The Prodigies (film)

The Prodigies is a 2011 French-British computer-animated science fiction, action, horror and psychological thriller film based on "La Nuit des enfants rois", a novel written by French writer Bernard Lenteric.
Released theatrically on 8 June 2011, the film received generally negative reviews from critics and was a box office bomb, grossing only $1 million against a budget of $31 million.
Plot.
Ten-year-old Jimbo Farrar is a gifted child who is misunderstood and regularly beaten by his parents. One day he is badly beaten by his father while his mother cheers him on, and Jimbo gets carried away by his anger and loses control of his abilities. When he wakes, he finds his mother's body on the floor, as she had been beaten to death by his father, who then hanged himself, all under the mental control of Jimbo. He is then sent away to a mental hospital, where Jimbo is visited by multi-billionaire Charles Killian, who decides to take him under his wing to help him control his abilities. Twenty years later, Jimbo has become a brilliant researcher in the Killian Foundation for Gifted Children, married to Ann with whom they are due to have a child. Jimbo has only one goal: to find young children who, like him, possess supernatural powers. Thus, he created an extremely complex online game "The Game" in the hopes that he'll be able to identify any such people around the United States. One night, five unrelated teenagers pass the game and hack Jimbo's computer. In desperation, Jimbo shuts his computer down and restarts it, only to find a message on his screen with the words: "Where Are You?". Jimbo immediately sets out to find them and bring them to the Foundation, but on his return he learns of the death of Killian. The Foundation therefore passes onto Melanie, Killian's daughter, who plans with Jenkins - her second-in-command - to end Jimbo's game and instead work on a TV show. In order to save the game - and the possibility of locating more "Prodigies" - Jimbo has the idea of combining the ideas: create a large-scale televised competition to reveal future geniuses. The show, American Genius, is launched, and five teenagers are announced as participants - hand-picked by Jimbo, having met and identified them as "Prodigies": Gil, an abused child who was like Jimbo when he was a child but darker; Liza, a young girl trained to be a top model; Lee, a young Asian immigrant who helps her parents in their trade; Harry, an African-American whose mother wastes all her money in gambling; and Sammy, the only son of a wealthy family and physical ungrateful. The five are identified immediately and Jimbo arranges to meet with them in secret in Central Park. No sooner are the teenagers gathered than two thugs assault and rape Liza. Jimbo, however, is not there: he has just learned that Ann is pregnant. He learns of the teenagers' situation too late and, by the time he arrives at the park, Liza is missing and the other four are on the floor, unconscious. However, through Liza's agony while she is being raped, her pain is telepathically extended to the other four teenagers and Jimbo, who unconsciously drive out the thugs using mind-controlling abilities of their own. As soon as Jimbo recovers his senses, he hurries to Liza and finds her in a coma. The next day he learns that Melanie wants to cover up the crime, in order to preserve the TV show, by claiming Liza was injured by a hit-and-run driver. Furious, Jimbo violently demands an explanation, and his anger almost makes him lose control of his abilities and as a result was fired from the Killian Foundation. After that, he vows to protect the other four, and locks himself away in his office with his computer, afraid because of how he had almost lost control like in the day of the death of his parents. Meanwhile, under the leadership of Gil, the five teenagers infiltrate the archives of the Killian group, where they find video recordings of Jimbo during his sessions in the mental hospital. Here he talks about his feelings of isolation caused by his supernatural abilities, as well as the possibility of others like him (even Charles Killian) being out there. The mention of him bringing them all together to avenge themselves for all the years of mistreatment entices Gil, Sammy, Lee and Harry to bring justice upon Liza's attackers, which they do by brutally killing them as well as the officer, who helped cover up the crime, and his wife using their powers. When Jimbo learns of this, he is very alarmed. Furthermore, Melanie refuses to recognize the truth if only to let the TV show continue, Meanwhile the teenagers are demanding justice. However, one evening, as he tries to reason with the teenagers (who are now murderers), they turn against him. Doubting his trust, they put him to the test by ordering him to kill Jenkins. but Jimbo says "No!", So the teenagers go on to make Jenkins beat up Jimbo (once again with their abilities) and kill Jenkins, then frame Jimbo for his murder. Although Jimbo initially attempts to explain to the policemen the truth about his and the teenagers' superpowers, but starts hallucinating when Gil and Lee tries to make him kill the Lieutenant who interrogating him, and then we see flashbacks of the four teenagers avenging Liza by killing Lorenzo, McKenzie, his wife and Jenkins and sees flashbacks of him being beating up by his parents until he uses his mental powers to kill them. As young Jimbo watches sadly as his father commits suicide with his own belt, After that, we later learn why Jimbo refuses to use his powers against or kill Jenkins when the four teenagers tell him to do, After killing a sparrow in a mental hospital, Killian tells Jim never use his powers again to kill or touch any living things. After that the policemen don't believe him, particularly due his supposed history of having schizophrenia. Jimbo eventually relents and is sent to prison, where he is kept under surveillance. In the meantime, Gil, Harry, Lee and Sammy make plans for causing large-scale destruction upon the United States, under the belief that this will exact justice for all the pain they had been subject to in the past. Shortly afterwards, Liza comes out of her coma, and Ann visits her to ask her for help, for she now knows of Jimbo's abilities from the police interview, as well as the teenagers' plans to infiltrate the White House to launch nuclear weapons. However, Ann angers Liza, who loses control of her powers and almost kills Ann's baby. In a desperate attempt to prevent the imminent destruction the other teenagers plan on causing, Ann reluctantly seeks help from Melanie, the organiser of the final of American Genius, which will take place in the White House, include the four teenagers plus another fifth contestant named Justin, and be attended by the President of the United States. When Jimbo learns of Liza harming Ann, he uses his powers to break free from prison and joins Liza to reach the other teenagers, as well as Melanie and Ann, at the White House. On site, when she and Jimbo are attempting to sneak into the White House, they are halted by guards and Liza uses her powers for the two of them to escape. This triggering an alarm and initiates a security procedure where everybody in the Oval Office (including the finalists of American Genius) must get to safety in a security bunker. But once inside and all exits are sealed, the four gifted teenagers manipulate the soldiers and bodyguards into killing each other, and Melanie is shot dead under Gil's will. Gil then begins the attacks by launching a nuke at Killian University, where Jimbo and Killian worked. Ann's life is spared when Sammy raises the possibility that her child, being Jimbo's as well, might also be a "golden child". Jimbo eventually arrives at the bunker with Liza, where he learns that Gil is the one leading the group into attacking the US. A fight ensues where Gil attacks Ann and Jimbo fights to protect her, until the fifth contestant Justin fires a gun at Gil when Jimbo is at the verge of being killed. But Jimbo, anticipating the bullet, pushes Gil away and instead receives the bullet in his heart. While Jimbo lies in Ann's arms, dying, Gil horribly slaps Liza for her refusal to cooperate with him, which brings Harry to his senses and convinces his friends to stop all the madness of attacking and killing masses of people across the United States. And so, while one controls Gil in order to prevent him from stopping them, Harry cancels the nuclear attack, saving Killian University by seconds. Shortly afterwards, Jimbo takes his final breath. Three months later, Killian's company has gone bankrupt. Ann, still pregnant, receives a package containing Jimbo's phone (which he had lost in the fight at the White House), which has a final video message from Jimbo. Ann does not know it was left by Liza, who has disappeared from the radar along with Harry, Sammy, Lee and Gil. Liza, Harry, Sammy and Lee now search for other gifted people like themselves, using Jimbo's game, but Gil now continues with his journey on his own, and it seems that he is plotting dark schemes.
Reception.
Box office.
"The Prodigies" grossed a worldwide total of $1.3 million against a budget of $31.6 million, making the film a box office bomb.
In France, the film was released in 282 theaters and grossed $957,287 in its opening weekend, ranking 11th. In its second weekend, the film grossed $322,595 from 279 theaters, falling down to 16th.
Critical reception.
On Rotten Tomatoes, the film holds an approval rating of 20% based on 5 reviews, with an average rating of 3.1/10.
Linda Barnard of "Toronto Star" wrote that the film was "too violent for youngsters and so poorly written it won't engage an older audience, it seems to be targeted towards youthful nerds nursing overwhelming revenge fantasies." Liz Braun of "Jam! Movies" wrote, "You wouldn't expose a teenager to this, that's for sure, but the storytelling is so ham-handed that few adults would sit still for it" Dave McGinn of "Globe and Mail" was critical, writing, ""The Prodigies" pulls together a lot of familiar tropes from superhero movies without adding anything new or compelling to the genre."
In contrast, Sarah Gopaul of "Digital Journal" gave the film a positive review, stating, ""The Prodigies" delivers a noteworthy new approach to the “teens with super powers” genre that is worth the big screen treatment."


Stringer (journalism)

In journalism, a stringer is a freelance journalist, photographer, or videographer who contributes reports, photos, or videos to a news organization on an ongoing basis but is paid individually for each piece of published or broadcast work.
As freelancers, stringers do not receive a regular salary and the amount and type of work is typically voluntary. However, stringers often have an ongoing relationship with one or more news organizations, to which they provide content on particular topics or locations when the opportunities arise.
The term is typically confined to news industry jargon. In print or in broadcast terms, stringers are sometimes referred to as correspondents or contributors; at other times, they may not receive any public recognition for the work they have contributed.
A reporter or photographer can "string" for a news organization in a number of different capacities and with varying degrees of regularity, so that the relationship between the organization and the stringer is typically very loose. When it is difficult for a staff reporter or photographer to reach a location quickly for breaking news stories, larger news organizations often rely on local stringers to provide rapid scene descriptions, quotations or photos. In this capacity, stringers are used heavily by most television news organizations and some print publications for video footage, photos, and interviews.
Etymology.
The etymology of the word is uncertain. Newspapers once paid stringers per inch of printed text they generated. The theory given in the "Oxford English Dictionary" is that a stringer is a person who strings words together, while others use the term because the reporter is "strung along" by a news organization, or kept in a constant state of uncertainty. Another possibility is that, using a sports analogy, the freelance journalist is seen as a "second string", whereas the staff journalist positions are more of the "first string". (This in turn
comes from music, where the first string is the premier violin in the orchestra, the second string is the next most talented player and so on.)
Another possible derivation of the term "stringer": journalists at newspapers and television news stations sometimes use the expression "I'm still gathering string" to refer to the initial stage of reporting or fact-finding. Put another way, "Still gathering string" is newsroom jargon for the process of "looking for something that you can't yet name." The "string" being "the stuff that accumulates in a journalist's pocket." "String" may be used by journalists or researchers to describe a piece of information discovered in the process of looking for something else or "the anomaly that jumps out at you" while conducting research. The significance, however, of this serendipitous discovery has yet to be determined.
Another derivation dates back to the time when part-time reporters were paid for each column inch of copy the newspaper printed. An explanation once common in newsrooms was that editors kept strings (knotted with one knot per inch) at their desks as a flexible alternative to rulers. According to a variant version "At the end of the week/month, they [writers] would measure the space their writing occupied in the newspaper by a length of string. They'd turn in the piece of string, and would be paid according to how long the string was."


Facultative

Facultative means "optional" or "discretionary" (antonym "obligate"), used mainly in biology in phrases such as:


Criticisms of foreign aid


Water transfer printing

Water transfer printing, also known as immersion printing, water transfer imaging, hydro dipping, watermarbling, cubic printing, Hydrographics, or HydroGraphics, is a method of applying printed designs to three-dimensional surfaces. The resulting combinations may be considered decorative art or applied art. The hydrographic process can be used on metal, plastic, glass, hard woods, and various other materials.
History.
The exact origin of the water transfer printing process is unclear. However, the first hydrographic apparatus registered for a US patent was by Motoyasu Nakanishi of Cubic Engineering KK on July 26, 1982. Its abstract reads, "[a] printing apparatus provided with a structure which supplies a transcription film into a transcription tub containing a liquid so that the transcription film is kept afloat on the liquid, a structure which makes the liquid flow in a direction in which the film is supplied, and a structure which slantingly immerses an article to be printed into the liquid in the transcription tub from an upstream position to a downstream position of the liquid."
Usage.
The water transfer printing process is extensively used to decorate items that range from entire all-terrain vehicles and car dashboards, to small items like bike helmets or other automotive trim. Films can be applied to all types of substrates including plastic, fiberglass, wood, ceramics, and metal. For the most part, if the item can be dipped in water and can be painted using traditional techniques then the hydrographic printing process can be used.
Process.
In the process, the substrate piece to be printed first goes through the entire painting process: surface preparation, priming, painting, and clear coating. After painting but before clear coating, the part is ready to be processed. A polyvinyl alcohol hydrographic film, which has been gravure-printed with the graphic image to be transferred, is carefully placed on the water's surface in the dipping tank. The clear film is water-soluble, and dissolves after applying an activator solution. Once dipping is begun, the surface tension of the water will allow the pattern to curve around any shape. Any remaining residue is then rinsed off thoroughly. The ink adheres to the desired surface and it cannot be washed off easily. It is then allowed to dry.
The adhesion is a result of the chemical components of the activator softening the base coat layer and allowing the ink to form a bond with it. One of the most common causes of a failure to achieve adhesion between the two layers is a poorly applied activator. This can be either too much activator being applied or too little.


Rolapitant

Rolapitant (INN, trade name Varubi in the US and Varuby in the European Union) is a drug originally developed by Schering-Plough and licensed for clinical development by Tesaro, which acts as a selective NK1 receptor antagonist (antagonist for the NK1 receptor). It has been approved as a medication for the treatment of chemotherapy-induced nausea and vomiting (CINV) after clinical trials showed it to have similar or improved efficacy and some improvement in safety over existing drugs for this application.
Medical uses.
Rolapitant is used in combination with other antiemetic (anti-vomiting) agents in adults for the prevention of delayed nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy, including, but not limited to, highly emetogenic chemotherapy. The approved antiemetic combination consists of rolapitant plus dexamethasone and a 5-HT3 antagonist.
Contraindications.
Under the US approval, rolapitant is contraindicated in combination with thioridazine, whose inactivation could be inhibited by rolapitant. Under the European approval, it is contraindicated in combination with St. John's Wort, which is expected to accelerate inactivation of rolapitant.
Side effects.
In studies comparing chemotherapy plus rolapitant, dexamethasone and a 5-HT3 antagonist to chemotherapy plus placebo, dexamethasone and a 5-HT3 antagonist, most side effects had comparable frequencies in both groups, and differed more between chemotherapy regimens than between rolapitant and placebo groups. Common side effects included decreased appetite (9% under rolapitant vs. 7% under placebo), neutropenia (9% vs. 8% or 7% vs. 6%, depending on the kind of chemotherapy), dizziness (6% vs. 4%), indigestion and stomatitis (both 4% vs. 2%).
Overdose.
Up to eightfold therapeutic doses have been given in studies without problems.
Interactions.
Rolapitant moderately inhibits the liver enzyme CYP2D6. Blood plasma concentrations of the CYP2D6 substrate dextromethorphan have increased threefold when combined with rolapitant; and increased concentrations of other substrates are expected. The drug also inhibits the transporter proteins ABCG2 (breast cancer resistance protein, BCRP) and P-glycoprotein (P-gp), which has been shown to increase plasma concentrations of the ABCG2 substrate sulfasalazine twofold and the P-gp substrate digoxin by 70%.
Strong inducers of the liver enzyme CYP3A4 decrease the area under the curve of rolapitant and its active metabolite (called M19); for rifampicin, this effect was almost 90% in a study. Inhibitors of CYP3A4 have no relevant effect on rolapitant concentrations.
Pharmacology.
Pharmacodynamics.
Both rolapitant and its active metabolite M19 block the NK1 receptor with high affinity and selectivity: to block the closely related receptor NK2 or any other of 115 tested receptors and enzymes, more than 1000-fold therapeutic concentrations are necessary.
Pharmacokinetics.
Rolapitant is practically completely absorbed from the gut, independently of food intake. It undergoes no measurable first-pass effect in the liver. Highest blood plasma concentrations are reached after about four hours. When in the bloodstream, 99.8% of the substance are bound to plasma proteins.
It is metabolized by the liver enzyme CYP3A4, resulting in the major active metabolite M19 (C4-pyrrolidine-hydroxylated rolapitant) and a number of inactive metabolites. Rolapitant is mainly excreted via the feces (52–89%) in unchanged form, and to a lesser extent via the urine (9–20%) in form of its inactive metabolites. Elimination half-life is about seven days (169 to 183 hours) over a wide dosing range.
Chemistry.
The drug is used in form of rolapitant hydrochloride monohydrate, a white to off-white, slightly hygroscopic crystalline powder. Its maximum solubility in aqueous solutions is at pH 2–4.


Burapitant

Burapitant (SSR-240,600) is a drug developed by Sanofi-Aventis which was one of the first compounds developed that acts as a potent and selective antagonist for the NK1 receptor. While burapitant itself did not proceed beyond early clinical trials and was never developed for clinical use in humans, promising animal results from this and related compounds have led to a number of novel drugs from this class that have now been introduced into medical use.


The Emotional Intelligence Appraisal

The Emotional Intelligence Appraisal is a skill-based self-report and 360-degree measure of emotional intelligence (EQ) developed as a measure of emotionally competent behavior that provides an estimate of one's emotional intelligence. Twenty-eight items are used to obtain a total EQ score and to produce four composite scale scores, corresponding to the four main skills of Daniel Goleman's model of emotional intelligence. The Emotional Intelligence Appraisal was created in 2001 by Drs. Travis Bradberry and Jean Greaves and comes in both booklet and online format, allowing participants to choose their preferred method of test taking.
Results obtained by The Emotional Intelligence Appraisal have been compared with those from the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT, an EI ability based assessment of emotional intelligence based on the model first proposed by Mayer and Salovey in 1990. While the results indicated a positive correlation this was non-significant. This suggests a distinction between the constructs being measured by these assessments. The MSEIT is ability-based whereas The Emotional Intelligence Appraisal adopts the mixed model proposed by Daniel Goleman.
The Emotional Competencies (Goleman) model.
The model introduced by Daniel Goleman focuses on EQ as a wide array of competencies and skills that drive leadership performance. Goleman's model outlines four main EQ constructs:


Mycoestrogen

Mycoestrogens are xenoestrogens produced by fungi. They are sometimes referred to as mycotoxins. Among important mycoestrogens are zearalenone, zearalenol and zearalanol. Although all of these can be produced by various "Fusarium" species, zearalenol and zearalanol may also be produced endogenously in ruminants that have ingested zearalenone. Alpha-zearalanol is also produced semisynthetically, for veterinary use; such use is prohibited in the European Union.
Mechanism of action.
Mycoestrogens act as agonists of the estrogen receptors, ERα and ERβ.
Sources.
Mycoestrogens are produced by various strains of fungi, many of which fall under the genus "fusarium". "Fusarium" fungi are filamentous fungi that are found in the soil and are associated with plants and some crops, especially cereals. Zearalenone is mainly produced by "F. graminearum" and "F. culmorum" strains, which inhabit different areas depending on temperature and humidity. "F. graminearum" prefers to inhabit warmer and more humid locations such as Eastern Europe, Northern America, Eastern Australia, and Southern China in comparison to "F. colmorum" which is found in colder Western Europe.
Health effects.
Mycoestrogens mimic natural estrogen in the body by acting as estrogen receptor (ER) ligands. Mycoestrogens have been identified as endocrine disruptors due to their high binding affinity for ERα and ERβ, exceeding that of well known antagonists such as bisphenol A and DDT. Studies have been performed that strongly suggest a relationship between detectable levels of mycoestrogen and growth and pubertal development. More than one study has shown that detectable levels of zearalenone and its metabolite alpha-zearalanol in girls are associated with significantly shorter heights at menarche. Other reports have documented premature onset of puberty in girls. Estrogen are known to cause decreased body weight in model animals, and the same effect has been seen in rats exposed to zearalenone. Interactions of ZEN and its metabolite with human androgen receptors (hAR) have also been documented.
Metabolism.
Zearalenone has two major phase I metabolites: α-zearalenol and β-zearalenol. When exposed orally ZEN is absorbed by the intestinal lining and metabolized there as well as in the liver. Research into the metabolism of ZEN has been difficult because of the significant difference in biotransformation between species making comparison challenging.
Phase I.
The first transformation of metabolism of ZEN will reduce the ketone group to an alcohol via aliphatic hydroxylation and result in the formation of the two zearalenol metabolites. This process is catalyzed by 3 α- and 3 β-hydroxy steroid dehydrogenase (HSD). CYP450 enzymes will then catalyze aromatic hydroxylation at the 13 or 15 position resulting in 13- or 15- catechols. Steric hindrance of at the 13 position is suspected to be the reason that in humans and rats there is more of the 15-catechol present. The catechols are the processed into mono-ethyl esters by catechol-o-methyl transferase (COMT) and S-adenosyl methionine (SAM). After this transformation they may be metabolized further to quinones which can cause the formation of reactive oxygen species (ROS) and cause covalent modification of DNA.
Phase II.
In phase-II metabolizing includes glucuronidation and sulfation of the mycoestrogen compound. Glucuronidation is the major phase II metabolic pathway. The transferase UGT (5'-diphosphate glucuronosyltransferase) adds a glucuronic acid group sourced from uridine 5'-diphosphate glucuronic acid (UDPGA).
Excretion.
Mycoestrogens and their metabolites are largely excreted in urine in humans and in feces in other animal systems.
In food.
Mycoestrogens are commonly found in stored grain. They can come from fungi growing on the grain as it grows, or after harvest during storage. Mycoestrogens can be found in silage. Some estimates state that 25% of global cereal production and 20% of global plant production may be at some point contaminated by mycotoxins of which mycoestrogens, especially those from "fusarium" strains, may make up a significant portion. Among mycoestrogens that contaminate plants are ZEN and its phase I metabolites. The limit for ZEN in unprocessed cereals, milling products, and cereal foodstuffs is 20-400 μg/kg (depending on the product in question).


Paul Berry (animator)

Paul Thomas Berry (13 March 1961 – 26 June 2001) was a stop-motion animator who first worked on Cosgrove Hall's "Wind In The Willows" before directing the 1991 Oscar-nominated short horror stop-motion animation film "The Sandman". In 1992 the film was awarded the Craft Prize for Best Animation at Ottawa International Animation Festival.
Career.
Other projects Paul Berry worked on included "The Nightmare Before Christmas" (animator), "James and the Giant Peach" (animation supervisor), "Monkeybone" (supervising animator) and the music video for Primus' cover of "The Devil Went Down to Georgia".
Death.
On 26 June 2001 Berry died of a brain tumour. He had stayed strong for several months prior to his death. He was 40 years old.


Glossary of geography terms

This glossary of geography terms is a list of definitions of terms and concepts used in geography and related fields, which describe and identify spatial dimension, geographic locations, topographical features, natural resources, and the collection, analysis, and visualization of geographic data. For related terms, see Glossary of geology and Glossary of environmental science.
Notes.
Much of this material was copied from U.S. government works which are in the because they are not eligible for copyright protection.


Transitus (education)

Transitus is the name given to a year in a number of independent schools in Scotland. As the name would suggest, this year is offered as a bridge between 'primary' and 'secondary' education.
Transitus replaces the final year of primary education used in state schools, often referred to as Primary 7 (P7). In preparatory schools, it may also share the 'P7' designation, although in this case it is instead the abbreviation of 'Prep'.


Hypertensive leukoencephalopathy

Hypertensive leukoencephalopathy refers to a degeneration of the white matter of the brain following a sudden increase in blood pressure.
Signs and symptoms.
Symptoms include sudden increase in blood pressure, acute confusional state, headaches, vomiting, and seizure. Retinal hemorrhages and hard exudates may be present on funduscopic exam. Hypertensive leukoencephalopathy may have concurrent cardiac ischemia and hematuria.
Diagnosis.
MRI shows hyperintensities on T2 weighted imaging, localized usually to the parietal and occipital regions.
Treatment.
Antihypertensives may be an effective treatment.


Intercalated cells of the amygdala

The intercalated (ITC) cells of the amygdala are a group of GABAergic neurons situated between the basolateral and central nuclei of the amygdala that are important for inhibitory control over the amygdala.
Function.
ITC cells are thought to play a role as the 'off switch' for the amygdala, inhibiting the amygdala's central nucleus output neurons and its basolateral nucleus neurons. Some researchers speculate that ITC cells, via their extensive local inhibition within the amygdala, could serve as a substrate for expression and storage of extinction memory.
Connectivity.
ITC cells receive strong projections from the infralimbic cortex (IL mPFC) in both primates and rodents, which may explain cortical control over emotional regulation processes such as extinction.


Vestipitant

Vestipitant (INN) is a drug developed by GlaxoSmithKline which acts as a selective antagonist for the NK1 receptor. It is under development as a potential antiemetic and anxiolytic drug, and as a treatment for tinnitus and insomnia.


Amino acid reuptake inhibitor

An amino acid reuptake inhibitor (AARI) is a type of drug which inhibits the reuptake of one or more amino acid neurotransmitters (i.e., glutamate, aspartate, GABA, and/or glycine) by blocking one or more of their respective transporters. They include excitatory amino acid reuptake inhibitors (or glutamate-aspartate reuptake inhibitors), GABA reuptake inhibitors, and glycine reuptake inhibitors.


Steven Allan Boggs

Steven Allan Boggs (March 15, 1946 – June 2, 2018) was an American physicist in the field of dielectrics and electrical insulation. He was a researcher in industry before becoming a tenured research professor at University of Connecticut from 1993 to 2013.
Early life and education.
Boggs was born on March 15, 1946 in Miami and raised around Portland, Oregon. His father was a professor of English. Boggs attended Lake Oswego High School and completed a B.A. in physics from Reed College in 1968. He completed an undergraduate thesis titled "The Covariant Presentation of a Postulatory Approach to Electromagnetism" with advisor Dennis G. Hoffman. Boggs earned a Ph.D. in physics in 1972 at University of Toronto. His doctoral advisor was Harry L. Welsh. He was a postdoctoral fellow at the Canada Centre for Remote Sensing.
Career.
Boggs was a researcher in the field of dielectrics and electrical insulation. He worked at Ontario Hydro from 1975 to 1987. He worked on the nature and measurement of partial discharge "in the ultra-high frequency range in gas-insulated substation and rotating machines. He also researched electric and water trees and developed methods to measure thermal impedance in "transmission-class power cables." He worked on a team with Frank Chu, Nobby Fujimoto, and Sil Rizzetto. His boss was Gary Ford. He completed a M.B.A. at University of Toronto in 1987. In February 1987, Boggs became the director of engineering and research at Underground Systems Incorporated (USi). He served as the vice president of the USi subsidiary, Chicago Condenser Corporation.
In 1993, Boggs became a tenured research professor at University of Connecticut (UConn). He served as the director of the Electrical Insulation Research Center at the Institute of Materials Science and held a joint appointment with the graduate programs in electrical engineering, physics, and materials science. He supervised over 20 students, with half of them being female. Boggs was a proponent of gender equality in STEM. He retired from UConn in September 2013. After retirement, he worked for his consulting company, NonLinear Systems Inc.
Personal life.
Boggs was married to fellow Reed College alumna Joan Raymond; they later divorced. He died on June 2, 2018 in Columbia, Maryland due to inoperable brain cancer.
Awards and honors.
Boggs was a fellow of the Institute of Electrical and Electronics Engineers and the recipient of the 2019 IEEE Herman Halperin Electric Transmission and Distribution Award.


Neocortex

The neocortex, also called the neopallium, isocortex, or the six-layered cortex, is a set of layers of the mammalian cerebral cortex involved in higher-order brain functions such as sensory perception, cognition, generation of motor commands, spatial reasoning and language. The neocortex is further subdivided into the true isocortex and the proisocortex.
In the human brain, the neocortex is the largest part of the cerebral cortex, which is the outer layer of the cerebrum, with the allocortex making up the rest. The neocortex is made up of six layers, labelled from the outermost inwards, I to VI. Of all the mammals studied to date (including humans), a species of oceanic dolphin known as the long-finned pilot whale has been found to have the most neocortical neurons.
Etymology.
The term is from "cortex", Latin, “bark” or “rind”, combined with "neo-", Greek, “new”. "Neopallium" is a similar hybrid, from Latin "pallium", “cloak”. "Isocortex" and "allocortex" are hybrids with Greek "isos", “same”, and "allos", “other”.
Anatomy.
The neocortex is the most developed in its organisation and number of layers, of the cerebral tissues. The neocortex consists of the grey matter, or neuronal cell bodies and unmyelinated fibers, surrounding the deeper white matter (myelinated axons) in the cerebrum. This is a very thin layer though, about 2–4 mm thick. There are two types of cortex in the neocortex, the proisocortex and the true isocortex. The pro-isocortex is a transitional area between the true isocortex and the periallocortex (part of the allocortex). It is found in the cingulate cortex (part of the limbic system), in Brodmann's areas 24, 25, 30 and 32, the insula and the parahippocampal gyrus.
Geometry.
The neocortex is smooth in rodents and other small mammals, whereas in primates and other larger mammals it has deep grooves (sulci) and ridges (gyri). These folds allow the surface area of the neocortex to be greatly increased. All human brains have the same overall pattern of main gyri and sulci, although they differ in detail from one person to another. The mechanism by which the gyri form during embryogenesis is not entirely clear, and there are several competing hypotheses that explain gyrification, such as axonal tension, cortical buckling or differences in cellular proliferation rates in different areas of the cortex.
Layers.
The neocortex contains both excitatory (~80%) and inhibitory (~20%) neurons, named for their effect on other neurons. The structure of the neocortex is relatively uniform (hence the alternative names "iso-" and "homotypic" cortex), consisting of six horizontal layers segregated principally by cell type and neuronal connections. However, there are many exceptions to this uniformity; for example, layer IV is small or missing in the primary motor cortex. There is some canonical circuitry within the cortex; for example, pyramidal neurons in the upper layers II and III project their axons to other areas of neocortex, while those in the deeper layers V and VI often project out of the cortex, e.g. to the thalamus, brainstem, and spinal cord. Neurons in layer IV receive the majority of the synaptic connections from outside the cortex (mostly from thalamus), and themselves make short-range, local connections to other cortical layers. Thus, layer IV is the main recipient of incoming sensory information and distributes it to the other layers for further processing.
Cortical columns.
The neocortex is often described as being arranged in vertical structures called cortical columns, patches of neocortex with a diameter of roughly 0.5 mm (and a depth of 2 mm, i.e., spanning all six layers). These columns are often thought of as the basic repeating functional units of the neocortex, but their many definitions, in terms of anatomy, size, or function, are generally not consistent with each other, leading to a lack of consensus regarding their structure or function or even whether it makes sense to try to understand neocortex in terms of columns.
Function.
The neocortex is derived embryonically from the dorsal telencephalon, which is the rostral part of the forebrain. The neocortex is divided, into regions demarcated by the cranial sutures in the skull above, into frontal, parietal, occipital, and temporal lobes, which perform different functions. For example, the occipital lobe contains the primary visual cortex, and the temporal lobe contains the primary auditory cortex. Further subdivisions or areas of neocortex are responsible for more specific cognitive processes. In humans, the frontal lobe contains areas devoted to abilities that are enhanced in or unique to our species, such as complex language processing localized to the ventrolateral prefrontal cortex (Broca's area). In humans and other primates, social and emotional processing is localized to the orbitofrontal cortex. (See Cerebral cortex and Cerebrum.)
The neocortex has also been shown to play an influential role in sleep, memory and learning processes. Semantic memories appear to be stored in the neocortex, specifically the anterolateral temporal lobe of the neocortex. It is also involved in instrumental conditioning; responsible for transmitting sensory information and information about plans for movement to the basal ganglia. The firing rate of neurons in the neocortex also has an effect on slow-wave sleep. When the neurons are at rest and are hyperpolarizing, a period of inhibition occurs during a slow oscillation, called the down state. When the neurons of the neocortex are in the excitatory depolarizing phase and are firing briefly at a high rate, a period of excitation occurs during a slow oscillation, called the up state.
Clinical significance.
Lesions that develop in neurodegenerative disorders, such as Alzheimer's disease, interrupt the transfer of information from the sensory neocortex to the prefrontal neocortex. This disruption of sensory information contributes to the progressive symptoms seen in neurodegenerative disorders such as changes in personality, decline in cognitive abilities, and dementia. Damage to the neocortex of the anterolateral temporal lobe results in semantic dementia, which is the loss of memory of factual information (semantic memories). These symptoms can also be replicated by transcranial magnetic stimulation of this area. If damage is sustained to this area, patients do not develop anterograde amnesia and are able to recall episodic information.
Evolution.
The neocortex is the newest part of the cerebral cortex to evolve (hence the prefix "neo" meaning new); the other part of the cerebral cortex is the allocortex. The cellular organization of the allocortex is different from the six-layered neocortex. In humans, 90% of the cerebral cortex and 76% of the entire brain is neocortex.
For a species to develop a larger neocortex, the brain must evolve in size so that it is large enough to support the region. Body size, basal metabolic rate and life history are factors affecting brain evolution and the coevolution of neocortex size and group size. The neocortex increased in size in response to pressures for greater cooperation and competition in early ancestors. With the size increase, there was greater voluntary inhibitory control of social behaviors resulting in increased social harmony.
The six-layer cortex appears to be a distinguishing feature of mammals; it has been found in the brains of all mammals, but not in any other animals. There is some debate, however, as to the cross-species nomenclature for "neocortex". In avians, for instance, there are clear examples of cognitive processes that are thought to be neocortical in nature, despite the lack of the distinctive six-layer neocortical structure. In a similar manner, reptiles, such as turtles, have primary sensory cortices. A consistent, alternative name has yet to be agreed upon.
Neocortex ratio.
The neocortex ratio of a species is the ratio of the size of the neocortex to the rest of the brain. A high neocortex ratio is thought to correlate with a number of social variables such as group size and the complexity of social mating behaviors. (See Dunbar's number) Humans have a large neocortex as a percentage of total brain matter when compared with other mammals. For example, there is only a 30:1 ratio of neocortical gray matter to the size of the medulla in the brainstem of chimpanzees, while the ratio is 60:1 in humans.


Gliclazide

Gliclazide, sold under the brand name Diamicron among others, is a sulfonylurea type of anti-diabetic medication, used to treat diabetes mellitus type 2. It is used when dietary changes, exercise, and weight loss are not enough. It is taken by mouth.
Side effect may include low blood sugar, vomiting, abdominal pain, rash, and liver problems. Use by those with significant kidney problems or liver problems or who are pregnant is not recommended. Gliclazide is in the sulfonylurea family of medications. It works mostly by increasing the release of insulin.
Gliclazide was patented in 1966 and approved for medical use in 1972. It is on the World Health Organization's List of Essential Medicines. It is not available for sale in the United States.
Medical uses.
Gliclazide is used for control of hyperglycemia in gliclazide-responsive diabetes mellitus of stable, mild, non-ketosis prone, type 2 diabetes. It is used when diabetes cannot be controlled by proper dietary management and exercise or when insulin therapy is not appropriate.
National Kidney Foundation (2012 Update) claims that Gliclazide does not require dosage uptitration even in end stage kidney disease.
Interactions.
Hyperglycemic action may be caused by danazol, chlorpromazine, glucocorticoids, progestogens, or β-2 agonists. Its hypoglycemic action may be potentiated by phenylbutazone, alcohol, fluconazole, β-blockers, and possibly ACE inhibitors. It has been found that rifampin increases gliclazide metabolism in humans in vivo.
Overdose.
Gliclazide overdose may cause severe hypoglycemia, requiring urgent administration of glucose by IV and monitoring.
Mechanism of action.
Gliclazide selectively binds to sulfonylurea receptors (SUR-1) on the surface of the pancreatic beta-cells. It was shown to provide cardiovascular protection as it does not bind to sulfonylurea receptors (SUR-2A) in the heart. This binding effectively closes these K+ ion channels. This decreases the efflux of potassium from the cell which leads to the depolarization of the cell. This causes voltage dependent Ca2+ ion channels to open increasing the Ca2+ influx. The calcium can then bind to and activate calmodulin which in turn leads to exocytosis of insulin vesicles leading to insulin release. The mouse model of MODY diabetes suggested that the reduced gliclazide clearance stands behind their therapeutic success in human MODY patients, but Urbanova et al. found that human MODY patients respond differently and that there was no consistent decrease in gliclazide clearance in randomly selected HNF1A-MODY and HNF4A-MODY patients.
Its classification has been ambiguous, as literature uses it as both a first-generation and second-generation sulfonylurea.
Properties.
According to the Biopharmaceutical Classification System (BCS), gliclazide falls under the BCS Class II drug, which is poorly soluble and highly permeable.
Water solubility = 0.027 mg/L
Metabolism.
Gliclazide undergoes extensive metabolism to several inactive metabolites in human beings, mainly methylhydroxygliclazide and carboxygliclazide. CYP2C9 is involved in the formation of hydroxygliclazide in human liver microsomes and in a panel of recombinant human P450s in vitro. But the pharmacokinetics of gliclazide MR are affected mainly by CYP2C19 genetic polymorphism instead of CYP2C9 genetic polymorphism.


Proisocortex

Proisocortex or pro-isocortex is one of two subtypes of cortical areas in the areas belonging to the neocortex. The other subtype is termed the true isocortex. Proisocortical areas are transitional areas placed between areas of true isocortex and areas of periallocortex (which themselves are transitional between "true" allocortex and proisocortex). The histological structure of proisocortex is also transitional between true isocortex and either peripaleocortex or periarchicortex, depending on with which subtype of periallocortex the given proisocortical area borders.
Proisocortex is found in the cingulate cortex (part of the limbic system), in Brodmann's areas 24, 25, 30 and 32, the insula and parahippocampal gyrus.
The transitional cortical areas from isocortical side (i.e. proisocortex) and from allocortical side (i.e. periarchicortex and peripaleocortex) together are called mesocortex. The mesocortex is essentially the same as paralimbic cortex, as all mesocortical transitional areas are found exclusively in paralimbic region, and vice versa - all the paralimbic cortex is mesocortical in its nature (embryonic and phylogenetic origins) and in its histology. But the term "mesocortex" represents a different concept from the term "paralimbic cortex". The mesocortex is distinguished from other cortical areas based on cytoarchitectonics and histology, while the paralimbic cortex is an anatomical designation, meaning cortical areas near subcortical limbic structures.


Anatopism

An anatopism (from the Ancient Greek , "against," and , "place") is something that is out of its proper place.
The concept of anatopism is less widely familiar than that of anachronism, perhaps because much that is anatopic is also anachronistic. Yet the distinction is a valid one; not all that is anatopic is necessarily also anachronistic.
The online "Collins English Dictionary" gives a synonym for "anatopism": "anachorism" (from Greek: + , "place"): "a geographical misplacement; something located in an incongruent position".
Examples.
Catherine Hardwicke's 2006 film "The Nativity Story" shows a field of maize in a Nazareth farming scene. Maize is native to Mesoamerica, not to the Middle East, and in pre-Columbian times was grown only in the Americas. The use of maize in this film is an anatopism as well as an anachronism.
The same anatopism appears in the first part ("The Warrior Pharaohs") of a three-part 2002 PBS documentary series on "Egypt's Golden Empire" depicting the history of ancient Egypt's New Kingdom: ears of maize corn are shown in a scene recreating the battle and siege of Megiddo in the 15th century BCE.
Ridley Scott's 2000 film, "Gladiator", set in 180 CE, features Roman soldiers riding horses using saddles with stirrups. While the Romans had had saddles since about 100 BCE, and stirrups had existed in the world since about 700 BCE, stirrups did not appear in Europe until about the 6th or 7th century CE, making them both anatopic and anachronistic.
The opening scene of Disney's 1994 film, "The Lion King", features a variety of African animals venturing to Pride Rock. However, the ants that appear in the scene hold leaves in their mandibles, behavior that only leaf cutter ants in Latin America exhibit.
John Ford's much-lauded 1939 film "Stagecoach" was filmed in Monument Valley on the Arizona-Utah border, but textually set in southern Arizona and southern New Mexico. The vegetation and topography of Monument Valley and the lower-altitude deserts are vastly different, rendering the film's actual location notably anatopic.
The Polish writer Bolesław Prus, for the sake of making a point, introduces into chapter 63 of his historical novel "Pharaoh", set in the ancient Egypt of 1087–1085 BCE, a substance that behaves like gunpowder. This appears to be both an anachronism and an anatopism, since gunpowder is thought to have been invented, some time later, in China or in Arabia. Another apparent anatopism introduced by the author (in chapter 45) is an object that resembles a telescope, that may also be an anachronism.


Acetohexamide

Acetohexamide (trade name Dymelor) is a first-generation sulfonylurea medication used to treat diabetes mellitus type 2, particularly in people whose diabetes cannot be controlled by diet alone.
Mechanism of action.
Acetohexamide lowers blood sugar by stimulating the pancreas to secrete insulin and helping the body use insulin efficiently. The pancreas must produce insulin for this medication to work. For this reason, acetohexamide is not used to treat diabetes mellitus type 1.
Risks.
Oral hypoglycemic drugs, including acetohexamide, have been associated with increased cardiovascular mortality. Talk to your doctor about the possible risks, benefits, and alternatives of using this drug for your condition.


Sacral ganglia

The sacral ganglia are paravertebral ganglia of the sympathetic trunk.:39 As the sympathetic trunk heads inferiorly down the sacrum, it turns medially. There are generally four or five sacral ganglia. In addition to gray rami communicantes, the ganglia send off sacral splanchnic nerves to join the inferior hypogastric plexus.
Recurrences of genital herpes are caused by herpes simplex virus which lies dormant in the sacral ganglia between bouts of active infection.
It innervates blood vessels and sweat glands in lower limbs.
Near the coccyx, the right and left sympathetic trunks join to form the ganglion impar.


Trinity term

Trinity term is the third and final term of the academic year at the University of Oxford, the University of Dublin, Canterbury Christ Church University, and some independent schools in the United Kingdom. It runs from about mid-April to about the end of June and is named after Trinity Sunday, which falls eight weeks after Easter, in May or June.
At the University of Oxford, following the resolution made by Council on 8 May 2002, Trinity Term begins on and includes 20 April or the Wednesday after Easter, whichever is the later, and ends on and includes 6 July. In Trinity Term, as in Michaelmas Term and in Hilary Term, there is a period of eight weeks known as Full Term, beginning on a Sunday, within which lectures and other instruction prescribed by statute or regulation are given. The dates on which each Full Term will begin and end in the next academic year but one are published by the Registrar in the University Gazette during Hilary Term.
At the University of Sydney, it was the second and coldest of the three terms, running from the 24th to the 34th Mondays of the year (late May to early August) in the middle of winter, until Sydney changed over to the two semester system in 1989.
The term is also one of four into which the legal year is divided by the Courts of England and Wales, from 22 May to 12 June, during which the superior courts were formerly open. "Trinity term" is also used for the sitting of the High Court of Justice of England between 9 June and 31 July also known as "Trinity sitting".
Schools.
Schools in the United Kingdom and Ireland which use the name 'Trinity term' include:


Tityustoxin peptide 2

Tityustoxin peptide 2 (TsPep2) is a peptide isolated from the venom of the "Tityus serrulatus" (Brazilian yellow scorpion). It belongs to a class of short peptides, together with Tityustoxin peptide 1 and Tityustoxin peptide 3.
Sources.
"Tityus serrulatus", also known as the Brazilian yellow scorpion, is from the genus "Tityus" belonging to the family "Buthidae".
TsPep2 is identified from the venom of "Tityus serrulatus" by using a cDNA primer sequence based on the C-terminal amino acid sequence of KTx2 from "Androctonus australis".
Chemistry.
The original encoded sequence of TsPep2 consists of 68 amino acids processed in a mature peptide of 29 amino acids with a final molecular weight of 2993.59 Da.
TsPep2 differs in the mature sequence from TsPep3 only in one amino acid and TsPep1 shows 58,6% of sequence homology with Tspep2 and TsPep3.
Eight cysteines establish four disulfide bridges and a C-terminal tyrosine amide is present in the 55th position.
Furthermore, TsPep2 sequence alignment shows that a part of the amino acid consensus sequence (CXXXKCCXC) involved in the pore blocking mechanism is present as in other known short scorpion toxins.
Target.
It seems likely that TsPep2 has inhibitory actions on potassium channels, based on its sequence similarities in the C-terminal beta sheet with the potassium channel inhibitory alpha family (α-KTX) and on its similarities in the patterns of disulfide bridges with other short scorpion venom toxins.
Toxicity.
The biological function of TsPep2 is not clear yet, except from a small displacement on the 125I-KTX binding site on rat brain synaptosomes. However, it has been shown that this peptide is not toxic to mice. The LD50 of TsPep2 is currently unknown.


Striatopallidal fibres

The striatopallidal fibres, also Wilson's pencils, pencil fibres of Wilson, and pencils of Wilson, are prominent myelinated fibres that connect the striatum to the globus pallidus.
Their distinctive appearance allows the putamen to be identified on light microscopy.


Hemitoxin

Hemitoxin (HTX; α-KTx6.15) is a 35-mer basic peptide from the venom of the Iranian scorpion "Hemiscorpius lepturus", which reversibly blocks Kv1.1, Kv1.2 and Kv1.3 voltage-gated K+ channels.
Sources.
HTX is a neurotoxin derived from the venom of the scorpion "Hemiscorpius lepturus", which is found in the southwest province of Iran, Khuzestan. Hemitoxin constitutes about 0.1% of all venom proteins found in the "Hemiscorpius lepturus" venom gland.
Chemistry.
HTX is a peptide composed of 35 amino acids including eight cysteine residues which are cross linked forming four intramolecular cystine amino acids via disulfide bridges. It belongs to subfamily 6 of the α-KTx family of potassium channel scorpion toxins and has the highest sequence similarity with Maurotoxin (MTX), which is derived from a Tunisian scorpion called "Scorpio maurus palmatus". MTX is also a K+ channel blocker but is composed of 34 amino acids instead of 35.
Target.
HTX is a voltage-gated K+ channel blocker peptide. It reversibly blocks type Kv1.1, Kv1.2 and Kv1.3 channels with IC50 values of 13, 16 and 2 nM, respectively. HTX has a different affinity for K+ channels. It appears to be 20 times less potent on Kv1.2 channels and 90 times more potent on Kv1.3 channels than the α-KTx6 family member MTX.
Mode of Action.
HTX causes reversible current inhibition on Kv1.1, Kv1.2 and Kv1.3 channels.
Toxicity.
Intracerebroventricular injection of HTX has been shown to cause neurotoxic symptoms in mice with an LD50 of 0.3 μg per 20 g body weight.


Otic placode

In embryology, the otic placode is a thickening of the ectoderm on the outer surface of a developing embryo from which the ear develops. The ear, including both the vestibular system and the auditory system, develops from the otic placode beginning the third week of development. During the fourth week, the otic placode invaginates into the mesenchyme adjacent to the rhombencephalon to form the otic pit, which then pinches off from the surface ectoderm to form the otic vesicle.


Hinterland

Hinterland is a German word meaning "the land behind" (a city, a port, or similar). The term's use in English was first documented by geographer George Chisholm in his "Handbook of Commercial Geography" (1888). Originally the term was associated with the area of a port where materials for export and import are stored and shipped. Subsequently, the use of the word expanded to include any area under the influence of a particular human settlement.
Breadth of knowledge.
A further sense in which the term is commonly applied, especially by British politicians, is in talking about an individual's depth and breadth of knowledge of other matters (or lack thereof), specifically of academic, artistic, cultural, literary and scientific pursuits. For instance, one could say, "X has a vast hinterland", or "Y has no hinterland". The spread of this usage is usually credited to Denis Healey (British Defence Secretary 1964–1970, Chancellor of the Exchequer 1974–1979) and his wife Edna Healey, initially in the context of the supposed lack of hinterland of former Prime Minister Margaret Thatcher.


Registration black

In CMYK printing, registration black refers to 100% coverage in each of the four process colors: cyan (C), magenta (M), yellow (Y), and black (K). More generally, if a different mixture of colors is being used, registration black marks in each of the colorants (inks) used.
It is therefore not correct to simply define registration color as 100% of C,M,Y,K, since it will rather be 100% of whichever colors are used in reproduction.
Registration black is used for printing crop marks, or "registration marks". When proofs for each color are generated on separate pieces of film, use of registration black makes crop marks visible on all channels, providing a useful reference for alignment. A thin line printed in registration black can also be used to check whether the printing plates are lined up.
PostScript.
The PostScript printer description languages supports registration black, starting with PostScript language level 2. This is done by referring to a spot color with the special name All. This never generates a spot plate. Instead it marks all of the plates that are there. The All color space can be used with a tint value between 0.0 (no mark) to 1.0 (full intensity). Generally, only 1.0 would be used.
The name "All" might not be used in the user interface of a design program, especially outside English language speaking areas. However, the spot color must have the exact name "All". As a side effect, it is impossible in PostScript to create a normal spot plate with this name.
PDF.
The Portable document format (PDF) also includes a spot color called All, with the same restrictions, starting with PDF 1.2. Note that a PDF spot color must also include a "tint transform" which translates spot values into a different color space for viewing on screen, or printing to printers without spot color support. There is no special rule for the name "All", so PDF creators must include a tint transform that converts to black in some color space, in order to maintain the same appearance as the final printed piece.


Total ionic strength adjustment buffer

A total ionic strength adjustment buffer ("TISAB") is a buffer solution which increases the ionic strength of a solution to a relatively high level. This is important for potentiometric measurements, including ion selective electrodes, because they measure the activity of the analyte rather than its concentration. TISAB essentially masks minor changes made in the ionic strength of the solution and hence increases the accuracy of the reading.
Theory.
TISAB is very commonly applied to fluoride ion analysis such as in fluoride ion selective electrodes.
There are four main constituents to TISAB, namely CDTA (cyclohexylenedinitrilotetraacetate), sodium hydroxide, sodium chloride and acetic acid (ethanoic acid), which are all dissolved in deionised water. Hence, TISAB has a density ~1.0 kg/L, though this can vary to 1.18 kg/L. Each constituent plays an important role in controlling the ionic strength and pH of the analyte solution, which may otherwise cause error and inaccuracy.
The activity of a substance in solution depends on the product of its concentration and the activity coefficient in that solution. The activity coefficient depends on the ionic strength of the solution in which the potentiometric measurements are made. This can be calculated for dilute solutions using the Debye–Hückel equation; for more concentrated solutions other approximations must be used. In most cases, the analyst's goal is simply to make sure that the activity coefficient is constant across a set of solutions, with the assumption that no significant ion pairing exists in the solutions.
Example: An ion-selective electrode might be calibrated using dilute solutions of the analyte in distilled water. If this calibration is used to calculate the concentration of the analyte in sea water (high ionic strength), significant error is introduced by the difference between the activity of the analyte in the dilute solutions and the concentrated sample. This can be avoided by adding a small amount of ionic-strength buffer to the standards, so that the activity coefficients match more closely.
Adding a TISAB buffer to increase the ionic strength of the solution helps to "fix" the ionic strength at a stable level, making a linear correlation between the logarithm of the concentration of analyte and the measured voltage. By also adding the TISAB buffer to the samples from which the potentiometric equipment are calibrated, the linear correlation can be used to calculate the concentration of analyte in the solution.
where formula_2 is measured voltage, formula_3 is the gas constant, formula_4 the temperature measured in kelvins, formula_5 is the Faraday constant and formula_6 the charge of the analyte. formula_7 is the concentration of analyte.
TISAB buffers often include chelators which bind ions that could otherwise interfere with the analyte.


Education 3.0

Education 3.0 is an umbrella term used by educational theorists to describe a variety of ways to integrate technology into learning. According to Jeff Borden, Education 3.0 entails a confluence of neuroscience, cognitive psychology, and education technology, using web-based digital and mobile technology, including apps, hardware and software, and "anything else with an "e" in front of it." Instead of viewing digital technology as a competitor to current teaching models, Education 3.0 means actively embracing new technologies to see how they can help students learn efficiently. Writer Michael Horn describes it as moving "beyond mass education to mass-customized education through blended learning," using the flexibility of technology to help students of varying backgrounds and skills. The term has been included in the term "Entrepreneurship Education 3.0" which denotes a broadening of entrepreneurship education with interdisciplinary appeal for non-business majors, according to a report in "Technically Philly" magazine.
With Education 3.0, classes move away from traditional lectures and instead focus on interactive learning, with question and answer sessions, reviews and quizzes, discussions, labs, and other project-based learning. It usually involves customization and personalization, such that educational content is tailored to meet the needs of specific students. It can mean reversing the traditional classroom learning, in which lectures happen in class and homework is done out of class, into flipped classrooms, such that new content is delivered online while students work on assignments together in class.
The term has been used by educational theorists in South Korea and in Latin America. According to a report in "Forbes magazine", schools such as the Korea Advanced Institute of Science and Technology or KAIST are actively exploring Education 3.0. In Latin America, "Educación 3.0" is being explored as a way to make education affordable to poor people throughout the region, and to help ameliorate poverty.


Synaptic pruning

Synaptic pruning, a phase in the development of the nervous system, is the process of synapse elimination that occurs between early childhood and the onset of puberty in many mammals, including humans. Pruning starts near the time of birth and continues into the mid-20s. During pruning, both the axon and dendrite decay and die off. It was traditionally considered to be complete by the time of sexual maturation, but this was discounted by MRI studies.
The infant brain will increase in size by a factor of up to 5 by adulthood, reaching a final size of approximately 86 (± 8) billion neurons. Two factors contribute to this growth: the growth of synaptic connections between neurons and the myelination of nerve fibers; the total number of neurons, however, remains the same. After adolescence, the volume of the synaptic connections decreases again due to synaptic pruning.
Pruning is influenced by environmental factors and is widely thought to represent learning.
Variations.
Regulatory pruning.
At birth, the neurons in the visual and motor cortices have connections to the superior colliculus, spinal cord, and pons. The neurons in each cortex are selectively pruned, leaving connections that are made with the functionally appropriate processing centers. Therefore, the neurons in the visual cortex prune the synapses with neurons in the spinal cord, and the motor cortex severs connections with the superior colliculus. This variation of pruning is known as large-scaled stereotyped axon pruning. Neurons send long axon branches to appropriate and inappropriate target areas, and the inappropriate connections are eventually pruned away.
Regressive events refine the abundance of connections, seen in neurogenesis, to create a specific and mature circuitry. Apoptosis and pruning are the two main methods of severing the undesired connections. In apoptosis, the neuron is killed and all connections associated with the neuron are also eliminated. In contrast, the neuron does not die in pruning, but requires the retraction of axons from synaptic connections that are not functionally appropriate.
It is believed that the purpose of synaptic pruning is to remove unnecessary neuronal structures from the brain; as the human brain develops, the need to understand more complex structures becomes much more pertinent, and simpler associations formed at childhood are thought to be replaced by complex structures.
Despite the fact it has several connotations with regulation of cognitive childhood development, pruning is thought to be a process of removing neurons which may have become damaged or degraded in order to further improve the "networking" capacity of a particular area of the brain. Furthermore, it has been stipulated that the mechanism not only works in regard to development and reparation, but also as a means of continually maintaining more efficient brain function by removing neurons by their synaptic efficiency.
Pruning in the maturing brain.
The pruning that is associated with learning is known as small-scale axon terminal arbor pruning. Axons extend short axon terminal arbors toward neurons within a target area. Certain terminal arbors are pruned by competition. The selection of the pruned terminal arbors follow the "use it or lose it" principle seen in synaptic plasticity. This means synapses that are frequently used have strong connections while the rarely used synapses are eliminated. Examples seen in vertebrate include pruning of axon terminals in the neuromuscular junction in the peripheral nervous system and the pruning of climbing fiber inputs to the cerebellum in the central nervous system.
In terms of humans, synaptic pruning has been observed through the inference of differences in the estimated numbers of glial cells and neurons between children and adults, which differs greatly in the mediodorsal thalamic nucleus.
In a study conducted in 2007 by Oxford University, researchers compared 8 newborn human brains with those of 8 adults using estimates based upon size and evidence gathered from stereological fractionation. They showed that, on average, estimates of adult neuron populations were 41% lower than those of the newborns in the region they measured, the mediodorsal thalamic nucleus.
However, in terms of glial cells, adults had far larger estimates than those in newborns; 36.3 million on average in adult brains, compared to 10.6 million in the newborn samples. The structure of the brain is thought to change when degeneration and deafferentation occur in postnatal situations, although these phenomena have not been observed in some studies. In the case of development, neurons which are in the process of loss via programmed cell death are unlikely to be re-used, but rather replaced by new neuronal structures or synaptic structures, and have been found to occur alongside the structural change in the sub-cortical gray matter.
Synaptic pruning is classified separately from the regressive events seen during older ages. While developmental pruning is experience dependent, the deteriorating connections that are synonymous with old age are not. The stereotyped pruning can be compared to the process of chiseling and molding of stone into a statue. Once the statue is complete, the weather will begin to erode the statue and this represents the experience-independent deletion of connections.
Forgetting problems with learning through pruning.
All attempts to construct artificial intelligence systems that learn by pruning connections that are disused have the problem that every time they learn something new, they forget everything they learned before. Since biological brains follow the same laws of physics as artificial intelligences, as all physical objects do, these researchers argue that if biological brains learned by pruning they would face the same catastrophic forgetting issues. This is pointed out as an especially severe problem if the learning is supposed to be part of a developmental process since retention of older knowledge is necessary for developmental types of learning, and as such it is argued that synaptic pruning cannot be a mechanism of mental development. It is argued that developmental types of learning must use other mechanisms that do not rely on synaptic pruning.
Energy saving for reproduction and discontinuous differences.
One theory of why many brains are synaptically pruned when a human or other primate grows up is that maintenance of synapses consume nutrients which may be needed elsewhere in the body during growth and sexual maturation. This theory presupposes no mental function of synaptic pruning. The empirical observation that human brains fall into two distinct categories, one that reduces synaptic density by about 41% while growing up and another synaptically neotenic type in which there is very little to no reduction of synaptic density, but no continuum between them, is explainable by this theory as an adaptation to physiologies with different nutritional needs in which one type needs to free up nutrients to get through puberty while the other can mature sexually by other redirections of nutrients that do not involve reducing the brain's consumption of nutrients. Citing that most of the nutrient costs in the brain are in maintaining the brain cells and their synapses, rather than the firing itself, this theory explains the observation that some brains appear to continue pruning years after sexual maturation as a result of some brains having more robust synapses, allowing them to take years of neglect before the synaptic spines finally disintegrate. Another hypothesis that can explain the discontinuity is that of limited functional genetic space restricted by the fact that most of the human genome needs to lack sequence-specific functions to avoid too many deleterious mutations, predicting that evolution proceeds by a few of the mutations happening to have large effects while most mutations do not have any effects at all.
Mechanisms.
The three models explaining synaptic pruning are axon degeneration, axon retraction, and axon shedding. In all cases, the synapses are formed by a transient axon terminal, and synapse elimination is caused by the axon pruning. Each model offers a different method in which the axon is removed to delete the synapse. In small-scale axon arbor pruning, neural activity is thought to be an important regulator, but the molecular mechanism remains unclear. Hormones and trophic factors are thought to be the main extrinsic factors regulating large-scale stereotyped axon pruning.
Axon degeneration.
In "Drosophila", there are extensive changes made to the nervous system during metamorphosis. Metamorphosis is triggered by ecdysone, and during this period, extensive pruning and reorganization of the neural network occurs. Therefore, it is theorized that pruning in "Drosophila" is triggered by the activation of ecdysone receptors. Denervation studies at the neuromuscular junction of vertebrates have shown that the axon removal mechanism closely resembles Wallerian degeneration. However, the global and simultaneous pruning seen in "Drosophilia" differs from the mammalian nervous system pruning, which occurs locally and over multiple stages of development.
Axon retraction.
Axon branches retract in a distal to proximal manner. The axonal contents that are retracted are thought to be recycled to other parts of the axon. The biological mechanism with which axonal pruning occurs still remains unclear for the mammalian central nervous system. However, pruning has been associated with guidance molecules in mice. Guidance molecules serve to control axon pathfinding through repulsion, and also initiate pruning of exuberant synaptic connections. Semaphorin ligands and the receptors neuropilins and plexins are used to induce retraction of the axons to initiate hippocampo-septal and infrapyramidal bundle (IPB) pruning. Stereotyped pruning of the hippocampal projections have been found to be significantly impaired in mice that have a Plexin-A3 defect. Specifically, axons that are connected to a transient target will retract once the Plexin-A3 receptors are activated by class 3 semaphorin ligands. In IPB, the expression of mRNA for Sema3F is present in the hippocampus prenatally, lost postnatally and returns in the stratum oriens. Coincidentally, onset IPB pruning occurs around the same time. In the case of the hippocampal-septal projections, expression of mRNA for Sema3A was followed by the initiation of pruning after 3 days. This suggests that pruning is triggered once the ligand reaches threshold protein levels within a few days after detectable mRNA expression. Pruning of axons along the visual corticospinal tract (CST) is defective in neuropilin-2 mutants and plexin-A3 and plexin-A4 double mutant mice. Sema3F is also expressed in the dorsal spinal cord during the pruning process. There is no motor CST pruning defect observed in these mutants.
Stereotyped pruning has also been observed in the tailoring of overextended axon branches from the retinotopy formation. Ephrin and the ephrin receptors, Eph, have been found to regulate and direct retinal axon branches. Forward signaling between ephrin-A and EphA, along the anterior-posterior axis, has been found to inhibit retinal axon branch formation posterior to a terminal zone. The forward signaling also promotes pruning of the axons that have reached into the terminal zone. However, it remains unclear whether the retraction mechanism seen in IPB pruning is applied in retinal axons.
Reverse signaling between ephrin-B proteins and their Eph receptor tyrosine kinases have been found to initiate the retraction mechanism in the IPB. Ephrin-B3 is observed to transduce tyrosine phosphorylation-dependent reverse signals into hippocampal axons that trigger pruning of excessive IPB fibers. The proposed pathway involves EphB being expressed on the surface of target cells that results in tyrosine phosphorylation of ephrin-B3. Ensuing binding of ephrin-B3 to the cytoplasmic adaptor protein, Grb4, leads to the recruitment and binding of Dock180 and p21 activated kinases (PAK). The binding of Dock180 increases Rac-GTP levels, and PAK mediates the downstream signaling of active Rac that leads to the retraction of the axon and eventual pruning.
Axon shedding.
Time-lapse imaging of retreating axons in neuromuscular junctions of mice have shown axonal shedding as a possible mechanism of pruning. The retreating axon moved in a distal to proximal order and resembled retraction. However, there were many cases in which remnants were shed as the axons were retracting. The remnants, named axosomes, contained the same organelles seen in the bulbs attached to the end of axons and were commonly found around the proximity of the bulbs. This indicates that axosomes are derived from the bulbs. Furthermore, axosomes did not have electron-dense cytoplasms or disrupted mitochondria indicating that they were not formed through Wallerian degeneration.
Potential Role in Schizophrenia.
Synaptic pruning has been suggested to have a role in the pathology of neurodevelopmental disorders such as schizophrenia, as well as in autism spectrum disorder. ""
Microglia have been implicated in synaptic pruning, as they have roles in both the immune response as macrophages as well as in neuronal upkeep and synaptic plasticity in the CNS during fetal development, early postnatal development, and adolescence, in which they engulf unneeded or redundant synapses via phagocytosis. "" Microglial synapse engulfment and uptake has been specifically observed to be upregulated in the isolated synaptosomes of male patients with schizophrenia compared to healthy controls, suggesting upregulated microglia-induced synaptic pruning in these individuals. Microglia-mediated synaptic pruning has also been observed to be upregulated during late adolescence and early adulthood, which could also account for the age of onset for schizophrenia often being reported around this time in development (late teens to early 20s for men, and mid-to-late 20s for women) The drug minocycline, a semisynthetic brain-penetrant tetracycline antibiotic, has been found to somewhat reverse these changes made to patient synaptosomes by downregulating synaptic pruning.
Genes in the Complement Component 4 (C4) locus of the major histocompatibility complex (MHC), which encode for complement factors, have also been tied to schizophrenia risk through gene linkage studies. The fact that some of these complement factors are involved in signaling during synaptic pruning also seems to suggest that schizophrenia risk may be linked to synaptic pruning. Specifically, complement factors C1q and C3 have been found to have a role in microglia-mediated synaptic pruning. "" Carriers of C4 risk variants have also been found to be tied to this kind of synapse overpruning in microglia. The proposed mechanism for this interaction is increased complement factor C3 deposition onto synaptosomes as a consequence of increased C4A expression in these risk variant carriers.


Uvula of cerebellum

The uvula (uvular lobe) forms a considerable portion of the inferior vermis; it is separated on either side from the tonsil by the sulcus vallecula, at the bottom of which it is connected to the tonsil by a ridge of gray matter, indented on its surface by shallow furrows, and hence called the furrowed band.


Superior cardiac nerve

The superior cardiac nerve arises by two or more branches from the superior cervical ganglion, and occasionally receives a filament from the trunk between the first and second cervical ganglia. It runs down the neck behind the common carotid artery, and in front of the Longus colli muscle; and crosses in front of the inferior thyroid artery, and recurrent nerve. The course of the nerves on the two sides then differs.
Right nerve.
The right nerve, at the root of the neck, passes either in front of or behind the subclavian artery, and along the innominate artery to the back of the arch of the aorta, where it joins the deep part of the cardiac plexus.
It is connected with other branches of the sympathetic; about the middle of the neck it receives filaments from the external laryngeal nerve; lower down, one or two twigs from the vagus; and as it enters the thorax it is joined by a filament from the recurrent laryngeal nerve.
Filaments from the nerve communicate with the thyroid branches from the middle cervical ganglion.
Left nerve.
The left nerve, in the thorax, runs in front of the left common carotid artery and across the left side of the aortic arch, to the superficial part of the cardiac plexus.


Meso-Butestrol

"meso"-Butestrol (developmental code name SC-3402), also known as 2,3-"bis"(4-hydroxyphenyl)butane, is a synthetic nonsteroidal estrogen which was never marketed. It is a so-called "short-acting" or "impeded" estrogen. "meso"-Butestrol is structurally related to diethylstilbestrol and other stilbestrols. The fully potent counterpart to "meso"-butestrol is "meso"-hexestrol, analogously to the relationship of dimethylstilbestrol to diethylstilbestrol.


Cognitive Neuroscience (journal)

Cognitive Neuroscience is a peer-reviewed academic journal published four times a year by the Taylor & Francis Group. It publishes empirical and theoretical articles on all topics in the field of cognitive neuroscience. These include perception, attention, memory, language, action, decision-making, emotion, and social cognition. It is co-Edited by Jamie Ward of the University of Sussex and Sharon Thompson-Schill of the University of Pennsylvania.
Aims and scope.
The focus of the journal is undergraduate and graduate level neuroscience. The intended audience is college and university neuroscience teachers and students, as well as clinical practitioners and researchers in the field.
The journal’s format is unusual in publishing shorter articles (of up to 4000 words) that are rapidly reviewed and published online. It also publishes longer (8000 word) discussion and review articles that evaluate current topics in the field, with critical analysis in the form of peer commentaries (800 words). The journal’s stated aim is to publish accepted discussion papers and short report articles in uncorrected form online within 7 days of acceptance. The journal also pledges to publish the final form of these articles online within 6 weeks of acceptance.
Abstracting and indexing.
The journal is indexed in the following databases:


Ralph Newman

Ralph Geoffrey Newman (3 November 1911 – 23 July 1998) was an American author and well known Abraham Lincoln scholar. He owned the Abraham Lincoln Book Shop in Chicago, Illinois, and hosted a monthly gathering known as the Civil War Round Table. He was an expert in Civil War-related manuscripts.
He played minor league second base for Tucson and Wichita.
Newman also was an appraiser who evaluated the papers of six United States presidents: Hoover, Truman, Eisenhower, Kennedy, Johnson, and Nixon.
Newman was indicted by a federal grand jury in July 1975 on charges of preparing a false affidavit that helped Richard Nixon obtain an illegal tax break on papers he donated and subsequently convicted in November 1975.
Family.
Ralph Newman married Estelle Hoffman and they had two daughters, Maxine Newman Brandenburg and Carol Newman Parry. He later remarried, to actress Patricia Lyons. His stepson is NPR host Scott Simon.