foremost, Murasaki's language, Heian-period court Japanese, was highly inflected and had very complex grammar. Another problem is that naming people was considered rude in Heian court society, so none of the characters are named within the work; instead, the narrator refers to men often by their rank or their station in life, and to women often by the color of their clothing, or by the words used at a meeting, or by the rank of a prominent male relative. This results in different appellations for the same character depending on the chapter.


title: The Tale of Genji

text: Another aspect of the language is the importance of using poetry in conversations. Modifying or rephrasing a classic poem according to the current situation was expected behavior in Heian court life, and often served to communicate thinly veiled allusions. The poems in the "Genji" are often in the classic Japanese form. Many of the poems were well known to the intended audience, so usually only the first few lines are given and the reader is supposed to complete the thought themselves, leaving the rest – which the reader would be expected to know – unspoken.


title: The Tale of Genji

text: As with most Heian literature, "Genji" was probably written mostly (or perhaps entirely) in kana (Japanese phonetic script) and not in kanji, because it was written by a woman for a female audience. Writing in kanji was at the time a masculine pursuit; women were generally discreet when using kanji, confining themselves mostly to native Japanese words ().


title: The Tale of Genji

text: Outside of vocabulary related to politics and Buddhism, "Genji" contains remarkably few Chinese loan words (). This has the effect of giving the story a very even, smooth flow. However, it also introduces confusion: there are a number of homophones (words with the same pronunciation but different meanings), and for modern readers, context is not always sufficient to determine which meaning was intended.


title: The Tale of Genji

text: The novel is traditionally divided into three parts, the first two dealing with the life of Genji and the last with the early years of two of Genji's prominent descendants, Niou and Kaoru. There are also several short transitional chapters which are usually grouped separately and whose authorships are sometimes questioned.


title: The Tale of Genji

text: The 54th and last chapter, "The Floating Bridge of Dreams", is sometimes argued by modern scholars to be a separate part from the Uji part. It seems to continue the story from the previous chapters but has an unusually abstract chapter title. It is the only chapter whose title has no clear reference within the text, although this may be due to the chapter being unfinished. This question is made more difficult by the fact that we do not know exactly when the chapters acquired their titles.


title: The Tale of Genji

text: The English translations here are taken from the Arthur Waley, the Edward Seidensticker, the Royall Tyler, and the Dennis Washburn translations. It is not known for certain when the chapters acquired their titles. Early mentions of the Tale refer to chapter numbers, or contain alternate titles for some of the chapters. This may suggest that the titles were added later. The titles are largely derived from poetry that is quoted within the text, or allusions to various characters.


title: The Tale of Genji

text: The additional chapter between 41 and 42 in some manuscripts is called which means "Vanished into the Clouds"—the chapter is a title only, and is probably intended to evoke Genji's death. Some scholars have posited the earlier existence of a chapter between 1 and 2 which would have introduced some characters that seem to appear very abruptly in the book as it stands.


title: The Tale of Genji

text: Later authors have composed additional chapters, most often either between 41 and 42, or after the end.


title: The Tale of Genji

text: The original manuscript written by Murasaki Shikibu no longer exists. Numerous copies, totaling around 300 according to Ikeda Kikan, exist with differences between each. It is thought that Shikibu often went back and edited early manuscripts introducing discrepancies with earlier copies.


title: The Tale of Genji

text: In the 13th century, two major attempts by Minamoto no Chikayuki and Fujiwara Teika were made to edit and revise the differing manuscripts. The Chikayuki manuscript is known as the ; edits were many beginning in 1236 and completing in 1255. The Teika manuscript is known as the ; its edits are more conservative and thought to better represent the original. These two manuscripts were used as the basis for many future copies.


title: The Tale of Genji

text: The category represents all other manuscripts not belonging to either or . This includes older but incomplete manuscripts, mixed manuscripts derived from both and , and commentaries.


title: The Tale of Genji

text: On March 10, 2008, it was announced that a late Kamakura period (1192–1333) manuscript had been found in Kyoto, containing the sixth chapter, ; the manuscript was 65 pages in length. Most remaining manuscripts are based on copies of the Teika manuscript which introduced revisions in the original; this manuscript, however, belongs to a different lineage and was not influenced by Teika. Professor Yamamoto Tokurō, who examined the manuscript, said, "This is a precious discovery as Kamakura manuscripts are so rare." Professor Katō Yōsuke said, "This is an important discovery as it asserts that non-Teika manuscripts were being read during the Kamakura period."


title: The Tale of Genji

text: On October 29, 2008, Konan Women's University announced that a mid-Kamakura period manuscript had been found,


title: The Tale of Genji

text: containing the 32nd chapter, . The manuscript was recognized as the oldest extant copy of this chapter, dating to between 1240 and 1280. The manuscript, considered to be of the category, is 74 pages in length and differs from manuscripts in at least four places, raising the "possibility that the contents may be closer to the undiscovered Murasaki Shikibu original manuscript".


title: The Tale of Genji

text: On October 9, 2019, it was announced that an original copy of Teika's had been found in Tokyo at the home of the current head of the Okochi-Matsudaira clan, who ran the Yoshida Domain. The manuscript is the 5th chapter, , and is the oldest version of the chapter. Blue ink common in Teika's manuscript and handwriting analysis confirmed that the manuscript was written by Teika, making it among the 5 original versions of the known to exist.


title: The Tale of Genji

text: Numerous illustrations of scenes from "Genji" have been produced, most notably a 12th-century scroll, the , containing illustrated scenes from "Genji" together with handwritten text. This scroll is the earliest extant example of a Japanese "picture scroll": collected illustrations and calligraphy of a single work. The original scroll is believed to have comprised 10–20 rolls and covered all 54 chapters. The extant pieces include only 19 illustrations and 65 pages of text, plus nine pages of fragments. This is estimated at 15% of the envisioned original.


title: The Tale of Genji

text: The Tokugawa Art Museum in Nagoya has three of the scrolls handed down in the Owari branch of the Tokugawa clan and one scroll held by the Hachisuka family is now in the Gotoh Museum in Tokyo. The scrolls are designated National Treasures of Japan. The scrolls are so fragile that they normally are not shown in public. The original scrolls in the Tokugawa Museum were shown from November 21 to November 29 in 2009. Since 2001, they have been displayed in the Tokugawa Museum annually for around one week in November. An oversize English photoreproduction and translation was published in limited edition in 1971 by Kodansha International.


title: The Tale of Genji

text: Other notable illustrated scrolls of "Genji" are by Tosa Mitsuoki, who lived from 1617 to 1691. His paintings are closely based on Heian style from the existing scrolls from the 12th century and are fully complete. The tale was also a popular theme in ukiyo-e prints from the Edo period.


title: The Tale of Genji

text: "The Tale of Genji" was written in an archaic court language, and a century after its completion it was difficult to read without specialized study. Annotated and illustrated versions existed as early as the 12th century. It was not until the early 20th century that "Genji" was translated into modern Japanese by the poet Akiko Yosano. Translations into modern Japanese have made it easier to read though changed some meaning, and has given names to the characters, usually the traditional names used by academics. This gives rise to anachronisms; for instance, Genji's first wife is named Aoi because she is known as the lady of the Aoi chapter, in which she dies.


title: The Tale of Genji

text: Because of the cultural differences, reading an annotated version of the "Genji" is quite common, even among Japanese readers. There are several annotated versions by novelists, including Seiko Tanabe, Jakucho Setouchi and Osamu Hashimoto. Many works, including a manga series and different television dramas, are derived from "The Tale of Genji". There have been at least five manga adaptations of "Genji". A manga version was created by Waki Yamato, ("The Tale of Genji" in English), and a current version by Sugimura Yoshimitsu is in progress. Another manga, , by Miyako Maki, won the Shogakukan Manga Award in 1989.


title: The Tale of Genji

text: The first partial translation of "Genji" into English was by Suematsu Kenchō, published in 1882. Arthur Waley published a six-volume translation of all but one chapter, with the first volume published in 1925 and the last in 1933. In 1976, Edward Seidensticker published the first complete translation into English, made using a self-consciously "stricter" approach with regards to content if not form. The English translation published in 2001 by Royall Tyler aims at fidelity in content and form to the original text.


title: The Tale of Genji

text: The major translations into English are each slightly different, mirroring the personal choices of the translator and the period in which the translation was made. Each version has its merits, its detractors and its advocates, and each is distinguished by the name of the translator. For example, the version translated by Arthur Waley would typically be referred to as "the Waley "Genji"".


title: The Tale of Genji

text: "The Tale of Genji" is an important work of Japanese literature, and modern authors have cited it as inspiration, such as Jorge Luis Borges who said of it, ""The Tale of Genji", as translated by Arthur Waley, is written with an almost miraculous naturalness, and what interests us is not the exoticism—the horrible word—but rather the human passions of the novel. Such interest is just: Murasaki's work is what one would quite precisely call a psychological novel ... I dare to recommend this book to those who read me. The English translation that has inspired this brief insufficient note is called "The Tale of Genji"." It is noted for its internal consistency, psychological depiction, and characterization. The novelist Yasunari Kawabata said in his Nobel Prize acceptance speech: ""The Tale of Genji" in particular is the highest pinnacle of Japanese literature. Even down to our day there has not been a piece of fiction to compare with it."


title: The Tale of Genji

text: The "Genji" is also often referred to as "the first novel", though there is considerable debate over this; other texts that predate "Genji", such as the 7th-century Sanskrit , or the Greek and Roman novels from classical antiquity, such as Daphnis and Chloe and the Satyricon, are considered to be novels, and there is debate around whether "Genji" can even be considered a "novel". Some consider the psychological insight, complexity and unity of the work to qualify it for "novel" status while simultaneously disqualifying earlier works of prose fiction. Others see these arguments as subjective and unconvincing.


title: The Tale of Genji

text: Related claims, perhaps in an attempt to sidestep these debates, are that "Genji" is the "first psychological novel" or "historical novel", "the first novel still considered to be a classic" or other more qualified terms. However, critics have almost consistently described "The Tale of Genji" as the oldest, first, and/or greatest novel in Japanese literature, though enthusiastic proponents may have later neglected the qualifying category of 'in Japanese literature', leading to the debates over the book's place in world literature. Even in Japan, the "Tale of Genji" is not universally embraced; the lesser-known has been proposed as the "world's first full-length novel", even though its author is unknown. Despite these debates, "The Tale of Genji" enjoys solid respect among the works of literature, and its influence on Japanese literature has been compared to that of Philip Sidney's "Arcadia" on English literature.


title: The Tale of Genji

text: The novel and other works by Lady Murasaki are staple reading material in the curricula of Japanese schools. The Bank of Japan issued the 2000 yen banknote in her honor, featuring a scene from the novel based on the 12th-century illustrated handscroll. Since a 1 November 1008 entry in "The Diary of Lady Murasaki" is the oldest date on which a reference to "The Tale of Genji" has appeared, November 1 was designated as the official day to celebrate Japanese classics. According to Act on Classics Day, the "classics" that are honored not only include literature, but encompass a wide range of arts such as music, art, traditional performing arts, entertainment, lifestyle art including tea ceremony and flower arrangement and other cultural products.


title: The Tale of Genji

text: The names of the chapters became a central element in a incense-based game called Genjikō, part of the larger practice of Monkō popular among the nobility. In Genjikō, players must match the scents of a series of five incense samples without being told the names of said samples. Each possible combination was matched to a symbol, called a , that represented a chapter from the story.


title: John Q.

text: John Q. is a 2002 American thriller drama film starring Denzel Washington and directed by Nick Cassavetes. The film tells the story of John Quincy Archibald (Denzel Washington), a father and husband whose son is diagnosed with an enlarged heart and who finds out he is unable to receive a transplant because HMO insurance will not cover it, before he decides to hold hostages at the hospital and force them to do it.


title: John Q.

text: The film co-stars Robert Duvall, Kimberly Elise, Anne Heche, James Woods, and Ray Liotta. The film was shot in Toronto, Hamilton, Ontario, and Canmore, Alberta, although the story takes place in Chicago. Shooting took place for 60 days from August 8 to November 3, 2000. The film was released on February 15, 2002. It received generally negative reviews from critics; however, the film grossed $102 million worldwide.


title: John Q.

text: A young woman is killed in a collision with a truck. Weeks earlier in Chicago, factory worker John Quincy Archibald and his wife Denise are behind with their house payments. One day after church they rush their young son Michael to the hospital after he collapses at his baseball game, and are told by cardiologist Dr. Raymond Turner and administrator Rebecca Payne that Michael needs a heart transplant. John and Denise have only $1,000 in savings, and they are informed that the hospital requires a $75,000 down payment of the procedure's $250,000 cost to simply place Michael on the organ transplant list. To make matters worse, John discovers that his work’s health insurance will not cover the surgery.


title: John Q.

text: John and Denise struggle to raise the money and the hospital prepares to send Michael home to die when the couple exhausts all their opportunities and still comes up short. Determined to save his son, John takes Dr. Turner and several patients and staff hostage at gunpoint in the ER. Police negotiator Lt. Frank Grimes makes contact with John, who demands Payne put Michael's name on the organ transplant list.


title: John Q.

text: Grimes clashes with his superior Chief Gus Monroe, while most of the hostages sympathize with John's plight and reflect on the flaws of America's healthcare system. One of the nurses revealed that Michael's condition could have been detected much earlier during routine checkup but the doctor ignored it to gain bonus from insurance company to keep his mouth shut to maintain their profit. Agreeing to release some of the patients, John is attacked by hostage Mitch, whose abused girlfriend Julie helps John subdue and handcuff Mitch. John frees expectant couple Steve and Miriam and immigrant mother Rosa with her infant son, who all declare their support for John to the news crews outside. Grimes and Payne reveal John's actions to Denise, and Payne places Michael on the list to perform the operation pro bono.


title: John Q.

text: Overriding Grimes, Monroe has a SWAT sniper enter the ER via an air shaft, luring John into the line of fire with a phone call from Denise. John speaks with Michael as his condition worsens, while a news crew hacks the police surveillance feed and broadcasts John's conversation with his family. John discovers the hacked news footage just as the sniper fires, wounding him in the shoulder. John overpowers the sniper and uses him as a human shield as he reiterates his demands in front of a cheering crowd. As night falls, Michael is removed from the ICU and brought to the ER in exchange for the sniper's release, while Denise waits at the police command post.


title: John Q.

text: John reveals his intention to die by suicide to save Michael with his own heart, and also reveals that his gun was empty all along. He persuades Turner to perform the operation, and Julie and security guard Max bear witness to John's impromptu will. He says his goodbyes to Michael, and prepares to end his own life using the only bullet he brought, when Denise brings news that the heart of a recently deceased organ donor – the motorist from the beginning of the film – is on the way. Once the heart arrives, John releases the hostages, including patient Lester, who surrenders to police posing as John. John, posing as a surgeon, accompanies Michael to the operating room where Grimes, who noticed the switch, allows him to watch Michael's operation before arresting him.


title: John Q.

text: Three months later, John's actions have sparked national debate about healthcare, and in court his family, friends and all the hostages testify on his behalf at trial. John is ultimately acquitted of attempted murder and armed criminal action, but convicted of kidnapping and false imprisonment. His lawyer assures him that he will likely serve no more than two years. As John is escorted from the courthouse, Lester proclaims him as a hero, and now-healthy Michael gains eye contact with his father, saying "Dad!" and then, "Thank you".


title: John Q.

text: According to the commentary on the Deleted Scenes with Cassavetes and writer James Kearns, the main theme of the movie was said to be "about a miracle and John's faith in God creating the miracle". They also mentioned how SWAT team advisors for the film related a similar true incident in Toronto where a man (Henry Masuka) took an ER hostage after it would not provide immediate service to his infant son on New Year's Eve 1999. When he exited the ER he was shot and killed and found to be carrying an unloaded pellet gun.


title: John Q.

text: "John Q." opened in first place, grossing $23.3 million during its first weekend. It ended up with a total domestic gross of $71 million and $102.2 million worldwide.


title: John Q.

text: On Rotten Tomatoes "John Q." holds an approval rating of 25% based on the 133 reviews, with an average rating of 4.5/10. The site's critics consensus reads, "Washington's performance rises above the material, but "John Q" pounds the audience over the head with its message." Metacritic gives the film a weighted average score of 30 out of 100, based on 33 critics, indicating "generally unfavorable reviews". Audiences polled by CinemaScore gave the film an average grade of "A" on an A+ to F scale.


title: John Q.

text: Zee Studios acquired the rights to "John Q."'s Hindi adaptation, titled "Sanak", with Vidyut Jammwal in the lead role. Streaming service Hotstar acquired the film's distribution rights and released it on 15 October 2021 to mixed reviews from critics.


title: Meal, Ready-to-Eat

text: A Meal, Ready-to-Eat (MRE) is a self-contained, individual field ration in lightweight packaging purchased by the United States Department of Defense for its service members for use in combat or field conditions where other food is not available. While MREs should be kept cool, they do not need to be refrigerated. The MRE replaced the canned MCI, or Meal, Combat, Individual rations, in 1981, and is the intended successor to the lighter LRP ration developed by the US Army for Special Forces and Ranger patrol units in Vietnam. MREs have also been distributed to civilians during natural disasters.


title: Meal, Ready-to-Eat

text: Since the 2010s, the term "MRE" is sometimes used informally in English (especially on the Internet) as a more general term for a field ration. The usage of the term was popular among YouTube users, most notably Steven Andrew Thomas, an American YouTube personality specializing in field rations from different countries.


title: Meal, Ready-to-Eat

text: The first U.S. soldier ration established by a Congressional Resolution, during the Revolutionary War, consisted of enough food to feed a man for one day, mostly beef, peas, and rice. During the Civil War, the U.S. military moved toward canned goods. Later, self-contained kits were issued as a whole ration and contained canned meat, bread, coffee, sugar and salt. During the First World War, canned meats were replaced with lightweight preserved meats (salted or dried) to save weight and allow more rations to be carried by soldiers carrying their supplies on foot. At the beginning of World War II, a number of new field rations were introduced, including the Mountain ration and the Jungle ration. However, cost-cutting measures by Quartermaster Command officials during the latter part of World War II and the Korean War again saw the predominance of heavy canned C rations issued to troops, regardless of operating environment or mission. During WWII, over 100 million cans of Spam were sent to the Pacific. The use of canned wet rations continued through the Vietnam War, with the improved MCI field ration.


title: Meal, Ready-to-Eat

text: After repeated experiences with providing prepared rations to soldiers dating from before World War II, Pentagon officials ultimately realized that simply providing a nutritionally balanced meal in the field was not adequate. Service members in various geographic regions and combat situations often required different subsets of ingredients for food to be considered palatable over long periods. Moreover, catering to individual tastes and preferences would encourage service members to actually consume the whole ration and its nutrition. Most importantly, the use of specialized forces in extreme environments and the necessity of carrying increasingly heavy field loads while on foot during extended missions required significantly lighter alternatives to standard canned wet rations.


title: Meal, Ready-to-Eat

text: In 1963, the Department of Defense began developing the "Meal, Ready to Eat," a ration that would rely on modern food preparation and packaging technology to create a lighter replacement for the canned Meal, Combat, Individual ration. In 1966, this led to the Long Range Patrol, or LRP ration, a dehydrated meal stored in a waterproof canvas pouch. However, just as with the Jungle ration, its expense compared to canned wet rations, as well as the costs of stocking and storing a specialized field ration, led to its limited usage and repeated attempts at discontinuance by Quartermaster Command officials.


title: Meal, Ready-to-Eat

text: Early MRE prototypes that involved freeze-dried and dehydrated foods were developed under Dr. Abdul Rahman, who later received the Meritorious Civilian Service Award for his work. However, further work was needed to develop a ration that did not require re-hydration (thus not requiring additional preparation time and water). Further effort, led by Dr. Rauno A. Lampi, Chief of Food Systems Equipment Division at the Natick Soldier Research, Development and Engineering Center, concentrated on the refinement of the retort pouch to contain a wet ration with a three-to-ten year shelf life that could be easily shipped, carried in the field, opened and consumed straight out of the package if necessary with no further heat or water. The resulting MRE went into special issue starting in 1981 and standard issue in 1986, using a limited menu of twelve entrées.