MDAT

6,7-Methylenedioxy-2-aminotetralin (MDAT) is a drug developed in the 1990s by a team at Purdue University led by David E. Nichols. It appears to act as a serotonin releasing agent based on rodent drug discrimination assays comparing it to MDMA, in which it fully substitutes for, and additionally lacks any kind of serotonergic neurotoxicity. Hence, MDAT is considered likely to be a non-neurotoxic, putative entactogen in humans.


Salih ibn Abd al-Rahman

Abū al-Walīd Ṣāliḥ ibn ʿAbd al-Rahmān al-Sijistānī () (died 721–724) was a leading bureaucrat in the central "dīwān" (tax bureau) of Iraq under the Umayyad governor al-Hajjaj ibn Yusuf (694–714) and then fiscal governor of the province under Caliph Sulayman ibn Abd al-Malik (). In 697, upon al-Hajjaj's order, he carried out the conversion of the Persian-language Iraqi "dīwān" into Arabic.
Origins.
The year of Salih's birth is not known. He was one of at least two sons of a "mawlā" (Muslim convert or freedman) originally from Sijistan called Abd al-Rahman. The latter had been taken captive in 650/51 by the troops of Rabi ibn Ziyad al-Harithi, an Arab commander dispatched to Sijistan by the governor of Basra, Abd Allah ibn Amir, who at the time was leading an expedition in Khurasan. Together with his wife, Abd al-Rahman, whose original name is not known, was captured in the village of Nashrudh during one of Rabi's raids in the vicinity of Zaranj. They were brought to the Arab garrison town and provincial center of Basra, where both were purchased by a certain Abla, a woman of the Banu Tamim, and then freed by her upon their conversion to Islam.
Career.
Administration of Iraq under al-Hajjaj.
During the governorship of al-Hajjaj ibn Yusuf over Iraq, Salih entered the "dīwān" (bureaucratic administration) of Basra under the mentorship of the Persian Zoroastrian administrator Zadhanfarrukh. At the time, the language of bureaucracy in Iraq and the eastern half of the Caliphate was Persian. Unlike Zadhanfarrukh, Salih was fluent in Arabic as well as Persian, due to his Muslim upbringing in Basra. This knowledge combined with his demonstrable competence and frugality caught the attention of al-Hajjaj. When the latter moved to convert the Persian tax records of Iraq's central "dīwān" to Arabic in 697, he entrusted Salih with the task.
The local and provincial "dīwāns" in Iraq and the eastern provinces remained Persian for many years after the change, and Salih was charged with training his bureaucrats to adopt the new Arabic system. His efforts were met with resistance by Zadhanfarrukh, the latter's son Mardanshah and the veteran Persian bureaucrats. Mardanshah attempted to convince him of the inability of Arabic to translate Persian fractions (Arabic did not have forms for fractions below tenths), which Salih solved by using tenths and half-tenths. Mardanshah also attempted to bribe Salih with 100,000 silver dirhams to persuade al-Hajjaj of his inability to effect the language changes, but Salih refused. Nonetheless, he did not inform al-Hajjaj of his colleagues' attempts to void his assignment, which would have led to their dismissals and possible executions. The next generation of Iraqi tax administrators were the pupils of Salih and held him in high esteem. The "kātib" (scribe) of Caliph Marwan II, Abd al-Hamid ibn Yahya, noted this, saying: "What a man Salih was! How great his favor to the scribes".
Despite his integral role in the administration, Salih did not hold an official post under al-Hajjaj; the caliphs Abd al-Malik () and al-Walid I () combined the military and fiscal responsibilities of Iraq and the east into the singular authority of al-Hajjaj. Salih was referred to as the "ṣāḥib dawāwīn", akin to the superintendent of Iraq's central tax bureaux in Wasit. When, in 702, al-Hajjaj built Wasit as the new capital of Iraq and the garrison of his elite Syrian troops, the costs of construction totaled 43,000,000 dirhams, a sum far more expensive than the governor had anticipated. To rectify the budget, Salih attributed about 80% of the cost to war expenses, and the remainder to construction.
Salih was suspected of harboring sympathies for proto-Shu'ubiyya Kharijites. To test his loyalty, al-Hajjaj, at the prodding of his protege Yazid ibn Abi Muslim, commanded Salih to execute the captive Kharijite leader Jawwab al-Dabbi. Fearing for the welfare of his daughters should he refuse, Salih carried out the killing.
Fiscal governor of Iraq.
Shortly after his accession, Caliph Sulayman ibn Abd al-Malik () removed the deputy governors and commanders appointed or associated with al-Hajjaj, including the latter's successor in Iraq, Yazid ibn Abi Muslim. In his place, he appointed Yazid ibn al-Muhallab as governor of Iraq for its military and religious affairs and Salih as fiscal governor of the province. Salih's appointment was recommended by Ibn al-Muhallab, who was disinterested in responsibility over tax collection. Nonetheless, as he was directly appointed by Sulayman, he answered to the caliph and was a near equal in rank to Ibn al-Muhallab. Though he generally did not restrict funding for the army or provisions, Salih frequently stopped attempts by Ibn al-Muhallab to squander treasury funds for personal use. Reflecting on his own role in Salih's appointment, Ibn al-Muhallab expressed his frustration: "This is what I have done to myself".
Sulayman charged Salih with the arrest, torture and execution of several member of the Abu Aqil clan to which al-Hajjaj belonged. Among the prisoners in Wasit, the headquarters of Salih, was the conqueror and governor of Sind, Muhammad ibn Qasim, and his brother al-Hajjaj ibn Qasim, the latter of whom had killed Salih's brother Adam for his active role with Kharijite rebels. Salih followed the order and charged Ibn al-Muhallab's brother, Abd al-Malik, with supervising the torture.
Among Salih's achievements was the construction of a governor's house in Basra. Though Wasit was established as Iraq's capital, Basra and Kufa still served as subgovernorships and Salih sought to replace the ruined clay palace built by a previous governor, Ubayd Allah ibn Ziyad. After gaining Sulayman's approval for the construction, Salih had a taller, less expensive palace built, the first in the city to consist of baked brick and gypsum.
Later life and death.
Salih's fortunes changed abruptly with the death of Sulayman and the accession Umar II () in September 717. Salih was dismissed by the caliph and likely retired from the public sector. At some point, he relocated the caliph's court in Syria during the reign of Caliph Yazid II (), who was deferential to Salih. Shortly after the accession of Yazid II, Ibn al-Muhallab raised a mass revolt against the Umayyads in Iraq, which was stamped out by the governor Umar ibn Hubayra al-Fazari and the caliph's brother Maslama ibn Abd al-Malik. Afterward, Ibn Hubayra sought to snuff out Ibn al-Muhallab's associates in the province and override the system of tax management established by Salih. He remained wary of the latter's influence. Seeking to find a cause to have him arrested, Ibn Hubayra charged a bureaucrat from Anbar with scouring the budget records to find any violations that Salih may have committed. They were not successful, but pinned on him a major discrepancy of 600,000 dirhams by Ibn al-Muhallab. Ibn Hubayra submitted the complaint to the caliph, who consequently arrested and sent Salih for prosecution in Iraq. There, Ibn Hubayra personally tortured him to death.
In the assessment of the historian Martin Sprengling, "Salih ibn Abdalrahman remains a sad, lonely figure, outstanding, of most extraordinary ability, rising for his moment to heights far above the average, then melting completely out of sight". His memory was preserved by his pupils and successors in Iraq's "dīwān". Among them were Ibn al-Muqaffa', who wrote of him fondly, the "mawlā" Abd al-Hamid ibn Yahya who considered Salih the greatest benefactor of the Umayyad-era scribes, and Qahdam, the Persian progenitor of several generations of scribes who were active during the early Abbasid Caliphate.


Genes to Cognition Project

Genes to Cognition (G2C) is a neuroscience research programme that studies genes, the brain and behaviour in an integrated manner. It is engaged in a large-scale investigation of the function of molecules found at the synapse. This is mainly focused on proteins that interact with the NMDA receptor, a receptor for the neurotransmitter, glutamate, which is required for processes of synaptic plasticity such as long-term potentiation (LTP). One key discovery that led to the G2C project was the characterization of a group of proteins that interact with this receptor, called the "NMDA Receptor Complex (NRC)" and the observation that dysfunctions of many of these proteins are characteristic of numerous diseases of the nervous system. The NRC contains 185 proteins, 48 of which have so far been implicated in 54 human nervous system disorders. The molecular evolution of the NRC is also an active area of research, and it has been shown that an increase in the complexity of these signaling proteins at synapses has evolved alongside the enhanced cognitive capacities of humans and other higher vertebrates.
Scientific Strategy.
The activities of the Genes to Cognition Project encompass a wide range of scientific specialisms, reflecting the diversity of information that must be integrated to advance understanding of the brain. Following from synapse proteomics experiments to identify candidate proteins for further investigation, G2C has undertaken to knock out many of these by gene targeting in mice and has established a number of high-throughput platforms for evaluating the effect of these genetic manipulations on brain function.
Information Sharing.
As well as sharing findings through open access articles in the scientific literature, Genes to Cognition maintains a database, G2Cdb and an educational web site, G2Conline.
G2Cdb: Genes to Cognition Database.
G2Cdb integrates information curated from the scientific literature and numerous online databases about genes and diseases of interest to Genes to Cognition. It also provides access to lists of genes derived from proteomics experiments characterising the composition of the complex of proteins present at the postsynaptic density. It will also provide data from experiments investigating the effects of genetic manipulation of these synaptic molecules.
G2Conline: Educational Web Site.
G2Conline is an interactive educational website that provides extensive background information on key topics in neuroscience and brain disorders. There are many video clips of interviews with scientists, including Nobel laureates James Watson and Eric Kandel.


Nimodipine

Nimodipine, sold under the brand name Nimotop among others, is a calcium channel blocker used in preventing vasospasm secondary to subarachnoid hemorrhage (a form of cerebral hemorrhage). It was originally developed for the treatment of high blood pressure, but is not used for this indication.
It was patented in 1971 and approved for medical use in the US in 1988. It was approved for medical use in Germany in 1985.
Medical use.
Because it has some selectivity for cerebral vasculature, nimodipine's main use is in the prevention of cerebral vasospasm and resultant ischemia, a complication of subarachnoid hemorrhage (a form of cerebral bleed), specifically from ruptured intracranial berry aneurysms irrespective of the patient's post-ictus neurological condition. Its administration begins within 4 days of a subarachnoid hemorrhage and is continued for three weeks. If blood pressure drops by over 5%, dosage is adjusted. There is still controversy regarding the use of intravenous nimodipine on a routine basis.
A 2003 trial (Belfort "et al.") found nimodipine was inferior to magnesium sulfate in preventing seizures in women with severe preeclampsia.
Nimodipine is not regularly used to treat head injury. Several investigations have been performed evaluating its use for traumatic subarachnoid hemorrhage; a systematic review of 4 trials did not suggest any significant benefit to the patients that receive nimodipine therapy. There was one report case of nimodipine being successfully used for treatment of ultradian bipolar cycling after brain injury and, later, amygdalohippocampectomy.
Dosage.
The regular dosage is 60 mg tablets every four hours. If the patient is unable to take tablets orally, it was previously given via intravenous infusion at a rate of 1–2 mg/hour (lower dosage if the body weight is <70 kg or blood pressure is too low), but since the withdrawal of the IV preparation, administration by nasogastric tube is an alternative.
Contraindications.
Nimodipine is associated with low blood pressure, flushing and sweating, edema, nausea and other gastrointestinal problems, most of which are known characteristics of calcium channel blockers. It is contraindicated in unstable angina or an episode of myocardial infarction more recently than one month.
While nimodipine was occasionally administered intravenously in the past, the FDA released an alert in January 2006, warning that it had received reports of the approved oral preparation being used intravenously, leading to severe complications; this was despite warnings on the box that this should not be done.
Side-effects.
The FDA has classified the side effects into groups based on dosages levels at q4h. For the high dosage group (90 mg) less than 1% of the group experienced adverse conditions including itching, gastrointestinal hemorrhage, thrombocytopenia, neurological deterioration, vomiting, diaphoresis, congestive heart failure, hyponatremia, decreasing platelet count, disseminated intravascular coagulation, deep vein thrombosis.
Pharmacokinetics.
Absorption.
After oral administration, it reaches peak plasma concentrations within one and a half hours. Patients taking enzyme-inducing anticonvulsants have lower plasma concentrations, while patients taking sodium valproate were markedly higher.
Metabolism.
Nimodipine is metabolized in the first pass metabolism. The dihydropyridine ring of the nimodipine is dehydrogenated in the hepatic cells of the liver, a process governed by cytochrome P450 isoform 3A (CYP3A). This can be completely inhibited however, by troleandomycin (an antibiotic) or ketoconazole (an antifungal drug).
Excretion.
Studies in non-human mammals using radioactive labeling have found that 40–50% of the dose is excreted via urine. The residue level in the body was never more than 1.5% in monkeys.
Mode of action.
Nimodipine binds specifically to -type voltage-gated calcium channels. There are numerous theories about its mechanism in preventing vasospasm, but none are conclusive.
Nimodipine has additionally been found to act as an antagonist of the mineralocorticoid receptor, or as an antimineralocorticoid.
Synthesis.
The key acetoacetate (2) for the synthesis of nimodipine (5) is obtained by alkylation of sodium acetoacetate with 2-methoxyethyl chloride, Aldol condensation of "meta"-nitrobenzene (1) and the subsequent reaction of the intermediate with enamine (4) gives nimodipine.
Stereochemistry.
Nimodipine contains a stereocenter and can exist as either of two enantiomers. The pharmaceutical drug is a racemate, an equal mixture of the ("R")- and ("S")- forms.


Milt Davis

Milton Eugene Davis (May 31, 1929 – September 29, 2008) was a defensive back who played four seasons in the NFL for the Baltimore Colts. He had 27 career interceptions with the Colts, and he led the NFL in interceptions in 1957 and 1959.
The defensive back was born May 31, 1929 on the Fort Gibson Indian reservation in Muskogee, Oklahoma to parents of African American and Native American ancestry. He moved as a toddler to Los Angeles
He attended Jefferson High School and Los Angeles City College, both in Los Angeles. He worked at the Vista Del Mar Jewish orphanage as a counselor while attending college. His track performance earned him a partial scholarship at the University of California, Los Angeles. He earned a spot on the UCLA Bruins football team in both 1952 and 1953 under coach Red Sanders, and played in the team's 1954 Rose Bowl 28-20 loss to the Michigan State Spartans.
The Detroit Lions drafted him in 1954, the same year he was drafted into the United States Army, serving there for two years. After his return from the Army, the Lions told him "We don't have a black teammate for you to go on road trips, therefore you can't stay on our team."
The Baltimore Colts gave Davis a tryout and signed him as a free agent. In his rookie season in 1957, he had 10 interceptions which were returned for a total of 219 yards, two of them for touchdowns including a return of 75 yards. He was on the Associated Press NFL All-Pro Team that season.
In the 1958 season, he had four interceptions, which he returned for a total of 40 yards. In the 1958 NFL Championship Game against the New York Giants, played at Yankee Stadium, Davis — despite playing with two broken bones in his right foot — forced one of two first-half fumbles by Giants running back Frank Gifford, both of which led to touchdowns by the Colts; The Colts won 23-17 in overtime in a game called "The Greatest Game Ever Played".
Davis had seven interceptions in the 1959 season, which he returned for 119 yards, including a 57-yard return for a touchdown. In the 1959 NFL Championship Game, the Colts beat the Giants for a second consecutive season, this time by a 31-16 score. In 1960, he had six interceptions which he returned for 32 yards.
Angered at the treatment of black players, including segregated hotels and restaurants, Davis retired after four seasons in the NFL and returned to complete work on a doctorate in education at UCLA. He worked as a scout for several NFL teams and taught at John Marshall High School. He was a professor of natural history at Los Angeles City College from 1964 to 1989, then retired to Oregon with his wife, where he raised cattle, llama and sheep. He died in Elmira, Oregon of brain cancer at age 79 on September 29, 2008.


James Vicary

James McDonald Vicary (April 30, 1915 – November 7, 1977) was a market researcher best known for pioneering the concept of subliminal advertising with an experiment in 1957. It was later suggested that the results of his experiments had been fraudulent. Vicary was unable to ever reproduce the results of his experiments.
Vicary himself admitted that he had never conducted the subliminal "experiment" — it was concocted as a gimmick to attract customers to his failing marketing business.
Biography.
Born in Detroit, and trained at the University of Michigan (A.B 1940), he pioneered the use of eye-blink analysis to obtain clues about subjects' levels of emotional tension when exposed to various stimuli. He also studied the phenomena of impulse buying and word association.
He was also known to have a childhood fascination with snakes. He was called Detroit's youngest snake charmer by the Detroit News.
He is most famous for having perpetrated a fraudulent subliminal advertising study in 1957. In it, he claimed that an experiment in which moviegoers were repeatedly shown 1/3000-second advertisements for Coca-Cola and popcorn significantly increased product sales. Based on his claims the CIA produced a report "The operational potential of subliminal perception" in 1958 that led to subliminal cuts being banned in the US. It suggested that "Certain individuals can at certain times and under certain circumstances be influenced to act abnormally without awareness of the influence". When challenged later to replicate the study, he failed to find significant results. Vicary provided no explanations for his results or any other details about his study to the public, claiming that it is part of a confidential patent. When Stuart Rogers interviewed the theater that supposedly conducted this experiment, the manager declared that there was no such test ever done (Rogers 1992)
In a television interview with Fred Danzig in 1962 for "Advertising Age", Vicary admitted that the original study was "a gimmick" and that the amount of data was "too small to be meaningful". He shied away from media attention after the disclosure. His papers are held by the Thomas J. Dodd Research Center at the University of Connecticut in Storrs. Numerous commentaries have appeared on this affair since 1957.
Popcorn experiment.
One of the most commonly known examples of subliminal messaging is Vicary’s movie theater "experiment" in 1957, purportedly in Fort Lee, NJ. In his press release, he claimed that 45,699 people were exposed to subliminal projections telling them to "Eat Popcorn" and "Drink Coca-Cola", causing a 57.5 percent sales increase for popcorn and an 18.1 percent increase in Coca-Cola sales. Vicary provided no explanations for his results making it impossible to reproduce his results. Taken in context with evidence that no experiment even took place, Vicary’s results can be considered completely fraudulent. Vicary later retracted his claims in a television interview, but Vicary’s original claims spread rapidly and lead to widespread acceptance of subliminal messaging, even today. (O’Barr 2005).


Psammon

Psammon (from Greek "psammos", "sand") is a group of organisms inhabiting coastal sand moist — biota buried in sediments. Psammon is a part of water fauna, along with periphyton, plankton, nekton, and benthos. Psammon is also sometimes considered a part of benthos due to its near-bottom distribution. Psammon term is commonly used to refer to freshwater reservoirs such as lakes.


Medulla oblongata

The medulla oblongata or simply medulla is a long stem-like structure which makes up the lower part of the brainstem. It is anterior and partially inferior to the cerebellum. It is a cone-shaped neuronal mass responsible for autonomic (involuntary) functions, ranging from vomiting to sneezing. The medulla contains the cardiac, respiratory, vomiting and vasomotor centers, and therefore deals with the autonomic functions of breathing, heart rate and blood pressure as well as the sleep wake cycle.
During embryonic development, the medulla oblongata develops from the myelencephalon. The myelencephalon is a secondary vesicle which forms during the maturation of the rhombencephalon, also referred to as the hindbrain.
The bulb is an archaic term for the medulla oblongata. In modern clinical usage, the word bulbar (as in bulbar palsy) is retained for terms that relate to the medulla oblongata, particularly in reference to medical conditions. The word bulbar can refer to the nerves and tracts connected to the medulla, and also by association to those muscles innervated, such as those of the tongue, pharynx and larynx.
Anatomy.
The medulla can be thought of as being in two parts:
External surfaces.
The anterior median fissure contains a fold of pia mater, and extends along the length of the medulla oblongata. It ends at the lower border of the pons in a small triangular area, termed the foramen cecum. On either side of this fissure are raised areas termed the medullary pyramids. The pyramids house the pyramidal tracts–the corticospinal and the corticobulbar tracts of the nervous system. At the caudal part of the medulla these tracts cross over in the decussation of the pyramids obscuring the fissure at this point. Some other fibers that originate from the anterior median fissure above the decussation of the pyramids and run laterally across the surface of the pons are known as the anterior external arcuate fibers.
The region between the anterolateral and posterolateral sulcus in the upper part of the medulla is marked by a pair of swellings known as olivary bodies (also called "olives"). They are caused by the largest nuclei of the olivary bodies, the inferior olivary nuclei.
The posterior part of the medulla between the posterior median sulcus and the posterolateral sulcus contains tracts that enter it from the posterior funiculus of the spinal cord. These are the gracile fasciculus, lying medially next to the midline, and the cuneate fasciculus, lying laterally. These fasciculi end in rounded elevations known as the gracile and the cuneate tubercles. They are caused by masses of gray matter known as the gracile nucleus and the cuneate nucleus. The soma (cell bodies) in these nuclei are the second-order neurons of the posterior column-medial lemniscus pathway, and their axons, called the internal arcuate fibers or fasciculi, decussate from one side of the medulla to the other to form the medial lemniscus.
Just above the tubercles, the posterior aspect of the medulla is occupied by a triangular fossa, which forms the lower part of the floor of the fourth ventricle. The fossa is bounded on either side by the inferior cerebellar peduncle, which connects the medulla to the cerebellum.
The lower part of the medulla, immediately lateral to the cuneate fasciculus, is marked by another longitudinal elevation known as the tuberculum cinereum. It is caused by an underlying collection of gray matter known as the spinal trigeminal nucleus. The gray matter of this nucleus is covered by a layer of nerve fibers that form the spinal tract of the trigeminal nerve.
The base of the medulla is defined by the commissural fibers, crossing over from the ipsilateral side in the spinal cord to the contralateral side in the brain stem; below this is the spinal cord.
Blood supply.
Blood to the medulla is supplied by a number of arteries.
Development.
The medulla oblongata forms in fetal development from the myelencephalon. The final differentiation of the medulla is seen at week 20 gestation.
Neuroblasts from the alar plate of the neural tube at this level will produce the sensory nuclei of the medulla. The basal plate neuroblasts will give rise to the motor nuclei.
Function.
The medulla oblongata connects the higher levels of the brain to the spinal cord, and is responsible for several functions of the autonomous nervous system which include:
Clinical significance.
A blood vessel blockage (such as in a stroke) will injure the pyramidal tract, medial lemniscus, and the hypoglossal nucleus. This causes a syndrome called medial medullary syndrome.
Lateral medullary syndrome can be caused by the blockage of either the posterior inferior cerebellar artery or of the vertebral arteries.
Progressive bulbar palsy (PBP) is a disease that attacks the nerves supplying the bulbar muscles. Infantile progressive bulbar palsy is progressive bulbar palsy in children.
Other animals.
Both lampreys and hagfish possess a fully developed medulla oblongata. Since these are both very similar to early agnathans, it has been suggested that the medulla evolved in these early fish, approximately 505 million years ago. The status of the medulla as part of the primordial reptilian brain is confirmed by its disproportionate size in modern reptiles such as the crocodile, alligator, and monitor lizard.


Aroma of Tacoma

The "Aroma of Tacoma", also known as the Tacoma Aroma, is a putrid and unpleasant odor associated with Tacoma, Washington. Tacoma is located in the western part of the state, in Pierce County. The smell has been described as similar to the odor of rotten eggs. The odor is not noticeable throughout the city, but is rather concentrated in the Tacoma Tideflats and is frequently smelled by motorists traveling that section of Interstate 5.
History and origins.
The odor has been commonly known by the name "Aroma of Tacoma" since at least the early 1940s, however, there are instances of the word "aroma" being associated with Tacoma dating back to 1901 when local resident George Francis Train penned a civic cheer:
A variety of causes have been attributed to the Aroma of Tacoma, including sediment in Commencement Bay, sulfur released from the Simpson Tacoma Kraft pulp and paper mill, a rendering plant, the U.S. Oil refinery, or a combination of all of these factors. In 1997, the odor was exacerbated for several weeks after municipal officials unsealed a sewage tank that had not been opened in 15 years during the height of a stretch of humid weather. By the early 2000s, the odor had been lessened, but not eliminated, after the Tacoma Kraft pulp and paper mill installed new combustion technologies.
Local impact.
The Aroma of Tacoma has been cited as the reason behind jokes about Tacoma once frequently made by residents elsewhere in Western Washington. Research in 2003 suggested the Aroma of Tacoma had contributed to a long-term depression of housing prices in the city. Journalist and author Timothy Egan called it "one of the longest lasting nicknames in the Pacific Northwest" and used it as an example of the many consequences of environmental destruction along Puget Sound.
During a concert stop at the Tacoma Dome in the mid 1980s, Bruce Springsteen reported the odor was so overwhelming that he was forced to leave town early. A local doctor said the noxious fumes were unhealthful. The EPA said the smell was due to total reduced sulfur (TRS) emitted by the downtown paper mill ( from the Tacoma Dome).
Popular culture and public science.
In the 1960s, Jim Torrence and Don Lemon with Diamond Jim and the Jazzmasters released a 45 rpm novelty single titled "The Aroma of Tacoma".
A rugby tournament held since the 1970s is called the "Tacoma Aroma", as well as a hip-hop band from the Tacoma area.
The Pacific Science Center held a symposium called "The science behind Tacoma's Aroma" in 2011.
The 1979 Frank Zappa song "Jewish Princess" mentions a "garlic aroma that could level Tacoma".


Ononetin

Ononetin is a natural product from the deoxybenzoin group, which is found in the Russian traditional medicine plant "Ononis spinosa". It acts as an inhibitor of the transient receptor potential ion channel TRPM3 and has analgesic effects in animal studies, as well as being used for research into the role of TRPM3 in the immune system dysfunction associated with chronic fatigue syndrome.


Postsynaptic density

The postsynaptic density (PSD) is a protein dense "specialization" attached to the postsynaptic membrane. PSDs were originally identified by electron microscopy as an electron-dense region at the membrane of a postsynaptic neuron. The PSD is in close apposition to the presynaptic active zone and ensures that receptors are in close proximity to presynaptic neurotransmitter release sites. PSDs vary in size and composition among brain regions, and have been studied in great detail at glutamatergic synapses. Hundreds of proteins have been identified in the postsynaptic density, including glutamate receptors, scaffold proteins, and many signaling molecules.
Structure.
The structure and composition of the PSD have been the focus of numerous molecular studies of synaptic plasticity, a cellular model of learning and memory. PSDs are sized on the order of 250 to 500 nanometres in diameter and 25 to 50 nanometres in thickness, depending on the activity state of the synapse. During synaptic plasticity, the total size of the PSD is increasing along with an increase in synaptic size and strength after inducing long-term potentiation at single synapses.
Composition.
Many proteins in the PSD are involved in the regulation of synaptic function. These include
As protein detection technologies have increased in sensitivity, such as with improvements in mass spectrometry techniques, more numerous proteins have been attributed to the PSD. Current estimates are greater than several hundred proteins are found at PSDs among brain regions and during different states of development and synaptic activity. PSDs also contain cell adhesion molecules and a diverse set of other signaling proteins. Many of the PSD proteins contain PDZ domains.
Function.
The PSD has been proposed to concentrate and organize neurotransmitter receptors in the synaptic cleft. The PSD also serves as a signaling apparatus. For instance kinases and phosphatases in the PSD are activated and released from the PSD to change the activity of proteins located in the spine or are transported to the nucleus to affect protein synthesis. Some of the features of the PSD are similar to the neuromuscular junction and other cellular junctions, as the PSD has been modeled as a specialized cellular junction that allows for rapid, asymmetrical signaling.


Brain and Neuroscience Advances


Under the crease


Upstate

The term upstate may refer to the northerly portions of several U.S. states. On the east coast, upstate generally refers to places away from the Atlantic Ocean. It also can refer to parts of states that have a higher elevation, away from sea level. These regions tend to be rural; exceptions include Delaware and Illinois.


Tanycyte

Tanycytes are special ependymal cells found in the third ventricle of the brain, and on the floor of the fourth ventricle and have processes extending deep into the hypothalamus. It is possible that their function is to transfer chemical signals from the cerebrospinal fluid to the central nervous system.
The term "tanycyte" comes from the Greek word tanus which means elongated.
Structure.
Tanycytes share some features with radial glial cells and astrocytes. Their form and location have led some authors to regard them as radial glial cells that remain in the hypothalamus throughout life. This has led some to believe that these cells share the same lineage.
Even so, tanycytes also display certain characteristics that distinguish them from radial glia cells. Tanycytes in rats begin to develop in the last two days of gestation and continue on until they reach their full differentiation in the first month of life. Radial glia cells on the other hand, are a key component of the embryonic brain. Tanycytes also contain many proteins not found in radial glia cells. Thus, evidence now suggests that tanycytes are genealogical descendants of radial glia cells that do not develop into astrocytes, but rather into their own subpopulation.
Location.
Tanycytes in adult mammals are found in the ventricular system and the circumventricular organs. They are most numerous in the third ventricle of the brain, are also found in the fourth ventricle, and can also be seen in the spinal cord radiating from the ependyma of the central canal to the spinal cord surface. Tanycytes represent approximately 0.6% of the population of the lateral ventricular wall.
Tanycytes have also been shown "in vivo" to serve as a diet-responsive neurogenic niche.
Function.
Recent work suggests that tanycyte cells bridge the gap between the central nervous system (CNS) via cerebrospinal fluid (CSF) to the hypophyseal portal blood. This may also link the CSF to neuroendocrine events.
Role in the release of gonadotropin-releasing hormone.
Researches in 2005 and 2010 found that tanycytes participate in the release of gonadotropin-releasing hormone (GnRH). GnRH is released by neurons located in the rostral hypothalamus. These nerve fibers are concentrated in the region that exactly matches the distribution of β1 tanycytes. β1 and β2 tanycytes are found nearer the arcuate nucleus and the median eminence.
Currently, it is thought that there are two different mechanisms by which tanycytes participate in the release of GnRH. One includes the cyclic remodeling of the spatial relationship between GnRH terminals, the tanycytes, and the perivascular space. The second is the cell to cell signaling mechanism mediated by specific tanycyte compounds. Recent evidence supports both mechanisms, and also the possibility that both are part of a single mechanism.
History.
The term tanycyte was coined by Horstmann in 1954 when he described a distinct structural feature of the cell, which is a single, long basal process that projects to a distinct region of the hypothalamus.
During the 1970s and 1980s, tanycytes were the subject of many research publications, ranging from their morphology to function. But the lack of advanced methodological tools stalled research and led to disagreements between researchers about the full role of tanycytes. Recent advances in immunocytochemistry have allowed for new research in this area.


Secondary sensory endings

Secondary sensory endings of the muscle spindle are composed of type II sensory fibers that terminate on nuclear chain fibers and static nuclear bag fibers, but not dynamic nuclear bag fibers. Whereas primary endings respond mostly to rate of change, secondary endings respond mostly to amount of stretch.


Homeostatic plasticity

In neuroscience, homeostatic plasticity refers to the capacity of neurons to regulate their own excitability relative to network activity. Homeostatic synaptic plasticity is a means of maintaining the synaptic basis for learning, respiration, and locomotion, in contrast to the Hebbian plasticity associated with learning and memory. Although Hebbian forms of plasticity, such as long-term potentiation and long-term depression occur rapidly, homeostatic plasticity (which relies on protein synthesis) and take hours or days. TNF-α and microRNAs are important mediators of homeostatic synaptic plasticity.
Homeostatic plasticity is thought to balance Hebbian plasticity by modulating the activity of the synapse or the properties of ion channels. Homeostatic plasticity in neocortical circuits has been studied in depth by Gina G. Turrigiano and Sacha Nelson of Brandeis University, who first observed compensatory changes in excitatory postsynaptic currents (mEPSCs) after chronic activity manipulations.
Synaptic scaling has been proposed as a potential mechanism of homeostatic plasticity. Homeostatic plasticity can be used to describe a process that maintains the stability of neuronal functions through a coordinated plasticity among subcellular compartments, such as the synapses versus the neurons and the cell bodies versus the axons.
Homeostatic plasticity also maintains neuronal excitability in a real-time manner through the coordinated plasticity of threshold and refractory period at voltage-gated sodium channels.
The term homeostatic plasticity derives from two opposing concepts: 'homeostatic' (a product of the Greek words for 'same' and 'state' or 'condition') and plasticity (or 'change'), thus homeostatic plasticity means "staying the same through change".
Homeostatic plasticity is also very important in the context of central pattern generators. In this context, neuronal properties are modulated in response to environmental changes in order to maintain an appropriate neural output.


Coupon (finance)

A coupon payment on a bond is the annual interest payment that the bondholder receives from the bond's issue date until it matures.
Coupons are normally described in terms of the "coupon rate", which is calculated by adding the sum of coupons paid per year and dividing it by the bond's face value. For example, if a bond has a face value of $1,000 and a coupon rate of 5%, then it pays total coupons of $50 per year. Typically, this will consist of two semi-annual payments of $25 each.
History: bearer bonds.
The origin of the term "coupon" is that bonds were historically issued in the form of bearer certificates. Physical possession of the certificate was (deemed) proof of ownership. Several coupons, one for each scheduled interest payment, were printed on the certificate. At the date the coupon was due, the owner would detach the coupon and present it for payment (an act called "clipping the coupon").
The certificate often also contained a document called a "talon", which (when the original block of coupons had been used up) could be detached and presented in exchange for a block of further coupons.
Zero-coupon bonds and valuation.
Not all bonds have coupons. Zero-coupon bonds are those that pay no coupons and thus have a coupon rate of 0%. Such bonds make only one payment: the payment of the face value on the maturity date. Normally, to compensate the bondholder for the time value of money, the price of a zero-coupon bond will always be less than its face value on any date before the maturity date. During the European sovereign-debt crisis, some zero-coupon sovereign bonds traded above their face value as investors were willing to pay a premium for the perceived safe-haven status these investments hold. The difference between the price and the face value provides the bondholder with the positive return that makes purchasing the bond worthwhile.
Between a bond's issue date and its maturity date (also called its redemption date), the bond's price is determined by taking into account several factors, including:


Quantal neurotransmitter release

Neurotransmitters are released into a synapse in packaged vesicles called quanta. One quantum generates what is known as a miniature end plate potential (MEPP) which is the smallest amount of stimulation that one neuron can send to another neuron. Quantal release is the mechanism by which most traditional endogenous neurotransmitters are transmitted throughout the body. The aggregate sum of many MEPPs is known as an end plate potential (EPP). A normal end plate potential usually causes the postsynaptic neuron to reach its threshold of excitation and elicit an action potential. Electrical synapses do not use quantal neurotransmitter release and instead use gap junctions between neurons to send current flows between neurons. The goal of any synapse is to produce either an excitatory postsynaptic potential (EPSP) or an inhibitory postsynaptic potential (IPSP), which generate or repress the expression, respectively, of an action potential in the postsynaptic neuron. It is estimated that an action potential will trigger the release of approximately 20% of an axon terminal's neurotransmitter load.
Quantal neurotransmitter release mechanism.
Neurotransmitters are synthesized in the axon terminal where they are stored in vesicles. These neurotransmitter-filled vesicles are the quanta that will be released into the synapse. Quantal vesicles release their contents into the synapse by binding to the presynaptic membrane and combining their phospholipid bilayers. Individual quanta may randomly diffuse into the synapse and cause a subsequent MEPP. These spontaneous occurrences are completely random and are not the result of any kind of signaling pathway.
Calcium ion signaling to the axon terminal is the usual signal for presynaptic release of neurotransmitters. Calcium ion diffusion into the presynaptic membrane signals the axon terminal to release quanta to generate either an IPSP or EPSP in the postsynaptic membrane. Release of different neurotransmitters will lead to different postsynaptic potentials. Action potentials that transmit down to the axon terminal will depolarize the terminal's membrane and cause a conformational change in the membrane's calcium ion channels. These calcium channels will adopt an "open" configuration that will allow only calcium ions to enter the axon terminal. The influx of calcium ions will further depolarize the interior of the axon terminal and will signal the quanta in the axon terminal to bind to the presynaptic membrane. Once bound, the vesicles will fuse into the membrane and the neurotransmitters will be released into the membrane by exocytosis.
The exact mechanism of calcium ion signaling to the presynaptic membrane is unknown, but it has been well established that calcium ion influxes in the axon terminal are linked to neurotransmitter release. Current research suggests that neurotransmitter release into neuromuscular junctions is signaled using a hierarchy of calcium ion channels and receptors in the presynaptic membrane, with different channels and receptors showing varying degrees of excitability in the presynaptic membrane. The variety in calcium channels suggests that more efficient channels are utilized first and that differing use of calcium ion channels leads to differing levels of quantal release.
Once in the synapse, neurotransmitters will rapidly move across the synapse to attach themselves to receptors on the postsynaptic membrane. Neurotransmitter receptors will either signal postsynaptic channels to "open" or "close" which will affect the rates that ions are able to cross the synaptic membrane. The relative change in ion flow will polarize the membrane based on the properties of the affected ion channel. For example, opening a potassium ion channel in the presynaptic membrane will create a flow of positive potassium ions out of the neuron; loss of the positively charged potassium ions will cause the neuron to become more negatively charged. It is through the use of a variety of neurotransmitters and receptors that neurons are able to send a plethora of potential signals to each other. Estimations of quantal release time courses can be roughly estimated from the original quantal release events following presynaptic simulation. Such estimations cannot be reliably used in all synapses, but can be useful tools in developing the understanding of neurotransmitter release time courses in general.
Synaptic vesicle recycling.
As described above, the synaptic vesicle will remain fused to the presynaptic membrane after its neurotransmitter contents have been released into the synapse. The repeated additions to the axon terminal membrane would eventually result in the uncontrolled growth of the axon terminal, which could lead to disastrous breakdown of the synaptic complex. The axon terminal compensates for this problem by reuptaking the vesicle by endocytosis and reusing its components to form new synaptic vesicles. The exact mechanism and signaling cascade which triggers synaptic vesicle recycling is still unknown.
No one method of synaptic vesicle recycling seems to hold true in all scenarios, which suggests the existence of multiple pathways for synaptic vesicle recycling. Multiple proteins have been linked with synaptic vesicle reuptake and then subsequently been linked to different synaptic vesicle recycling pathways. Clathrin-mediated endocytosis (CME) and activity-dependent bulk endocytosis (ADBE) are the two most predominant forms of synaptic vesicle recycling, with ADBE being more active during periods of high neuronal activity and CME being active for long periods of time after neuronal activity has ceased.


Special visceral afferent fiber

A Special visceral afferent fibers (SVA) is a afferent fiber that develop in association with the gastrointestinal tract. They carry the special senses of smell (olfaction) and taste (gustation). The cranial nerves containing SVA fibers are the olfactory nerve (I), the facial nerve (VII), the glossopharyngeal nerve (IX), and the vagus nerve (X). The facial nerve receives taste from the anterior 2/3 of the tongue; the glossopharyngeal from the posterior 1/3, and the vagus nerve from the epiglottis. The sensory processes, using their primary cell bodies from the inferior ganglion, send projections to the medulla, from which they travel in the tractus solitarius, later terminating at the rostral nucleus solitarius.


Lesser occipital nerve

The lesser occipital nerve or small occipital nerve is a cutaneous spinal nerve arising between the first and second cervical vertebrae, along with the greater occipital nerve. It innervates the scalp in the lateral area of the head posterior to the ear.
Path.
The lesser occipital nerve is one of the four cutaneous branches of the cervical plexus. It arises from the lateral branch of the ventral ramus of the second cervical nerve, sometimes also from the third; it curves around and ascends along the posterior border of the Sternocleidomastoideus.
Near the cranium it perforates the deep fascia, and is continued upward along the side of the head behind the auricula, supplying the skin and communicating with the greater occipital, the great auricular, and the posterior auricular branch of the facial.
The smaller occipital varies in size, and is sometimes duplicated.
It gives off an auricular branch, which supplies the skin of the upper and back part of the auricula, communicating with the mastoid branch of the great auricular.
This branch is occasionally derived from the greater occipital nerve.
Clinical significance.
Disorder in this nerve causes occipital neuralgia.


Milos Novotny

Milos V. Novotny (born 1942) is an American chemist, currently the Distinguished Professor Emeritus and Director of the Novotny Glycoscience Laboratory and the Institute for Pheromone Research at Indiana University, and also a published author. Milos Novotny received his Bachelor of Science from the University of Brno, Czechoslovakia in 1962. In 1965, Novotny received his Ph.D. at the University of Brno. Novotny also holds honorary doctorates from Uppsala University, Masaryk University and Charles University, and he has been a major figure in analytical separation methods. Novotny was recognized for the development of PAGE Polyacrylamide Gel-filled Capillaries for Capillary Electrophoresis in 1993. In his years of work dedicated to analytical chemistry he has earned a reputation for being especially innovative in the field and has contributed a great deal to several analytical separation methods. Most notably, Milos has worked a great deal with microcolumn separation techniques of liquid chromatography, supercritical fluid chromatography, and capillary electrophoresis. Additionally, he is highly acclaimed for his research in proteomics and glycoanalysis and for identifying the first mammalian pheromones.
Awards.
In 1986, Novotny was given the Award in Chromatography from the American Chemical Society. Novotny received the ANACHEM award in 1992. This award is given to outstanding analytical chemists for teaching, research, administration or other activities which have advanced of the field.
Novotny was also selected as the LCGC Lifetime Achievement award recipient in 2019.
Awards received in the 1980s.
Chairman, Gordon Research Conference on Analytical Chemistry; James B. Himes Merit Award of the Chicago Chromatography Discussion Group; M.S. Tswett Award and Medal in Chromatography; American Chemical Society Award in Chromatography; ISCO Award in Biochemical Instrumentation; Eastern Analytical Symposium Award in Chromatography; Chemical Instrumentation Award of the American Chemical Society; Distinguished Faculty Research Lecture, Indiana University.
Awards received in the 1990s.
Keene P. Dimick Award in Chromatography, Third International Symposium on Supercritical Fluid Chromatography Award for Pioneering Work in the Development of SFC; Marcel J.E. Golay Award and Medal, International Symposium on Capillary Chromatography; American Chemical Society Award in Separation Science and Technology; American Chemical Society Exceptional Achievement Award as a Capillary Gas Chromatography Short Course Instructor; R&D 100 Award for technologically significant new product: -PAGE Polyacrylamide Gel-filled Capillaries for Capillary Electrophoresis”; Jan E. Purkynje Memorial Medal of the Czech Academy of Sciences; R&D Magazine Scientist of the Year Award; M.S. Tswett Memorial Medal of the Russian Academy of Sciences; A.J.P. Martin Gold Medal of the Chromatographic Society of Great Britain; Theophilus Redwood Award, The Royal Society of Chemistry, Great Britain; Distinguished Teaching and Mentoring Award of the University Graduate School, Indiana University; Elected as a Foreign Member of the Royal Society of Sciences (Sweden); College of Arts & Sciences Distinguished Faculty Award, Indiana University.
Awards received in the 2000s.
COLACRO (Congreso Latinoamericano de Cromatografia) Merit Medal; Pittsburgh Analytical Chemistry Award; Eastern Analytical Symposium Award for Outstanding Achievements in the Fields of Analytical Chemistry; Tracy M. Sonneborn Award for Outstanding Research and Teaching, Indiana University; Dal Nogare Award in Chromatography; CaSSS (California Separation Science Society) Award for Excellence in Separation Science; Honorary Member of the Slovak Pharmaceutical Society; Foreign Member of the Learned Society of the Czech Republic (Czech Academy of Sciences); American Chemical Society Award in Analytical Chemistry; Jan Weber Prize and Medal, Slovak Pharmaceutical Society, Slovakia; Ralph N. Adams Award in Bioanalytical Chemistry.
Awards received in the 2010s.
Honorary Membership of the Czech Society for Mass Spectrometry; Lifetime Achievement Award in Chromatography by the LC-GC Magazine, Europe; Giorgio Nota Award, Italian Chemical Society; Heyrovsky Medal in Chemical Sciences, Prague, Czech Republic.
Faculty Positions.
On the faculty of Indiana University, Bloomington, since 1971. 1978 – Professor of Chemistry. 1980 – Visiting Scientist, Department of Immunogenetics, Max Planck Institute for Biology, Tubingen, Germany. 1988 – James H. Rudy Professor of Chemistry. 1999 – Distinguished Professor of Chemistry. 1999 – Director of the Institute for Pheromone Research. 2000-2015 – Lilly Chemistry Alumni Chair. 2004 – Adjunct Professor of Medicine, Indiana University School of Medicine. 2004-2009 – Director of the National Center for Glycomics and Glycoproteomics. 2010 – Director of the Novotny Glycoscience Laboratory. 2011 – Distinguished Professor Emeritus of Chemistry.


Proxyfan

Proxyfan is a histamine H3 receptor ligand which is a "protean agonist", producing different effects ranging from full agonist, to antagonist, to inverse agonist in different tissues, depending on the level of constitutive activity of the histamine H3 receptor. This gives it a complex activity profile "in vivo" which has proven useful for scientific research.


Subiculum

The subiculum (Latin for "support") is the most inferior component of the hippocampal formation. It lies between the entorhinal cortex and the CA1 subfield of the hippocampus proper.
The subicular complex comprises a set of related structures including (as well as subiculum proper) prosubiculum, presubiculum, postsubiculum and parasubiculum.
Name.
The Subiculum got its name from Karl Friedrich Burdach in his three-volume work "Vom Bau und Leben des Gehirns" (Vol. 2, §199). He originally named it subiculum cornu ammonis and so associated it with the rest of the hippocampal subfields.
Structure.
It receives input from CA1 and entorhinal cortical layer III pyramidal neurons and is the main output of the hippocampus. The pyramidal neurons send projections to the nucleus accumbens, septal nuclei, prefrontal cortex, lateral hypothalamus, nucleus reuniens, mammillary nuclei, entorhinal cortex and amygdala.
The pyramidal neurons in the subiculum exhibit transitions between two modes of action potential output: bursting and single spiking. The transitions between these two modes is thought to be important for routing information out of the hippocampus.
Four component areas have been described: parasubiculum (adjacent to the parahippocampal gyrus), presubiculum, postsubiculum, and prosubiculum.
Parasubiculum.
The parasubiculum contains grid cells, which are neurons responsive to movements in particular directions over particular distances.
Presubiculum.
The presubiculum is part of the posterior cortex corresponding to Brodmann's area 27, and forms part of the cortical input to the entorhinal-hippocampal spatial/memory system.
Postsubiculum.
The dorsal part of the presubiculum is more commonly known as the postsubiculum and is of interest because it contains head direction cells, which are responsive to the facing direction of the head.
Prosubiculum.
Prosubiculum is a term often used in reference to monkey anatomy but rarely in rodents, referring to a region located between the CA1 region of the hippocampus and the subiculum, and distinguished by higher cell density and smaller cell sizes.
Function.
It is believed to play a role in some cases of human epilepsy.
It has also been implicated in working memory and drug addiction.
It has been suggested that the dorsal subiculum is involved in spatial relations, and the ventral subiculum regulates the hypothalamic-pituitary-adrenal axis.
Clinical significance.
Potential role in Alzheimer's disease.
Rat studies indicate that lesioning of the subiculum decreases the spread of amyloid-beta in rat models of Alzheimer's disease. Alzheimer's disease pathology is thought to have prion-like properties. The disease tends to spread in characteristic sequence from the entorhinal cortex through the subiculum.


Somatosensory disorder

A somatosensory disorder is an impairment of the somatosensory system.
Signs and symptoms.
People may experience numbness, prickling or tingling sensations (paresthesias), or the feeling a limb has "fallen asleep" (an indicator of nerve compression), burning, cutting or other sensations.
Seizures.
Certain types of seizures are associated with the somatosensory system. Cortical injury may lead to loss of thermal sensation or the ability to discriminate pain. An aura involving thermal and painful sensations is a phenomenon known to precede the onset of an epileptic seizure or focal seizure. Another type of seizure, called a sensory Jacksonian seizure involves an abnormal, localizable, cutaneous sensation but does not have apparent stimulus. This sensation may progress along a limb or to adjacent cutaneous body areas, reflecting abnormal neuronal firing in the postcentral gyrus where an epileptic discharge is propagated. These episodes in which patients are consciously aware during a seizure have been useful for identifying problems associated with the somatosensory cortex. Patients can describe the nature of the seizure and how they feel during it.
Mechanism.
The absence of proprioception or two-point tactile discrimination on one side of the body suggests injury to the contralateral side of the primary somatosensory cortex. However, depending on the extent of the injury, damage can range in loss of proprioception of an individual limb or the entire body. A deficit known as cortical astereognosis of the receptive type describes an inability to make use of tactile sensory information for identifying objects placed in the hand. For example, if this type of injury effects the hand region in the primary somatosensory cortex for one cerebral hemisphere, a patient with closed eyes cannot perceive the position of the fingers on the contralateral hand and will not be able to identify objects such as keys or a cell phone if they are placed into that hand.
Diagnosis.
Evaluation of any suspected disease of the somatosensory system is included in a neurological examination of the peripheral nervous system. Modern techniques for testing somatosensory function are still quite crude compared to testing motor function. Evaluation of somatosensory stimuli are limited by the patient's interpretation of sensation in response to testing.
Tactile sensation is tested with a cotton wisp or light touch with a finger. Pain is assessed by pinprick or pinwheel (Wartenberg wheel). A 128 Hz tuning fork is used for testing vibrations.


Lapisteride

Lapisteride (INN; CS-891) is a dual inhibitor of both isoforms of the enzyme 5α-reductase. It was under investigation for the treatment of benign prostatic hyperplasia (BPH) and androgenic alopecia, but was never marketed.


Sensory unit

A sensory unit is a single afferent neuron with all its receptor endings. It is the smallest unit of sensory response.


Ability to benefit

Ability to benefit (ATB) is a term used in the context of post-secondary education in the United States to refer to students who have sufficient competency to benefit from post-secondary education but do not have a high school diploma or the Certificate of High School Equivalency. ATB, as assessed by government-approved tests, or high school Ed plan with 504 (IEP) with at least 1 year overlapping S.E.L.P.A as long as the student has taken and passed 5 hours of college or honors credits while on higher education plans. This is required for receiving financial aid by most US public colleges that admit students without a high school diploma or the certificate of equivalency. Until July 2012, such students could also receive student loans and grants from the US government if they had passed an approved ATB examination. However, the provision was dropped as part of the cuts to the Federal budget for fiscal year 2012.
In some US states such as California, even when such students are not requesting financial aid, private post-secondary institutions are "required, prior to executing an enrollment agreement with an ATB student, to have the student take and pass an independently administered examination from the list of examinations prescribed by the United States Department of Education" or have passed the 5 post Ed credits listed above.
According to "Inside Higher Ed", in 2012 about 82,000 students at US public two-year colleges had been admitted under ATB (approximately 1% of the total community college population) although not all of them were receiving financial aid. A longitudinal study from the National Center for Education Statistics found that only 33% of students admitted under ATB in 2003 had earned a college credential by 2009. Evidence also suggested that they were more likely to default on student loans.
The US Government Accountability Office expressed concern, in 2009, that some for-profit colleges were helping students to cheat on the ATB examination or were falsifying the results in order for their students to receive Federal financial aid. Students who had received a Federal direct loan or a Federal Family Education Loan via ATB prior to 2012 can apply to have the loan forgiven or discharged if they can demonstrate that their school falsely certified their ability to benefit from its training.


Ganglion cell

A ganglion cell is a cell found in a ganglion. Examples of ganglion cells include:


Two-point discrimination

Two-point discrimination (2PD) is the ability to discern that two nearby objects touching the skin are truly two distinct points, not one. It is often tested with two sharp points during a neurological examination and is assumed to reflect how finely innervated an area of skin is.
In clinical settings, two-point discrimination is a widely used technique for assessing tactile perception. It relies on the ability and/or willingness of the patient to subjectively report what they are feeling and should be completed with the patient’s eyes closed. The therapist may use calipers or simply a reshaped paperclip to do the testing. The therapist may alternate randomly between touching the patient with one point or with two points on the area being tested (e.g. finger, arm, leg, toe). The patient is asked to report whether one or two points was felt. The smallest distance between two points that still results in the perception of two distinct stimuli is recorded as the patient's two-point threshold. Performance on the two extremities can be compared for discrepancies. Although the test is still commonly used clinically, it has been roundly criticized by many researchers as providing an invalid measure of tactile spatial acuity, and several highly regarded alternative tests have been proposed to replace it.
Normal and impaired performance.
Body areas differ both in tactile receptor density and somatosensory cortical representation. Normally, a person should be able to recognize two points separated by 2 to 8 mm on fingertips. On the lips, it is 2 to 4 mm, and on the palms, it is 8 to 12 mm and 30–40 mm on the shins or back (assuming the points are at the same dermatome). The posterior column-medial lemniscus pathway is responsible for carrying information involving fine, discriminative touch. Therefore, two-point discrimination can be impaired by damage to this pathway or to a peripheral nerve.
Criticisms.
Although two-point testing is commonly used clinically, evidence accumulated from many research studies indicates that 2PD is a flawed measure of tactile spatial acuity. Research studies have shown that the two-point test may have low sensitivity, failing to detect or underestimating sensory deficits, that it only poorly tracks recovery of function following nerve injury and repair, that it has poor test-retest reliability, and that it fails to correlate with validated measures of tactile spatial acuity such as grating orientation discrimination. Two-point testing has been criticized for yielding highly variable performance both across and within participants, for being reliant on the subjective criterion adopted by the participant for reporting "one" compared to "two," and for resulting in performance that is "too good to be true," as the measured two-point threshold can fall — unrealistically — well below the skin's receptor spacing.
Why is 2PD unreliable as a measure of tactile spatial acuity? It has long been recognized that, if not pressed precisely simultaneously, two points may evoke temporally distinguishable neural activations; two points may be distinguished from one, then, not because two points are perceived spatially, but because two contacts are perceived temporally. Furthermore, neurophysiological recordings have shown that two points evoke a different number of action potentials in the receptor population than one point does; two points may be distinguished from one, then, not because two points are actually perceived, but merely because the two-point configuration produces a different overall response magnitude. In summary, the two-point task can present both a non-spatial temporal cue and a non-spatial magnitude cue. To an observant participant, these unintended non-spatial cues could signal the presence of two points compared to one, even when the points are placed closer together than the participant's spatial resolution.
On the basis of these observations, several researchers have strongly warned against the use of the 2PD task. Pointing to “the enormous and implausible variability in reported 2PD levels after nerve repair,” the authors of one article “conclude that ... 2PD ... as the sole test for tactile gnosis recovery should be seriously questioned.” Comparing 2PD thresholds to functional recovery in patients following nerve repair, another author states "The conclusion to be drawn from this data is that 2 P.D. is not a valid index of the sensory capacity underlying integrated hand function." The author of a book on nerve repair concludes that 2PD is a “convenient but critically flawed procedure” that “presents nonspatial cues that can be learned to improve performance without physiologic change”. The authors of an article tersely entitled "The two-point threshold: Not a measure of tactile spatial resolution" recommend alternative tests to supplant the 2PD test. The authors of yet another research article concur and strongly recommend “that clinicians and researchers simply set aside the 2PD task and replace it with one that ensures a more purely spatial measure of acuity".
Alternative tests.
Several highly regarded tactile tests have been developed as rigorous replacements to the 2PD test. In psychophysics research laboratories, a favored test of tactile spatial acuity has for many years been the grating orientation task (GOT). In the GOT, the participant attempts to discern the orientation of parallel grooves pressed either along or across the fingertip. The GOT threshold is the groove width at which the participant performs with some specified level of accuracy (e.g., 75% correct). The GOT is considered to yield a valid measure of tactile spatial acuity and has been used in many research studies, with both manual and automated stimulus delivery protocols. For example, the GOT has been used to map spatial acuity on different body areas, to characterize how tactile spatial acuity is affected by age, sex, skin characteristics, and blindness, and to track the changes in tactile spatial acuity that occur during perceptual learning and recovery from nerve injury.
Although it is very popular in tactile research labs, the GOT is admittedly less practical for clinical use, as it requires specialized pre-constructed stimulus objects, which span a fixed spatial range, rather than a single continuously adjustable calipers. The comparative simplicity and flexibility of the 2PD test have encouraged the continuation of its use by clinicians, despite the test's acknowledged flaws. To remedy this situation, two-point orientation discrimination (2POD) has been proposed as a test that combines the convenience of 2PD with the validity of the GOT. In the 2POD task, the patient attempts to discern the orientation (e.g., along or across the finger) created by two sharp points of contact on the skin; the 2POD threshold is the distance between the points at which the participant performs with some specified level of accuracy (e.g., 75% correct).
As explained above, the validity of the 2PD task has been called into question because it allows the participant to rely on non-spatial cues. By contrast, the GOT and 2POD tasks are considered to yield valid measures of tactile spatial acuity, because in order to perform these tasks, the participant must discern the spatial modulation of the neural discharge of underlying skin receptors and cannot rely on non-spatial cues. The following figure, from a study that evaluated both 2PD and 2POD on the fingertip, finger base, palm and forearm, demonstrates that 2PD is contaminated by non-spatial cues, whereas 2POD provides an uncontaminated measure of tactile spatial acuity.


Cross modal plasticity

Cross modal plasticity is the adaptive reorganization of neurons to integrate the function of two or more sensory systems. Cross modal plasticity is a type of neuroplasticity and often occurs after sensory deprivation due to disease or brain damage. The reorganization of the neural network is greatest following long-term sensory deprivation, such as congenital blindness or pre-lingual deafness. In these instances, cross modal plasticity can strengthen other sensory systems to compensate for the lack of vision or hearing. This strengthening is due to new connections that are formed to brain cortices that no longer receive sensory input.
Plasticity in the blind.
Even though the blind are no longer able to see, the visual cortex is still in active use, although it deals with information different from visual input. Studies found that the volume of white matter (myelinated nerve connections) was reduced in the optic tract, but not in the primary visual cortex itself. However, grey matter volume was reduced by up to 25% in the primary visual cortex. The atrophy of grey matter, the neuron bodies, is likely due to its association with the optic tract. Because the eyes no longer receive visual information, the disuse of the connected optic tract causes a loss of grey matter volume in the primary visual cortex. White matter is thought to atrophy in the same way, although the primary visual cortex is less affected.
For example, blind individuals show enhanced perceptual and attentional sensitivity for identification of different auditory stimuli, including speech sounds. The spatial detection of sound can be interrupted in the early blind by inducing a virtual lesion in the visual cortex using transcranial magnetic stimulation.
The somatosensory cortex is also able to recruit the visual cortex to assist with tactile sensation. Cross modal plasticity reworks the network structure of the brain, leading to increased connections between the somatosensory and visual cortices. Furthermore, the somatosensory cortex acts as a hub region of nerve connections in the brain for the early blind but not for the sighted. With this cross-modal networking the early blind are able to react to tactile stimuli with greater speed and accuracy, as they have more neural pathways to work with. One element of the visual system that the somatosensory cortex is able to recruit is the dorsal-visual stream. The dorsal stream is used by the sighted to identify spatial information visually, but the early blind use it during tactile sensation of 3D objects. However, both sighted and blind participants used the dorsal stream to process spatial information, suggesting that cross modal plasticity in the blind re-routed the dorsal visual stream to work with the sense of touch rather than changing the overall function of the stream.
Experience dependence.
There is evidence that the degree of cross modal plasticity between the somatosensory and visual cortices is experience-dependent. In a study using tactile tongue devices to transmit spatial information, early blind individuals were able to show visual cortex activations after 1 week of training with the device. Although there were no cross modal connections at the start, the early blind were able to develop connections between the somatosensory and visual cortices while sighted controls were unable to. Early or congenitally blind individuals have stronger cross modal connections the earlier they began learning Braille. An earlier start allows for stronger connections to form as early blind children have to grow up using their sense of touch to read instead of using their sight. Perhaps due to these cross modal connections, sensory testing studies have shown that people who are born blind and read braille proficiently perceive through touch more rapidly than others. Furthermore, tactile spatial acuity is enhanced in blindness and this enhancement is experience-dependent.
Plasticity in the deaf.
Cross modal plasticity can also occur in pre-lingual deaf individuals. A functional magnetic resonance imaging (fMRI) study found that deaf participants use the primary auditory cortex as well as the visual cortex when they observe sign language. Although the auditory cortex no longer receives input from the ears, the deaf can still use specific regions of the cortex to process visual stimuli. Primary sensory abilities like brightness discrimination, visual contrast sensitivity, temporal discrimination thresholds, temporal resolution, and discrimination thresholds for motion directions do not appear to change in the loss of a modality like hearing. However, higher-level processing tasks may undergo compensating changes. In the case of auditory deprivation, some of these compensations appear to affect visual periphery processing and movement detection in peripheral vision.
Deaf individuals lack auditory input, so the auditory cortex is instead used to assist with visual and language processing. Auditory activations also appear to be attention-dependent in the deaf. However, the process of visual attention in the deaf is not significantly different from that of hearing subjects. Stronger activations of the auditory cortex during visual observation occur when deaf individuals pay attention to a visual cue, and the activations are weaker if the cue is not in the direct line of sight. One study found that deaf participants process peripheral visual stimuli more quickly than hearing subjects. Deafness appears to heighten spatial attention to the peripheral visual field, but not the central one. The brain thus seems to compensate for the auditory loss within its visual system by enhancing peripheral field attention resources; however, central visual resources may suffer.
Improvements tend to be limited to areas in the brain dedicated to both auditory and visual stimuli, not simply rewriting audio-dedicated areas into visual areas. The visual enhancements seem to be especially focused in areas of the brain that normally process convergence with auditory input. This is specifically seen in studies showing changes in the posterior parietal cortex of deaf individuals, which is both one of the main centers for visual attention but also an area known for integrating information from various senses.
Recent research indicates that in attention-based tasks such as object tracking and enumeration, deaf subjects perform no better than hearing subjects. Improvement in visual processing is still observed, even when a deaf subject is not paying attention to the direct stimulus. A study published in 2011 found that congenitally deaf subjects had significantly larger neuroretinal rim areas than hearing subjects, which suggests that deaf subjects may have a greater concentration of retinal ganglion cells.
Sign language.
Deaf individuals often use sign language as their mode of communication. However, sign language alone does not appear to significantly change brain organization. In fact, neuroimaging and electrophysiology data studying functional changes in visual pathways, as well as animal studies of sensory deprivation, have shown that the enhancement in attention of peripheral visual processing found in deaf individuals is not found in hearing signers.
The peripheral visual changes are seen in all forms of deaf individuals – signers, oral communicators, etc. Comparative fMRIs of hearing speakers and hearing early signers, on the other hand, show comparable peripheral activation. The enhancement in attention of peripheral visual processing found in deaf individuals has not been found in hearing signers. It is therefore unlikely that signing causes the neurological differences in visual attention.
Cochlear implants.
Another way to see cross modal plasticity in the deaf is when looking at the effects of installing cochlear implants. For those who became deaf pre-lingually, cross modal plasticity interfered with their ability to process language using a cochlear implant. For the pre-lingual deaf, the auditory cortex has been reshaped to deal with visual information, so it cannot deal as well with the new sensory input that the implant provides. However, for post-lingual deaf their experience with visual cues like lip reading can help them understand speech better along with the assistance of a cochlear implant. The post-lingual deaf do not have as much recruitment of the auditory cortex as the early deaf, so they perform better with cochlear implants. It was also found that the visual cortex was activated only when the sounds that were received had potential meaning. For instance, the visual cortex activated for words but not for vowels. This activation is further evidence that cross modal plasticity is attention dependent.
Plasticity after olfactory deficit or whisker trimming.
Cross-modal plasticity can be mutually induced between two sensory modalities. For instance, the deprivation of olfactory function upregulate whisker tactile sensation, and on the other hand, the trimming of whiskers upregulates olfactory function. In terms of cellular mechanisms, the coordinated plasticity between cortical excitatory and inhibitory neurons is associated with these upregulations of sensory behaviors.


Fascia dentata

The fascia dentata is the earliest stage of the hippocampal circuit. Its primary input is the perforant path from the superficial layers of entorhinal cortex. Its principal neurons are tiny granule cells which give rise to unmyelinated axons called the mossy fibers which project to the hilus and CA3. The fascia dentata of the rat contains approximately 1,000,000 granule cells. It receives feedback connections from mossy cells in the hilus at distant levels in the septal and temporal directions. The fascia dentata and the hilus together make up the dentate gyrus. As with all regions of the hippocampus, the dentate gyrus also receives GABAergic and cholinergic input from the medial septum and the diagonal band of Broca.


Modularity (biology)

Modularity refers to the ability of a system to organize discrete, individual units that can overall increase the efficiency of network activity and, in a biological sense, facilitates selective forces upon the network. Modularity is observed in all model systems, and can be studied at nearly every scale of biological organization, from molecular interactions all the way up to the whole organism.
Evolution of Modularity.
The exact evolutionary origins of biological modularity has been debated since the 1990s. In the mid 1990s, Günter Wagner argued that modularity could have arisen and been maintained through the interaction of four evolutionary modes of action:
[1] Selection for the rate of adaptation: If different complexes evolve at different rates, then those evolving more quickly reach fixation in a population faster than other complexes. Thus, common evolutionary rates could be forcing the genes for certain proteins to evolve together while preventing other genes from being co-opted unless there is a shift in evolutionary rate.
[2] Constructional selection: When a gene exists in many duplicated copies, it may be maintained because of the many connections it has (also termed pleiotropy). There is evidence that this is so following whole genome duplication, or duplication at a single locus. However, the direct relationship that duplication processes have with modularity has yet to be directly examined.
[3] Stabilizing selection: While seeming antithetical to forming novel modules, Wagner maintains that it is important to consider the effects of stabilizing selection as it may be "an important counter force against the evolution of modularity". Stabilizing selection, if ubiquitously spread across the network, could then be a "wall" that makes the formation of novel interactions more difficult and maintains previously established interactions. Against such strong positive selection, other evolutionary forces acting on the network must exist, with gaps of relaxed selection, to allow focused reorganization to occur.
[4] Compounded effect of stabilizing and directional selection: This is the explanation seemingly favored by Wagner and his contemporaries as it provides a model through which modularity is constricted, but still able to unidirectionally explore different evolutionary outcomes. The semi-antagonistic relationship is best illustrated using the corridor model, whereby stabilizing selection forms barriers in "phenotype space" that only allow the system to move towards the "optimum" along a single path. This allows directional selection to act and inch the system closer to optimum through this evolutionary corridor.
For over a decade, researchers examined the dynamics of selection on network modularity. However, in 2013 Clune and colleagues challenged the sole focus on selective forces, and instead provided evidence that there are inherent "connectivity costs" that limit the number of connections between nodes to maximize efficiency of transmission. This hypothesis originated from neurological studies that found that there is an inverse relationship between the number of neural connections and the overall efficiency (more connections seemed to limit the overall performance speed/precision of the network). This connectivity cost had yet to be applied to evolutionary analyses. Clune et al. created a series of models that compared the efficiency of various "evolved" network topologies in an environment where performance, their only metric for selection, was taken into account, and another treatment where performance as well as the connectivity cost were factored together. The results show not only that modularity formed ubiquitously in the models that factored in connection cost, but that these models also outperformed the performance-only based counterparts in every task. This suggests a potential model for module evolution whereby modules form from a system’s tendency to resist maximizing connections to create more efficient and compartmentalized network topologies.


Neurosphere

A neurosphere is a culture system composed of free-floating clusters of neural stem cells. Neurospheres provide a method to investigate neural precursor cells "in vitro". Putative neural stem cells are suspended in a medium lacking adherent substrates but containing necessary growth factors, such as epidermal growth factor and fibroblast growth factor. This allows the neural stem cells to form into the characteristic 3-D clusters. However, neurospheres are not identical to stem cells; rather, they only contain a small percent of neural stem cells.
The predominant use of the neurosphere is in the neurosphere assay. However, in vitro and in vivo environments have shown to have different inductive effects on precursor cells. The creation of the neurosphere assay is highly sensitive; it is still unclear as to the exact differing effects that environment produces, relative to the "in vivo" environment.
History.
Reynolds and Weiss first described the neurosphere method of investigating neural precursor cells in 1992. The method was continued through the work of Angelo Viscovi and Derek van der Kooy and colleagues.
Reynolds and Weiss.
In 1992, Brent A. Reynolds and Samuel Weiss attempted to isolate EGF-responsive cells from an adult mouse central nervous system (CNS). They dissociated the striata of 3 to 18-month old mice via enzymes and plated them in a serum-free culture containing 20 ng of EGF per milliliter. After two days in vitro, most of the cells had died, but 15±2 cells for each plate were undergoing cell division. This continued for two to three days, after which the proliferating clusters of cells detached and formed a sphere of proliferating cells. After this discovery of a spherical formation of cells, the two assessed the antigenic properties of the cells within these spheres. They found that cells in the spheres were nearly all immunoreactive for nestin, an intermediate filament found in neuroepithelial stem cells. The cells were not immunoreactive for neurofilament, neuron-specific enolase (NSE), and glial fibrillary acidic protein (GFAP). After more proliferation and longer days in vitro in the presence of EGF, cells eventually became immunoreactive to neurofilament, NSE, and GFAP. The cells that had this immunoreactivity were then tested for CNS neurotransmitters with indirect immunocytochemistry. Reynolds and Weiss found that, at 21 days, in vitro cultures of spheres and associated cells contained two of the major neurotransmitters of the adult striatum. These spheres of cells that Reynolds and Weiss discovered in 1992 were the first neurosphere formations created and analyzed.
Neurosphere (Stemness) Assay.
The neurosphere assay examines three fundamental characteristics of neural stem cells: proliferation, self-renewal, and multipotency. Self-renewal and multipotency are the requirements for cells to be considered stem cells. The neurosphere assay, or stemness assay, has been used to confirm that neurospheres contain neural stem cells. Neurospheres are dissociated and distributed into single-cell wells to examine self-renewal through clonal analysis. A small percentage of cells reform into a secondary neurosphere. The secondary neurospheres are then transferred into a culture medium containing growth factors that promote cell differentiation. The presence of varying cell types, including neurons, astrocytes, and oligodendrocytes, confirms the multipotency of these precursor cells. The evidence of self-renewal and multipotency serves to confirm the presence of neural stem cells within neurospheres, and emphasizes that neural stem cells comprise only a fraction of the neurosphere.
Clinical Applications.
Since the neurosphere assay's goal is to develop neural stem cells in vitro, the clinical applications of such an achievement can be highly beneficial. Neural stem cells that are transplanted are able to cross the blood–brain barrier and integrate themselves into the host's brain without disrupting normal function. This therapeutic application of neural stem cells derived from neurospheres is still in its infancy with respect to efficacy, but it has a high potential for success in treating many diseases.
Another aspect of clinical applications regarding neural stem cells is versatility. There have been neural stem cell transplants into various tissues with a successful differentiation and proliferation in these tissues. This broader differentiation "spectrum" would be highly exploitable in a clinical setting.
Neurospheres have also been used for peripheral nerve regeneration
Auditory Restoration.
Researchers are exploring the use of neural stem cells (NSCs) obtained from neurospheres to aid in the regrowth of inner ear neurons and hair cells. Hu et al. transplanted adult mice NSCs into normal and deafened inner ears of guinea pigs. Prior to implantation, the NSCs were treated with neurogenin 2 protein to encourage proliferation of the intended inner ear cells. They concluded that adult NSCs were indeed able to survive and differentiate in the injured inner ear, and that this type of therapy could possibly act to restore auditory function in hearing impaired subjects. This experiment also indicates that genetic engineering can contribute to the success of generating specific progenitor cells of interest.
Limitations.
However useful the neurosphere culture has been for biological studies of developmental processes and the functional assay for testing neuronal characteristics, there are several limitations to the method.
First, the neurosphere culture formation is highly sensitive to the procedure, as the creation is contingent on the system used to create the culture. Variation in cell density, different constituents or concentrations of factors in the media and method, method and frequency of passaging, and whether the neurosphere is dissociated before differentiation can lead to differences in both the composition of cell types and properties within each neurosphere. This poses a problem for consolidating and interpreting data, even within the same study.
Another problem with the system arises from the nature of suspension cultures (in vitro) : individual cells cannot easily be carefully monitored. Since the neuronic capacity of the neurosphere-expanded cells diminishes after an extended number of passages, the lack of monitoring adds further complexity to the neurosphere method.
Finally, only a small percentage of cells within each heterogeneous sphere have the potential to form neurospheres, and even fewer cells actually fulfill the criteria for being neural stem cells. Neurospheres each contain cells at multiple stages of differentiation, including stem cells, proliferating neural progenitor cells, postmitotic neurons, and glia. Moreover, the heterogeneity of the neurosphere increases with its size, since more and varied cell types arise with a longer time in culture.


Useful field of view

In human vision, the useful field of view (or UFOV) is the visual area from which one can briefly extract information without eye or head movements. UFOV size generally decreases with age, most likely due to decreases in visual processing speed, reduced attentional resources, and reduced ability to ignore distracting information. UFOV performance is correlated with a number of important real-world issues including risk of an automobile crash. Performance can be improved by computer-based training.
History.
UFOV assessment and training programs were primarily developed by Karlene Ball of the University of Alabama at Birmingham, and Daniel Roenker of Western Kentucky University. The first versions of the assessment and training programs were produced more than 20 years ago at Northwestern University by Robert Sekuler and Karlene Ball. These programs were originally made available through Visual Awareness Inc.
UFOV assessment.
The traditional UFOV assessment is a computer-based visual test containing three subtests.
1. Processing Speed: Determines a person's threshold for discriminating stimuli presented in central vision.
2. Divided Attention: Same as Subtest 1 but with the addition of a concurrent peripheral target location task.
3. Selective Attention: Same as Subtest 2 but with the addition of distracters.
The threshold scores are combined to produce an overall performance score.
Impact of UFOV.
Performance on the UFOV assessment is correlated with several real-world functions:
UFOV training.
UFOV performance can be improved by computer-based training. Multiple studies have shown that improved UFOV performance generalizes to several real-world functions. UFOV training has been shown to:
Note: UFOV is not the same as a visual field or perimetry test that examines the ability of the visual system to processes light falling on various regions of the retina. Perimetry tests check for the integrity of the visual system while UFOV tests a person's ability to pay attention to the information in the visual field particularly when under situations of increased attentional demand.


Normosmia

Normosmia is the normal sensitivity of stimulus within the olfactory system. It contrasts with the various olfactory disorders, like anosmia, hyposmia, and dysosmia.


MCD peptide

Mast cell degranulating (MCD) peptide is a cationic 22-amino acid residue peptide, which is a component of the venom of the bumblebee ("Megabombus pennsylvanicus"). At low concentrations, MCD peptide can stimulate mast cell degranulation. At higher concentrations, it has anti-inflammatory properties. In addition, it is a potent blocker of voltage-sensitive potassium channels.
Sources.
MCD peptide is a component of bumblebee ("Megabombus pennsylvanicus") venom. In addition to MCD peptide, melittin and apamin have also been identified in this venom and are also described as voltage-dependent channel blockers. MCD peptide is also present in the venom of the honey bee "Apis mellifera".
Chemistry.
MCD peptide is a cationic 22-amino acid residue peptide with two disulfide bridges. Although the MCD peptide sequence shows similarity with apamin, they have different toxic properties. MCD peptide belongs to a large family composed of numerous derivatives detecting specific targets and displaying different toxic effects.
Targets.
MCD peptide has immunotoxic as well as neurotoxic properties due to different active sites of the MCD peptide. The MCD peptide has an immunotoxic effect on mast cells by releasing histamine from these cells. MCD peptide has also been described as a potent modulator of voltage-gated ionic channels. It binds to several subclasses of voltage-gated potassium channels (Kv channels), including Kv1.1, Kv1.6, and less potently to Kv1.2. Accordingly, MCD peptide can act in various regions of rat brain, including cerebellum, brainstem, hypothalamus, striatum, midbrain, cortex, and hippocampus. However, MCD peptide shows no binding activity in the peripheral neuronal system.
Mode of action.
For its immunotoxic properties, a low concentration of MCD peptide can cause mast cell degranulation by releasing histamine; at higher concentrations it displays anti-inflammatory activities.
Through its effect on ionic channels, MCD peptide can induce long term potentiation (LTP) in CA1 region of hippocampus. It binds and inactivates voltage-dependent K+ channels, including fast-inactivating (A-type) and slow-inactivating (delayed rectifier) K+ channels. The binding site of the MCD peptide on the K+ ion channel protein complex is a multimeric protein, consisting of polypeptide chains of molecular weight between 76,000-80,000 and 38,000 Daltons. By blocking potassium channels, the MCD peptide can increase the duration of action potentials and increase neuronal excitability.
Toxicity.
The neurotoxicity of MCD peptide is distincted from its histamine releasing function. The histamine releasing function of MCD peptide, at low concentrations, causes the degranulation of mast cell
, and shows anti-inflammatory activity at higher concentrations. These actions of MCD peptide on mast cells is thought to be involved in allergic and inflammatory processes related to type I hypersensitivity reaction.
MCD peptide shows neurotoxicity by inducing epileptiform seizures in rat, when intraventricularly injected. This toxicity is caused by the blockage of voltage-gated potassium channels by the MCD peptide. However, there is no toxicity of MCD administered peripherally, even at high doses.
Therapeutic use.
As a mast cell activator, the MCD peptide evokes large increases in antigen-specific serum immunoglobulin G (IgG) responses. Therefore, it is used as a vaccine adjuvant. MCD peptide analogs, such as [Ala12] MCD, provide a base for designing agents that can prevent IgE/Fc-RIa interactions and reduce allergic conditions.


Krasnodon

Krasnodon (Ukrainian, Russian: Краснодон) is a city in Luhansk Oblast (region) of eastern Ukraine. It is incorporated as a city of oblast significance and serves as the administrative center of Krasnodon Raion (district), though it does not belong to the raion. Its population is approximately .
Population of Krasnodon in 1972 was 70,400, in 1989 it was around 53,000, in 2001 it was 49,921.
In 2016 the city was renamed Sorokyne (; ) as part of decommunization in Ukraine. The city's name change process has been temporarily suspended as it is not controlled by the government of Ukraine.
History.
Krasnodon was established in 1914 along the banks of the Velyka Kamyanka, a tributary of the Seversky Donets River, as the settlement of Sorokino. It soon became one of the centers of the coal mining industry of the Donbass region. By the "Decision of the Presidium of the Supreme Soviet of the USSR", on 28 October 1938 it was renamed to "Krasnodon".
A local newspaper is published in the city since September 1930.
During the German-Soviet War, Krasnodon was occupied by Nazi Germany from July 20, 1942 to February 14, 1943. The Soviet Komsomol organization resistance Young Guard operated in the city from October 1942 to January 1943, when most of its members were arrested and executed. The "Young Guard" are commemorated with monuments and a memorial complex in Krasnodon.
Since 2014, Krasnodon has been controlled by the Luhansk People's Republic and not the Ukrainian authorities.
Demographics.
As of the Ukrainian Census of 2001: