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A-level Biology/Mammalian Physiology and Behavior/Sense organs and the reception of stimuli

=Eye=

Structure
An image of the eye can be see to the below right:

Focussing
Light must be focussed onto the retina, the most sensitive section of this, and the only place where we can perceive colour, is the fovea. Light rays are travelling parallel until they reach the cornea, where they are refracted inwards as they pass through the eye. The cornea does most of the focussing, and the lens does fine adjustments to the refraction, so that rays from different distances can be brought to focus on the retina. The closer an object is, the more accommodation is required as the lens thickens and becomes more convex. This accommodation - the shape changing - is achieved by varying the tension of the suspensory ligaments which hold the lens in position.

This varying tension is occurs in a rather strange way - there is always pressure and tension inside the eye, and to stretch the lens - make it less spherical - the ciliary muscle relaxes, and thus the pressure pushes the sclera out wide, increasing tension on the sunspensory ligaments, flattening the lens. When the ciliary muscles are contracted, the diameter of the circle decreases and loosens the tension on suspensory ligaments, allowing the lens to become more spherical.

Retina
The retina is sensitive to light and energy that comes in the form of light rays is converted to nerve impulses that are carried in the optic nerve.

Structure

 * Contains rods/cones - photoreceptor cells
 * These cells are precisely arranged into a single layer
 * Pigmented epithelium in contact with this single layer
 * Also contains special neurones known as bi-polar and ganglion cells which convey information to the optic nerve
 * Light passes through these cell layers before it reaches the rods and cones, except in fovea
 * The blind spot - where the optic nerve leaves the brain, no photoreceptor cells.

Rods/Cones
Rods and cones have similar structures. The part of the cell facing the outside of the eye is the outer segment and the inner facing side is the inner segment. The end of the inner segment forms synapses with other cells in the retina. The outer segment contains many stages of membranes, formed from invaginations of the plasma membrane. In a rod cell the invaginations pinch off leaving a stage of unconnected discs, but in a cone cell they stay attached. These discs provide a large surface area of membrane that contains visual pigments, for reactions with light.

In a rod cell the pigment molecule consists of a protein known as opsin plus a compound known as retinal, and the molecule is known as rhodopsin. Pigments in a cone cell are similar except there are 3 different types of opsin, one for each of the primary colours of light. Rod cells are much more sensitive to light for reasons that will be explained later on.

Rods/Cones:

Bi-Polar/Ganglion Cells
Bipolar cells
 * Central body from which two sets of processes arise;
 * Those nearest to the rod/cone layer are short and branch into many endings which form synapses with a single cone or a number of rods.
 * The other process is longer and forms synapses with a ganglion cell.
 * Their role is to transfer information from rods/cones to ganglion cells.

Ganglion cells
 * Inner layer of retina
 * Numerous dendrites from synapses with bipolar cells
 * Location of action potential generation
 * Axons of ganglion cells make up the optic nerve

The neurotransmitter released by resting rod/cone cells reaches a bi-polar cell which can either increase or decrease the amount of neurotransmitter substance that it releases. Some ganglion cells fire more slowly, some more quickly in response to this change in the neurotransmitter substance it receives.

Rod Cells
A rod cell without light maintains a difference in electrical potential across its plasma membrane, but this is usually around -40mV (compared to the -60mV of a normal neurone) due to channels for both sodium and potassium to flow freely in and out. When light hits a rod cell, the retinal part of rhodopsin changes shape, from a carbon-tail-kinked 11-cis-retinal to an all-trans-retinal, which results in retinal no longer being able to bind with opsin. The rhodopsin molecule changes into an unstable form, causing those sodium/potassium channels to close and a greater potential difference -70mV builds up. The rod cell is now said to be hyperpolarised.

Cone Cells
Cone cells respond in a similar way, but cone cells require much more light before the cells hyperpolarize, and this is why rods are more sensitive to light (among other reasons). The three pigments are for red blue and green, and the brain judges colour by the intensity of signals from each type of cone.

Neurotransmitter
Rod/Cone cells are constantly releasing neurotransmitter - until light falls on them, when they stop

Visual Acuity
The reason we have lower visual acuity with rod cells is because several of them interface with one bipolar cell whereas cone cells interface with only one ganglion cell. This aids the detection of dim light as the small responses are pooled to produce a larger response.

Ageing
With ageing comes two main problems - loss of visual acuity and cataracts. The loss of visual acuity is due to the loss of elasticity in their lenses, and so the lens cannot return to its correct shape after near focussing. Cataracts are the result of proteins denaturing and coagulating, resulting in that part of the lens becoming cloudy white and impairing vision. It can be fixed with glasses or surgery.

=Ear=

The ear is responsible for hearing and balance.

Structure
The ear can be divided into three parts, outer, middle and inner ear.

Outer ear:

 * Pinna - Collects sound waves and directs them towards tympanic membrane (ear drum).
 * Auditory canal - Sound travels along here
 * Tympanic membrane - Sound turns to vibrations here

Middle ear

 * Auditory ossicles - malleus (hammer), incus (anivil) and stapes (stirrup) - transmit vibrations from tympanic membrane to oval window membrane.
 * Eustaschian tube - air filled passage that maintains air pressure on both sides

Inner ear

 * Contains fluid
 * Embedded within the bones of the skull
 * Cochlea - contains receptor cells that convert energy in sound waves into a nerve impulse
 * Organ of Corti - the receptor cells inside the cochlear that runs along the basilar membrane throughout the length of the coiled cochlea. When the oval window vibrates, the vibrations are transmitted through the fluid in the cochlea and cause these receptor cells to vibrate.
 * The receptor cells also have stereocilia on their upper surface which are embedded in another membrane, and are in close contact with the neurones that form the cochlear nerve.
 * Three semi-circular canals, with two chambers called utriculus and sacculus. All full of fluid and contain hair cells. This is the area responsible for balance, and impulses pass from it to the vestibular nerve, which joins with the cochlear nerve, forming the auditory nerve.

Hearing
The above section described how vibrations in the air are transmitted to the hair cells which then vibrate. These hair cells were previously maintaining a resting potential across their plasma membranes, same as neurones, and when they vibrate they are depolarised, causing them to release neurotransmitter. This in turn depolarises the endings of nerve cells in the cochlear nerve. This creates action potentials which are then carried into the brain.

Loudness
The brain determines the loudness of a sound by the amplitude vibration which is converted into an increased rate of action potentials. Also, some cells only fire if there is an extremely loud sound.

Frequency
The frequency (pitch) of a sound is detected by the brain knowing which neurones are conducting nerve impulses into it. The hair cells in the basilar membrane closest to the oval window are receptive to high frequency sounds whilst the furthest away are for low-frequency sounds.

Direction
The direction a sound is coming from is determined by the loudness and the timing of the sound arriving in each ear.

Balance
Our sense of balance is provided by the receptor cells in the semicircular canals, the utriculus and the sacculus. The receptor cells synapse with the sensory endings of the vestibular nerve. In both semicircular canals, there is a patch of cells called a macula, and this is covered with a gelatinous layer containing crystals of calcium carbonate called otoliths. Each macula also contains numerous hair cells which have stiff stereocilia projecting from their upper surfaces, and the ends of the cilia are embedded in the gelatin layer, forming synapses with the neurones of the vestibular nerve.

The crystals of calcium carbonate, the otoliths, are heavy and are pulled downwards by gravity, and they pull the hairs of the hair cells with them, depolarising the ones they pull with them, changing the pattern of action potentials transmitted along the vestibular nerve. The macula in the two semicircular canals are arranged differently providing a 3D image to the brain of how the head is positioned. The hair cells in the utriculus are in the horizontal plane, sensing the orientation of the head when you are upright, whereas those in the sacculus are in the vertical plane, sensing the orientation of the head when you are lying down.

The semicircular canals are filled with viscous fluid and have a swelling at the end called an ampulla. In each ampulla there is a gelatinous structure called a cupula with stereocilia from hair cells embedded in it. When the head moves the fluid stays where it is (inertia) and so collects in the ampulla. This bends the cupula to one side, pulling the cilia and causing depolarisation of the hair cells. The three ampullae are orientated differently so at least two will detect a movement, regardless of direction.


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A-level Biology/Mammalian Physiology and Behavior/Behavior

=Behaviour=

Behaviour is everything an animal does, and is influenced by both nature (genes) and nurture (envrionment).

Innate
Innate (instinctive) behaviour is defined as inherited, pre-set behaviour that doesn't require learning or practice.

Genes
You'll remember the concept of alleles being selected for in a population as part of natural selection - the same is true for alleles for evolutionary-advantageous behaviour, and so the behaviour becomes more common. However, a lot of behaviour we used to consider completely innate we are now not so sure about - an animal's genes produce the basic structure of its body, and the behaviour it shows is an interaction between these features and the environment that the animal has developed in.

Reflexes
Reflexes are rapid, automatic responses to stumulus, such as pulling your hand away when you touch something hot - the signals are not passed to the brain before we act, as to speed up our reaction. Removing your hand from something hot, or ducking when you see something flying toward you are examples of innate reflexes. We can also develop condition reflexes, as shown by Pavlov's dogs for example.

Experience
Innate behaviour can be influenced by experience, for example in birds that feed their young by fetching food for them and putting it in their beaks. To begin with the chicks just open and close their beaks but after a few days they learn how to twist their heads in order to grab the parent's beak to get at the food quicker - the basis is innate, but the refinement is learning.

=The Nature of Learning=

Learning is a change in behaviour as the result of experience, and you are required to know three case studies on learning performed in the last century.

Skinner
B.F. Skinner became well known for studying operant conditioning with the use of his 'Skinner box', which isn't as dangerous as it sounds. It is a cage in which an animal is placed, and inside the cage there is a lever that can be depressed that will produce a reward. At first, the animal wanders around looking for a way out, but by accident hits the lever and food appears. After a few times of doing this, the animal begins to purposefully press the lever, and this shows that the animal has learned to associate the behaviour with the reward.

Pavlov
Ivan Pavlov worked on classical conditioning, with dogs as the subject of his experiments. Pavlov measured the salivation of dogs when meat powder was puffed into their mouths, and then began to introduce some other stimulus right before the food - a bell. The bell was rung, and the food was given, and after several occurrences of this the dog began to salivate upoun just hearing the bell - classical conditioning.

Initially the dog had a reflex, producing saliva in response to food, an unconditioned stimulus, but the sound of the bell that was associated with the food is known as the conditioned stimulus. The response, combined with the stimulus is known as a conditioned reflex.

Advantages
The adaptative value of conditioning can be valuable indeed – the animal learns to change its behaviour based on a reinforcer, a reward or a negative event that tells it to do or not to do the action. This can be seen for example with animals who might try and eat a wasp, and be stung. The yellow and black colours of a wasp will in the future cause the animal to back off since it has learned that it will be hurt if it does try to eat the wasp.

Kohler
Kohler worked on more complex types of learning than simple association, known as insight learning. He studied primates, chimpanzees. A chimp with a stick inside its cage and a banana outside of the cage quickly learned to use the stick to reach the banana to eat it – a reward. Once this had been learnt, the chimp was given two sticks that fit together end to end, and the banana was placed such that it would require both sticks to reach it. The chimp attempted to reach it with just the one but could not, and quickly gave up.

The chimp then began to play with the sticks, and during this realised that he could fit the two sticks together, and immediately rushed back to the banana and retrieved it with the extended stick. This is known as insight learning – applying one situation to another, since the chimp was not doing something directly related to food but connected it to food.

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


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A-level Biology/Mammalian Physiology and Behavior/The Nervous System

=Organisation=

The nervous system of mammals has two major cells - neurones and glial cells. The neurones transmit action potentials whilst the glial cells help nutrients from the blood into the neurones and maintain the correct balance of ions in the tissue fluid surrounding them. Schwann cells are glial cells. The nervous system has two major components - central and peripheral.

Central
The central nervous system comprises the brain and spinal cord - it has mostly intermediate neurone (short dendrited) and many synapses, with further neighbouring neurones. These neurones receive and integrate information arriving via the synapses and then pass off the information via an action potential to other neurones.

The spinal cord extends from the base of the brain, down to the first lumbar vertebra. It comprises a canal in the centre containing cerebrospinal fluid, and at the centre of the cord there is unmyelinated neurones which appear grey, and the rest appears white. The brain is simply an extension of the spinal cord.

Peripheral
Peripheral nervous system includes all the neurones that are outside of the brain and spinal cord - sensory and motor neurones. Sensory neurones are situated just outside the spinal cord, in the dorsal root and pickup information at receptors and transmit action potential from the receptor toward their cell bodies. The action potential then goes to the central nervous system. Motor neurones carry action potentials from the central nervous system to effectors, and the cell bodies of them are usually in the spinal cord - their long axons pass from the spinal cord to the effectors.

Cell bodies of sensory neurones are situated in the dorsal root ganglia just outside the spinal cord. A ganglion is a group of nerve cell bodies.

The cell bodies of motor neurones are in the spinal cord and their axons pass out of the spinal cord and towards effectors.

Axons and dendrons are arranged in bundles known as nerves. They leave and enter the spinal cord in spinal nerves, each with a dorsal root, which carrys impulses towards the spinal cord and a ventral root, which carries the impulses towards effectors.

The peripheral nervous system has two further subsections - the somatic and the autonomic nervous system - the somatic is all sensory neurones, and motor neurones that take information to skeletal muscles, for example a typical reflex arc involvement is only somatic. The autonomic will be discussed in the next section.

=Autonomic=

The autonomic nervous system is all the motor neurones that supply the internal organs - autonomic means self-adjusting and this is because we do not usually voluntarily control it. It controls the activity of all smooth muscle in the body e.g. walls of arterioles and alimentary canal, the rate of beating in the cardiac muscle in the heart and activities of exocrine glands e.g. salivary glands. It is further divided into sympathetic and parasympathetic.

Sympathetic
The sympathetic nervous system can be summarised as the fight or flight system. The motor neurone cell bodies lie in the ganglia outside the spinal cord - their axons pass out through the ventral roo, synapsing with the motor neurone cell bodies in these ganglia, where they pass to all organs within the body. Synapses to the heart muscle, smooth muscles are formed, and the transmitter across most of these substances is noradrenaline, stimulating them.

Its effects are;

 * Heart - increases rate and force of contraction.
 * Digestive system - contracts sphincter, releases glucose into blood.
 * Eye - dilates, relaxs ciliary muscles for distant vision.
 * Skin - increases sweating, vasoconstriction.

Parasympathetic
The parasympathetic nervous system's nerve pathways all begin in the brain, and the neurone which carries the impulse of the brain keeps going until it is inside the organ that it will stimulate the effector neurone of. The parasympathetic nervous system usually utilises acetylcholine, which often as an inhibitory effect on organs.

Its effects are;

 * Heart - reduces rate and force.
 * Digestive system - stimulates gland secretion, relaxes sphincter muscles, glycogen production increased.
 * Eye - constricts, ciliary muscles contract for near vision.
 * Skin - slight increase in palm sweat.

=Brain= [[Image:Brainlobes.png|right|framed|The lobes of the brain. *Red: Frontal lobe
 * Orange: Parietal lobe
 * Yellow: Occpital lobe
 * Green: Temporal lobe
 * Blue: Cerebellum
 * Black: Medoullea oblongata + brain stem]]

The brain is studied in a variety of ways - CAT, PET, MRI scans, and studying people who have brain damage. For example, Pierre Broca studied people who could not speak or write intelligibly, dissecting their brains and he found a small area near the front of the left side that was damaged - now know as the Broca's area, the section of the brain responsible for the production of language.

Structure
The brain is an extended spinal cord, and his highly specialised. It contains ventricles filled with cerebro -spinal fluid and is made up of neurones. The largest section of the brain is the cerebrum, divided into right and left hemispheres, connected by the corpus callosum. The surface of each hemisphere is covered by a highly folded layer of tissue known as the cerebral cortex. The parts of ceberal cortex have been given different names (see picture to the right). Within the cereberum, there are several areas with their own names, such as the hippocampus and the amygdala.

Inside the brain itself is the diencephalon, containing the thalmus and the hypothalmus (closely associated with the pituitary gland). Behind the thalamus is the midbrain, and above this is the cerebellum, like the cerebrum has a folded surface and is divided into several lobes. Below the cerebellum is the medulla oblongata which merges into the spinal cord.

This diagram is highly recommended:

Cerebrum Function
The cerebrum is responsible for all higher-level processes, thinking, language and emotions for example. It is much larger in humans than other animals. The cerebral cortex of both hemispheres receives sensory impulses from many different sources. The part of the cerebral cortex that first receive this information are known as primary sensory areas. Association areas integrate the information for the primnary sensory areas, or receive information from them.

Cerebellum Function
The cerebellum is the control center for movement and posture, and receives inputs from all other parts of the central nervous system to do this, and some directly from sensory neurones. Impulses are then sent to other parts of the brain, such as the motor centre.

Medulla Oblongata Function
The medulla oblongata is a small section at the base of the brain. It controls breathing, heart rate and blood pressure. The medulla oblongata's groups of neurone produce rhythmic patterns of impulses which pass to the muscles of the diaphragm and intercostal muscles, and this pattern can be changed by CO2 concentration in the blood, and the breathing rate will be increased.

A different section controls heart rate and blood pressure by receiving information from baroreceptors (pressure) - connected to the autonomic nervous system going to the SAN in the heart and can increase or decrease the heart beat. High CO2 concentrations, or low blood pressure increases the rate and the reverse has the reverse effect.

Hypothalmus Function
The hypothalamus receives information in the form of nerve impulses from many parts of the brain. This information is about the body, and the hypothalamus integrates it and the brings about responses either through the autonomic nervous systems or pituitary gland secretions. An example of this is in homeostasis - the hypothalamus receives information about skin temperature from sensory neurones, and receptors inside the hypothalamus itself, which measures blood temperature. It can then send impulses which bring about appropriate responses.

The hypothalamus helps to control the secretion of hormones from endocrine glands, and is directly connected to the pituitary gland.

Pituitary gland
The posterior pituitary gland are controlled by neurones running straight from the hypothalamus, the role of which is to secrete the hormones (very unusual for a neurone). These hormones are carried to their endings and released similar to a neurotransmitter. ADH and oxytocin are produced in this way.

The anterior pituitary gland uses neurones in the hypothalamus to produce several hormones and secrete these into the surrounding blood vessels. The hormones are then carried through those blood vessels into the anterior pituitary gland where they affect the production (stimulation: releasing hormones, inhibition: inhibiting hormones) and release a variety of other hormones.

Alzheimer's
Alzheimer's disease is a form of dementia, a general loss and reduction in mental abilities.

Symptoms
Physiological symptoms in the brain include neurones which had bundles of fibres in them, called tangles, and dark-staining deposits between the neurones known as plaques, but these are only visible post-mortem. CAT or MRI scans show a reduction in brain size.

However, generic symptoms are increasing loss of memory, anxiety, hallucinations, personality changes.

Causes
The tangles in the neurones are made of a protein known as tau, and that the plaques contain a peptide known as beta amyloid. This peptide is made from a large protein molecule called beta amyloid precursor protein (APP), an enzyme of which the function is not known. The plaques form because far too much beta amyloid is secreted, and this abnormal metabolism could be the cause of Alzheimers. Inherited Alzheimers often shows different allele of the gene that codes for APP. However, genetics cannot explain it purely, but there is another gene that codes for a protein that is suspect. Over half of all people with ALzheimers have a particular allele of the gene that codes for APOe, and evidence shows that this may increase the rate at which beta amyloid is deposited into plaques.

Ageing is also a risk factor, as is severe blows to the head especially for the elderly.

Treatment
There is as of yet no cure for alzheimers, or effective treatment.


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Metabolomics/Analytical Methods/Mass Spectrometry/Tandem-MS

Back to Previous Chapter: Hormones

Next chapter: Computational Modeling of Metabolic Control

Next Category: Sample Preparation

Go to: GC-MS

Go back to: LC-MS

Tandem mass spectrometry, also known as MS/MS, involves multiple steps of mass spectrometry selection, with some form of fragmentation occurring in between the stages. Fragmentation of gas-phase ions is very important in MS/MS, and it takes place between various stages of mass analysis. (http://en.wikipedia.org/wiki/Tandem_mass_spectrometry) Different fragmentation methods are: In-source fragmentation and Post-source fragmentation. Tandem mass spectrometry is used to identify chemicals, that are very hard or impossible to identify by any other methods due to their low concentrations, polarity, or lack of chromophore. It is a powerful tool in identification of inherited metabolic disorders, when an accurate and timely diagnostics of which can be essential to the wellbeing of the patient.

Article 1:

Clinical applications of tandem mass spectrometry: ten years of diagnosis and screening for inherited metabolic diseases.
(By: Mohamed S. Rashed)

URL: http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6TG9-433PCKJ-3&_user=47004&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000005018&_version=1&_urlVersion=0&_userid=47004&md5=9382088a05662f18a95f6bfb87888334

General Overview:

The main focus of this article is to provide a detailed explanation of the two main Tandem Mass Spectrometry (MS-MS) screening methods, such as MS–MS-based newborn screening, and MS–MS-based selective. The review contains information about the evolution and development of MS-MS from fast atom bombardment MS-MS to electrospray ionization MS-MS. The author shows the unique advantages of MS-MS for use in genetic laboratories and at the newborn screening programs around the world. Also the review points out benefits of the tandem mass spectrometry over the other analytical methods available.

New Terms:

Beta-ketothiolase deficiency – a rare, autosomal recessive metabolic disorder in which the body cannot properly process the amino acid isoleucine or the products of lipid breakdown. http://en.wikipedia.org/wiki/Beta-ketothiolase_deficiency

Maple syrup urine disease (MSUD) – also called branched-chain ketoaciduria, is an autosomal recessive metabolic disorder affecting branched-chain amino acids. It is one type of organic acidemia. http://en.wikipedia.org/wiki/Maple_syrup_urine_disease

Sudden infant death syndrome (SIDS) – is a syndrome marked by the symptoms of sudden and unexplained death of an apparently healthy infant aged one month to one year. http://en.wikipedia.org/wiki/Sudden_infant_death_syndrome

Mitochondrial trifunctional protein deficiency – is an autosomal recessive fatty acid oxidation disorder that prevents the body from converting certain fats to energy, particularly during periods without food. People with this disorder have inadequate levels of an enzyme that breaks down a certain group of fats called long-chain fatty acids. http://en.wikipedia.org/wiki/Mitochondrial_trifunctional_protein_deficiency

Propionic academia – also known as propionic aciduria, or sometimes referred to as ketotic glycinemia, is an autosomal recessive amino acid disorder, classified as a branched-chain organic acidemia, which presents in the early neonatal period with progressive encephalopathy. http://en.wikipedia.org/wiki/Propionic_acidemia

Metabolomics Relevance:

The article points out new methods for identification of metabolic disorders, which are caused by mitochondrial enzyme defects, and mitochondrial fatty acid oxidation defects, in which acetyl-CoA accumulates in mitochondria. L-carnitine helps remove acetyl-CoA through formation of acylcarnitine esters, restoring mitochondrial homeostasis. Acylcarnitine can be considered a unique chemical fingerprint, which metabolomics is a study of.

Article 2:

Screening blood spots for inborn errors of metabolism by electrospray tandem mass spectrometry with a microplate batch process and a computer algorithm for automated flagging of abnormal profiles.
(by: Mohamed S. Rashed et al.)

URL: http://www.clinchem.org/cgi/content/abstract/43/7/1129

General Overview:

This article focuses on ESI-MS/MS (electrospray tandem mass spectrometry) and how it is paving the way for new opportunities. The introduction of ESI-MS/MS as a diagnostic tool in our metabolic unit has had a great impact on the number of cases diagnosed as organic acidemias or aminoacidopathies from sick children. It focuses on the research that is being done in order to find biomarkers in metabolomics in order to better understand the human body.

New Terms:

Neonatal screening - Newborn screening is the process of testing newborn babies for treatable genetic, endocrinologic, metabolic and hematologic diseases. http://en.wikipedia.org/wiki/Neonatal_screening

Hypermethioninemia - an excess of the amino acid methionine, in the blood. This condition can occur when methionine is not broken down properly in the body. http://en.wikipedia.org/wiki/Hypermethioninemia

Homocystinuria - also known as Cystathionine beta synthase deficiency, is an inherited disorder of the metabolism of the amino acid methionine, often involving cystathionine beta synthase. It is an inherited autosomal recessive trait, which means a child needs to inherit the defective gene from both parents to be affected. http://en.wikipedia.org/wiki/Homocystinuria

Galactosemia - is a rare genetic metabolic disorder which affects an individual's ability to properly metabolize the sugar galactose. http://en.wikipedia.org/wiki/Galactosemia

Acylcarnitines - are fatty acids or organic acids that are bound to carnitine. http://www.idph.state.il.us/HealthWellness/msmsfaq.htm

Metabolomics Relevance:

MS/MS detects abnormal levels of amino acids and acylcarnitines. Abnormal elevations of these amino acids may indicate the newborn is at risk for disorders of amino acid metabolism. This is relevant to what we have learned so far in the course in that we have talked about free carnitine as a chemical that acts as a transporter of fatty acids into and out of the mitochondria, and is necessary for normal energy metabolism. Acylcarnitines are fatty acids or organic acids that are bound to carnitine. These acylcarnitines vary in size, based on the number of carbon atoms and the type of chemical bonds within the molecule. Abnormal levels of these acylcarnitines can act as markers for certain organic acid and fatty acid oxidation metabolic disorders.

Articles and Web Pages for Review and Inclusion
Peer-Reviewed Article #1:

Towards de novo identification of metabolites by analyzing tandem mass spectra

'''Bioinformatics 2008 24(16):i49-i55'"

Main Focus

 * Identify the main focus of the resource. Possible answers include specific organisms, database design, intergration of information, but there are many more possibilities as well.

New Terms

 * New Term 1: Definition. (source: http://)
 * New Term 2: Definition. (source: http://)
 * New Term 3: Definition. (source: http://)
 * New Term 4: Definition. (source: http://)
 * New Term 5: Definition. (source: http://)
 * New Term 6: Definition. (source: http://)
 * New Term 7: Definition. (source: http://)
 * New Term 8: Definition. (source: http://)
 * New Term 9: Definition. (source: http://)
 * New Term 10: Definition. (source: http://)

Summary

 * Enter your article summary here. Please note that the punctuation is critical at the start (and sometimes at the end) of each entry. It should be 300-500 words. What are the main points of the article? What questions were they trying to answer? Did they find a clear answer? If so, what was it? If not, what did they find or what ideas are in tension in their findings?

Relevance to a Traditional Metabolism Course

 * Enter a 100-150 word description of how the material in this article connects to a traditional metabolism course. Does the article relate to particular pathways (e.g., glycolysis, the citric acid cycle, steroid synthesis, etc.) or to regulatory mechanisms, energetics, location, integration of pathways? Does it talk about new analytical approaches or ideas? Does the article show connections to the human genome project (or other genome projects)?


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Talk:Pakistani History

What this book is (and is not) about?
This page would grow over the days to assemble all articles from the Wikipedia into a book-like manner related the the history of the Islamic Republic of Pakistan. Here, we would discuss what this book should and should not have. Arunreginald (talk) 22:47, 8 May 2008 (UTC)

Merge
I agree with the merger from History of Sindh. Both books have little content and so the merged content would be very easy to integrate here. – Adrignola discuss 02:57, 5 March 2011 (UTC)

title: Talk:Pakistani History


text: User talk:148.197.5.20

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User:Arabicpod

ArabicPod.net one of the first sites that is found to teach Arabic via podcast. http://www.arabicpod.net

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Wikibooks:Subject pages

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 * 1) A list of books in that subject. You can use to produce this automatically
 * 2) A list of topic books in other categories, such as Category:Books with print version, Category:Books with PDF version, and Category:Featured books. You can find books that are simultaneously in two categories at once using the template.
 * 3) A list of books in similar topics, but not in this topic. Use to create these lists
 * 4) Links to information on the topic on other Wikimedia projects, such as Wikipedia, Wikiversity, and Wiktionary. Use Sisterlinks or Associated Wikimedia for this.
 * 5) A link to a parent category. It's important that all subject pages have a parent. This makes them easier to find. To put a subject page into the category of a parent, use the subjects template.

Feel free to get creative with these lists. The more relevant information that you can present to readers, the better.

Subject casing
Books and their categories are title cased. Partly to reduce conflicts where possible, Subject pages and their corresponding categories are sentence cased.

History
Subject pages were implemented in August 2007 and the decision to phase out bookshelves in November 2007.

title: Wikibooks:Subject pages


text: User talk:72.78.117.34

title: User talk:72.78.117.34


text:
Metabolomics/Hormones/Adiponectin

Back to Previous Chapter: Metabolites Next chapter: Analytical Methods Go to: Ghrelin Go back to: Leptin

Introduction
Adiponectin (Acrp30) is a protein hormone that is secreted adipocytes, also known as fat cells. The adipocytes are the only producers and secretors of this hormone. Two receptors for adiponectin are known to date, AdipoR1 and AdipoR2; which are expressed on the liver and skeletal muscle. The protein is produced as a monomer and it can then assemble into higher order complexes (trimers, hexamers, oligomers), the full length protein can also be cleaved to produce the globular head. The different forms of the hormone show different signaling affects. This hormone affects a range of metabolic processes such as glucose flux, lipid catabolism and response to insulin. Specifically, the release of adiponectin causes an increased tolerance to glucose as well as an increased sensitivity to insulin in peripheral tissues of the body. Low levels of adiponectin have been linked to increased risk of heart attack, obesity, and type 2 diabetes; while high levels of this hormone show decreased weight gain and risk of heart attack.

Adiponectin and Mitochondrial Function
Mitochondrial function is crucial for adiponectin production in adipocytes. Rosiglitazone and mitochondrial biogenesis enhancement (Ad-NRF-1) treatments have been discovered to increase adiponectin synthesis. Chemicals that are detrimental to mitochondrial function and mitochondrial biogenesis reduction (mtTFA-specific siRNA) treatments lead to attenuated adiponectin synthesis. The impairment of mitochondrial function has also proven to place stress on the endoplasmic reticulum (ER), which results in overall decreased adiponectin transcription.

It is an established fact that adiponectin synthesis is elevated in small fat cells, as a result of enhanced mitochondrial function. By contrast, hypertrophied fat cells experience decreased adiponectin synthesis, as a result of impaired mitochondrial function. Obese individuals are proven to have a high number of hypertrophied fat cells, which provides an explanation for reduced levels of adiponectin. Researchers have assumed that adiponectin synthesis is regulated by the cellular energy-production system of mitochondria, because adipocytes are known to produce large quantities of adiponectin, when compared to other proteins.

Calcium-handling and protein-folding processes in the ER require large amounts of ATP, glucose deprivation and hypoxia – all of which are stimuli that elicit ER stress. Impaired mitochondrial function has also proven to place stress upon the ER. This stress was reversed in the event of enhanced mitochondrial biogenesis. By comparison, impaired mitochondrial function was discovered to activate c-Jun NH2-terminating kinase (JNK) and the activating transcription factor (ATF3), both of which are proven to be activated in the event of ER stress. JNK and ATF3 inhibition reverses mitochondrial function and reduces adiponectin transcription. This further demonstrates that reduced adiponectin transcription is a result of mitochondrial dysfunction.

Adiponectin expression is also impaired by elevated levels of reactive oxygen species (ROS) and increased CHOP10 expression. These factors inhibit adiponectin gene expression via CCAAT/enhancer-binding protein-binding region interference of the adiponectin gene promoter.

A number of hormones and transcription factors that are involved in adiponectin synthesis have been identified in previous studies. These include TNF- and interleukin-6, which are both known to reduce adiponectin synthesis. These adipocytokines are also believed to contribute to the reduced adiponectin levels in obesity. Researchers have also proven that TNF- reduces mitochondrial biogenesis, while increasing the potential for mitochondrial injury. The impact of rosiglitazone on adiponectin synthesis is believed to involve mechanisms that are independent of mitochondrial function. Specifically, PPAR /retinoid X receptors bind directly to functional PPAR-responsive elements in human adiponectin promoters, which increases the promoter activity.

It has been established that adiponectin levels increase mitochondrial number and function in skeletal muscle via 5-AMP-activated protein kinase activation. This activation has also been proven to stimulate skeletal muscle mitochondrial biogenesis. This presents the potential for mitochondrial or metabolic activity in adipocytes to regulate mitochondrial, metabolic, or insulin activity in skeletal muscle by way of adiponectin.

Researchers have surmised that mitochondrial function is directly linked to adiponectin synthesis in adipocytes. The impaired mitochondrial function in adipose tissue is also believed to contribute to decreased plasma adiponectin levels, during obesity. Adiponectin synthesis has been proven to be onset by the activation of mechanisms involving ER stress, JNK, and ATF3 that result from impaired mitochondrial function. Mitochondrial dysfunction and ER stress have been identified as determinants of insulin resistance, in tissue samples from obese subjects.

Link to article:

http://diabetes.diabetesjournals.org/cgi/content/full/56/12/2973#SEC3

=Resources=

1)  Mechanisms regulating energy metabolism by adiponectin in obesity and diabetes  http://www.biochemsoctrans.org/bst/034/0798/0340798.pdf

This, fairly short, journal article, gives a broad overview of the interaction of the hormone adiponectin on metabolism by looking at its structure, function, and regulation. Adiponectin is a protein hormone that is secreted from fat cells. The authors show that adiponectin’s structure relates to function, adiponectin can exist in multiple forms (monomers, trimers, hexamers, oligomers, and as the globular C-terminal domain) and that each form produces a different affect on different tissues. The article also explains that adiponectin acts by binding to two receptors (AdipoR1 and AdipoR2) and that the expression of the receptors can be changed to regulate the action of adiponectin; also liver and skeletal muscle show different profiles of expression for AdipoR1 and AdipoR2. The authors point out the downstream molecules that adiponectin signaling affects, some of them include: AMP-activated protein kinase (AMPK), p38, and cAMP. The author demonstrated the insulin sensitizing effects of adiponectin by injecting mice with it and by creating knockout mice. Injection of adiponectin increased blood glucose uptake in normal mice and prevented insulin-resistance in obese mice. Expression of globular adiponectin in transgenic ob/ob mice showed decreased insulin resistance and diabetes compared with transgenic ob/ob mice not expressing globular adiponectin. From their research the authors concluded that regulation of adiponectin is complicated; that it plays a role in obesity and diabetes type 2 by affects on glucose uptake and insulin sensitivity.

New Terms:

Adipokines – a group of cytokines secreted by adipose tissue

Hyperinsulinaemia – excessively high levels of insulin in blood

Metabolic syndrome – a combination of disorders that increase risk of cardiovascular disease and diabetes

Pathophysiology – functional changes due to disease

Ameliorating – to make better or improve

2)  Adiponectin: A Fat Cell Hormone That Promotes Insulin Sensitivity

http://www.medscape.com/viewarticle/438373 (need to google address to see page: http://www.google.com/search?client=safari&rls=en&q=http://www.medscape.com/viewarticle/438373&ie=UTF-8&oe=UTF-8)

This web resource summarizes speeches and articles about the function of adiponectin. It states that adiponectin increases insulin sensitivity, decreases gluconeogenesis, and activates AMP-activated protein kinase and protein kinase B. It says that research suggests that adiponectin regulation may relate to the distribution, as opposed to amount, of body fat (shown in rats). The article says that regulation of adiponectin secretion is affected by glucocorticoids, proliferators-activated receptor gamma (PPAR) agonists, testosterone, estrogen, and prolactin. The article also explores research looking at defects in adiponectin and insulin resistance; adiponectin gene polymorphisms are shown to be linked to type 2 diabetes. It then goes on to say that further research is being done on adiponectin for potential therapeutic use.

New Terms:

Hyperinsulinemic euglycemic clamp – a test to quantify insulin resistance

Thiazolidinediones – a type of drug used to treat type 2 diabetes

Metformin – a type of drug used to treat type 2 diabetes

Glucocorticoids – a group of hormones produced by the adrenal cortex and involved in carbohydrate, protein, and fat metabolism

Adiposity – synonym for obesity

3)  Adiponectin Receptor-1 &-2 (AdipoR1 & AdipoR2) two recently identified receptors

http://www.phoenixbiotech.net/Catalog%20Files/Adiponectin/adiponectin-receptor.htm

This web resource gives an overview of the adiponectin receptors one and two, also known as AdipoR1 and AdipoR2. The article focuses on how the two receptors were discovered and provides summaries for three experiments that were based around adiponectin receptors. This article goes into depth on the different analyses for the receptors including western blot analysis and immuno-staining. Five new words I encountered while reading this resource include: Immunohistochemistry, atherosclerotic lesions, leptin, LXR ligands, and lipolysis. Immunohistochemistry is the microscopic localization of specific antigens in tissues by staining with antibodies labeled with fluorescent or pigmented material. Atherosclerotic lesions are characterized by foam cells derived from cholesterol-loaded macrophages. Leptin is a peptide hormone neurotransmitter produced by fat cells and involved in the regulation of appetite. LXR ligands are metabolites of cholesterol, such as 22(R)-hydroxycholesterol, 24(S),25-epoxycholesterol and 27-hydroxycholesterol, and are known to activate both LXR and LXRβ. Lipolysis is the hydrolysis of fats into fatty acids and glycerol, by lipase. Adiponectin effects gluconeogenesis and glucose uptake via increased tolerance to glucose and increased sensitivity to insulin in peripheral tissues. The receptors for Adiponectin allow it to help regulate these pathways through concentration levels of these receptors and the adiponectin itself.

New Terms:

Immunohistochemistry - A type of assay in which specific antigens are made visible by the use of fluorescent dye or enzyme markers.

Atherosclerotic lesions - Formed via inflammation leading to formation of atheromatous plaques in the arterial tunica intima which then rupture to form lesions.

Leptin - A peptide hormone that is produced by fat cells. It plays a role in body weight regulation by acting on the hypothalamus to suppress appetite and burn fat stored in adipose tissue.

LXR ligands - ligand-activated transcription factors that regulate the expression of genes controlling lipid metabolism.

Lipolysis - The hydrolysis of triglycerides into free fatty acids and glycerol.

4)  Reduced response to adiponectin and lower abundance of adiponectin receptor proteins in type 2 diabetic monocytes

http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T36-4SCTWNX-4&_user=47004&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000005018&_version=1&_urlVersion=0&_userid=47004&md5=bac23b7223919347d2bf3f392c20ee6e

This journal resource focuses mainly on the abundance of the adiponectin receptors and the effects of the antidiabetic adipokine adiponectin in monocytes of normal-weight, overweight controls, and type two diabetic patients. The journal goes into specific detail regarding adiponectin resistance in monocytes as well as it’s upregulation of interleukin. The new definition terms I have found while viewing this journal are as follows: antiatherosclerotic, metformin, p38 MAPK, statins, and fibrates. Metformin is an oral antidiabetic agent, C4H11N5, that decreases glucose production by the liver and lowers plasma glucose levels. P38 MAPK is the archetypal member of the third MAPK-related pathway in mammalian cells. Statins are any of a class of lipid-lowering drugs that reduce serum cholesterol levels by inhibiting a key enzyme involved in the biosynthesis of cholesterol. Fibrates are a class of amphipathic carboxylic acids. They are used for a range of metabolic disorders, mainly hypercholesterolemia (high cholesterol), and are therefore hypolipidemic agents. This journal resource reviews adiponectin’s effect as an upregulator for IL-6 and IL-8 through the p38 MAPK pathway. It also touches upon the effect the concentration of adiponectin receptors one and two have on the activity of adiponectin.

New Terms:

Antiatherosclerotic - formation of multiple plaques within the arteries which cause a range of effects to the individual.

Metformin - an antidiabetic drug (trade name Glucophage) prescribed to treat type II diabetes.

p38 MAPK - protein kinase activated by environmental stress such as ultraviolet radiation and osmotic shock and by pro-inflammatory cytokines such as tumor necrosis factor (TNF)

Statins - a class of hypolipidemic agents, used as pharmaceutical agents to lower cholesterol levels in people with or at risk for cardiovascular disease.

Fibrates - a group of cholesterol-moderating drugs in use since the early 1960s that includes bezafibrate, gemfibrozil, and fenofibrate. Fibrates are used primarily to treat high triglyceride levels. They can also help to increase HDL levels.

=Articles and Web Pages for Review and Inclusion=

title: Metabolomics/Hormones/Adiponectin


text: User talk:ClubJWP

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text: User talk:202.121.60.121

title: User talk:202.121.60.121


text: User talk:Mooseofdoom

title: User talk:Mooseofdoom


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User talk:Voidvector

Welcome message
Welcome to Wikibooks, Voidvector!

title: User talk:Voidvector


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German/Appendices/Vocabulary/Tools

(The plural article is always "die".)

Vocabulary/Tools

title: German/Appendices/Vocabulary/Tools


text:
Hebrew/Aleph-Bet/Test

 Aleph-Bet Test

Welcome to the final Aleph-Bet test! This will examine your knowledge of what you've learned so far in the Aleph-Bet level. Unlike the exercises, the test will include open questions. You must print it out, fill it, look at the answers and mark using the given points each question is worth.

Good luck!

Letters
What is the name of each letter? (1 point each.) Score: ___/20

Match the letter with the sound that it makes (1 point each pair).

1. Score: ___/10

2. Score: ___/10 Section score:___/40

Niqqud
Match each niqqud symbol with its name and the sound it makes (maybe you'll have to draw several lines to the same sound) (1 point each).

Section score:___/12

Roles and positions of letters
Under each word circle the correct role of the vowel letter in it:

1. The role of the Aleph is: a. Indicates the word start with a vowel. b. Glottal stop. c. "A" sound.

2. The role of the Vav is: a. "V" sound. b. "O" sound. c. "U" sound. d. "W" sound.

3. The role of the Aleph is: a. Indicates the word start with a vowel. b. Glottal stop. c. "A" sound.

4. The role of the Aleph is: a. Indicates the word start with a vowel. b. Glottal stop. c. "A" sound.

5. The role of the Vav is: a. "V" sound. b. "O" sound. c. "U" sound. d. "W" sound.

6. The role of the Yod is: a. "Y" sound. b. "I" sound.

7. The role of the Vav is: a. "V" sound. b. "O" sound. c. "U" sound. d. "W" sound.

8. The role of the Yod is: a. "Y" sound. b. "I" sound.

9. The role of the Vav is: a. "V" sound. b. "O" sound. c. "U" sound. d. "W" sound.

10. The role of the Yod is: a. "Y" sound. b. "I" sound.

Score: ___/10

Determine which of the following words are correct regarding final letters, and which aren't. If the word is incorrect, correct it (one point each). Example: — Incorrect, .

Score:___/10 Section score:___/20

Reading
Transliterate each word (you don't have to know what they mean) (one point each). Example: Aba Score: ___/10

Read and transliterate the following text (18 points). (Genesis 1: 1-5)

Score: ___/5 Section score:___/15

Total score: ___/87

Answers >>>

title: Hebrew/Aleph-Bet/Test


text: User talk:88.173.75.230

title: User talk:88.173.75.230


text: User talk:92.43.64.77

title: User talk:92.43.64.77


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Hebrew/Aleph-Bet/Test/Answers

 Aleph-Bet Test — Answers

Welcome to the answer page to the Hebrew Aleph-Bet test. You have filled the test and you may now check your answers here.

1

 * c
 * f
 * h
 * d
 * a
 * j
 * b
 * i
 * e
 * g

2

 * g
 * e
 * a
 * c
 * i
 * j
 * b
 * h
 * f
 * d

Niqqud

 * 1) j 2
 * 2) h 6
 * 3) g 1
 * 4) f 2
 * 5) b 5
 * 6) c 6
 * 7) d 3
 * 8) k 3
 * 9) a 1
 * 10) l 2
 * 11) e 4
 * 12) i 6

1

 * c
 * b
 * a
 * b
 * d
 * b
 * a
 * a
 * c
 * b

2

 * 1) Correct.
 * 2) Incorrect —.
 * 3) Incorrect —.
 * 4) Correct.
 * 5) Incorrect —.
 * 6) Correct.
 * 7) Incorrect —.
 * 8) Incorrect —.
 * 9) Correct.
 * 10) Correct.

Reading

 * 1) Meħuyyavut
 * 2) Itstadyon
 * 3) Arba‘-‘Esreh
 * 4) Miflagah
 * 5) Tizmun
 * 6) Adrikhalut
 * 7) Metushelaħ
 * 8) Afarseq
 * 9) Higayon
 * 10) Amsterdam

* If you didn't make the Aleph silent - that's okay ** If you didn't make the Yod silent - that's okay

1. Bereshit* bara Elohim et hashamayim ve’et ha’arets.

2. Veha’arets haytah tohu vavohu veħoshekh ‘al penei tehom veruaħ Elohim meraħefet ‘al penei hamayim.

3. Vayomer* Elohim yehi or vayehi or.

4. Vayar* Elohim et ha’or ki tov vayyavdel Elohim ben** ha’or uven haħoshekh.

5. Vayiqra Elohim la’or yom velahaħoshekh qara laylah vayehi ‘erev vayehi boqer yom eħad.

That's it! You now know the Hebrew Alphabet!

Mazal tov!

Introduction: Basic Hebrew >>>

title: Hebrew/Aleph-Bet/Test/Answers


text:
User talk:MagnusA

 * Please use my user talk page at svwp: w:sv:User talk:MagnusA. I speak swedish and english.

title: User talk:MagnusA


text: User talk:216.120.137.146

title: User talk:216.120.137.146


text: User talk:219.95.18.143

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Talk:XForms/Delete

The following text has been copied from the module to the discussion page
 * m_ptrReality begin
 * First forgive my poor english.
 * I use

.xf-repeat-index {background-color :red;} in the style file and it works as expected.
 * btw, you can change the code

 Selected Row=
 * to:

 Selected Row=
 * then it will change it's value dynamicly as you select a line from the "repeat"
 * m_ptrReality end

Copied by --Dom (talk) 14:09, 9 May 2008 (UTC)

title: Talk:XForms/Delete


text: User talk:130.13.232.199

title: User talk:130.13.232.199


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Hebrew/Aleph-Bet/Introduction

Welcome to the Aleph-Bet level of Learning Hebrew!

This level is aimed at junior-high students and older, and can be used by anyone with firm foundations in the English language who wants to begin to learn the Hebrew language or any language that uses the Hebrew alphabet (Yiddish, Ladino, Aramaic etc.).

The goal of this level is to make you capable of reading Hebrew. Any vocabulary or grammar information you may learn in any of the lesson is given to you to enhance your reading and interpreting skills. You will re-learn them anyway in the next lessons. This is also true for the vocabulary exercises.

The lessons are cumulative, which means that they are based on the presumption that you know the material learned in the former lesson.

Lesson Layout
Every lesson is structured in the following way:
 * Centred title in which you are given the chronological position of the lesson and the letters you will learn in it.
 * A brief introduction that states what letters and niqqud symbols you will learn.
 * Each letter will be written using the Hebrew-Huge template.
 * Under the letter will be the letter's name and position in the alphabet, its pronunciation, IPA equivalent and example from the English or closely-related languages.
 * Some further notes will be given about the letter's final and "soft" form (if it has any).
 * Niqqud symbols would be placed under either Ħet, Vav, Shin or Bet, though the standard is on Bet.
 * Under the niqqud symbol would be the symbol's name and sound, as well as some extra notes if there is need of any.
 * Grammar notes if any.
 * Vocabulary that can be put together from the letters and/or vowels you've learned. Again, any vocabulary or grammar information you may learn in any of the lesson is given to you to enhance your reading and interpreting skills. It is of no importance in regards to your knowledge of the Hebrew language, and you will re-learn it anyway.
 * Summary of what you have learned in the lesson.
 * Link to the corresponding exercise page. Each exercises page would include letters and niqqud exercises, vocabulary exercises and reading-without-vowels exercises, at the end of which you would be directed to either the corresponding lesson or to the next lesson.
 * Link to the next lessons.
 * Every five lessons there would be a review of what you've learned in the past five lessons.

Good luck!

Lesson: Aleph-Bet 1 >>>

title: Hebrew/Aleph-Bet/Introduction


text:
User talk:207.193.177.3

about species
what is species ?

title: User talk:207.193.177.3


text:
Hebrew/Aleph-Bet/7

 Aleph-Bet Lesson 7 —

Welcome to the seventh lesson of the Hebrew alphabet! In this lesson you will learn two new Hebrew letters - and  - and the niqqud symbol ħataf-segol.

Tet
The ninth letter in the Hebrew alphabet is Tet. Like Tav, it makes the "t" sound (IPA: /t/, "t" as in "tomato").

Kaf
The eleventh letter in the Hebrew alphabet is Kaf. It has three forms:
 * When the dot is inside, it makes the "k" sound (IPA: /k/, "k" as in "kitten").
 * When there is no dot inside, it makes the same sound as Ħet. For spelling distinction purposes, Ħet (Het, Chet) is transliterated as "ħ" whilst Khaf is transliterated as "kh".
 * At the end of a word, it changes form . This form is known as Khaf Sofit. There is a hard K final form, but it is rarely used.

It is about time for the dot to be explained. This dot, appearing in the letters Bet, Gimmel , Dalet , Kaf , a letter we haven't learned yet and Tav , is known as dagesh ("emphasis"). What it does is to make sounds "harder": "v" to "b", "kh" to "k", and in ancient times "th" to "t", "dh" to "d" etc. Do not confuse the dagesh with mappiq (which indicates that He needs to be pronounced at the end of a word) or dagesh ħazaq (which indicates that a consonant must be emphasized, as in ).

Vowels
One more and we're done!

Ħataf-Segol
The shva and segol under the Bet are the Ħataf-Segol.

It produces the "e" sound (IPA: /e/, "e" as in "bet").

Words
tov good, well (masculine, singular) elohim God mitah bed (feminine, singular) kakh like this, like so kelev dog, hound (masculine, singular) ħatul cat (masculine, singular) ken yes lo no

Summary
In this lesson, you've learned: Practice what you've learned in the exercises.
 * The letters and forms Tet, Kaf , Khaf and Khaf Sofit.
 * The niqqud symbol ħataf-segol.
 * The words and.

Next lesson: Aleph-Bet 8 >>>

title: Hebrew/Aleph-Bet/7


text:
Hebrew/Aleph-Bet/8

 Aleph-Bet Lesson 8 —

Welcome to the eighth lesson of the Hebrew alphabet! In this relatively short lesson you will learn two new Hebrew letters - and.

Samekh
The fifteenth letter in the Hebrew alphabet is Samekh. Like Sin, it makes the "s" sound (IPA: /s/, "s" as in "safe").

Qof
The nineteenth letter in the Hebrew alphabet is Qof (many Israelis pronounce the letter's name as "Quf"). Like Kaf, it makes the "k" sound (IPA: /k/, "k" as in "kitten").

In order to make the distinction between Qof and Kaf (something which will assist you in spelling), Qof is transliterated as a Q. Traditionally, Qof is pronounced as IPA: /q/, same as Kaf only that you make the sound deeper in your throat. The International Phonetic Alphabet symbol for this sound, as well as the common transliteration of it in Semitic languages, is Q - which is why this letter was chosen for that purpose.

Full Writing - Ktiv Malei
As we have already learned, in most texts niqqud aren't written. But there are some letters - Aleph, Vav and Yod - that also produce the "a", "o", "u" and "i" sounds respectively. How can these be expressed when there are no vowels?

These letters are used to assist the reader in distinguishing between words. For instance:

Ktiv ħasser ("empty writing, with niqqud, without vowel letters): mitah bed Ktiv malei ("full writing", without niqqud, with vowel letters):  mitah bed

This form - without niqqud, but with vowel letters for support - is known as ktiv malei "full writing" - because it incorporates the "full" form of the word, with the most letters.

Note: There is no vowel letter for the "e" sound, though it's supposed to be Yod. Also, Aleph is rarely used in Hebrew as a vowel letter, mostly in foreign words (as in varshah Warsaw).

Words
sliħah excuse me, pardon, sorry, forgiveness (feminine, singular) daqqah minute, thin (feminine, singular) sukkot Sukkot, Feast of Booths, Feast of Tabernacles (Jewish holiday) (feminine, plural) (full writing: ) siman sign, symbol, mark  (masculine, singular) sagol purple (masculine, singular) (FW: ) qof monkey, ape (masculine, singular) qemaħ flour (masculine, singular) mas tax (masculine, singular)

Summary
In this lesson, you've learned: Practice what you've learned in the exercises.
 * The letters Samekh and Qof.
 * The words and.
 * "Full writing" - writing with vowel letters replacing niqqud symbols.

Next lesson: Aleph-Bet 9 >>>

title: Hebrew/Aleph-Bet/8


text:
Hebrew/Aleph-Bet/9

 Aleph-Bet Lesson 9 —

Welcome to the ninth lesson of the Hebrew alphabet! In this lesson we will do some reviewing, and you will learn two new Hebrew letters - and  onto its many forms.

Review
We've been through 8 lessons and we've learned a lot. Let's look at the letters we've learned:

Letters
Aleph: makes the "a" sound, makes the glottal stop (’) or simply indicates the word starts with a vowel.

Bet: makes the "b" sound. When there is no dot, it makes the "v" sound.

Gimmel: makes the "g" sound.

Dalet: makes the "d" sound.

He: makes the "h" sound. When at the end of a word it makes the "a" sound.

Vav: makes the "v", "o" and "u" sounds.

Zayin: makes the "z" sound.

Ħet: makes the "kh" sound.

Tet: makes the "t" sound.

Yod: makes the "y" and "i" sounds.

Kaf: makes the "k" sound. When there is no dot, it makes the "kh" sound. Changes form when at the end of a word.

Lamed: makes the "l" sound.

Mem: makes the "m" sound. Changes form when at the end of a word.

Nun: makes the "n" sound. Changes form when at the end of a word.

Samekh: makes the "s" sound.

Qof: makes the "k" sound.

Resh: makes the "r" sound.

Shin: makes the "sh" sound when the dot is on the right; when it's on the left, it makes the "s" sound.

Tav: makes the "t" sound.

Vowels
And we've covered all the vowels:

Shva: marks the end of a syllable or makes the "ə" sound.

Pataħ: makes the "a" sound.

Qamats: makes the "a" sound.

Tsere: makes the "e" sound.

Segol: makes the "e" sound.

Ħiriq: makes the "i" sound.

Qubbuts: makes the "u" sound.

Ħolam: makes the "o" sound.

Shuruq: makes the "u" sound.

Ħataf-Qamats: makes the "o" sound.

Ħataf-Pataħ: makes the "a" sound.

Ħataf-Segol: makes the "e" sound.

New Letters
Three to go!

‘Ayin
The sixteenth letter in the Hebrew alphabet is ‘Ayin. Like Aleph, it stands for the glottal stop (co’operate) or silent if it is at the end of a syllable.

Words
‘ivrit the Hebrew language ‘af‘af eyelid (masculine, singular) peh mouth (masculine, singular) safah language, lip, edge (feminine, singular) sefer book (masculine, singular) mispar number (masculine, singular) ‘of fowl, chicken meat (masculine, singular) pas line, strip (masculine, singular)

Summary
In this lesson, you've learned: Practice what you've learned in the exercises.
 * The letters and forms ‘Ayin, Pe , Fe and Fe Sofit.
 * The words and.

Next lesson: Aleph-Bet 10 >>>

title: Hebrew/Aleph-Bet/9


text:
Hebrew/Aleph-Bet/10

 Aleph-Bet Lesson 10 — + Numbers

Welcome to the tenth and last lesson in the Hebrew alphabet! In this lesson we'll learn and traditional numbers in Hebrew.

Tsadi צ
The eighteenth letter in the Hebrew alphabet is Tsadi. It makes the "ts" sound (IPA: //, "zz" as in "pizza", or "ts" as in "Tsar").

When it is at the end of a word, it changes form. This final form is known as Tsadi Sofit.

That's it, you've learned them all!

Words
mitsrayim Egypt ‘ets tree (masculine, singular) tsahov yellow (masculine, singular) (FW: ) tseva‘ color (masculine, singular) ‘etsem bone (feminine, singular), object (masculine, singular) tsorfat France bots mud (masculine, singular [no pl.]) (FW: ) tsayid hunt (masculine, singular [no pl.]

Numbers
In traditional Jewish texts (in any Orthodox text, really) a numeric system, based on the letters of the alphabet is used. This system is known as gematria. In everyday secular life, the Arabic numerical system (1, 2, 3) is used.

Summary
In this lesson, you've learned: Practice what you've learned in the exercises.
 * The forms of the letter Tsadi, Tsadi Sofit.
 * The words and.
 * The Hebrew nummerical system - gematria.

Review: Aleph-Bet 11 >>>

title: Hebrew/Aleph-Bet/10


text:
Hebrew/Aleph-Bet/11

 Aleph-Bet Lesson 11 —     Review

Aleph-Bet Test >>>

We have finally completed the Hebrew alphabet course! Let's review what you learned in this level:

Letters
Here, each consonant is shown in its own box. Each line contains the name of the letter in English, the actual letter, the transliteration used throughout the book and the IPA equivalent.

Niqqud
The symbols are arranged by pronunciation.

Letters that sound the same
Traditional Hebrew had many phonemes that don't exist today. Most of these sounds are called by linguists "pharyngealised", that is, to produce them you need to "voice" (use your vocal cords) while sticking the root of your tongue to the pharynx. Many European Jews found it impossible to make such sounds, so they replaced them with regular consonants, all of which were already existent in Hebrew. For instance:

Kaf used to be a regular "k" sound (k). Qof used to be a pharyngealised "k" sound (q). Eventually Qof was pronounced the same as the regular "k".

As a result of this merging, many sounds have two letters to represent them. To prevent confusion, here are all the common sounds:

 * Aleph and ‘Ayn  both make the glottal stop (’).
 * Vet and Vav  both make the "v" sound (v).
 * At the end of a word, Aleph and He  both make the "a" sound (a).
 * Ħet and Khaf  both make the "kh" sound (χ).
 * Tet and Tav  both make the "t" sound (t).
 * Kaf and Qof  both make the "k" sound (k).
 * Samekh and Sin  both make the "s" sound (s).

Letters that look the same
Many letters in Hebrew are based on other letters. One could almost call them diacritics. For example:

 * Resh
 * Yod
 * Vav

Many inexperienced readers tend to confuse these letters.

 * Zayin
 * Vav
 * Nun Sofit
 * Mem Sofit
 * Samekh
 * He
 * Ħet
 * Tav
 * Kaf
 * Bet
 * Gimmel
 * Nun
 * Dalet
 * Resh
 * Kaf Sofit

Foreign transliteration
The fact that there are multiple letters for the same sounds, creates a problem. What letters would you use for foreign words, using the Hebrew alphabet? Can you use any of them?

The answer is no. While Tet and Tav, for instance, sound the same, and supposedly we could use both of them, only Tet can be used for the "t" sound. This is because in foreign transliterations Tav might represent the "th" sound ( plimuth Plymouth).

European Languages

 * A — Aleph
 * V — Vav in the beginning of syllables; Vet anywhere else
 * Ch, kh, h — Khaf in German and Greek; Ħet  anywhere else
 * T — Tet
 * Th — Tav, Thav
 * S — Samekh
 * Sh — Shin
 * Ts, tz, z — Tsadi
 * K — Qof
 * Any form of R — Resh
 * Tch (as in "chair") — Tchadi
 * Zh, j, s (as in "pleasure") — Zhayin
 * J, dzh (as in "jam") — Jimmel

Arabic
These transliterations apply only to words of Arabic origin:
 * T — Tav
 * Th — Thav
 * Dj — Jimmel
 * Ħ — Ħet
 * Kh — Khet
 * Dh — Dhal
 * S' — Tsadi
 * D' — Dadi
 * T' — Tet
 * Dh' — Dhet
 * Gh — Ghayin
 * Q — Qof
 * K — Kaf

Niqqud
When writing foreign words, always use the vowel letters Aleph, Vav and.

There are many exceptions regarding Aleph, but don't take the risk.

For example: based on the former table, Tokaj (a town in Hungary famous for its wine) would never be written with Kaf and Tav (then it would be Thokhaj), but rather with Qof and Tet, respectively. But what niqqud would be used?

There are some rules:

 * Never use ħataf forms.
 * "O" is always written with ħolam malei.
 * "U" is always shuruq, never qubbuts.
 * As stated before, always use vowel letters, or in other words, malei forms . It doesn't matter whether the word is written with niqqud or without.
 * Write the "e" without using any vowel letter (this might cause confusion between "e" and "ְ" but this is something you'd have to guess).
 * You can use either Qamats or Pataħ for "a", Segol or Tsere for "e".

Then the word Tokaj would be written.

Aleph-Bet Test >>>

title: Hebrew/Aleph-Bet/11


text: User talk:209.173.14.125

title: User talk:209.173.14.125


text:
Metabolomics/Hormones/Somatostatin

Back to Previous Chapter: Metabolites Next chapter: Analytical Methods Go to: Corticosteroids Go back to: Glucagon

= Introduction =

Somatostatin (SS) was first discovered in hypothalamic extracts. It is defined as a polypeptide hormone that inhibited secretion of other hormones, especially growth hormone, glucagons, insulin, thyrotropin, gastrin, and etc, depending on physiologic situation. Besides hypothalamus, it is found to be secreted by many other tissues such as pancreas, intestinal tract, and regions of the central nervous system outside the hypothalamus. Regardless where it is found, the synthesis and structure appears to be identical. Also, no matter where it is found, the action of it is always inhibitory.

Link to the website:

= Structure and Synthesis =

Somatostatin is synthesized as a 116 amino acid preprohormone that is subsequently cleaved to two forms. The two forms are SS-14 and SS-28 amino acid coupounds. They reflect their amino acid length. Both forms of somatostatin are produced by proteolytic cleavage of prosomatostatin, which itself is derived from preprosomatostatin. Two cysteine residules in SS-14 allow the peptide to form an internal disulfide bond.

Fig. 1: Shows the formation of SS-14 and SS-28

The production amount of the two forms, SS-14 and SS-28, depends upon the tissue they are being secreted in. SS-14 is the predominates in the hypothalamus and endocrine pancreas. SS-28 is more abundant in the GI tract. The two forms also can have the different biological potencies.

Receptors and Mechanism of Action
Somatostatin acts by both endocrine and paracrine pathways to affect its target cells. There are all together five stomatostatin receptors that are recognized and characterized. All of them five belong to G protein-coupled receptor superfamily. Each of the receptors activates different signaling mechanisms within cells. However, all inhibit adenylyl cyclase. It is found that four of the five receptors do not differentiate SS-14 from SS-28.

Effects on the Pituitary Gland
Fig. 2: Pituitary GH and hepatic IGF-1 secretion in the hypothalamic-pituitary feedback system.

Growth hormones is produced in the pituitary and it is stimulated by hypothalamic growth hormone releasing hormone (GHRH). The growth hormone secretion is controlled by the interaction of somatostatin and growth hormone. The figure above shows the feedback system how the inhibition takes place.

Effects on the Pancreas
Fig. 3: Shows the pancreatic islet and what is secreted in it.

The diagram shows cells within pancreatic islets secrete insulin, glucagon and somatostatin. Somatostatin appears to act primarily in a paracrine manner to inhibit the secretion of both insulin and glucagon. It also has the effect in suppressing pancreatic exocrine secretions, by inhibiting cholecystokinin-stimulated enzyme secretion and secretin-stimulated bicarbonate secretion.

Effects on the Gastrointestinal Tract
Somatostatin is secreted by scattered cells in the GI epithelium. Somatostatin shows the inhibition of many GI hormones such as gastrin, cholecystokinin, secretin, and so on. It also suppresses the secretion of gastric and pepsin which lowers the rate of gastric emptying and reduces smooth muscle contractions and blood flow within the intestine. Overall, these effects tend to decrease the rate of nutrient absorption.

Effects on the Nervous System
Somatostatin is also produced in the nervous system. It has neuromodulatory activity within the central nervous system. It has a variety of complex effects on neural transmission. For example, injection of somatostatin into the brain of rodents leads to such things as increased arousal and decreased sleep, and impairment of some motor responses.

Pharmacologic Uses
Somatostatin and its synthetic analogs are used clinically due to its ability to inhibit certain hormones secretion. It is used to treat a variety of neoplasms such as giantism and acromegaly.

Somatostatin Analogs for Diagnosis and Staging of Tumors
http://www.med.harvard.edu/JPNM/TF93_94/Mar8/WriteUpMar8.html

This article is a case presentation of a 49 year old female who was diagnosed with non-Hodgkin’s lymphoma stage IIIA in 1983. After successful chemotherapy, the cancer went into remission. However, in 1990 a recurrence was detected using a gallium-67 scintigraphy which suggested that the tumor was an indolent tumor. Since most human tumors originating from somatostatin target tissue have conserved their somatostatin receptors, a somatostatin analog, octreotide, was given to the patient and traced inside her body. This analog has all of the same pharmaceutical properties as somatostatin, except that it stays in the body much longer. Using in vitro audiography with 25-I-Tyr-3-Octreotide, the somatostatin receptor’s status was evaluated in the tumor cells. It showed that the high grade lymphomas expressed a very high density of receptors. The low to intermediate grade lymphomas also expressed a moderate density of receptors.

This relates to the course because it shows that the hormone somatostatin is still present on tumor cells. It has some functionality in the regulation of the tumor because the tumor cells exhibit different densities of somatostatin receptors at different stages of the cancer.

Somatostatin
http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/otherendo/somatostatin.html

This article gives a summary of somatostatin and its regulation and effects on different organs or glands in the body. Somatostatin has two polypeptide forms, a 14 amino acid chain (SS-14) and a 28 amino acid chain (SS-28). These are both generated by the cleavage of prosomatostatin. The effects of somatostatin can be summarized in that it inhibits the secretion of many other hormones. Specifically, somatostatin affects the pituitary gland in that it causes inhibition of secretion of growth hormone which is vital to cells in growth and metabolism. In the pancreas, somatostatin inhibits the secretion of insulin and glucagon which play an important role in glucose regulation in the body.

Somatostatin affects the gastrointestinal tract (GI) by inhibiting the secretion of gastrin, cholecystokinin, secretin and vasoactive intestinal peptide. Finally, injection of somatostatin into the nervous system of rodents can cause increased arousal, decreased sleep, and an impairment of some motor responses.

This article relates to the course because it talks about somatostatin’s role in the pancreas in which it affects insulin and glucagon. Insulin and glucagon regulate the body’s glucose levels. The regulation of these hormones were studied in-depth, but without much talk on somatostatin. This article shows that somatostatin has a regulation effect on these hormones.

Can somatostatin control acute bleeding from oesophageal varices in Schistosoma mansoni patients?
http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=539281&blobtype=pdf

This article deals with a proposed study on subjects infected with Schistosoma mansoni. People infected by the parasite suffer from fibrosis, hepatomegaly, splenomegaly, haematemesis, varices, portal hypertension, ascites formation and eventually can lead to death. Portal hypertension can lead to the formation of gastro-oesophageal varices. Due to their fragility, these gastro-oesophageal varices are prone to bleed and can lead to death. So far, treatments such as praziquantel are effective against the worm stages of the parasite but they are not effective against the bleeding. The neuropeptide, somatostatin, has been proposed to be able to reduce bleeding in Schistosoma mansoni infected subjects. A research study is to be put underway in which adolescent subjects, age range varying from 12–17 years, will be chosen who are infected with the parasite and will be split into two groups. One group will be given praziquantel and somatostatin, while the other will be given praziquantel and propanolol. The results of this have not been included in the article. However it is believed that the patients who are given somatostatin will stop bleeding immediately and delay rebleeding and mortality. Even though this article talks about medical uses of somatostatin, which was not covered in the course, it still has relations to the course. This article gives a medical use of somatostatin, a hormone, which is involved in regulation of growth and metabolism of cells. In many of the chapters studied, biochemistry has been linked with medicine.

A pilot study of a long acting somatostatin analogue for the treatment of refractory rheumatoid arthritis
http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=1753815&blobtype=pdf

This article deals with a study for treatment of rheumatoid arthritis with long acting somatostatin. Chronic inflammation, which is caused by this arthritis, can lead to development of a pannus, which causes progressive destruction of the joints. In vitro studies of somatostatin have shown to inhibit the proliferation of human lymphocytes, the production of immunoglobulins by B lymphocytes, and neutrophilchemotaxis. Activated T lymphocytes, macrophages, B cells and the cytokines they produce are involved in the aggravated inflammatory tissue which develops into the pannus. From this past research, researches set out to test the effect of a somatostatin analogue on patients with rheumatoid arthritis. Ten patients (all of whom were women age 18-70) with longstanding rheumatoid arthritis who had no reaction to multiple disease modifying antirheumatic drugs (DMARDs) were chosen for this experiment. These patients were treated with monthly injections of 20 mg Sandostatin-Lar, which contains an analogue of somatostatin, for three months. The results showed that six patients responded achieving an ACR 20 response. This concluded that treatment of somatostatin on patients with active, refractory rheumatoid arthritis led to significant clinical improvements that were also safe. This article relates to the class because, like the Schistosomiosis paper, it relates biochemistry to medicine and how the hormone somatostatin can play a part in medicinal purposes.

=Oxidative Phosphorylation & Molecular Oxygen Regulation=

Somatostatin has been proven to be incapable of affecting changes of O2 consumption (ΔO2) that had been stimulated by mitochondrial fuels. It was once assumed that somatostatin is produced during alterations in respiratory control of oxidative phosphorylation. Findings indicated that the hormone directly inhibits oxidative phosphorylation at a step prior to the TCA cycle.

An 8-CPT stable membrane permeable cAMP analog has been proven to not inhibit ΔO2 by somatostatin, which removed the possibility of reduced levels of cytosolic cAMP being involved in this inhibition. However, the molecular target(s) for this inhibition remain unknown.

The inhibition of ΔO2 by the somatostatin receptor type- (sstr) selective analogs is in support of the effects of somatostatin developing exclusively through binding to sstr5. This sstr5 is responsible for mediating activation of the KATP channel, and inhibiting the secretion of insulin in mice, rats, and men.

O2 reduction can occur via the mitochondrial electron transport chain, or NAD(P)H oxidase activity and superoxide production. A range of NAD(P)H oxidase isoforms have been identified as being expressed within pancreatic islet tissue. The p47PHOX isoform has been discovered to be predominantly expressed in pancreatic beta-cells, at the plasma membrane. Somatostatin was discovered to inhibit ΔO2 without mechanisms involving NAD(P)H oxidase activity. Furthermore, the inhibition of the mitochondrial reduction of O2 by azides was proven to nullify the effect of somatostatin on ΔO2. This indicates that azides have no effect on the oxidase activity of NAD(P)H. Overall, the role of NAD(P)H oxidases in the effect of somatostatin on ΔO2 is still undetermined.

Link to article:

http://endo.endojournals.org/cgi/content/full/147/3/1527#SEC3

Glossary of terms:
Scintigraphy: A diagnostic technique in which a two-dimensional picture of a bodily radiation source is obtained by the use of radioisotopes.

Octreotide: A potent, long-acting somatostatin octapeptide analog which has a wide range of physiological actions.

Mediastinal: Of or pertaining to a space in the thoracic cavity behind the sternum and in between the two pleural sacs (containing the lungs).

Indolent tumor: Causing little or no pain; inactive or relatively benign.

Astrocytoma: A neuro-ectodermal tumor arising from astrocytes (The largest and most numerous neuroglial cells found in the brain and spinal cord).

Prosomatostatin: Precursor to somatostatin.

Pancreatic islets: Groups of cells found within the pancreas.

Cholecystokinin: A 33-amino acid peptide secreted by the upper intestinal mucosa and also found in the central nervous system. It causes gallbladder contraction, release of pancreatic exocrine (or digestive) enzymes, and affects other gastrointestinal functions.

Enteric nervous system: Local nervous system of the digestive tract.

Pepsin: Principal proteases in gastric secretions of adult mammals.

Gastrin: A major physiological regulator of gastric acid secretion.

Paracrine: Form of signaling in which the target cell is close to the signal releasing cell.

Oesophageal varices: Abnormal dilation of the veins in the oesophagus that occurs as the result of cirrhotic liver disease. Oesophageal varices are prone to bleed due to their fragility.

Portal hypertension: Any increase in the portal vein (in the liver) pressure due to anatomic or functional obstruction (for example alcoholic cirrhosis) to blood flow in the portal venous system.

Schistosomiosis: Disease caused by digenetic trematode worms of the genus Schistosoma, the adults of which live in the urinary or mesenteric blood vessels.

Fibrosis: The formation of fibrous tissue, fibroid or fibrous degeneration.

Oesophageal varices: Abnormal dilation of the veins in the oesophagus that occurs as the result of cirrhotic liver disease.

Rheumatoid arthritis: Chronic, multisystem autoimmune disease characterized by persistent synovitis.

Synovitis: Inflammation of a synovial membrane (a membrane which secretes a transparent, viscid, lubricating fluid which contains mucin.

Human lymphocytes: White blood cell, with two main classes: T lymphocytes and B lymphocytes.

Pannus: An aggressive inflammatory tissue where activated T lymphocytes, macrophages, B cells and the cytokines they produce, as well as active angiogenesis play a major part in the progressive destruction of the joints.

ACR 20: The criteria for improvement in rheumatoid arthritis according to the American College of Rheumatology (ACR).

Endocrine action: the hormone is distributed in blood and binds to distant target cells.

Paracrine action: the hormone acts locally by diffusing from its source to target cells in the neighborhood.

Online dictionary: http://cancerweb.ncl.ac.uk/omd/

=Articles and Web Pages for Review and Inclusion=

title: Metabolomics/Hormones/Somatostatin


text: User talk:99.140.170.128

title: User talk:99.140.170.128


text:
Chess Opening Theory/1. e4/1...g5

= Borg Defence =

1...g5?!
The Borg (Grob spelt backwards) or Basmaniac Defence. A rare defence that Michael Basman employed in the 1980 British Championship. Although this move is generally considered inferior and weakens the kingside severely, according to Modern Chess Openings, Black is only somewhat worse.

Theory table
1. e4 g5?!

title: Chess Opening Theory/1. e4/1...g5


text:
Chess Opening Theory/1. e4/1...c5/2. c4

= Sicilian - Staunton-Cochrane variation (English variation) =

2. c4, the purpose here is to restrict Black from the freeing move d5 and bring a Maróczy Bind. The downside is that White is no longer able to support d4 with a pawn.

Theory table
.

'''1. e4 c5 2. c4'''

title: Chess Opening Theory/1. e4/1...c5/2. c4


text:
Chess Opening Theory/1. e4/1...c5/2. f4

= Sicilian - Grand Prix Attack = 2. f4, with the idea of an aggressive attack against the Black King. Black can neutralise the threat with an immediate d5; for this reason the attack is often played in the move order 2. Nc3 followed with f4.

Theory table
.

1.e4 c5 2.f4

title: Chess Opening Theory/1. e4/1...c5/2. f4


text:
Dutch Empire/Dutch Kings and Queens

Here are the Kings and Queens of the Netherlands, since the modern government was formed in 1815.

title: Dutch Empire/Dutch Kings and Queens


text:
Dutch Empire/Stadtholders of Holland

This is a list of Stadtholders of Holland since Independence was declared in 1581.

title: Dutch Empire/Stadtholders of Holland


text:
Chess Opening Theory/1. e4/1...c5/2. Nf3/2...g6

= Sicilian - Hyper-Accelerated Dragon =

2...g6
This early g6 in the Sicilian signifies the Hyper-Accelerated Dragon, also called the Hungarian variation (not to be mistaken with the Hungarian Defense, which appears after 1.e4 e5 2.Nf3 Nc6 3.Bc4 Be7). The main idea in the Hyper-Accelerated Dragon (HAD) is to delay d6, in order to be able to play the liberating d5 push in one go. This move is a gambit but is sound and is considered mainline. The advantage of this is that if white goes for the classical moves 3.d4 c.cxd4 4.Nxd4 Nc6 5.Nc3, Black can choose to prevent White from having the usual setup with Be3, Bc4, Qd2, and O-O-O. He can also transpose back into the regular dragon by playing d6.

The main drawback of this variation is that having delayed Nf6, White can play c4 before Nc3, setting up a Maroczy bind. The position is still equal, but black must know how to respond effectively, because it is easy to suffocate in this cramped position.

The main 5.Nc3 (or 6.Nc3 if 5.Be3) goes : 1.e4 c5 2.Nf3 g6 3.d4 cxd4 4.Nxd4 Nc6 5.Nc3 Bg7 6.Be3 Nf6 7.Bc4 O-O 8.Bb3 a5 9.f3 d5 blasting the position open before white can castle queenside. White's best response is 10.exd5, and it is important for black to study the plans and tactics involved beforehand.

The 4.Qxd4 line is perfectly fine for black : 1.e4 c5 2.Nf3 g6 3.d4 cxd4 4.Qxd4 Nf6 5.e5 Nc6 followed by Nd5.

The Maroczy bind variation with an early c4 (due to black delaying Nf6) can be fought via different means by Black. It can be met with 1.e4 c5 2.Nf3 g6 3.d4 cxd4 4.Nxd4 Nc6 5.c4 Nf6 6.Be3 d6 with the idea of exchanging the knights on d4 to prevent the Be3/Qd2 battering ram that would take away Black's strongest piece, its g7 bishop. This is the line that has been played in recent years as an attempt to fight the Maroczy setup. Another possible way of playing it is like the regular Accelerated Dragon (Bg7 d6 etc.), with ideas of Qa5 or Qb6. These variations are critical for Black, as his position remains cramped for quite a long time. However, with good play, black is fine.

The other Maroczy bind line goes '''1.e4 c5 2.Nf3 g6 3.d4 cxd4 4.Nxd4 Nc6 5.c4 Bg7 6.Be3 Nf6 7.Nc3 Ng4!? 8.Qxg4 Nxd4 9.Qd1 Ne6'''. At this point, White must choose between a few options : Qd2, Be2, and Rc1 are the most popular. 10.Be2 is considered inferior, as Black has the unorthodox reply 10...Bxc3 !. The idea is that, after doubling white pawns, the pawn on c4 is weaker, as it can't be defended with the rook via c1. The setup for white after this is a hedgehog setup, where he keeps moving his pieces to threaten c4 and e4. The light-squared bishop usually moves quite a lot, on the squares c8-b7-a6-c6. The pawns on the queen side usually go on b6 and d6, with the formation Qc7, Rac8, Rfd8, preparing Nc5. Therefore, 10.Rc1 and 10.Qd2 are prefered, when Black can continue with the regular Qa5 plan.

An attempt to avoid the regular Maroczy is for black to delay cxd4. E.g. 1.e4 c5 2.Nf3 g6 3.d4 Bg7. If White plays 4.c4, then Black has the possiblity of 4...Qb6!, transposing into a variation of the Modern Defense, and with the idea of having an active queen on the dark squares. However, this is considered inferior, not because of 4.d5 (although playable) but because of the line 4.dxc5 Qa5+ 5.c3 Qxc5 6.Na3!, where White has the better game.

Yet another plan can be played to fight the Maroczy bind, which has been played up to the 70's, but lost popularity over the years. The idea is to play Nh6 with Nxd4 and f5. However, this is rarely played nowadays, as black usually has to exchange the dark-squared bishops, and has trouble on the dark-squares afterwards. Black has, however, active pieces, and can be a try for the well-prepared club player, preferring dynamic positions.

Theory table
For explanation of notation, see Chess Opening Theory Table.

1.e4 c5 2.Nf3 g6


text:
Chess Opening Theory/1. e4/1...c5/2. Nf3/2...a6

{{Chess Opening Theory/Position|=
 * Sicilian - O'Kelly variation|

|rd|nd|bd|qd|kd|bd|nd|rd|= | |pd|  |pd|pd|pd|pd|pd|= |pd| |  |  |  |  |  |  |= | |  |pd|  |  |  |  |  |= | |  |  |  |pl|  |  |  |= | |  |  |  |  |nl|  |  |= |pl|pl|pl|pl| |pl|pl|pl|= |rl|nl|bl|ql|kl|bl| |rl|=

Truth
White's attack is way too }} =Sicilian - O'Kelly variation=

2...a6
This early a6 prevents White from occupying b5, so after 3. d4 cxd4 4. Nxd4 Nf6 5. Nc3 e5 and then 6. Nb5 is prevented. The main problem with this variation is how to deal with 3. c3, which transposes to an Alapin Sicilian with the useless a6 move. Another problem is 3. c4 d6 d4 Bg4 dxc5 Bxf3 gxf3! dxc5 (An alternative is Qa5+ Nc3 Qxc5 (dxc5?! Qb3 (Ra7!?) Qc7? (Black would have done better to give up a pawn) Bf4! with a winning attack) Be3 Qc6 with a huge lead in development and two Bishops). Qxd8+ Kxd8. For the ruined structure, white has a crushing attack and 2 Bishops. d4 is also absolutely normal move

Theory table
For explanation of notation, see Chess Opening Theory Table.

1.e4 c5 2.Nf3 a6


text: Wikibooks:Requests for deletion/Steer trippin


text: Wikibooks:Requests for deletion/Ear piercing again


text:
Talk:Algorithms/Randomization

Added in a shuffle algorithm I used in a card game. Formating isn't perfect and there is little in the way of explanation.

Here is a source code for find-median that uses the idea presented in the text, excluding the separation into 'partition' and 'find'. This code works (well at least for a bunch of tests that I did). It partially sorts the array, so that values on the left hand side of the array are less then values on the right hand side of it. Its time complexity is O(n), because it make one pass, and its memory complexity is O(n), because it creates a copy of the array, in order not to change the original. If original array is allowed to be changed, then, this can be modified so that memory complexity is constant.

I hope this code will help the writers of this section or anybody else. the programming language is JAVA. The license is GFDL of cource:) -- codalyzer-93.173.252.100 (talk) 14:24, 13 May 2009 (UTC)

Algorithm in that code is not randomized at all and doesn't compute median either (try to set that array to (10,7,3,88,55,21,-2,3,0,1,65,35,25,90,2) ). On basis of writer having obviously no clue, I'm gonna remove his edits... MacHala (discuss • contribs) 13:14, 21 December 2012 (UTC)

title: Talk:Algorithms/Randomization


text:
Chess Opening Theory/1. e4/1...c5/2. Nf3/2...Nf6

= Sicilian - Nimzowitsch Variation =

2...Nf6
This attack on the e4 pawn is similar to the Alekhine's Defence. White normally plays e5 to attack the knight on f6.

Theory table
For explanation of notation, see Chess Opening Theory Table.

1.e4 c5 2.Nf3 Nf6


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Yours, Keegan Peterzell Community Liaison, Wikimedia Foundation 23:23, 17 March 2015 (UTC)

Renamed
 This account has been renamed as part of single-user login finalisation. If you own this account you can |log in using your previous username and password for more information. If you do not like this account's new name, you can choose your own using this form after logging in: . -- Keegan (WMF) (talk) 05:08, 19 April 2015 (UTC)

title: User talk:Kerwyn~enwikibooks


text:
User talk:Kerwynsteele

Welcome to Wikibooks, Kerwynsteele!

title: User talk:Kerwynsteele


text:
Chess Opening Theory/1. e4/1...c5/2. Nf3/2...b6

=Sicilian - Katalimov variation=

2...b6
This fianchetto of the Queen's Bishop leaves Black with many weak white colored squares on the Queenside where allowing a possible Bb5 or Nb5, while it does nothing to develop on the Kingside. White's best move is '''3. d4''' and sets a trap if Black plays 7...d6??, White can win a queen with 8. Bb5+! (see diagram below).

Theory table
For explanation of notation, see Chess Opening Theory Table.

1.e4 c5 2.Nf3 b6


text:
User talk:98.221.171.223

Welcome!
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– Mike.lifeguard  | talk 00:03, 10 May 2008 (UTC)

title: User talk:98.221.171.223


text: User talk:74.206.91.194

title: User talk:74.206.91.194


text:
Ktorrent

KTorrent is an advanced BitTorrent client for the K Desktop Environment.

Note:
KTorrent was last updated Jan 17 2013, and the original website, ktorrent.org, has been abandoned since.

Last Known Info:

Website: [ https://www.kde.org/applications/internet/ktorrent/ ]

Last Post: [ https://www.linux-apps.com/content/show.php?content=26353 ]

Table of Contents

 * 1) Introduction
 * 2) What is BitTorrent?
 * 3) How do I download files using BitTorrent?
 * 4) *Opening a New Torrent
 * 5) *Importing a Torrent With Existing Data (a partial download)
 * 6) Configuring KTorrent
 * 7) *Downloads
 * 8) **Queue Manager
 * 9) **Preferences
 * 10) **Attention/forward port
 * 11) *General
 * 12) **Folders
 * 13) **system tray icon
 * 14) **Custom IP
 * 15) **DHT
 * 16) **Encryption
 * 17) *Advanced
 * 18) **Performance
 * 19) **Data Checking
 * 20) **Networking
 * 21) *Plugin Options
 * 22) *ScanFolder plugin
 * 23) *Log viewer plugin
 * 24) *UPnP plugin
 * 25) *Info widget
 * 26) *Search plugin
 * 27) *Webinterface plugin
 * 28) *Scheduler plugin
 * 29) *IP blocking filter
 * 30) Using KTorrent
 * 31) *Starting a torrent
 * 32) *A look into torrent statics
 * 33) *Using the Queuemanager
 * 34) *Info Widget
 * 35) **Status
 * 36) **Files
 * 37) **Peers
 * 38) **Trackers
 * 39) *Controlling torrents
 * 40) *Grouping panel
 * 41) *Bandwidth scheduler
 * 42) *Logviewer
 * 43) *IP Filter
 * 44) *Web interface plugin
 * 45) Command Reference
 * 46) *The Help Menu
 * 47) Questions and Answers
 * 48) Credits and License

A. Installation B. Meaning of used terms in this handbook
 * How to obtain KTorrent
 * Requirements
 * Compilation and Installation

title: Ktorrent


text: User talk:86.105.181.238

title: User talk:86.105.181.238