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🔗 Pharmacology

Eroom's law is the observation that drug discovery is becoming slower and more expensive over time, despite improvements in technology (such as high-throughput screening, biotechnology, combinatorial chemistry, and computational drug design), a trend first observed in the 1980s. The cost of developing a new drug roughly doubles every nine years (inflation-adjusted). In order to highlight the contrast with the exponential advancements of other forms of technology (such as transistors) over time, the law was deliberately spelled as Moore's law spelled backwards.

The article proposing and naming the law attributes it to four main causes.

• the 'better than the Beatles' problem: the sense that new drugs only have modest incremental benefit over drugs already widely considered as successful, such as Lipitor, and treatment effects on top of already effective treatments are smaller than treatment effects versus placebo. The smaller size of these treatment effects mandates an increase in clinical trial sizes to show the same level of efficacy. This problem was phrased as "better than the Beatles" to highlight the fact that it would be difficult to come up with new successful pop songs if all new songs had to be better than the Beatles.
• the 'cautious regulator' problem: the progressive lowering of risk tolerance seen by drug regulatory agencies that makes R&D both costlier and harder. After older drugs (such as Thalidomide or Vioxx) are removed from the market due to safety reasons, the bar on safety for new drugs is increased.
• the 'throw money at it' tendency: the tendency to add human resources and other resources to R&D, which may lead to project overrun.
• the 'basic research–brute force' bias: the tendency to overestimate the ability of advances in basic research and brute force screening methods to show a molecule as safe and effective in clinical trials. From the 1960s to the 1990s (and later), drug discovery has shifted from whole-animal classical pharmacology testing methods (phenotypic screening) to reverse pharmacology target-approaches that result in the discovery of drugs that may tightly bind with high-affinity to target proteins, but which still often fail in clinical trials due to an under-appreciation of the complexity of the whole organism. Furthermore, drug discovery techniques have shifted from small-molecule and iterative low-throughput search strategies to target-based high-throughput screening (HTS) of large compound libraries. But despite being faster and cheaper, HTS approaches may be less productive.

While some suspect a lack of "low-hanging fruit" as a significant contribution to Eroom's law, this may be less important than the four main causes, as there are still many decades' worth of new potential drug targets relative to the number of targets which already have been exploited, even if the industry exploits 4 to 5 new targets per year. There is also space to explore selectively non-selective drugs (or "dirty drugs") that interact with several molecular targets, and which may be particularly effective as central nervous system (CNS) therapeutics, even though few of them have been introduced in the last few decades.

🔗 Biography 🔗 Law 🔗 Computer Security 🔗 Computer Security/Computing 🔗 Biography/science and academia 🔗 Florida

Jonathan Joseph James (December 12, 1983 – May 18, 2008) was an American hacker who was the first juvenile incarcerated for cybercrime in the United States. The South Florida native was 15 years old at the time of the first offense and 16 years old on the date of his sentencing. He died at his Pinecrest, Florida home on May 18, 2008, of a self-inflicted gunshot wound.

🔗 Law 🔗 Geography

The Zone of Death is the name given to the 50 sq mi (129.50 km²) Idaho section of Yellowstone National Park in which, as a result of a purported loophole in the Constitution of the United States, a criminal could theoretically get away with any crime, up to and including murder.

🔗 United States 🔗 Biography 🔗 Physics 🔗 Biography/science and academia 🔗 Physics/Biographies 🔗 United States/Washington - Seattle 🔗 Buddhism 🔗 Invention

Chester Floyd Carlson (February 8, 1906 – September 19, 1968) was an American physicist, inventor, and patent attorney born in Seattle, Washington.

He is best known for inventing electrophotography, the process performed today by millions of photocopiers worldwide. Carlson's process produced a dry copy, as contrasted with the wet copies then produced by the mimeograph process. Carlson's process was renamed xerography, a term that means "dry writing."

🔗 Mathematics

Visual calculus, invented by Mamikon Mnatsakanian (known as Mamikon), is an approach to solving a variety of integral calculus problems. Many problems that would otherwise seem quite difficult yield to the method with hardly a line of calculation, often reminiscent of what Martin Gardner called "aha! solutions" or Roger Nelsen a proof without words.

🔗 Dentistry

Palmer notation (sometimes called the "Military System" and named for 19th-century American dentist Dr. Corydon Palmer from Warren, Ohio) is a dental notation (tooth numbering system). Despite the adoption of the FDI World Dental Federation notation (ISO 3950) in most of the world and by the World Health Organization, the Palmer notation continued to be the overwhelmingly preferred method used by orthodontists, dental students and practitioners in the United Kingdom as of 1998.

The notation was originally termed the Zsigmondy system after Hungarian dentist Adolf Zsigmondy, who developed the idea in 1861 using a Zsigmondy cross to record quadrants of tooth positions. Adult teeth were numbered 1 to 8, and the child primary dentition (also called deciduous, milk or baby teeth) were depicted with a quadrant grid using Roman numerals I, II, III, IV, V to number the teeth from the midline. Palmer changed this to A, B, C, D, E, which made it less confusing and less prone to errors in interpretation.

The Palmer notation consists of a symbol (⏌⎿ ⏋⎾) designating in which quadrant the tooth is found and a number indicating the position from the midline. Adult teeth are numbered 1 to 8, with deciduous (baby) teeth indicated by a letter A to E. Hence the left and right maxillary central incisor would have the same number, "1", but the right one would have the symbol "⏌" underneath it, while the left one would have "⎿".

🔗 Computing 🔗 Computing/Software

The Pick operating system (often called just "the Pick system" or simply "Pick") is a demand-paged, multiuser, virtual memory, time-sharing computer operating system based around a unique MultiValue database. Pick is used primarily for business data processing. It is named after one of its developers, Dick Pick.

The term "Pick system" has also come to be used as the general name of all operating environments which employ this multivalued database and have some implementation of Pick/BASIC and ENGLISH/Access queries. Although Pick started on a variety of minicomputers, the system and its various implementations eventually spread to a large assortment of microcomputers, personal computers and mainframe computers.

🔗 United States 🔗 Books 🔗 Reference works 🔗 English Language

The New Oxford American Dictionary (NOAD) is a single-volume dictionary of American English compiled by American editors at the Oxford University Press.

NOAD is based upon the New Oxford Dictionary of English (NODE), published in the United Kingdom in 1998, although with substantial editing, additional entries, and the inclusion of illustrations. It is based on a corpus linguistics analysis of Oxford's 200 million word database of contemporary American English.

NOAD includes a diacritical respelling scheme to convey pronunciations, as opposed to the Gimson phonemic IPA system that is used in NODE.

🔗 Graphic design

A visiting card, also known as a calling card, is a small card used for social purposes. Before the 18th century, visitors making social calls left handwritten notes at the home of friends who were not at home. By the 1760s, the upper classes in France and Italy were leaving printed visiting cards decorated with images on one side and a blank space for hand-writing a note on the other. The style quickly spread across Europe and to the United States. As printing technology improved, elaborate color designs became increasingly popular. However, by the late 1800s, simpler styles became more common.

By the 19th century, men and women needed personalized calling or visiting cards to maintain their social status or to move up in society. These small cards, about the size of a modern-day business card, usually featured the name of the owner, and sometimes an address. Calling cards were left at homes, sent to individuals, or exchanged in person for various social purposes. Knowing and following calling card “rules” signaled one’s status and intentions.

🔗 Finance & Investment 🔗 Economics

In finance, the greater fool theory suggests that one can sometimes make money through the purchase of overvalued assets — items with a purchase price drastically exceeding the intrinsic value — if those assets can later be resold at an even higher price.

In this context, one "fool" might pay for an overpriced asset, on the assumption that he can probably sell it to an even "greater fool" and make a profit. This only works as long as there are new "greater fools" willing to pay higher and higher prices for the asset. Eventually, investors can no longer deny that the price is out of touch with reality, at which point a sell-off can cause the price to drop significantly until it is closer to its fair value.