Phrenic plexus

The phrenic plexus accompanies the inferior phrenic artery to the diaphragm, some filaments passing to the suprarenal gland.
It arises from the upper part of the celiac ganglion, and is larger on the right than on the left side.
It receives one or two branches from the phrenic nerve.
At the point of junction of the right phrenic plexus with the phrenic nerve is a small ganglion ("ganglion phrenicum").
This plexus distributes branches to the inferior vena cava, and to the suprarenal and hepatic plexuses.


Motor unit

A motor unit is made up of a motor neuron and the skeletal muscle fibers innervated by that motor neuron's axonal terminals. Groups of motor units often work together to coordinate the contractions of a single muscle; all of the motor units within a muscle are considered a motor pool. The concept was proposed by Charles Scott Sherrington.
All muscle fibers in a motor unit are of the same fiber type. When a motor unit is activated, all of its fibers contract. In vertebrates, the force of a muscle contraction is controlled by the number of activated motor units.
The number of muscle fibers within each unit can vary within a particular muscle and even more from muscle to muscle; the muscles that act on the largest body masses have motor units that contain more muscle fibers, whereas smaller muscles contain fewer muscle fibers in each motor unit. For instance, thigh muscles can have a thousand fibers in each unit, while extraocular muscles might have ten. Muscles which possess more motor units (and thus have greater individual motor neuron innervation) are able to control force output more finely.
Motor units are organized slightly differently in invertebrates; each muscle has few motor units (typically less than 10), and each muscle fiber is innervated by multiple neurons, including excitatory and inhibitory neurons. Thus, while in vertebrates the force of contraction of muscles is regulated by how many motor units are activated, in invertebrates it is controlled by regulating the balance between excitatory and inhibitory signals.
Recruitment.
The central nervous system is responsible for the orderly recruitment of motor neurons, beginning with the smallest motor units. Henneman's size principle indicates that motor units are recruited from smallest to largest based on the size of the load. For smaller loads requiring less force, slow twitch, low-force, fatigue-resistant muscle fibers are activated prior to the recruitment of the fast twitch, high-force, less fatigue-resistant muscle fibers. Larger motor units are typically composed of faster muscle fibers that generate higher forces.
The central nervous system has two distinct ways of controlling the force produced by a muscle through motor unit recruitment: spatial recruitment and temporal recruitment. Spatial recruitment is the activation of more motor units to produce a greater force. Larger motor units contract along with small motor units until all muscle fibers in a single muscle are activated, thus producing the maximum muscle force. Temporal motor unit recruitment, or rate coding, deals with the frequency of activation of muscle fiber contractions. Consecutive stimulation on the motor unit fibers from the alpha motor neuron causes the muscle to twitch more frequently until the twitches "fuse" temporally. This produces a greater force than singular contractions by decreasing the interval between stimulations to produce a larger force with the same number of motor units.
Using electromyography (EMG), the neural strategies of muscle activation can be measured. Ramp-force threshold refers to an index of motor neuron size in order to test the size principle. This is tested by determining the recruitment threshold of a motor unit during isometric contraction in which the force is gradually increased. Motor units recruited at low force (low-threshold units) tend to be small motor units, while high-threshold units are recruited when higher forces are needed and involve larger motor neurons. These tend to have shorter contraction times than the smaller units. The number of additional motor units recruited during a given increment of force declines sharply at high levels of voluntary force. This suggests that, even though high threshold units generate more tension, the contribution of recruitment to increase voluntary force declines at higher force levels.
To test motor unit stimulation, electrodes are placed extracellularly on the skin and an intramuscular stimulation is applied. After the motor unit is stimulated, its pulse is then recorded by the electrode and displayed as an action potential, known as a motor unit action potential (MUAP). When multiple MUAP’s are recorded within a short time interval, a motor unit action potential train (MUAPT) is then noted. The time in between these pulses is known as the inter-pulse interval (IPI). In medical electrodiagnostic testing for a patient with weakness, careful analysis of the MUAP size, shape, and recruitment pattern can help in distinguishing a myopathy from a neuropathy.
Motor unit types.
Motor units are generally categorized based upon the similarities between several factors:
The typing of motor units has thus gone through many stages and reached a point where it is recognized that muscle fibers contain varying mixtures of several myosin types that can not easily be classified into specific groups of fibers. The three (or four) classical fiber types represent peaks in the distribution of muscle fiber properties, each determined by the overall biochemistry of the fibers.
Estimates of innervation ratios of motor units in human muscles:


Muscle spindle

Muscle spindles are stretch receptors within the body of a skeletal muscle that primarily detect changes in the length of the muscle. They convey length information to the central nervous system via afferent nerve fibers. This information can be processed by the brain as proprioception. The responses of muscle spindles to changes in length also play an important role in regulating the contraction of muscles, for example, by activating motor neurons via the stretch reflex to resist muscle stretch.
The muscle spindle has both sensory and motor components.
Structure.
Muscle spindles are found within the belly of a skeletal muscle. Muscle spindles are fusiform (spindle-shaped), and the specialized fibers that make up the muscle spindle are called intrafusal muscle fibers. The regular muscle fibers outside of the spindle are called extrafusal muscle fibers. Muscle spindles have a capsule of connective tissue, and run parallel to the extrafusal muscle fibers.
Composition.
Muscle spindles are composed of 5-14 muscle fibers, of which there are three types: dynamic nuclear bag fibers (bag1 fibers), static nuclear bag fibers (bag2 fibers), and nuclear chain fibers.
Primary type Ia sensory fibers (large diameter) spiral around all intrafusal muscle fibres, ending near the middle of each fibre.
Secondary type II sensory fibers (medium diameter) end adjacent to the central regions of the static bag and chain fibres.
These fibres send information by stretch-sensitive mechanically-gated ion-channels of the axons.
The motor part of the spindle is provided by motor neurons: up to a dozen gamma motor neurons also known as "fusimotor neurons". These activate the muscle fibres within the spindle. Gamma motor neurons supply only muscle fibres within the spindle, whereas beta motor neurons supply muscle fibres both within and outside of the spindle. Activation of the neurons causes a contraction and stiffening of the end parts of the muscle spindle muscle fibers.
Fusimotor neurons are classified as static or dynamic according to the type of muscle fibers they innervate and their effects on the responses of the Ia and II sensory neurons innervating the central, non-contractile part of the muscle spindle.
Efferent nerve fibers of gamma motor neurons also terminate in muscle spindles; they make synapses at either or both of the ends of the intrafusal muscle fibers and regulate the sensitivity of the sensory afferents, which are located in the non-contractile central (equatorial) region.
Function.
Stretch reflex.
When a muscle is stretched, primary type Ia sensory fibers of the muscle spindle respond to both changes in muscle length and velocity and transmit this activity to the spinal cord in the form of changes in the rate of action potentials. Likewise, secondary type II sensory fibers respond to muscle length changes (but with a smaller velocity-sensitive component) and transmit this signal to the spinal cord. The Ia afferent signals are transmitted monosynaptically to many alpha motor neurons of the receptor-bearing muscle. The reflexly evoked activity in the alpha motor neurons is then transmitted via their efferent axons to the extrafusal fibers of the muscle, which generate force and thereby resist the stretch. The Ia afferent signal is also transmitted polysynaptically through interneurons (Ia inhibitory interneurons), which inhibit alpha motorneurons of antagonist muscles, causing them to relax.
Sensitivity modification.
The function of the gamma motor neurons is not to supplement the force of muscle contraction provided by the extrafusal fibers, but to modify the sensitivity of the muscle spindle sensory afferents to stretch. Upon release of acetylcholine by the active gamma motor neuron, the end portions of the intrafusal muscle fibers contract, thus elongating the non-contractile central portions (see "fusimotor action" schematic below). This opens stretch-sensitive ion channels of the sensory endings, leading to an influx of sodium ions. This raises the resting potential of the endings, thereby increasing the probability of action potential firing, thus increasing the stretch-sensitivity of the muscle spindle afferents.
How does the central nervous system control gamma fusimotor neurons? It has been difficult to record from gamma motor neurons during normal movement because they have very small axons. Several theories have been proposed, based on recordings from spindle afferents.
Development.
It is also believed that muscle spindles play a critical role in sensorimotor development.
Clinical significance.
After stroke or spinal cord injury in humans, spastic hypertonia (spastic paralysis) often develops, whereby the stretch reflex in flexor muscles of the arms and extensor muscles of the legs is overly sensitive. This results in abnormal postures, stiffness and contractures. Hypertonia may be the result of over-sensitivity of alpha motor neurons and interneurons to the Ia and II afferent signals.


Meciadanol

Meciadanol is a synthetic O-methylated flavanol. It is the 3-"O"-methylation of catechin.
It inhibits histidine decarboxylase in rats.


Olfactory epithelium

The olfactory epithelium is a specialized epithelial tissue inside the nasal cavity that is involved in smell. In humans, it measures
9 cm2 (3 centimetres by 3 centimetres) and lies on the roof of the nasal cavity about 7 cm above and behind the nostrils. The olfactory epithelium is the part of the olfactory system directly responsible for detecting odors.
Structure.
Olfactory epithelium consists of four distinct cell types:
Olfactory sensory neurons.
The olfactory receptor neurons are sensory neurons of the olfactory epithelium. They are bipolar neurons and their apical poles express odorant receptors on non-motile cilia at the ends of the dendritic knob, which extend out into the airspace to interact with odorants. Odorant receptors bind odorants in the airspace, which are made soluble by the serous secretions from olfactory glands located in the lamina propria of the mucosa. The axons of the olfactory sensory neurons congregate to form the olfactory nerve (CN I). Once the axons pass through the cribriform plate, they terminate and synapse with the dendrites of mitral cells in the glomeruli of the olfactory bulb.
Supporting cells.
Analogous to neural glial cells, the supporting cells are non-neural cells in the olfactory epithelium that are located in the apical layer of the pseudostratified ciliated columnar epithelium. There are two types of supporting cells in the olfactory epithelium: sustentacular cells and microvillar cells. The sustentacular cells function as metabolic and physical support for the olfactory epithelium. Microvillar cells are another class of supporting cells that are morphologically and biochemically distinct from the sustentacular cells, and arise from a basal cell population that expresses the c-KIT cell surface protein.
Basal cells.
Resting on or near the basal lamina of the olfactory epithelium, basal cells are stem cells capable of division and differentiation into either supporting or olfactory cells. While some of these basal cells divide rapidly, a significant proportion remain relatively quiescent and replenish olfactory epithelial cells as needed. This leads to the olfactory epithelium being replaced every 6–8 weeks.
Basal cells can be divided on the basis of their cellular and histological features into two populations: the horizontal basal cells, which are slowly dividing reserve cells that express p63; and globose basal cells, which are a heterogeneous population of cells consisting of reserve cells, amplifying progenitor cells, and immediate precursor cells.
Brush cells.
A brush cell is a microvilli-bearing columnar cell with its basal surface in contact with afferent nerve endings of the trigeminal nerve (CN V) and is specialized for transduction of general sensation.
Olfactory (Bowman's) glands.
Tubuloalveolar serous secreting glands lying in the lamina propria of the olfactory mucosa. These glands deliver a proteinaceous secretion via ducts onto the surface of the mucosa. The role of the secretions are to trap and dissolve odiferous substances for the bipolar neurons. Constant flow from the olfactory glands allows old odors to be constantly washed away.
Development.
The olfactory epithelium derives from two structures during embryonic development: the olfactory placode, which was long believed to be its sole origin; and neural crest cells, whose contributions have been identified more recently through fate mapping studies.
The embryonic olfactory epithelium consists of fewer cell types than in the adult, including apical and basal progenitor cells, as well as immature olfactory sensory neurons. Early embryonic neurogenesis relies mostly on the apical cells, while later stage embryonic neurogenesis and secondary neurogenesis in adults relies on basal stem cells. The axons of the immature olfactory sensory neurons, along with a mixed population of migratory cells, including immature olfactory ensheathing cells and gonadotropin-releasing hormone neurons form a “migratory mass” that travels towards the olfactory bulb. At the end of the embryonic stage, the epithelium develops into a pseudostratified columnar epithelium and begins secondary neurogenesis.
Olfactory placode.
Placodes are transient, focal aggregations of ectoderm located in the developmental region of the future vertebrate head, and give rise to sensory organs. Early cranial sensory placodes are marked by expression of Six1, part of the Six family of transcription factors that regulate preplacodal ectoderm specification. The olfactory placode forms as two thickenings of non-neural region of embryonic ectoderm. In mice, the olfactory placode derives from an anterior portion of the neural tube, ~9-9.5 days into development and not long after the closure of the neural plate. Development of the olfactory placode requires the presence underlying neural crest-derived mesenchymal tissue. The specification of the olfactory placode tissue involves signaling of multiple gene networks, beginning with signals from bone morphogenetic proteins (BMP), retinoic acid (RA), and fibroblast growth factor (FGF), specifically FGF8. The resulting regulated downstream expression of transcription factors, such as Pax6, Dlx3, Sox2, and others, within the presumptive olfactory placode are crucial for sub-regionalization within the future olfactory epithelium and is responsible for the diversity of cells that compose the future epithelium.
Similar to the other embryonic placodes, the olfactory placode gives rise to both neural and non-neural structures, ultimately resulting in the formation of the nasal epithelium. The specification of neural versus non-neural tissue involves signals both within the olfactory placode, and between the olfactory placode and the underlying mesenchymal compartment. Continued signaling by BMP, FGF, and RA, the morphogens that initially induced placode formation, collectively coordinate the patterning of olfactory placode tissue into the future distinct cell types that make up the olfactory epithelium. The cell types derived from the olfactory placode include:
However, there is significant evidence for an additional neural crest-origin for many of these cell types as well.
Olfactory sensory neuron development.
Olfaction results from the proper development and interaction of the two components of the primary olfactory pathway: the olfactory epithelium and the olfactory bulb. The olfactory epithelium contains olfactory sensory neurons, whose axons innervate the olfactory bulb. In order for olfactory sensory neurons to function properly, they must express odorant receptors and the proper transduction proteins on non-motile cilia that extend from the dendritic knob in addition to projecting their axons to the olfactory bulb.
The cells of the olfactory epithelium, including olfactory sensory neurons, begin to differentiate soon after the induction of the olfactory placode. Once the olfactory sensory neurons differentiate, they express odorant receptors, which transduce odorant information from the environment to the central nervous system and aids in the development of the odorant map. The differentiated olfactory sensory neurons extend pioneering axons, which follow guidance cues released by the underlying mesenchyme, as well as other chemotrophic cues released from the telencephalon. As development of the olfactory pathway progresses, more axons innervate the olfactory bulb, which develops from the rostral-most region of telencephalon. The organization and subsequent processing of odorant information is possible due to the convergence of olfactory sensory neuron axons expressing the same odorant receptors onto the same glomerulus at the olfactory bulb.
Clinical significance.
The olfactory epithelium can be damaged by inhalation of toxic fumes, physical injury to the interior of the nose, and possibly by the use of some nasal sprays. Because of its regenerative capacity, damage to the olfactory epithelium can be temporary but in extreme cases, injury can be permanent, leading to anosmia.


Shit on a shingle


Derek Aucoin

Derek Alfred Aucoin (27 March 1970 – 26 December 2020) was a Major League Baseball pitcher. Aucoin pitched in two games for the Montreal Expos in the 1996 season. He had a 0–1 record, in 2.2 innings, with a 3.38 ERA. He died from brain cancer on 26 December 2020.
He was signed by the Expos as an amateur free agent in 1989.
Professional baseball career.
Montreal Expos.
In his first professional season, , with the Gulf Coast League Expos he went 2–1 with a 2.66 ERA in seven games, three starts.
While with the Short-Season Jamestown Expos in Aucoin compiled a record of 1–3 with a 4.46 ERA in eight games, all starts.
His next two seasons, and , were spent at the Class-A level. In 1991 he went 3–6 with a 4.28 ERA in 41 games, four starts with the Sumter Flyers. In 1992 he went 3–2 with a 3.00 ERA in 39 games, two starts with the Rockford Expos.
Aucoin was promoted to the Advanced-A West Palm Beach Expos in . He compiled a record of 4–4 with a 4.24 ERA in 38 games, six starts.
In Aucoin split the season between West Palm Beach and the Double-A Harrisburg Senators of the Eastern League He went a combined 3–4 with a 2.82 ERA in 38 games. Staying at Harrisburg in he went 2–4 with a 4.96 ERA in 29 games.
Aucoin split the season between the Expos and the Triple-A Ottawa Lynx of the International League. With Ottawa he went 3–5 with a 3.96 ERA in 52 games. On 21 May he made his Major League debut against the San Francisco Giants. In of an inning he gave up one earned run and registering a loss. He would finish his Major Career going 0–1 with a 3.39 ERA in two games.
With West Palm Beach and Ottawa in he went a combined 0–1 with a dismal 11.37 ERA in 25 games.
New York Mets.
In his final season, , Aucoin split the season between the Gulf Coast League Mets, the Advanced-A St. Lucie Mets, the Double-A Binghamton Mets and the Triple-A Norfolk Tides. He went a combined 1–0 with a 6.21 ERA in 28 games.
Personal life.
In April 2011, Derek married Isabelle Rochefort. They had a son, Dawson Paul Aucoin, named after Hall of Fame player Andre Dawson.
References.


Pseudounipolar neuron

A pseudounipolar neuron is a type of neuron which has one extension from its cell body. This type of neuron contains an axon that has split into two branches; one branch travels to the peripheral nervous system and the other to the central nervous system. A single process arises from the cell body and then divides into an axon and a dendrite. They develop embryologically as bipolar in shape, and are thus termed pseudounipolar instead of unipolar.
Structure.
A pseudounipolar neuron has one axon that projects from the cell body for relatively a very short distance, before splitting into two branches — one that extends to the central nervous system, and the other that extends to the peripheral nervous system. Pseudounipolar neurons are sensory neurons that have no dendrites, the branched axon serving both functions. The peripheral branch extends from the cell body to organs in the periphery including skin, joints and muscles, and the central branch extends from the cell body to the spinal cord.
In the dorsal root ganglia.
The cell body of a pseudounipolar neuron is located within a dorsal root ganglion. The axon leaves the cell body (and out of the dorsal root ganglion) into the dorsal root, where it splits into two branches. The central branch goes to the dorsal columns of the spinal cord, where it forms synapses with other neurons. The peripheral branch travels through the distal dorsal root into the spinal nerve all the way until skin, joint, and muscle.
In most sensory ganglia of cranial nerves.
Pseudounipolar neurons are found in the sensory ganglia of most cranial nerves.
Specifically the:
Pseudounipolar neurons in cranial nerve sensory ganglia synapse in the main sensory trigeminal nucleus, spinal trigeminal nucleus or solitary nucleus.
While the vestibulocochlear nerve has two ganglia associated with it (spiral ganglion and vestibular ganglion), both contain bipolar neurons, not pseudounipolar.
In the mesencephalic nucleus.
The mesencephalic nucleus is made up of pseudounipolar neurons which migrated into the brainstem during embryological development. It is the only location in the central nervous system where the cell bodies of pseudounipolar neurons are found.
Function.
All pseudounipolar neurons are sensory neurons. The ones found in the dorsal root ganglia, and majority of those in cranial nerve sensory ganglia carry information about touch, vibration, proprioception, pain and temperature.
Pseudounipolar neurons in the geniculate ganglion, inferior ganglion of the glossopharyngeal nerve and inferior ganglion of the vagus nerve also carry information about taste from taste buds.
Some of the pseudounipolar neurons in the inferior ganglion of the glossopharyngeal nerve carry information from the carotid body and carotid sinus.
The pseudounipolar neurons in the mesencephalic nucleus carry proprioceptive information from the muscle of mastication.


Head of Holofernes


Value numbering

Value numbering is a technique of determining when two computations in a program are equivalent and eliminating one of them with a semantics preserving optimization.
Global value numbering.
Global value numbering (GVN) is a compiler optimization based on the static single assignment form (SSA) intermediate representation. It sometimes helps eliminate redundant code that common subexpression elimination (CSE) does not. At the same time, however, CSE may eliminate code that GVN does not, so both are often found in modern compilers. Global value numbering is distinct from local value numbering in that the value-number mappings hold across basic block boundaries as well, and different algorithms are used to compute the mappings.
Global value numbering works by assigning a value number to variables and expressions. The same value number is assigned to those variables and expressions which are provably equivalent. For instance, in the following code:
 w := 3
 x := 3
 y := x + 4
 z := w + 4
a good GVN routine would assign the same value number to codice_1 and codice_2, and the same value number to codice_3 and codice_4. For instance, the map formula_1 would constitute an optimal value-number mapping for this block.
Using this information, the previous code fragment may be safely transformed into:
 w := 3
 x := w
 y := w + 4
 z := y
Depending on the code following this fragment, copy propagation may be able to remove the assignments to codice_2 and to codice_4
The reason that GVN is sometimes more powerful than CSE comes from the fact that CSE matches lexically identical expressions whereas the GVN tries to determine an underlying equivalence. For instance, in the code:
 a := c × d
 e := c
 f := e × d
Without copy propagation, CSE would "not" eliminate the recomputation assigned to codice_7, but even a poor GVN algorithm should discover and eliminate this redundancy.
SSA form is required to perform GVN so that false {variable name → value name} mappings are not created.
Local value numbering.
Local value numbering (LVN) is a compiler optimization that aims to find multiple instances of equivalent expressions (i.e. expressions which yield the same result) and replace them with the first occurrence. LVN is a local optimization, meaning that unlike global value numbering it operates on a single basic block at a time.
Local value numbering works by assigning a unique number to each operation and remembering these associations. Subsequent instructions are then looked up and, in case an identical instruction has already been registered replaced with the previous' instruction's result. For example:
 a ← 4 a is tagged as #1
 b ← 5 b is tagged as #2
 c ← a + b c (#1 + #2) is tagged as #3
 d ← 5 d is tagged as #2, the same as b
 e ← a + d e, being '#1 + #2' is tagged as #3
By assigning numbers to instructions comparing for duplicates is turned into simple integer comparisons. In this particular example 'c' and 'e' are assigned the same number (#3), thus signalling to the compiler that any references to e may simply be replaced with ones to c.
Difficulties and extensions.
A naive implementation might attempt to perform the optimization by directly using the variable names instead of numbers. However, this approach does not work when the values of variables can change. Consider the pseudocode:
 a ← 1 a is tagged as #1
 b ← 2 b is tagged as #2
 c ← a + b c is tagged as #3
 b ← 3
 d ← a + b d is incorrectly tagged as #3
In this scenario 'd' is incorrectly assigned the number 3 because the arguments match those of 'c'. This is incorrect, however, because 'b' has changed value from 2 to 3, making the actual results differ.
A simple implementation might also be unable to catch all equivalent expressions, even when they only differ by the order of their operands. In the following example 'a' and 'b' could be assigned the same number:
 a ← 1 + 2
 b ← 2 + 1
This issue can easily be resolved either by assigning the same number to both cases (i.e. "a + b" and "b + a" are both recorded with the same number) or by sorting the operands before checking for equivalents.
Local value numbering optimizers may also be aware of mathematical identities. Assuming 'a' is an integer number all of the following expressions can be assigned the same value:
 b ← a + 0
 c ← a * 1
 d ← min(a, MAX_INT)
 e ← max(a, a)
 f ← a & 0xFF..FF (assuming '&' denotes the bitwise operation)


Overprinting

Overprinting refers to the process of printing one colour on top of another in reprographics. This is closely linked to the reprographic technique of 'trapping'. Another use of overprinting is to create a rich black (often regarded as a colour that is "blacker than black") by printing black over another dark colour.
It is also the term used in the production of envelopes customised to order by printing images (such as logos) and texts (such as slogans) on mass-produced machine-made envelopes; the alternative way of producing such envelopes is to print "on the flat" and then cut out the individual shapes and fold them to form the envelopes. However the latter method is generally only economically viable for large print runs offering returns to scale.
Overprinting also refers to the printing of additional information onto self-adhesive labels and product packaging. "Best Before", "Use By" dates and batch codes are printed in situ onto product
packaging as the items are packed. Generally thermal printers, ink jet printers or laser printers are used.


Serlopitant

Serlopitant (INN, codenamed VPD-737) is a drug which acts as an NK1 receptor antagonist. It was assessed in clinical trials for the treatment of urinary incontinence and overactive bladder, but while it was superior to placebo it provided no advantage over existing approved drugs, and was not approved for further development for this indication. Serlopitant is now undergoing clinical trials for the treatment of chronic pruritus (itch)


Superoptimization

Superoptimization is the process of automatically finding the optimal code sequence for one loop-free sequence of instructions. It is performed in and by a type of computer software termed a compiler. Real-world compilers generally cannot produce genuinely "optimal" code. While most standard compiler optimizations only improve code partly, a superoptimizer's goal is to find the optimal sequence, the canonical form. Superoptimizers can be used to improve conventional optimizers by highlighting missed opportunities so a human can write additional rules.
History.
The term superoptimization was first coined by Alexia Massalin in the 1987 paper "Superoptimizer: A Look at the Smallest Program".
In 1992, the GNU Superoptimizer (GSO) was developed to integrate into the GNU Compiler Collection (GCC). Later work further developed and extended these ideas.
Techniques.
Typically, superoptimizing is performed via exhaustive brute-force search in the space of valid instruction sequences. This is a costly method, and thus impractical for general-purpose compilers. Yet, it has been shown to be useful in optimizing performance-critical inner loops. It is also possible to use a SMT solver to approach the problem.
In 2001, goal-directed superoptimizing was demonstrated in the Denali project by Compaq research. In 2006, answer set declarative programming was used for superoptimising in the Total Optimisation using Answer Set Technology (TOAST) project at the University of Bath.
Superoptimization can be used to automatically generate general-purpose peephole optimizers.
Publicly available superoptimizers.
Several superoptimizers are available for free download.


Cardiovascular centre

The cardiovascular centre is a part of the human brain which regulates heart rate through the nervous and endocrine systems. It is considered one of the vital centres of the medulla oblongata.
Structure.
The cardiovascular centre, or cardiovascular center, is part of the medulla oblongata of the brainstem. Normally, the heart beats without nervous control. In some situations, such as exercise, and major trauma, the cardiovascular centre is responsible for altering heart rate. It also mediates respiratory sinus arrhythmia.
Function.
The cardiovascular centre responds to a variety of types of sensory information, such as:
The cardiovascular centre affects changes to the heart rate by sending a nerve impulse to the cardiac pacemaker via two sets of nerves:
The cardiovascular centre also increases the stroke volume of the heart (that is, the amount of blood it pumps). These two changes help to regulate the cardiac output, so that a sufficient amount of blood reaches tissues. This function is so significant to normal functioning of the circulatory system that the cardiovascular centre is considered a vital centre of the medulla oblongata.
Hormones like epinephrine and norepinephrine can affect the cardiovascular centre and cause it to increase the rate of impulses sent to the sinoatrial node, resulting in faster and stronger cardiac muscle contraction. This increases heart rate.
Clinical significance.
Many anaesthetics depress the activity of the cardiovascular center. Phencyclidine may be a useful anaesthetic because it does not impact the cardiovascular center. This also contrasts phencyclidine from many other recreational drugs.


Tolazamide

Tolazamide is an blood glucose lowering drug used for people with Type 2 diabetes. It is part of the sulfonylurea family (ATC A10BB).
Synthesis.
"para"-Toluenesulfonamide is converted to its carbamate with ethyl chloroformate in the presence of a base. Heating that intermediate with 1-amino-azepane leads to the displacement of the ethoxy group and the formation of tolazemide:
Azepane proper would lead to [13078-23-4].


Cervical spinal nerve 8

The cervical spinal nerve 8 (C8) is a spinal nerve of the cervical segment.
It originates from the spinal column from below the cervical vertebra 7 (C7).
Innervation.
The C8 nerve forms part of the radial and ulnar nerves via the brachial plexus, and therefore has motor and sensory function in the upper limb.
Sensory.
The C8 nerve receives sensory afferents from the C8 dermatome. This consists of all the skin on the little finger, and continuing up slightly past the wrist on the palmar and dorsal aspects of the hand and forearm. Clinically a test of the pad of the little finger is often used to assess C8 integrity.
Motor.
The C8 nerve contributes to the motor innervation of many of the muscles in the trunk and upper limb. Its primary function is the flexion of the fingers, and this is used as the clinical test for C8 integrity, in conjunction with the finger jerk reflex.
The particular muscles receive innervation from C8 (shown by specific nerve and spinal nerve segments; muscles in italics only have a minor contribution from C8) :


Butyltolylquinuclidine

2-Butyl-3-(p-tolyl)quinuclidine (BTQ) is a stimulant DRI. It is one of a number of substituted quinuclidine derivatives developed as potential medications for the treatment of cocaine abuse, and produces similar effects to cocaine in animal studies, although milder and longer-lasting.


Bass chorus

A bass chorus is an electronic effect used with the electric bass. It creates the same "shimmering" sound as a chorus effect for electric guitar chorus pedals, which recreates the sound of having multiple instruments doubling the same musical line (as with a string orchestra). The difference is that bass chorus pedals are modified in various ways to suit the low pitch register of the electric bass. While several bass chorus pedal manufacturers have modified the chorus circuit so that it does not affect the lower register, others have designed the effect so that it can have an effect on even very low pitches.
The requirements for a chorus effect using a pedal or effect unit can vary depending on the type of instrument being used. Bass is a good example because it operates at a lower frequency range than a guitar. As such, a standard multi-level chorus can make the sound of the bass notes much thinner. This problem can be corrected by either mixing more of the un-affected ("dry") signal into the mix or by increasing the amount of bass frequency chorused in the sound. Pedals such as the "I90" chorus from bass amplifier manufacturer Eden Electronics allow the musician to control both of these elements. As some guitar chorus pedals pass the whole, unmodified signal and only apply chorus to higher frequencies, some bass players prefer the sound of some guitar-oriented pedals.
Examples.
The Boss CEB-3: Bass Chorus, for example, "offers a split-frequency chorus effect capable of applying warm, rich chorusing to the higher frequencies without muddying up the lows."
Digitech's Bass Multi Chorus™ is "designed specifically for bass". The manufacturer claims that "it keeps your low notes clean while giving you up to 16 bass chorus voices at the same time."
The MXR Bass Chorus Deluxe has a crossover which lessens "modulation in low frequencies is...at 100Hz", thus "keeping the low end in tune." The MXR outputs in stereo, creating a stereo chorus effect if used with two amplifiers. It won an Editor's award from Bass Player magazine. The review stated that the pedal uses "analog bucket-brigade technology—in which the signal runs through a series of capacitors to create an organic, warm-sounding effect."
The Carl Martin Bass Chorus is designed to avoid the "mid-range heavy" sound that the manufacturer claims is produced by some bass chorus pedals. The Carl Martin Bass Chorus can apply the effect even "down as [deep as a] low B."


Gianroberto Casaleggio

Gianroberto Casaleggio (; 14 August 1954 – 12 April 2016) was an Italian entrepreneur and political activist, born in Milan.
He was co-founder and chairman of Casaleggio Associati srl, an internet and publishing company that advises on network strategies, and editor of Beppe Grillo's blog. He was also co-founder, with Beppe Grillo, of the Five Star Movement, of which he was sometimes called "guru". In the Italian context, Casaleggio promoted the Web as a medium for political communication.
Biography.
Casaleggio began his career working at Olivetti, then, in the late 1990s, became CEO at Webegg, an internet consulting company. Webegg suffered heavy losses (over €20 million) in the period 2002–2003, and Casaleggio was replaced as CEO in 2003 by Giuseppe Longo. In 2004, Casaleggio founded Casaleggio Associati, an internet consulting company that carries out research on e-commerce in Italy and whose findings are presented at a conference held in Milan every spring (since 2006).
Casaleggio Associati became the editor of Beppe Grillo's blog in 2005, as well as of some of Grillo's books. Casaleggio Associati was also editor of the web-blog of Antonio Di Pietro until 2010, and the website of Chiarelettere, an editor, until 2013, when he was dismissed following disagreement over the editorial strategy.
Casaleggio died on 12 April 2016 in Milan, at the age of 61, after a long period of illness.
Family.
After Gianroberto's death, his son Davide was appointed to replace him as president of Casaleggio Associati.


Guidepost cells

Guidepost cells are cells which assist in the subcellular organization of both neural axon growth and migration. They act as intermediate targets for long and complex axonal growths by creating short and easy pathways, leading axon growth cones towards their target area.
Identification.
In 1976, guideposts cells were identified in both grasshopper embryos and "Drosophila". Single guidepost cells, acting like "stepping-stones" for the extension of Ti1 pioneer growth cones to the CNS, were first discovered in grasshopper limb bud. However, guidepost cells can also act as a group. There is a band of epithelial cells, called floor-plate cells, present in the neural tube of Drosophilia available for the binding of growing axons. These studies have defined guidepost cells as non-continuous landmarks located on future paths of growing axons by providing high-affinity substrates to bind to for navigation.
Guidepost cells are typically immature glial cells and neuron cells, that have yet to grown an axon. They can either be labeled as short range cells or axon dependent cells.
To qualify as a guidepost cell, neurons hypothesized to be influenced by a guidance cell are examined during development. To test the guidance cell in question, neural axon growth and migration is first examined in the presence of the guidance cell. Then, the guidance cell is destroyed to further examine neural axon growth and migration in the absence of the guidance cell. If the neuronal axon extends towards the path in the presence of the guidance cell and loses its path in the absence of the guidance cell, it is qualified as a guidepost cell. Ti1 pioneer neurons is a common example neurons that require guidepost cells to reach its final destination. They have to come in contact with three guidepost neurons to reach the CNS: Fe1, Tr1, and Cx1. When Cx1 is destroyed, the Ti1 pioneer is unable to reach the CNS.
Roles in formation.
Lateral olfactory tract.
The lateral olfactory tract (LOT) is the first system where guideposts cells were proposed to play a role in axonal guidance. In this migrational pathway, olfactory neurons move from the nasal cavities to the mitral cells in the olfactory bulb. The mitral primary axons extend and form a bundle of axons, called the LOT, towards higher olfactory centers: anterior olfactory nucleus, olfactory tubercle, piriform cortexr, entorhinal cortex, and cortical nuclei of the amygdala. "Lot cells", the first neurons to appear in the telencephalon, are considered to be guideposts because they have cellular substrates to attract LOX axons. To test their role in guidance, scientists ablated lot cells with a toxin called 6-OHDA. As a result, LOT axons were stalled in the areas where lot cells were destroyed, which confirmed lot cells as guidepost cells.
Entorhinal projections.
Cajal-Retzius cells are the first cells to cover the cortical sheet and hippocampal primordium, and regulate cortical lamination by Reelin. In order to make connections with GABAergic neurons in different regions of the hippocampus (stratum oriens, stratum radiatum, and inner molecular layer), pioneer entorhinal neurons make synaptic contacts with Cajal-Retzius cells. To test their role in guidance, scientists (Del Rio and colleagues) ablated Cajal-Retzius cells with 6-OHDA. As a result, entorhinal axons did not grow in the hippocampus and ruled Cajal-Retzius cells as guidepost cells.
Thalamocortical connections.
Perirecular cells (or internal capsule cells) are neuronal guidepost cells located along the path of creating the internal capsule. They provide a scaffold for corticothalamic and thalamocortical axons (TCAs) to send messages to the thalamus. There are transcription factors associated with perirecular cells: "Mash1", "Lhx2", and "Emx2". When guidepost cells are mutated with knock out expressions of these factors, the guidance of TCAs are defected.
Corridor cells are another set of guidepost cells present for TCA guidance. These GABAergic neurons migrate to form a "corridor" between proliferation zones of the medial ganglionic eminence and globus pallidus. Corridor cells provide TCA growth through MGE-derived regions. However, the Neurgulin1 signaling pathway needs to be activated, with the expression of ErbB4 receptors on the surface of TCAs, for the connection to occur between corridor cells and TCAs.
Corpus callosum.
There are subpopulations of glial cells that provide guidance cues for axonal growth. The first set of cells, called the "mid-line glial zipper", regulate the midline fusion and guidance of pioneer axons to the septum towards the contralateral hemisphere. The "glial sling" is a second set, located at the corticoseptal boundary, which provide cellular substrates for callosal axon migration across the dorsal midline. The "glial wedge" is made up of radial fibers, secreting repellent cues to prevent axons from entering the septum and positioning them towards the corpus callosum. The last set of glial cells, located in the induseum griseum, control the positioning of pioneer cingulate neurons in the corpus callosum region.


Interventricular foramina (neuroanatomy)

In the brain, the interventricular foramina (or foramina of Monro) are channels that connect the paired lateral ventricles with the third ventricle at the midline of the brain. As channels, they allow cerebrospinal fluid (CSF) produced in the lateral ventricles to reach the third ventricle and then the rest of the brain's ventricular system. The walls of the interventricular foramina also contain choroid plexus, a specialized CSF-producing structure, that is continuous with that of the lateral and third ventricles above and below it.
Structure.
The interventricular foramina are two holes (, pl. "foramina") that connect the left and the right lateral ventricles to the third ventricle. They are located on the underside near the midline of the lateral ventricles, and join the third ventricle where its roof meets its anterior surface. In front of the foramen is the fornix and behind is the thalamus. The foramen is normally crescent-shaped, but rounds and increases in size depending on the size of the lateral ventricles.
Development.
The development and shape of the ventricular system relates to the differential development of different parts of the brain, with the ventricular system ultimately arising from the neural tube. The lateral ventricles remain connected to the third ventricle throughout development, themselves developing as outpouchings from the third ventricle. The foramina develop slowly in a forward and outward direction as the fornix grows in size.
Function.
The interventricular foramina connect the lateral ventricles to the third ventricle. This allows cerebrospinal fluid produced in the lateral ventricles to reach the third ventricle and then the rest of the brain's ventricular system.
The walls of the interventricular foramina contain choroid plexus, a specialized structure that produces cerebrospinal fluid. The choroid plexus of the third ventricles continues through the foramina into the lateral ventricles.
End branches of the medial posterior choroidal arteries, superior thalamostriate, superior choroid veins and septal veins also pass through the foramen.
Clinical significance.
The interventricular foramina give rise to disease when they are narrowed or blocked. Narrowing of the foramen is more common in children and linked to: inflammation and scarring from congenital infections, particularly TORCH infections; developmental abnormalities, including of the basilar artery and choroid plexus; and abnormal surrounding tissue growths, such as colloid cysts, subependymal giant-cell tumours, nodules and harmatomas.
The most common symptom of blockage is headache; other symptoms include fainting, dementia, and coma, all of which are associated with obstructive hydrocephalus of the affected side or sides. Hydrocephalus can be identified by a CT scan or MRI scan of the brain, and treatment involves a neurosurgical operation in which an endoscope (i.e., a tiny camera and tools) is used to widen the foramen or create a new opening through the septum pellucidum between the lateral ventricles. If an obstructing mass is too large or too difficult to remove endoscopically, an open operation or the insertion of an artificial path between the ventricles and peritoneum may be required. Because of the intimate nature of pathways within the brain, such operations may result in damage to nearby structures, with complications including anterograde amnesia, inability to move half the body, akinetic mutism and disconnection syndromes.
History.
The foramina were named after the Scottish physician and University of Edinburgh graduate Alexander Monro, who first described an enlarged foramen in the context of hydrocephalus in a presentation to the Philosophical Society of Edinburgh in 1764, and subsequently in his 1783 publication, "Observations on the Structure and Functions of the Nervous System".
In this publication, Monro notes that the ventricular system has been noted to be connected, implying the presence of the foramen, since the time of the physician anatomist Galen. Monro described it as:
Monro's original description, of two lateral ventricles joined by a foramen that then joined the third ventricle, is in fact incorrect. As noted by Monro himself, previous authors have also described the ventricles as having connections; consequently, the eponym of "Monro" has been disputed.


Posterior branches of the lumbar nerves

The posterior branches of the lumbar nerves branch from the dorsal rami of the lumbar nerves.


Superior medullary velum

The superior medullary velum (anterior medullary velum) is a thin, transparent lamina of white matter, which stretches between the superior cerebellar peduncles; on the dorsal surface of its lower half the folia and lingula are prolonged.
It forms, together with the superior cerebellar peduncle, the roof of the upper part of the fourth ventricle; it is narrow above, where it passes beneath the facial colliculi, and broader below, where it is continuous with the white substance of the superior vermis.
A slightly elevated ridge, the frenulum veli, descends upon its upper part from between the inferior colliculi, and on either side of this the trochlear nerve emerges.
Blood is supplied by branches from the superior cerebellar artery.


Methedrone

Methedrone ("para"-methoxymethcathinone, 4-methoxymethcathinone, bk-PMMA, PMMC, methoxyphedrine, 4-MeOMC) is a recreational drug of the cathinone chemical class. Chemically, methedrone is closely related to "para"-methoxymethamphetamine (PMMA), methylone and mephedrone. Methedrone received media attention in 2009 after the death of two young Swedish men. In both cases toxicology analysis showed methedrone was the only drug present in both men during the time of their overdose and subsequent deaths.
Discovery.
The synthesis of methedrone was first reported in 1933.
Structure and reactivity.
Structure.
Methedrone is a synthetic cathinone. It is related to the parent compound cathinone. Methedrone belongs to the phenethylamine family due to the presence of the cyclic group of atoms C6H5 in which six carbons bind to form a hexagonal ring with five hydrogens each bonding to a carbon and the remaining carbon bonded to an atom or group of atoms other than hydrogen.
Reactivity.
There are no articles found about the reactivity of methedrone.
Synthesis.
The synthesis of methedrone is described in figure 1. and can be written as the following steps.
The synthesis of mephedrone, a structurally similar compound with only one less ether group than methedrone, is well documented.
Availability.
Methedrone can be purchased legally in Europe (excluding Sweden) and in most states in the US on the Internet, but also it can also be found at head shops and other retailers. It is, along with other new or unregulated synthetic drugs and research chemicals, commonly labeled as a "bath salt".
Administration.
Methedrone is a research chemical and its euphoric and stimulant properties can be abused. Similarly to MDMA it can be administered through insufflation, ingestion, smoking, rectal, and intravenous routes; however, it differs greatly in both duration and toxicity and great care should be taken when used due to the lack of medical literature available common among designer drugs.
Mechanism of action.
Methedrone has been found to be a potent serotonin transporter (SERT) and norepinephrine transporter (NET) inhibitor, but a weak dopamine transporter (DAT) inhibitor. Clinically, the DAT/SERT ratio of methedrone is less than one. Other analog compounds commonly have a DAT/SERT ratio less than half, meaning unlike other MDMA-like compounds methedrone does not prefer inhibition of the NET and DAT over the SERT. The resulting lack of inhibition despite its proclivity to release DAT can lead to a life-threatening adrenergic storm. Methedrone's high selectivity for SERT places it among the highest selectivity when compared to structurally similar compounds.
Methedrone induces the transportation mediated release of NE, DA and 5-HT from cells preloaded with monoamines making it a serotonin-norepinephrine-dopamine (SNDRA) releasing agent, also known as triple releasing agent (TRA), which is a common characteristic among drugs of abuse.
It has been found that methedrone is similar to MDMA in terms of the monoamine transporter interactions but an in vivo study of the drug resulted in a stronger hyperthermic reaction than what is normally reported in studies of MDMAs. Methedrone's affects on the serotonin transporter, SERT, can interfere and cause complications in individuals co-administrating with serotonin altering medications such as selective serotonin reuptake inhibitors (SSRIs).
Metabolism.
To consider how methedrone (4-MeOMC) acts in a biological system, it is necessary to study the stability in an aqueous solution. Because, when tested directly in blood or urine, it is not known whether the compound will be degraded by enzymes available in the biological solutions or cause the chemical mechanisms, such as pH or dissolved oxygen. The length of the half-life of the compound has been examined and the percent remaining after 12 hours in buffers with various pHs. The tested pHs were 4, 7, 10 and 12.
The conclusions are that methedrone, just as most analogs, is stable in acid solutions. However, in neutral and basic solutions it is decomposed, where a stronger decomposing takes place as the solution turns more basic.
When comparing methdrone with its analogs, it has been found that there are several factors which affect their stability:
Methedrone and four other analogs have their groups substituted in the meta- or para-positions. For these compounds the rate constant, k, has been determined and a Hammett plot was constructed by plotting the decomposition rate constant (0.693/half-life) in the pH of 12 against their Hammett constants, taken from literature. This again shows that methedrone is a relatively stable compound even in basic solution.
Another conclusion based on the results from the literature is that there is negative charge built up in the transition state during the rate determining step. This reasoning is based on the good linear correlation (r=0.9805) and the positive slope (determined as 1.76).
There are two possible metabolites known for methedrone:
Dosage and side effects.
Dosage.
There is little information available about how Methedrone is dosed. According to users, a single dose of Methedrone varies from 50 to 500 mg with effects lasting 45 minutes to two hours. There are at least two cases known of fatal intoxications with Methedrone. In the first case, the postmortem femoral blood sample of the patient contained a concentration of 8.4 µg/g Methedrone, the patient died 16 hours after consumption (with polysubstance use detected). In the second body the concentration in the femoral blood sample was 9.6 µg/g, with Methedrone being the only toxic compound detected. The scientific investigation of these cases suggests that the Methedrone alone was responsible for these deaths and that the concentrations in the femoral blood represent the fatal levels of methedrone. These studies show that the therapeutic index (or safety ratio) is low compared to other illegal drugs like Amphetamine. A fatal dose is likely to be around 8 µg/g whereas the dose among users varies from 0.1 to 4.8 µg/g blood according to studies.
Side effects.
Anecdotal and case reports of human use of "bath salts", such as methedrone, suggest that these substances produce powerful psychological effects. These psychological effects include psychotic behavior, paranoia, delusions, hallucinations and also self-injury.
There is very little known of the physical effects of methedrone in humans, but there have been some studies to the effects of methedrone in animals, so we focused on the effects in mice.
Studies to the effects of Methedrone in mice show that Methedrone produces a significant increase in circling, beam breaks and hyperactivity. Furthermore, the mice also showed a significant increase in salivation, head weaving and stimulation. Methedrone is currently a legal drug in many jurisdictions, however studies show that it shares major pharmacological properties with drugs that have been banned, such as mephedrone and methylone. Also, the effects of Methedrone are very similar to the effects of banned drugs in mice. This suggests that Methedrone may be just as harmful as most commonly found Illicit drugs.
Toxicity.
Acute toxicity.
There is little research regarding the toxicity of methedrone. Research has been done by animal-testing on mice once. Also, the lethal doses found in the two Swedish methedrone-victims have been compared to the methedrone concentrations in the blood of two other males dying in similar conditions.
The mean of the methedrone concentrations in the blood of the two deceased was 1.3 μg/g blood. One of these victims had a very high concentration of Methedrone in the blood, approximately 4.8 μg/g blood. The mean of the concentrations found in the blood of the deceased victims was 8.0 μg/g blood. None of the non-lethal doses or lethal doses is known, suggesting that the safety gap between a lethal and non-lethal dose of methedrone is probably very small, thus making use of this drug dangerous because poisonings, and simultaneously death, are accidental.
In a study of the effects of synthetic cathiones in ‘bath salts’ the effects of methedrone on mice were tested, these effects were compared to the effects of cocaine and methamphetamine. Different tests were performed to get insight into motor coordination, balance and overall behavioral effects. The mice did not show any difference in motor coordination or balance (doses administered were 10.0 mg/kg and 30.0 mg/kg). However significant changes were shown in overall behavioral effects. Administration of methedrone led to:
These effects are related with addiction potential. Excessive salivation is not an effect that is typically reported in humans. It is suggested that methedrone increases salivation via brain systems that primarily regulate autonomic responses.
Compared with mephedrone, methylenedioxypyrovalerone (MDPV) and 4-fluoromethcathinone (4-FMC), methedrone has a relatively slow onset. Thereby increasing the risk; because effects are not immediately shown, this could lead to an accidental overdose. It could also make the drug less popular, because humans tend to favor drugs that cause large, rapid initial increases in locomotor activity.
Chronic toxicity.
Even in comparison with acute toxicity, chronic toxicity is poorly researched. Only the post-mortem study did little investigation on this subject. The findings of this study only showed that hair of the deceased victims contained methedrone, however, no conclusions were made regarding these findings.
No studies have examined the effect of methedrone-use during or before pregnancy by a pregnant female on the embryo, nor is the carcinogenicity researched.
Health risks.
The health risks associated with methedrone are mostly unknown, but are expected to be similar to other cathinones. Methedrone was almost immediately withdrawn from sale by initial vendors after reports of adverse health effects. Some amphetamine analogs containing a "para"-methoxy group are known to cause severe hyperthermia and even death due to concurrent MAOI and monoamine releasing action.
Overdose.
The deaths of two young men in southeast Sweden in 2009 were attributed to methedrone overdose.
Both were comatose when found. One suffered cardiorespiratory arrest on the way to the hospital, while the second survived for 16 hours in the emergency department.
Effects on animals.
Mice.
Methedrone has been found to have an effect on the overall behavior of mice which includes:
Legality.
Its sale has been banned in Sweden since December 9, 2009.
It is a controlled substance in China since October 1, 2015.


Supramammillary nucleus

The supramammillary nucleus (SuM), or supramammillary area, is a thin layer of cells in the brain that lies above the mammillary bodies. It can be considered part of the hypothalamus and diencephalon. The nucleus can be divided into medial and lateral sections. The medial SuM, or SuMM, is made of smaller cells which release dopamine and give input to the lateral septal nucleus. The lateral SuM, or SuML, is made of larger cells that project to the hippocampus.
Functions.
Although the exact function of the supramammillary nucleus is still not clear, it is known that the SuM plays a role in modulating theta frequencies. Because of its role in modulating hippocampal theta, it is implicated in spatial and emotional memory formation.The axons of SuM neurons make monosynaptic connections to granule cells and GABAergic interneurons in the dentate gyrus. The SuM projects it's afferent signals exclusively to the dentate gyrus and CA2 region of the hippocampus. These SuM neurons will co-release glutamate and GABA, but these inputs will not fully excite the granule cells. Although it will not cause an action potential alone, SuM neurons can have excitatory impact on granule cells with the help of perforant path inputs. The perforant pathway are fibers that connect the entorhinal cortex with the hippocampus. This pathway accounts for the major inputs to the hippocampus and dentate gyrus. Ultimately, the SuM will modulate the granule cell outputs causing it to influence the dentate gyrus information processing.


Secondary somatosensory cortex

The human secondary somatosensory cortex (S2, SII) is a region of cortex in the parietal operculum on the ceiling of the lateral sulcus.
Region S2 was first described by Adrian in 1940, who found that feeling in cats' feet was not only represented in the primary somatosensory cortex (S1) but also in a second region adjacent to S1. In 1954, Penfield and Jasper evoked somatosensory sensations in human patients during neurosurgery by electrically stimulating the ceiling of the lateral sulcus, which lies adjacent to S1, and their findings were confirmed in 1979 by Woolsey et al. using evoked potentials and electrical stimulation. Experiments involving ablation of the second somatosensory cortex in primates indicate that this cortical area is involved in remembering the differences between tactile shapes and textures. Functional neuroimaging studies have found S2 activation in response to light touch, pain, visceral sensation, and tactile attention.
In monkeys, apes and hominids, including humans, region S2 is divided into several "areas". An area at the entrance to the lateral sulcus, adjoining the primary somatosensory cortex (S1), is called the parietal ventral (PV) area. Posterior to PV is the secondary somatosensory "area" (area S2, which must not be confused with "region S2" which designates the entire secondary somatosensory cortex, of which area S2 is a part). Deeper in the lateral sulcus lies the ventral somatosensory (VS) area, whose outer edge adjoins areas PV and S2 and inner edge adjoins the insular cortex.
In humans, the secondary somatosensory cortex includes parts of Brodmann area (BA) 40 and 43.
Areas PV and S2 both map the body surface. Functional neuroimaging in humans has revealed that in areas PV and S2 the face is represented near the entrance to the lateral sulcus, and the hands and feet deeper in the fissure. Individual neurons in areas PV and S2 receive input from wide areas of the body surface (they have large "receptive fields"), and respond readily to stimuli such as wiping a sponge over a large area of skin.
Area PV connects densely with BA 5 and the premotor cortex. Area S2 is interconnected with BA 1 and densely so with BA 3b, and projects to PV, BA 7b, insular cortex, amygdala and hippocampus. Areas S2 in the left and right hemispheres are densely interconnected, and stimulation on one side of the body will activate area S2 in both hemispheres.


Tree shaking

In computing, tree shaking is a dead code elimination technique that is applied when optimizing code written in ECMAScript dialects like Dart, JavaScript, or TypeScript into a single bundle that is loaded by a web browser. Often contrasted with traditional single-library dead code elimination techniques common to minifiers, tree shaking eliminates unused functions from across the bundle by starting at the entry point and only including functions that may be executed. It is succinctly described as "live code inclusion".
History.
Dead code elimination in dynamic languages is a much harder problem than in static languages. The idea of a "treeshaker" originated in LISP in the 1990s. The idea is that all possible execution flows of a program can be represented as a tree of function calls, so that functions that are never called can be eliminated.
The algorithm was applied to JavaScript in Google Closure Tools and then to Dart in the dart2js compiler also written by Google, presented by Bob Nystrom in 2012 and described by the book "Dart in Action" by author Chris Buckett in 2013:
The next wave of popularity of the term is attributed to Rich Harris's Rollup project developed in 2015.
Relation to ECMAScript 6 modules.
The popularity of tree shaking in JavaScript is based on the fact that in distinction from CommonJS modules, ECMAScript 6 module loading is static and thus the whole dependency tree can be deduced by statically parsing the syntax tree. Thus tree shaking becomes an easy problem. However, tree shaking does not only apply at the import/export level: it can also work at the statement level, depending on the implementation.


Brain Mapping Foundation

The Brain Mapping Foundation is a neuroscience organization established in 2004 by Babak Kateb to advance cross-pollination of ideas across physical sciences into biological sciences and neuroscience. The organization provides funding to the members of the Society for Brain Mapping and Therapeutics (SBMT). One of the focuses of the foundation is to further establish and fund the National Center for NanoBioElectronics (NCNBE) to rapidly integrate nanotechnology, devices, imaging, cellular and stem cell therapy. The organization has played a significant role in President Obama's BRAIN initiative.
Definition of brain mapping.
The study of the anatomy and function of the brain and spinal cord through the use of imaging (including intra-operative, Microscopic, Endoscopic and Multi-Modality imaging), Immunohistochemistry, Molecular & optogenetics, Stem cell and Cellular Biology, Engineering (material, electrical and biomedical), Neurophysiology and Nanotechnology (See Brain Mapping for more information).
Special projects.
Currently the organization is focused on establishing Global Alliance for Nano-Bio-Electronics through its National Center for NanoBioElectronic and has shaped policies in the field of Nanoneuroscience and Nanoneurosurgery. In this regard, the foundation has established significant ties with international partners and plans to launch a global consortium in Neuroscience with a specific aim of integrating nanotechnology, device, imaging and cellular therapy. BMF has signed a formal consortium agreement with Dr. Charlie Teo's Cure Brain Cancer Foundation in Australia, which is focused on eradicating brain cancers. NCNBE has also launched a graduate training program in NanoBioElectronic, which will be offering a doctoral degree in NanoBioElectronics.
Publications.
BMF has been a major supporter of the Society for Brain Mapping and Therapeutics (SBMT) annual meetings and its publications. The Foundation supported series of special issue publications with NeuroImage, in which members of the Society published their findings. The articles these publications were discontinued when the Society went into partnership with PLOS ONE on the ″NeuroMapping & Therapeutics Collection″. BMF also played a major role in publishing the first Textbook of Nanoneuroscience and Nanoneurosurgery.
Funded projects.
The foundation funds multidisciplinary translation research such as:
The Brain Mapping Foundation has been supporting annual meetings of Society for Brain Mapping and Therapeutics in the last 10 years.
Brain Mapping Day at the US Congress.
Brain Mapping Foundation in collaboration with the Society for Brain Mapping and Therapeutics (SBMT), hold the Brain Mapping Days at the US Congress and Canadian Parliament to educate policymakers about the state-of-the-art research in neuroscience. More information about the Brain Mapping Days can be found at https://web.archive.org/web/20131022180145/http://www.worldbrainmapping.org/brain-mapping-day and http://www.worldbrainmapping.org/brain-research-day.
Several notable scientists, such as Dr. Keith L. Black and Jean Paul Allain, have briefed congressional leaders during the Brain Mapping Days organized by BMF and SMBT.
Awards.
Brain Mapping Foundation has partnered with Society for Brain Mapping and Therapeutics (SBMT) to identify the most important scientific and clinical contributions to the field, and recognize them with the prestigious “Pioneer” awards. The awards are presented in partnership with SBMT, industry leaders and other foundations to highlight the significant work done by scientists, industry leaders, individuals, and policymakers.
U.S. congresswoman Gabby Giffords is the only award recipient who has been recognized twice by the Society and the Foundation for her courage and dedication toward raising awareness for neurotrauma as well as her role in healthcare reform. She was awarded a Beacon of courage and dedication and Pioneer in healthcare policy award by the Foundation and the Society.
Global Physicians and Scientists (GPS).
GPS is a humanitarian program, which is focused on mobilizing physicians, scientists and surgeons to serve for few weeks in the poor and rural areas of the United States and abroad. This program collaborates with industry and government officials and uses the national and international SBMT centers as bases of operations. The program is designed to help alleviate healthcare disparities by bringing world class physicians to poor areas, and to help improve local economies through micro and neuro economics.


Acoustic bass guitar

The acoustic bass guitar (sometimes shortened to acoustic bass or initialized ABG) is a bass instrument with a hollow wooden body similar to, though usually larger than a steel-string acoustic guitar. Like the traditional electric bass guitar and the double bass, the acoustic bass guitar commonly has four strings, which are normally tuned E-A-D-G, an octave below the lowest four strings of the 6-string guitar, which is the same tuning pitch as an electric bass guitar.
Because it can sometimes be difficult to hear an acoustic bass guitar without an amplifier, even in settings with other acoustic instruments, most acoustic basses have pickups, either magnetic or piezoelectric or both, so that they can be amplified with a bass amp.
Traditional music of Mexico features several varieties of acoustic bass guitars, such as the guitarrón, a very large, deep-bodied Mexican 6-string acoustic bass guitar played in Mariachi bands, the león, plucked with a pick, and the bajo sexto, with six pairs of strings.
History.
The Bassoguitar built by the Regal Musical Instrument Company is likely the first mass-produced acoustic bass to make use of a guitar-like body. This was an upright instrument, too big to play in a transverse position. The first modern acoustic bass guitar was developed in the mid-1950s by Kay of Chicago Harptone started producing their B4 model in 1965 under the name Supreme; production ended in 1975. They also made a very limited number under the Standel logo. Ernie Ball of San Luis Obispo, California, began producing a model in the early 70's. Ball's aim was to provide bass guitarists with a more acoustic-sounding instrument that would match better with the sound of acoustic guitars. Ball stated that "...if there were electric bass guitars to go with electric guitars then you ought to have acoustic basses to go with acoustic guitars." Ball notes that "...the closest thing to an acoustic bass was the Mexican guitarron...in mariachi bands, so I bought one down in Tijuana and tinkered with it."
Ball collaborated with George William Fullerton, a former employee at Fender, to develop the Earthwood acoustic bass guitar, which was introduced in 1972. Production of this instrument ceased in 1974, resuming a few years later under the direction of Ernie Ball's employee Dan Norton, until production finally ended again in 1985. The Earthwood acoustic bass guitar was quite large (and deep) in contrast to most instruments in current production, which gave it more volume, especially in the low register.photo 1photo 2photo 3 The Ernie Ball company describes Ball's design as "an idea before its time"; the instrument was little used in acoustic musical performances until the late 1980s, when the acoustic basses were used in performances on the "MTV Unplugged" television program. The Earthwood was quickly supplanted by the Washburn AB-40 designed by Mick Donner and Richard Siegle. The AB-40 and the more affordable AB-20 became the instrument of choice for bass players appearing on "Unplugged".
Folk bass player Ashley Hutchings used the acoustic bass guitar with his Etchingham Steam Band in 1974 and 1975. An early user of the acoustic bass guitar in rock was English multi-instrumentalist and composer Mike Oldfield, who had one custom-built for him by luthier Tony Zemaitis in the mid-1970s and used the bass on a number of his recordings from that time onwards, a prominent example being his 1975 album "Ommadawn".
Construction and tuning.
Unlike the electric bass guitar, which is generally a solid body instrument, the acoustic bass guitar usually has a hollow wooden body similar to (though usually somewhat larger than) that of the steel-string acoustic guitar. The majority of acoustic basses are fretted, but a significant number are fretless instead. Semi-fretted versions also exist, although they are quite rare.
Like the traditional electric bass and the double bass, the acoustic bass guitar commonly has four strings, which are normally tuned E-A-D-G, an octave below the lowest four strings of the 6-string guitar. Like the electric bass guitar, models with five or more strings have been produced, although these are less common. In part, this is because the body of an acoustic bass guitar is too small to produce a resonance of acceptable volume at lower pitches on the low "B" string. One solution uses the five string acoustic bass to add an additional high string ("E-A-D-G-C") instead of adding a low "B". Another solution is to rely on amplification to reproduce the low "B" string's notes, or by making the body a little bit larger.
There are also semi-acoustic models, fitted with pickups, for use with an amplifier. The soundbox of these instruments is not large enough to amplify the sound. Instead, it produces a distinctive tone when amplified, similarly to semi-acoustic electric guitars. Thin-body semi-acoustic basses such as the violin-shaped Höfner made famous by the early Beatles and several Fender models are not normally regarded as acoustic basses at all, but rather as hollow-bodied bass guitars. There are also semi-acoustic basses such as Godin Guitars' "A-Series" that, once amplified, sound much closer between acoustic bass guitars and upright basses (double bass), and have been used in professional circles to "simulate" one when it would be impractical for transportation and other reasons to use a full-sized upright bass. As with semi-acoustic electric guitars, the line between
acoustic instruments fitted with pickups and electric instruments with tone-enhancing bodies is sometimes hard to draw, especially
when some instruments can also be equipped with a variety of pickups such as piezo pickups, the "standard" of acoustic-electric instruments as well as synth pickups that can replay "virtual" upright bass sounds and bring a semi-acoustic bass much closer to a double bass sonically.
Saga Musical Instruments produces a four-string bass resonator guitar under their "Regal" brand name.videos National Reso-Phonic Guitars also produce three models of resonator bass guitar.
Manufacturers.
Other manufacturers of acoustic bass guitars (not mentioned above) include Alvarez, Ibanez, Boulder Creek Guitars, Breedlove, Chesbro Music Company (Teton Guitars), Cort, Crafter, Jerzey, Dean, Eko, Epiphone, Eston, Furch, Guild, Washburn, Maton, Ovation and its subsidiary Applause, Michael Kelly, Prestige, Ribbecke Halfling Bass, Sunlite, Sandberg, Stagg, Takamine, Tacoma, Tanglewood, Taylor, Larrivée, Lindo Guitars, Warwick, Fender, Gibson and Martin.
Mexican bass guitars.
Traditional music of Mexico features varieties of acoustic bass guitars. The guitarrón is a very large, deep-bodied Mexican 6-string acoustic bass guitar played in Mariachi bands. The bajo sexto, with six pairs of strings, resembles a twelve-string guitar tuned an octave lower. The heavy gauge strings generate a large string tension, yet the guitar is built relatively lightly. Musicians began to adopt the bajo sexto in Texas in the 1920s with the rise of "Tex-Mex" music, and remains in common use to play parts that would be played by the piano in traditional American popular music. The tuning of these instruments is (capital letters are an octave lower than small letters):
Other Latin American acoustic bass guitars exist as well, such as the Bordonua.


Inferior cervical ganglion

The inferior cervical ganglion is situated between the base of the transverse process of the last cervical vertebra and the neck of the first rib, on the medial side of the costocervical artery.
Its form is irregular; it is larger in size than the middle cervical ganglion, and is frequently fused with the first thoracic ganglion, under which circumstances it is then called the "stellate ganglion."
Structure.
It is connected to the middle cervical ganglion by two or more cords, one of which forms a loop around the subclavian artery and supplies offsets to it. This loop is named the "ansa subclavia" (Vieussenii).
The ganglion sends gray rami communicantes to the seventh and eighth cervical nerves.
Branches.
The inferior cervical ganglion gives off two branches:
Development.
It is probably formed by the coalescence of two ganglia which correspond to the seventh and eighth cervical nerves.


Redundancy principle (biology)

The redundancy principle in biology expresses the need of many copies of the same entity (cells, molecules, ions) to fulfill a biological function. Examples are numerous: disproportionate numbers of spermatozoa during fertilization compared to one egg, large number of neurotransmitters released during neuronal communication compared to the number of receptors, large numbers of released calcium ions during transient in cells and many more in molecular and cellular transduction or gene activation and cell signaling. This redundancy is particularly relevant when the sites of activation is physically separated from the initial position of the molecular messengers. The redundancy is often generated for the purpose of resolving the time constraint of fast-activating pathways. It can be expressed in terms of the theory of extreme statistics to determine its laws and quantify how shortest paths are selected. The main goal is to estimate these large numbers from physical principles and mathematical derivations.
When large distance separate the source and the target (a small activation site), the redundancy principle explains that this geometrical gap can be compensated by large number. Had nature used less copies than normal, activation would have taken a much longer time, as finding a small target by chance is a rare events and falls into narrow escape problems.
Molecular rate.
The time for the fastest particles to reach a target in the context of redundancy depends on the numbers and the local geometry of the target. In most of the time, it is the rate of activation. This rate should be used instead of the classical Smoluchowski's rate describing the mean arrival time, but not the fastest. The statistics of the minimal time to activation set kinetic laws in biology, which can be quite different from the ones associated to average times.
Physical models.
Stochatic processes.
The motion of a particle located at position formula_1 can be described by the Smoluchowski's limit of the Langevin equation:
formula_2
where formula_3 is the diffusion coefficient of the particle, formula_4 is the friction coefficient per unit of mass, formula_5 the force per unit of mass, and formula_6 is a Brownian motion. This model is classically used in molecular dynamics simulations.
Jump processes.
formula_7, which is for example a model of telomere length dynamics. Here formula_8 , with formula_9.
Directed motion process.
formula_10 where formula_11 is a unit vector chosen from a uniform distribution. Upon hitting an obstacle at a boundary point formula_12, the velocity changes to formula_13 where formula_14 is chosen on the unit sphere in the supporting half space at formula_15 from a uniform distribution, independently of formula_11. This rectilinear with constant velocity is a simplified model of spermatozoon motion in a bounded domain formula_17. Other models can be diffusion on graph, active graph motion.
Mathematical formulation: Computing the rate of arrival time for the fastest.
The mathematical analysis of large numbers of molecules, which are obviously redundant in the traditional activation theory, is used to compute the in vivo time scale of stochastic chemical reactions. The computation relies on asymptotics or probabilistic approaches to estimate the mean time of the fastest to reach a small target in various geometries.
With N non-interacting i.i.d. Brownian trajectories (ions) in a bounded domain Ω that bind at a site, the shortest arrival time is by definition
formula_18 where formula_19 are the independent arrival times of the N ions in the medium. The survival distribution of arrival time of the fastest formula_20 is expressed in terms of a single particle, formula_21. Here formula_22 is the survival probability of a single particle prior to binding at the target.This probability is computed from the solution of the diffusion equation in a domain formula_23:
formula_24
formula_25
where the boundary formula_26 contains NR binding sites formula_27 (formula_28). The single particle survival probability is
formula_29 so that formula_30where
formula_31and formula_32.
The probability density function (pdf) of the arrival time is
formula_33 which gives the MFPT
formula_34 The probability formula_35 can be computed using short-time asymptotics of the diffusion equation as shown in the next sections.
Explicit computation in dimension 1.
The short-time asymptotic of the diffusion equation is based on the ray method approximation. For an semi-interval formula_36, the survival pdf is solution of
formula_37
that isformula_38
The survival probability with D=1 is formula_39. To compute the MFPT, we expand the complementary error function
formula_40 which givesformula_41,
leading (the main contribution of the integral is near 0) to formula_42
This result is reminiscent of using the Gumbel's law. Similarly, escape from the interval [0,a] is computed from the infinite sum
formula_43.The conditional survival probability is approximated by
formula_44, where the maximum occurs at formula_45 min[y,a-y] for 0<y\bar{\tau}^{1}= \int\limits\limits_0 ^{\infty} \left[ \Pr\{t_{1}>t\} \right]^N dt \approx
e^{-\delta^2/16t}\right) \right\}dt \approx \frac{\delta^2}{16D\ln\frac{2N}{\sqrt{\pi}}}\quad\mbox{for}\ N\gg1. </math>
Arrival times of the fastest in higher dimensions.
The arrival times of the fastest among many Brownian motions are expressed in terms of the shortest distance from the source S to the absorbing window A, measured by the distance formula_46where d is the associated Euclidean distance. Interestingly, trajectories followed by the fastest are as close as possible from the optimal trajectories. In technical language, the associated trajectories of the fastest among N, concentrate near the optimal trajectory (shortest path) when the number N of particles increases. For a diffusion coefficient D and a window of size a, the expected first arrival times of N identically independent distributed Brownian particles initially positioned at the source S are expressed in the following asymptotic formulas :
formula_47
formula_48
formula_49
These formulas show that the expected arrival time of the fastest particle is in dimension 1 and 2, O(1/\log(N)). They should be used instead of the classical forward rate in models of activation in biochemical reactions. The method to derive formulas is based on short-time asymptotic and the Green's function representation of the Helmholtz equation. Note that other distributions could lead to other decays with respect N.
Optimal Paths.
Minimizing The optimal path in large N.
The optimal paths for the fastest can be found using the Wencell-Freidlin functional in the Large-deviation theory. These paths correspond to the short-time asymptotics of the diffusion equation from a source to a target. In general, the exact solution is hard to find, especially for a space containing various distribution of obstacles.
The Wiener integral representation of the pdf for a pure Brownian motion is obtained for a zero drift and diffusion tensor formula_50 constant, so that it is given by the probability of a sampled path until it exits at the small window formula_51at the random time T
formula_52
formula_53
where
formula_54 in the product and T is the exit time in the narrow absorbing window formula_55 Finally,
formula_56
where formula_57 is the ensemble of shortest paths selected among n Brownian trajectories, starting at point y and exiting between time t and t+dt from the domain formula_23. The probabilityformula_59 is used to show that the empirical stochastic trajectories of formula_60 concentrate near the shortest paths starting from y and ending at the small absorbing window formula_61, under the condition that formula_62.  The paths of formula_57 can be approximated using discrete broken lines among a finite number of points and we denote the associated ensemble by formula_64.  Bayes'rule leads toformula_65 where formula_66 is the probability that a path of formula_64  exits in m-discrete time steps. A path made of broken lines (random walk with a time stepformula_68) can be expressed using Wiener path-integral.  The probability of a Brownian path x(s) can be expressed in the limit of a path-integral with the functional:
formula_69
The Survival probability conditioned on starting at y is given by the Wiener representation:
formula_70
where formula_71 is the limit Wiener measure: the exterior integral is taken over all end points x and the path integral is over all paths starting from x(0). When we consider n-independent paths formula_72 (made of points with a time step formula_68 that exit in m-steps, the probability of such an event is
formula_74.Indeed, when there are n paths of m steps, and the fastest one escapes in m-steps, they should all exit in m steps. Using the limit of path integral, we get heuristically the representation
<math>Pr \{ \hbox{ Path }\sigma \in \tilde S_n(y)|m, \tau_{\sigma}=m \Delta t \}= \left(\int\limits_


Tactile pad

A tactile pad is an area of skin that is particularly sensitive to pressure, temperature, or pain. Tactile pads are characterized by high concentrations of free nerve endings. In primates, the last phalanges in the fingers and toes have tactile pads, allowing very accurate manipulation of objects. This precision grip was an important evolutionary advance in primates.


Alpha-Methylhistamine

α-Methylhistamine is a histamine agonist selective for the receptor subtype H3. It causes lowering of blood pressure and a decrease of heart rate in animal models.


Kishinouyei

Kishinouyei is a new Latin adjective referring to Japanese marine biologist Kamakichi Kishinouye (1867–1929).


Lugaro cell

Lugaro cells are primary sensory interneurons of the cerebellum, that have an inhibitory function. They are fusiform, having a spindle shape that tapers at each end. They were first described by Ernesto Lugaro in the early 20th century. Lugaro cells are found just beneath the layer of Purkinje cells between the molecular layer and the granular layer. They have thick principal dendrites coming from opposite poles of their bodies. These dendrites are very long and travel along the boundary between the Purkinje layer and the granular layer. They seem to contact from 5 to 15 Purkinje cells in a horizontal direction. They can also sense stimuli close to the Purkinje cells and their dendrites form a large receptive area that monitors the environment near to the Purkinje cells. Whilst their dendrites make contact with the Purkinje cells they also receive inputs from branches of the Purkinje axons by which they seem to have a sampling and integration role.
The Lugaro cell has a major role in the cerebellum, interconnecting many neurons located in all layers of the cortex. It samples information from the Purkinje cell axon collaterals and forwards this information to the molecular and granular layers of the cerebellum. The axons of the Lugaro cells only contact inhibitory interneurons such as the basket, stellate and Golgi cells. The parallel axon targets stellate and basket cells and the transverse axon targets Golgi cells.
The Lugaro cell axon can sometimes take a curving detour through the granular layer, before running its parallel course in the molecular layer. The axon dips through the granular layer, into the white matter, before going up to terminate on basket or stellate cells in the molecular layer.
Sometimes the Lugaro cell axon will also terminate on Golgi cells in the granular layer without going on up again to the molecular layer, so that the Golgi cells are the target. According to Dieudonne, the Lugaro cell forms a major input to Golgi cells, and one Lugaro cell may contact up to 100 Golgi cells.


2-Pyridylethylamine

2-Pyridylethylamine is a histamine agonist which is selective for the H1 subtype.


Supratentorial region

In anatomy, the supratentorial region of the brain is the area located above the tentorium cerebelli. The area of the brain below the tentorium cerebelli is the infratentorial region. The supratentorial region contains the cerebrum, while the infratentorial region contains the cerebellum.
Although the Roman era anatomist Galen commented upon it, the functional significance of this neuroanatomical division was first described using ‘modern’ terminology by John Hughlings Jackson, founding editor of the medical journal, Brain.
From extensive studies of anatomy and behaviour, Hughlings Jackson established the existence of a clear division of cognitive functionality located at or around the tentorium cerebelli. In his proposed scheme, while the supratentorial parts (mainly the cerebrum) were responsible for planning and control of movement in the world, the infratentorial parts (mainly the cerebellum) were responsible for planning and control of bodily motion per se.
Slang: Medical personnel, when referring to a patient that is a hypochondriac, will sometimes say the problem is ‘supratentorial’ - even using this notation in the chart, to convey their true meaning, it's all in the patient's head.


Phenylisobutylamine

Phenylisobutylamine, also known as α-ethylphenethylamine, Butanphenamine, B or AEPEA, is a stimulant drug of the phenethylamine class. It is a higher homologue of amphetamine, differing from amphetamine's molecular structure only by the substitution of the methyl group at the alpha position of the side chain with an ethyl group. Compared to amphetamine, phenylisobutylamine has strongly reduced dopaminergic effects, and instead acts as a selective norepinephrine releasing agent. The dextroisomer of phenylisobutylamine partially substitutes for dextroamphetamine in rats.
A number of derivatives of phenylisobutylamine are known, including BDB, MBDB, EBDB, butylone (bk-MBDB), eutylone (bk-EBDB), Ariadne (α-Et-DOM), 4-CAB, and 4-MAB.
"Phenylisobutylamine" is in fact a chemical misnomer because isobutylamine itself contains a branched chain. The correct name after this style for this class of compound would be "phenyl"sec"butylamine".