Phrenic nerve

The phrenic nerve is a mixed motor/sensory nerve which originates from the C3-C5 spinal nerves in the neck. The nerve is important for breathing because it provides exclusive motor control of the diaphragm, the primary muscle of respiration. In humans, the right and left phrenic nerves are primarily supplied by the C4 spinal nerve, but there is also contribution from the C3 and C5 spinal nerves. From its origin in the neck, the nerve travels downward into the chest to pass between the heart and lungs towards the diaphragm.
In addition to motor fibers, the phrenic nerve contains sensory fibers, which receive input from the central tendon of the diaphragm and the mediastinal pleura, as well as some sympathetic nerve fibers. Although the nerve receives contributions from nerves roots of the cervical plexus and the brachial plexus, it is usually considered separate from either plexus.
The nerve is named from the Ancient Greek "phren", meaning diaphragm.
Structure.
The phrenic nerve originates in the phrenic motor nucleus in the ventral horn of the cervical spinal cord. It descends obliquely with the internal jugular vein across the anterior scalene, deep to the prevertebral layer of deep cervical fascia and the transverse cervical and suprascapular arteries. On the left, the phrenic nerve crosses anterior to the first part of the subclavian artery. On the right, it lies on the anterior scalene muscle and crosses anterior to the 2nd part of the subclavian artery. On both sides, the phrenic nerve usually runs posterior to the subclavian vein as it enters the thorax where it runs anterior to the root of the lung and between the fibrous pericardium and mediastinal parietal pleura.
The pericardiacophrenic arteries and veins travel with their respective phrenic nerves.
The phrenic nerve can be marked by a line connecting these two points:
Variation.
As with most nerves in the neck, multiple anatomic variants have been described. Notably, there may be variability in the course of the phrenic nerve in the retroclavicular region such that the nerve courses anterior to the subclavian vein, rather than its typical position posterior to the vein (between the subclavian vein and artery). This variant may predispose the phrenic nerve to injury during subclavian vascular cannulation.
In addition, an accessory phrenic nerve is commonly identified, present in up to 75% of a cadaveric study.
In canines the phrenic nerve arises from C5-C7 with occasional small contributions from C4. In the cat, horse, ox, and small ruminant the phrenic nerve arises variably from C4-C7.
Function.
Both of these nerves supply motor fibers to the diaphragm and sensory fibers to the fibrous pericardium, mediastinal pleura, and diaphragmatic peritoneum.
Some sources describe the right phrenic nerve as innervating the gallbladder, other sources make no such mention.
The right phrenic nerve may also supply the capsule of the liver.
Clinical significance.
Pain arising from structures supplied by the phrenic nerve is often "referred" to other somatic regions served by spinal nerves C3-C5. For example, a subphrenic abscess beneath the right diaphragm might cause a patient to feel pain in the right shoulder.
Irritation of the phrenic nerve (or the tissues it supplies) leads to the hiccup reflex. A hiccup is a spasmodic contraction of the diaphragm, which pulls air against the closed folds of the larynx.
The phrenic nerve must be identified during thoracic surgery and preserved. To confirm the identity of the phrenic nerve, a doctor may gently manipulate it to elicit a dartle (diaphragmatic startle) response. The right phrenic nerve may be crushed by the vena cava clamp during liver transplantation. Severing the phrenic nerve, or a phrenectomy, will paralyse that half of the diaphragm. Bilateral diaphragmatic paralysis or BDP can also be caused by spinal cord injury, motor neuron disease, infection, pneumonia, sarcoidosis, multiple sclerosis, polyneuropathy, myopathy and amyotrophy, cardiac surgery, lung transplantation, or mediastinal tumors. Diaphragm paralysis is best demonstrated by sonography. Breathing will be made more difficult but will continue provided the other nerve is intact.
The phrenic nerve arises from the neck (C3-C5) and innervates the diaphragm, which is much lower. Hence, patients suffering spinal cord injuries below the neck are still able to breathe effectively, despite any paralysis of the lower limbs.
Brachial plexus injuries can cause paralysis to various regions in the arm, forearm, and hand depending on the severed nerves. The resulting palsy has been clinically treated using the phrenic nerve as a donor for neurotization of the musculocutaneous nerve and the median nerve. This treatment has a high success rate (84.6%) in partial to full restoration of the innervation to the damaged nerve. Furthermore, this procedure has resulted in restored function to nerves in the brachial plexus with minimal impact to respiratory function of the phrenic nerve. The instances where pulmonary vital capacity is reduced have typically been a result of use of the right phrenic as the donor for the neurotization whereas use of left phrenic nerve has not been significantly linked to reduced pulmonary vital capacity.


Purkinje effect

The Purkinje effect (sometimes called the Purkinje shift) is the tendency for the peak luminance sensitivity of the eye to shift toward the blue end of the color spectrum at low illumination levels as part of dark adaptation. In consequence, reds will appear darker relative to other colors as light levels decrease. The effect is named after the Czech anatomist Jan Evangelista Purkyně. While the effect is often described from the perspective of the human eye, it is well established in a number of animals under the same name to describe the general shifting of spectral sensitivity due to pooling of rod and cone output signals as a part of dark/light adaptation.
This effect introduces a difference in color contrast under different levels of illumination. For instance, in bright sunlight, geranium flowers appear bright red against the dull green of their leaves, or adjacent blue flowers, but in the same scene viewed at dusk, the contrast is reversed, with the red petals appearing a dark red or black, and the leaves and blue petals appearing relatively bright.
The sensitivity to light in scotopic vision varies with wavelength, though the perception is essentially black-and-white. The Purkinje shift is the relation between the absorption maximum of rhodopsin, reaching a maximum at about 500 nm, and that of the opsins in the longer-wavelength cones that dominate in photopic vision, about 555 nm (green).
In visual astronomy, the Purkinje shift can affect visual estimates of variable stars when using comparison stars of different colors, especially if one of the stars is red.
Physiology.
The Purkinje effect occurs at the transition between primary use of the photopic (cone-based) and scotopic (rod-based) systems, that is, in the mesopic state: as intensity dims, the rods take over, and before color disappears completely, it shifts towards the rods' top sensitivity.
The effect occurs because in mesopic conditions the outputs of cones in the retina, which are generally responsible for the perception of color in daylight, are pooled with outputs of rods which are more sensitive under those conditions and have peak sensitivity in blue-green wavelength of 507 nm.
Use of red lights.
The insensitivity of rods to long-wavelength light has led to the use of red lights under certain special circumstances—for example, in the control rooms of submarines, in research laboratories, aircraft, or during naked-eye astronomy.
Red lights are used in conditions where it is desirable to activate both the photopic and scotopic systems. Submarines are well lit to facilitate the vision of the crew members working there, but the control room must be lit differently to allow crew members to read instrument panels yet remain dark adjusted. By using red lights or wearing red goggles, the cones can receive enough light to provide photopic vision (namely the high-acuity vision required for reading). The rods are not saturated by the bright red light because they are not sensitive to long-wavelength light, so the crew members remain dark adapted.
Similarly, airplane cockpits use red lights so pilots can read their instruments and maps while maintaining night vision to see outside the aircraft.
Red lights are also often used in research settings. Many research animals (such as rats and mice) have limited photopic vision, as they have far fewer cone photoreceptors.
The animal subjects do not perceive red lights and thus experience darkness (the active period for nocturnal animals), but the human researchers, who have one kind of cone (the "L cone") that is sensitive to long wavelengths, are able to read instruments or perform procedures that would be impractical even with fully dark adapted (but low acuity) scotopic vision.
For the same reason, zoo displays of nocturnal animals often are illuminated with red light.
History.
The effect was discovered in 1819 by Jan Evangelista Purkyně. Purkyně was a polymath who would often meditate at dawn during long walks in the blossomed Bohemian fields. Purkyně noticed that his favorite flowers appeared bright red on a sunny afternoon, while at dawn they looked very dark. He reasoned that the eye has not one but two systems adapted to see colors, one for bright overall light intensity, and the other for dusk and dawn.
Purkyně wrote in his "Neue Beiträge:"
Objectively, the degree of illumination has a great influence on the intensity of color quality. In order to prove this most vividly, take some colors before daybreak, when it begins slowly to get lighter. Initially one sees only black and grey. Particularly the brightest colors, red and green, appear darkest. Yellow cannot be distinguished from a rosy red. Blue became noticeable to me first. Nuances of red, which otherwise burn brightest in daylight, namely carmine, cinnabar and orange, show themselves as darkest for quite a while, in contrast to their average brightness. Green appears more bluish to me, and its yellow tint develops with increasing daylight only.


Society of Neuroscientists of Africa

The Society of Neuroscientists of Africa (SONA) is a non-profit organisation registered in Nairobi, Kenya, which acts as the umbrella organisation for different neuroscience groups and societies in Africa. They organise the bi-annual SONA conference. The current president of the society is Prof. James Olukayode Olopade.
History.
SONA was founded in 1993 by James Kimani. The goal of the society is to promote neuroscience research and teaching in Africa. In its history the society has organised 14 international meetings in Africa, of which the first was organized in 1993.


Control Factor

Control Factor is a 2003 Sci Fi Pictures science fiction TV-movie.
Plot.
After a mysterious, disheveled man nearly kills him, insurance salesman Lance Bishop hears a voice in his head urging him to murder his wife. When he discovers he has become part of a government mind-control project, he and others similarly being experimented on fight back.


Histamine agonist

A histamine agonist is a drug which causes increased activity at one or more of the four histamine receptor subtypes.
H2 : Betazole and Impromidine are examples of agonists used in diagnostics to increase histamine.
H3 : Betahistine is a weak Histamine1 agonist and a very strong Histamine3 antagonist (paradoxically histamine increasing).


Evolutionary neuroscience

Evolutionary neuroscience is the scientific study of the evolution of nervous systems. Evolutionary neuroscientists investigate the evolution and natural history of nervous system structure, functions and emergent properties. The field draws on concepts and findings from both neuroscience and evolutionary biology. Historically, most empirical work has been in the area of comparative neuroanatomy, and modern studies often make use of phylogenetic comparative methods. Selective breeding and experimental evolution approaches are also being used more frequently.
Conceptually and theoretically, the field is related to fields as diverse as cognitive genomics, neurogenetics, developmental neuroscience, neuroethology, comparative psychology, evo-devo, behavioral neuroscience, cognitive neuroscience, behavioral ecology, biological anthropology and sociobiology.
Evolutionary neuroscientists examine changes in genes, anatomy, physiology, and behavior to study the evolution of changes in the brain. They study a multitude of processes including the evolution of vocal, visual, auditory, taste, and learning systems as well as language evolution and development. In addition, evolutionary neuroscientists study the evolution of specific areas or structures in the brain such as the amygdala , forebrain and cerebellum as well as the motor or visual cortex.
History.
Studies of the brain began during ancient Egyptian times but studies in the field of evolutionary neuroscience began after the publication of Darwin's On the Origin of Species in 1859. At that time, brain evolution was largely viewed at the time in relation to the incorrect scala naturae. Phylogeny and the evolution of the brain were still viewed as linear. During the early 20th century, there were several prevailing theories about evolution. Darwinism was based on the principles of natural selection and variation, Lamarckism was based on the passing down of acquired traits, Orthogenesis was based on the assumption that tendency towards perfection steers evolution, and Saltationism argued that discontinuous variation creates new species. Darwin's became the most accepted and allowed for people to starting thinking about the way animals and their brains evolve.
The 1936 book "The Comparative Anatomy of the Nervous System of Vertebrates Including Man" by the Dutch neurologist C.U. Ariëns Kappers (first published in German in 1921) was a landmark publication in the field. Following the Evolutionary Synthesis, the study of comparative neuroanatomy was conducted with an evolutionary view, and modern studies incorporate developmental genetics. It is now accepted that phylogenetic changes occur independently between species over time and can not be linear. It is also believed that an increase with brain size correlates with an increase in neural centers and behavior complexity.
Major Arguments.
Over time, there are several arguments that would come to define the history of evolutionary neuroscience. The first is the argument between Etienne Geoffro St. Hilaire and George Cuvier over the topic of "common plan versus diversity". Geoffrey argued that all animals are built based on a single plan or archetype and he stressed the importance of homologies between organisms, while Cuvier believed that the structure of organs was determined by their function and that knowledge of the function of one organ could help discover the functions of other organs. He argued that there were at least four different archetypes. After Darwin, the idea of evolution was more accepted and Geoffrey's idea of homologous structures was more accepted. The second major argument is that of the Scala Naturae (scale of nature) versus the phylogenetic bush. The Scala Naturae, later also called the phylogenetic scale, was based on the premise that phylogenies are linear or like a scale while the phylogenetic bush argument was based on the idea that phylogenies were nonlinear and resembled a bush more than a scale. Today it is accepted that phylogenies are nonlinear. A third major argument dealt with the size of the brain and whether relative size or absolute size was more relevant in determining function. In the late 18th century, it was determined that brain to body ratio reduces as body size increases. However more recently, there is more focus on absolute brain size as this scales with internal structures and functions, with the degree of structural complexity, and with the amount of white matter in the brain, all suggesting that absolute size is much better predictor of brain function. Finally, a fourth argument is that of natural selection (Darwinism) versus developmental constraints (concerted evolution). It is now accepted that the evolution of development is what causes adult species to show differences and evolutionary neuroscientists maintain that many aspects of brain function and structure are conserved across species.
Techniques.
Throughout history, we see how evolutionary neuroscience has been dependent on developments in biological theory and techniques. The field of evolutionary neuroscience has been shaped by the development of new techniques that allow for the discovery and examination of parts of the nervous system. In 1873, Camillo Golgi devised the silver nitrate method which allowed for the description of the brain at the cellular level as opposed to simply the gross level. Santiago Ramon and Pedro Ramon used this method to analyze numerous parts of brains, broadening the field of comparative neuroanatomy. In the second half of the 19th century, new techniques allowed scientists to identify neuronal cell groups and fiber bundles in brains. In 1885, Vittorio Marchi discovered a staining technique that let scientists see induced axonal degeneration in myelinated axons, in 1950, the “original Nauta procedure” allowed for more accurate identification of degenerating fibers, and in the 1970s, there were several discoveries of multiple molecular tracers which would be used for experiments even today. In the last 20 years, cladistics has also become a useful tool for looking at variation in the brain.
Evolution of the Human Brain.
Darwin's theory allowed for people to start thinking about the way animals and their brains evolve.
Reptile Brain.
The cerebral cortex of reptiles resembles that of mammals, although simplified. Although the evolution and function of the human cerebral cortex is still shrouded in mystery, we know that it is the most dramatically changed part of the brain during recent evolution.
Visual perception.
Research about how visual perception has developed in evolution is today best understood through studying present-day primates, since the organization of the brain cannot be ascertained only by analyzing fossilized skulls.
Auditory Perception.
The organization of human auditory cortex is divided into core, belt and parabelt. This closely resembles that of present-day primates.
Language development.
Evidence of a rich cognitive life in primate relatives of humans are extensive, and a wide range of specific behaviors in line with Darwinian theory are well documented. However, until recently, research has disregarded nonhuman primates in the context of evolutionary linguistics, primarily because unlike vocal learning birds, our closest relatives seem to lack imitative abilities. Evolutionary speaking, there is great evidence suggesting a genetical groundwork for the concept of languages has been in place for millions of years, as with many other capabilities and behaviors observed today.
While evolutionary linguists agree on the fact that volitional control over vocalizing and expressing language is a quite recent leap in the history of the human race, that is not to say auditory perception is a recent development as well. Research has shown substantial evidence of well defined neural pathways linking cortices to organize auditory perception in the brain. Thus, the issue lies in our abilities to imitate sounds.
Beyond the fact that primates may be poorly equipped to learn sounds, studies have shown them to learn and use gestures far better. Visual cues and motoric pathways developed millions of years earlier in our evolution, which seems to be one reason for an earlier ability to understand and use gestures.


Flocculus

The flocculus (Latin: "tuft of wool", diminutive) is a small lobe of the cerebellum at the posterior border of the middle cerebellar peduncle anterior to the biventer lobule. Like other parts of the cerebellum, the flocculus is involved in motor control. It is an essential part of the vestibulo-ocular reflex, and aids in the learning of basic motor skills in the brain.
It is associated with the nodulus of the vermis; together, these two structures compose the vestibular part of the cerebellum.
At its base, the flocculus receives input from the inner ear's vestibular system and regulates balance. Many floccular projections connect to the motor nuclei involved in control of eye movement.
Structure.
The flocculus is contained within the flocculonodular lobe which is connected to the cerebellum. The cerebellum is the section of the brain that is essential for motor control. As a part of the cerebellum, the flocculus plays a part of the vestibulo-ocular reflex system, a system that controls the movement of the eye in coordination with movements of the head. There are five separate “zones” in the flocculus and two halves, the caudal and rostral half.
Circuitry of the flocculus.
The flocculus has a complex circuitry that is reflected in the structure of the zones and halves. These "zones" of the flocculus refer to five separate groupings of Purkinje cells that project to different areas of the brain. Depending upon where stimulus occurs in the flocculus, signals can be projected to very different parts of the brain. The first and third zones of the flocculus project to the superior vestibular nucleus, the second and fourth zone projects to the medial vestibular nucleus, and the fifth zone projects to the interposed posterior nucleus, a part of the cerebellum.
The anatomy of the flocculus shows that it is composed of two disjointed lobes or halves. The “halves” of the flocculus refer to the caudal half and the rostral half, and they indicate from where fiber projections are received and the path in which a signal travels. The caudal half of the flocculus receives mossy fiber projections mainly from the vestibular system and tegmental pontine reticular nucleus, an area within the floor of the midbrain that affects the axonal projections or images received by the cerebellum. Vestibular inputs are also carried through climbing fibers that project into the flocculus, stimulating Purkinje cells. Leading research would suggest that climbing fibers play a specific role in motor learning. The climbing fibers then send the image or projection to the part of the brain that receives electrical signals and generates movement. From the midbrain, corticopontine fibers carry information from the primary motor cortex. From there, projections are sent to the ipsilateral pontine nucleus in the ventral pons, both of which are associated with projections to the cerebellum. Finally, pontocerebellar projections carry vestibulo-occular signals to the contralateral cerebellum via the middle cerebellar peduncle. The rostral half of the flocculus also receives mossy fiber projections from the pontine nuclei; however, it receives very little projection from the vestibular system.
Function.
The flocculus is a part of the vestibulo-ocular reflex system and is used to help stabilize gaze during head rotation about any axis of space. Neurons in both the vermis of cerebellum and flocculus transmit an eye velocity signal that correlates with smooth pursuit.
Flocculus role In learning basic motor functions.
The idea that the flocculus is involved in motor learning gave rise to the “flocculus hypothesis.” This hypothesis argues that the flocculus plays a key role in the vestibulo-ocular system, most importantly the ability for the vestibular system to adapt to a shift in the visual field. The learning of basic motor skills, including walking, balancing, and the ability to sit up, can be attributed to early patterns and pathways associated with the vestibulo-occular reflex and the pathways formed in the cerebellum. Within the cerebellum pathways that contribute to the learning of basic motor skills. Also
The flocculus appears to be included a VOR pathway that aids in the adaptation to a repeated shift in the visual field. A shift in the visual field affects an individuals spatial recognition. The leading research would suggest that flocculus aids in the synchronization of eye and motor functions after a visual shift occurs in order for the visual field and the motor skills to function together. If this shift is repeated the flocculus essentially trains the brain to fully readjust to this repeated stimuli.
Location.
Constituted by two disjointed-shaped lobes, the flocculus is positioned within the lowest level of the cerebellum. There are three main subdivisions in the cerebellum and the flocculus is contained within the most primitive the vestibulocerebellum.
Its lobes are linked through a circuit of neurons connecting to the vermis, the medial structure in the cerebellum. Extensions leave the base of the follucular's lobes which then connect to the spinal cord. The cerebellum, which houses the flocculus, is located in the back and at the base of the human brain, directly above the brainstem.
Clinical significance.
The flocculus is most important for the pursuit of movements with the eyes. Lesions in the flocculus impair control of the vestibulo-ocular reflex, and gaze holding also known as vestibulocerebellar syndrome. The deficits observed in patients with lesions to this area resemble dose-dependent effects of alcohol on pursuit movements. Bilateral lesions of the flocculus reduce the gain of smooth pursuit, which is the steady tracking of a moving object by the eyes. Instead, the bilateral lesions of the flocculus result in saccadic pursuit, in which smooth tracking is replaced by simultaneous rapid movements, or jerking motions, of the eye to follow an object toward the ipsilateral visual field. These lesions also impair the ability to hold the eyes in the eccentric position, resulting in gaze-evoked nystagmus toward the affected side of the cerebellum. Nystagmus is the constant involuntary movements of the eyes; a patient can have either horizontal nystagmus (side-to-side eye movements), vertical nystagmus (up and down eye movements), or rotary nystagmus (circular eye movements). The flocculus also plays a role in keeping the body oriented in space. A lesion in this area will result in ataxia, a neurological disorder that results in the deterioration of the coordination of muscle movements, and unsteady bodily movements such as swaying and staggering.
Associated conditions.
The conditions and systems associated with floccular loss are considered to be a subset of a vestibular disease. Some symptoms of common vestibular diseases include: head tilting, an inability to stand, ataxia, dizziness, vomiting and strabismus. Because of the flocculus’ role in the vestibular system, the inner ear, equilibrioception, and both peripheral and central vision is affected by any loss or damage to the Flocculus. These systems are affected because damage to the flocculus prevents any changes from being stored in regards to visual and motor communication, meaning that although the VOR is still intact these systems are unable to store changes in gain or eye movement as you rotate your head back and forth.


Subject (documents)

In library and information science documents (such as books, articles and pictures) are classified and searched by subject – as well as by other attributes such as author, genre and document type. This makes "subject" a fundamental term in this field. Library and information specialists assign subject labels to documents to make them findable. There are many ways to do this and in general there is not always consensus about which subject should be assigned to a given document. To optimize subject indexing and searching, we need to have a deeper understanding of what a subject is. The question: "what is to be understood by the statement 'document A belongs to subject category X'?" has been debated in the field for more than 100 years (see below).
Definition.
Hjørland defined subjects as the "epistemological potentials of documents". This definition is in line with the request oriented understanding of indexing quoted below. The idea is that a document is assigned a subject to ease retrieval and findability. And the criteria for what should be found – what constitutes knowledge – is in the end an epistemological question.
Theoretical view.
Charles Ammi Cutter (1837–1903).
For Cutter the stability of subjects depends on a social process in which their meaning is stabilized in a name or a designation. A subject "referred [...] to those intellections [...] that had received a name that itself represented a distinct consensus in usage" (Miksa, 1983a, p. 60) and: the "systematic structure of established subjects" is "resident in the public realm" (Miksa, 1983a, p. 69); "[s]ubjects are by their very nature locations in a classificatory structure of publicly accumulated knowledge (Miksa, 1983a, p. 61). Bernd Frohmann adds:
"The stability of the public realm in turn relies upon natural and objective mental structures which, with proper education, govern a natural progression from particular to general concepts.
Since for Cutter, mind, society, and SKO [Systems of Knowledge Organization] stand one behind the other, each supporting each, all manifesting the same structure, his discursive construction of subjects invites connections with discourses of mind, education, and society. The Dewey Decimal Classification (DDC), by contrast, severs those connections. Melvil Dewey emphasized more than once that his system maps no structure beyond its own; there is neither a "transcendental deduction" of its categories nor any reference to Cutter's objective structure of social consensus. It is content-free: Dewey disdained any philosophical excogitation of the meaning of his class symbols, leaving the job of finding verbal equivalents to others. His innovation and the essence of the system lay in the notation. The DDC is a poorly semiotic system of expanding nests of ten digits, lacking any referent beyond itself. In it, a subject is wholly constituted in terms of its position in the system. The essential characteristic of a subject is a class symbol which refers only to other symbols. Its verbal equivalent is accidental, a merely pragmatic characteristic...
The conflict of interpretations over "subjects" became explicit in the battles between "bibliography" (an approach to subjects having much in common with Cutter's) and Dewey's "close classification". William Fletcher spoke for the scholarly bibliographer... Fletcher's "subjects", like Cutter's, referred to the categories of a fantasized, stable social order, whereas Dewey's subjects were elements of a semiological system of standardized, techno-bureaucratic administrative software for the library in its corporate, rather than high culture, incarnation". (Frohmann, 1994, 112–113).
Cutter's early view on what a subject is, is probably wiser than most understandings that dominated the 20th century – and also the understanding reflected in the ISO-standard quoted below. The early statements quoted by Frohmann indicate that subjects are somehow shaped in social processes. When that is said, it should be added that they are not particularly detailed or clear. We only get a vague idea of the social nature of subjects.
S. R. Ranganathan (1892–1972).
A system, which has en explicit theoretical foundation is Ranganathan's Colon Classification. Ranganathan provided an explicit definition of the concept of "subject":

A related definition is given by one of Ranganathan's students:
Ranganathan's definition of "subject" is strongly influenced by his Colon Classification system. The colon system is based on the combination of single elements from facets to subject designation. This is the reason why the combined nature of subjects are emphasized so strongly. It leads, however, to absurdities such as the claim that gold cannot be a subject (but is alternatively termed "an isolate"). This aspect of the theory has been criticized by Metcalfe (1973, p. 318). Metcalfe's skepticism regarding Ranganathan's theory is formulated in hard words (op. cit., p. 317): "This pseudo-science imposed itself on British disciples from about 1950 on...".
It seems unacceptable that Ranganathan defines the word subject in a way that favors his own system. A scientific concept like "subject" should make it possible to compare different ways of establishing access to information. Whether or not subjects are combined or not should be examined once their definition has been given, it should not determined a priori, in the definition.
Besides the emphasis on the combined, organizing and systematizing nature of subjects contains Ranganathan's definition of subject the pragmatic demand, that a subject should be determined in a way that suits a normal person's competency or specialization. Again we see a strange kind of wishful thinking mixing a general understanding of a concept with demands put by his own specific system. One thing is what the word subject means, quite another issue is how to provide subject descriptions that fulfill demands such as the specificity of a given information retrieval language which fulfill demands put on the system, such as precision and recall. If researchers too often define terms in ways that favor specific kinds of systems, that are such definitions not useful to provide more general theories about subjects, subject analysis and IR. Among other things are comparative studies of different kinds of systems made difficult.
Based on these arguments (as well as additional arguments which have been used in the literature) we may conclude that Ranganathan's definition of the concept "subject" is not suited for scientific use. Like the definition of "subject" given by the ISO-standard for topic maps may Ranganathan's definition be useful within his own closed system. The purpose of a scientific and scholarly field is, however, to examine the relative fruitfulness of systems such as topic maps and Colon classification. For such purpose is another understanding of "subject" necessary.
Patrick Wilson (1927–2003).
In his book Wilson (1968) examined – in particular by thought experiments – the suitability of different methods of examining the subject of a document. The methods were:
Patrick Wilson shows convincingly that each of these methods are insufficient to determine the subject of a document and is led to conclude ( p. 89): "The notion of the subject of a writing is indeterminate..." or, on p. 92 (about what users may expect to find using a particular position in a library classification system): "For nothing definite can be expected of the things found at any given position". In connection to the last quote has Wilson an interesting footnote in which he writes that authors of documents often use terms in ambiguous ways ("hostility" is used as an example). Even if the librarian could personally develop a very precise understanding of a concept, he would be unable to use it in his classification, because none of the documents use the term in the same precise way. Based on this argumentation is Wilson led to conclude: "If people write on what are for them ill-defined phenomena, a correct description of their subjects must reflect the ill-definedness".
Wilson's concept of subject was discussed by Hjørland (1992) who found that it is problematic to give up the precise understanding of such a basic term in LIS. Wilson's arguments led him to an agnostic position which Hjørland found unacceptable and unnecessary. Concerning the authors' use of ambiguous terms, the role of the subject analysis is to determine which documents would be fruitful for users to identify whether or not the documents use one or another term or whether a given term in a document is used in one or another meaning. Clear and relevant concepts and distinctions in classification systems and controlled vocabularies may be fruitful even if they are applied to documents with ambiguous terminology.
"Content oriented" versus "request oriented" views.
Request oriented indexing is indexing in which the anticipated request from users is influencing how documents are being indexed. The indexer ask himself: "Under which descriptors should this entity be found?" and "think of all the possible queries and decide for which ones the entity at hand is relevant" (Soergel, 1985, p. 230).
Request oriented indexing may be indexing that is targeted towards a particular audience or user group. For example, a library or a database for feminist studies may index documents different compared to a historical library. It is probably better, however, to understand request oriented indexing as policy based indexing: The indexing is done according to some ideals and reflects the purpose of the library or database doing the indexing. In this way it is not necessarily a kind of indexing based on user studies. Only if empirical data about use or users are applied should request oriented indexing be regarded as a user-based approach.
The subject knowledge view.
Rowley & Hartley (2008, p. 109) wrote "In order to achieve good consistent indexing, the indexer must have a through appreciation of the structure of the subject and the nature of the contribution that the document is making to the advancement of knowledge within a particular discipline". This is accordance with Hjørland's definition given above.
Other views and definitions.
In the ISO-standard for topic maps the concept of subject is defined this way:
"Subject
Anything whatsoever, regardless of whether it exists or has any other specific characteristics, about which anything whatsoever may be asserted by any means whatsoever." ISO 13250-1, here cited from draft: http://www1.y12.doe.gov/capabilities/sgml/sc34/document/0446.htm#overview)
This definition may work well with the closed system of concepts provided by the topic maps standard. In broader contexts, however, is not fruitful because it does not contain any specification of what to identify in a document or in a discourse when ascribing subject identification terms or symbols to it. If different methods of subject analysis imply different results, which of these results can then be said to reflect the (true) subject? (Given that the expression "a true subject assignment" is meaningful at all, which is an important part of the problem). Different persons may have different opinions about what the subject of a specific document is. How can a theoretical understanding of the term "subject" be helpful deciding principles of subject analysis?
Related concepts.
Indexing words versus concepts versus subjects.
A proposal for the differentiation between concept indexing and subject indexing was given by Bernier (1980). In his opinion subject indexes are different from, and can be contrasted with, indexes to concepts, topics and words. Subjects are what authors are working and reporting on. A document can have the subject of Chromatography if this is what the author wishes to inform about. Papers using Chromatography as a
research method or discussing it in a subsection do not have Chromatography as subjects. Indexers can easily drift into indexing concepts and words rather than subjects, but this is not good indexing. Bernier does not, however, differentiate author's subjects from those of the information seeker. A user may want a document about a subject, which is different from the one intended by its author. From the point of view of information systems, the subject of a document is related to the questions that the document can answer for the users (cf. the distinction between a content oriented and a request-oriented approach).
Hjørland & Nicolaisen (2005) investigated the concept of subject in relation to Bradford's law of scattering and made a distinction between three kinds of scattering:
Isness.
"The FRSAR Working Group is aware that some controlled vocabularies provide terminology to express other aspects of works in addition to subject (such as form, genre, and target audience of resources). While very important and the focus of many user queries, these aspects describe isness or what class the work belongs to based on form or genre (e.g., novel, play, poem, essay, biography, symphony, concerto, sonata, map, drawing, painting, photograph, etc.) rather than what the work is about." (IFLA, 2010, p. 10).
Ofness.
"Those LIS authors who have focused on the subjects of visual resources, such as artworks and photographs, have often been concerned with how to distinguish between the "aboutness" and the "ofness" (both specific and generic depiction or representation) of such works (Shatford, 1986). In this sense, "aboutness" has a narrower meaning than that used above. A painting of a sunset over San Francisco, for instance, might be analyzed as being (generically) "of" sunsets and (specifically) "of" San Francisco, but also "about" the passage of time." (IFLA, 2010, p. 11).
See also: Baca & Harpring (2000) and Shatford (1986).
Further reading.
Drake, C. L. (1960). What is a subject? Australian Library Journal, 9, 34–41.
Englebretsen, George (1987). Subjects. Studia Leibnitiana, Bd. 19, H. 1, pp. 85–90. Published by: Franz Steiner Verlag.
Hjørland, Birger (1997): Information Seeking and Subject Representation. An Activity-theoretical approach to Information Science. Westport & London: Greenwood Press.
Hjørland, Birger (2009). Book review of: Rowley, Jennifer & Hartley, Richard (2008). Organizing Knowledge. An Introduction to Managing Access to Information. Aldershot: Ashgate Publishing Limited. IN: Journal of Documentation, 65(1), 166–169. Manuscript retrieved 2011-10-15 from: http://arizona.openrepository.com/arizona/bitstream/10150/106533/1/Book_review_Rowley_&_Hartley.doc
Hjørland, Birger (2017). Subject (of documents). Knowledge Organization, vol. 44, Issue 1, pp. 55-64.Also in ISKO Encyclopedia of Knowledge Organization: https://www.isko.org/cyclo/subject
IFLA (2010).Functional Requirements for Subject Authority Data (FRSAD): A Conceptual Model. By IFLA Working Group on the Functional Requirements for Subject Authority Records (FRSAR). Edited by Marcia Lei Zeng, Maja umer, Athena Salaba. International Federation of Library Associations and Institutions. Berlin: De Gruyter. Retrieved 2011-09-14 from: http://www.ifla.org/files/classification-and-indexing/functional-requirements-for-subject-authority-data/frsad-final-report.pdf
Miksa, F. (1983b): The Subject in the Dictionary Catalog from Cutter to the Present. Chicago: American Library Association.
Welty, C. A. (1998). The Ontological Nature of Subject Taxonomies. IN: N. Guarino (ed.), Proceedings of the First Conference on Formal Ontology and Information Systems, Amsterdam, IOS Press. http://www.cs.vassar.edu/faculty/welty/papers/fois-98/fois-98-1.html


Stealth edit

A stealth edit occurs when an online resource is changed without any record of the change being preserved. The term has a negative connotation, as it is a technique which allows an author to attempt to retroactively change what he or she said.
A common scenario would be a reporter posting a diatribe against something, followed by a blogger posting that the reporter is too extreme, followed by the reporter stealth editing the original post to be less extreme. The result is that the blogger looks like the one who is too extreme, since the public can't tell that the original post has been changed.
The existence of stealth edits may often be detected by comparing the current contents of a web page against Google's cache of the same page. In some cases, stealth editing of online content can be manually identified by making use of a web archiving service.
Non-stealthy edit.
A variety of non-stealthy techniques exist when making corrections or updates:
The common feature is that all these methods explicitly let the reader know that an edit has been made. A grey area exists when the edit is trivial (such as a typographic error). Some organizations flag all updates; others make a judgment call about what is considered a substantive update.


Journal of Neurochemistry

The Journal of Neurochemistry is a biweekly peer-reviewed scientific journal covering all aspects of neurochemistry. It is published by Wiley-Blackwell on behalf of the International Society for Neurochemistry and was established in 1956. The editor-in-chief is Jörg Schulz (Uniklinikum Aachen).
Abstracting and indexing.
The journal is abstracted and indexed in:
According to the "Journal Citation Reports", the journal has a 2017 impact factor of 4.609.
Editors-in-chief.
The following persons have been editor-in-chief of the journal:


Superior mesenteric ganglion

The superior mesenteric ganglion is a ganglion in the upper part of the superior mesenteric plexus. It lies close to the origin of the superior mesenteric artery.
Structure.
The superior mesenteric ganglion is the synapsing point for one of the pre- and post-synaptic nerves of the sympathetic division of the autonomous nervous system. Specifically, contributions to the superior mesenteric ganglion arise from the lesser splanchnic nerve, which typically arises from the spinal nerve roots of T10 and T11. This nerve goes on to innervate the jejunum, the ileum, the ascending colon and the transverse colon. While the sympathetic input of the midgut is innervated by the sympathetic nerves of the thorax, parasympathetic innervation is done by the vagus nerve, which travels along the plexuses that arise from the anterior and posterior vagal trunks of the stomach.


Sympathetic trunk

The sympathetic trunks (sympathetic chain, gangliated cord) are a paired bundle of nerve fibers that run from the base of the skull to the coccyx. They are a major component of the sympathetic nervous system.
Structure.
The sympathetic trunk lies just lateral to the vertebral bodies for the entire length of the vertebral column. It interacts with the anterior rami of spinal nerves by way of rami communicantes. The sympathetic trunk permits preganglionic fibers of the sympathetic nervous system to ascend to spinal levels superior to T1 and descend to spinal levels inferior to L2/3.
The superior end of it is continued upward through the carotid canal into the skull, and forms a plexus on the internal carotid artery; the inferior part travels in front of the coccyx, where it converges with the other trunk at a structure known as the ganglion impar.
Along the length of the sympathetic trunk are sympathetic ganglia known as paravertebral ganglia.
Function.
The sympathetic trunk is a fundamental part of the sympathetic nervous system, and part of the autonomic nervous system. It allows nerve fibres to travel to spinal nerves that are superior and inferior to the one in which they originated. Also, a number of nerves, such as most of the splanchnic nerves, arise directly from the trunks.


Brain vesicle

Brain vesicles are the bulge-like features of the early development of the neural tube in vertebrates. Vesicle formation begins shortly after anterior neural tube closure at about embryonic day 9.0 in the mouse and the fourth and fifth gestational week in human development. In zebrafish and chicken embryos, brain vesicles form by about 24 hours and 48 hours post-conception, respectively. Initially there are three primary brain vesicles: prosencephalon, mesencephalon, and rhombencephalon. These develop into five secondary brain vesicles – the prosencephalon is subdivided into the telencephalon and diencephalon, and the rhombencephalon into the metencephalon and myelencephalon. During these early vesicle stages, the walls of the neural tube contain neural stem cells in a region called the neuroepithelium or ventricular zone. These neural stem cells divide rapidly, driving growth of the early brain, but later, these stem cells begin to generate neurons through the process of neurogenesis.


Oxomemazine

Oxomemazine is an antihistamine and anticholinergic of the phenothiazine chemical class for the treatment of cough.


Immethridine

Immethridine is a histamine agonist selective for the H3 subtype.


Hobart Hurd Willard

Hobart Hurd Willard (June 3, 1881 – May 7, 1974) was an analytical chemist and inorganic chemist who spent most of his career at the University of Michigan. He was known for his teaching skill and his authorship of widely used textbooks. His research interests were wide-ranging and involved the characterization of perchloric acid and periodic acid salts.
Early life and education.
Willard was born on June 3, 1881 in Erie, Pennsylvania. His family relocated to Union City, Michigan in 1883 and he spent the rest of his early life there. His father and later his high school teachers encouraged his interest in chemistry, which he pursued as an undergraduate at the University of Michigan. He received his A.B. in 1903 and his M.A. in 1905. Meanwhile, he was briefly hired as an instructor of chemistry, but at the encouragement of coworkers he decided to pursue his Ph.D. at Harvard University. He received his Ph.D. in 1909 under the supervision of Theodore William Richards.
Academic career.
After finishing his Ph.D., Willard returned to Michigan to rejoin the faculty; he became a full professor in 1922 and retired from the university, assuming professor emeritus status, in 1951. He was designated the Henry Russel Lecturer in 1948, noted as the university's highest distinction. He was known for his strong teaching skills and continued teaching at a variety of institutions after his retirement.
During his tenure at Michigan, Willard wrote several widely used and positively reviewed chemistry textbooks and laboratory course manuals, often with former students as coauthors. He also performed consulting work for local industry throughout his career, serving as the Director of the Chemistry and Metallurgy Laboratories for Detroit's Bureau of Aircraft Production in 1917-18 and as a long-term consultant for the Parker Rust-Proof Company.
Willard served as a director of the American Chemical Society from 1934 to 1940 and received the ACS' Fisher Award in Analytical Chemistry in 1951. He was the inaugural recipient of the Anachem Award given by the Association of Analytical Chemists in 1953.
Research.
Willard's research interests focused on analytical chemistry and quantitative analysis of inorganic substances. With student G. Frederick Smith, he was particularly productive in studying perchloric acid and periodic acid salts. In addition, he is credited with important work in determining precise atomic weights of chemical elements such as lithium, silver, and antimony, and with development of metal alloy techniques.
Personal life.
Willard and his wife Margaret had two daughters, Ann and Nancy. Willard was a photography enthusiast and hobbyist who occasionally sold his work. He died in Ann Arbor, Michigan on May 7, 1974. Michigan holds a named professorship in his honor; the current Willard Professor of Chemistry is Robert T. Kennedy.


Paleothalamus

The paleothalamus is an obsolete term for the portion of the thalamus that is believed to be phylogenetically (or evolutionarily) older than other parts of the thalamus. Specifically, the midline and medial nuclei of the thalamus, as well as the intralaminar nucleus are considered to belong to the paleothalamus
The term "paleothalamus" is opposed to the paired (and also considered to be obsolete) term neothalamus, which designates the phylogenetically (or evolutionarily) newer or younger parts of the thalamus, specifically, lateral nuclei of the thalamus, the pulvinar and the geniculate bodies.
Initially, the paleothalamus was distinguished from other parts of the thalamus (i.e. from the neothalamus) on the basis that paleothalamic nuclei were believed to lack reciprocal connections with neocortex (isocortex), unlike neothalamic nuclei, which have manifold reciprocal connections to the neocortex. Today it is known that thalamic nuclei which were previously termed "paleothalamic", also have such reciprocal connections with neocortex. This was the main reason why the terms "paleothalamus" and "neothalamus" were felt obsolete and fell into disfavor.


Escape analysis

In compiler optimization, escape analysis is a method for determining the dynamic scope of pointers where in the program a pointer can be accessed. It is related to pointer analysis and shape analysis.
When a variable (or an object) is allocated in a subroutine, a pointer to the variable can "escape" to other threads of execution, or to calling subroutines. If an implementation uses tail call optimization (usually required for functional languages), objects may also be seen as escaping to "called" subroutines. If a language supports first-class continuations (as do Scheme and Standard ML of New Jersey), portions of the call stack may also escape.
If a subroutine allocates an object and returns a pointer to it, the object can be accessed from undetermined places in the program the pointer has "escaped". Pointers can also escape if they are stored in global variables or other data structures that, in turn, escape the current procedure.
Escape analysis determines all the places where a pointer can be stored and whether the lifetime of the pointer can be proven to be restricted only to the current procedure and/or thread.
Optimizations.
A compiler can use the results of escape analysis as a basis for optimizations:
Practical considerations.
In object-oriented programming languages, dynamic compilers are particularly good candidates for performing escape analysis. In traditional static compilation, method overriding can make escape analysis impossible, as any called method might be overridden by a version that allows a pointer to escape. Dynamic compilers can perform escape analysis using the available information on overloading, and re-do the analysis when relevant methods are overridden by dynamic code loading.
The popularity of the Java programming language has made escape analysis a target of interest. Java's combination of heap-only object allocation, built-in threading, the Sun HotSpot dynamic compiler, and OpenJ9's just-in-time compiler (JIT) creates a candidate platform for escape analysis related optimizations (see Escape analysis in Java). Escape analysis is implemented in Java Standard Edition 6. Some JVMs support a stronger variant of escape analysis called "partial escape analysis" that makes scalar replacement of an allocated object possible even if the object escapes in some paths of a function.
Example (Java).
class Main {
 public static void main(String[] args) {
 example();
 public static void example() {
 Foo foo = new Foo(); //alloc
 Bar bar = new Bar(); //alloc
 bar.setFoo(foo);
class Bar {
 private Foo foo;
 public void setFoo(Foo foo) {
 this.foo = foo;
In this example, two objects are created (commented with alloc), and one of them is given as an argument to a method of another. The method codice_1 stores a reference to a received Foo object. If the Bar object was on the heap then the reference to Foo would escape. But in this case a compiler can determine, with escape analysis, that the Bar object itself does not escape the invocation of codice_2. Which implies that a reference to Foo cannot escape either. So the compiler can safely allocate both objects on the stack.
Examples (Scheme).
In the following example, the vector "p" does not escape into "g", so it can be allocated on the stack and then removed from the stack before calling "g".
 (let ((p (make-vector 10000)))
 (fill-vector-with-good-stuff p)
 (g (vector-ref p 7023))))
If, however, we had
 (let ((p (make-vector 10000)))
 (fill-vector-with-good-stuff p)
 (g p)))
then either "p" would need to be allocated on the heap or (if "g" is known to the compiler when "f" is compiled, and behaves well) allocated on the stack in such a fashion that it can remain in place when "g" is called.
If continuations are used to implement exception-like control structures, escape analysis can often detect this to avoid having to actually allocate a continuation and copy the call stack into it. For example, in
 (call/cc (lambda (continuation)
 (define (get-numbers)
 (let ((next-object (read)))
 (cond
 ((eof-object? next-object) '())
 ((number? next-object) (cons next-object (get-numbers)))
 (else (continuation #f)))))
 (get-numbers))))
escape analysis will determine that the continuation captured by "call/cc" doesn't escape, so no continuation structure needs to be allocated, and invoking the continuation by calling "continuation" can be implemented by truncating the stack.


Binocular summation

Binocular summation refers to the improved visual performance of binocular vision compared to that of monocular vision. The most vital benefit of binocular vision is stereopsis or depth perception, however binocular summation does afford some subtle advantages as well. By combining the information received in each eye, binocular summation can improve visual acuity, contrast sensitivity, flicker perception, and brightness perception. Though binocular summation generally enhances binocular vision, it can worsen binocular vision relative to monocular vision under certain conditions. Binocular summation decreases with age and when large interocular differences are present.
Visual Improvements.
Some of the ways in which binocular summation improves binocular visual performance are
A practical measure of binocularity is the binocular summation ratio BSR, which is the ratio of binocular contrast sensitivity to the contrast sensitivity of the better eye.
Models for binocular brightness.
One might expect the inputs from each eye to simply add together, and that the perceived brightness with two eyes is twice that of a single eye. However, the perceived brightness with two eyes is only slightly higher compared to a single eye. If one eye sees a bright scene, the perceived brightness will actually decrease if the other eye is presented with a dim light. This counterintuitive phenomenon is known as Fechner's Paradox. Several different models have been proposed to explain how the inputs from each eye are combined.
The renowned physicist Erwin Schrödinger, known for his contributions to quantum theory, had a fascination for psychology and he explored topics related to color perception. Schrödinger (1926) put forth an equation for binocular brightness and contrast combination where each monocular input is weighted by the ratio of the signal strength from that eye to the sum of the signal from both eyes. The inputs formula_2 and formula_2 are monocular brightness flux signals. This equation can be thought of as the sum of the lengths of two vectors.
MacLeod (1972) expanded upon Schrödinger's work by proposing the following formula for the signal strength of a neural signal formula_5 in terms of internal noise formula_6, luminance difference across the contour formula_7, and threshold luminance difference formula_8.
Process.
It is still uncertain exactly how this process is performed by the brain and remains an active area of research. The mechanism can be explained by some combination of probability summation, neural summation, and effects due to binocular-monocular differences in pupil size, accommodation, fixation, and rivalry. Probability summation comes from the principle that there is a greater chance of detecting a visual stimulus with two eyes than with one eye.
There are five possible results when the input stimuli are summed together. These are
Binocular Fusion.
Both motor fusion and sensory fusion mechanisms are used to combine the two images into a single perceived image. Motor fusion describes the vergence eye movements that rotate the eyes about the vertical axis. Sensory fusion is the psychological process of the visual system that creates a single image perceived by the brain.


Turosteride

Turosteride (FCE-26,073) is a selective inhibitor of the enzyme 5α-reductase which was under investigation by GlaxoSmithKline for the treatment of benign prostatic hyperplasia (BPH), but was never marketed. Similarly to finasteride, turosteride is selective for the type II isoform of 5α-redcutase, with about 15-fold selectivity for it over type I isoform of the enzyme. In animal studies it has been shown to inhibit prostate size and retard tumor growth. It may also be useful for the treatment of acne and hair loss.


Odorant-binding protein

Odorant-binding proteins (OBPs) are small (10 to 30 kDa) soluble proteins secreted by auxiliary cells surrounding olfactory receptor neurons, including the nasal mucus of many vertebrate species and in the sensillar lymph of chemosensory sensilla of insects. OBPs are characterized by a specific protein domain that comprises six α-helices joined by three disulfide bonds. Although the function of the OBPs as a whole is not well established, it is believed that they act as odorant transporters, delivering the odorant molecules to olfactory receptors in the cell membrane of sensory neurons.
The olfactory receptors of terrestrial animals exist in an aqueous environment, yet detect odorants that are primarily hydrophobic. The aqueous solubility of hydrophobic odorants is greatly enhanced via odorant-binding proteins, which exist in the extracellular fluid surrounding the odorant receptors. This family is composed of pheromone binding proteins (PBP), which are male-specific and associate with pheromone-sensitive neurons and general-odorant-binding proteins (GOBP).
These proteins were initially identified on the basis of their ability to bind with moderate-affinity radioactively labeled odorants.
Structure.
OBPs are small proteins on the order of 14 kDa in size. All odorant binding proteins are believed to have a common structure despite their genetic diversity and highly variable primary structures. In vertebrates, OBPs are a part of the lipocalin family. They are structurally characterized by a β-barrel motif composed of antiparallel β-sheets. Insect OBPs share very little amino acid sequence similarity to vertebrate OBPs as they mainly contain α-helical domains. OBPs are divergent across and within species. The percentage of conserved residues between species has been shown to be as low as 8%. OBPs' have a characteristic signature that is recognized by a conserved pattern of six cysteines that are connected in the protein by three disulfide bridges. Their structures have been investigated to explore new bio-inspired repellents against mosquitoes, with potentially improved OBP binding affinity, selectivity, and reduced volatility.
Function.
The functions of odorant binding proteins as a whole is not well understood. They are generally believed to increase the solubility of hydrophobic odorants by binding them and transporting them across the aqueous sensillum lymph to receptors in the dendrites, and several studies support a role for OBPs in olfactory perception "in vivo". Some odorant binding proteins are hypothesized to hasten odor response termination by extracting odorant molecules from the sensillar lymph or from receptors themselves. Presently, just one OBP, Obp76a, has been thoroughly investigated in the olfactory system of "Drosophila" and has a known physiological role. Obp76a, better known as LUSH, is located trichoid sensilla and is necessary for normal response of the odor receptor Or67d to its pheromone ligand cis-vaccenyl acetate (cVA), although responses of Or67d to cVA have been detected in the absence of Obp76a LUSH has also been found to bind cVA "in vitro" and is known to bind other insect pheromones, short-chain alcohols, and phthalates.
In 2016, Larter et al. found that the deletion of the sole abundant OBP, Obp28a, in ab8 sensilla of "Drosophila" does not reduce the magnitude of their olfactory responses, suggesting that Obp28a is not required for odorant transport and that ab8 sensilla do not require an abundant OBP. Their results further suggest Obp28a may be buffering changes in the odor environment, possibly as molecular gain control, which has not been previously reported for OBPs.
OBPs are thought to have multiple roles besides olfaction, including reproduction, egg laying and antiinflammatory responses.
Expression.
OBPs are numerous and diverse. In "Drosophila", they are encoded by 52 genes of the same family yet only share 20% amino acid similarity between themselves. Some are encoded by the most abundant mRNAs of the antennae. Within and between species, OBPs are expressed in several different tissues, including the antennal sensilla, the taste system, and chemosensory organs. They are also known to be ectopically expressed in tissues such as the gut.
Genomic analysis of "Drosophila" and other insect species ("Anopheles gambiae", "Apis mellifera," "Bombyx mori", and "Triboliumcastaneum") has revealed that the OBP genes significantly differ between species. The OBP family contains 21 (in A. "mellifera") to 66 genes (in "A. gambiae"), whereas it ranges from 52 members in "Drosophila" to 20 in "T. castaneum". Generally these genes are irregularly scattered across the genome. Most (69% of the OBP genes in "Drosophila") are arranged in small clusters from 2 to 6 OBP genes. The "Drosophila" OBP gene family has been classified into several subfamilies based on structural features, functional information, and phylogenetic relationships: the Classic, Minus-C, Plus-C, Dimer, PBP/GOBP, ABPI and ABPII, CRLBP, and D7 subfamilies. These subfamilies are unequally distributed across arthropods, even among the dipterans and are totally absent in some species.


Camera-ready

Camera-ready is a common term used in the commercial printing industry meaning that a document is, from a technical standpoint, ready to "go to press", or be printed.
History.
The term camera-ready was first used in the photo offset printing process, where the final layout of a document was attached to a "mechanical" or "paste up". Then, a stat camera was used to photograph the mechanical, and the final offset printing plates were created from the camera's negative.
In this system, a final paste-up that needed no further changes or additions was ready to be photographed by the process camera and subsequently printed. This final document was "camera-ready".
This artwork may have looked messy to the naked eye or to a modern consumer digital camera - covered in various pieces of paper attached with adhesive or wax and composited with white out, gouache, tape and blue pencil (non-reproducible) and red masking film, black or clay-based paint (reproducible as black) - but appeared perfectly uniform to the monochrome reproducing camera used for print reproduction.
Present usage.
In recent years, the use of paste-ups has been steadily replaced by desktop publishing software, which allows users to create entire document layouts on the computer. In the meantime, many printers now use technology to take these digital files and create printing plates from them without use of a camera and negative. Despite this, the term "camera-ready" continues to be used to signify that a document is ready to be made into a printing plate.
In this new digital-to-plate system, a digital file is usually considered "camera-ready" if it meets several conditions:


Basal forebrain

The basal forebrain structures are located in the forebrain to the front of and below the striatum. They include the ventral basal ganglia (including nucleus accumbens and ventral pallidum), nucleus basalis, diagonal band of Broca, substantia innominata, and the medial septal nucleus. These structures are important in the production of acetylcholine, which is then distributed widely throughout the brain. The basal forebrain is considered to be the major cholinergic output of the central nervous system (CNS) centred on the output of the nucleus basalis. The presence of non-cholinergic neurons projecting to the cortex have been found to act with the cholinergic neurons to dynamically modulate activity in the cortex.
Function.
Acetylcholine is known to promote wakefulness in the basal forebrain. Stimulating the basal forebrain gives rise to acetylcholine release, which induces wakefulness and REM sleep, whereas inhibition of acetylcholine release in the basal forebrain by adenosine causes slow wave sleep. The nucleus basalis is the main neuromodulator of the basal forebrain and gives widespread cholinergic projections to the neocortex. The nucleus basalis is an essential part of the neuromodulatory system that controls behaviour by regulating arousal and attention. The nucleus basalis is also seen to be a critical node in the memory circuit.
The importance of non-cholinergic neurons in the basal forebrain structures has been shown in working together with the cholinergic neurons in a dynamically modulatory way. This is seen to play a significant role in cognitive functions.
Adenosine acts on A1 receptors of cholinergic neurons in the basal forebrain. This results in hyperpolarization of cholinergic neurons, which inhibits the release of acetylcholine.
Nitric oxide production in the basal forebrain is both necessary and sufficient to produce sleep.
Clinical significance.
Acetylcholine affects the ability of brain cells to transmit information to one another, and also encourages neuronal plasticity, or learning. Thus, damage to the basal forebrain can reduce the amount of acetylcholine in the brain and impair learning. This may be one reason why basal forebrain damage can result in memory impairments such as amnesia and confabulation. One common cause of basal forebrain damage is an aneurysm of the anterior communicating artery.
It is thought that damage to the nucleus basalis and its cortical projections are implicated in forms of dementia, notably Alzheimer's dementia and Parkinson's disease dementia. There have been studies on the use of deep brain stimulation to the nucleus basalis, in the treatment of dementia, and while giving some positive results trials are still being undertaken.


Natural competence

In microbiology, genetics, cell biology, and molecular biology, competence is the ability of a cell to alter its genetics by taking up extracellular ("naked") DNA from its environment in the process called transformation. Competence may be differentiated between "natural competence", a genetically specified ability of bacteria which is thought to occur under natural conditions as well as in the laboratory, and "induced" or "artificial competence", which arises when cells in laboratory cultures are treated to make them transiently permeable to DNA. Competence allows for rapid adaptation and DNA repair of the cell. This article primarily deals with natural competence in bacteria, although information about artificial competence is also provided.
History.
Natural competence was discovered by Frederick Griffith in 1928, when he showed that a preparation of killed cells of a pathogenic bacterium contained something that could transform related non-pathogenic cells into the pathogenic type. In 1944 Oswald Avery, Colin MacLeod, and Maclyn McCarty demonstrated that this 'transforming factor' was pure DNA
. This was the first compelling evidence that DNA carries the genetic information of the cell.
Since then, natural competence has been studied in a number of different bacteria, particularly "Bacillus subtilis", "Streptococcus pneumoniae" (Griffith's "pneumococcus"), "Neisseria gonorrhoeae", "Haemophilus influenzae" and members of the "Acinetobacter" genus. Areas of active research include the mechanisms of DNA transport, the regulation of competence in different bacteria, and the evolutionary function of competence.
Mechanisms of DNA uptake.
In the laboratory, DNA is provided by the researcher, often as a genetically engineered fragment or plasmid. During uptake, DNA is transported across the cell membrane(s), and the cell wall if one is present. Once the DNA is inside the cell it may be degraded to nucleotides, which are reused for DNA replication and other metabolic functions. Alternatively it may be recombined into the cell's genome by its DNA repair enzymes. If this recombination changes the cell's genotype the cell is said to have been transformed. Artificial competence and transformation are used as research tools in many organisms ("see Transformation (genetics)").
In almost all naturally competent bacteria components of extracellular filaments called type IV pili (a type of fimbria) bind extracellular double stranded DNA. The DNA is then translocated across the membrane (or membranes for gram negative bacteria) through multi-component protein complexes driven by the degradation of one strand of the DNA. Single stranded DNA in the cell is bound by a well-conserved protein, DprA, which loads the DNA onto RecA, which mediates homologous recombination through the classic DNA repair pathway.
Regulation of competence.
In laboratory cultures, natural competence is usually tightly regulated and often triggered by nutritional shortages or adverse conditions. However the specific inducing signals and regulatory machinery are much more variable than the uptake machinery, and little is known about the regulation of competence in the natural environments of these bacteria. Transcription factors have been discovered which regulate competence; an example is sxy (also known as tfoX) which has been found to be regulated in turn by a 5' non-coding RNA element. In bacteria capable of forming spores, conditions inducing sporulation often overlap with those inducing competence. Thus cultures or colonies containing sporulating cells often also contain competent cells. Recent research by Süel "et al." has identified an excitable core module of genes which can explain entry into and exit from competence when cellular noise is taken into account.
Most competent bacteria are thought to take up all DNA molecules with roughly equal efficiencies, but bacteria in the families Neisseriaceae and Pasteurellaceae preferentially take up DNA fragments containing short DNA sequences, termed DNA uptake sequence (DUS) in Neisseriaceae and uptake signal sequence (USS) in Pasteurellaceae, that are very frequent in their own genomes. Neisserial genomes contain thousands of copies of the preferred sequence GCCGTCTGAA, and Pasteurellacean genomes contain either AAGTGCGGT or ACAAGCGGT.
Evolutionary functions and consequences of competence.
Most proposals made for the primary evolutionary function of natural competence as a part of natural bacterial transformation fall into three categories: (1) the selective advantage of genetic diversity; (2) DNA uptake as a source of nucleotides (DNA as “food”); and (3) the selective advantage of a new strand of DNA to promote homologous recombinational repair of damaged DNA (DNA repair). A secondary suggestion has also been made, noting the occasional advantage of horizontal gene transfer.
Hypothesis of genetic diversity.
Arguments to support genetic diversity as the primary evolutionary function of sex (including bacterial transformation) are given by Barton and Charlesworth . and by Otto and Gerstein. However, the theoretical difficulties associated with the evolution of sex suggest that sex for genetic diversity is problematic. Specifically with respect to bacterial transformation, competence requires the high cost of a global protein synthesis switch, with, for example, more than 16 genes that are switched on only during competence of "Streptococcus pneumoniae". However, since bacteria tend to grow in clones, the DNA available for transformation would generally have the same genotype as that of the recipient cells. Thus, there is always a high cost in protein expression without, in general, an increase in diversity. Other differences between competence and sex have been considered in models of the evolution of genes causing competence; these models found that competence's postulated recombinational benefits were even more elusive than those of sex.
Hypothesis of DNA as food.
The second hypothesis, DNA as food, relies on the fact that cells that take up DNA inevitably acquire the nucleotides the DNA consists of, and, because nucleotides are needed for DNA and RNA synthesis and are expensive to synthesize, these may make a significant contribution to the cell's energy budget. Some naturally competent bacteria also secrete nucleases into their surroundings, and all bacteria can take up the free nucleotides these nucleases generate from environmental DNA. The energetics of DNA uptake are not understood in any system, so it is difficult to compare the efficiency of nuclease secretion to that of DNA uptake and internal degradation. In principle the cost of nuclease production and the uncertainty of nucleotide recovery must be balanced against the energy needed to synthesize the uptake machinery and to pull DNA in. Other important factors are the likelihoods that nucleases and competent cells will encounter DNA molecules, the relative inefficiencies of nucleotide uptake from the environment and from the periplasm (where one strand is degraded by competent cells), and the advantage of producing ready-to-use nucleotide monophosphates from the other strand in the cytoplasm. Another complicating factor is the self-bias of the DNA uptake systems of species in the family "Pasteurellaceae" and the genus "Neisseria", which could reflect either selection for recombination or for mechanistically efficient uptake.
Hypothesis of repair of DNA damage.
In bacteria, the problem of DNA damage is most pronounced during periods of stress, particularly oxidative stress, that occur during crowding or starvation conditions. Under such conditions there is often only a single chromosome present. The finding that some bacteria induce competence under such stress conditions, supports the third hypothesis, that transformation exists to permit DNA repair. In experimental tests, bacterial cells exposed to agents damaging their DNA, and then undergoing transformation, survived better than cells exposed to DNA damage that did not undergo transformation (Hoelzer and Michod, 1991). In addition, competence to undergo transformation is often inducible by known DNA damaging agents (reviewed by Michod "et al"., 2008 and Bernstein "et al"., 2012). Thus, a strong short-term selective advantage for natural competence and transformation would be its ability to promote homologous recombinational DNA repair under conditions of stress. Such stress conditions might be incurred during bacterial infection of a susceptible host. Consistent with this idea, Li et al. reported that, among different highly transformable "S. pneumoniae" isolates, nasal colonization fitness and virulence (lung infectivity) depends on an intact competence system.
A counter argument was made based on the 1993 report of Redfield who found that single-stranded and double-stranded damage to chromosomal DNA did not induce or enhance competence or transformation in "B. subtilis" or "H. influenzae", suggesting that selection for repair has played little or no role in the evolution of competence in these species
However more recent evidence indicates that competence for transformation is, indeed, specifically induced by DNA damaging conditions. For instance, Claverys "et al". in 2006 showed that the DNA damaging agents mitomycin C (a DNA cross-linking agent) and fluoroquinolone (a topoisomerase inhibitor that causes double-strand breaks) induce transformation in "Streptococcus pneumoniae". In addition, Engelmoer and Rozen in 2011 demonstrated that in "S. pneumoniae" transformation protects against the bactericidal effect of mitomycin C. Induction of competence further protected against the antibiotics kanomycin and streptomycin. Although these aminoglycoside antibiotics were previously regarded as non-DNA damaging, recent studies in 2012 of Foti "et al". showed that a substantial portion of their bactericidal activity results from release of the hydroxyl radical and induction of DNA damages, including double-strand breaks.
Dorer "et al"., in 2010, showed that ciprofloxacin, which interacts with DNA gyrase and causes production of double-strand breaks, induces expression of competence genes in "Helicobacter pylori", leading to increased transformation. In 2011 studies of "Legionella pneumophila", Charpentier "et al". tested 64 toxic molecules to determine which ones induce competence. Only six of these molecules, all DNA damaging agents, strongly induced competence. These molecules were norfloxacin, ofloxacin and nalidixic acid (inhibitors of DNA gyrase that produce double strand breaks), mitomycin C (which produces inter-strand cross-links), bicyclomycin (causes single- and double-strand breaks), and hydroxyurea (causes oxidation of DNA bases). Charpentier "et al". also showed that UV irradiation induces competence in "L. pneumophila" and further suggested that competence for transformation evolved as a response to DNA damage.
Horizontal gene transfer.
A long-term advantage may occasionally be conferred by occasional instances of horizontal gene transfer also called "lateral gene transfer", (which might result from non-homologous recombination after competence is induced), that could provide for antibiotic resistance or other advantages.
Regardless of the nature of selection for competence, the composite nature of bacterial genomes provides abundant evidence that the horizontal gene transfer caused by competence contributes to the genetic diversity that makes evolution possible.


5-HT2B receptor

5-Hydroxytryptamine receptor 2B (5-HT2B) also known as serotonin receptor 2B is a protein that in humans is encoded by the "HTR2B" gene. 5-HT2B is a member of the 5-HT2 receptor family that binds the neurotransmitter serotonin (5-hydroxytryptamine, 5-HT).
Tissue distribution and function.
The 5-HT2 receptors (of which the 5-HT2B receptor is a subtype) mediate many of the central and peripheral physiologic functions of serotonin. Cardiovascular effects include contraction of blood vessels and shape changes in platelets; central nervous system effects include neuronal sensitization to tactile stimuli and mediation of some of the effects of hallucinogenic substituted amphetamines. The 5-HT2B receptor is highly expressed in the liver and kidney, with lower levels of expression being seen in the cerebral cortex, whole brain, pancreas, and spleen.
The 5-HT2B receptor subtype is involved in:
Clinical significance.
5-HT2B receptors have also been strongly implicated in drug-induced valvular heart disease. In this context, it is generally considered to be an antitarget.
The structure of the 5-HT2B receptor was resolved in a complex with the valvulopathogenic drug ergotamine.
Ligands.
As of 2009, few highly selective 5-HT2B receptor ligands have been discovered, although numerous potent non-selective compounds are known, particularly agents with concomitant 5-HT2C binding. Research in this area has been limited due to the cardiotoxicity of 5-HT2B agonists, and the lack of clear therapeutic application for 5-HT2B antagonists, but there is still a need for selective ligands for scientific research.
Possible applications.
5-HT2B antagonists have previously been proposed as treatment for migraine headaches, and RS-127,445 was trialled in humans up to Phase I for this indication, but development was not continued. More recent research has focused on possible application of 5-HT2B antagonists as treatments for chronic heart disease. Research claims serotonin 5-HT2B receptors have effect on liver regeneration.


Peripheral vision

Peripheral vision, or "indirect vision", is vision as it occurs outside the point of fixation, i.e. away from the center of gaze or, when viewed at large angles, in (or out of) the "corner of one's eye". The vast majority of the area in the visual field is included in the notion of peripheral vision. "Far peripheral" vision refers to the area at the edges of the visual field, "mid-peripheral" vision refers to medium eccentricities, and "near-peripheral", sometimes referred to as "para-central" vision, exists adjacent to the center of gaze.
Boundaries.
Inner boundaries.
The inner boundaries of peripheral vision can be defined in any of several ways depending on the context. In everyday language the term "peripheral vision" is often used to refer to what in technical usage would be called "far peripheral vision." This is vision outside of the range of stereoscopic vision. It can be conceived as bounded at the center by a circle 60° in radius or 120° in diameter, centered around the fixation point, i.e., the point at which one's gaze is directed. However, in common usage, peripheral vision may also refer to the area outside a circle 30° in radius or 60° in diameter. In vision-related fields such as physiology, ophthalmology, optometry, or vision science in general, the inner boundaries of peripheral vision are defined more narrowly in terms of one of several anatomical regions of the central retina, in particular the fovea and the macula.
The fovea is a cone-shaped depression in the central retina measuring 1.5 mm in diameter, corresponding to 5° of the visual field. The outer boundaries of the fovea are visible under a microscope, or with microscopic imaging technology such as OCT or microscopic MRI. When viewed through the pupil, as in an eye exam (using an ophthalmoscope or retinal photography), only the central portion of the fovea may be visible. Anatomists refer to this as the clinical fovea, and say that it corresponds to the anatomical foveola, a structure with a diameter of 0.35 mm corresponding to 1 degree of the visual field. In clinical usage the central part of the fovea is typically referred to simply as the fovea.
In terms of visual acuity, "foveal vision" may be defined as vision using the part of the retina in which a visual acuity of at least 20/20 (6/6 metric or 0.0 LogMAR; internationally 1.0) is attained. This corresponds to using the foveal avascular zone (FAZ) with a diameter of 0.5 mm representing 1.5° of the visual field. Although often idealized as perfect circles, the central structures of the retina tend to be irregular ovals. Thus, foveal vision may also be defined as the central 1.5–2° of the visual field. Vision within the fovea is generally called central vision, while vision outside of the fovea, or even outside the foveola, is called peripheral, or indirect vision.
A ring-shaped region surrounding the fovea, known as the parafovea, is sometimes taken to represent an intermediate form of vision called paracentral vision. The parafovea has an outer diameter of 2.5 mm representing 8° of the visual field.
The macula, the next larger region of the retina, is defined as having at least two layers of ganglia (bundles of nerves and neurons) and is sometimes taken as defining the boundaries of central vs. peripheral vision (but this is controversial). Estimates of the macula’s size differ, its diameter estimated at 6° – 10° (corresponding to 1.7 – 2.9 mm), up to 17° of the visual field (5.5 mm). The term is familiar in the general public through the widespread macular degeneration (AMD) at older age, where central vision is lost.
When viewed from the pupil, as in an eye exam, only the central portion of the macula may be visible. Known to anatomists as the clinical macula (and in clinical setting as simply the macula) this inner region is thought to correspond to the anatomical fovea.
A dividing line between near and mid peripheral vision at 30° radius can be based on several features of visual performance.
Visual acuity declines systematically up to 30° eccentricity: At 2°, acuity is half the foveal value, at 4° one-third, at 6° one-fourth etc. At 30°, it is one-sixteenth the foveal value. From thereon the decline is steeper. (Note that it would be wrong to say, the value were halved "every" 2°, as said in some textbooks or in previous versions of this article.)
Color perception is strong at 20° but weak at 40°. In dark-adapted vision, light sensitivity corresponds to rod density, which peaks just at 18°. From 18° towards the center, rod density declines rapidly. From 18° away from the center, rod density declines more gradually, in a curve with distinct inflection points resulting in two humps. The outer edge of the second hump is at about 30°, and corresponds to the outer edge of good night vision.
Outer boundaries.
The outer boundaries of peripheral vision correspond to the boundaries of the visual field as a whole. For a single eye, the extent of the visual field can be (roughly) defined in terms of four angles, each measured from the fixation point, i.e., the point at which one's gaze is directed. These angles, representing four cardinal directions, are 60° upwards, 60° nasally (towards the nose), 70–75° downwards, and 100–110° temporally (away from the nose and towards the temple). For both eyes the combined visual field is 130–135° vertically and 200–220° horizontally.
Characteristics.
The loss of peripheral vision while retaining central vision is known as tunnel vision, and the loss of central vision while retaining peripheral vision is known as central scotoma.
Peripheral vision is weak in humans, especially at distinguishing detail, color, and shape. This is because the density of receptor and ganglion cells in the retina is greater at the center and lowest at the edges, and, moreover, the representation in the visual cortex is much smaller than that of the fovea (see visual system for an explanation of these concepts). The distribution of receptor cells across the retina is different between the two main types, rod cells and cone cells. Rod cells are unable to distinguish color and peak in density in the near periphery (at 18° eccentricity), while cone cell density is highest in the very center, the fovea. Note that this does not mean that there is a lack of cones representing in the periphery; colors can be distinguished in peripheral vision.
Flicker fusion thresholds decline towards the periphery, but do that at a lower rate than other visual functions; so the periphery has a relative advantage at noticing flicker. Peripheral vision is also relatively good at detecting motion (a feature of Magno cells).
Central vision is relatively weak in the dark (scotopic vision) since cone cells lack sensitivity at low light levels. Rod cells, which are concentrated further away from the fovea, operate better than cone cells in low light. This makes peripheral vision useful for detecting faint light sources at night (like faint stars). Because of this, pilots are taught to use peripheral vision to scan for aircraft at night.
The distinctions between foveal (sometimes also called central) and peripheral vision are reflected in subtle physiological and anatomical differences in the visual cortex. Different visual areas contribute to the processing of visual information coming from different parts of the visual field, and a complex of visual areas located along the banks of the interhemispheric fissure (a deep groove that separates the two brain hemispheres) has been linked to peripheral vision. It has been suggested that these areas are important for fast reactions to visual stimuli in the periphery, and monitoring body position relative to gravity.
Functions.
The main functions of peripheral vision are:
Extreme peripheral vision.
When viewed at large angles, the iris and pupil appear to be rotated toward the viewer due to the optical refraction in the cornea. As a result, the pupil may still be visible at angles greater than 90°.
Cone-rich rim of the retina.
The rim of the retina contains a large concentration of cone cells. The retina extends farthest in the superior-nasal 45° quadrant (in the direction from the pupil to the bridge of the nose) with the greatest extent of the visual field in the opposite direction, the inferior temporal 45° quadrant (from the pupil of either eye towards the bottom of the nearest ear). Vision at this extreme part of the visual field is thought to be possibly concerned with threat detection, measuring optical flow, color constancy, or circadian rhythm.