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Long-term depression

In neurophysiology, long-term depression (LTD) is an activity-dependent reduction in the efficacy of neuronal synapses lasting hours or longer following a long patterned stimulus. LTD occurs in many areas of the CNS with varying mechanisms depending upon brain region and developmental progress.

As the opposing process to long-term potentiation (LTP), LTD is one of several processes that serves to selectively weaken specific synapses in order to make constructive use of synaptic strengthening caused by LTP. This is necessary because, if allowed to continue increasing in strength, synapses would ultimately reach a ceiling level of efficiency, which would inhibit the encoding of new information. Both LTD and LTP are forms of synaptic plasticity.

Characterisation
LTD in the hippocampus and cerebellum have been the best characterized, but there are other brain areas in which mechanisms of LTD are understood. LTD has also been found to occur in different types of neurons that release various neurotransmitters, however, the most common neurotransmitter involved in LTD is L-glutamate. L-glutamate acts on the N-methyl-D- aspartate receptors (NMDARs), α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors (AMPARs), kainate receptors (KARs), and metabotropic glutamate receptors (mGluRs) during LTD. It can result from strong synaptic stimulation (as occurs in the cerebellar Purkinje cells) or from persistent weak synaptic stimulation (as in the hippocampus). Long-term potentiation (LTP) is the opposing process to LTD; it is the long-lasting increase of synaptic strength. In conjunction, LTD and LTP are factors affecting neuronal synaptic plasticity. LTD is thought to result mainly from a decrease in postsynaptic receptor density, although a decrease in presynaptic neurotransmitter release may also play a role. Cerebellar LTD has been hypothesized to be important for motor learning. However, it is likely that other plasticity mechanisms play a role as well. Hippocampal LTD may be important for the clearing of old memory traces. Hippocampal/cortical LTD can be dependent on NMDA receptors, metabotropic glutamate receptors (mGluR), or endocannabinoids. The result of the underlying-LTD molecular mechanism in cerebellum is the phosphorylation of AMPA glutamate receptors and their elimination from the surface of the parallel fiber-Purkinje cell (PF-PC) synapse.

Neural homeostasis
It is highly important for neurons to maintain a variable range of neuronal output. If synapses were only reinforced by positive feedback, they would eventually come to the point of complete inactivity or too much activity. To prevent neurons from becoming static, there are two regulatory forms of plasticity that provide negative feedback: metaplasticity and scaling. Metaplasticity is expressed as a change in the capacity to provoke subsequent synaptic plasticity, including LTD and LTP. The Bienenstock, Cooper and Munro model (BCM model) proposes that a certain threshold exists such that a level of postsynaptic response below the threshold leads to LTD and above it leads to LTP. BCM theory further proposes that the level of this threshold depends upon the average amount of postsynaptic activity. Scaling has been found to occur when the strength of all of a neuron’s excitatory inputs are scaled up or down. LTD and LTP coincide with metaplasticity and synaptic scaling to maintain proper neuronal network function.

General forms of LTD
Long-term depression can be described as either homosynaptic plasticity or heterosynaptic plasticity. Homosynaptic LTD is restricted to the individual synapse that is activated by a low frequency stimulus. In other words, this form of LTD is activity-dependent, because the events causing the synaptic weakening occur at the same synapse that is being activated. Homosynaptic LTD is also associative in that it correlates the activation of the postsynaptic neuron with the firing of the presynaptic neuron. Heterosynaptic LTD, in contrast, occurs at synapses that are not potentiated or are inactive. The weakening of a synapse is independent of the activity of the presynaptic or postsynaptic neurons as a result of the firing of a distinct modulatory interneuron. Thus, this form of LTD impacts synapses nearby those receiving action potentials.

Hippocampus
LTD affects hippocampal synapses between the Schaffer collaterals and the CA1 pyramidal cells. LTD at the Schaffer collateral-CA1 synapses depends on the timing and frequency of calcium influx. LTD occurs at these synapses when Schaffer collaterals are stimulated repetitively for extended time periods (10–15 minutes) at a low frequency (approximately 1 Hz). Depressed excitatory postsynaptic potentials (EPSPs) result from this particular stimulation pattern. The magnitude of calcium signal in the postsynaptic cell largely determines whether LTD or LTP occurs. NMDA-receptor dependent LTD is induced by moderate rises in postsynaptic calcium levels. When Ca2+ entry is below threshold, it leads to LTD. The threshold level in area CA1 is on a sliding scale that depends on the history of the synapse. If the synapse has already been subject to LTP, the threshold is raised, increasing the probability that a calcium influx will yield LTD. In this way, a "negative feedback" system maintains synaptic plasticity. Activation of NMDA-type glutamate receptors, which belong to a class of ionotropic glutamate receptors (iGluRs), is required for calcium entry into the CA1 postsynaptic cell. Change in voltage provides a graded control of postsynaptic Ca2+ by regulating NMDAR-dependent Ca2+ influx, which is responsible for initiating LTD.

While LTP is in part due to the activation of protein kinases, which subsequently phosphorylate target proteins, LTD arises from activation of calcium-dependent phosphatases that dephosphorylate the target proteins. Selective activation of these phosphatases by varying calcium levels might be responsible for the different effects of calcium observed during LTD. The activation of postsynaptic phosphatases causes internalization of synaptic AMPA receptors (also a type of iGluRs) into the postsynaptic cell by clathrin-coated endocytosis mechanisms, thereby reducing sensitivity to glutamate released by Schaffer collateral terminals.

Cerebellum
LTD occurs at synapses in cerebellar Purkinje neurons, which receive two forms of excitatory input, one from a single climbing fiber and one from hundreds of thousands of parallel fibers. LTD decreases the efficacy of parallel fiber synapse transmission, though, according to recent findings, it also impairs climbing fiber synapse transmission. Both parallel fibers and climbing fibers must be simultaneously activated for LTD to occur. With respect to calcium release however, it is best if the parallel fibers are activated a few hundred milliseconds before the climbing fibres. In one pathway, parallel fiber terminals release glutamate to activate AMPA and metabotropic glutamate receptors in the postsynaptic Purkinje cell. When glutamate binds to the AMPA receptor, the membrane depolarizes. Glutamate binding to the metabotropic receptor activates phospholipase C (PLC) and produces diacylglycerol (DAG) and inositol triphosphate (IP3) second messengers. In the pathway initiated by activation of climbing fibers, calcium enters the postsynaptic cell through voltage-gated ion channels, raising intracellular calcium levels. Together, DAG and IP3 augment the calcium concentration rise by targeting IP3-sensitive receptors triggering release of calcium from intracellular stores as well as protein kinase C (PKC) activation (which is accomplished jointly by calcium and DAG). PKC phosphorylates AMPA receptors, which promotes their dissociation from scaffold proteins in the post-synaptic membrane and subsequent internalization. With the loss of AMPA receptors, the postsynaptic Purkinje cell response to glutamate release from parallel fibers is depressed. Calcium triggering in the cerebellum is a critical mechanism involved in long-term depression. Parallel fibre terminals and climbing fibres work together in a positive feedback loop for invoking high calcium release. LTD is involved in predictive control exerted by cerebellar circuitry and cerebellar reserve.

Ca2+ involvement
Further research has determined calcium's role in long-term depression induction. While other mechanisms of long-term depression are being investigated, calcium's role in LTD is a defined and well understood mechanism by scientists. High calcium concentrations in the post-synaptic Purkinje cells is a necessity for the induction of long-term depression. There are several sources of calcium signaling that elicit LTD: climbing fibres and parallel fibres which converge onto Purkinje cells. Calcium signaling in the post-synaptic cell involved both spatial and temporal overlap of climbing fibre induced calcium release into dendrites as well as parallel fibre induced mGluRs and IP3 mediated calcium release. In the climbing fibres, AMPAR-mediated depolarization induces a regenerative action potential that spreads to the dendrites, which is generated by voltage-gated calcium channels. Paired with PF-mediated mGluR1 activation results in LTD induction. In the parallel fibres, GluRs are activated by constant activation of the parallel fibres which indirectly induces the IP3 to bind to its receptor (IP3) and activate calcium release from intracellular storage. In calcium induction, there is a positive feedback loop to regenerate calcium for long-term depression. Climbing and parallel fibres must be activated together to depolarize the Purkinje cells while activating mGlur1s. Timing is a critical component to CF and PF as well, a better calcium release involves PF activation a few hundred milliseconds before CF activity.

AMPAR phosphorylation
There is a series of signaling cascades, MAPK, in the cerebellum that plays a critical role in cerebellum LTD. The MAPK cascade is important in information processing within neurons and other various types of cells. The cascade includes MAPKKK, MAPKK, and MAPK. Each is dual phosphorylated by the other, MAPKKK dual phosphorylates MAPKK and in turn dual phosphorylates MAPK. There is a positive feedback loop that results from a simultaneous input of signals from PF-CF and increases DAG and Ca2+ in Purkinje dendritic spines. Calcium and DAG activate conventional PKC (cPKC), which then activates MAPKKK and the rest of the MAPK cascade. Activated MAPK and Ca2+ activate PLA2, AA and cPKC creating a positive feedback loop. Induced cPKC phosphorylates AMPA receptors and are eventually removed from the postsynaptic membrane via endocytosis. The timescale is for this process is approximately 40 minutes. Overall, the magnitude of the LTD correlates with AMPAR phosphorylation.

Striatum
The mechanisms of LTD differ in the two subregions of the striatum. LTD is induced at corticostriatal medium spiny neuron synapses in the dorsal striatum by a high frequency stimulus coupled with postsynaptic depolarization, coactivation of dopamine D1 and D2 receptors and group I mGlu receptors, lack of NMDA receptor activation, and endocannabinoid activation.

In the prelimbic cortex of the striatum, three forms or LTD have been established. The mechanism of the first is similar to CA1-LTD: a low frequency stimulus induces LTD by activation of NMDA receptors, with postsynaptic depolarization and increased postsynaptic calcium influx. The second is initiated by a high frequency stimulus and is arbitrated by presynaptic mGlu receptor 2 or 3, resulting in a long term reduction in the involvement of P/Q-type calcium channels in glutamate release. The third form of LTD requires endocannabinoids, activation of mGlu receptors and repetitive stimulation of glutamatergic fibers (13 Hz for ten minutes), resulting in a long-term decrease in presynaptic glutamate release. It is proposed that LTD in GABAergic striatal neurons leads to a long-term decrease in inhibitory effects on the basal ganglia, influencing the storage of motor skills.

Visual cortex
Long-term depression has also been observed in the visual cortex, and it is proposed to be involved in ocular dominance. Recurring low-frequency stimulation of layer IV of the visual cortex or the white matter of the visual cortex causes LTD in layer III. In this form of LTD, low-frequency stimulation of one pathway results in LTD only for that input, making it homosynaptic. This type of LTD is similar to that found in the hippocampus, because it is triggered by a small elevation in postsynaptic calcium ions and activation of phosphatases. LTD has also been found to occur in this fashion in layer II. A different mechanism is at work in the LTD that occurs in layer V. In layer V, LTD requires low frequency stimulation, endocannabinoid signaling, and activation of presynaptic NR2B-containing NMDA receptors.

It has been found that paired-pulse stimulation (PPS) induces a form of homosynaptic LTD in the superficial layers of the visual cortex when the synapse is exposed to carbachol (CCh) and norepinephrine (NE).

The magnitude of this LTD is comparable to that which results from low frequency stimulation, but with fewer stimulation pulses (40 PPS for 900 low frequency stimulations). It is suggested that the effect of NE is to control the gain of NMDA receptor-dependent homosynaptic LTD. Like norepinephrine, acetylcholine is proposed to control the gain of NMDA receptor-dependent homosynaptic LTD, but it is likely to be a promoter of additional LTD mechanisms as well.

Prefrontal cortex
The neurotransmitter serotonin is involved in LTD induction in the prefrontal cortex (PFC). The serotonin system in the PFC plays an important role in regulating cognition and emotion. Serotonin, in cooperation with a group I metabotropic glutamate receptor (mGluR) agonist, facilitates LTD induction through augmentation of AMPA receptor internalization. This mechanism possibly underlies serotonin's role in the control of cognitive and emotional processes that synaptic plasticity in PFC neurons mediates.

Perirhinal cortex
Computational models predict that LTD creates a gain in recognition memory storage capacity over that of LTP in the perirhinal cortex, and this prediction is confirmed by neurotransmitter receptor blocking experiments. It is proposed that there are multiple memory mechanisms in the perirhinal cortex. The exact mechanisms are not completely understood, however pieces of the mechanisms have been deciphered. Studies suggest that one perirhinal cortex LTD mechanism involves NMDA receptors and group I and II mGlu receptors 24 hours after the stimulus. The other LTD mechanism involves acetylcholine receptors and kainate receptors at a much earlier time, about 20 to 30 minutes after stimulus.

Role of endocannabinoids
Endocannabinoids affect long-lasting plasticity processes in various parts of the brain, serving both as regulators of pathways and necessary retrograde messengers in specific forms of LTD. In regard to retrograde signaling, cannabinoid receptors function widely throughout the brain in presynaptic inhibition. Endocannabinoid retrograde signaling has been shown to effect LTD at corticostriatal synapses and glutamatergic synapses in the prelimbic cortex of the nucleus accumbens (NAc), and it is also involved in spike-timing-dependent LTD in the visual cortex. Endocannabinoids are implicated in LTD of inhibitory inputs (LTDi) within the basolateral nucleus of the amygdala (BLA) as well as in the stratum radiatum of the hippocampus. Additionally, endocannabinoids play an important role in regulating various forms of synaptic plasticity. They are involved in inhibition of LTD at parallel fiber Purkinje neuron synapses in the cerebellum and NMDA receptor-dependent LTD in the hippocampus.

Spike timing-dependent plasticity
Spike timing-dependent plasticity (STDP) refers to the timing of presynaptic and postsynaptic action potentials. STDP is a form of neuroplasticity in which a millisecond-scale change in the timing of presynaptic and postsynaptic spikes will cause differences in postsynaptic Ca2+ signals, inducing either LTP or LTD. LTD occurs when postsynaptic spikes precede presynaptic spikes by up to 20-50 ms. Whole-cell patch clamp experiments "in vivo" indicate that post-leading-pre spike delays elicit synaptic depression. LTP is induced when neurotransmitter release occurs 5-15 ms before a back-propagating action potential, whereas LTD is induced when the stimulus occurs 5-15 ms after the back-propagating action potential. There is a plasticity window: if the presynaptic and postsynaptic spikes are too far apart (i.e., more than 15 ms apart), there is little chance of plasticity. The possible window for LTD is wider than that for LTP – although it is important to note that this threshold depends on synaptic history.

When postsynaptic action potential firing occurs prior to presynaptic afferent firing, both presynaptic endocannabinoid (CB1) receptors and NMDA receptors are stimulated at the same time. Postsynaptic spiking alleviates the Mg2+ block on NMDA receptors. The postsynaptic depolarization will subside by the time an EPSP occurs, enabling Mg2+ to return to its inhibitory binding site. Thus, the influx of Ca2+ in the postsynaptic cell is reduced. CB1 receptors detect postsynaptic activity levels via retrograde endocannabinoid release.

STDP selectively enhances and consolidates specific synaptic modifications (signals), while depressing global ones (noise). This results in a sharpened signal-to-noise ratio in human cortical networks that facilitates the detection of relevant signals during information processing in humans.

Motor learning and memory
Long-term depression has long been hypothesized to be an important mechanism behind motor learning and memory. Cerebellar LTD is thought to lead to motor learning, and hippocampal LTD is thought to contribute to the decay of memory. However, recent studies have found that hippocampal LTD may not act as the reverse of LTP, but may instead contribute to spatial memory formation. Although LTD is now well characterized, these hypotheses about its contribution to motor learning and memory remain controversial.

Studies have connected deficient cerebellar LTD with impaired motor learning. In one study, metabotropic glutamate receptor 1 mutant mice maintained a normal cerebellar anatomy but had weak LTD and consequently impaired motor learning. However the relationship between cerebellar LTD and motor learning has been seriously challenged. A study on rats and mice proved that normal motor learning occurs while LTD of Purkinje cells is prevented by (1R-1-benzo thiophen-5-yl-2[2-diethylamino)-ethoxy] ethanol hydrochloride (T-588). Likewise, LTD in mice was disrupted using several experimental techniques with no observable deficits in motor learning or performance. These taken together suggest that the correlation between cerebellar LTD and motor learning may have been illusory.

Studies on rats have made a connection between LTD in the hippocampus and memory. In one study, rats were exposed to a novel environment, and homosynaptic plasticity (LTD) in CA1 was observed. After the rats were brought back to their initial environment, LTD activity was lost. It was found that if the rats were exposed to novelty, the electrical stimulation required to depress synaptic transmission was of lower frequency than without novelty. When the rat was put in a novel environment, acetylcholine was released in the hippocampus from the medial septum fiber, resulting in LTD in CA1. Therefore, it has been concluded that acetylcholine facilitates LTD in CA1.

LTD has been correlated with spatial learning in rats, and it is crucial in forming a complete spatial map. It suggested that LTD and LTP work together to encode different aspects of spatial memory.

New evidence suggests that LTP works to encode space, whereas LTD works to encode the features of space. Specifically, it is accepted that encoding of experience takes place on a hierarchy. Encoding of new space is the priority of LTP, while information about orientation in space could be encoded by LTD in the dentate gyrus, and the finer details of space could be encoded by LTD in the CA1.

Cocaine as a model of LTD in drug addiction
The addictive property of cocaine is believed to occur in the nucleus accumbens (NAc). After chronic cocaine use, the amount of AMPA receptors relative to NMDA receptors decreases in the medium spiny neurons in the NAc shell. This decrease in AMPA receptors is thought to occur through the same mechanism as NMDAR-dependent LTD, because this form of plasticity is reduced after cocaine use. After, the amount of AMPA receptors is ramped up in the NAc neurons during withdrawal. This is possibly due to homeostatic synaptic scaling. This increase in AMPA receptors causes a hyperexcitability in the NAc neurons (GABAergic MSNs). This leads to an increase of GABA release by projections from the NAc to the ventral tegmental area (VTA), making the dopaminergic neurons in the VTA less likely to fire, and thus resulting in the symptoms of withdrawal.

Current research
Research on the role of LTD in neurological disorders such as Alzheimer's disease (AD) is ongoing. It has been suggested that a reduction in NMDAR-dependent LTD may be due to changes not only in postsynaptic AMPARs but also in NMDARs, and these changes are perhaps present in early and mild forms of Alzheimer-type dementia.

Additionally, researchers have recently discovered a new mechanism (which involves LTD) linking soluble amyloid beta protein (Aβ) with the synaptic injury and memory loss related to AD. While Aβ's role in LTD regulation has not been clearly understood, it has been found that soluble Aβ facilitates hippocampal LTD and is mediated by a decrease in glutamate recycling at hippocampal synapses. Excess glutamate is a proposed contributor to the progressive neuronal loss involved in AD. Evidence that soluble Aβ enhances LTD through a mechanism involving altered glutamate uptake at hippocampal synapses has important implications for the initiation of synaptic failure in AD and in types of age-related Aβ accumulation. This research provides a novel understanding of the development of AD and proposes potential therapeutic targets for the disease. Further research is needed to understand how soluble amyloid beta protein specifically interferes with glutamate transporters.

In the field of research of cerebellum disorders, auto-antigens are involved in molecular cascades for induction of LTD of synaptic transmissions between parallel fibers (PFs) and Purkinje cells (PCs), a mechanism of synaptic plasticity in the cerebellum. Anti-VGCC, anti-mGluR1, and anti-GluR delta Abs-associated cerebellar ataxias share one common pathophysiological mechanism: a deregulation in PF-PC LTD. This causes an impairment of restoration or maintenance of the internal model hold by the cerebellum and triggers cerebellar ataxias. These diseases are LTDpathies.

The mechanism of long-term depression has been well characterized in limited parts of the brain. However, the way in which LTD affects motor learning and memory is still not well understood. Determining this relationship is presently one of the major focuses of LTD research.

Neurodegeneration
Neurodegenerative diseases research remains inconclusive as to the mechanisms that triggers the degeneration in the brain. New evidence demonstrates there are similarities between the apoptotic pathway and LTD which involves the phosphorylation/activation of GSK3β. NMDAR-LTD(A) contributes to the elimination of excess synapses during development. This process is downregulated after synapses have stabilized, and is regulated by GSK3β. During neurodegeneration, there is the possibility that there is deregulation of GSK3β resulting in 'synaptic pruning'. If there is excess removal of synapses, this illustrates early signs of neurodegeration and a link between apoptosis and neurodegeneration diseases.

title: Long-term depression


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Neocortex

The neocortex, also called the neopallium, isocortex, or the six-layered cortex, is a set of layers of the mammalian cerebral cortex involved in higher-order brain functions such as sensory perception, cognition, generation of motor commands, spatial reasoning and language. The neocortex is further subdivided into the true isocortex and the proisocortex.

In the human brain, the cerebral cortex consists of the larger neocortex and the smaller allocortex, respectively taking up 90% and 10%. The neocortex is made up of six layers, labelled from the outermost inwards, I to VI.

Etymology
The term is from cortex, Latin, "bark" or "rind", combined with neo-, Greek, "new". Neopallium is a similar hybrid, from Latin pallium, "cloak". Isocortex and allocortex are hybrids with Greek isos, "same", and allos, "other".

Anatomy
The neocortex is the most developed in its organisation and number of layers, of the cerebral tissues. The neocortex consists of the grey matter, or neuronal cell bodies and unmyelinated fibers, surrounding the deeper white matter (myelinated axons) in the cerebrum. This is a very thin layer though, about 2–4 mm thick. There are two types of cortex in the neocortex, the proisocortex and the true isocortex. The pro-isocortex is a transitional area between the true isocortex and the periallocortex (part of the allocortex). It is found in the cingulate cortex (part of the limbic system), in Brodmann's areas 24, 25, 30 and 32, the insula and the parahippocampal gyrus.

Of all the mammals studied to date (including humans), a species of oceanic dolphin known as the long-finned pilot whale has been found to have the most neocortical neurons.

Geometry
The neocortex is smooth in rodents and other small mammals, whereas in elephants, dolphins and primates and other larger mammals it has deep grooves (sulci) and ridges (gyri). These folds allow the surface area of the neocortex to be greatly increased. All human brains have the same overall pattern of main gyri and sulci, although they differ in detail from one person to another. The mechanism by which the gyri form during embryogenesis is not entirely clear, and there are several competing hypotheses that explain gyrification, such as axonal tension, cortical buckling or differences in cellular proliferation rates in different areas of the cortex.

Layers
The neocortex contains both excitatory (~80%) and inhibitory (~20%) neurons, named for their effect on other neurons. The human neocortex consists of hundreds of different types of cells. The structure of the neocortex is relatively uniform (hence the alternative names "iso-" and "homotypic" cortex), consisting of six horizontal layers segregated principally by cell type and neuronal connections. However, there are many exceptions to this uniformity; for example, layer IV is small or missing in the primary motor cortex. There is some canonical circuitry within the cortex; for example, pyramidal neurons in the upper layers II and III project their axons to other areas of neocortex, while those in the deeper layers V and VI often project out of the cortex, e.g. to the thalamus, brainstem, and spinal cord. Neurons in layer IV receive the majority of the synaptic connections from outside the cortex (mostly from thalamus), and themselves make short-range, local connections to other cortical layers. Thus, layer IV is the main recipient of incoming sensory information and distributes it to the other layers for further processing.

Cortical columns
The neocortex is often described as being arranged in vertical structures called cortical columns, patches of neocortex with a diameter of roughly 0.5 mm (and a depth of 2 mm, i.e., spanning all six layers). These columns are often thought of as the basic repeating functional units of the neocortex, but their many definitions, in terms of anatomy, size, or function, are generally not consistent with each other, leading to a lack of consensus regarding their structure or function or even whether it makes sense to try to understand the neocortex in terms of columns.

Function
The neocortex is derived embryonically from the dorsal telencephalon, which is the rostral part of the forebrain. The neocortex is divided into regions demarcated by the cranial sutures in the skull above, into frontal, parietal, occipital, and temporal lobes, which perform different functions. For example, the occipital lobe contains the primary visual cortex, and the temporal lobe contains the primary auditory cortex. Further subdivisions or areas of neocortex are responsible for more specific cognitive processes. In humans, the frontal lobe contains areas devoted to abilities that are enhanced in or unique to our species, such as complex language processing localized to the ventrolateral prefrontal cortex (Broca's area). In humans and other primates, social and emotional processing is localized to the orbitofrontal cortex.

The neocortex has also been shown to play an influential role in sleep, memory and learning processes. Semantic memories appear to be stored in the neocortex, specifically the anterolateral temporal lobe of the neocortex. It is also involved in instrumental conditioning; responsible for transmitting sensory information and information about plans for movement to the basal ganglia. The firing rate of neurons in the neocortex also has an effect on slow-wave sleep. When the neurons are at rest and are hyperpolarizing, a period of inhibition occurs during a slow oscillation, called the down state. When the neurons of the neocortex are in the excitatory depolarizing phase and are firing briefly at a high rate, a period of excitation occurs during a slow oscillation, called the up state.

Clinical significance
Lesions that develop in neurodegenerative disorders, such as Alzheimer's disease, interrupt the transfer of information from the sensory neocortex to the prefrontal neocortex. This disruption of sensory information contributes to the progressive symptoms seen in neurodegenerative disorders such as changes in personality, decline in cognitive abilities, and dementia. Damage to the neocortex of the anterolateral temporal lobe results in semantic dementia, which is the loss of memory of factual information (semantic memories). These symptoms can also be replicated by transcranial magnetic stimulation of this area. If damage is sustained to this area, patients do not develop anterograde amnesia and are able to recall episodic information.

Evolution
The neocortex is the newest part of the cerebral cortex to evolve (hence the prefix neo meaning new); the other part of the cerebral cortex is the allocortex. The cellular organization of the allocortex is different from the six-layered neocortex. In humans, 90% of the cerebral cortex and 76% of the entire brain is neocortex.

For a species to develop a larger neocortex, the brain must evolve in size so that it is large enough to support the region. Body size, basal metabolic rate and life history are factors affecting brain evolution and the coevolution of neocortex size and group size. The neocortex increased in size in response to pressures for greater cooperation and competition in early ancestors. With the size increase, there was greater voluntary inhibitory control of social behaviors resulting in increased social harmony.

The six-layer cortex appears to be a distinguishing feature of mammals; it has been found in the brains of all mammals, but not in any other animals. There is some debate, however, as to the cross-species nomenclature for neocortex. In avians, for instance, there are clear examples of cognitive processes that are thought to be neocortical in nature, despite the lack of the distinctive six-layer neocortical structure. Evidence suggest the avian pallium to be broadly equivalent to the mammalian neocortex. In a similar manner, reptiles, such as turtles, have primary sensory cortices. A consistent, alternative name has yet to be agreed upon.

Neocortex ratio
The neocortex ratio of a species is the ratio of the size of the neocortex to the rest of the brain. A high neocortex ratio is thought to correlate with a number of social variables such as group size and the complexity of social mating behaviors. Humans have a large neocortex as a percentage of total brain matter when compared with other mammals. For example, there is only a 30:1 ratio of neocortical gray matter to the size of the medulla oblongata in the brainstem of chimpanzees, while the ratio is 60:1 in humans.

license: Creative Commons - Attribution Share-Alike - https://creativecommons.org/licenses/by-sa/4.0/

title: Neocortex


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Single-pair high-speed digital subscriber line

Single-pair high-speed digital subscriber line (SHDSL) is a form of symmetric digital subscriber line (SDSL), a data communications technology for equal transmit and receive (i.e. symmetric) data rate over copper telephone lines, faster than a conventional voiceband modem can provide. As opposed to other DSL technologies, SHDSL employs trellis-coded pulse-amplitude modulation (TC-PAM). As a baseband transmission scheme, TC-PAM operates at frequencies that include those used by the analog voice plain old telephone service (POTS). As such, a frequency splitter, or DSL filter, cannot be used to allow a telephone line to be shared by both an SHDSL service and a POTS service at the same time. Support of symmetric data rates made SHDSL a popular choice by businesses for private branch exchange (PBX), virtual private network (VPN), web hosting and other data services.

SHDSL features symmetrical data rates in both the upstream and downstream directions, from 192 kbit/s to 2,312 kbit/s of payload in 8 kbit/s increments for one pair and 384 kbit/s to 4,624 kbit/s in 16 kbit/s increments for two pairs of wires. The reach varies according to the loop rate and noise conditions (more noise or higher rate means decreased reach) and may be up to 3,000 meters. The two pair feature may alternatively be used for increased reach applications by keeping the data rate low. Halving the data rate per pair will provide similar speeds to single pair lines while increasing the error/noise tolerance.

With the 32-TC-PAM modulation scheme described in Annexes F and G, symmetric data rates of up to 5,696 kbit/s are permitted on one pair in the optional extended SHDSL mode. Up to four pairs of wires may be bonded using M-pair bonding to produce data rates as high as M5,696 kbit/s. By using four bonded wire pairs, a single SHDSL interface can transmit up to 22,784 kbit/s.

The SHDSL payload may be either 'clear channel' (unstructured), T1 or E1 (full rate or fractional), multiple ISDN Basic Rate Interface (BRI), Asynchronous Transfer Mode (ATM) cells or Ethernet packets. A 'dual bearer' mode allows a mixture of two separate streams (e.g. T1 and ATM) to share the SHDSL bandwidth.

SHDSL standards
The industry standard for SHDSL is defined by ITU-T recommendation G.991.2. This was first published in February 2001. SHDSL equipment is also known by the standard's draft name of G.SHDSL. Major updates to G.991.2 were released in December 2003. Equipment conforming to the 2003 version of G.991.2 is often referred to by the standard's draft name of G.SHDSL.bis or just SHDSL.bis. The updated G.991.2 features:
 * Optional support for up to four copper pair connections (M-pair)
 * Optional extensions to allow user data rates up to 5696 kbit/s per pair, described in Annexes F and G
 * Optional support for dynamic rate repartitioning, allowing flexible change of the SHDSL data rate without service interruption, described in Annex E.10.3
 * New payload definitions including Ethernet packet transfer mode (PTM), described in Annex E.11

SHDSL supersedes the older HDSL symmetric DSL technology defined in ITU-T G.991.1. SHDSL has largely been replaced by VDSL2 because of greater bandwidth, less interference and greater utilization.

In Europe, a variant of SHDSL was standardized by the European Telecommunications Standards Institute (ETSI) using the name 'SDSL'. This ETSI variant is compatible with the ITU-T SHDSL standardized regional variant for Europe and must not be confused with the usage of the term SDSL in North America to refer to symmetric digital subscriber line.


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List of wiki software

This is a list of wiki software programs. They are grouped by use case: standard wiki programs, personal wiki programs, hosted-only wikis, wiki-based content management software, and wiki-based project management software. They are further subdivided by the language of implementation: JavaScript, Java, PHP, Python, Perl, Ruby, and so on.

JavaScript-based

 * TiddlyWiki is a HTML-JavaScript-based server-less wiki in which the entire site/wiki is contained in a single file, or as a Node.js-based wiki application. It is designed for maximum customization possibilities.
 * Wiki.js is an open-source, Node.js-based wiki application using git as the back end storage mechanism and automatically syncs with any git repository. It provides a visual Markdown editor with assets management, authentication system and a built-in search engine.

Java-based

 * XWiki is a free wiki software platform written in Java with a design emphasis on extensibility. XWiki is an enterprise wiki engine with a complete wiki feature set (version control, attachments, etc.) and a database engine and programming language which allows database driven applications to be created using the wiki interface.

Perl-based

 * Foswiki is a structured wiki, typically used to run a collaboration platform, knowledge or document management system a knowledge based, or team portal. is a structured wiki, which enables users to create "wiki applications".
 * ikiwiki, a "wiki compiler" - can use Subversion or git as the back end storage mechanism. ikiwiki converts wiki pages into HTML pages suitable for publishing on a website.
 * TWiki is a flexible, powerful, secure, simple Enterprise wiki and application platform. is a structured wiki, typically used to run a project development space, a document management system, a knowledge base, or any other groupware tool. Also available as a VMware appliance.
 * UseModWiki is a wiki software written in Perl and licensed under General Public License. Created by Clifford Adams in 2000, it is a clone of AtisWiki.
 * WikiWikiWeb, the first wiki and its associated software.

PHP-based

 * BookStack is released under the MIT License. It uses the ideas of books to organize pages and store information.
 * DokuWiki is a wiki application licensed under GPLv2 and written in PHP. It is aimed at the documentation needs of a small company. DokuWiki was built for small companies and organizations that need a simple way to manage information, build knowledge bases and collaborate. It uses plain text files and has a simple but powerful syntax which ensures the datafiles remain readable outside the wiki.
 * MediaWiki is a free and open-source wiki software package written in PHP. It serves as the platform for Wikipedia and the other Wikimedia projects. MediaWiki is used for projects run by the Wikimedia Foundation, which operates Wikipedia. It is also publicly available for use in other wikis, and has widespread popularity among smaller, non-Wikimedia wikis. MediaWiki is a free and open-source wiki software. It was developed for use on Wikipedia in 2002, and given the name "MediaWiki" in 2003.
 * Semantic MediaWiki lets you store and query data within the wiki's pages like a database. It is also designed to ease and combine collaborative authoring within a wiki with semantic technology.
 * BlueSpice extends MediaWiki in usability, quality management, process support, administration, editing and security.
 * MindTouch is an application that began as a fork of MediaWiki; it has a C# back-end and a PHP front-end.
 * PhpWiki is a WikiWikiWeb clone in PHP.
 * PmWiki is a PHP-based wiki. Features include: GPL-licensed, easy installation/customization, designed for collaborative authoring and maintenance of web sites, and support for internationalization. Does not require a database.

Python-based

 * LocalWiki is a wiki engine based on Django, with mapping features and a WYSIWYG editor. The LocalWiki project was founded by DavisWiki creators Mike Ivanov and Philip Neustrom and is a 501 nonprofit organization based in San Francisco.
 * MoinMoin is a wiki engine written in Python.
 * Trac is an enhanced wiki and issue tracking system for software development projects.

Ruby-based

 * Gollum uses git as the backend storage mechanism. It is written mostly in Ruby and was originally used as GitHub's wiki system.

Other languages

 * Cliki is written in Common Lisp.
 * FlexWiki is written in C#, uses the .NET framework, and stores data in files or Microsoft SQL Server. Development stopped in 2009.
 * Swiki is written in Squeak. It runs on common platforms, including Macintosh, Windows, Linux, and others.
 * Wiki Server is proprietary software distributed with Mac OS X Server.

Personal wiki software

 * ConnectedText was a commercial Windows-based personal wiki system with features including full text searches, visual link tree, customizable interface, image and file control, CSS-based page display, exports to HTML and HTML Help, and plug-ins.
 * Journler was a free, open-source personal information manager with personal wiki features for OS X.
 * MyInfo is a commercial, Windows-based personal information manager with wiki features.
 * Obsidian is a knowledge base and note-taking software application that operates on Markdown files.
 * TiddlyWiki is a free, open-source personal use (single-machine) wiki based on HTML/JavaScript for any browser and OS. It supports customization and a wide range of add-ons.
 * Vimwiki is a personal wiki for the text editor Vim. It operates on interlinked, plain text files written in one of several markup languages and provides features such as HTML export, search, outlined notes and tasks, tagging and auto-formatted tables.
 * WhizFolders was a commercial Windows-based personal wiki software with rich text wiki items that support inserting links to other wiki items or external files.
 * Zim is a free, open-source standalone wiki based on Python and GTK with a WYSIWYG editor.

Hosted-only software

 * Knowledge Plaza is a knowledge management tool that provides both wiki environments for collaborative topic/project work and an enterprise bookmarking tool.

Java-based

 * ConcourseConnect is a freely available J2EE application made by Concursive which brings together Corporate Social Networking, Online Community, Business directory, and Customer relationship management capabilities. Features include wiki, blog, document management, ratings, reviews, online classified advertising, and project management modules. The wiki allows both wiki markup and WYSIWYG editing.
 * Confluence is a commercial J2EE application which combines wiki and some blog functionality. Its features include PDF page export and page refactoring, and it can be run on any application server using any RDBMS backend.
 * IBM Connections is an Enterprise Social Software made by IBM which combines Wikis, Blogs, Files, Forums, Microblogging, Social Analytics, and document management.
 * Jive (formerly known as Clearspace, Jive SBS and Jive Engage) is a commercial J2EE application, made by Jive Software, which combines wiki, blog and document management functionality. Jive uses WYSIWYG editing, and includes workflow management.
 * Liferay is an open source enterprise portal project with a built-in web content management and web application framework. Core portlets offer a great number of functionalities, including Wiki (both Creole and MediaWiki syntax).
 * Mindquarry creates a WYSIWYG wiki for each team. It is built using Apache Cocoon and thus based on Java (Mozilla Public License)
 * Traction TeamPage is a commercial enterprise wiki also incorporating blog, project management, document management, discussion and tagging capabilities. The wiki has a draft moderation capability allowing administrators to indicate who can read published vs. draft versions, and who can publish vs. author and edit. The dynamic view architecture allows for easy organization of pages and to collect any set of pages for view, email or export. It is based on the principles of Douglas Engelbart's On-Line System (NLS) which aggregates multiple blog/wiki spaces using a sophisticated permission and inline comment model.
 * XWiki includes the standard wiki functionality as well as WYSIWYG editing, OpenDocument based document import/export, semantic annotations and tagging, and advanced permissions management.

Perl-based

 * Socialtext is a company based in Palo Alto, California, that produces enterprise social software, enterprise wiki and weblog engine partially derived from open-source Kwiki. Socialtext is available as a hosted service, or a dedicated hardware appliance.

PHP-based

 * Drupal installations can be configured as wikis with MediaWiki-style wiki markup.
 * Tiki Wiki CMS Groupware is one of the larger and more ambitious wiki development projects, including a variety of additional groupware features (message forums, articles, etc.).

Other languages

 * Microsoft SharePoint is a web-based collaborative platform that integrates with Microsoft Office. Launched in 2001, SharePoint is primarily sold as a document management and storage system, but the product is highly configurable and its usage varies substantially among organizations. It has built-in wiki support. It is built on ASP.NET, C# language and Microsoft SQL Server.
 * Telligent, A Verint Company is an enterprise collaboration and community software business founded in 2004 by Rob Howard. The company changed its name to Zimbra, Inc in September 2013 after completing the acquisition of Zimbra from VMWare. In August 2015 Zimbra's Telligent business was acquired by Verint Systems.

Project management software with wiki functionality

 * Altova MetaTeam integrates a wiki and glossary with project management, collaborative decision-making and team performance management
 * Code Co-op is a distributed revision control system with wiki functionality.
 * Fossil is a distributed revision control system that integrates a distributed wiki capability, written in C.
 * Redmine is a project management web application.
 * Trac integrates simple issue tracking and an interface to Subversion.

title: List of wiki software


text:
I Feel Sick

I Feel Sick is a comic book created by artist Jhonen Vasquez, with colors by Rosearik Rikki Simons. Published in August 1999 through May 2000, it is a spin-off of Vasquez's comic book series Johnny the Homicidal Maniac. I Feel Sick revolves around Devi D, a graphic designer who must face the same supernatural and psychological forces that drove Johnny C. to lunacy.

Published by Slave Labor Graphics, it was originally intended as a single paperback but was split into two issues. Vasquez said the creation process of I Feel Sick was cathartic. Devi's problems working for Nerve Publishing and neglecting her own work are reminiscent of the pressure Vasquez experienced working on Invader Zim, an animated television series he created for Nickelodeon.

Issue 1
The first issue is published through Slave Labor Graphics in November 1999. It is later republished with paperback.

Summary
The series begins as Devi attempts to destroy her own painting, but finds the painting untouched afterward. Tenna, her neighbor and friend, comes upstairs to check on her. This leads to a flashback about a date Devi had with a boy named Eddie. After the two fail to connect, Devi asks to go home and Eddie makes a forceful move on her while driving. The two crash into a tree where they are trapped in the car. Eddie has lost an eye and has glass shards inside of his brain. The only thing keeping him alive is the thought he still has a chance of sleeping with Devi. They are trapped in his car overnight until Eddie is eventually killed by a deployed airbag.

The flashback ends and Devi explains that the painting was one she never finished, and it has started talking to her. She has nicknamed the painting "Sickness," and the only way to silence it is by working. Tenna suggests that she is just working too hard, but Devi believes supernatural forces are interfering with her painting, and past experiences have given her good reason to isolate herself. She tells a story about another date with a man who defecated himself at the dinner table (as seen in Issue 2 of Johnny the Homicidal Maniac). In another flashback, Devi is approached in a nightclub by a man dressed as a vampire. He tells her about his strange obsession with vampires. When he uses a smoke bomb to dramatically leave the conversation, he sets himself on fire. On another date, Devi joked about her date being a zombie, and he bites a waiter's brain out of his skull.

Tenna is still unconvinced and asks why the "spooky painting" wants to make her go insane. Devi doesn't know, but ever since she started a new freelance job, things have gotten worse. Constant distractions stop her from painting, like phone calls and people coming over. Even Tenna has become a huge distraction, and Devi asks her to leave.

Alone now, Devi asks the painting what it wants and why it's distracting her from her work. The painting says it's simply a voice in her head and not to bother fighting. It and its colleagues are professionals who have done this before. Devi vows to work as hard as she can until the painting dries up, and she stops talking. However, she accidentally injures her hands, meaning she can no longer paint to fight Sickness.

Issue 2
The second issue is first published through Slave Labor Graphics in January 2000, then experienced republishings through Slave Labor Graphics from 2003 to 2004. The latest edition (sixth edition) is published with paperback through SLG Publishing in January 2008.

Summary
Devi promises to fight Sickness even without using her hands. Sickness says she is not the first person to catch them, one being the person who introduced the force to her. Devi realizes she is late for a meeting about a job illustrating a children's book and rushes to meet her eccentric new boss, Mr. Nerves. He orders several outlandish changes to her painting for the book. During his lecture, Devi has a flashback to her date with Johnny the Homicidal Maniac. While overlooking the town, Johnny asks what happens when someone loses their defining trait, in this case, Johnny's ability to paint.

After connecting Johnny's story with her own, Devi quits her job and rushes home, determined to beat Sickness. Several distractions in her apartment's hallway hinder her progress, and her morbidly obese neighbor blocks the hallway. Devi attempts to squeeze by and gets trapped. She hears a voice that claims to be the neighbor's fat. It tells Devi that it's psychic and will attempt to help her. It shows her a scene from her childhood when a boy by the name of Spidgey Simons gives her a Valentine's Day card. Devi coughs chalk into his face and crumples up the card. The fat says Spidgey later died of a chalk-induced asthma attack, and he was the only boy that could ever understand her.

Devi escapes and makes it to her room, finding Sickness now in the form of a doll. Sickness reveals it is using Devi's mind to grow a real body, and if Devi tries to resist again, it will kill her. After Devi quit her job, Sickness had to accelerate its plans. It offers her powers similar to Johnny's, and Devi appears to accept them. When Sickness lets down its guard, Devi pins it to a canvas with a paintbrush and removes its eyeballs. Devi says she has won and has complete control over her mind again. Now that she has Sickness's eyes, it will become a tortured audience to her life. The series ends with Devi and Tenna overlooking the town, watching a plane crash into their apartment building.

Devi D.
The protagonist, Devi, is an introvert attacked by the same forces attacking Johnny, the protagonist of Johnny the Homicidal Maniac. He was her love interest until he tried to kill her to "immortalize the moment". Their date left Johnny with severe head trauma and made Devi into a recluse. Since then, Devi's love life has consisted of a string of disastrous dates.

Since her appearance in JtHM issue 7, she has quit her job at the local bookstore to become a graphic designer and cover artist for Nerve Publishing.

Tenna
Tenna is Devi's friend and neighbor who owns a squeaky toy named Spooky whom she talks to constantly. She believes Devi's problems stem from her lack of social contact. She first appears in the fourth issue of JtHM, then called Tonja. A doll version of Spooky appears in Layla Miller's room during the Marvel Comics House of M event.

Psychic Fat Lady
An obese woman with psychic fat who shares her visions that Devi will die in a plane crash. She lives downstairs from Devi and hasn't left her apartment for at least a decade.

Eddie
One of Devi's dates, who gets in a car accident with her, trapping the two inside the vehicle.

Eric
A teenager obsessed with vampires. He first appeared in a Meanwhile section in JTHM and also briefly in Invader Zim, in another form.

Mr. Nevers
Devi's boss in the Graphic Arts department of Nerve Publishing. He received a lobotomy to remove the creative centers of his brain.

Spidgey Simons
According to the psychic fat, the only boy who would ever truly understand Devi and her last chance at true love. She rejected his Valentine's Day card in first grade and coughed chalk into his face. He later died of a chalk-induced asthma attack.

Johnny C.
The main character from Johnny the Homicidal Maniac, Johnny C. makes a cameo appearance. In a flashback, Devi remembers what led to their disastrous date in issue #2 of JtHM and realizes Johnny had the same sickness she has.

title: I Feel Sick


text:
User talk:Cyberied

Hi there. Welcome to Wikipedia! Thanks for all your work on stuff related to neuroscience. If you want, drop us a note at New user log to introduce yourself.

If you need editing help, visit How does one edit a page. For format questions, visit our manual of style

Some time when you're bored, you can read through our policies and guidelines. If you made any edits before you got an account, you might be interested in assigning those to your username.

If you have any other questions about the project then check out Help or add a question to the Village pump. You can also drop me a question on my talk page.

Happy editing, Isomorphic 08:02, 25 Feb 2004 (UTC)
 * Thanks for your note on the new user log. Glad to have you here.  Isomorphic 19:22, 25 Feb 2004 (UTC)

Hey, I would like to start working on some of the neuro stuff this year, but probably not right now... Maybe in summer quarter. For now I'm just doing little stuff. I'll keep an eye on what you're up to though and if you want any specific backup I'll do the best I can. My best subjects are probably electrophysiology, channelology, gap junctions, sensory systems (especially visual, auditory), EEG, and vesicle cycling. --Chinasaur 17:24, Feb 26, 2004 (UTC)

 * We really need to get an article on the basilar membrane and auditory transduction. Right now the only page I could find was ear and their information on the cochlea is pretty much wrong.  I'll work on it Sunday; pass it on to other neuroscience people if you know any.  This topic needs a lot of work!

 * Chinasaur 20:17, Feb 28, 2004 (UTC)

title: User talk:Cyberied


text:
Attacker

In some team sports, an attacker is a specific type of player, usually involved in aggressive play. Heavy attackers are, usually, placed up front: their goal is to score the most possible points for the team. In association football, attackers are also referred to as forwards or strikers.

title: Attacker


text:
Wikipedia:WikiProject Film/Film awards task force

Welcome to the Film awards task force of WikiProject Film! We are a task force dedicated to building a comprehensive and detailed guide on Wikipedia about notable film awards.

Goals:
 * To standardize the awards articles in Wikipedia.
 * To improve Wikipedia coverage of film awards by adding, expanding and improving relevant articles
 * To serve as a central point of discussion for issues related to film awards articles

Scope
This task force is a merger of the old Academy Awards WikiProject, with an expansion of the scope to cover all notable film awards. (As such, much task force material is currently biased towards the Academy Awards - however, these articles can just as easily serve as model articles for other film awards articles.) The articles relevant to this work group should all be contained in Category:Film awards or one of its subcategories.

Tagging and assessment
Any article related to this task force should be marked by adding  to the Film project banner at the top of its talk page (see the project banner instructions for more details on the exact syntax). This will automatically place it into Category:Film awards task force articles.

Templates

 * For main project templates, see the sidebar.
 * Userbox: User Film awards task force

Infobox

 * Number: ## format, just the number, the template will automatically convert it to an ordinal.
 * Image: Any image that best represents that particular ceremony (favorably a ceremony poster).
 * Date: Date at which the ceremony occurred
 * Site: Venue and city where the ceremony occurred
 * Network: The television network where it was broadcasted in the United States
 * Preshow: Began in the 71st Awards - Include who participated
 * Host: The host of the ceremony
 * Director: The director of the ceremony
 * Duration: How long it lasted
 * Ratings: How many people on average watched the telecast and the percentage of households tuning in based on Nielsen ratings

Footers

 * Use Academy Awards to create:

 * For Best Picture winners, use AcademyAwardBestPicture:

 * Note: Adding "1927-1940," "1941-1960," "1961-1980," "1981-2000," or "2001-2020" will give a more specific template box.

Categories
Add categories for each Academy Awards ceremony article in the following format:

 * Academy Awards

Note that the second Category, yyyy is replaced by the year of film release on which the ceremonies were based. The annual film awards categories in Wikipedia were based on film release years, not the years each ceremony was held.

For example, the 75th Academy Awards ceremony was held in 2003, but awarded films released in 2002. Therefore, the categories for that article are:

To-do

 * Tag articles and re-tag articles originally given WP Academy Awards tags.
 * Recruit interested editors.
 * Collect categories, resource links, and templates.
 * Expand the open task listing above.
 * Peer review the article Golden Film
 * Add things here!

Resources

 * Add things here!

Annotated bibliography
Please use the following format when adding works:
 * Content:
 * Reviews:
 * Editor comments:
 * Reviews:
 * Editor comments:
 * Editor comments:

Template for Academy Awards pages

 * Note: Below template is from the 53rd Academy Awards.

Official websites

 * Academy Award ceremony website (should be placed on ongoing ceremony and removed when next ceremony occurs)
 * Academy Press Release (corresponding to year ceremony was held. Example: )
 * List of eligible films (list of films eligible for the particular ceremony. Example: )

News resources

 * ABC News: Academy Awards Coverage (Example: )
 * CNN Academy Awards Spotlight (Example: )
 * Yahoo! Movies Academy Awards (Remove to proper ceremony. Example: )

Analysis

 * Tim Dirk's film analysis (Example: )


text:
Inverted sugar syrup

Inverted sugar syrup, also called invert syrup, invert sugar, simple syrup, sugar syrup, sugar water, bar syrup, syrup USP, or sucrose inversion, is a syrup mixture of the monosaccharides glucose and fructose, that is made by hydrolytic saccharification of the disaccharide sucrose. This mixture's optical rotation is opposite to that of the original sugar, which is why it is called an invert sugar.

It is 1.3x sweeter than table sugar, and foods that contain invert sugar retain moisture better and crystallize less easily than do those that use table sugar instead. Bakers, who call it invert syrup, may use it more than other sweeteners.

Additives
Commercially prepared enzyme-catalyzed solutions are inverted at 60 °C. The optimum pH for inversion is 5.0. Invertase is added at a rate of about 0.15% of the syrup's weight, and inversion time will be about 8 hours. When completed the syrup temperature is raised to inactivate the invertase, but the syrup is concentrated in a vacuum evaporator to preserve color.

Though inverted sugar syrup can be made by heating table sugar in water alone, the reaction can be sped up by adding lemon juice, cream of tartar, or other catalysts, often without changing the flavor noticeably. Common sugar can be inverted quickly by mixing sugar and citric acid or cream of tartar at a ratio of about 1000:1 by weight and adding water. If lemon juice, which is about five percent citric acid by weight, is used instead then the ratio becomes 50:1. Such a mixture, heated to 114 °C and added to another food, prevents crystallization without tasting sour.

Commercially prepared hydrochloric-acid catalyzed solutions may be inverted at the relatively low temperature of 50 °C. The optimum pH for acid-catalyzed inversion is 2.15. As the inversion temperature is increased, the inversion time decreases. They are then given a pH neutralization when the desired level of inversion is reached.

In confectionery and candy making, cream of tartar is commonly used as the acidulant, with typical amounts in the range of 0.15–0.25% of the sugar's weight. The use of cream of tartar imparts a honey-like flavor to the syrup. After the inversion is completed, it may be neutralized with baking soda using a weight of 45% of the cream of tartar's weight.

For fermentation
All constituent sugars (sucrose, glucose, and fructose) support fermentation, so invert sugar solutions of any composition can be fermented.

Syrup is used to feed microbiological life, which requires oxygen found in the water. For example, kombucha is produced by fermenting inverted sugar syrup with tea using a symbiotic culture of bacteria and yeast (SCOBY), and yeast in winemaking is used for ethanol fermentation. Cold water can hold more dissolved oxygen than warm water, but granulated sugar does not dissolve easily in cold water.

Water in a container with wide bottom surface area allows for faster dissolving of the sucrose, which only has to be mixed a few times periodically to form a homogeneous solution. Also, a mixer or blender may be used to rotate the sugar, in turns, if necessary.

In other foods and products

 * Honey which is mostly a mixture of glucose and fructose, being similar to invert syrup therefore, can remain a liquid for longer periods of time.
 * Jam contains invert sugar formed by the heating process and the acid content of the fruit. This sugar preserves the jam for long periods of time.
 * Golden syrup is a syrup of about 55% invert syrup and 45% table sugar (sucrose).
 * Fondant filling for chocolates is unique in that the conversion enzyme is added, but not activated by acidification (microenvironment pH adjustment) or cofactor addition depending on the enzymes, before the filling is enrobed with chocolate. The very viscous (and thus formable) filling then becomes less viscous with time, giving the creamy consistency desired. This results from the sub-optimal enzymes conditions purposely created by withholding activation factors, which allows only a fraction of the enzymes to be active, or allows all enzymes to proceed at only a fraction of the biological rate [biologically, it's realistically a combination of both: a reduced number of functional enzymes, with the ones that do function having reduced catalytic kinetics/rates].
 * Cadbury Creme Eggs are filled with inverted sugar syrup produced by processing fondant with invertase.
 * Sour Patch Kids also contain inverted sugar to add sweet flavor.

Sweetened beverages
Inverted sugar syrup is the basis in sweetened beverages.

 * Sweet reserve is a wine term referring to a portion of selected unfermented grape must, free of microorganisms, to be added to wine as a sweetening component. When wine ferments, glucose is fermented at a faster rate than fructose. Thus, arresting fermentation after a significant portion of the sugars have fermented results in a wine where the residual sugar consists mainly of fructose, while the use of sweet reserve will result in a wine where the sweetness comes from a mixture of glucose and fructose.
 * Alcoholic beverage manufacturers often add invert sugar in the production of drinks like gin, beer and sparkling wines for flavoring. Candi sugar, similar to invert sugar, is used in the brewing of Belgian-style beers to boost alcohol content without drastically increasing the body of the beer; it is frequently found in the styles of beer known as dubbel and tripel.

Chemistry
Table sugar (sucrose) is converted to invert sugar by hydrolysis. Heating a mixture or solution of table sugar and water breaks the chemical bond that links together the two simple-sugar components.

The balanced chemical equation for the hydrolysis of sucrose into glucose and fructose is:

 * Sugar-inversion.png

 * C12H22O11 (sucrose) + H2O (water) → C6H12O6 (glucose) + C6H12O6 (fructose)

Optical rotation
Once a sucrose solution has had some of its sucrose turned into glucose and fructose the solution is no longer said to be pure. The gradual decrease in purity of a sucrose solution as it is hydrolyzed affects a chemical property of the solution called optical rotation that can be used to figure out how much of the sucrose has been hydrolyzed and therefore whether the solution has been inverted or not.

Definition and measurement
Plane polarized light can be shone through a sucrose solution as it is heated up for hydrolysis. Such light has an 'angle' that can be measured using a tool called a polarimeter. When such light is shone through a solution of pure sucrose it comes out the other side with a different angle than when it entered, which is proportional to both the concentration of the sugar and the length of the path of light through the solution; its angle is therefore said to be 'rotated' and how many degrees the angle has changed (the degree of its rotation or its 'optical rotation') is given a letter name, $$\alpha$$ (alpha). When the rotation between the angle the light has when it enters and when it exits is in the clockwise direction, the light is said to be 'rotated right' and $$\alpha$$ is given to have a positive angle such as 64°. When the rotation between the angle the light has when it enters and when it exits is in the counterclockwise direction, the light is said to be 'rotated left' and $$\alpha$$ is given a negative angle such as −39°.

Definition of the inversion point
When plane polarized light enters and exits a solution of pure sucrose its angle is rotated 66.5° (clockwise or to the right). As the sucrose is heated up and hydrolyzed the amount of glucose and fructose in the mixture increases and the optical rotation decreases. After $$\alpha$$ passes zero and becomes a negative optical rotation, meaning that the rotation between the angle the light has when it enters and when it exits is in the counter clockwise direction, it is said that the optical rotation has 'inverted' its direction. This leads to the definition of an 'inversion point' as the per cent amount sucrose that has to be hydrolyzed before $$\alpha$$ equals zero. Any solution which has passed the inversion point (and therefore has a negative value of $$\alpha$$) is said to be 'inverted'.

Chirality and specific rotation
As the shapes of the molecules ('chemical structures') of sucrose, glucose, and fructose are all asymmetrical the three sugars come in several different forms, called stereoisomers. The existence of these forms is what gives rise to these chemicals' optical properties. When plane polarized light passes through a pure solution of one of these forms of one of the sugars it is thought to hit and 'glance off' certain asymmetrical chemical bonds within the molecule of that form of that sugar. Because those particular bonds (which in cyclic sugars like sucrose, glucose, and fructose include an anomeric bond) are different in each form of the sugar, each form rotates the light to a different degree.

When any one form of a sugar is purified and put in water, it rapidly takes other forms of the same sugar. This means that a solution of a pure sugar normally has all of its stereoisomers present in the solution in different amounts which usually do not change much. This has an 'averaging' effect on all of the optical rotation angles ($$\alpha$$ values) of the different forms of the sugar and leads to the pure sugar solution having its own 'total' optical rotation, which is called its 'specific rotation' or 'observed specific rotation' and which is written as $$[\alpha]$$.

In the circumstance of 20 °C, the specific optical rotation of sucrose is known to be 66.6°, glucose is 52.2°, and fructose is −92.4°.

Effects of water
Water molecules do not have chirality, therefore they do not have any effect on the measurement of optical rotation. When plane polarized light enters a body of pure water its angle is no different from when it exits. Thus, for water, $$[\alpha]$$ = 0°. Chemicals that, like water, have specific rotations that equal zero degrees are called 'optically inactive' chemicals and like water, they do not need to be considered when calculating optical rotation, outside of the concentration and path length.

Mixtures in general
The overall optical rotation of a mixture of chemicals can be calculated if the proportion of the amount of each chemical in the solution is known. If there are $$N$$-many optically active different chemicals ('chemical species') in a solution and the molar concentration (the number of moles of each chemical per liter of liquid solution) of each chemical in the solution is known and written as $$C_i$$ (where $$i$$ is a number used to identify the chemical species); and if each species has a specific rotation (the optical rotation of that chemical were it made as a pure solution) written as $$[\alpha]_i$$, then the mixture has the overall optical rotation$$\displaystyle \alpha = \frac{\sum_{i=1}^N C_i [\alpha]_i}{\sum_{i=1}^N C_i} = \sum_{i=1}^N \left(\frac{C_i}{\sum_{i=1}^N C_i}\right)[\alpha]_i = \sum_{i=1}^N \chi_i[\alpha]_i$$Where $$\chi_i$$ is the mole fraction of the $$i \mathrm{^{th}}$$ species.

Fully hydrolyzed sucrose
Assuming no extra chemical products are formed by accident (that is, there are no side reactions) a completely hydrolyzed sucrose solution no longer has any sucrose and is a half-and-half mixture of glucose and fructose. This solution has the optical rotation $$\displaystyle \alpha = \frac{1}{2}[\alpha]_{\text{glucose}} + \frac{1}{2}[\alpha]_{\text{fructose}} = \frac{1}{2}(52.7^\circ - 92.0^\circ) = -19.7^\circ$$

Partly hydrolyzed sucrose
If a sucrose solution has been partly hydrolyzed, then it contains sucrose, glucose and fructose and its optical rotation angle depends on the relative amounts of each for the solution;$$\displaystyle \alpha = \chi_s[\alpha]_s +\chi_g[\alpha]_g +\chi_f[\alpha]_f$$Where $$s$$, $$g$$, and $$f$$ stand for sucrose, glucose, and fructose.

The particular values of $$\chi$$ do not need to be known to make use of this equation as the inversion point (per cent amount of sucrose that must be hydrolyzed before the solution is inverted) can be calculated from the specific rotation angles of the pure sugars. The reaction stoichiometry (the fact that hydrolyzing one sucrose molecule makes one glucose molecule and one fructose molecule) shows that when a solution begins with $$x_0$$ moles of sucrose and no glucose nor fructose and $$x$$ moles of sucrose are then hydrolyzed the resulting solution has $$x_0-x$$ moles of sucrose, $$x$$ moles of glucose and $$x$$ moles of fructose. The total number of moles of sugars in the solution is therefore $$x+x_0$$and the reaction progress (per cent completion of the hydrolysis reaction) equals $$\frac{x}{x_0} \times 100 \%$$. It can be shown that the solution's optical rotation angle is a function of (explicitly depends on) this per cent reaction progress. When the quantity $$\frac{x}{x_0}$$ is written as $$r$$ and the reaction is $$r \times 100\%$$ done, the optical rotation angle is $$\displaystyle \alpha_{r} = \frac{(x_0-x)[\alpha]_s +x[\alpha]_g +x[\alpha]_f}{x_0 + x} = \frac{1}{1 + r}\left([\alpha]_s + ([\alpha]_g + [\alpha]_f - [\alpha]_s) r\right) $$

By definition, $$\alpha$$ equals zero degrees at the 'inversion point'; to find the inversion point, therefore, alpha is set equal to zero and the equation is manipulated to find $$r$$. This gives$$\displaystyle r_{\text{inversion}} = \frac{[\alpha]_s}{[\alpha]_s - [\alpha]_g - [\alpha]_f} = 0.629 $$Thus it is found that a sucrose solution is inverted once at least $$62.9 \%$$ of the sucrose has been hydrolyzed into glucose and fructose.

Monitoring reaction progress
Holding a sucrose solution at temperatures of 50 - 60 °C hydrolyzes no more than about 85% of its sucrose. Finding $$\alpha$$ when r = 0.85 shows that the optical rotation of the solution after hydrolysis is done is −12.7° this reaction is said to invert the sugar because its final optical rotation is less than zero. A polarimeter can be used to figure out when the inversion is done by detecting whether the optical rotation of the solution at an earlier time in its hydrolysis reaction equals −12.7°.

title: Inverted sugar syrup


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Robert Nixon (politician)

Robert Fletcher Nixon (born July 17, 1928) is a retired Canadian politician in the province of Ontario, Canada. The son of former Premier of Ontario Harry Nixon, he was first elected to the Legislative Assembly of Ontario in a 1962 by-election following his father's death. The younger Nixon was elected leader of the Ontario Liberal Party in 1967 and led them through three provincial elections, the first two where the Liberals retained their standing as the second-largest party and official opposition in the legislature.

Nixon resigned as party leader in 1976, and was succeeded by Stuart Smith after a leadership convention. Nixon remained a prominent member of the Liberal caucus after standing down from the party leadership, including two stints as interim opposition leader, and served as Provincial Treasurer and Deputy Premier in the government of David Peterson from 1985 to 1990.

Background
Nixon is the son of former Premier Harry Nixon and father of former federal MP Jane Stewart. When his father, who had been a member of the legislature since the 1919 provincial election, died on October 22, 1961, Nixon was chosen to run under the Liberal banner as his replacement. On January 18, 1962, he was elected as the member for the rural, southwestern Ontario riding of Brant. At this time, Ontario was dominated by the Progressive Conservative Party, then led by John Robarts. The PC party had won 71 of 98 seats in the previous general election, and had governed the province since 1943. Nixon was re-elected in the 1963 provincial election.

Leadership
The Liberal Party had previously chosen Andy Thompson as its leader in September 1964, with the expectation that he would lead the party in the next provincial election. However, Thompson suffered a physical breakdown in late 1966 as a result of his involvement in an automobile accident in which two elderly women were seriously injured, and withdrew from the position on the advice of his doctors. Nixon was chosen as the party's interim leader on November 16, 1966, and soon declared his candidacy to become the party's full-time leader. When no other candidates came forward, Nixon was acclaimed as party leader and Leader of the Opposition on January 7, 1967.

Nixon led the Liberal Party into the 1967 provincial election, held in October of that year. His campaign attempted to draw attention to water pollution and the high cost of housing in the province, though his efforts on the latter front were undercut by the federal Liberal government's decision to increase interest payments on the National Housing Act in mid-campaign. Nixon increased the party's caucus in the Legislative Assembly from 23 to 28 seats (the total number of MPPs was increased from 108 to 117 in this election, and that the third-place New Democratic Party increased its representation from seven MPPs to twenty).

1970s
John Robarts stepped down as Tory leader and Premier in 1971, and was replaced by William Davis. Davis led the Tories to an increased majority in the 1971 provincial election. Nixon's Liberals were reduced to 20 seats, only one more than the NDP, and the party's share of the popular vote sank to its lowest level in nearly fifty years. Nixon had previously predicted 40 seats for his party, and decided to step down as leader after the election'. He formally resigned in 1972, remaining as interim leader until a permanent successor could be chosen. The convention was scheduled for October 1973. The Davis government was weakened by a series of corruption scandals. Nixon changed his mind about retirement and entered the leadership contest to succeed himself. He defeated Norman Cafik on the third ballot, and resumed his official duties as party leader and leader of the opposition.

1975 election
By the 1975 election, the Tories had been in power for thirty-two years. Nixon and the Liberals, along with Stephen Lewis and the Ontario New Democratic Party, led aggressive campaigns against Davis, with Nixon and Davis personally trading barbs. Polls taken shortly before the election showed the Liberals with a provincial lead. The Tories were reduced to a minority government for the first time since 1945. While the Liberals increased their caucus from 20 to 35 seats, however, the NDP caucus increased from 19 to 38 seats, and became the Official Opposition for the first time since 1951. Due to the almost even split between opposition parties and the fact that both the Liberals and the NDP hoped to win the next election, the two opposition parties were unable and unwilling to form a coalition to replace the Conservatives, and the Davis government was able to survive. For the next two years, the NDP offered unofficial support to the Davis government on several issues. Nixon resigned as leader for a second time and was replaced by Stuart Smith in 1976.

Remaining in politics
Nixon remained in the legislature, however, although he did not have any official parliamentary duties from 1976 to 1982. When Smith resigned as leader following a poor performance in the 1981 provincial election, Nixon briefly returned as interim leader of the opposition from January 25 to February 21, 1982, when David Peterson was chosen as Smith's replacement.

There are reports that Nixon wanted to resign from provincial politics in 1984, and that he was actively seeking an appointment to the Canadian Senate. He was eventually talked out of this by Liberal organizer Keith Davey, who emphasized that Peterson needed his experience and argued that the Liberals could win the next provincial election. Nixon remained, and surprised some reporters prior to the 1985 provincial election by openly speculating about a future Liberal-NDP coalition.

Provincial Treasurer
The election itself produced no clear winner. The Progressive Conservatives, now under Frank Miller, were again reduced to a minority government, winning 52 seats out of 125. Unlike the situation in 1975, however, the Liberals clearly emerged as the dominant opposition party with 48 seats and a narrow victory over the Tories in the popular vote. Nixon took part in post-election negotiations with the third-place NDP, and helped bring about a two-year accord between the two parties, in which the NDP gave support to the Liberals in return for progressive legislation in certain fields.

The Progressive Conservative government was defeated in the house on June 26, 1985, and Nixon was sworn in as Peterson's Treasurer, Minister of Economics, Minister of Revenue and Government House Leader in the first Ontario Liberal administration in forty-two years. From June 17, 1986, until the 1987 provincial election, he also served as interim Chair of the Management Board of Cabinet.

The Liberals won a majority in the 1987 election, and Nixon was appointed as Deputy Premier on September 29 of that year, also retaining the positions of Treasurer, Minister of Economics and Minister of Financial Institutions. He remained in these positions for the remainder of Peterson's time in government. His government produced balanced budgets in 1989 and 1990, although some opposition members later criticized the methodology used to calculate revenues and expenditures in this period. In 1989, Nixon eliminated individual Ontario Health Insurance Plan premium charges.

Back to Opposition
Nixon's tenure as Treasurer ended with the provincial election of 1990, as Peterson's Liberals were upset by the NDP under Bob Rae. Peterson lost his seat, and Nixon fell below 50% support in his own riding for the only time in his career as he defeated an NDP challenger by about 1,500 votes. Peterson resigned as Liberal leader immediately after the election, and Nixon once again became his party's interim leader on September 13, 1990, as well as leader of the opposition when the legislature returned to sit in November 1990.

Retirement
Nixon resigned from the legislature on July 31, 1991, accepting a federal appointment from the Mulroney government to conduct a review of Atomic Energy of Canada Limited (Nixon later served as chair of this crown corporation from 1994 to 2001). He and his father had represented the riding of Brant continuously from 1919 until 1991. In the 1993 federal election, the riding elected Nixon's daughter, Jane Stewart to the House of Commons of Canada, where she served in the Cabinet of Jean Chrétien.

In 1992 Nixon was appointed Agent-General of Ontario to the United Kingdom. He held this position until the London office, and 18 other offices throughout the world, was closed by Bob Rae's NDP government as an economy measure in the mid-90s. Nixon supported Gerard Kennedy for the leadership of the provincial Liberal Party in 1996 and former Ontario New Democratic Party leader and Premier Bob Rae for the federal Liberal leadership in the 2006 leadership race.

In the 2013 Ontario Liberal Party leadership election Nixon endorsed Sandra Pupatello. In 2015, he was made a member of the Order of Ontario.

title: Robert Nixon (politician)