Subliminal stimuli

Subliminal stimuli () (the prefix sub- literally means "below, or less than"), contrary to supraliminal stimuli or "above threshold", are any sensory stimuli below an individual's threshold for conscious perception. A 2012 review of functional magnetic resonance imaging (fMRI) studies showed that subliminal stimuli activate specific regions of the brain despite participants' unawareness. Visual stimuli may be quickly flashed before an individual can process them, or flashed and then masked to interrupt processing. Audio stimuli may be played below audible volumes or masked by other stimuli.
Effectiveness.
Applications of subliminal stimuli are often based on the persuasiveness of a message. Research on action priming has shown that subliminal stimuli can only trigger actions a receiver of the message plans to perform anyway. However, consensus of subliminal messaging remains unsubstantiated by other research. Most actions can be triggered subliminally only if the person is already prepared to perform a specific action.
The context that the stimulus is presented in affects their effectiveness. For example, if the target is thirsty then a subliminal stimuli for a drink is likely to influence the target to purchase that drink if it is readily available. The stimuli can also influence the target to choose the primed option over other habitually chosen options. If the subliminal stimuli is for a product that is not quickly accessible or if there is no need for it within a specific context then the stimuli will have little to no effect. Subliminal priming can direct people's actions even when they believe they are making free choices. When primed to push a button with their off-hand, people will use that hand even if they are given a free choice between using their off-hand and their dominant hand. However, a meta analysis of many strong articles displaying effectiveness of subliminal messaging revealed its effects on actual consumer purchasing choices between two alternatives are not statistically significant; subliminal messaging is only effective in very specific contexts.
Method.
In subliminal stimuli research, the threshold is the level at which the participant is not aware of the stimulus being presented. Researchers determine a threshold for the stimulus that is used as the subliminal stimulus. That stimulus is then presented during the study at some point and measures are taken to determine the effects of the stimulus. The way in which studies operationally define thresholds depends on the methods of the particular article. The methodology of the research also varies by the type of subliminal stimulus (auditory or visual) and the dependent variables they measure.
Objective threshold.
The objective threshold is found using a forced choice procedure, in which participants must choose which stimulus they saw from options given to them. For example, participants are flashed a stimulus (like the word "orange") and then given a few choices and asked which one they saw. Participants must choose an answer in this design. The objective threshold is obtained when participants are at the chance level of performance in this task. The length of presentation that causes chance performance on the forced choice task is used later in the study for the subliminal stimuli.
Subjective threshold.
The subjective threshold is determined when the participant reports that their performance on the forced choice procedure approximates chance. The subjective threshold is 30 to 50 ms slower than the objective threshold, demonstrating that participants' ability to detect the stimuli is earlier than their perceived accuracy ratings would indicate; that is, stimuli presented at a subjective threshold have a longer presentation time than those presented at an objective threshold. When using the objective threshold, priming stimuli neither facilitated nor inhibited the recognition of a color. However, the longer the duration of the priming stimulus, the greater effect it had on subsequent responding. These findings indicate that the results of some studies may be due to their definition of below threshold.
Direct and indirect measures.
Perception without awareness can be demonstrated through the comparison of direct and indirect measures of perception. Direct measures use responses to task definitions in accordance to the explicit instructions given to the subjects, while indirect measures use responses that are not a part of the task definition given to subjects. Both direct and indirect measures are displayed under comparable conditions except for the direct or indirect instruction. For example, in a typical Stroop test, subjects are asked to name the color of a patch of ink. A direct measure is accuracy—true to the instructions given to the participants. The popular indirect measure used in the same task is response time—subjects are not told that they are being measured for response times.
Similarly, a direct effect is the effect of a task stimulus on the instructed response to it, and is usually measured as accuracy. An indirect effect is an uninstructed effect of the task stimulus on behavior, sometimes measured by including an irrelevant or distracting component in the task stimulus and measuring its effect on accuracy. These effects are then compared on their relative sensitivity: an indirect effect that is greater than a direct effect indicates that unconscious cognition exists.
Visual stimuli.
In order to study the effects of subliminal stimuli, researchers often prime participants with specific visual stimuli, and determine if those stimuli elicit different responses.<ref name="doi10.1002/hbm.20208"></ref> Subliminal stimuli have mostly been studied in the context of emotion; in particular, researchers have focused a lot of attention to the face perception and how subliminal presentation to different facial expression affects emotion.<ref name="doi10.1016/0022-10319090068-W"></ref> Visual subliminal stimuli have also been used to study emotion eliciting stimuli and simple geometric stimuli. A significant amount of research has been produced throughout the years to demonstrate the effects of subliminal visual stimuli.
Images.
Attitudes can develop without being aware of their antecedents. Individuals viewed slides of people performing familiar daily activities after being exposed to either an emotionally positive scene, such as a romantic couple or kittens, or an emotionally negative scene, such as a werewolf or a dead body between each slide and the next. After exposure from something which the individuals consciously perceived as a flash of light, the participants exhibited more positive personality traits to those people whose slides were associated with an emotionally positive scene and vice versa. Despite the statistical difference, the subliminal messages had less of an impact on judgment than the slide's inherent level of physical attractiveness.
Individuals show right amygdala activity in response to subliminal fear, and a greater left amygdala response to supraliminal fear. In a 2005 study, participants were exposed to a subliminal image flashed for 16.7 milliseconds that could signal a potential threat and again with a supraliminal image flashed for half a second. Furthermore, supraliminal fear showed more sustained cortical activity, suggesting that subliminal fear may not entail conscious surveillance while supraliminal fear entails higher-order processing.
Emotion eliciting stimuli.
A subliminal sexual stimulus has a different effect on men compared to women. In a study by Omri Gilliath "et al.", men and women were subliminally exposed to either a sexual or a neutral picture, and their sexual arousal was recorded. Researchers examined the accessibility of sex-related thoughts after following the same procedure with either a pictorial judgment task or lexical decision task. The results revealed that the subliminal sexual stimuli did not have an effect on men, but for women, lower levels of sexual arousal were reported. However, in conditions related to accessibility of sex-related thoughts, the subliminal sexual stimuli led to higher accessibility for both men and women.
Subliminal stimuli can elicit significant emotional changes, but these changes are not valuable for a therapeutic effect. Spider-fearful and non-fearful undergraduates experienced either a positive, negative, or neutral subliminal priming stimulus followed immediately by a picture of a spider or a snake. Using visual analogue scales, the participants rated the affective quality of the picture. No evidence was found to support that the unpleasantness of the pictures can be modulated by subliminal priming. Non-fearful participants rated the spiders as being more frightening after being primed with a negative stimulus, but the event was not found in fearful participants.
Simple geometric stimuli.
Laboratory research on unconscious perception often employs simple stimuli (e.g., geometric shapes or colors) in which visibility is controlled by visual masking. Masked stimuli are then used to prime the processing of subsequently presented target stimuli. For instance, in the response priming paradigm, participants have to respond to a target stimulus (e.g. by identifying whether it is a diamond or a square) which is immediately preceded by a masked priming stimulus (also a diamond or a square). The prime has large effects on responses to the target: it speeds responses when it is consistent with the target, and slows responses when it is inconsistent. Response priming effects can be dissociated from visual awareness of the prime, such as when prime identification performance is at chance, or when priming effects increase despite decreases in prime visibility.
The presentation of geometric figures as subliminal stimuli can result in below threshold discriminations. The geometric figures were presented on slides of a tachistoscope followed by a supraliminal shock for a given slide every time it appeared. The shock was administered after a five-second interval. Electrical skin changes of the participants that occurred before the reinforcement (shock) or non-reinforcement were recorded. The findings indicate that the proportion of electrical skin changes that occurred following subliminal visual stimuli was significantly greater than expected, while the proportion of electrical skin changes that occurred in response to the stimuli which were not reinforced was significantly less. As a whole, participants were able to make below threshold discriminations.
Word and non-word stimuli.
Another form of visual stimuli are words and non-words. In a set of experiments, words and non-words were used as subliminal primes. Priming stimuli that work best as subliminal stimuli are words that have been classified several times before they are used to prime. Word primes can also be made from parts of practiced words to create new words. In this case, the actual word used to prime can have the opposite meaning of the words it came from (its "parents"), but it will still prime for the meaning of the parent words. Non-words created from previously practiced stimuli have a similar effect, even when they are unpronounceable (e.g. made of all consonants). These primes generally only increase response times for later stimuli for a very short period of time (milliseconds).
Masking visual stimuli.
Visual stimuli are often masked by forward and backward masks so that they can be displayed for longer periods of time without the subject being able to recognize the priming stimuli. A forward mask is briefly displayed before the priming stimulus and a backward mask usually follows it to prevent the subject from recognizing the stimulus.
Auditory stimuli.
Auditory masking.
One method for creating subliminal auditory stimuli is masking, which involves hiding the target auditory stimulus in some way. Auditory subliminal stimuli are shown to have some effect on the participant, but not a large one. For example, one study used other speechlike sounds to cover up the target words, and it found evidence of priming in the absence of awareness of the stimuli. The effects of these subliminal stimuli were only seen in one of the outcome measures of priming, while the effects of conscious stimuli were seen in multiple outcome measures. However, the empirical evidence for the assumption of an impact of auditory subliminal stimuli on human behavior remains weak; in an experimental study on the influence of subliminal target words (embedded into a music track) on choice behavior for a drink, authors found no evidence for a manipulative effect.
Self-help audio recordings.
A study investigated the effects on self-concept of rational emotive behavior therapy and auditory subliminal stimulation (separately and in combination) on 141 undergraduate students with self-concept problems. They were randomly assigned to one of four groups receiving either rational-emotive therapy, subliminal stimulation, both, or a placebo treatment. Rational-emotive therapy significantly improved scores on all dependent measures (cognition, self-concept, self-esteem, anxiety) except behavior. Results for the subliminal stimulation group were similar to those of the placebo treatment except for a significant self-concept improvement and a decline in self-concept related irrational cognitions. The combined treatment yielded results similar to those of rational-emotive therapy, with tentative indications of continued improvement in irrational cognitions and self-concept from posttest to follow-up.
Consumption and television.
Some studies looked at the efficacy of subliminal messaging in television. Subliminal messages produce only one-tenth of the effects of detected messages and the findings related to the effects of subliminal messaging were relatively ambiguous. Participants’ ratings of positive responses to commercials were not affected by subliminal messages in the commercials.
Johan Karremans suggests that subliminal messages have an effect when the messages are goal-relevant. In a study, researchers made half of the 105 volunteers feel thirsty by giving them food with lots of salt before performing the experiment. At the end, as predicted, they found that the subliminal message had succeeded among the thirsty. 80% of them chose "Lipton Ice" versus the 20% of the control group that were not exposed to the message. However, those who were not thirsty did not choose the drink in question, despite the subliminal message. The experiment showed that in certain circumstances subliminal advertising worked.
Karremans did a study assessing whether subliminal priming of a brand name of a drink would affect a person's choice of drink, and if this effect was caused by the individual's feelings of being thirsty. In another study, participant's ratings of thirst were higher after viewing an episode of "The Simpsons" that contained single frames of the word "thirsty" or of a picture of a Coca-Cola can. Some studies showed greater effects of subliminal messaging with as high as 80% of participants showing a preference for a particular rum when subliminally primed by the name placed in an ad backward. Martin Gardner, however, criticizes claims, such as those by Wilson Bryan Key, by pointing out that "recent studies" serving as the basis for his claims were not identified by place or experimenter. He also suggests that claims about subliminal images are due to the "tendency of chaotic shapes to form patterns vaguely resembling familiar things". In 2009, the American Psychological Association defended that subliminal stimuli are subordinated to previously structured associative stimuli and that their only role is to reinforce a certain behavior or a certain previous attitude, without there being conclusive evidence that the stimulus that provokes these behaviors is properly subliminal.
There is still speculation about this effect; in their journal, the American Psychological Association showed that subliminal stimuli are subordinated to previously structured associative stimuli and that their only role is to reinforce a certain behaviour or a certain previous attitude, without there being conclusive evidence that the stimulus that provokes these behaviors is properly subliminal.
Many authors have continued to argue for the effectiveness of subliminal cues in changing consumption behavior, citing environmental cues as a main culprit of behavior change. Authors who support this line of reasoning cite findings such as Ronald Millman's research that showed slow-paced music in a supermarket was associated with more sales and customers moving at a slower pace. Findings such as these support the notion that external cues can affect behavior, although the stimulus may not fit into a strict definition of subliminal stimuli because although the music may not be attended to or consciously affecting the customers, they are certainly able to perceive it.
Subliminal messaging is prohibited in advertising in the United Kingdom.
Studies on advertising with subliminal stimuli in still images.
Among the researchers in favor of subliminal stimuli is Wilson Bryan Key. One of Key's most cited studies is a whisky ad in which he found several hidden figures in ice cubes. However, for other researchers Key is someone with a sexual fixation.
Luís Bassat suggests an interesting observation by indicating that the current objective of advertising is "to get the consumer to take into account the brand when making the decision", a trend opposed to the objective of subliminal advertising. In turn, Fernando Ocaña showed that the essential thing in the field of media planning is to obtain the greatest possible memory, which implies a conscious perception and not an unconscious one as it should be the case.


Cave of septum pellucidum

The cave of septum pellucidum (CSP), cavum septi pellucidi, or cavity of septum pellucidum, is a slit-like space in the septum pellucidum that is present in fetuses but usually fuses during infancy. The septum pellucidum is a laminated thin translucent vertical membrane in the midline of the brain separating the anterior horns of the right and left ventricles. It lies posterior to the corpus callosum. Persistence of the cave of septum pellucidum after infancy has been loosely associated with neural maldevelopment and several mental disorders that correlate with decreased brain tissue.
The cave of septum pellucidum is bounded anteriorly by the genu of the corpus callosum, superiorly by the body of the corpus callosum, posteriorly by the anterior limb and pillars of the fornix, inferiorly by the anterior commissure and the rostrum of the corpus callosum, and laterally by the leaflets of the septum pellucidum.
In prenatal development of the fetus, the laminae of the septum pellucidum separate to form a small cavity – the cave of septum pellucidum. This is an important normal structure to identify in the sonographic assessment of the fetal brain. In post-natal life, the laminae of the septum pellucidum usually fuse, which obliterates the cavum. The cavity contains cerebrospinal fluid (CSF) that filters from the ventricles through the septal laminae.
There are individual differences in the degree of CSP; whereas some have complete closure of the cavum, others present with a small degree (4–6 mm wide, in the coronal plane) of incomplete closure. The most common type of CSP is noncommunicating; that is, it does not connect to the brain's ventricular system. Because of this lack of communication, the previous use of the term "fifth ventricle" is no longer used, and the fifth ventricle is the name often used for the terminal ventricle.
CSP is present in 100% of fetuses, but over 85% of them fuse by 3–6 months after birth.
Cause.
The cause of CSP is basically unknown, although it is thought that prenatal alcohol exposure plays a significant role.
Marker for fetal neural maldevelopment.
CSP is a marker for fetal neural maldevelopment. The septum pellucidum is a thin, triangular, vertical membrane separating the anterior horns of the left and right lateral ventricles of the brain. It runs as a sheet from the corpus callosum down to the fornix. During fetal development at approximately the twelfth week of gestation, a space forms between two laminae, which is the CSP. At approximately the twentieth week of gestation, the laminae start to close. This closure ends shortly after birth (3–6 months postnatally). Fusion of the CSP is attributed to rapid development of the alvei of the hippocampus, amygdala, septal nuclei, fornix, corpus callosum and other midline structures. Lack of such limbic development interrupts this posterior-to-anterior fusion, resulting in preservation of the CSP into adulthood.
Association with mental disorders.
CSP has been loosely associated with schizophrenia, post-traumatic stress disorder, traumatic brain injury, as well as with antisocial personality disorder. CSP is one of the distinguishing features of individuals displaying symptoms of dementia pugilistica (chronic traumatic encephalopathy).


Synaptogenesis

Synaptogenesis is the formation of synapses between neurons in the nervous system. Although it occurs throughout a healthy person's lifespan, an explosion of synapse formation occurs during early brain development, known as exuberant synaptogenesis. Synaptogenesis is particularly important during an individual's critical period, during which there is a certain degree of synaptic pruning due to competition for neural growth factors by neurons and synapses. Processes that are not used, or inhibited during their critical period will fail to develop normally later on in life.
Formation of the neuromuscular junction.
Function.
The neuromuscular junction (NMJ) is the most well-characterized synapse in that it provides a simple and accessible structure that allows for easy manipulation and observation. The synapse itself is composed of three cells: the motor neuron, the myofiber, and the Schwann cell. In a normally functioning synapse, a signal will cause the motor neuron to depolarize, by releasing the neurotransmitter acetylcholine (ACh). Acetylcholine travels across the synaptic cleft where it reaches acetylcholine receptors (AChR) on the plasma membrane of the myofiber, the sarcolemma. As the AChRs open ion channels, the membrane depolarizes, causing muscle contraction. The entire synapse is covered in
a myelin sheath provided by the Schwann cell to insulate and encapsulate the junction.
Another important part of the neuromuscular system and central nervous system are the astrocytes. While originally they were thought to have only functioned as support for the neurons, they play an important role in functional plasticity of synapses.
Origin and movement of cells.
During development, each of the three germ layer cell types arises from different regions of the growing embryo. The individual myoblasts originate in the mesoderm and fuse to form a multi-nucleated myotube. During or shortly after myotube formation, motoneurons from the neural tube form preliminary contacts with the myotube. The Schwann cells arise from the neural crest and are led by the axons to their destination. Upon reaching it, they form a loose, unmyelinated covering over the innervating axons. The movement of the axons (and subsequently the Schwann cells) is guided by the growth cone, a filamentous projection of the axon that actively searches for neurotrophins released by the myotube.
The specific patterning of synapse development at the neuromuscular junction shows that the majority of muscles are innervated at their midpoints. Although it may seem that the axons specifically target the midpoint of the myotube, several factors reveal that this is not a valid claim. It appears that after the initial axonal contact, the newly formed myotube proceeds to grow symmetrically from that point of innervation. Coupled with the fact that AChR density is the result of axonal contact instead of the cause, the structural patterns of muscle fibers can be attributed to both myotatic growth as well as axonal innervation.
The preliminary contact formed between the motoneuron and the myotube generates synaptic transmission almost immediately, but the signal produced is very weak. There is evidence that Schwann cells may facilitate these preliminary signals by increasing the amount of spontaneous neurotransmitter release through small molecule signals. After about a week, a fully functional synapse is formed following several types of differentiation in both the post-synaptic muscle cell and the pre-synaptic motoneuron. This pioneer axon is of crucial importance because the new axons that follow have a high propensity for forming contacts with well-established synapses.
Post-synaptic differentiation.
The most noticeable difference in the myotube following contact with the motoneuron is the increased concentration of AChR in the plasma membrane of the myotube in the synapse. This increased amount of AChR allows for more effective transmission of synaptic signals, which in turn leads to a more-developed synapse. The density of AChR is > 10,000/μm2 and approximately 10/μm2 around the edge. This high concentration of AChR in the synapse is achieved through clustering of AChR, up-regulation of the AChR gene transcription in the post-synaptic nuclei, and down-regulation of the AChR gene in the non-synaptic nuclei. The signals that initiate post-synaptic differentiation may be neurotransmitters released directly from the axon to the myotube, or they may arise from changes activated in the extracellular matrix of the synaptic cleft.
Clustering.
AChR experiences multimerization within the post-synaptic membrane largely due to the signaling molecule Agrin. The axon of the motoneuron releases agrin, a proteoglycan that initiates a cascade that eventually leads to AChR association. Agrin binds to a muscle-specific kinase (MuSK) receptor in the post-synaptic membrane, and this in turn leads to downstream activation of the cytoplasmic protein Rapsyn. Rapsyn contains domains that allow for AChR association and multimerization, and it is directly responsible for AChR clustering in the post-synaptic membrane: rapsyn-deficient mutant mice fail to form AChR clusters.
Synapse-specific transcription.
The increased concentration of AChR is not simply due to a rearrangement of pre-existing synaptic components. The axon also provides signals that regulate gene expression within the myonuclei directly beneath the synapse. This signaling provides for localized up-regulation of transcription of AChR genes and consequent increase in local AChR concentration. The two signaling molecules released by the axon are calcitonin gene-related peptide (CGRP) and neuregulin, which trigger a series of kinases that eventually lead to transcriptional activation of the AChR genes.
Extrasynaptic repression.
Repression of the AChR gene in the non-synaptic nuclei is an activity-dependent process involving the electrical signal generated by the newly formed synapse. Reduced concentration of AChR in the extrasynaptic membrane in addition to increased concentration in the post-synaptic membrane helps ensure the fidelity of signals sent by the axon by localizing AChR to the synapse. Because the synapse begins receiving inputs almost immediately after the motoneuron comes into contact with the myotube, the axon quickly generates an action potential and releases ACh. The depolarization caused by AChR induces muscle contraction and simultaneously initiates repression of AChR gene transcription across the entire muscle membrane. Note that this affects gene transcription at a distance: the receptors that are embedded within the post-synaptic membrane are not susceptible to repression.
Pre-synaptic differentiation.
Although the mechanisms regulating pre-synaptic differentiation are unknown, the changes exhibited at the developing axon terminal are well characterized. The pre-synaptic axon shows an increase in synaptic volume and area, an increase of synaptic vesicles, clustering of vesicles at the active zone, and polarization of the pre-synaptic membrane. These changes are thought to be mediated by neurotrophin and cell adhesion molecule release from muscle cells, thereby emphasizing the importance of communication between the motoneuron and the myotube during synaptogenesis. Like post-synaptic differentiation, pre-synaptic differentiation is thought to be due to a combination of changes in gene expression and a redistribution of pre-existing synaptic components. Evidence for this can be seen in the up-regulation of genes expressing vesicle proteins shortly after synapse formation as well as their localization at the synaptic terminal.
Synaptic maturation.
Immature synapses are multiply innervated at birth, due to the high propensity for new axons to innervate at a pre-existing synapse. As the synapse matures, the synapses segregate and eventually all axonal inputs except for one retract in a process called synapse elimination. Furthermore, the post-synaptic end plate grows deeper and creates folds through invagination to increase the surface area available for neurotransmitter reception. At birth, Schwann cells form loose, unmyelinated covers over groups of synapses, but as the synapse matures, Schwann cells become dedicated to a single synapse and form a myelinated cap over the entire neuromuscular junction.
Synapse elimination.
The process of synaptic pruning known as synapse elimination is a presumably activity-dependent process that involves competition between axons. Hypothetically, a synapse strong enough to produce an action potential will trigger the myonuclei directly across from the axon to release synaptotrophins that will strengthen and maintain well-established synapses. This synaptic strengthening is not conferred upon the weaker synapses, thereby starving them out. It has also been suggested that in addition to the synaptotrophins released to the synapse exhibiting strong activity, the depolarization of the post-synaptic membrane causes release of synaptotoxins that ward off weaker axons.
Synapse formation specificity.
A remarkable aspect of synaptogenesis is the fact that motoneurons are able to distinguish between fast and slow-twitch muscle fibers; fast-twitch muscle fibers are innervated by "fast" motoneurons, and slow-twitch muscle fibers are innervated by "slow" motoneurons. There are two hypothesized paths by which the axons of motoneurons achieve this specificity, one in which the axons actively recognize the muscles that they innervate and make selective decisions based on inputs, and another that calls for more indeterminate innervation of muscle fibers. In the selective paths, the axons recognize the fiber type, either by factors or signals released specifically by the fast or slow-twitch muscle fibers. In addition, selectivity can be traced to the lateral position that the axons are predeterminately arranged in order to link them to the muscle fiber that they will eventually innervate. The hypothesized non-selective pathways indicate that the axons are guided to their destinations by the matrix through which they travel. Essentially, a path is laid out for the axon and the axon itself is not involved in the decision-making process. Finally, the axons may non-specifically innervate muscle fibers and cause the muscles to acquire the characteristics of the axon that innervates them. In this path, a "fast" motoneuron can convert any muscle fiber into a fast-twitch muscle fiber. There is evidence for both selective and non-selective paths in synapse formation specificity, leading to the conclusion that the process is a combination of several factors.
Central nervous system synapse formation.
Although the study of synaptogenesis within the central nervous system (CNS) is much more recent than that of the NMJ, there is promise of relating the information learned at the NMJ to synapses within the CNS. Many similar structures and basic functions exist between the two types of neuronal connections. At the most basic level, the CNS synapse and the NMJ both have a nerve terminal that is separated from the postsynaptic membrane by a cleft containing specialized extracellular material. Both structures exhibit localized vesicles at the active sites, clustered receptors at the post-synaptic membrane, and glial cells that encapsulate the entire synaptic cleft. In terms of synaptogenesis, both synapses exhibit differentiation of the pre- and post-synaptic membranes following initial contact between the two cells. This includes the clustering of receptors, localized up-regulation of protein synthesis at the active sites, and neuronal pruning through synapse elimination.
Despite these similarities in structure, there is a fundamental difference between the two connections. The CNS synapse is strictly neuronal and does not involve muscle fibers: for this reason the CNS uses different neurotransmitter molecules and receptors. More importantly, neurons within the CNS often receive multiple inputs that must be processed and integrated for successful transfer of information. Muscle fibers are innervated by a single input and operate in an all or none fashion. Coupled with the plasticity that is characteristic of the CNS neuronal connections, it is easy to see how increasingly complex CNS circuits can become.
Factors regulating synaptogenesis in the CNS.
Signaling.
The main method of synaptic signaling in the NMJ is through use of the neurotransmitter acetylcholine and its receptor. The CNS homolog is glutamate and its receptors, and one of special significance is the N-methyl-D-aspartate (NMDA) receptor. It has been shown that activation of NMDA receptors initiates synaptogenesis through activation of downstream products. The heightened level of NMDA receptor activity during development allows for increased influx of calcium, which acts as a secondary signal. Eventually, immediate early genes (IEG) are activated by transcription factors and the proteins required for neuronal differentiation are translated. The NMDA receptor function is associated with the estrogen receptor in hippocampal neurons. Experiments conducted with estradiol show that exposure to the estrogen significantly increases synaptic density and protein concentration.
Synaptic signaling during synaptogenesis is not only activity-dependent, but is also dependent on the environment in which the neurons are located. For instance, brain-derived neurotrophic factor (BDNF) is produced by the brain and regulates several functions within the developing synapse, including enhancement of transmitter release, increased concentration of vesicles, and cholesterol biosynthesis. Cholesterol is essential to synaptogenesis because the lipid rafts that it forms provide a scaffold upon which numerous signaling interactions can occur. BDNF-null mutants show significant defects in neuronal growth and synapse formation. Aside from neurotrophins, cell-adhesion molecules are also essential to synaptogenesis. Often the binding of pre-synaptic cell-adhesion molecules with their post-synaptic partners triggers specializations that facilitate synaptogenesis. Indeed, a defect in genes encoding neuroligin, a cell-adhesion molecule found in the post-synaptic membrane, has been linked to cases of autism and mental retardation. Finally, many of these signaling processes can be regulated by matrix metalloproteinases (MMPs) as the targets of many MMPs are these specific cell-adhesion molecules.
Morphology.
The special structure found in the CNS that allows for multiple inputs is the dendritic spine, the highly dynamic site of excitatory synapses. This morphological dynamism is due to the specific regulation of the actin cytoskeleton, which in turn allows for regulation of synapse formation. Dendritic spines exhibit three main morphologies: filopodia, thin spines, and mushroom spines. The filopodia play a role in synaptogenesis through initiation of contact with axons of other neurons. Filopodia of new neurons tend to associate with multiply synapsed axons, while the filopodia of mature neurons tend to sites devoid of other partners. The dynamism of spines allows for the conversion of filopodia into the mushroom spines that are the primary sites of glutamate receptors and synaptic transmission.
Environmental enrichment.
Rats raised with environmental enrichment have 25% more synapses than controls. This effect occurs whether a more stimulating environment is experienced immediately following birth, after weaning, or during maturity. Stimulation effects not only synaptogenesis upon pyramidal neurons but also stellate ones.
Contributions of the Wnt protein family.
The (Wnt) family, includes several embryonic morphogens that contribute to early pattern formation in the developing embryo. Recently data have emerged showing that the Wnt protein family has roles in the later development of synapse formation and plasticity. Wnt contribution to synaptogenesis has been verified in both the central nervous system and the neuromuscular junction.
Central nervous system.
Wnt family members contribute to synapse formation in the cerebellum by inducing presynaptic and postsynaptic terminal formation. This brain region contains three main neuronal cell types- Purkinje cells, granule cells and mossy fiber cells. Wnt-3 expression contributes to Purkinje cell neurite outgrowth and synapse formation. Granule cells express Wnt-7a to promote axon spreading and branching in their synaptic partner, mossy fiber cells. Retrograde secretion of Wnt-7a to mossy fiber cells causes growth cone enlargement by spreading microtubules. Furthermore, Wnt-7a retrograde signaling recruits synaptic vesicles and presynaptic proteins to the synaptic active zone. Wnt-5a performs a similar function on postsynaptic granule cells; this Wnt stimulates receptor assembly and clustering of the scaffolding protein PSD-95.
In the hippocampus Wnts in conjunction with cell electrical activity promote synapse formation. Wnt7b is expressed in maturing dendrites, and the expression of the Wnt receptor Frizzled (Fz), increases highly with synapse formation in the hippocampus. NMDA glutamate receptor activation increases Wnt2 expression. Long term potentiation (LTP) due to NMDA activation and subsequent Wnt expression leads to Fz-5 localization at the postsynaptic active zone. Furthermore, Wnt7a and Wnt2 signaling after NMDA receptor mediated LTP leads to increased dendritic arborization and regulates activity induced synaptic plasticity. Blocking Wnt expression in the hippocampus mitigates these activity dependent effects by reducing dendritic arborization and subsequently, synaptic complexity.
Neuromuscular junction.
Similar mechanisms of action by Wnts in the central nervous system are observed in the neuromuscular junction (NMJ) as well. In the Drosophila NMJ mutations in the Wnt5 receptor Derailed (drl) reduce the number of and density of synaptic active zones. The major neurotransmitter in this system is glutamate. Wnt is needed to localize glutamatergic receptors on postsynaptic muscle cells. As a result, Wnt mutations diminish evoked currents on the postsynaptic muscle.
In the vertebrate NMJ, motor neuron expression of Wnt-11r contributes to acetylcholine receptor (AChR) clustering in the postsynaptic density of muscle cells. Wnt-3 is expressed by muscle fibers and is secreted retrogradely onto motor neurons. In motor neurons, Wnt-3 works with Agrin to promote growth cone enlargement, axon branching and synaptic vesicle clustering.


Rimose

Rimose is an adjective used to describe a surface that is cracked or fissured. The term is often used in describing crustose lichens. A rimose surface of a lichen is sometimes contrasted to the surface being areolate. Areolate is an extreme form of being rimose, where the cracks or fissures are so deep that they create island-like pieces called areoles, which look the "islands" of mud on the surface of a dry lake bed. Rimose and areolate are contrasted with being verrucose, or "warty". Verrucose surfaces have warty bumps which are distinct, but not separated by cracks.


Conus medullaris

The conus medullaris (Latin for "medullary cone") or conus terminalis is the tapered, lower end of the spinal cord. It occurs near lumbar vertebral levels 1 (L1) and 2 (L2), occasionally lower. The upper end of the conus medullaris is usually not well defined, however, its corresponding spinal cord segments are usually S1-S5.
After the spinal cord tapers out, the spinal nerves continue to branch out diagonally, forming the cauda equina.
The pia mater that surrounds the spinal cord, however, projects directly downward, forming a slender filament called the filum terminale, which connects the conus medullaris to the back of the coccyx. The filum terminale provides a connection between the conus medullaris and the coccyx which stabilizes the entire spinal cord.
Blood supply.
The blood supply consists of three spinal arterial vessels— the anterior median longitudinal arterial trunk and the right and left posterior spinal arteries. Other less prominent sources of blood supply include radicular arterial branches from the aorta, lateral sacral arteries, and the fifth lumbar, iliolumbar, and middle sacral arteries. The latter contribute more to the vascular supply of the cauda equina.
Pathology.
Conus medullaris syndrome is a collection of signs and symptoms associated with injury to the conus medullaris. It typically causes back pain and bowel and bladder dysfunction, spastic or flaccid weakness depending on the level of the lesion, and bilateral sensory loss. Comparatively, cauda equina syndrome may cause radicular pain, bowel/bladder dysfunction, patchy sensory loss or saddle anesthesia and lower extremity weakness at the level of the lumbar and sacral roots.
Pediatric patients may have a syrinx associated with their Chiari malformation and the conus medullaris will be located at or below the L2-L3 lumbar vertebrae disk space.


Glenn Brenner

Glenn Brenner (January 2, 1948 – January 14, 1992) was a broadcast journalist and sports commentator in Washington, D.C., in the United States from 1977 to 1991. He was best known as the sports anchor for WUSA-TV from 1977 until 1991. At the time of his death in 1992 from a brain tumor, he was not only the most highly paid broadcast journalist in Washington but also the most popular broadcaster in the D.C. metropolitan area.
Life and career.
Early life.
Glenn Brenner was born on January 2, 1948, in Philadelphia, Pennsylvania, to Bill and Edie Brenner. At the age of four, he wanted to be a major league baseball player.
Brenner attended Abraham Lincoln High School. By the time he was in his senior year, however, basketball seemed to be in Brenner's future, as he was already tall. He led his high school basketball team to 26 straight victories. In his senior year in 1965, Lincoln High School lost the city championship game to Bishop Neumann High School, 75 to 66. Baseball remained Brenner's dream, however. Even though he only had one good pitch (a fastball), the New York Mets signed him to a minor league contract after he graduated from high school. He played for the Marion Mets in the Appalachian League, and eventually was brought up to play Class AA baseball. But in 1969, Brenner hurt his arm while playing in the Florida Instructional League, and the Mets sold him to the Philadelphia Phillies. He played Class AAA baseball in the Mexican League, but continuing problems with his throwing arm forced him to quit baseball in 1972.
Brenner knew early that he was not going to have much of a career in professional baseball. While still playing with the Mets, coach Birdie Tebbetts watched him pitch a terrible game. When Tebbetts came out to the mound, Brenner asked him what was wrong. Tebbetts replied, "Horse-spit pitcher"—and Brenner knew his time in the big leagues was finished. While playing minor league baseball, Brenner attended Temple University and then Saint Joseph's University in Philadelphia. He graduated from Saint Joseph's with a bachelor's degree in political science and Communication studies.
Early broadcasting career.
Brenner sold cars for a few months before turning to sports broadcasting after leaving the Phillies. His first job was with radio station WMVB in Millville, New Jersey. He read an advertisement for the position, and applied. He later said, "I lied so bad to get that first job. I told the boss I was an announcer from Philadelphia, and he took that to mean I was a Philadelphia announcer. I had never even been inside a radio station." Brenner was paid $79 a week, and commuted from Philadelphia to Millville very day. The lasted only a short period of time, and Brenner moved to New Haven, Connecticut, to seek work. After living there only a short time, he returned to Philadelphia and joined radio station WFIL, where he worked for two years as a news reporter and in promotions. Brenner turned to sportscasting in 1975, and took a position at WOWK-TV in Huntington, West Virginia.
Brenner's big break came in 1976, when he joined KYW-TV in Philadelphia. Brenner developed his on-air personality during his stint at KYW, becoming well known for his humor and irreverence. He often called the scoreboard the "boreboard", and made jokes about himself, sports teams, and athletes on the air (much to management's discomfort). In one well-known incident, KYW introduced a flashy, high-technology set that resembled the bridge of the Starship "Enterprise". When the news anchor turned to Brenner to ask for the sports report, Brenner stood and announced, "We, the jury, find the defendant not guilty!" The angry news director resolved to fire Brenner as soon as a replacement could be found.
Career at WUSA.
KYW's news director happened to know Jim Snyder, the news director at WTOP-TV (as WUSA was then known) in Washington, D.C. He mentioned Brenner's on-air stunt, and told Snyder that Brenner would be let go in a short time. Intrigued with Brenner's on-air personality, Snyder reviewed tapes of Brenner's work and liked what he saw.
WTOP-TV was seeking a new sports anchor to replace local sports broadcaster Warner Wolf, who had left the WTOP-TV for a job with ABC Sports. The station had hired Mike Wolfe as the weeknight sportscaster, while weekend duties were held by Klaus Wagner. But Wagner wasn't working out, and WTOP-TV declined to renew his one-year contract. Brenner made his D.C. debut on March 4, 1977. Wolfe was fired on March 22, and Brenner appointed his replacement. Wolfe adopted a very macho and aggressive style on the air, including an unbuttoned dress shirt and a "take it or shove it" attitude towards fans and athletes that grated on many viewers. When evening news ratings began to decline, the station dismissed Wolfe with nine months left in his contract. Brenner was named the weeknight sportscaster.
Brenner's on-air style was to mix humor with sports. He told "The Washington Post", "I'm talking to a group of people who are not that interested in what I have to say. They've proven that statistically. So what I want to do is keep their interest. And the way I can best do that is to relate to them." One of his signature bits included the "Weenie of the Week", in which he poked fun at bombastic professional athletes or unsportsmanlike behavior. When egotistical athletes did things which embarrassed others, Brenner often took them to task during the "Weenie of the Week" segment. In November 1987, Washington Redskins football players Clarence Verdin and Ricky Sanders performed "The Star-Spangled Banner" at Madison Square Garden (forgetting the words and singing off-key) on Veterans Day; Brenner mixed footage of their performance with footage of actress Pia Zadora similarly mangling the national anthem at a National Basketball Association game. Hundreds of angry fans complained, and Brenner apologized at both the 6:00 p.m. and 11:00 p.m. newscasts the next day. But he refused to read an additional statement on the air, and was given a one-day suspension. Jibes at athletes, sports team owners, and others were common during Brenner's career, and yet he was so respected and well-liked that few people ever became angry with him.
Another of Brenner's gimmicks was his Friday night "mystery picker"—a local or national celebrity who would be asked to pick winners of various athletic contests. Among the "mystery pickers" were CBS News co-anchor Connie Chung, former Washington Redskins quarterback Sonny Jurgensen, boxer Sugar Ray Leonard, CBS News anchor Dan Rather, comedian Paul Reubens, Redskins quarterback Mark Rypien, actor William Shatner, singing group The Temptations, and local nun Sister Marie Louise Kirkland. Sister Marie Louise turned out to be a phenomenally good sports prognosticator, and Brenner's repeated use of her became an international story. "People" magazine made it a cover story.
Viewers also enjoyed Brenner's banter with WTOP-TV news anchor Gordon Peterson, an authoritative figure in a three-piece suit with much on-air gravitas. Brenner often ribbed Peterson for his lifelong support of the also-ran Boston Red Sox major league baseball team. Brenner and Peterson became best of friends, and their jokes at one another's expense became local legend. One of Peterson's favorite bits was to keep speaking, using up the five minutes allotted to Brenner for sports news. Brenner would be forced to read the sports news as fast as he could, and then collapsed on the desk as if exhausted. In another common gag, Brenner would turn to Peterson and say, "You can ask me anything you want because you're the anchor"—at which point Petersen would attempt to stump Brenner with sports trivia or ask some embarrassing question.
Later at WTOP-TV, Brenner invented "Encore Wednesday". Since sports news was slow during mid-week, Brenner decided to highlight great sports moments each Wednesday night as a means of filling time and giving sports fans knowledge about their sport's great moments.
Brenner also moved beyond nightly news. In the early 1980s, Brenner teamed with former Redskins quarterback Sonny Jurgensen to host the popular "Redskins Sidelines" Sunday afternoon sports show, which focused on the Redskins football team.
Brenner became one of the city's most popular broadcasters. His fans included President Ronald Reagan (himself a former sportscaster), Reagan's successor as president, George H. W. Bush, his wife Barbara, and CBS News anchor Dan Rather.
In 1981, Brenner signed a contract with what was by then WDVM-TV (which WTOP-TV had changed its call letters to on June 26, 1978) that paid him $750,000 a year, paid his children's college tuition, and included a $1 million life insurance policy. The long-term contract was believed by "The Washington Post" to be a record for both the high level of pay and benefits as well as the long number of years it covered. On July 4, 1986, WDVM-TV changed its call letters to WUSA.
Brenner signed a five-year contract with WUSA in 1991 which paid him almost $1 million a year. The contract included a deferred salary, and paid his children's college tuition.
Brenner was nominated for and won numerous Associated Press and United Press International local broadcasting awards. The National Association of Sportswriters and Sportscasters named him "Washington Sportscaster of the Year" in 1989 and 1990.
Death.
On November 3, 1991, Brenner participated in the Marine Corps Marathon in Washington, D.C. He fell ill after crossing the finish line, and his physicians diagnosed a "vascular event". Two blood vessels in his head had ruptured and he had numbness on his left side, slight slurring of speech, and double vision. His doctors at George Washington University Hospital ruled out a stroke, however. Brenner began physical therapy. But on November 17, 1991, "The Washington Post" reported that Brenner's doctor, Arthur I. Kobrine, confirmed the broadcaster had suffered a cerebral hemorrhage. He underwent an MR angiogram and a radiographical angiogram, but neither showed anything abnormal.
Brenner's physical condition initially improved. He was released from the hospital after Thanskgiving. He began to regain use of his left arm, he was walking again, and the double vision had largely gone away. Although he was expected to return to the air in early January, Brenner began suffering from vomiting and dizziness. WUSA said he would not return to the air for another four to six weeks. On Friday, January 10, 1992, Brenner's physical condition declined rapidly and he was taken to George Washington University Hospital. An MRI later that day revealed a large mass in the brainstem. At 9:30 a.m. on January 11, surgeons operated on Brenner for four hours and discovered an inoperable malignant brain tumor. Bleeding in the brain had masked the tumor in previous exams. His prognosis was "poor," and he was listed in critical condition.
On Sunday, January 12, the Washington Redskins dedicated their NFC Championship game to Brenner. The Redskins handily defeated the Detroit Lions, 41-to-10, and went on to win Super Bowl XXVI two weeks later. Redskins coach Joe Gibbs brought the Championship game ball to Brenner in the hospital.
Brenner died at 7:58 a.m. on Tuesday, January 14, 1992 (just 12 days after his 44th birthday) at George Washington University Hospital. WUSA aired a half-hour special that night covering his career. Many citizens in the D.C. area were in shock for several days. President George H. W. Bush issued a statement upon Brenner's death, which said, "Barbara and I are greatly saddened by the untimely death of Glenn Brenner, a man whose wit and ability has endeared him to so many Washingtonians. The suddenness of his death, and the warmth of his personality, leave all of us with a painful emptiness." Former President Ronald Reagan also issued a statement, in which he said, "Today the entire Washington community mourns the loss of Glenn Brenner, a dear friend to all of us who knew him. He truly was a broadcasting great, bringing sports to life with his talent and dedication. Glenn set a wonderful example by his constant involvement in local causes and displayed a real concern for his community."
Brenner's funeral was held at National Presbyterian Church in Washington, D.C. on January 17, 1992. More than 1,500 mourners attended. He was buried at Oak Hill Cemetery in the Georgetown neighborhood of the city.
Legacy.
In a 2010 retrospective, former WTTG and WUSA sportscaster Brett Haber noted that Brenner was well known outside the mid-Atlantic region. Brenner also continued to be the standard to which all regional sports broadcasters aspired, even 18 years after his death.
The "Washington City Paper" said that sportscaster George Michael might have been better-known nationwide due to his "George Michael's Sports Machine", but that Michael remained the Salieri to Brenner's Mozart. The newspaper's Dave McKenna noted, "I worshipped Brenner. Everybody I knew around here when Brenner was on the air worshipped the guy."
The Washington, D.C. chapter of the National Academy of Television Arts and Sciences named its Glenn Brenner Award for Excellence in Sportscasting after him.


Thiazolidinedione

The thiazolidinediones , abbreviated as TZD, also known as glitazones after the prototypical drug ciglitazone, are a class of heterocyclic compounds consisting of a five-membered C3NS ring. The term usually refers to a family of drugs used in the treatment of diabetes mellitus type 2 that were introduced in the late 1990s.
Mechanism of action.
Thiazolidinediones or TZDs act by activating PPARs (peroxisome proliferator-activated receptors), a group of nuclear receptors, specific for "PPARγ" (PPAR-gamma, PPARG). They are thus the PPARG agonists subset of PPAR agonists. The endogenous ligands for these receptors are free fatty acids (FFAs) and eicosanoids. When activated, the receptor binds to DNA in complex with the retinoid X receptor (RXR), another nuclear receptor, increasing transcription of a number of specific genes and decreasing transcription of others. The main effect of expression and repression of specific genes is an increase in the storage of fatty acids in adipocytes, thereby decreasing the amount of fatty acids present in circulation. As a result, cells become more dependent on the oxidation of carbohydrates, more specifically glucose, in order to yield energy for other cellular processes.
PPARγ transactivation.
The activated PPAR/RXR heterodimer binds to peroxisome proliferator hormone response elements upstream of target genes in complex with a number of coactivators such as nuclear receptor coactivator 1 and CREB binding protein, this causes upregulation of genes (for a full list see PPARγ):
TZDs also increase the synthesis of certain proteins involved in fat and glucose metabolism, which reduces levels of certain types of lipids, and circulating free fatty acids. TZDs generally decrease triglycerides and increase high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C). Although the increase in LDL-C may be more focused on the larger LDL particles, which may be less atherogenic, the clinical significance of this is currently unknown. Nonetheless, rosiglitazone, a certain glitazone, was suspended from allowed use by medical authorities in Europe, as it has been linked to an increased risk of heart attack and stroke.
PPARγ transrepression.
Binding of PPARγ to coactivators appears to reduce the levels of coactivators available for binding to pro-inflammatory transcription factors such as NF-κB; this causes a decrease in transcription of a number of pro inflammatory genes, including various interleukins and tumour necrosis factors.
Members of the class.
Chemically, the members of this class are derivatives of the parent compound thiazolidinedione, and include:
Experimental, failed and non-marketed agents include:
Replacing one oxygen atom in a thiazolidinedione with an atom of sulfur gives a rhodanine.
Uses.
The only approved use of the thiazolidinediones is in diabetes mellitus type 2. According to a 2014 Cochrane systematic review of four randomized controlled trials, PPARγ-agonists may be effective in preventing further strokes in those who have already had a stroke or a transient ischemic attack (TIA) and may stabilize atherosclerotic plaques in the carotid arteries.
Research.
Experimental investigations on TZDs have been carried out since 2005 in polycystic ovary syndrome (PCOS), non-alcoholic steatohepatitis (NASH), psoriasis, autism, ovarian hyperstimulation syndrome (by VEGF inhibition in granulosa cells), lichen planopilaris, and other conditions.
Several forms of lipodystrophy cause insulin resistance, which has responded favorably to thiazolidinediones. There are some indications that thiazolidinediones provide some degree of protection against the initial stages of breast carcinoma development.
Evidence was emerging in 2008 that vitamin E with thiazolidinediones is effective in the treatment of non-alcoholic steatohepatitis due to their combined antioxidant and insulin sensitizing effects, producing histological improvements in steatosis severity.
Side effects and contraindications.
The withdrawal of troglitazone has led to concerns of the other thiazolidinediones also increasing the incidence of hepatitis and potential liver failure, an approximately 1 in 20,000 individual occurrence with troglitazone. Because of this, the FDA recommends two to three month checks of liver enzymes for the first year of thiazolidinedione therapy to check for this rare but potentially catastrophic complication. To date, 2008, the newer thiazolidinediones, rosiglitazone and pioglitazone have been free of this problem.
The main side effect of all thiazolidinediones is water retention, leading to edema, generally a problem in less than 5% of individuals, but a big problem for some and potentially, with significant water retention, leading to a decompensation of potentially previously unrecognized heart failure. Therefore, thiazolidinediones should be prescribed with both caution and patient warnings about the potential for water retention/weight gain, especially in patients with decreased ventricular function (NYHA grade III or IV heart failure).
Though older studies suggested there may be an increased risk of coronary heart disease and heart attacks with rosiglitazone, pioglitazone treatment, in contrast, has shown significant protection from both micro- and macro-vascular cardiovascular events and plaque progression. These studies led to a period of Food and Drug Administration advisories (2007 - 2013) that, aided by extensive media coverage, led to a substantial decrease in rosiglitazone use. In November 2013, the FDA announced it would remove the usage restrictions for rosiglitazone in patients with coronary artery disease. The new recommendations were largely based on the reasoning that prior meta-analyses leading to the original restrictions were not designed to assess cardiac outcomes and, thus, not uniformly collected or adjudicated. In contrast, one of the largest trials (RECORD trial) that was specifically designed to assess cardiac outcomes found no increased risk of myocardial infarction with rosiglitazone use, even after independent re-evaluation for FDA review.
A 2013 meta-analysis concluded that use of pioglitazone is associated with a slightly higher risk of bladder cancer compared to the general population. The authors of the same analysis recommended that other blood sugar lowering agents be considered in people with other risk factors for bladder cancer such as cigarette smoking, family history, or exposure to certain forms of chemotherapy.
Thiazolidinediones reduce bone mineral density and increase the risk of fractures in women, possibly as a result of biasing the differentiation of bone marrow stromal cells away from osteoblast differentiation and toward adipocyte formation.
Thiazolidinediones increase expression of angiotensin-converting enzyme 2 (ACE2). It is hypothesized that this increases the chance of serious infection with the SARS-CoV-2 virus, which causes COVID-19.


Occipital face area

The occipital face area (OFA) is a region of the human cerebral cortex which is specialised for face perception. The OFA is located on the lateral surface of the occipital lobe adjacent to the inferior occipital gyrus. The OFA comprises a network of brain regions including the fusiform face area (FFA) and posterior superior temporal sulcus (STS) which support facial processing.
Structure.
Like other regions of cerebral cortex, the OFA is functionally defined by using neuroimaging techniques to localise changes in neural activity in response to different face stimuli. Typically, participants will view different kinds of face stimuli which can be contrasted with scrambled images, letter strings or non-face objects to localise the OFA. While the exact location of the OFA varies between individuals and according to the specific paradigm used, it usually corresponds to Brodmann areas 18 or 19.
Function.
The OFA is believed to be functionally necessary for some face computations. Lesion studies using patients with prosopagnosia show that brain damage overlapping with the OFA is associated with impaired facial recognition. TMS studies using healthy participants have shown that temporary inactivation of the OFA can produce deficits in various aspects of face perception including face recognition, face identity perception and facial feature processing.
Compared to lower visual cortical areas such as V1, the OFA is believed to support face processing by representing higher-order features such as faces or facial features compared with lower-order features such as edges or contours. For example, it has been suggested that the OFA may represent faces using a topographic face map whereby neighbouring areas of the cortical surface reflect physically neighbouring regions of a face. These representations likely emerge as a result of feedback connections between neighbouring cortical areas such as the OFA and FFA which provide fine-grained analysis and a general face-template respectively. This suggestion is supported by evidence of reciprocal connectivity between the OFA and FFA, among other regions of visual cortex.
Patient P.S..
Examining case studies of individuals with lesions to the OFA provides more insight into the functional role of the OFA. Prosopagnosic patients have been essential for this initiative, especially patient P.S., a right handed woman with a lesion extending from the posterior part of the right inferior occipital gyrus into the posterior fusiform gyrus. This lesion left patient P.S. without a right OFA and she exhibited great difficulty with facial recognition in daily life and facial gender discrimination, and could not match unfamiliar faces seen from different viewing angles. Despite the extensive cortical damage she suffered, patient P.S. exhibited a normal right FFA when compared to age matched controls using a standard fMRI localizer. She was unimpaired with basic-level and within-class object discrimination and recognition tasks. Results like these demonstrate that face information can still be processed in the right FFA despite the absence of the right OFA, thus suggesting the presence of alternate cortical routes between the early visual cortex and fusiform gyrus.


Neural groove

The neural groove is a shallow median groove of the neural plate between the neural folds of an embryo. The neural plate is a thick sheet of ectoderm surrounded on either side by the neural folds, two longitudinal ridges in front of the primitive streak of the developing embryo.
The groove gradually deepens as the neural folds become elevated, and ultimately the folds meet and coalesce in the middle line and convert the groove into a closed tube, the neural tube or canal, the ectodermal wall of which forms the rudiment of the nervous system.
After the coalescence of the neural folds over the anterior end of the primitive streak, the blastopore no longer opens on the surface but into the closed canal of the neural tube, and thus a transitory communication, the neurenteric canal, is established between the neural tube and the primitive digestive tube. The coalescence of the neural folds occurs first in the region of the hind-brain, and from there extends forward and backward; toward the end of the third week the front opening (anterior neuropore) of the tube finally closes at the anterior end of the future brain, and forms a recess which is in contact, for a time, with the overlying ectoderm; the hinder part of the neural groove presents for a time a rhomboidal shape, and to this expanded portion the term sinus rhomboidalis has been applied. Before the neural groove is closed a ridge of ectodermal cells appears along the prominent margin of each neural fold; this is termed the neural crest or ganglion ridge, and from it the spinal and cranial nerve ganglia and the ganglia of the sympathetic nervous system are developed. By the upward growth of the mesoderm the neural tube is ultimately separated from the overlying ectoderm.
The cephalic end of the neural groove exhibits several dilatations, which, when the tube is closed, assume the form of three vesicles; these constitute the three primary cerebral vesicles, and correspond respectively to the future fore-brain (prosencephalon), mid-brain (mesencephalon), and hind-brain (rhombencephalon). The walls of the vesicles are developed into the nervous tissue and neuroglia of the brain, and their cavities are modified to form its ventricles. The remainder of the tube forms the medulla spinalis or spinal cord; from its ectodermal wall the nervous and neuroglial elements of the medulla spinalis are developed while the cavity persists as the central canal.


Active sensory systems

Active sensory systems are sensory receptors that are activated by probing the environment with self-generated energy. Examples include echolocation of bats and dolphins and insect antennae. Using self-generated energy allows more control over signal intensity, direction, timing and spectral characteristics. By contrast, passive sensory systems involve activation by ambient energy (that is, energy that is preexisting in the environment, rather than generated by the user). For example, human vision relies on using light from the environment.
Active sensory systems receive information with or without direct contact. "Teleceptive active sensory systems" collect information by directing propagating energy and detecting objects using cues such as time delay and intensity of return signal. Examples include echolocation of bats and electrosensory detection of electric fish. "Contact active sensory systems" use physical contact between stimuli and organism. Insect antennae and whiskers are examples of contact active sensory systems.
Examples.
Active electrolocation.
Bioluminescence: Adult firefly uses self-generated light to locate mates. In deep oceans, barbeled dragonfish produces near infrared light.
Electrostatic field: Electric fishes probe the environment and create active electrodynamic imaging.
Mechanosensory.
Active touching: Nocturnal animals depend on whiskers to navigate by gathering information about position, size, shape, orientation and texture of objects. Insects use antennae to probe the environment during locomotion. Human's reaching out to objects with hands is an analogy.
Echolocation.
Echolocation: Active acoustic sensing of self-produced sounds. Bats emit echolocation calls for detecting prey in flight. Toothed whales use echolocation in water.
Chemical.
Because propagation of chemicals take longer than other sources, only organisms with slow locomotion can utilize chemical signals to probe the environment. The slime mold "Dictyostelium discoideum" uses ammonia to probe the environment to avoid obstacles during formation of fruiting body. Deploying chemical signal is also limited by lack of return signals.
Physical and ecological constraints.
Energy propagation.
An important constraint in teleceptive active sensory systems is generating energy with return signal above threshold of detection. Self-generated energy needs to be strong enough to detect objects at a distance. Due to geometric spreading, energy emitted uniformly will spread over a sphere of increasing surface area. Signal strength depends on the square of distance between organism and target. In teleceptive active sensing, geometric spread cost is doubled, because signal is emitted and returned. As a result, fraction of energy returned decreases as the fourth power of the distance between organism and target.
Directionality also plays a role in energy expenditure in producing signals. Increase in directionality and narrow range result in longer attenuation length. A bat has a wider detection range to target small insects flying at high velocity. A dolphin produces a more narrow echolocation beam which propagates further. Electric fishes emit signals that envelope the whole body, thus have a shorter propagation distance.
Attenuation.
Attenuation: In addition to geometric spreading, absorption and scattering of energy during propagation results in the loss of energy. The attenuation length is the distance at which intensity drops to 1/e(37%) to initial intensity. Environmental factors such as fog, rain and turbulence disturb signal transmission and decreases attenuation length.
Length of appendages.
For contact sensory system, only targets within reach of contact appendages are detectable. Increase in length of appendages adds physical energy costs by adding weight during locomotion and investment for growth. As a compromise, whiskers of rats cover only 35% of their body. To minimize cost, rhythmic movements are coupled with stepping mechanisms of insects.
Conspicuousness.
Energy released into the environment by organisms is prone to detection by other organisms. The detection by predators and competing individuals of same species provides a strong evolutionary pressure. When active sensing is used, energy levels detected at the target are greater than those of the returning signal. Prey or predators evolved to eavesdrop on active sensing signals . For example, most flying insect preys of bats developed sensitivity to echolocation call frequency. When stimulated by a high-pitched sound, moths engage in dodging flight pathway. Dolphins can also detect killer whales' ultrasonic clicks. In return, killer whales produce more irregular, isolated sonar clicks to make less conspicuous signals. In case of barbeled dragonfish, it utilizes red light that other deep-sea fishes can't detect.
Related concepts.
Corollary Discharge refers to the ability to differentiate one's own movements and responses to external motor events. Orientation and actions are mapped on neuronal level and remembered in the brain. Corollary discharge allows one to incorporate sensory intake as a result of sensory system and serves as a feedback system.
Jamming Avoidance Response Conspecific signals interfere active sensing of individuals sharing habitats. Electric fishes such as Eigenmannia developed reflexive shift in discharge frequencies in order to avoid frequency interference.


High-touch

High-touch refers to the involvement of personal attention and service. In business, the term often refers to situations where trust between the customer and employed individual(s) is necessary. High-touch areas include: medicine, wealth management, real estate, and legal. Stock trading done by humans, as opposed to automated trading or using online brokers, is also referred to as high-touch.
Origins.
The term was coined in 1982 by John Naisbitt in his book "Megatrends". It was explored further by Naisbitt in his follow-up book "High Tech/High Touch".
In Medicine.
High-touch may also refer to the frequency in which a surface is touched.
In pharmacology, high-touch may refer to medicines that require temperature control, ongoing drug management, or compliance monitoring.
Related to High-Tech.
High-touch was coined as a term in response to "high tech." High-tech, as opposed to high-touch, is when customers don't need human interaction to perform activities such as onboarding, ordering, and account management. High-tech services, such at chatbots, allow customers to get what they want on-demand.


Fried brain sandwich

A fried brain sandwich is a sandwich that is generally served as sliced calves' brains on sliced bread.
Thinly sliced fried slabs on white toast became widespread on menus in St. Louis, Missouri, after the rise of the city's stockyards in the late 1880s, although demand there has so dwindled that only a handful of restaurants still offer them. They remain popular in the Ohio River valley, where they are served heavily battered on hamburger buns. In Evansville, Indiana, they are still offered at several "mom and pop" eateries, specifically the Hilltop Inn, and remain a favorite dish, featured at the city's annual West Side Nut Club Fall Festival. Kissner's, a traditional workman's taproom in Defiance, Ohio, has offered a brain sandwich since 1928.
Replacement with pig's brain over health concerns.
Brains from cows over 30 months old at slaughter are no longer permitted to be sold for human consumption in the United States. Some restaurants have taken to serving pigs' brains instead of cows' brains due to concerns regarding bovine spongiform encephalopathy, commonly known as "mad cow disease". Because pigs' brains are substantially smaller than cows' brains, the amount of preparation required for each sandwich increases. Each brain must be cleaned before being sliced and pigs' brains produce fewer slices.


Peripaleocortex

Peripaleocortex is one of two subtypes of periallocortex, the other being periarchicortex. Peripaleocortex is formed at borders between isocortex (neocortex) and paleocortex (a subtype of allocortex). It shows slow histological transition from the three-layered structure characteristic of paleocortex to the typical six-layered structure characteristic of isocortex. The main peripaleocortex area is anterior insular cortex.
Peripaleocortex does not histologically transit directly to the true isocortex. Instead, at borders between peripaleocortex and isocortex, there are other transitional areas from the isocortex side, called proisocortex. Thus, at borders between paleocortex and isocortex, there are two transitional areas. One transitional area, which is anatomically located closer to the paleocortex side and histologically, too, more resembling "true" paleocortex, is called peripaleocortex area. Another transitional area, which is anatomically located close to the true isocortex side and histologically more resembling it too, is called proisocortex area.


Triflin

Triflin is a cysteine-rich secretory protein (CRISP), which is excreted by the venom gland of the Habu snake ("Trimeresurus flavoviridis"). Triflin reduces high potassium-induced smooth muscle contraction, suggesting a blocking effect on L-type calcium channels.
Sources.
Triflin is a toxin derived from snake venom. The toxin is produced in the gland of the Habu snake, "Trimeresurus flavoviridis".
Chemistry.
Triflin is a cysteine-rich secretory protein, which means it belongs to the CRISP family. This is a group of single chain polypeptides found in various organisms.
Triflin weighs 25 kDa and consists of 221 amino-acid residues.
The first 163 residues of the N-terminal domain forms an α-β-α sandwich core. This domain is comparable with group 1 plant pathogenesis-related protein (PR-1).
The C-terminal domain, has five disulfide bridges. This domain is responsible for the selectivity of the protein and consists of two subdomains: N-terminal subdomain (Cys 167 to Cys 179) and C-terminal subdomain (42 amino-acids residues).
The N-terminal subdomain is connected with N-terminal domain through two main-chain hydrogen bonds between β11 and β2 and is thereby part of the PR-1 domain.
The C-terminal subdomain is stabilized by three disulfide bridges and it is remarkable that this domain does not interact with either the PR-1 domain or the N-terminal sub-domain. The C-terminal subdomain consists of particles, including some hydrophobic residues that are exposed to the solvent. These hydrophobic residues might mediate the interaction with the target proteins and therefore receptor recognition.
There are some homologous toxins to Triflin with different percentages of amino-acid sequence similarity, such as Ablomin, Latisemin, Stecrip (88%), Helothermine (49%), Pseudechetoxin (62%), Pseudesin (61%). The snake venoms which belong to CRISP family seem to be homologous to each other, however there are differences in their protein targets.
Target.
Triflin reduces high potassium induced smooth muscle contraction, suggesting a blocking effect on L-type calcium channels.
Treatment.
One of the small serum proteins (SSP-2), a substance produced by "Trimeresurus flavoviridis" itself, has high affinity for Triflin, and may thus work as a defensive mechanism against accidental self-poisoning, suggesting a possible role for SSP-2 as an antidote to triflin.


Waterlogging (archaeology)

In archaeology, waterlogging refers to the long-term exclusion of air by groundwater, which creates an anaerobic environment that can preserve artifacts perfectly. Such waterlogging preserves perishable artifacts. Thus, in a site which has been waterlogged since the archaeological horizon was deposited, exceptional insight may be obtained by study of artifacts made of leather, wood, textile or similar materials. 75-90% of the archaeological remains at wetland sites are found to be organic material. Tree rings found from logs that have been preserved allow archaeologists to accurately date sites. Wetland sites include all those found in lakes, swamps, marshes, fens, and peat bogs.
Peat bogs, nearly all of which occur in northern latitudes, are some of the most important environments for wetland archaeology. Peat bogs have likewise preserved many wooden trackways, including the world's oldest road, which is a 6,000-year-old one-mile stretch of track.
Bog bodies are the best-known finds from the peat bogs of northwest Europe, with most of them dating from the Iron Age. Most corpses that were found were individuals that met a violent death and were probably either executed as criminals or killed as a sacrifice before thrown into the bog. For example, the Old Croghan Man was stabbed, decapitated, mutilated, and tied down to the bottom of a bog pool. His body is an amazing display of how splendidly waterlogging can preserve a body, as his hands, skin, fingernails, and stomach were amazingly intact. Another example of a waterlogging artifact or mummy was Ötzi, found by two tourists near the border of Austria and Italy. Ötzi is now displayed in Bolzano, Italy, in the South Tyrol Museum of Archaeology.
Occasionally, waterlogged conditions can occur inside burial mounds. The oak-coffin burials of Bronze Age northern Europe, and most notably those of Denmark, date to about 1000 BC. These coffins had an inner core of stones packed round the tree-trunk coffin, with a round barrow built above. Water then infiltrated the inside of the mound and by combining with tannin exuding from the tree trunks, set up acidic conditions which destroyed the skeleton but preserved the skin, hair, ligaments, and clothing of the individuals.
Perhaps the most interesting wetland archaeological find was the Ozette site. In 1750, a huge mudslide buried a whale-hunting settlement on the coast of Washington, which protected the organic artifacts from the oxygen that would lead to their deterioration. Over 50,000 artifacts were found in a fine state of preservation, with almost half of them being wood or plant material. The most fascinating thing they found was a meter-high block of cedar that was carved in the shape of a whale's dorsal fin.
The major archaeological problem with waterlogged finds, particularly wood, is that they deteriorate rapidly when they are uncovered, beginning to dry and crack almost at once. They therefore need to be kept wet until treated in a laboratory. Conservation measures explain why wet archaeology costs around four times as much as dry archaeology.


Bill Black

William Patton Black Jr. (September 17, 1926 – October 21, 1965) was an American musician and bandleader who is noted as one of the pioneers of rock and roll. He was the bassist in Elvis Presley's early trio. Black later formed Bill Black's Combo.
Early life and career.
Black was born in Memphis, Tennessee, to a motorman for the Memphis Street Railway Co. He was the oldest of nine children. His father played popular songs on the banjo and fiddle to entertain the family. Black learned to play music at the age of 14 on an instrument made by his father—a cigar box with a board nailed to it and strings attached. At the age of sixteen, Black was performing "honky-tonk" music on acoustic guitar in local bars.
During World War II, Black was stationed with the U.S. Army at Fort Lee in Virginia. While in the Army, he met Evelyn, who played guitar as a member of a musical family. They married in 1946 and returned to Memphis. Black worked at the Firestone plant.
He began playing the upright bass fiddle, modeling his "slap bass" technique after one of his idols, Fred Maddox, of Maddox Brothers and Rose. Black also developed a "stage clown" persona in the same way that Maddox entertained audiences. Black performed as an exaggerated hillbilly with blacked-out teeth, straw hat and overalls. According to his son, Black said his goal was always to give his audience "a few moments of entertainment and maybe a little bit of humor that'll tickle 'em for a while."
In 1952, Black began playing in clubs and on radio shows with the guitarist Scotty Moore. Along with two other guitarists and a fiddler, they performed country music tunes by Hank Williams and Red Foley in Doug Poindexter's band, the Starlight Wranglers. Black and Moore also played in a band with Paul Burlison, Johnny Burnette, Dorsey Burnette on steel guitar, and a drummer.
The Blue Moon Boys.
In July 1954, Sam Phillips, of Sun Records, asked Black and Moore to play backup for the as-yet-unknown Elvis Presley. Black played slap bass with Moore on the guitar, while Presley played rhythm guitar and sang lead. Neither musician was overly impressed with Presley, but they agreed a studio session would be useful to explore his potential.
On July 5, 1954, the trio met at Sun studios to rehearse and record a handful of songs. According to Moore, the first song they recorded was "I Love You Because", but after a few country music songs that weren't impressive they decided to take a break. During the break, Presley began "acting the fool" with Arthur Crudup's "That's All Right (Mama)," a blues song. When the other two musicians joined in, Phillips taped the song. The upbeat sound was original. Black remarked, "Damn. Get that on the radio and they'll run us out of town."
The next day, the group recorded four more songs, including “Blue Moon of Kentucky," by the bluegrass musician Bill Monroe, which he had written and recorded as a slow waltz. Sources credit Black with initiating the song, with Presley and Moore joining in. Moore said, "Bill is the one who came up with "Blue Moon of Kentucky." ... We're taking a little break and he starts beating on the bass and singing "Blue Moon of Kentucky," mocking Bill Monroe, singing the high falsetto voice. Elvis joins in with him, starts playing and singing along with him ..." They ended up with a fast version of the song in 4/4 time. After an early take, Phillips can be heard on tape saying, "Fine, man. Hell, that’s different—that's a pop song now, nearly ʼbout."
Phillips took several acetates of the session to DJ Dewey Phillips (no relation) of Memphis radio station WHBQ's "Red, Hot and Blue" show. From August 18 through December 8, "Blue Moon of Kentucky" was consistently higher on the charts, and then both sides began to chart across the South.
Black and Moore became Presley's backup group and were paid 25% of his earnings. Moore and Black left the Starlite Wranglers after the success of "That's All Right," jealousy within the group forcing them to split. Their recordings at Sun were released with the credits as "Elvis Presley, Scotty and Bill." The group was later billed as "Elvis Presley and the Blue Moon Boys."
Over the next 15 months, the trio released five singles, toured across the South, and appeared regularly on the "Louisiana Hayride". They had auditioned for the Grand Ole Opry in October 1954, but they failed to impress the people in charge, or the audience, and were not invited back.
In 1955, Black went to RCA along with Presley and Moore when Presley's contract was sold to that company. Except for the RCA reissue of "Mystery Train" and "I Forgot to Remember to Forget" (“with Scotty and Bill”), they were no longer credited on record labels.
Black played on early Presley recordings including "Good Rockin' Tonight", "Heartbreak Hotel", "Baby Let's Play House", "Mystery Train", "That's All Right", and "Hound Dog", and eventually became one of the first bass players to use the Fender Precision Bass (bass guitar) in popular music, on "Jailhouse Rock", in the late 1950s.
Black, Moore and the drummer D. J. Fontana toured extensively during Presley's early career. Black continued his onstage "clown" persona and developed comedy routines with Presley. Black's onstage personality was a sharp contrast to the introverted stage presence of Moore. The balance fit the group's performances.
According to Black's son Louis, Moore said, "Elvis used to just stand up there and not move, and Bill would jump around on the bass. Your daddy would come down through there and get everybody to laughing and loosen them up." Fontana called Black the mainstay of the band in the early days. "He was a comedian who could warm up a crowd. That was necessary for us because we played for a lot of country crowds that weren't used to people jumping up and down on stage."
Bill Black's Combo.
In 1959 Black joined a group of musicians which became Bill Black's Combo. The lineup was Black (bass), Joe Lewis Hall (piano), Reggie Young (guitar), Martin Willis (saxophone), and Jerry Arnold (drums). There were several personnel changes. While Young was in the army, his position was filled by Hank Hankins, Chips Moman and Tommy Cogbill. On sax, Ace Cannon took over touring duties from Willis who remained in Memphis for the studio work and movie appearances. Carl McVoy replaced Hall in the studio, while Bobby Emmons replaced him on tour.
The band released blues instrumental "Smokie" for Hi Records in December 1959. "Smokie, Part 2" became a No. 17 U.S. pop hit, and made number one on the "black" music charts. It sold over one million copies, and was awarded a gold disc by the RIAA. A follow-up release, "White Silver Sands" (Hi 2021), was a Top 10 hit (#9) and, like its predecessor, topped the R&B charts for four weeks.
Eight of the recordings by Bill Black's Combo placed in the Top 40 between 1959 and 1962. Advertised as "Terrific for Dancing" their "Saxy Jazz" album spent a record whole year in the top 100.
The Combo appeared in the 1961 film "Teenage Millionaire" and on "The Ed Sullivan Show", where they performed a medley of "Don't Be Cruel," "Cherry Pink," and "Hearts of Stone", and were voted Billboard's number one instrumental group of 1961.
Albums with themes included "Bill Black's Combo Plays Tunes by Chuck Berry", "Bill Black's Combo Goes Big Band", "Bill Black's Combo Goes West", and "Bill Black's Combo Plays the Blues". The Combo's sound of danceable blues became a popular accompaniment for striptease dancers. Another characteristic of the Combo was Reggie Young thwacking on the guitar with a pencil.
Lyn-Lou Studio.
In 1962, Bill Black opened a recording studio called "Lyn-Lou Studios" (a shortened nickname "Linda-Lou" he had for his daughter Nancy), and a record label named "Louis" after his son, on Chelsea Street in Memphis, Tennessee, with Larry Rogers (Studio 19, Nashville) as his engineer and producer. Johnny Black, Bill's brother and also upright bass player, who knew Elvis at Lauderdale Courts before Bill, recalls visiting Bill at the studio and reported that Bill would be totally absorbed mixing and playing back tracks.
Bob Tucker and Larry Rogers purchased Lyn-Lou Studios after Bill Black's death in 1965. The studio recorded many Bill Black Combo albums (with billings such as "The Best Honky Tonk Band in America" and "The band who opened for the Beatles") and produced number-one country hits for Charly McClain, T.G. Shepard, Billy Swan and others. The house band for these sessions was the Shylo Band, featuring guitarist/songwriter Ronnie Scaife, nephew of Cecil Scaife, famed Sun Studio engineer.
Early in 1963, Black sent from two to five different versions of the Combo to different regions of the country at the same time, while staying off the road himself, wanting to concentrate on his business, family and his health.
Illness and death.
In 1963, Bob Tucker joined the Bill Black Combo as a road manager and guitar/bass player.
Black himself had been ill for the past year and a half and unable to travel. Nonetheless, he insisted that the band continue without him. The Bill Black Combo created musical history in 1964 when they became the opening act for the Beatles (at their request) on their historic 13-city tour of America after their appearance on "The Ed Sullivan Show". Black himself was not well enough to make the tour.
After two surgeries and lengthy hospital stays, Black died of a brain tumor on October 21, 1965, at age 39. His death occurred during his third operation that doctors had hoped would eradicate the tumor permanently. Black's body was buried, next to his father, William Patton Black, Sr., at Forest Hill Cemetery in Memphis, Tennessee. Presley was criticized for not attending the funeral, but he believed that his presence would turn it into a media frenzy. He decided instead to visit the family privately after the service to express his condolences. According to Louis Black, Presley said, "If there's anything that y'all need, you just let me know and it's yours."
Black's widow sold Bob Tucker and Larry Rogers the rights to use the name Bill Black's Combo. The band changed to country music when it joined Columbia Records, and won Billboard's Country Instrumental Group of the Year award in 1976.
Legacy.
Bill Black's Combo cut more than 20 albums, toured the United States and Europe and won awards as the best instrumental group in America in 1966 and 1967. Bob Tucker worked for the University of Memphis as Professor of Music Business while leading the combo.
Black's main stand-up bass is today owned by ex-Beatle Paul McCartney, who received the instrument as a birthday present from his wife Linda in the late 1970s. The bass can be seen in the video clip to McCartney's song "Baby's Request". In the documentary film "In the World Tonight", McCartney can be seen playing it and singing his version of "Heartbreak Hotel". In 1995, he played it on "Real Love", the last "new" Beatles record (one of two in which McCartney, George Harrison and Ringo Starr overdubbed a full arrangement onto a John Lennon home recording from the late 1970s).
Actor Elliott Street portrayed Black in the TV movie "Elvis", starring Kurt Russell.
Actor Blake Gibbons portrayed Black in the short-lived 1990 TV series "Elvis", starring Michael St. Gerard.
In 2005, Clay Steakley portrayed Black in the 2005 CBS miniseries "Elvis", starring Jonathan Rhys Meyers.
In 2007, Black was inducted into the Musicians Hall of Fame and Museum.
On April 4, 2009, Bill Black was inducted into the Rock and Roll Hall of Fame.


Bond duration closed-form formula


Progesterone vaginal ring

Progesterone vaginal ring, also known as progesterone-only vaginal ring, is a form of vaginal ring used for birth control when breastfeeding. Use can begin at four weeks and continue for at least up to a year following childbirth. Failure rates with usual use is about 1.5 per 100 women. It is used within the vagina with one ring lasting three months. The woman is able to place and remove the ring herself. It is sold under the brand names Progering among others.
Side effects include vaginal discharge and pain with urination. It does not appear to be associated with serious side effects. With use menstrual periods often do not resume. It was specifically made for use with breastfeeding as it does not affect milk production. It works by gradually releasing the hormone progesterone.
Progesterone vaginal rings have been approved for medical use since 1998. It is on the World Health Organization's List of Essential Medicines, the safest and most effective medicines needed in a health system. As of 2014 they are available in a number of South and Central American countries. As of 2016 it is not available in the United States. It was developed by the Population Council.


Medial pontine reticular formation

The medial pontine reticular formation (MPRF) is a part of the human brain located in the pons of the brainstem (specifically the central pontine reticular formation). It plays a critical function in the generation of REM sleep.
Role in REM sleep.
GABAergic neurons of the MPRF are activated by Acetylcholine (released by the Pedunculopontine tegmental nucleus), and in turn activate cells in the basal forebrain -- namely the Dorsal raphe nucleus (which produces serotonin) and the Locus coeruleus (which produces Norepinephrine). This activation will stimulate cortical activity, which is characteristic of the low amplitude / high frequency EEG patterns observed during REM sleep. As well, lesions of the MPRF will cause a great decrease of REM sleep.