OpenLLM-France/wikimedia huggingface dataset:
# Sonic the Hedgehog 2/Emerald Hill Zone

A green island with big fields and beaches and other tropical islands in the distance.

## Act 2
### Boss

The boss of this Zone is comprised of a car equipped with a drill bit in front and driven by Dr. Robotnik. After seven hits, Eggman shoots the drill bit at Sonic; one more hit destroys his machine.
# Sonic the Hedgehog 2/Hill Top Zone

Hill Top Zone is a dichotomy, featuring both lava-pits and icy elements.

## Act 1

Some enemies here are hard to avoid, such as an enemy type that shoots out 4 fireballs.

## Act 2

Act 2 plays similar to Act 1, except for the addition of a Boss.

## Boss

The boss fight takes place in a lava pit. Here Robotnik shoots the player character with fireballs. Consistant attacks are a good strategy.
# Sonic the Hedgehog 2/Chemical Plant Zone

A zone themed on a large industrial plant, producing the deadly Megatox compound (the strange pink water).

## Act 2
### Boss

The Boss of this zone is a goo shooter piloted by Robotnik. The platforms on the left and right keep disappearing. You will loose if you fall down. Robotnik will suck up water in his machine and when full will aim the bucket at you. Robotnik is vulnerable while he is sucking up the water, however he does it over the disappearing platforms.
# Sonic the Hedgehog 2/Death Egg Zone

In this zone Sonic must battle against 2 bosses, a silver Sonic robot and Mecha-Robotnik (a giant armored battle suit). There are no rings available and Sonic is alone without Tails for help.
After defeating the bosses Sonic will run out of the exploding Death Egg and skydive back down, and is caught by Tails' plane (unless you have managed to collect all the Chaos Emeralds; in that case Super Sonic flies alongside the plane).
# Sonic the Hedgehog 2/Metropolis Zone

The longest stage, composed of three acts, as in the first Sonic game. It consists of a mechanical complex or city, with various machinery, gadgets and devices.
# Sonic the Hedgehog 2/Mystic Cave Zone
## Act 1

Jump to dodge the long spiky bricks.
The only badnik you should be worried about is a bug enemy who turns yellow. While this enemy is yellow, it cannot be hit.

## Act 2

Act 2 plays similarly to Act 1 except for the boss.

## Boss

Dodge spike-like rubble and hit him 8 times to win.
# Speech-Language Pathology/Stuttering/VoiceAmp

* Anti-stuttering technology: ???
* Pocket-size.
* Monaural (one ear)?
* Website: http://www.voiceamp.net
* Price: US$1850

## Personal Experiences Using Defstut

Please read Speech-Language Pathology/Stuttering/How to Participate in this Wikibook before adding material.
# Structural Biochemistry/Enzyme/Acetyltransferase

An acetyltransferase is an enzyme that catalyzes the transfer of acetyl groups.

### p300/CBP

p300 and CREB binding protein (CBP) are both acetyltransferases that are highly conserved. Both have specific domains within the enzyme: three cysteine-histidine rich domains, bromodomain, and acetyltransferase domain. CBP/p300 phosphorylation activates acetyltransferase activity, which increases histone acetylation at target promoters and facilitates CBP/p300-dependent transactivation of genes. The acetyltransferase domains in these enzymes also uncovered autoacetylation activity. Autoacetylation of these enzymes causes a conformational change of the histone as well as the enzyme itself that directly affects the enzyme's ability to interact with Mediator, which is a multi-protein complex that plays an important role in the beginning stages of transcriptional activation.

### TIP60

TIP60 is party of the MYST family of acetyltransferases conserved from yeast to humans. It acetylates core histones H2A, H3, and H4. This enzyme plays a crucial role in DNA damage response and apoptosis. TIP60 acetylizes the ataxia telangiectasia mutated (ATM) kinase, which is the central kinase in the repair pathways started by DNA lesions. Studies also show that ATF2 interacts with TIP60 and modulates its function at the DNA damage response step. Before DNA damage, ATF2 has low TIP60 levels by facilitationg TIP60 degradation. After DNA damage, TIP60 and ATF2 are more loosely associated. In addition, the sumoylation of TIP60 plays a key role in the localization and catalytic activity of the enzyme, influencing the enzyme's ability to help with DNA damage. Through experiments and observations, researchers have concluded that there is an important link between TIP60 levels and the signals generated by DNA damage response pathways. Evidence shows that human prostate cancer samples display loss of TIP60 and human lymphomas and mammary tumors display loss of TIP60.

## Reference

Mellert, Hestia S. and McMahon, Steven B. "Biochemical pathways that regulate acetyltransferase and deacetylase activity in mammalian cells." Trends in Biochemical Sciences Vol. 34 No. 11. 2009.
# Structural Biochemistry/Enzyme/Affinity Labels (reactive substrate analogs)
## Definition

Affinity label or reactive substrate analog are molecules that have a similar structure to the substrate allowing them to covalently bind to the active site of the enzyme. They react with the substrate, inhibiting the enzyme. Essentially, affinity labels mimic the functional properties of the substrate, but consequently irreversibly inhibits the enzyme through the strong covalent bonding. Because of its similarity to the substrate, it initially binds at the active site; however, the covalent bonds it forms irreversibly modify the enzyme. They are much more specific than group specific inhibitors. They are usually highly reactive. Also, there will be alkylate nucleophilic amino acids in the enzyme. However, their properties are rather non-selective and toxic, making them not as useful in many situations.
Substrate analogs that bind to active sites of enzymes to form product of covalent bond that is stable on binding site to inhibit chemical reaction; irreversible enzyme inhibitor that react with functional group of enzyme and has more specificity for enzyme.

## Use of Affinity Labels

Affinity labelling can be used to localize a given site within a protein of a known amino acid sequence. It allows comparisons to be made between the substrate sites of the enzyme in the solution and the sites localized within the crystalline form through X-ray diffraction. This can test whether the compound that is bound irreversibly at the substrate site can influence the enzyme conformation, subunit interaction, or the reactivity of other ligand sites.

## Example of an Affinity Label

Tosyl phenylalanyl chloromethyl ketone is a substrate analog for chymotrypsin. This molecules binds at the active site and then react irreversibly with histidine residue at that site, inhibiting the enzyme. File:800px-Tosyl phenylalanyl chloromethyl ketone.PNG
# Structural Biochemistry/Enzyme/Apoenzyme and Holoenzyme
## Cofactor: A Definition

Many enzymes require an additional small molecule, known as a cofactor to aid with catalytic activity. A cofactor is a non-protein molecule that carries out chemical reactions that cannot be performed by the standard 20 amino acids. Cofactors can be either inorganic molecules (metals) or small organic molecules (coenzymes).
Cofactors, mostly metal ions or coenzyme, are inorganic and organic chemicals that function in reactions of enzymes. Coenzymes are organic molecules that are nonproteins and mostly derivatives of vitamins soluble in water by phosphorylation; they bind apoenzyme protein molecule to produce active holoenzyme.
Figure 1-1: A flow chart of the two types of cofactors.
Apoenzyme- An enzyme that requires a cofactor but does not have one bound. An apoenzyme is an inactive enzyme, activation of the enzyme occurs upon binding of an organic or inorganic cofactor.
Holoenzyme- An apoenzyme together with its cofactor. A holoenzyme is complete and catalytically active. Most cofactors are not covalently bound but instead are tightly bound. However, organic prosthetic groups such as an iron ion or a vitamin can be covalently bound. Examples of holoenzymes include DNA polymerase and RNA polymerase which contain multiple protein subunits. The complete complexes contain all the subunits necessary for activity.
Figure 1-2: Illustrates that an Apoenzyme + Cofactor = Holoenzyme.

## Examples of Holoenzymes

DNA polymerase is a holoenzyme that catalyzes the polymerization of deoxyribonucleotides into a DNA strand. DNA polymerase is an active participant in DNA replication. It reads the intact DNA strand as a template and uses it to synthesize the new strand. The newly polymerized DNA strand is complementary to the template strand and identical to template's original partner strand. DNA polymerase uses a magnesium ion for catalytic activity.
Figure 1-3: Illustrates the holoenzyme DNA polymerase a multi-subunit complex.
RNA polymerase is also a holoenzyme that catalyzes RNA. RNA polymerase is needed for constructing RNA chains from DNA genes as templates, a process known as transcription. It polymerizes ribonucleotides at the 3' end of an RNA transcript.
Figure 1-4: Illustrates the holoenzyme RNA polymerase a subunit complex.

## References

Berg, Jeremy M., et al. "Biochemistry". 6th ed. W.H. Freeman and Company, NY, 2006.
# Structural Biochemistry/Enzyme/Binding energy
## Structure

The binding energy is the free energy that is released by the formation of weak interactions between a complementary substrate and enzyme. The binding energy is maximized since only the correct substrate can interact with an enzyme and is released when the enzyme facilitates formation of the transition state. This interaction between the enzyme and the transition state gives way to the maximum binding state. Upon formation of the transition state, the activation energy is lowered, which will speed up the reaction.
Binding energy is known as separation energy that is the requirement for dissociation of chemical substance to its constituent components. There are different binding energies at different molecular level such as electron binding energy, atomic binding energy, nuclear binding energy, and gravitational binding energy.
With the units of eV, electron binding energy is the energy required to release an electron from its atomic or molecular orbital. According to Moseley's law, the binding energies of 1s electron are proportional to(Z-1)$^2$.
To dissemble an atom into free electrons and nucleus, atomic binding energy is required. It is the energy that was derived from electromagnetic interaction.
Nuclear binding energy is also known as binding energy of nucleons into a nuclide. It was derived from the strong nuclear force and is the energy required to disassemble a nucleus into the same number of free unbound neutrons and protons that its contained. Such that the particles are far enough from one another so that the strong nuclear force can no longer cause the particles to interact. In bound systems, the mass must be subtracted from the mass of the unbound system, if the binding energy is removed from the system, because this energy has mass. If subtracted from the system at the time it is bound, the mass of the system will be removed. Since the system is not closed during the binding process, system mass is not conserved.
* Wikipedia-Binding Energy
* Nuclear Binding Energy
* ↑ , Wikipedia-Binding Energy
* ↑ , Nuclear Binding Energy
# Structural Biochemistry/Enzyme/Catalysis By Approximation
## Catalysis by Approximation

Substrates that happen to come together through random collisions have an even smaller possibility of contact with the reactive portions of the substrate. Thus, enzymes can employ a strategy known as catalysis by approximation by which the enzyme brings together two substrates in order to increase the rate of reaction. This strategy takes advantage of binding energy and positions the substrates in the correct orientation for the reaction to proceed. Usually in a reaction, there will be a loss in translational entropy and rotational entropy. In the reaction, the transition state is much more ordered than it is at ground state, making delta S negative. This reaction takes place in the active site of an enzyme and the substrate and the catalytic group will than act as one molecule, preventing the loss of translational and rotational energy. The reaction first begins with two molecules that are able to find each other, which makes the rate of reaction dependent on the concentrations of the reactants. This is due to the higher probability of molecules to find each other.

## Some Examples

An example of catalysis by approximation is when NMP kinases bring two nucleotides together to facilitate the transfer of a phosphoryl group from one nucleotide to the other. With the addition of adenosine triphosphate (ATP), a phosphate group is placed adjacently to the phosphate group of the NMP kinase. This facilitates in the transfer of the phosphate between the two molecules.
# Regular Expressions/operator/pipe

A pipe symbol allows regular expression components to be logically ORed. For example, the following regular expression matches lines that start with the word "Germany" or the word "Netherlands". Note that parentheses are used to group the two expressive components.

## Precedence

The alternation operator has a low precedence within a regular expression, so applies to the largest possible components either side:
Note that parentheses can be used to override the precedence to change the behaviour of the above expression:

## The alternation operator is not recognized by some Unix tools

Some Unix tools do not recognize the pipe symbol as an alternation operator.
# Regular Expressions/posix modern regular expression
### POSIX modern (extended) regular expressions

The more modern "extended" regular expressions can often be used with modern Unix utilities by including the command line flag "-E".
POSIX extended regular expressions are similar in syntax to the traditional Unix regular expressions, with some exceptions. The following metacharacters are added:
* + — Match the last "block" one or more times - "ba+" matches "ba", "baa", "baaa" and so on
* ? — Match the last "block" zero or one times - "ba?" matches "b" or "ba"
* | — The choice (or set union) operator: match either the expression before or the expression after the operator - "abc|def" matches "abc" or "def".
Also, backslashes are removed: \{...\} becomes {...} and \(...\) becomes (...). Examples:
* "[hc]+at" matches with "hat", "cat", "hhat", "chat", "hcat", "ccchat" etc.
* "[hc]?at" matches "hat", "cat" and "at"
* "([cC]at)|([dD]og)" matches "cat", "Cat", "dog" and "Dog"
Since the characters '(', ')', '[', ']', '.', '*', '?', '+', '^' and '$' are used as special symbols they have to be escaped if they are meant literally. This is done by preceding them with '\' which therefore also has to be escaped this way if meant literally. Examples:
    "a\.(\(|\))" matches with the string "a.)" or "a.("
# Regular Expressions/operator/hook

The hook operator is used to match 0 or 1 of the preceding expression. For example, "ab?c" matches "abc" or "ac" not "abbc". Also (ab)?c matches "abc" or "c".
# Regular Expressions/Syntaxes

There are several variants of regular expressions. These variants differ not only in their concrete syntax but also in their capabilities. Individual tools that support regular expressions also have their own peculiarities.
* Simple Regular Expressions - widely used for backwards compatibility, but deprecated on POSIX-compliant systems.
* Basic Regular Expressions - used by some Unix shell tools
* Perl-Compatible Regular Expressions - used by Perl and some application programs
* POSIX Basic Regular Expressions - provides extensions for consistency between utility programs. These extensions are not supported by some traditional implementations of Unix tools.
* POSIX-Extended Regular Expressions - may be supported by some Unix utilities via the -E command line switch
* Non-POSIX Basic Regular Expressions - provides additional character classes not supported by POSIX
* Emacs Regular Expressions - used by the Emacs editor
* Shell Regular Expressions - a limited form of regular expression used for pattern matching and filename substitution

### Greedy expressions

Quantifiers such as * and + match as much as they can: they are greedy. For some uses, their greediness does not fit. For example, let as assume you want to find the first string enclosed in quotation marks, in the following text:
    These words include "cat", "mat", and "pat".
The pattern ".*" matches the italicized part of the text below, that is, "cat", "mat", and "pat" instead of the desired "cat":
    These words include "cat", "mat", and "pat".
To fix this, some flavours of regular expressions provide non-greedy operators such as *?, +?, and }?. In PHP, adding a "U" at the end of the regexp makes the quantifier non-greedy, as in /".*"/U. In flavours that support neither of the two options, you can specify what is not to be matched, as in ("[^"]*") to fix the discussed example. However, when dealing with bracketed expressions, (\[\[[^\]]*\]\]) fails to match on A B C [[D E] F G]].

### Comparison table

A comparison table or matrix that shows which features or flavors of regular expressions are available in which tool or programming language is available from regular-expressions.info.
← Introduction · Implementation →
# Structural Biochemistry/Enzyme Catalytic Mechanism/Summary
## Enzyme Catalysis: Summary

Enzymes accelerate reactions using :
Proximity and orientation effects
Electrostatic catalysis
Preferential Transition State Binding
Induced fit
General acid/base catalysis
Covalent catalysis
Metal ion catalysis
Enzymes accelerate chemical reactions by lowering the activation energy, DG‡.
Strong binding of the transition state and weak binding of the substrate leads to the maximum rate because all the binding energy is used to lower DG‡.
Any process that uses some of the binding energy for another purpose, e.g., a protein conformational change, will lower the maximum rate.
Under physiological conditions, the maximum rate is achieved by maximizing kcat/Km AND having Km greater than the physiological [S]. This means that most of the enzyme will be free to interact with a substrate molecule and that every encounter will lead to a reaction.

## Reference

http://www.bmb.psu.edu/courses/bmb401_spring2004/lecture_notes/lecture11_2004.pdf
# Structural Biochemistry/Enzyme Catalytic Mechanism/pingpong mechanism

Ping Pong is also called the double placement reaction and it means that one or more products are released before all substrates bind the enzyme. One key character of this reaction is the existence of a substituted enzyme intermediate, in which the enzyme is temporarily modified. Classic examples of this mechanism are reactions that shuttle amino groups between amino acids and a-ketoacids.
The enzyme aspartate aminotransferase catalyzes the transfer of an amino group from aspartate to a-ketoglutarate. After aspartate binds to the enzyme, the enzyme accepts aspartate’s amino group to form the substituted intermediate. The first product, oxaloacetate, departs after that. Glutamate is released as the final product after the second substrate, a-ketoglutarate binds to the enzyme and accepts the amino group from this modified enzyme.
Enzymes with a ping-pong mechanism can exist in two states, E and a chemically modified form of the enzyme E*; this modified enzyme is known as an intermediate. In such mechanisms, substrate A binds, changes the enzyme to E* by, for example, transferring a chemical group to the active site, and is then released. Only after the first substrate is released can substrate B bind and react with the modified enzyme, regenerating the unmodified E form.
Enzymes with ping–pong mechanisms include some oxidoreductases such as thioredoxin peroxidase, transferases such as acylneuraminate cytidylyltransferase, and serine proteases such as trypsin and chymotrypsin. Serine proteases are a very common and diverse family of enzymes, including digestive enzymes (trypsin, chymotrypsin, and elastase), several enzymes of the blood clotting cascade and many others. In these serine proteases, the E* intermediate is an acyl-enzyme species formed by the attack of an active site serine residue on a peptide bond in a protein substrate. A short animation showing the mechanism of chymotrypsin is linked here.
The name pingpong reaction came for the substrates appearing to bounce on and off the enzyme to a pingpong ball in the Cleland notation.
# Structural Biochemistry/Enzyme Catalytic Mechanism/Restriction Enzyme
## Overview

Restriction enzymes are DNA-cutting enzymes found in bacteria (and harvested from them for use). Because they cut within the molecule, they are often called restriction endonucleases.
In order to be able to sequence DNA, it is first necessary to cut it into smaller fragments. Many DNA-digesting enzymes (like those in your pancreatic fluid) can do this, but most of them are no use for sequence work because they cut each molecule randomly. This produces a heterogeneous collection of fragments of varying sizes. What is needed is a way to cleave the DNA molecule at a few precisely-located sites so that a small set of homogeneous fragments are produced. The tools for this are the restriction endonucleases. The rarer the site it recognizes, the smaller the number of pieces produced by a given restriction endonuclease.

## Reference

http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/R/RestrictionEnzymes.html
# Structural Biochemistry/Enzyme Regulation/Adenylation

Adenylation is the covalent attachment for AMP to a protein side chain. It is known two serve two functions: one as a stable post-translational modification and the other is to generate an efficient leaving group in mechanisms that use energy from the free energy of hydrolysis of phosphoanhydride bond of ATP to allow thermodynamically unfavorable overall reactions to occur.
The activity of glutamine synthetase, an enzyme that plays a key role in the metabolism of nitrogen, is regulated by adenylation. The rate of adenylation depends on the ratio of glutamine to α-ketoglutarate. A low ratio is a sign of cellular nitrogen sufficiency, whereas a high ratio is evidence of a limited nitrogen supply and the need for ammonia fixation by glutamine synthetase.
Adenylation of glutamine synthetase, which is catalyzed by the enzyme adenylyl transferase, involves the phosphodiester bond between the hydroxyl group of the tyrosine residue in glutamine synthetase and the phosphate group of an AMP nucleotide. A complex of adenylyl transferase and a regulatory protein known as PII, which may exist unmodified as PII (also known as P$_A$) and uridylylated as PII-UMP (also known as P$_D$), causes an AMP molecule to either attach to or be removed from the glutamine synthetase, respectively.
A complex of PII with adenylyl transferase catalyzes the attachment of an AMP molecule to glutamine synthetase, forming an adenylated glutamine synthetase that is inactive. On the other hand, a complex of PII-UMP and adenylyl transferase activates deadenylation and removes the AMP from glutamine synthetase, creating deadenylated glutamine synthetase that is active. When there is a higher glutamine to α-ketoglutarate ratio, more monomers of glutamine synthetase are adenylated, thereby producing lower activity. A lower ratio leads to less monomers being adenylated and higher activity of glutamine synthetase.
Adenylation is an important form of regulation for amplifying signals such as for blood clotting and control of glycogen metabolism. Because adenylation is an enzymatic cascade, it is easier for allosteric control, as each enzyme can be a target for regulation. This is important for nitrogen metabolism in cells as it creates many regulatory sites, allowing a cell to fine tune its nitrogen production.

## References

* Berg, Jeremy Mark. Biochemistry/ Jeremy M. Berg, John L. Tymoczko, Lubert Stryer. -7th ed. P749-750.
* Garrett, R.H., and C.M. Grisham. Biochemistry. 3rd ed. Belmont, CA: Thomas, 2007.
* Itzen A, Blankenfeldt W, Goody RS. Adenylylation: renaissance of a forgotten post-translational modification. Trends Biochem Sci. 2011 Apr;36(4):221-8. Epub 2011 Jan 20.