Wide dynamic range neuron

The wide dynamic range (WDR) neuron was first discovered by Mendell in 1966. Early studies of this neuron established what is known as the gate control theory of pain. The basic concept is that non-painful stimuli block the pathways for painful stimuli, inhibiting possible painful responses. This theory was supported by the fact that WDR neurons are responsible for responses to both painful and non-painful stimuli, and the idea that these neurons couldn't produce more than one of these responses simultaneously. WDR neurons respond to all types of somatosensory stimuli, make up the majority of the neurons found in the posterior grey column, and have the ability to produce long range responses including those responsible for pain and itch.
Anatomy and physiology.
WDR neurons are found in the posterior grey column of the spinal cord. This area of the spinal cord houses two different types of neurons involved in the process of pain: WDR neurons and nociceptive specific neurons (NS). As the name implies, NS neurons give specific short range responses. WDR neurons are able to give long range responses for a large variety of stimuli giving them the ability to help identify the location and intensity of painful stimulation (sensory discrimination).
WDR neurons differ from most other neurons in that they are theorised to experience what is called a ‘wind up’. This allows for the intensity of their response to increase with an increased frequency of stimulus. Most other neurons fire repeated action potentials of the same magnitude as a reaction to an increase in stimulus intensity. The intensity of the stimulus will only boost the frequency of action potentials, not their magnitude. However, WDR neurons exhibit increased action potential intensity with more presentations of a stimulus. This allows for plasticity of synapses and creates flexibility in the neuronal response. Though this may be of some benefit to the organism, this over excitation of the neurons can result in chronic pain.
Role in pain responses.
When there is a painful stimulus there are two pathways that can be taken. The nociceptive neurons in lamina 1 become compromised or the WDR neurons become compromised. The WDR neurons can respond to electrical, mechanical, and thermal stimulation. The dorsal cord has faulty plasticity, which encourages the development of neuropathic pain after an injury to a nerve. This allows for the over-excitation discussed previously, resulting in chronic pain. The unique pain pathway of the WDR neurons allows information about the stimulus to be used to map out the intensity of the pain through sensory discrimination.
There are two main types of pain that we experience in our bodies: pain caused by damage of body tissue and pain caused by nerve damage. Nociceptive pain serves as a warning or signal for tissue damage and works to preserve the body’s equilibrium and functionality. This pain is signaled by the interworkings of both the peripheral and central nervous systems. Another type of pain, known as neuropathic pain, is caused by a direct problem or disease that affects the nerves in the central nervous system.
A subset of this neuropathic pain, known as chronic neuropathic pain, is characterized by its long lasting and high pain intensity. Although there is still a lot unknown about the direct cause of this chronic pain, it has been linked to WDR neurons. These neurons show significant activation by sympathetic stimulation while neurons, such as NS neurons, do not show the same level of activation. The blocking of sympathetic pathways seemed to decrease pain and once unblocked, symptoms of pain persisted. This indicates that one of the many complex mechanisms contributing to this neuropathic chronic pain is the overstimulation of the WDR neurons by sympathetic stimulation.
Another aspect that plays a role in neuropathic pain is the transient receptor channel called TRPA1. This channel is known to have influenced chronic pain injuries and diseases such as inflammation, diabetes, fibromyalgia, bronchitis, and emphysema. WDR neurons are a huge part of the somatosensory system, helping to send and receive signals based on sensory changes in the body. The TRPA1 channel has been closely associated with temperature and pain sensation in primary afferent sensory neurons and are largely found in nociceptive sensory neurons in the dorsal root ganglia. The inhibition of TRPA1 is known to contribute to different inflammatory and neuropathic diseases by amplifying the pain and hypersensitivity. This is an area of study that is beneficial to continue to study and learn how to target and control aspects of chronic inflammatory and neuropathic diseases involved in sensory responses that WDR neurons play a role in.
Role in itch responses.
Additionally, the itch pathway has also been linked with WDR neurons because itch and pain pathways are closely associated. As there are transient receptor channels present in the pain pathway, they are also present in the itch pathway. In the itch pathway, when the transient receptor channels are activated an itch response can be elicited. Itch responses can also be controlled by temperature changes (too high or too low), much like pain. This mechanism of control occurs when a stimulus is at an extremely low or extremely high temperature. The organism's sensitivity to the stimulus increases, meaning the pain or itch elicited will be greater at those temperatures than they would be at room temperature. Though these pathways display many similarities, there are other mechanisms by which itch sensations can be controlled, such as those through nerve growth factor and substance-P.
Brain imaging indicates similar activity in many areas of the brain such as prefrontal, supplementary motor areas, premotor cortex, anterior insular cortex, and many others when itch and pain regions are activated. A better understanding of both these pathways will provide a greater understanding of WDR neurons.


Von Kries coefficient law

The von Kries coefficient law in color adaptation describes the relationship between the illuminant and the human visual system sensitivity. The law accounts for the approximate color constancy in the human visual system. It is the oldest and most widely used law to quantify color adaptation, and is used widely in the field of vision and chromatic adaptation.
The von Kries coefficient law compensates for the illumination change using a purely diagonal scaling of the cone absorptions. While the law does not provide a precise indication of the correction, it typically provides a reasonable approximation.
History.
Helmholtz and the Young–Helmholtz theory.
The von Kries coefficient law built upon theories and research done by Hermann von Helmholtz. A German physicist and physician, Helmholtz asserted that “the nervous substance in question is less sensitive to reacting light falling on it than the rest of the retina that was not previously stimulated”. Helmholtz, along with Thomas Young, proposed the trichromatic theory, or the Young–Helmholtz theory, that stated that the retina contains three types of cones, which respond to light of three different wavelengths, corresponding to red, green, or blue. Activation of these cones in different combinations and to different degrees results in the perception of other colors.
Experiments.
While von Kries and the other researchers did not have the means to test out the results of his stated law, others tested out his coefficient law by estimating the eigenvectors of the measured linear transformations. Many researchers, including Eileen Wassof (1959), Burnham et al. (1957), and Macadam [12] rejected his law as being insufficiently accurate. There were frequently reported systematic discrepancies between prediction and experiment.
Chromatic adaptation.
The law assumes that although the responses of the three cone types (R, G, and B) are affected differently by chromatic adaptation, the spectral sensitivities of each of the three cone mechanisms remains unchanged. Therefore, if one of the three cones are less stimulated than the others, the sensitivity is proportionally reduced. The specific amount that this number is reduced by is inversely related to the relative strengths of activation by the energy distribution of the particular light in question.
Equations.
The von Kries coefficient law can be expressed by the following equations:
, where formula_4 and formula_5 are the cone responses of the same observer, and formula_6 and formula_7 are all cone responses of the same observer; the only difference is that formula_4 and formula_5 are viewed under a reference illuminant while the other set of values is experimental. α, β, and γ are the von Kries coefficients corresponding to the reduction in sensitivity of the three cone mechanisms due to chromatic adaptation.
If formula_10 and formula_11 are defined as the cone responses for the reference white under the reference and test illuminants, and formula_12 and formula_13 are cone responses for the test illuminants, then
Using these to solve for the coefficients, we get:
αformula_17
βformula_18
γformula_19
This law holds for the color space of the cones, although it has been proven applicable to other color spaces.
Evaluation/effectiveness of the law.
Many studies have been conducted to study the precision and applicability of the law. Most studies conclude that the law is a general approximation that cannot take into account all of the specificity needed to get a precise answer; different studies and their results will be summarized below.
Wirth, in research done from 1900 to 1903, demonstrated through his studies that the law can be considered “nearly valid for reacting lights that are not too weak”. The theory on sensitivity and reacting light was also evaluated and emphasized by Wright in 1934 studies, where he stated, “Now suppose R’, G’, and B’ are hypothetical stimuli that produce responses along A, B, and C,… three independent set of fibers to the brain. Then a reduction in sensitivity produced by light adaptation will, for a test colour that stimulates A alone, produce an intensity depression of R’ but no colour change; similarly if B or C are stimulated alone.”
The von Kries coefficient law has also been known to be an inaccurate predictor of asymmetric matching experiments. However, this might be seen as a way to moderate color constancy - models display color constancy only as far as the von Kries coefficient law displays color constancy. Therefore, any discrepancies in calculations are due to the visual system behaving in accordance with newer models
Further research by Brian Wandell on Wassof's findings revealed that when objects analyzed by the coefficient law are in the same context, the rates of cone absorption as realized by the law match up with experimental values. However, when the two objects are seen under different illuminants, the cone absorptions do not correlate with the true values. Within each context the observer uses the pattern of cone absorption to infer color appearance, probably by comparing the relative cone absorption rates. Color appearance is an interpretation of the physical properties of the objects in the image.
Prevalence.
Applications.
Despite the various inconsistencies seen in the von Kries coefficient law, the law is widely used in many color and vision applications and papers. For example, many chromatic adaptation platforms (CATs) are based on the von Kries coefficient law. It has been used in many applications, especially in many psychophysical research. It has been used in applications ranging from psychophysical work by researchers such as Takasari, Judd, and Pearson; it has also been used in electrophysiological experiments.
Alternatives to the von Kries coefficient law, while they have been brought up and studied (for example, Jameson and Hurvich's induced opponent response chromatic adaptation theory), have never reached the level of prevalence found by the simplicity of the von Kries coefficient law.
Nearly all commercial digital cameras use the von Kries coefficient law to model the variation and chromatic adaptation.
von Kries transform.
One of the derivations of the von Kries coefficient law is the von Kries transform, a chromatic adaptation method that is sometimes used in camera image processing. Using the coefficient law, cone responses formula_20 from two radiant spectra can be matched by appropriate choice of diagonal adaptation matrices "D"1 and "D"2:
where formula_22 is the "cone sensitivity matrix" and formula_23 is the spectrum of the conditioning stimulus. This leads to the "von Kries transform" for chromatic adaptation in LMS color space (responses of long-, medium-, and short-wavelength cone response space):


Acidimetry


Visual word form area

The visual word form area (VWFA) is a functional region of the left fusiform gyrus and surrounding cortex (right-hand side being part of the fusiform face area) that is hypothesized to be involved in identifying words and letters from lower-level shape images, prior to association with phonology or semantics. Because the alphabet is relatively new in human evolution, it is unlikely that this region developed as a result of selection pressures related to word recognition per se; however, this region may be highly specialized for certain types of shapes that occur naturally in the environment and are therefore likely to surface within written language.
In addition to word recognition, the VWFA may participate in higher-level processing of word meaning.
In 2003, functional imaging experiments have also raised doubts about whether the VWFA is an actual region. This skepticism has largely disappeared; however, there seems to be much variability in its size. An area that may fall within this mental organ in one person may fall outside it in someone else
Anomalies in the activation of this region have been linked to reading disorders. If the area is subjected to a surgical lesion, the patient will suffer a clear impairment to reading ability but not to recognition of objects, names, or faces or to general language abilities. There will be some improvement over the next six months, but reading will still take twice as long as it had before surgery. Electrical brain stimulation to the VWFA causes reading-specific disruptions and can cause letter misperception.
Visual word form hypotheses.
Pre-lexical visual word form hypothesis.
Put forward by Cohen and colleagues (2000). The basics of this theory state that the neurons in the ventral occipital-temporal cortex (vOT) – which the posterior fusiform gyrus is a part of – have receptive fields that are sensitive to bigrams, or two letter combinations that commonly occur in words. The neurons sense and process the bigrams, to detect their legality. Here the posterior left fusiform gyrus (part of the vOT), is thought to be one station in a long line of processing areas. The processing starts with visual feature detectors in extrastriate cortex, proceeding through letter detectors and letter-cluster detectors in the posterior fusiform, and then activating lexical representations stored in more anterior multimodal fusiform area. The theory states the function of the VWFA is pre-lexical as it occurs before the word is understood to have meaning.
Lexical visual word form hypothesis.
Put forward by Kronbilcher et al. (2004), was based on functional imaging data that showed, in a parametric fMRI study, that a decrease in activation in the left fusiform gyrus was seen in response to an increase in the frequency of the word - where the frequency is how common the word is. This data refutes the previous pre-lexical theory as if the VWFA was pre-lexical one would expect equal activation throughout all frequencies. Instead a lexical theory was proposed where the left fusiform gyrus neurons are thought not to detect words by attempting to match them to stored representations of known words. This would explain the data as more common words would take less time to detect than the less common words, reducing the energy needed for computation and therefore potentially reducing the magnitude of the haemodynamic response that is detected by BOLD fMRI.
A recent intracranial electrocorticography study shows that the activity in the VWFA goes through multiple stages of processing. Using classification with direct neural recordings from the VWFA, Hirshorn et al. showed that early VWFA activity, from approximately 100-250 milliseconds after reading a word, is consistent with a pre-lexical representation and later activity, from approximately 300-500 milliseconds is consistent with a lexical representation. These results potentially mediate between the pre-lexical and lexical hypotheses by showing that both levels of representation may be seen in the VWFA, but at different latencies after reading a word. Previous studies using fMRI did not have the temporal resolution to differentiate between these two stages.
Alternative functions for the cortical area ascribed to the VWFA.
Devlin et al. (2006) state that the left posterior fusiform gyrus is not a 'word form area' as such, but instead hypothesizes that the area is dedicated to determining word meaning. That is to say, that this area of the brain is where bottom-up information (visual shapes of words (form), and other visual attributes if necessary) comes into contact with top-down information (semantics and phonology of words). Therefore, the left fusiform gyrus is thought to be the interface in the processing of the words not a dictionary that computes a word based on its form alone, as the lexical word form hypothesis states. This paper also presents evidence that refutes the lexical hypothesis.
Another major difference between this hypothesis and the prior ones mentioned is that it is not limited to words alone but to any "meaningful stimulus", in fact non-sensical objects may activate the posterior fusiform cortex in order to extract their meaning from higher-level processes. However, the finding that disruption of the VWFA due to surgical lesions or electrical brain stimulation has little impact on a person's ability to extract meaning from non-word stimuli provides strong evidence that the function of the VWFA is primarily restricted to processing words and not "any meaningful stimulus."
However, there is some evidence that the VWFA is not specialized for reading specifically but instead has a set of specific properties and functions that make it useful for reading—and particularly important for fluid reading—but may also allow it to play roles in other forms of visual processing. VWFA involvement appears to depend partly on the visual complexity of a stimulus, and it appears to process recognizable visual stimuli that are grouped together. This may explain why "letter by letter" reading is still possible even when the VWFA suffers lesions that otherwise interfere with fluid reading ability. This may also address why the VWFA is activated even more strongly by line drawings and Amharic characters than by written words familiar to study participants.
Involvement in Hyperlexia and Dyslexia.
Hyperlexia.
Some research suggests that children with autism spectrum disorders (ASD) may rely more heavily on visual perception areas—including the VWFA—and less heavily on phonological areas during reading tasks compared to non-ASD children. Greater activation of the VWFA may be particularly significant in children with hyperlexia, or reading ability beyond one's training. Hyperlexia is thought to be associated with ASD, with estimates of prevalence in autistic children ranging from 6 to 20.7%. One study of a hyperlexic child with ASD showed elevated activation compared to controls of the right posterior inferior temporal sulcus, where the right VWFA (R-VWFA) is thought to be located. This region is active during early stages of reading development, while a non-ASD child of the subject's reading level would be expected to make less use of this region in favor of phonological ("letter-to-sound") processes.
Dyslexia.
Meta-analysis of studies of children and adults with dyslexia suggests that underactivation of the left occipitotemporal region—particularly the VWFA—may be involved in dyslexics' difficulty with fluid reading. These reading difficulties may also be related to poor connectivity between the VWFA and associated regions in the parietal cortex responsible for visual attention.


Ventral pallidum

The ventral pallidum (VP) is a structure within the basal ganglia of the brain. It is an output nucleus whose fibres project to thalamic nuclei, such as the ventral anterior nucleus, the ventral lateral nucleus, and the medial dorsal nucleus.
The VP is a core component of the reward system which forms part of the limbic loop of the basal ganglia, a pathway involved in the regulation of motivational salience, behavior, and emotions. It is involved in addiction.
The VP contains one of the brain's pleasure centers, which mediates the subjective perception of pleasure that results from "consuming" certain rewarding stimuli (e.g., palatable food).
Anatomy.
The ventral pallidum lies within the basal ganglia, a group of subcortical nuclei. Along with the external globus pallidus, it is separated from other basal ganglia nuclei by the anterior commissure.
Limbic loop.
The limbic loop is a functional pathway of the basal ganglia, in which the ventral pallidum is involved. It (and the internal globus pallidus and substantia nigra pars reticulata) receives input from the temporal lobes, and the hippocampus via the ventral striatum. The information is relayed to the medial dorsal and ventral anterior nuclei of the thalamus.
Role in addiction.
The ventral pallidum receives dopaminergic inputs from the ventral tegmental area. The ventral pallidum also receives GABAergic inputs from the nucleus accumbens. It acts in part as a relay nucleus from the nucleus accumbens to the medial dorsal nucleus. The nucleus accumbens projects to the medial dorsal nucleus via GABAergic medium spiny neurons. The rewarding effects of addictive drugs are mediated in part through their effect on the VP.


Termination option


Orvepitant

Orvepitant (GW823296) is a drug developed by GlaxoSmithKline which acts as a selective antagonist for the NK1 receptor. It was under development as a potential antidepressant drug, and early stage human clinical trials showed it to have some antidepressant effects, though not with sufficient efficacy to justify further development for this application. It was however considered a successful proof of concept for NK1 antagonists as potential antidepressants, and efforts are continuing to find more potent compounds which might be more effective.


Pointer analysis

In computer science, pointer analysis, or points-to analysis, is a static code analysis technique that establishes which pointers, or heap references, can point to which variables, or storage locations. It is often a component of more complex analyses such as escape analysis. A closely related technique is shape analysis.
Example.
For the following example program, a points-to analysis would compute that the points-to set of codice_1 is {codice_2, codice_3}.
int x;
int y;
int* p = unknown() ? &x : &y;
Introduction.
As a form of static analysis, fully precise pointer analysis can be shown to be undecidable. Most approaches are sound, but range widely in performance and precision. For large programs, some tradeoffs may be necessary to make the analysis finish in reasonable time and space. Two examples of these tradeoffs are:
The disadvantage of these simplifications is that the calculated set of objects pointed to may become less precise.
Context-Insensitive, Flow-Insensitive Algorithms.
Pointer analysis algorithms are used to convert collected raw pointer usages (assignments of one pointer to another or assigning a pointer to point to another one) to a useful graph of what each pointer can point to.
Steensgaard's algorithm and Andersen's algorithm are common context-insensitive, flow-insensitive algorithms for pointer analysis. They are often used in compilers, and have implementations in the LLVM codebase.
Flow-Insensitive Approaches.
Many approaches to flow-insensitive pointer analysis can be understood as forms of abstract interpretation, where heap allocations are abstrated by their allocation site (i.e., a program location).
Many flow-insensitive algorithms are specified in Datalog, including those in the Soot analysis framework for Java.
Context-sensitive, flow-insensitive algorithms achieve higher precision, generally at the cost of some performance, by analyzing each procedure several times, once per "context". Most analyses use a "context-string" approach, where contexts consist of a list of entries (common choices of context entry include call sites, allocation sites, and types). To ensure termination (and more generally, scalability), such analyses generally use a "k"-limiting approach, where the context has a fixed maximum size, and the least recently added elements are removed as needed. Three common variants of context-sensitive, flow-insensitive analysis are:
Call-site sensitivity.
In call-site sensitivity, the points-to set of each variable (the set of abstract heap allocations each variable could point to) is further qualified by a context consisting of a list of callsites in the program. These contexts abstract the control-flow of the program.
The following program demonstrates how call-site sensitivity can achieve higher precision than a flow-insensitive, context-insensitive analysis.
int *id(int* x) {
 return x;
int main() {
 int y;
 int z;
 int *y2 = id(&y); // call-site 1
 int *z2 = id(&z); // call-site 2
 return 0;
For this program, a context-insensitive analysis would (soundly but imprecisely) conclude that can point to either the allocation holding or that of , so and may alias, and both could point to either allocation. A callsite-sensitive analysis would analyze twice, once for call-site 1 and once for call-site 2, and the points-to facts for would be qualified by the call-site, enabling the analysis to deduce that when returns, can only point to the allocation holding and can only point to the allocation holding .
Object sensitivity.
In an object sensitive analysis, the points-to set of each variable is qualified by the abstract heap allocation of the receiver object of the method call. Unlike call-site sensitivity, object-sensitivity is "non-syntactic" or "non-local": the context entries are derived during the points-to analysis itself.
Type sensitivity.
Type sensitivity is a variant of object sensitivity where the allocation site of the receiver object is replaced by the class/type containing the method containing the allocation site of the receiver object. This results in strictly fewer contexts than would be used in an object-sensitive analysis, which generally means better performance.


Cerebral aqueduct

The cerebral aqueduct (aqueductus mesencephali, mesencephalic duct, sylvian aqueduct or aqueduct of Sylvius) is a conduit for cerebrospinal fluid (CSF) that connects the third ventricle to the fourth ventricle of the ventricular system of the brain. It is located in the midbrain dorsal to the pons and ventral to the cerebellum. The cerebral aqueduct is surrounded by an enclosing area of gray matter called the periaqueductal gray, or central gray.
It was first named after Franciscus Sylvius.
Structure.
Development.
The cerebral aqueduct, as other parts of the ventricular system of the brain, develops from the central canal of the neural tube, and it originates from the portion of the neural tube that is present in the developing mesencephalon, hence the name "mesencephalic duct."
Function.
The cerebral aqueduct acts like a canal that passes through the midbrain and connects the third ventricle with the fourth ventricle of the brain and the cerebrospinal fluid (CSF) finds its natural pathway through the cerebral ventricles and the canal connecting these ventricles.
Clinical significance.
Aqueductal stenosis, a narrowing of the cerebral aqueduct, obstructs the flow of CSF and has been associated with non-communicating hydrocephalus. Such narrowing can be congenital, arise via tumor compression (e.g. pinealoblastoma), or through cyclical gliosis secondary to an initial partial obstruction.


Sahifah

Ṣaḥīfah or sahifa () is the Arabic word for 'page'. In Persian, the word is pronounced "sahifeh".


RhTx

RhTx is a small peptide toxin from "Scolopendra subspinipes mutilans", also called the Chinese red-headed centipede. RhTx binds to the outer pore region of the temperature regulated TRPV1 ion channel, preferably in activated state, causing a downwards shift in the activation threshold temperature, which leads to the immediate onset of heat pain.
Sources.
RhTx is a component of the venom of the "S. subspinipes mutilans", also called the Chinese red-headed centipede.
Chemistry.
RhTx is a small peptide toxin, with a compact 3D-structure. The gene encoding for RhTx translates into a 69 amino acid peptide that shows no homology to any known animal toxin. This peptide, after post- translational modifications, yields a mature toxin of 27 amino acids. RhTx has two pairs of disulfide bonds. While the N-terminus of the peptide contains no charged amino acids, the C-terminus of the peptide is rich in charged amino acids. In the folded peptide, these charged amino acids are all located on the same side of the peptide, making RhTx a polar molecule.
Target.
RhTx binds to the outer pore region of the polymodal TRPV1 ion channel. The toxin preferably binds to TRPV1 in the activated state of the channel. RhTx has a high affinity for the TRPV1 ion channel, which results in very rapid binding and slow unbinding.
The TRPV1 channel is a non-selective cation channel, with a high permeability to Ca2+.
TRPV1 is mainly expressed in sensory neurons and can be activated by different stimuli, including high temperatures (heat), acids, pollutants with negative electric charge and endogenous metabolites such as anandamide. The channel is also targeted by the active component of chilli peppers capsaicin, and the spider toxins Vanillotoxin and DkTx.
Mode of action.
After binding to the outer pore region of the TRPV1, RhTx can interact with both the turret and the pore helix through electrostatic and hydrophobic interactions. RhTx binding is expected to induce conformational changes to the outer pore, which are thought to be the cause of the drop of the activation threshold for the TRPV1 channel. These changes strongly promote the opening of the TRPV1 channel at the normal body temperature of the organism, resulting in intense burning pain.
It is hypothesized that RhTx binding might also interfere with ion permeation due to its interaction with the pore helix.
Toxicity.
In mice, injections of RhTx induced pain behavior, which was distinct from pain behavior mediated by inflammation, but similar to the behavior elicited by capsaicin injection. Injections in mice also caused a rapid drop of core body temperature at normal conditions, by less than 1 degree Celsius. The EC50 in mice is estimated to be 500 nM.
While the effect of isolated RhTx administration is not known in humans, bites of the "S. subspinipes mutilans" species generally cause immediate localized burning pain, followed by edema, erythema and other localized symptoms. Serious morbidity is very uncommon and treatment is supportive, focusing on treating symptoms.


Continuous tone

A continuous tone image (contone for short, or CT even shorter) is one where each color at any point in the image is reproduced as a single tone, and not as discrete halftones, such as one single color for monochromatic prints, or a combination of halftones for color prints.
The most common continuous tone images are film photographs (digital latitude is not continuous!) Also see film latitude. Every single dot of which can take a continuous range of colors depending on the quantity of captured radiance. On the other hand, at a microscopic level, developed black-and-white photographic film consists of only two colors, and not an infinite range of continuous tones. For details, see film grain.
An example of a continuous-tone device is a CRT computer screen. Here, any pixel can represent any color, because the color components of the pixel are analog and can vary in infinite steps, and hence do not need halftones to make the colors. Of course, because the computer is a digital device, it cannot provide the CRT with infinite tone variations. In 24-bit color mode, it provides the monitor with 256 discrete steps for each channel (red, green, and blue), for a total of 16,777,216 (2563) discrete colors. A purely analog video signal (one that has not been manipulated by a computer of any kind) can provide infinite tone variations inside its own gamut.
A halftone device, in contrast, uses discrete dots of color, which at a certain distance look closely like the intended color. Examples of this are inkjet printers. Magazines and most printed material also use this technique to create the colors.


International Journal of Neural Systems

The International Journal of Neural Systems is a bimonthly peer-reviewed scientific journal founded in 1989. It is published by World Scientific and covers information processing in natural and artificial neural systems.
Abstracting and indexing.
The journal is abstracted and indexed in:


Paul Daniels

Newton Edward Daniels (6 April 1938 – 17 March 2016), known professionally as Paul Daniels, was an English magician and television presenter. He achieved international fame through his television series "The Paul Daniels Magic Show", which ran on the BBC from 1979 to 1994. He was known for his catchphrase, "You'll like this... not a lot, but you'll like it!" and for his marriage to his assistant, Debbie McGee. He was awarded the "Magician of the Year" Award by the Academy of Magical Arts in 1982, the first magician from outside the United States to receive it. He also won the Golden Rose of Montreux in 1985.
He was a Member of the Inner Magic Circle with Gold Star. He has been described as "The Godfather of Magic" and has been repeatedly credited with inspiring many top professional magicians to start in the profession.
Daniels was outspoken on matters including politics, current affairs, magic, entertainment, and fellow celebrities. He also appeared in reality television shows. He was described by Lord Michael Grade, former controller of both the BBC and ITV, when talking of Paul on BBC News in 2016, as 'a genius', 'a brilliant showman' and a 'pillar of Saturday Night for the BBC in their golden era of ratings'.
Early life.
Newton Edward Daniels was born on 6 April 1938 in the South Bank area of Middlesbrough, the son of Handel Newton "Hughie" Daniels and Nancy ("née" Lloyd). He was of Welsh descent. His father was a cinema projectionist at the Hippodrome Theatre and a worker for ICI in Wilton, North Riding of Yorkshire. After completing his education at Sir William Turners Grammar School on Coatham Road in Coatham, North Riding of Yorkshire and holding his first job as a junior clerk in the treasurer's office of Eston Council, Daniels served as a conscript in the 1st Battalion, Green Howards, during his national service. He was posted to the British garrison in Hong Kong before training as an accountant in local government.
Even in his early age, Daniels had thinning hair, which he claimed to be an act of "magic". He later sported a wig for much of his television career. After working as a junior clerk and then as an auditor in local government, he joined his parents in their grocery business. He later set up his own shop, at one point a mobile shop, but eventually gave this up in favour of his growing career as a magician.
In 2012 Daniels explained the origin of his stage name to "The Guardian", saying: "I borrowed the name Paul from my first son, who was born in 1960. I was born Newton Edward Daniels, everyone called me Ted, but Paul worked better for showbusiness".
Showbusiness career.
Daniels' interest in magic began at the age of 11 when, during a holiday, he read a book called "How to Entertain at Parties". He began performing magic as a hobby, occasionally entertaining at parties and youth clubs and later doing shows for fellow servicemen during his national service. After returning to civilian life he continued to develop his magic by performing in clubs in the evenings while working at his grocery business during the day. At one point he worked with his first wife Jackie under the name of "The Eldani's", an anagram of Daniels. It was while working the clubs that he developed what would become his long-running catchphrase, "You'll like this ... not a lot, but you'll like it." He stated that he first came up with the line at a club in Bradford as a way to deal with a heckler.
A major turning point in Daniels' career came in 1969 when he was offered a summer season in Newquay in Cornwall. He decided to sell his grocery business and try magic as a full-time career. He made his television debut on the long-running talent show "Opportunity Knocks" in 1970, and came second. Television producer Johnnie Hamp saw Daniels in that show and later gave him a regular spot on a show compèred by Bernard Manning, "The Wheeltappers and Shunters Social Club", for Granada Television.
In 1978 ITV gave Daniels his own Sunday night show, "Paul Daniels' Blackpool Bonanza". His first series for the BBC was "For My Next Trick", where Daniels appeared with several other magicians and singer Faith Brown. This led to Daniels presenting his own television series, "The Paul Daniels Magic Show", on BBC1 from 1979 until 1994. As well as featuring tricks and illusions for pure entertainment, he also included a regular segment (the "Bunco Booth") in which he exposed the confidence tricks of street charlatans. He also replicated the kind of results that have impressed researchers of the paranormal and parapsychologists in a segment called "Under Laboratory Conditions", thereby demonstrating his scepticism about claims made in these fields.
Daniels starred in his own stage show, "It's Magic", at the Prince of Wales Theatre from 10 December 1980 until 6 February 1982. At that time, the show was one of the longest-running magic shows ever staged in London. By this point he was already working with his future wife, Debbie McGee, whose role as his assistant would become a major feature of his act. She had first worked with him on his summer season show in Great Yarmouth in 1979.
In addition to his magic shows he hosted other television series during the 1980s and 1990s, including three BBC1 quiz shows: "Odd One Out", "Every Second Counts" and "Wipeout" (all of which were based on short-lived American game shows), and the children's television programme "Wizbit" (also for the BBC), about a magician called Wizbit and a rabbit called Woolly, who lived in Puzzleopolis.
In 1987, Daniels hosted a controversial Halloween live special of his magic show where he replicated a Harry Houdini escape from an iron maiden. The trick was deliberately staged to give the illusion that the escape had gone tragically wrong and Daniels had been killed – it was later broadcast that he had successfully escaped from the device.
He was the subject of "This Is Your Life" in 1988 when he was surprised by Michael Aspel.
Daniels and McGee were the focus of one of the episodes of the 2001 BBC documentary series "When Louis Met...", presented by Louis Theroux, with Daniels additionally appearing on "Da Ali G Show" in an Ali G costume, and was interviewed by Caroline Aherne in her guise as Mrs Merton. In 2004, Daniels and McGee appeared in the Channel 5 reality TV show, "The Farm", and in 2006, they appeared in the ITV show "". They were the first act voted off the show, after singing "Let Me Entertain You" by Robbie Williams. Daniels and McGee also made a guest appearance in the "Wife Swap" series in early 2007, with McGee changing places with journalist and presenter Vanessa Feltz.
In 2010, he competed in "Strictly Come Dancing" with his partner Ola Jordan. They were consistently criticised by the judges and were the second couple to leave the competition.
In August 2011, while filming a scene for ITV's "Sooty", Daniels was struck by a flying pizza, thrown by the puppet Sooty. He got a piece of pizza in his eye and called in to a cottage hospital for them to rinse it out. Later that month, he appeared with his son, Martin, on episode 9 of the first season of "".
On 10 October 2012, Daniels and McGee appeared on "All Star Mr & Mrs" on ITV.
In 2008 and 2010, Daniels toured with 'The Best of British Variety Tour', with acts including Cannon and Ball, Christopher Biggins, Frank Carson and The Krankies, where he closed the first half of the show.
In 2013, Daniels and Debbie McGee toured their 'First Farewell Tour', followed by a tour 'comically' entitled 'Back Despite Popular Demand Tour' a year later. They toured 'The Intimate Tour' in 2015.
They starred in the Pantomime 'Aladdin', at the Ipswich Regent Theatre from December 2015 until January 2016, completing the run a few days before Paul was taken ill.
Awards.
Daniels was awarded the "Zina Bennett Trophy" from the British Ring of the International Brotherhood of Magicians in 1964 while he was known as "Ted Daniels"
Daniels was awarded the "Magician of the Year’" Award by the Academy of Magical Arts in 1982, becoming the first magician from outside the US to receive it. An Easter special of "The Paul Daniels Magic Show" won the Golden Rose of Montreux Award at the International TV Festival in Switzerland in 1985.
Daniels was the recipient of "The Maskelyne", awarded for services to British Magic by The Magic Circle in 1988.
He was awarded "The Devant", for services to International Magic by The Magic Circle in 2007 and was bestowed "The Carlton Comedy Award" in 2012 by the same organization.
Daniels was also awarded the "Great Lafayette Award" by the Edinburgh International Magic Festival in 2011.
Politics and other views.
Daniels was a supporter of the Conservative Party. He was reported to have considered leaving the UK with the election of a Labour Party government at the 1997 general election. Daniels later said that his views had been misrepresented and he would only have considered leaving if they raised income tax. Daniels stated that he had limited sympathy with the homeless because he had come from a "very poor" background and "grafted" to achieve his success. In 2011, he tweeted that he did not consider the term "Paki" to be any more offensive than the word "Brit" and described those who held the opposite view of being excessively politically correct. Daniels was personally affected by the winter storms of 2013–2014 and described himself in an interview for "Channel 4 News" as a climate change sceptic, instead attributing flooding to changes in procedures of The Environment Agency, particularly with regard to dredging. He supported the hereditary system in the House of Lords, expressing pro-aristocratic views. On the subject of criminal justice, he once publicly offered to help murderer Ian Huntley end his own life.
Daniels refused to attend magic conferences in the UK since they "...were ruined for me by bitchiness and jealousy...now I only go to foreign conventions where, to be honest, I am greeted with respect and civility AND I have tons of 'foreign' magician friends." He was dismissive of modern illusionists, once describing David Blaine as "not very original". He commented on other television personalities such as Anne Robinson and Chris Morris, claiming that Robinson had hated him ever since his 1987 Halloween special hoax performance, while describing Morris as "just nasty." He was dismissive of the younger generation of impressionists, saying: "Forget Alistair McGowan. There's been no-one good since Mike Yarwood." Daniels was also critical of journalists, stating "I don't really understand why journalism has to be so nasty, so sarcastic and intrusive".
Following the Jimmy Savile sexual abuse scandal in 2012, Daniels said that while he believed Savile, a fellow BBC broadcaster, was "undoubtedly a bad guy", he questioned whether some accusers were "for real". His comments were criticised by the NSPCC and Mark Williams-Thomas, the former child protection officer who had exposed Savile's crimes. Williams-Thomas accused Daniels of "belittling" the victims of Jimmy Savile in one of his blog posts. The entry was later removed from the blog.
Personal life.
Daniels married his first wife, Jacqueline Skipworth (born 1942), in 1960; she was 17 and he was 21. They had three sons together: Gary, Paul, and magician Martin. All three sons occasionally appeared on "The Paul Daniels Magic Show" in varying capacities. Daniels's father often made props for the show, such as wooden boxes for the Selbit Sawing illusion, whilst his mother sewed the stage curtains for his theatre tours.
Daniels married his second wife, long-time assistant Debbie McGee, on 2 April 1988 in Buckinghamshire. The couple met in London in May 1979 during rehearsals for Daniels's summer season show in Great Yarmouth that year. When they married, he was 50 and she was 29. McGee went on to work with Daniels in his 1980 summer show in Bournemouth and then his London stage show "It's Magic" before being offered the role of assistant in his long-running television series. Their relationship gradually became more established, and he proposed in 1987. Early in their marriage, they lived in a house in Denham that once belonged to Roger Moore. In 1998, they moved to a house on the banks of the River Thames in Wargrave, Berkshire.
Daniels's autobiography, "Under No Illusion", includes descriptions of his and McGee's joking life: "I was writing and needed to concentrate, so I had a 'Do Not Disturb' sign on my back. Eventually I went to bed and Debbie was lying stark naked on the bed – eat your heart out fellas! She was wearing the sort of sleeping blindfold you get on long-haul flights. Printed on it was 'Do Not Disturb'. But further down her body she had a sign that said 'Disturb'!"
Daniels also claimed in the book to have had, as of 2000, sexual relations with more than 300 women. He said that he had a "passionate" encounter with a schoolgirl hitch-hiker in 1969 when he was aged 30, though he ejected her from the car upon realising her age.
Daniels maintained a website that included personal information, a detailed blog, and podcasts.
In 2012, Daniels cut off his left index finger and the tip of his ring finger in an accident with a circular saw, in the garden shed of his Wargrave home. He drove himself from his home to hospital in Henley-on-Thames, where the index finger was reattached.
Health problems and death.
On 20 February 2016, Daniels had a fall and was taken to hospital, where he was treated by medical staff for suspected pernicious anemia. However it was later discovered that he had an incurable brain tumour. He died less than a month later, on 17 March, at the age of 77. Tributes included one from fellow magician Dynamo: “Paul was truly a giant of the entertainment world who really defined magic for over 20 years,” he said. “As a working-class magician from the North, he was personally a huge inspiration for me and I know that he has inspired countless magicians around the world and will forever be known as one of the all-time greats.”


Disopyramide

Disopyramide (INN, trade names Norpace and Rythmodan) is an antiarrhythmic medication used in the treatment of ventricular tachycardia. It is a sodium channel blocker and therefore classified as a Class 1a anti-arrhythmic agent. Disopyramide has a negative inotropic effect on the ventricular myocardium, significantly decreasing the contractility. Disopyramide also has an anticholinergic effect on the heart which accounts for many adverse side effects. Disopyramide is available in both oral and intravenous forms, and has a low degree of toxicity.
Mechanism of action.
Disopyramide's Class 1a activity is similar to that of quinidine in that it targets sodium channels to inhibit conduction. Disopyramide depresses the increase in sodium permeability of the cardiac myocyte during Phase 0 of the cardiac action potential, in turn decreasing the inward sodium current. This results in an increased threshold for excitation and a decreased upstroke velocity. Disopyramide prolongs the PR interval by lengthening both the QRS and P wave duration. This effect is particularly well suited in the treatment of ventricular tachycardia as it slows the action potential propagation through the atria to the ventricles. Disopyramide does not act as a blocking agent for beta or alpha adrenergic receptors, but does have a significant negative inotropic effect on the ventricular myocardium. As a result, the use of disopyramide may reduce contractile force up to 42% at low doses and up to 100% in higher doses leading to heart failure.
Levites proposed a possible secondary mode of action for disopyramide, against reentrant arrhythmias after an ischemic insult. Disopyramide decreases the inhomogeneity between infarcted and normal myocardium refractory periods; in addition to lengthening the refractory period. This decreases the chance of re-entry depolarization, because signals are more likely to encounter tissue in a refractory state which cannot be excited. This provides a possible treatment for atrial and ventricular fibrillation, as it restores pacemaker control of the tissue to the SA and AV nodes.
Obstructive hypertrophic cardiomyopathy.
Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease, occurring in 1:500 individuals in the general population. It is estimated that there are 600,000 individuals in the United States with hypertrophic cardiomyopathy. The most common variant of HCM presents with left ventricular (LV) intracavitary obstruction due to systolic anterior motion of the mitral valve, and mitral-septal contact, diagnosed readily with echocardiography. Pharmacologic treatment with negative inotropic drugs is first-line therapy. Beta-blockers are used first, and while they improve symptoms of shortness of breath, chest pain and exercise intolerance, they do not reduce resting LV intraventricular pressure gradients and often are inadequate to control symptoms. Many investigators and clinicians believe that disopyramide controlled release is the most potent agent available for reducing resting pressure gradients and improving symptoms. Disopyramide has been actively used for more than 30 years. Disopyramide administration for obstructive HCM has a IIa recommendation in the 2011 American Heart Association/American College of Cardiology Foundation guidelines for treatment of obstructive HCM. A IIa treatment recommendation indicates that benefits outweigh risk, and that it is reasonable to administer treatment.
Negative inotropes improve LV obstruction by decreasing LV ejection acceleration and hydrodynamic forces on the mitral valve. Disopyramide's particular efficacy is due to its potent negative inotropic effects; in head-to-head comparison, it is more effective for gradient reduction than either beta-blocker or verapamil. Disopyramide is most often administered with beta-blockade. When used in patients resistant to beta-blockade, disopyramide is effective in 60% of cases, reducing symptoms and gradient to the extent that invasive procedures such as surgical septal myectomy are not required.
Disopyramide, despite its efficacy, has one main side effect that has limited its use in the US, though it has seen wider application in Canada, UK and Japan. Vagal blockade predictably causes dry mouth, and in men with prostatism, may cause urinary retention. Teichman et al. showed that pyridostigmine used in combination with disopyramide substantially alleviates vagolytic side effects without compromising antiarrhythmic efficacy. This combination has also been shown to be effective and safe in obstructive HCM in a large cohort of patients. Some clinicians prescribe pyridostigmine sustained release (marketed in the US as Mestinon Timespan) to every patient begun on disopyramide. This combination increases acceptance of higher disopyramide dosing, important since there is a dose-response correlation in obstructive HCM, higher doses yielding lower gradients.
Another concern about disopyramide has been the hypothetical potential for inducing sudden death from its type 1 anti-arrhythmic effects. However, a multicenter registry and two recent cohort registries have largely reduced this concern, by showing sudden death rates lower than that observed from the disease itself.
These concerns about the drug must be viewed from the clinical perspective that disopyramide is generally the last agent that is tried for patients before they are referred for invasive septal reduction with surgical septal myectomy (an open-heart operation) or alcohol septal ablation (a controlled heart attack). Both of these invasive procedures have risk of morbidity and mortality.
For selected patients, a trial of oral disopyramide is a reasonable approach before proceeding to invasive septal reduction. Patients who respond to disopyramide are continued on the drug. Those who continue to have disabling symptoms or who experience side effects are promptly referred for septal reduction. Using such a stepped strategy, investigators have reported that survival does not differ from that observed in the age-matched normal United States population.
Extracardiac effects.
Atropine like effects (anticholinergic)
Additionally, disopyramide may enhance the hypoglycaemic effect of gliclazide, insulin, and metformin.


Nodule of vermis

The nodule (nodular lobe), or anterior end of the inferior vermis, abuts against the roof of the fourth ventricle, and can only be distinctly seen after the cerebellum has been separated from the medulla oblongata and pons.
On either side of the nodule is a thin layer of white substance, named the posterior medullary velum.
It is semilunar in form, its convex border being continuous with the white substance of the cerebellum; it extends on either side as far as the flocculus.


Japan Society of Neurovegetative Research

This is main scientific society in Japan interested in the study of the Autonomic Nervous System. It is affiliated with the "Japanese Association of Medical Sciences". Its official journal is "The Autonomic Nervous System" (Jiritsu shinkei; ISSN 0288-9250) founded in 1964.


Intermediate horn cell


Naldecon

Naldecon, a brand name for phenylephrine, is an antihistamine and decongestant commonly prescribed in the 1950s.
In popular culture.
Elvis' pill bottle, with the Naldecon removed, was sold at auction for over $2,600.


Kan-on

 is one of the sources of pronunciation of Japanese kanji. They were borrowed during the Tang dynasty (7th to 9th century), introduced by, among others, envoys from Japanese missions to Tang China. This period corresponds with the Japanese Nara period. Not to be confused with Tō-on "Tang sound", which actually refers to later phonetic loans.
"Kan-on" is based on the central Chang'an pronunciation. The name "Kan" could refer to the Han dynasty, which also had Chang'an as its capital city. Furthermore, "Kan" has also become a description for all things Chinese, e.g., Kanji ('Chinese characters').
Kan'on partly displaced the earlier "go'on", which were "just imitations of Korean imitations, but "Kan-on" were imitations of the real things."
A minority of characters never had their "Kan-on" transmitted to Japan; their "Kan-on" are sometimes reconstructed in Japanese dictionaries although not specifically marked as such. A few dictionaries go as far as to discard attested "Kan-on" in favour of more systematic pronunciations.


Phototaxis

Phototaxis is a kind of taxis, or locomotory movement, that occurs when a whole organism moves towards or away from a stimulus of light. This is advantageous for phototrophic organisms as they can orient themselves most efficiently to receive light for photosynthesis. Phototaxis is called positive if the movement is in the direction of increasing light intensity and negative if the direction is opposite.
Two types of positive phototaxis are observed in prokaryotes. The first is called scotophobotaxis (from the word "scotophobia"), which is observed only under a microscope. This occurs when a bacterium swims by chance out of the area illuminated by the microscope. Entering darkness signals the cell to reverse flagella rotation direction and reenter the light. The second type of phototaxis is true phototaxis, which is a directed movement up a gradient to an increasing amount of light. This is analogous to positive chemotaxis except that the attractant is light rather than a chemical.
Phototactic responses are observed in many organisms such as "Serratia marcescens", "Tetrahymena", and "Euglena". Each organism has its own specific biological cause for a phototactic response, many of which are incidental and serve no end purpose.
Phototaxis in zooplankton.
Phototaxis in zooplankton is well studied in the marine annelid "Platynereis dumerilii":
"Platynereis dumerilii" trochophore and metatrochophore larvae are positively phototactic. Phototaxis there is mediated by simple eyespots that consists of a pigment cell and a photoreceptor cell. The photoreceptor cell synapses directly onto ciliated cells, which are used for swimming. The eyespots do not give spatial resolution, therefore the larvae are rotating to scan their environment for the direction where the light is coming from.
"Platynereis dumerilii" nectochaete larvae can switch between positive and negative phototaxis. Phototaxis there is mediated by two pairs of more complex pigment cup eyes. These eyes contain more photoreceptor cells that are shaded by pigment cells forming a cup. The photoreceptor cells do not synapse directly onto ciliated cells or muscle cells but onto inter-neurons of a processing center. This way the information of all four eye cups can be compared and a low-resolution image of four pixels can be created telling the larvae where the light is coming from. This way the larva does not need to scan its environment by rotating. This is an adaption for living on the bottom of the sea the lifestyle of the nectochaete larva while scanning rotation is more suited for living in the open water column, the lifestyle of the trochophore larva. Phototaxis in the "Platynereis dumerilii" nectochaete larva has a broad spectral range which is at least covered by three opsins that are expressed by the cup eyes: Two rhabdomeric opsins and a Go-opsin.
However, not every behavior that looks like phototaxis is phototaxis: "Platynereis dumerilii" nechtochate and metatrochophore larvae swim up first when they are stimulated with UV-light from above. But after a while, they change the direction and avoid the UV-light by swimming down. This looks like a change from positive to negative phototaxis (see video left), but the larvae also swim down if UV-light comes non-directionally from the side. And so they do not swim to or away from the light, but swim down, this means to the center of gravity. Thus this is a UV-induced positive gravitaxis. Positive phototaxis (swimming to the light from the surface) and positive gravitaxis (swimming to the center of gravity) are induced by different ranges of wavelengths and cancel out each other at a certain ratio of wavelengths. Since the wavelengths compositions change in water with depth: Short (UV, violet) and long (red) wavelengths are lost first, phototaxis and gravitaxis form a ratio-chromatic depth gauge, which allows the larvae to determine their depth by the color of the surrounding water. This has the advantage over a brightness based depth gauge that the color stays almost constant independent of the time of the day or whether it is cloudy.
Phototaxis in jellyfish.
Positive and negative phototaxis can be found in several species of jellyfish such as those from the genus Polyorchis. Jellyfish use ocelli to detect the presence and absence of light, which is then translated into anti-predatory behaviour in the case of a shadow being cast over the ocelli, or feeding behaviour in the case of the presence of light. Many tropical jellyfish have a symbiotic relationship with photosynthetic zooxanthellae that they harbor within their cells. The zooxanthellae nourish the jellyfish, while the jellyfish protects them, and moves them toward light sources such as the sun to maximize their light-exposure for efficient photosynthesis. In a shadow, the jellyfish can either remain still, or quickly move away in bursts to avoid predation and also re-adjust toward a new light source.
This motor response to light and absence of light is facilitated by a chemical response from the ocelli, which results in a motor response causing the organism to swim toward a light source.
Phototaxis in insects.
Positive phototaxis can be found in many flying insects such as moths, grasshoppers, and flies. "Drosophila melanogaster" has been studied extensively for its innate positive phototactic response to light sources, using controlled experiments to help understand the connection between airborne locomotion toward a light source. This innate response is common among insects that fly primarily during the night utilizing transverse orientation vis-à-vis the light of the moon for orientation. Artificial lighting in cities and populated areas results in a more pronounced positive response compared to that with the distant light of the moon, resulting in the organism repeatedly responding to this new supernormal stimulus and innately flying toward it.
Evidence for the innate response of positive phototaxis in "Drosophila melanogaster" was carried out by altering the wings of several individual specimens, both physically (via removal) and genetically (via mutation). In both cases there was a noticeable lack of positive phototaxis, demonstrating that flying toward light sources is an innate response to the organisms' photoreceptors receiving a positive response.
Negative phototaxis can be observed in larval "drosophila melanogaster" within the first three developmental instar stages, despite adult insects displaying positive phototaxis. This behaviour is common among other species of insects which possess a flightless larval and adult stage in their life cycles, only switching to positive phototaxis when searching for pupation sites. "Tenebrio molitor" by comparison is one species which carries its negative phototaxis into adulthood.
Relation to magnetic fields.
Under experimental conditions, organisms that use positive phototaxis have also shown a correlation with light and magnetic fields. Under homogeneous light conditions with a shifting magnetic field, "Drosophila melanogaster" larvae reorient themselves toward predicted directions of greater or lesser light intensities as expected by a rotating magnetic field. In complete darkness, the larvae orient randomly without any notable preference. This suggests the larvae can observe a visible pattern in combination with light.


Tick-tock (journalism)

In journalism, a tick-tock is a type of story that focuses on chronological order of events.


Arab-Berber

Arab-Berbers ( "al-ʿarab wa-l-barbar") are an ethnolinguistic group of the Maghreb, a vast region of North Africa in the western part of the Arab world along the Mediterranean Sea and the Atlantic Ocean. Arab-Berbers are people of mixed Arab and Berber origin, most of whom speak a variant of Maghrebi Arabic as their native language, although about 16 to 25 million speak various Berber languages. Many Arab-Berbers identify primarily as Arab and secondarily as Berber.
Most genetic studies have determined that Maghrebi Arabs and Maghrebi Berbers are genetically nearly identical, thus making Arabization more of a cultural phenomenon rather than a genetic one. The Arab-Berber identity came into being as a direct result of the Arab conquest of North Africa, and the intermarriage between the Arabian and Persian people who immigrated to those regions and local mainly Roman Africans and other Berber people; in addition, Banu Hilal and Sulaym Arab tribes originating in the Arabian Peninsula invaded the region and intermarried with the local rural mainly Berber populations, and were a major factor in the linguistic, cultural and ethnic Arabization of the Maghreb.
Arabized Berbers form the core and vast majority of the native populations of Algeria, Libya, Morocco, and Tunisia, and about one-third of the population of Mauritania.
Arab-Berbers primarily speak variants of Maghrebi Arabic which form a dialect continuum of more-or-less mutually intelligible varieties known as (Darija or Derja (). which means "everyday/colloquial language". Maghrebi Arabic preserves a significant Berber, Latin and possibly Neo-Punic substratum which makes them both quite distinct and largely mutually unintelligible to other varieties of Arabic spoken outside Maghreb. Moreover, they also have many loanwords from French, Turkish, Italian and the languages of Spain. Modern Standard Arabic is used as the lingua franca.
Historical perspective.
Medieval Arabic sources refers to Northwest Africa as "Ifriqiya", "Mauretania" or as "Bilad Al Barbar" (; ). This designation may have given rise to the term Barbary Coast which was used by Europeans until the 19th century to refer to coastal Northwest Africa.
Since the populations were partially affiliated with the Arab Muslim culture, Northwest Africa also started to be referred to by the Arabic speakers as "Al-Maġrib", the Maghreb (meaning "The West") as it was considered as the western part of the known world. For historical references, medieval Arab and Muslim historians and geographers used to refer to Morocco as "Al-Maghrib al Aqşá" ("The Farthest West"), disambiguating it from neighboring historical regions called "Al-Maghrib al Awsat" ("The Middle West", Algeria) and "Al-Maghrib al Adna" ("The Nearest West", Ifriqiya (Tunisia)).
The Maghreb was gradually arabized with the spread of Islam in the 7th century AD, when the liturgical language Arabic was first brought to the Maghreb. However, the bulk of the population of northwestern Africa remained Berber or Roman Africans at least until the 14th century. Arabization was at least partly strengthened in the rural areas in the 11th century with the emigration of the Banu Hilal tribes from Egypt. However, many parts of the Maghreb were only arabized relatively recently in the 19th and 20th centuries, such as the area of the Aurès (Awras) mountains. Lastly, the mass education and promotion of Arabic language and culture through schools and mass media, during the 20th century, by the maghrebis governments, is regarded as the strongest contributor to the Arabization process in the Maghreb.
Population genetics.
Various population genetics studies along with historians such as Gabriel Camps and Charles-André Julien lend support to the idea that the bulk of the gene pool of modern Maghrebis, irrespective of linguistic group, is derived from the Berber populations of the pre-Islamic period.


Spatial view cells

Spatial view cells are neurons in primates' hippocampus; they respond when a certain part of the environment is in the animal's field of view.
They are related to place cells and head direction cells. Spatial view cells differ from place cells, since they are not localized in space. They also differ from head direction cells since they don't represent a global orientation (like a compass), but the direction towards a specific object. Spatial view cells are the cells that respond in the hippocampus when a particular location is being recalled. These cells are identified in the hippocampus of test subjects by monitoring individual neurons while the test subject is moved around in a cue controlled spatial environment. The spatial view cells are the cells that fire consistently when the monkey is looking at a certain direction in the environment; this is independent of the head direction or the location of the monkey. Also, these cells are confirmed to be spatial view cells by observing that there is minimal randomized firing of the cells without the appropriate stimulus present.
Characteristics.
Spatial view cells can be characterized by the following features:
The spatial view cells that respond in the absence of visual cues are generally found in the Cornu Ammonis area 1, the parahippocampal gyrus, and the presubiculum, while the ones that do not respond are found in the Cornu Ammonis region 3. The cells found in the CA1, parahippocampal gyrus, and presubiculum regions often provide a longer response even after the stimulus is removed for up to several minutes in complete darkness. Spatial view cells update their representations by the use of idiothetic inputs in the dark and these cells are commonly found in the CA1, parahippocampal gyrus, and presubiculum regions.
Uses.
Spatial view cells are used by primates for storing an episodic memory that helps with remembering where a particular object was in the environment. Imaging studies have shown that the hippocampus plays an important role in spatial navigation and episodic memories. Also, spatial view cells enable them to recall locations of objects even if they are not physically present in the environment. The neurons associated with remembering the location and object are often found in the primate hippocampus. These spatial view cells do not only recall specific locations, but they also remember distances between other landmarks around the place in order to gain a better understanding of where the places are spatially.
In real world applications, monkeys remember where they saw ripe fruit with the aid of spatial view cells. Humans use spatial view cells when they try to recall where they may have seen a person or where they left their keys. Primates' highly developed visual and eye movement control systems enables them to explore and remember information about what's present at places in the environment without having to physically visit those places. These sorts of memories would be useful for spatial navigation in which the primates visualize everything in an allocentric, or worldly manner that allows them to convey directions to others without physically going through the entire route. These cells are used by primates in regular day-to-day lives.
Removal of Spatial View Cell.
Diseases and illnesses that harm the brain and the hippocampus can also damage spatial view cells, which are located in the hippocampus. Strokes, meningitis, and encephalitis are only a few of the various illnesses that can cause harm to the spatial view cells. Some clinical symptoms present in patients with damage to the central nervous system include: fever, altered mental status, and neck stiffness. Lesion studies have shown that damage to the hippocampus or to some of its connections, such as the fornix, in monkeys produces deficits in learning about the places of objects and about the places where responses should be made. This sort of damage to the brain often results in impaired object-place memory. Object-place memory tasks require the monkey to not only remember the object seen, but they must also remember where the object was seen in the environment. It has been shown that posterior para-hippocampal lesions in macaques impair even a simple type of object-place learning in which only one pair of unique stimuli are needed for memory.
Relationship to Other Diseases.
Patients with damage to spatial view cells will often show similar symptoms from other diseases such as: Vascular Dementia, Alzheimer's Disease, Amnesia Fugue, Macular degeneration, and optic nerve damage. Another illness that reflects signs of spatial view damage is fornix lesions that impair conditional left-right discrimination learning. Patients with damage to the temporal lobe which also includes the hippocampus can sometimes have Amnesia. Patients with amnesia often have memory impairments in which they have difficulty remembering both what they saw and where they saw the object or event take place. These signs point to the possible damage to spatial view cells found in the hippocampus.
Current Research Involving Spatial View Cells.
Optimal Firing Rate.
Current research shows that the maximum firing rate of spatial view cells is obtained when the test agent is allowed to explore the environment freely. Tests in which the monkey was not allowed to have active locomotion provided very few results of spatial view cells being detected in the hippocampus. Majority of the experiments conducted for spatial view cells involved the use of macaque monkeys as test subjects. These types of cells are identified by monitoring the hippocampus of the monkeys while the brains are stimulated by presenting various images and objects in the monkey's vision. Various researchers use different methodologies in sync with the experiment being conducted in order to identify these spatial view cells. For example, in a delayed spatial response task, the monkey is shown a stimulus on one side of a screen and then the stimulus is taken away. After a short while, the stimulus is again presented to the monkey in the same location and the firing of the cell in the hippocampus that is specifically associated with the location at which the monkey is looking and is independent of the location of the monkey helps identify the spatial view cell. The monkeys in this of experiment are encouraged by rewarding them with fruit juice when they correctly identify the same object in the same location twice in a row and if they get it incorrect, the monkeys receive a saline taste.
Association with Episodic Memories.
The experiments often use object-place memory tasks because they are representative of episodic memories and often employ similar parts of the brain. It is also believed that whenever an episodic memory is stored, part of the context from that event is also stored along with it. As a result, recalling a certain place can link up the emotions at that time. These recollections do not only happen if a place is recalled, but they are prone to occur if the person is in the same mood as they were at the time of the event. Rewards are also remembered along with the place at which it was received. Spatial view cells have been proven to be independent of head direction and place cells. Spatial view cells have been shown to respond even in the dark without any visual cues as long as the test subject was facing in the proper direction. It is believed that in the absence of visual cues, spatial view cells respond from the inputs being received from head direction cells and place cells along with eye position of the primate. The use of the vestibular system and proprioceptive cues also provide a sense of direction the animal is facing in the dark.
Ability to Update with New Information.
Research has led to the finding the spatial view cells are consistently updated with other inputs from the body. For example, when a monkey is oriented in a different position spatially such as being upside down, the spatial view cells still respond when the test subject faces the appropriate direction. This implies that there is stream of new information being received by the spatial view cells constantly. This integration from various inputs develops continuous attractor networks. Continuous attractor neural networks, also known as CANN, are routinely used when studying spatial view cells from an idiothetic stand point. CANNs allow researchers to closely monitor the associated head direction cells and place cells along with the spatial view cells as one close "packet of neural activity".


Transliteracy

Transliteracy is "a fluidity of movement across a range of technologies, media and contexts" (Sukovic, 2016). It is an ability to use diverse techniques to collaborate across different social groups.
Transliteracy combines a range of capabilities required to move across a range of contexts, media, technologies and genres. Conceptually, transliteracy is situated across five capabilities: information capabilities (see information literacy), ICT (information and communication technologies), communication and collaboration, creativity and critical thinking. It is underpinned by literacy and numeracy. (See figure below) The concept of transliteracy is impacting the system of education and libraries.
History.
While the term appears to come from the prefix 'trans-' (across) and the word 'literacy', the scholars who coined it say they developed it from the practice of transliteration, which means to use the letters of one language to write down a different language.
The study of transliteracy was first developed in 2005 by the Transliteracies Research Project, directed by University of California at Santa Barbara Professor Alan Liu. The concept of 'transliteracies' was developed as part of research into online reading. It was shared and refined at the Transliteracies conference, held at UC Santa Barbara in 2005. The conference inspired the at the time De Montfort University Professor, Sue Thomas, to create the Production in Research and Transliteracy (PART) group, which evolved into the Transliteracy Research Group. The current meaning of transliteracy was defined in the group's seminal paper "Transliteracy: crossing divides" as "the ability to read, write, and interact across a range of platforms, tools, and media from signing and orality through handwriting, print, TV, radio, and film, to digital social networks." The concept was enthusiastically adopted by a number of professional groups, notably in the library and information field. "Transliteracy Research Group Archive 2006-2013" curates numerous resources from this period.
For a number of years, there was a gap between significant interest in transliteracy among professional groups and the scarcity of research. A group of academics from the University of Bordeaux considered transliteracy mainly in the school context. Freelance writer and consultant, Sue Thomas, studied transliteracy and creativity, while Suzana Sukovic, executive director of educational research and evidence-based practice at HETI, researched transliteracy in relation to digital storytelling. The first book on the topic, "Transliteracy in complex information environment" by Sukovic, is based on research and experience with practice-based projects.
Transliteracy in Education.
Transliteracy is making an impact on the classroom setting because of how technologically advanced younger generations are today. In 2012, Adam Marcus, a teacher and librarian at NYCDOE, decided to incorporate transliteracy into his school's public library summer reading program. He had a desire to enhance the experience of reading for his students by allowing them to connect to the text differently by using social media. He used a tool called "VoiceThread" in order to have his students "take part in conversations, formulate ideas, and share higher-order thinking through a variety of media channels: video, audio, text, images, and music (Marcus, 2013)." Students were also enabled to communicate with the book's author through blogs and websites, and were given multiple modes of media to comprehend and engage with the text on a deeper level. Some of these examples include an audio-video glossary and web links that aimed to bring the details of the text to life. The results of his experiment were deemed to have a positive effect on the program as students responded well to this interactive experience they were given. Marcus believes that it is important for educators and librarians to enhance storytelling for children by providing them with a modern and transliterate experience that one could not receive back then.
The Agence nationale de la recherche funded a program at a French high school from 2013 to 2015, where the transliteracy skills of students were tested and observed. Students were placed in groups of three or four members and were required to use all sorts of media and tools in order to collect data for their projects. They were not allowed to only use digital sources, and were advised to use a diversity of sources. The focus of this experiment was to observe "the possible diversity of media and tools employed, on the ways of and reasons for switching from one to another, on how these different media and tools are distributed within contexts, according to the academic requirements and tasks individually and collectively performed by the students. (Aillerie, 2017)." The conclusions of the experiment dealt with physical space and organization being an issue for students and teachers to deal with. Spatially, it was challenging for students to navigate through different mediums when their space inside the classroom was limited. It was noticed that students were prone to use something that took up less space, rather than focusing on expanding their diversity of sources. Organizationally, it was challenging for students to organize all of the information they collected since everything was not being search and collected for digitally. In addition, students were not allotted a lot of time to complete their projects which also impacted their final product.
Transliteracy in Libraries.
In 2009, Dr. Susie Andretta, senior lecturer in Information Management at London Metropolitan University, conducted interviews with four different information professionals including an academic librarian, an outreach librarian, a content manager, and a scholar within the library science and information discipline. She was aiming to explore how transliteracy was colliding and combining with the print-world of libraries. Dr. Andretta defines transliteracy as "an umbrella term encompassing different literacies and multiple communication channels that require active participation with and across a range of platforms, and embracing both linear and non-linear messages (3)." The goals of these interviews ranged from the following: to test the information professional's awareness of transliteracy, to have them identify transliteracy and how it is integrated into their work, and to explain the impact transliteracy has had on they library they work at. Andretta found that out of all the information professionals interviewed, it was only the academic librarian who was vaguely familiar with the concept of transliteracy. Bernadette Daly Swanson, an Academic Librarian at UC Davis, expresses in her interview with Dr. Andretta how she would "like to think that the transliterate library is more of an environment where we do different things [...] I would take maybe about a third of the first floor of our library and transform it into a lab [...] where we can start to evolve [..] explore, and experiment in media development, content development, and do it not just with librarians; so open up the space for other people [...] so you don't get people working in isolation." Although the other three candidates that Dr. Andretta interviewed had not heard of the term "transliteracy," they responded well to the concept once it was explained to them and agreed with its impact on the workplace. Dr. Michael Stephens, an assistant professor in the Graduate School of Library and Information Science at Dominican University, explains in his interview how the term transliteracy describes the courses he teaches on libraries and Web 2.0 technologies. Dr. Stephens states that students being educated in Web 2.0 technologies gives them "the opportunity to experience what the channel can be and the potential for that sharing learning, for asking questions, just for out loud thinking- I think it's incredibly valuable. [..] this is where this wonderful concept comes in, it was teaching them transliteracy and the fact that they can move across channels without getting worried about it (Andretta, 5)."
Dr. Andretta concluded from her interviews how although transliteracy may not be a very well-known term yet, it has nonetheless established itself into the intuition of libraries while also transforming the traditional library to a world of enhanced and expanded services. "Inherent in this transition are the challenges of having to adapt to a constantly changing technological landscape, the multiple literacies that this generates, and the need to establish a multifaceted library profession that can speak the multiple-media languages of its diverse users (Andretta, 12)."
Thomas Ipri, a librarian at the University of Nevada, advocates for libraries needing to make a change in their literary functions. He argues that the divide between digital and print makes it harder for libraries to accommodate their patrons and to share information. He focuses on how libraries need to establish their relationship with transliteracy because transliteracy "explores the participatory nature of new means of communicating, which breaks down barrier between academia and the wider community and calls into question standard notions of what constitutes authority by emphasizing the benefits of knowledge sharing via social networks." Ipri argues how established experts are no longer the only ones in charge of producing and spreading information, but it is also the personal experiences and knowledge of people that are valuable in expanding and evolving bases. In what he describes, "the heart of librarianship," it is the duty of librarians to undergo this development by modernizing their movements of communication and information.
Relationship to other terms.
Related terms are "media and information literacy", "information literacy", "digital literacy", "multiliteracies" and "metaliteracy". Transliteracy is a unifying framework rather than a replacement of existing literacies. It considers "movement across" which requires a range of capabilities.


John Bay

John Marshall Bay (November 30, 1928 – November 7, 1982) was an American actor and playwright.
Personal.
Bay was born in Chicago, the location of his family's company, Bays English Muffins.
He was married to the actress Elaine Stritch for nine years until his death.
Career.
Bay appeared in many productions, including the "Doctor Who" story "The Crusade" in 1965, playing the fourth Earl of Leicester. He also originated the role of Samovar in the original London production of "A Day in Hollywood / A Night in the Ukraine". Bay also toured the United States in the early 1980s with his one-man play "An Elephant in My Pajamas," based on the life of Groucho Marx.


Distribution law

Distribution law or the Nernst's distribution law gives a generalisation which governs the distribution of a solute between two non miscible solvents. This law was first given by Nernst who studied the distribution of several solutes between different appropriate pairs of solvents.
C1/C2 = Kd
Where Kd is called the distribution coefficient or the partition coefficient.
Concentration of X in solvent A/concentration of X in solvent B=Kď
If C1 denotes the concentration of solute X in solvent A & C2 denotes the concentration of solute X in solvent B; Nernst's distribution law can be expressed as C1/C2 = Kd. This law is only valid if the solute is in the same molecular form in both the solvents. Sometimes the solute dissociates or associates in the solvent.
In such cases the law is modified as,
D(Distribution factor)=concentration of solute in all forms in solvent 1/concentration of solute in all forms in solvent 2.
See also.
ITIES


Postsynaptic potential

Postsynaptic potentials are changes in the membrane potential of the postsynaptic terminal of a chemical synapse. Postsynaptic potentials are graded potentials, and should not be confused with action potentials although their function is to initiate or inhibit action potentials. They are caused by the presynaptic neuron releasing neurotransmitters from the terminal bouton at the end of an axon into the synaptic cleft. The neurotransmitters bind to receptors on the postsynaptic terminal, which may be a neuron or a muscle cell in the case of a neuromuscular junction. These are collectively referred to as postsynaptic receptors, since they are on the membrane of the postsynaptic cell.
The role of ions.
One way receptors can react to being bound by a neurotransmitter is to open or close an ion channel, allowing ions to enter or leave the cell. It is these ions that alter the membrane potential. Ions are subject to two main forces, diffusion and electrostatic repulsion. Ions will tend towards their equilibrium potential, which is the state where the diffusion force cancels out the force of electrostatic repulsion. When a membrane is at its equilibrium potential, there is no longer a net movement of ions. Two important equations that can determine membrane potential differences based on ion concentrations are the Nernst Equation and the Goldman Equation.
Relation to action potentials.
Neurons have a resting potential of about −70 mV. If the opening of the ion channel results in a net gain of positive charge across the membrane, the membrane is said to be depolarized, as the potential comes closer to zero. This is an excitatory postsynaptic potential (EPSP), as it brings the neuron's potential closer to its firing threshold (about −55 mV).
If, on the other hand, the opening of the ion channel results in a net gain of negative charge, this moves the potential further from zero and is referred to as hyperpolarization. This is an inhibitory postsynaptic potential (IPSP), as it changes the charge across the membrane to be further from the firing threshold.
Neurotransmitters are not inherently excitatory or inhibitory: different receptors for the same neurotransmitter may open different types of ion channels.
EPSPs and IPSPs are transient changes in the membrane potential, and EPSPs resulting from transmitter release at a single synapse are generally far too small to trigger a spike in the postsynaptic neuron. However, a neuron may receive synaptic inputs from hundreds, if not thousands, of other neurons, with varying amounts of simultaneous input, so the combined activity of afferent neurons can cause large fluctuations in membrane potential or subthreshold membrane potential oscillations. If the postsynaptic cell is sufficiently depolarized, an action potential will occur. For example, in low-threshold spikes depolarizations by the T-type calcium channel occur at low, negative, membrane depolarizations resulting in the neuron reaching the threshold. Action potentials are not graded; they are all-or-none responses.
Termination.
Postsynaptic potentials begin to be terminated when the neurotransmitter detaches from its receptor. The receptor is then free to return to its previous structural state. Ion channels that had been opened by the receptor when the neurotransmitter was bound to it will now close. Once the channels are closed, ions return to their equilibrium states, and the membrane is returned to its equilibrium potential.
Algebraic summation.
Postsynaptic potentials are subject to summation, spatially and/or temporally.
Spatial summation: If a cell is receiving input at two synapses that are near each other, their postsynaptic potentials add together. If the cell is receiving two excitatory postsynaptic potentials, they combine so that the membrane potential is depolarized by the sum of the two changes. If there are two inhibitory potentials, they also sum, and the membrane is hyperpolarized by that amount. If the cell is receiving both inhibitory and excitatory postsynaptic potentials, they can cancel out, or one can be stronger than the other, and the membrane potential will change by the difference between them.
Temporal summation: When a cell receives inputs that are close together in time, they are also added together, even if from the same synapse. Thus, if a neuron receives an excitatory postsynaptic potential, and then the presynaptic neuron fires again, creating another EPSP, then the membrane of the postsynaptic cell is depolarized by the total of the EPSPs.


Glimepiride

Glimepiride, is a medication used to treat diabetes mellitus type 2. It is less preferred than metformin. Use is recommended together with diet and exercise. It is taken by mouth. Glimepiride takes up to three hours for maximum effect and lasts for about a day.
Common side effects include headache, nausea, and dizziness. Serious side effects may include low blood sugar. Use during pregnancy and breastfeeding is not recommended. It works mainly by increasing the amount of insulin released from the pancreas. It is classified as a second-generation sulfonylurea.
Glimepiride was patented in 1979 and approved for medical use in 1995. It is available as a generic medication. In 2018, it was the 71st most commonly prescribed medication in the United States, with more than 11million prescriptions.
Medical uses.
Glimepiride is indicated to treat type 2 diabetes mellitus; its mode of action is to increase insulin secretion by the pancreas. However it requires adequate insulin synthesis as prerequisite to treat appropriately. It is not used for type 1 diabetes because in type 1 diabetes the pancreas is not able to produce insulin.
Contraindications.
Its use is contraindicated in patients with hypersensitivity to glimepiride or other sulfonylureas.
Adverse effects.
Side effects from taking glimepiride include gastrointestinal tract (GI) disturbances, occasional allergic reactions, and rarely blood production disorders including thrombocytopenia, leukopenia, and hemolytic anemia. In the initial weeks of treatment, the risk of hypoglycemia may be increased. Alcohol consumption and exposure to sunlight should be restricted because they can worsen side effects.
Interactions.
Nonsteroidal anti-inflammatory drugs (such as salicylates), sulfonamides, chloramphenicol, coumadin and probenecid may potentiate the hypoglycemic action of glimepiride. Thiazides, other diuretics, phothiazides, thyroid products, oral contraceptives, and phenytoin tend to produce hyperglycemia.
Mechanism of action.
Like all sulfonylureas, glimepiride acts as an insulin secretagogue. It lowers blood sugar by stimulating the release of insulin by pancreatic beta cells and by inducing increased activity of intracellular insulin receptors.
Not all secondary sulfonylureas have the same risk of hypoglycemia. Glibenclamide (glyburide) is associated with an incidence of hypoglycemia of up to 20–30%, compared to as low as 2% to 4% with glimepiride. Glibenclamide also interferes with the normal homeostatic suppression of insulin secretion in reaction to hypoglycemia, whereas glimepiride does not. Also, glibenclamide diminishes glucagon secretion in reaction to hypoglycemia, whereas glimepiride does not.
Pharmacokinetics.
Gastrointestinal absorption is complete, with no interference from meals. Significant absorption can occur within one hour, and distribution is throughout the body, 99.5% bound to plasma protein. Metabolism is by oxidative biotransformation, it is hepatic and complete. First, the medication is metabolized to M1 metabolite by CYP2C9. M1 possesses about of pharmacological activity of glimepiride, yet it is unknown if this results in clinically meaningful effect on blood glucose. M1 is further metabolized to M2 metabolite by cytosolic enzymes. M2 is pharmacologically inactive. Excretion in the urine is about 65%, and the remainder is excreted in the feces.


Oblique dendrite

An oblique dendrite is a dendrite that branches from an apical dendrite that emerges from the apex of a pyramidal cell. Oblique dendrites typically branch one to two times before terminating. Dendrites are extensions of the cell body of a neuron.
Growth and Development.
The growth and development of oblique dendrites in rats has been linked to the type of environment, or condition, they are placed in. This is also known as environmental enrichment. The three types of conditions used in studies are an enriched conditioned, standard condition, and impoverished condition. The enriched condition contains mazes, an exercise wheel, other rats, and toys. The standard condition generally has a wheel for voluntary exercise and other rats. The impoverished condition only contains fellow rats.
Animals placed in an enriched environment had heavier, thicker cortexes and an increase in the number of dendritic branches (including oblique dendrites) in the hippocampus than the standard or impoverished condition. This phenomenon is known as neuroplasticity. Furthermore, the enriched condition may show in increase in monoamine neurotransmitter release such as serotonin and noradrenaline which have been linked to synaptic plasticity and learning. This is important because an increase in oblique dendrites and dendritic branching allows for increased neurotransmitter uptake. Environmental enrichment is crucial in early brain development due to increase formation of synapses, or synaptogenesis. This results in an increase in oblique dendrites and dendritic branching.
Effects on Oblique Dendrites from Alzheimer’s Disease.
The beta amyloid peptide, which may lead to the formation of amyloid plaques, has been linked to Alzheimer's Disease. The peptide has been shown to block A-type voltage-gated potassium channel in pyramidal cell dendrites; the thin branches of the oblique dendrites are especially susceptible to disruption from the beta amyloid blockage of the A-type potassium channels which may lead to decline in cognitive function in the early stages of Alzheimer's Disease.
References.
Dailey ME and Smith SJ, "The Dynamics of Dendritic Structure in Developing Hippocampal Slices". J Neurosci 16(9), 1996 pp. 2983-2994.
Watson, Neil V., and S. Marc. Breedlove, "The Mind's Machine: Foundations of Brain and Behavior". Sunderland, MA: Sinauer Associates, 2012. N. pag. Print.
van Praag, Henriette, Gerd Kempermann, and Fred H. Gage. "Neural consequences of environmental enrichment." Nature Reviews Neuroscience 1.3 (2000): 191-198.
Morse, Thomas M., Nicholas T. Carnevale, Pradeep G. Mutalik, Michele Migliore, and Gordon M. Shepherd. "Abnormal excitability of oblique dendrites implicated in early Alzheimer's: a computational study." National Center for Biotechnology Information. U.S. National Library of Medicine, 31 May 2010.


SCN4B

Sodium channel β-subunit 4, also known as SCN4B or Naβ4, is an auxiliary sodium channel subunit that can alter the kinetics of sodium channels. The protein is encoded by the "SCN4B" gene. Mutations in the "SCN4B" are associated with long QT syndrome.
SCN4B might additionally function as a cell adhesion molecule.