OpenLLM-France/wikimedia huggingface dataset:
# Structural Biochemistry/Membrane Proteins/Study of Protein structure in lipid bilayer: Electron crystallography

Introduction:
Electron crystallography is an excellent technique to study the structures of proteins in their natural bilayer environment and the biological mechanism through freeze-trapping of transitional states. The technique also shows how the proteins in situ are designed and carries out their membrane specific tasks. In 1975, the seven membrane-spanning α-helices of bacteriorhodopsin were resolved, providing the view of polypeptide chains traversing the lipid bilayer. After that, an atomic model of bacteriorhodopsin was obtained.
Sheets and Tubes:
The most informative density maps of membrane protein was studied with Electron crystallographic on protein-lipid arrays in the form of sheets ( 2 dimensional crystals) or tubes( tubular crystals). Two-dimensional crystals may contain thousands of unit cells, providing extensive averaging to improve the signal-to-noise ratio. However, to obtain the three dimensional analysis, the sheets need to be tilted. Tubular crystals contain less unit cells. But the molecules are arranged on the surface lattice with helical symmetry; therefore, give many different views and do not need to be tilted. By averaging the unit cells in each image, the technique enhances the poor signal-to-noise ratio owing to the weak electron does. The lattice and symmetry elements also provide good position and orientation of each molecule. The averaging of isolated membrane proteins to obtain structures is also feasible (>250kDa) The producing of protein-lipid arrays from detergent-solubilised, purified protein, both in Sheet and Tube forms has been developed. Even though the extensive robotic screens developing for Tubes have not been achieved, Tube form has provided many advantages. Ex: many different views of the same molecules that can reconstruct it roughly in three dimensions; there is no ‘missing cone’ of formation, etc...
Freeze-trapping different conformational states: Scientists can use electron crystallography as a direct means to probe the biological mechanism of protein in lipid. The step in preparation is plunge-freezing of the electron microscope grid into liquid nitrogen-cooled ethane, which cools the specimen rapidly( ~106 oC/s) . It permits efficient trapping of a transient structure that has a lifetime of a millisecond or longer. Protein is then activated by using light, or spraying the appropriate ligand onto the grid just before the grid hits the ethane surface. This technique has been applied to ACh receptor channel, using tubular crystals, and yielded a good data collection. The difficult step is the spray-freeze-trapping treatment. So far, freeze-trapping has not been used widely, and still under developed

## References

Yoshinori Fujiyoshi , Nigel Unwin, Electron crystallography of proteins in membranes, Current Opinion in Structure Biology, 2008.
# Structural Biochemistry/Siderochromes

Bacteria and fungi also synthesize iron transfer compounds, called siderochromes.The common structures are complex hydroxamates (also called ferrichromes or ferrioxamines) or complex catechols (enterobactin). They have peptide backbones and are very strong chelating agents (K$_f$ ~ 10$^{30}$ to 10$^{50}$), allowing the organism to extract iron from surroundings that contain very little iron or are basic enough that iron is present as insoluble hydroxides or oxides. Some of these compounds act as growth factors for bacteria and others act as antibiotics. There are also examples in which the iron is bound by a mixture of phenolic hydroxyl, hydroxamate, amine and alcoholic hydroxyl groups. Siderochromes are substances which are excreted into the culture medium by micro- organisms in iron-deficient conditions. These compounds characteristically bind Fe3 + very strongly, and a number of them participate in the transport of iron into the cells. Siderochromes are synthesized in large amounts and excreted into the culture medium only when the bacteria have insufficient iron, and it forms a very stable complex with Fe(II).

## References

Gary L. Miessler, Donald A. Tarr, Inorganic Chemistry, Third Edition, 2004.
# Structural Biochemistry/Selman A. Waksman
## Introduction

Researcher, scientist, biochemist, Selman Abraham Waksman (1888-1973) did research on soil microbes in hopes to isolate effective antibiotics. He was successful in discovering the existence and isolating antibiotic Streptomycin. In the years after that, he was able to isolate many other antibiotics that were able to treat many disease such as tuberculosis, and other infections that were resistant to Penicillin. In 1952, Waksman was awarded the Nobel Prize in Physiology or Medicine for his accomplishment in discovering streptomycin. This was considered the first antibiotic that was actively against tuberculosis. Waksman earned himself the title of "Father of Antibiotics"

## Early Life

Born in 1888 in the small rural Ukrainian town of Novaya Priluka, Waksman was surrounded by fields of rich soil. Although agriculture was abundant around him, Wakman did not do much farming. However, it did plant a seed of curiosity as to what was in the soils that gave so much nutrition and even remedies that helped people. So in 1910, he did what many of his relatives were doing- move to america. Again, moving to a small town, Waksman enrolled in a small college - Rugers College, while working on a small family farm. It was during these early years that he was exposed to bacteria, as he started working in a lab. Getting introduced to such cultures such as the actinomycetes, his interest in microbes in the soil was growing. Watksman graduated with a Bachelor of Science in Agriculture.
In 1918, Watkins received his Ph. D in Biochemistry from the University of California, Berkeley, and returned to Rutger's University where he continued to research on microflora.

## Research and Discovery

Inspired by a fellow researcher, Rene Dubois, who worked in his laboratory and isolated soil bacterium, Streptococcus pneumoniae, Waksman was motivated to look beyond the pre-existing antibacterial organisms. So he and his team structured their research so as to inhibit zones of colones that isolated soil microbes. These were grown under many different conditions and tested. After many test and trials, Waksman and his team isolated Actinomyces antibioticus, which was part of the actinomycetes family. But soon it was found that the actinomycin that was excreted was extremely toxic to the experimental organisms.
His research did not stop here, he continued until finally in 1944, he was able to discover the existence of streptomycin. This along with more than 20 new substances (that includes neomycin) were isolated. It was Waksman that coined the term "antibiotics" along the path of his research for inhibitors of natural growth.

## References

1. http://www.jbc.org/content/279/48/e7.full
2. Waksman, S. A., and Woodruff, H. B. (1940) The soil as a source of microorganisms antagonistic to disease-producing bacteria. J. Bacteriol.
3. Trial, Richelle. UCSD Bacteriology (Bimm 120) Lecture 10/30/2012 "Bacterial Development"
# Definition

Intradermal (ID) drug administration is the injection of a small amount of fluid into the dermal layer of the skin. The needle most commonly used for this technique is the tuberculin syringe with a 26-gauge needle, which is about one-fourth to one-half inch in length. A small amount of swelling in the skin after injection is to be expected.

# References

. "ADMINISTER AN INTRADERMAL INJECTION."Administer Intramuscular, Subcutaneous, and Intradermal Injections. Brookside Associates, n.d. Web.
# Definition

An intravenous (IV) injection is a drug delivery method which the drug is directly injected into the bloodstream. With this method, the onset of the action is much rapid since the drug is being administered directly into the bloodstream. Delivering a drug intravenously can be beneficial when using irritating material since blood vessel walls are highly insensitive to irritants. High concentrations and dosages of drugs can be delivered intravenously much quicker than other methods, which can be beneficial, yet dangerous at the same time.

## Disadvantages with using Intravenous Injections

Although intravenous injections can be quick, there are some disadvantages with using this method. A major disadvantage of using IV injections is that repeated injections at the same site results in the area surrounding vein injection site losing its strength and elasticity. In worst case scenarios, if a particular injection site has been punctured into several times, the wall of the vein collapses and blood will no longer move through it. Another concern of using IV injections is the transmission of infections. Contaminated needles and syringes should not be used more than once; nor should they be shared between patients.$^{[1]}$

## References

* Hart, Carl. Drugs, Society, and Human Behavior. 12th. McGraw-Hill Humanities, 2008. Print.
# Structural Biochemistry/Intraarterial
## Definition

Intraarterial means that action is happening inside an artery or to its structure.

## Inhalation Advantages

An advantage about using intraarterial inhalation is that it is a method of inhalation that more effectively controls the dose of the injection. The patient is able to control how much of the drug that they will receive, since they will be able to titrate it.

## Inhalation Disadvatage

A disadvantage about using intraarterial inhalation is that this action takes longer. This route is slower because the lungs has to take it in. From the lungs, it has to travel to the systemic circulation.

## Injection Advantages

The advantages about using intraarterial injection is that it is pretty fast, it takes about fifteen to thirty seconds for intravenous and three to five minutes for intramuscular as well as subcutaneous. Another advantage is that the bioavailability of this is 100%. A third advantage is a single injection can last for days or months. This method is suitable for drugs that cannot be absorbed through the digestive system. This is also suitable if the drug is too irritating. One more advantage is that continuous medication can be delivered.

## Injection Disadvantages

The disadvantages about using intraarterial injection is that there is a higher risk to addiction and overdosing if abusive drugs are injected. This is due to the quickness of the drug. Another disadvantage is that self-administration cannot typically be done by patients. Belonephobia is another disadvantage, which is fearing needles and injection itself. Sharing of needles can leave to infectious diseases such as HIV. This type of administration is one of the most dangerous. Most of our body's natural defenses is bypassed by intraarterial injection. This exposes the patient to health problems. These include infections, abscesses, hepatitis, and contaminants or undissolved particles. Air bubbles may occur if this is not done correctly.
# Structural Biochemistry/Intranasal Route

Intranasal drug administration is an attractive option for local and systemic delivery of many drugs. The nasal mucosa is – in other words, nose – easily accessible. Intranasal drug administration is noninvasive, almost painless and the most susceptible way of administrating drugs for children. Application can be performed easily by patients or by physicians in emergency settings. Intranasal drug delivery offers a rapid onset of therapeutic effects (local or systemic). Nasal application circumvents gastrointestinal degradation and hepatic first-pass metabolism of the drug. The drug, the vehicle and the application device form an undividable triad. Its selection is there- fore essential for the successful development of effec- tive nasal products. This paper discusses the feasibility and potential of intranasal administration. However, there are still many debatable topics on the following topics:
* the intended use (therapeutic considerations)
* the drug
* the vehicle
* the application device

## Reference

http://content.karger.com/ProdukteDB/Katalogteile/isbn3_8055/_96/_15/CUPDE40_04.pdf
# Structural Biochemistry/Inherited Human Diseases Resulting from Abnormal Accumulations of Membrane Lipids

Polar lipids of membranes consistently undergo metabolic turnover. The rate of the synthesis is equal to the rate of the breakdown. The breakdown is generally promotedy by hydrolytic enzymes in lysosoms. However, a serious disese can occur if there is an accumulation of the partial breakdown products in the tissue caused by a dfect in the enzymes that is responsible for sphingolipid degradation.
An example of this is the Niemann-Pick disease that is caused by a genetic defect in sphingomyelinase, an enzyme that cleaves phosphocholine from sphingomyelin. Sphingomyelin is found in the brain, spleen, and liver. The disease causes infants to have mental retardation and may result in an early death. Another example is the Tay-Sachs disease, where the body has a lack of enzyme hexosaminidase. The lack of the enzyme causes the build up of ganglioside GM2, which ultimately leads to the Tay-sachs disease. The symptoms of this disease includes progressive retardation in development, paralysis, lindness, and death in three or four years.
A way to detect these diseases is by testing prospective parents and then testing their DNA to determine the exact nature of the defect and the probability it would be passed on to the offspring. If the female is pregnant then doctors would test the cells inside the placenta or the fluid surrounding the baby.

## Reference

1. Nelson, David L., Michael M. Cox, and Albert L. Lehninger. "Inherited Human Diseases Resulting from Abnormal Accumulations of Membrane Lipids." Lehninger: Principles of Biochemistry. New York: W. H. Freeman and, 2005. N. pag. Print.
# Definition

An intramuscular (IM) injection is a drug administration route in which a drug is injected into a muscle. In terms of absorption, the injection methods that delivers the drug quickest to slowest is intravenous, intramuscular then subcutaneous. It is favored due to its fast-acting as well as long-lasting capabilities. These injections are inserted into the deep muscle tissue where the deposition of medication is absorbed gradually into the bloodstream.

## Absorption

The three main sites of intramuscular injection is in the deltoid muscle of the arm, buttocks and the thighs. Absorption is quickest when injecting into the arm and slowest in the buttocks.

## Advantages

When injecting into the muscle, there is less chance of irritation due to greater blood supply and faster absorption. Also, when wanting to inject larger amounts of drugs, it is best to inject into the muscular region instead of injecting subcutaneously.

## Procedure

Needle should not be smaller than an inch nor exceed one and a half inches in length. The maximum volume of medication recommended should be five milliliters at one site per adult.

# References

* Hart, Carl. Drugs, Society, and Human Behavior. 12th. McGraw-Hill Humanities, 2008. Print.
"ADMINISTER AN INTRAMUSCULAR INJECTION."Administer Intramuscular, Subcutaneous, and Intradermal Injections. Brookside Associates, n.d. Web.
# Suicide/Radical Islam
## Radical Islam
### Suicide Bombing

* Number of suicide bomb attacks in Afghanistan 2002-2008 (Source: UNAMA. Figures include 17 in 2006, 68 in 2007, and 93 in 2008 that were not detonated).
* Number of suicide bomb attacks in Afghanistan 2002-2008 (Source: UNAMA. Figures include 17 in 2006, 68 in 2007, and 93 in 2008 that were not detonated).
# Suicide/Speed of effect

When ingested a lethal dose of 10 - 15 grams by mouth, death occurs within 2 hours.
# Suicide/Moral Reasoning
## An Act of Despair

"The man, who in a fit of melancholy, kills himself today, would have wished to live had he waited a week."

### Lost Love

"When I am dead, and over me bright April Shakes out her rain drenched hair, Tho you should lean above me broken hearted, I shall not care. For I shall have peace. As leafey trees are peaceful When rain bends down the bough. And I shall be more silent and cold hearted Than you are now."

### Political Statement

Suicide is often used as a show of ultimate protestation against political movements, decisions or to cause society to reexamine the morals or goals of political figures. Such actions were more common in the higher strata of society in ancient times as only those would make a public statement. One of the most famous events of this nature was the suicide of Marcus Porcius Cato Uticensis (95 BC, Rome – April 46 BC, Utica), commonly known as Cato the Younger (Cato Minor), a statesman in the late Roman Republic. Cato had fought Caesar, a de facto dictator, on the side of Pompey, that refused to align to the new power. After a reversal, where Caesar defeated most of the supporters of Pompey, Cato escaped to the province of Africa, to Utica, without conceding defeat, and was pursued by Caesar.
In Utica, after a major battle, where outnumbered Caesarian legions defeated the opposing army. He committed suicide in an attempt to deny any political gain of being captured, or even to permit Caesar the opportunity to grant him a pardon.

#### According to Plutarch surviving writings, in April 46 BC Cato botched an attempt to kill himself, due to an injured hand. Plutarch wrote

"Cato did not immediately die of the wound; but struggling, fell off the bed, and throwing down a little mathematical table that stood by, made such a noise that the servants, hearing it, cried out. And immediately his son and all his friends came into the chamber, where, seeing him lie weltering in his own blood, great part of his bowels out of his body, but himself still alive and able to look at them, they all stood in horror. The physician went to him, and would have put in his bowels, which were not pierced, and sewed up the wound; but Cato, recovering himself, and understanding the intention, thrust away the physician, plucked out his own bowels, and tearing open the wound, immediately expired."
# Suicide/The Right to Die

"The act of taking my own life is not something I am doing without a lot of thought. I don't believe that people should take their own lives without deep and thoughtful reflection over a considerable period of time. I do believe strongly, however, that the right to do so is one of the most fundamental rights that anyone in a free society should have. For me much of the world makes no sense, but my feelings about what I am doing ring loud and clear to an inner ear and a place where there is no self, only calm. Love always, Wendy."
# Super Mario World/Chocolate Island
## Chocolate Island

* Chocolate Island 1
* Choco-Ghost House
* Chocolate Island 2
* Chocolate Secret
* Chocolate Island 3
* Chocolate Fortress
* Chocolate Island 4
* Chocolate Island 5
* Wendy's Castle
# Super Mario World/Chocolate Island/Choco-Ghost House

On this level, beware of the moving gaps in the floor. Use the ghost blocks to get to the door in the second phase...be careful because they turn into ghosts if you turn away.
# Super Mario World/Chocolate Island/Chocolate Island 3

This level has 2 exits, when you get to the end, there is a blank yellow box, the kind you can break. Hit this and a vine appears, climb up this vine for the normal exit. For the alternate exit you need a cape or a blue yoshi. Right after the yellow box with the vine is 3 arrow signs, fly in that direction and dont stop flying till you're gone past the goals.
# Super Mario World/Chocolate Island/Chocolate Island 4

Chocolate Island 4
Chocolate Island 4 is an undergroun maze inside a volcano with mega-moles, moving platforms and cocoa lava.
# Super Mario World/Caped status
## Getting Cape Mario

* If Mario grabs a feather, he becomes Cape Mario.

## Abilities

Cape Mario is generally considered the best Mario.
* Cape Mario can fly.
* Cape Mario can jump further than other Marios by gliding as he falls.
* Cape Mario can perform a cape spin. Cape spin can kill some enemies that cannot be killed by jump, such as Jumpin' Piranha Plants.
* Cape Mario can break yellow blocks using spin jump.
* He can also flip yellow blocks using his cape spin.
* After flying up, Mario can smash down on the ground. This creates an earthquake which kills certain enemies.
* If cape Mario is hit he does not die. Instead he becomes small Mario.

## Miscellaneous

Cape is not available until Donut Plains 1.
# Super Mario World/Chocolate Island/Chocolate Island 1

In order to beat this stage, go into the last gray pipe that you see. This will shoot you across the gap that you can't simply jump over. If you attempt to jump this gap to the goalpost without a cape, you will surely die. So use the gray pipe, and then the trampoline to gain the highest possible score on the goalpoast.
# Super Mario World/Chocolate Island/Chocolate Island 2

Getting the Key Near the start, a notification block informs you that the level changes based on the time remaining. In order to obtain the key (which will get you to Chocolate Secret), you need to complete the level in as little time as possible. (Timer must read at least 250 at the second pipe) First, jump on the chocolate platforms in front of Mario, and get over to the far right. There you will find a green pipe. Take the pipe, and if you get to an area with many red koopa paratroopa's, you are nearly done. If not, you will not get the key.
Once again, speed is a priority, so use the Koopas as your platform. If you have a cape feather and a Yoshi, this area should be a snap, since Mario can glide on top of each of his foes, which then extend his jump. If you lose Yoshi, however, don't be afraid; It's still possible to get the key.
Once you've completed this area, you should finally happen on a large number of Chucks that are throwing Baseballs toward Mario. If you do, then you will soon have the Key, which is located about 4 blocks away from the keyhole. Congratulations!
--65.92.154.165 22:12, 4 Mar 2005 (UTC)Derek M.

## alternate exit

Complete move to the green tube at the end of the first screen (lower right) with less than 100 seconds of game play remaining to find the alternate exit.
# Super Mario World/Chocolate Island/Chocolate Island 5

Beware the begining of this level. You have some spiky creatues and a power switch. You hit the switch and you will have to fend off the creatures. I advise that you ignore the switch if you dont need the practice.
There are three squaddies at the end of this level and one placed dangerously at the top of a pipe. Either aim to jump on or under him.
# Super Mario World/Chocolate Island/Chocolate Fortress

This fortress may be the most difficult fortress so far along the game. The first part is fairly easy and takes mostly patience. The next part is the hard part containing many Thwomp. It will probably take many tries to defeat this. Bringing in a cape, and keeping one in reserve, may help. Later you fing a brown metal bolted door that leads to the reznor
# Super Mario World/Chocolate Island/Wendy's Castle

You're now meeting with the first Castle (2nd Fortress or so)with what every Mario player hates: the spikes of doom. Avoid at all costs, and Wendy is harder, as there's 2 fire balls bouncing around. Do what you did last on Castle 3 --Vanilla Dome--