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#2456. In which part of the human body is Hypopyon associated?

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#6229.

2230) Katalin Karikó

Gist:

Work

A vaccine prevents diseases by stimulating the body's immune system to develop a defense against the infectious agent. One type of vaccine uses mRNA, which transfers genetic information from DNA to stimulate protein production. In 2005 Katalin Karikó and Drew Weissman discovered that certain modifications of the building blocks of RNA prevented unwanted inflammatory reactions and increased the production of desired proteins. The discovery laid the foundation for effective mRNA vaccines against COVID-19 during the pandemic that began in early 2020.

Summary

Katalin Karikó (born January 17, 1955, Kisújszállás, Hungary) is a Hungarian-born biochemist known for her pioneering research into RNA (ribonucleic acid) therapeutics, particularly the development of messenger RNA (mRNA) vaccines. Karikó’s investigation into the ability of mRNA nucleosides (structural subunits of nucleic acids) to trigger immune responses against specific pathogens (disease-causing agents) greatly facilitated the development of the first mRNA vaccines—a breakthrough that occurred in 2021, during the coronavirus disease 2019 (COVID-19) pandemic. For their discoveries relating to mRNA nucleosides, which opened the way to the development of effective COVID-19 mRNA vaccines, Karikó and her colleague American immunologist Drew Weissman were awarded the 2023 Nobel Prize in Physiology or Medicine.

Education and early career

Karikó grew up in a small village in Hungary, where from an early age she expressed an interest in nature and excelled academically in science. In 1978, after graduating with a doctoral degree from the University of Szeged, she accepted a position at the Biological Research Centre (BRC), Szeged. There she studied the antiviral activity of short segments of RNA and began her investigations of modified nucleosides, a type of synthetic mRNA in which specific nucleosides have been altered or replaced, typically with either synthetic nucleosides or naturally modified nucleosides.

In 1985, with no further funding to support her research at the BRC, Karikó moved to the United States, where she accepted a position as a postdoctoral researcher at Temple University in Philadelphia. Four years later she took a position at the University of Pennsylvania (Penn). There, with American cardiologist Elliot Barnathan, she demonstrated that mRNA, when inserted into cells, could be used to direct the production of new proteins. The breakthrough inspired her to pursue the study of mRNA-based gene therapy.

By the late 1990s, however, Karikó’s work on mRNA and gene therapy had stalled—again, for lack of funding. She considered leaving Penn for another research institution or pursuing different work entirely, but then she began collaborating at Penn with Weissman. Both researchers were interested in the possibility of using mRNA to stimulate the body to develop immunity against viral pathogens. In initial studies, they discovered that mRNA is highly immunogenic, provoking counterproductive immune responses in the body. However, when Karikó carried out experiments with a different type of RNA molecule, transfer RNA (tRNA), she did not observe the same immunogenic effects. That observation encouraged her and Weissman to experiment with modified nucleosides, which she had known about from her work at the BRC. The researchers went on to identify associations between specific modified mRNA nucleosides and reduced immunogenicity—a breakthrough that resulted in a technology known as non-immunogenic, nucleoside-modified RNA, which was developed and patented (2005) by Karikó and Weissman.

Karikó and Weissman subsequently started a company called RNARx, which aimed to commercialize non-immunogenic, nucleoside-modified RNA. The researchers eventually licensed the technology to two biotechnology companies, Moderna and BioNTech. In 2013 Karikó took a position as senior vice president at BioNTech, overseeing the company’s work on mRNA. In the following years, although both companies had multiple RNA therapeutics in clinical trials, none had yet proved successful. In 2021, however, a major breakthrough came during the COVID-19 pandemic, fueled by the urgency to develop a vaccine that could help prevent or reduce the severity of infection with SARS-CoV-2, the virus that causes COVID-19. Unlike traditional vaccine development, the generation of mRNA vaccines is relatively rapid, relying primarily on synthetic technologies, without any need for actual virus particles. Within months of obtaining the genetic code of SARS-CoV-2, scientists at Moderna and Pfizer-BioNTech had experimental mRNA vaccines ready for testing.

Awards

In addition to the Nobel Prize, Karikó’s work on RNA therapeutics was recognized with numerous honours, including the Lewis S. Rosenstiel Award for Distinguished Work in Basic Medical Research (2020), the Lasker-DeBakey Clinical Medical Research Award (2021), and the Louisa Gross Horwitz Prize (2021); all three awards were shared with Weissman.

Details

Katalin Karikó (born 17 January 1955) is a Hungarian-American biochemist who specializes in ribonucleic acid (RNA)-mediated mechanisms, particularly in vitro-transcribed messenger RNA (mRNA) for protein replacement therapy. Karikó laid the scientific groundwork for mRNA vaccines, overcoming major obstacles and skepticism in the scientific community. Karikó received the Nobel Prize in Physiology or Medicine in 2023 for her work, along with American immunologist Drew Weissman.

Karikó co-founded and was CEO of RNARx from 2006 to 2013. From 2013 to 2022, she was associated with BioNTech RNA Pharmaceuticals, first as a vice president and promoted to senior vice president in 2019. In 2022, she left BioNTech to devote more time to research. In 2021, she received an honorary doctorate from the University of Szeged in Hungary, where she has since become a professor. While Karikó has also been associated with the University of Pennsylvania, which would benefit financially from her eventual discovery, the university had actively discouraged her from pursuing research by underfunding and deprioritizing work on mRNA. After being demoted by the University of Pennsylvania in 1995, Karikó was never granted tenure and joined BioNTech in 2013 after the university had declined to reinstate her.

Karikó's work includes scientific research on RNA-mediated immune activation, resulting in the co-discovery with Drew Weissman of the nucleoside modifications that suppress the immunogenicity of RNA. This is seen as a further contribution to the therapeutic use of mRNA. Together with Weissman, she holds United States patents for the application of non-immunogenic, nucleoside-modified RNA. This technology has been licensed by BioNTech and Moderna to develop their protein replacement technologies, but it was also used for their COVID-19 vaccines.

The messenger RNA-based technology developed by Karikó and the two most effective vaccines based on it, BioNTech/Pfizer and Moderna, have formed the basis for the effective and successful fight against SARS-CoV-2 virus worldwide and have contributed significantly to the containment of the COVID-19 pandemic. For their work, Karikó and Weissman have received numerous other awards besides the Nobel, including the Lasker–DeBakey Clinical Medical Research Award, Time Magazine's Hero of the Year 2021, and the Tang Prize Award in Biopharmaceutical Science in 2022.

2376) Shinkansen

Gist

The Shinkansen, or "Bullet Train," is Japan's high-speed railway network, known for its speed, reliability, and advanced technology. Opened in 1964 to connect distant regions and facilitate economic growth, the Shinkansen network allows passengers to travel efficiently between major cities like Tokyo, Osaka, and Fukuoka. The trains are characterized by their aerodynamic, bullet-shaped noses and operate on dedicated tracks, with a central management system ensuring high levels of safety.

The Shinkansen, or "Bullet Train," is Japan's high-speed railway network, known for its speed, reliability, and advanced technology. Opened in 1964 to connect distant regions and facilitate economic growth, the Shinkansen network allows passengers to travel efficiently between major cities like Tokyo, Osaka, and Fukuoka. The trains are characterized by their aerodynamic, bullet-shaped noses and operate on dedicated tracks, with a central management system ensuring high levels of safety.

Summary

The Shinkansen, colloquially known in English as the bullet train, is a network of high-speed railway lines in Japan. It was initially built to connect distant Japanese regions with Tokyo, the capital, to aid economic growth and development. Beyond long-distance travel, some sections around the largest metropolitan areas are used as a commuter rail network. It is owned by the Japan Railway Construction, Transport and Technology Agency and operated by five Japan Railways Group companies.

Starting with the Tokaido Shinkansen (515.4 km; 320.3 mi) in 1964, the network has expanded to consist of 2,951.3 km (1,833.9 mi) of lines with maximum speeds of 260–320 km/h (160–200 mph), 283.5 km (176.2 mi) of Mini-shinkansen lines with a maximum speed of 130 km/h (80 mph), and 10.3 km (6.4 mi) of spur lines with Shinkansen services. The network links most major cities on the islands of Honshu and Kyushu, and connects to Hakodate on the northern island of Hokkaido. An extension to Sapporo is under construction and was initially scheduled to open by fiscal year 2030, but in December 2024, it was delayed until the end of FY2038. The maximum operating speed is 320 km/h (200 mph) (on a 387.5 km (241 mi) section of the Tōhoku Shinkansen). Test runs have reached 443 km/h (275 mph) for conventional rail in 1996, and up to a world record 603 km/h (375 mph) for SCMaglev trains in April 2015.

The original Tokaido Shinkansen, connecting Tokyo, Nagoya, and Osaka —three of Japan's largest cities — is one of the world's busiest high-speed rail lines. In the one-year period preceding March 2017, it carried 159 million passengers, and since its opening more than six decades ago, it has transported more than 6.4 billion total passengers. At peak times, the line carries up to 16 trains per hour in each direction with 16 cars each (1,323-seat capacity and occasionally additional standing passengers) with a minimum headway of three minutes between trains.

The Shinkansen network of Japan had the highest annual passenger ridership (a maximum of 353 million in 2007) of any high-speed rail network until 2011, when the Chinese high-speed railway network surpassed it at 370 million passengers annually.

Details

Shinkansen, pioneer high-speed passenger rail system of Japan, with lines on the islands of Honshu, Kyushu, and Hokkaido. It was originally built and operated by the government-owned Japanese National Railways and has been part of the private Japan Railways Group since 1987.

The first section of the original line, a 320-mile (515-km) stretch between Tokyo and Ōsaka, was opened in 1964. Known as the New Tōkaidō Line, it generally follows and is named for the historic and celebrated Tōkaidō (“Eastern Sea Road”) highway that was used especially during the Edo (Tokugawa) period (1603–1867). Inauguration of the line, just before the start of the Tokyo 1964 Olympic Games, was greeted by widespread international acclaim, and the Shinkansen was quickly dubbed the “bullet train” for the great speed the trains obtained and for the aerodynamic bullet shape of their noses. Many innovations, such as the use of prestressed concrete ties and mile-long welded sections of track, were introduced in the line’s construction. A 100-mile (160-km) extension of that line westward from Ōsaka to Okayama was completed in 1972, and its final segment, a 244-mile (393-km) stretch between Okayama and the Hakata station in Fukuoka, northern Kyushu, opened in 1975.

Other lines radiating northward from Tokyo were completed in 1982 to the cities of Niigata (the Jōetsu line) and Morioka (the Tōhoku line), the Tōhoku line subsequently being extended northward to Hachinohe in 2002. Work to build a link to Aomori, northwest of Hachinohe, began in the late 1990s. When that segment opened in 2010, the Shinkansen was essentially complete for the entire length of Honshu. However, plans had long been in place to connect all three main Japanese islands by Shinkansen with a line northward into Hokkaido (via the Seikan Tunnel under Tsugaru Strait). Construction on the Hokkaido line began in 2005 on the segment between Aomori and Hakodate in southern Hokkaido, the ultimate goal being to extend the line to Sapporo. The line between Aomori and Hakodate opened in 2016. Construction on the section from Hakodate to Sapporo was begun in 2012 and expected to be completed in 2031.

Branches from the Tōhoku line to Yamagata opened in 1992 (extended north to Shinjo in 1999) and to Akita in 1997; a branch from the Jōetsu line to Nagano also opened in 1997. Segments of a further extension of the Nagano branch westward to Toyama and Kanazawa opened in 2015. In addition, a line was completed between Yatsushiro and Kagoshima in southwestern Kyushu in 2004. In the late 1990s work commenced to extend that line northward from Yatsushiro to Hakata, and the opening of the segment in 2011 completed the full north-south route of the Shinkansen on Kyushu. Work began in 2008 on a branch from the Kyushu line southwestward to Nagasaki, and it opened in 2022.

Much of the system’s track runs through tunnels, including one under Shimonoseki Strait between Honshu and Kyushu, another on the Tokyo-Niigata line that is 14 miles (23 km) long, and another near Aomori with a record length (for a double-tracked inland tunnel) of 16.5 miles (26.5 km) when the bore was finished in 2005. Several hundred trains operate daily on the Shinkansen system. The most-frequent service is between Tokyo and Ōsaka, especially during the morning and evening rush hours, when trains depart at intervals of 10 minutes or less. The fastest trains can make the trip from Tokyo to Hakata in about five hours, and the quickest from Tokyo to Aomori take about three hours.

The electric multiple-unit trains, which can seat 1,000 passengers or more, derive their power from an overhead wire system. Trains originally reached top speeds of 130 miles (210 km) per hour, but improvements in track, train cars, and other components have made possible maximum speeds of between 150 and 185 miles (240 and 300 km) per hour. In early 2013 some trains began operating at up to 200 miles (320 km) per hour. Such high speeds made it necessary to develop elaborate safety features. Each car, for example, is equipped with brakes consisting of cast-iron discs and metallic pad linings specially designed not to distort under emergency braking. Moreover, all movements of the trains are monitored and controlled by a central computerized facility in Tokyo.

Additional Information

Japan's main islands of Honshu, Kyushu and Hokkaido are served by a network of high speed train lines that connect Tokyo with most of the country's major cities. Japan's high speed trains (bullet trains) are called shinkansen and are operated by Japan Railways (JR).

Running at speeds of up to 320 km/h, the shinkansen is known for punctuality (most trains depart on time to the second), comfort (relatively silent cars with spacious, always forward-facing seats), safety (no fatal accidents in its history) and efficiency. Thanks to various rail passes, the shinkansen can also be a cost-effective means of travel.

Shinkansen network

The shinkansen network consists of multiple lines, among which the Tokaido Shinkansen (Tokyo - Nagoya - Kyoto - Osaka) is the oldest and most popular. All shinkansen lines (except the Akita and Yamagata Shinkansen) run on tracks that are exclusively built for and used by shinkansen trains. Most lines are served by multiple train categories, ranging from the fastest category that stops only at major stations to the slowest category that stops at every station.

Individuals differ from one another in their ability to understand complex ideas, to adapt effectively to the environment, to learn from experience, to engage in various forms of reasoning, to overcome obstacles by taking thought. Although these individual differences can be substantial, they are never entirely consistent: a given person's intellectual performance will vary on different occasions, in different domains, as judged by different criteria. Concepts of "intelligence" are attempts to clarify and organize this complex set of phenomena. Although considerable clarity has been achieved in some areas, no such conceptualization has yet answered all the important questions, and none commands universal assent. Indeed, when two dozen prominent theorists were recently asked to define intelligence, they gave two dozen, somewhat different, definitions.

Human

Human intelligence is the intellectual power of humans, which is marked by complex cognitive feats and high levels of motivation and self-awareness. Intelligence enables humans to remember descriptions of things and use those descriptions in future behaviors. It gives humans the cognitive abilities to learn, form concepts, understand, and reason, including the capacities to recognize patterns, innovate, plan, solve problems, and employ language to communicate. These cognitive abilities can be organized into frameworks like fluid vs. crystallized and the Unified Cattell-Horn-Carroll model, which contains abilities like fluid reasoning, perceptual speed, verbal abilities, and others.

Intelligence is different from learning. Learning refers to the act of retaining facts and information or abilities and being able to recall them for future use. Intelligence, on the other hand, is the cognitive ability of someone to perform these and other processes.

Intelligence quotient (IQ)

There have been various attempts to quantify intelligence via psychometric testing. Prominent among these are the various Intelligence Quotient (IQ) tests, which were first developed in the early 20th century to screen children for intellectual disability. Over time, IQ tests became more pervasive, being used to screen immigrants, military recruits, and job applicants. As the tests became more popular, belief that IQ tests measure a fundamental and unchanging attribute that all humans possess became widespread.

An influential theory that promoted the idea that IQ measures a fundamental quality possessed by every person is the theory of General Intelligence, or g factor. The g factor is a construct that summarizes the correlations observed between an individual's scores on a range of cognitive tests.

Today, most psychologists agree that IQ measures at least some aspects of human intelligence, particularly the ability to thrive in an academic context. However, many psychologists question the validity of IQ tests as a measure of intelligence as a whole.

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#2455. What does the medical term Growth factor signigy?

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#6228.

Zach Alie,

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