OpenLLM-France/wikimedia huggingface dataset:
# Sport Innovation/TI Network/BMC 4

Week 4 - Customer Discovery Business Model Canvas
Attached on the right hand side of this page is the Week 4 - Customer Discovery Business Canvas Model. (Enlarge the attached Business Model Canvas by left-clicking on the enlarge symbol in the lower right hand corner of the photo. Then click on Full Resolution.)
This is the revised Business Canvas Model due to the responses received from the Week 3 Questionnaires and Interviews.
The main change made to the Business Model Canvas was maintaining the $20 one time sign up fee for High School, College and Amateur Athletes, but increasing the Professional Athletes one time sign up fee to $30. Based on the responses received, this change was made because the data shows the professional athletes were willing to pay more due to the fact that they have more to gain. This was especially true with professional althetes looking for sponsorship.
The previous statement also led to one other change, which was updating and revising the Professional Athlete Customer Segment to those athletes only looking for sponsorship.
Evolution of the Business Model Canvas for Talent Identification Network(TTIM.COM) Post Customer Discovery
BMC Post CDP
# Principles of Finance/Contributors

The following people have recorded their contribution to the development of this book.

## Active Contributors

The following Wikibookians are actively editing this Wikibook, as of February 2007. All participants in the project are welcome to add their name, email address, contribution, and affiliation to the following list. Please keep the list in alphabetical order, based on last name.
The following Wikibookians have contributed or are currently contributing to this Wikibook as of February 2007.
| Name | Role | Affiliation/Qualification |
| Venkatesh Sridhar | Editor | MBA in Finance S P Jain Center of Management, Dubai, UAE |
| Jakob Lewis | Contributor | Principles of Finance Student at University of Exeter |
# Structural Biochemistry/Drug regulation enzymes

Drug metabolism can occur in every tisuue, however the major drug metabolizing enzymes( DMEs) are ezpressed at the highest levels in the liver. Drug metabolism serves to control the exposure of a potentially harmful substance. DMEs also help to regulate endogenous function.
CYP3A4 is a drug-metabolizing enzyme in the intestines that increases or alters blood vessels of certain medications in people.

## Cytochrome P450(CYP459)

CYP450 named based on its light absorption at 450nm when completed with carbon monoxide.It is a cytochrome enzyme that processes essential molecules such as hormones and vitamins as well as metabolize hundreds of prescribed medicines and natural substances. It is a "super family" of enzyme with a very broad substrate selectivity.CYP450 is based on shared homology of amino acid sequence. Drug metabolism: the cycle involves four steps
1. Oxidized (Fe3+) CYP450 combines with a drug substrate to form a binary complex.
2. NADPH donates an electron to the CYP450 reductase, which turn reduces the oxidized CYP450 drug complex.
3. A second electron is introduced from NADPH via the same CYP450 reductase, which serves to reduce molecular oxygen and form an" activated oxygen"-CYP450 substrate complex.
4. This complex in turn transfers" activated" oxygen to the drug substrate to form the oxidized product. The potent oxidizing properties of this activated oxygen permit oxidation of a large number of substrates.
Source: Davis, Alison. (2006). Medicines By Design. National Institutes of Health, 8.
# Structural Biochemistry/Drug Delivery
### Control of drug releasing

1. Yan Hu., Sophia B. Georghiou., Alan J. Kelleher, Raffi V. Aroian, "Bacillus thuringiensis Cry5B Protein Is Highly Efficacious as a Single-Dose Therapy against an Intestinal Roundworm Infection in Mice"
2.Sailor Group website: http://sailorgroup.ucsd.edu/research/porous_Si_intro.html
3. Elizabeth C. Wu, Ji-Ho Park, Jennifer Park, Ester Segal, Fre#de#rique Cunin, and Michael J. Sailor, "Oxidation-Triggered Release of Fluorescent Molecules or Drugs from Mesoporous Si Microparticles", ACS Nano, 2008, 2 (11), 2401-2409 • Publication Date (Web): 08 November 2008
4. Michelle Y. Chen and Michael J. Sailor, "Charge-Gated Transport of Proteins in Nanostructured Optical Films of Mesoporous Silica"
5. Jennifer S. Andrew, Emily J. Anglin, Elizabeth C. Wu, Michelle Y. Chen, Lingyun Cheng, William R. Freeman, and Michael J. Sailor, "Sustained Release of a Monoclonal Antibody from Electrochemically Prepared Mesoporous Silicon Oxide"
6.http://en.wikipedia.org/wiki/Porous_silicon
7.http://baike.baidu.com/view/653736.htm
# Structural Biochemistry/Drug Platform
## Nanodrug Platform

Different administration of drugs is to enhance the drug effects on the body, depending on the symptom of the patient. Below is an illustration showing therapeutic window. The goal and the challenge of the researchers is to minimize the drug toxicity to the body and to maximize the drug activity inside the body. In order to keep the drug concentration inside of blood at the therapeutic window, a sustainable drug release is desired. To achieve this, many nanotechnology drug platforms are available. The most common ones are liposomes and hydrogels.

### Hydrogel

Hydrogel can encapsulate drugs inside its core. When the environment changes, the hydrogel is able to swell, which causes the release of drug.

#### Types of hydrogel
##### Acidic or basic hydrogel

change in pH causes swelling causes release of drug

##### ionic hydrogel

change in ionic strength causes change in concentration of ions inside the gel causes change in swelling causes release of drug

##### hydrogel containing electron-accepting groups

Electron-donating compounds causes formation of charge and transfer complex causes change in swelling causes the release of drug.

##### Hydrogel containing immobilized enzymes

A substrate is present, and enzymatic conversion causes the product the change and swell, which causes the release of drug.

##### Magnetic particles disperse in alginate microshapes

A magnetic field is applied to change the pores in gel to change in swelling and thus release of drug.

##### Thermoresponsive hydrogel

A change in temperature causes change in polymer-polymer and water-polymer interactions that changes the shape of hydrogel and causes the release of drug.

##### Polyeeletrolyte hydrogel

An electric field is applied that causes the membrane the charge and causes the electrophoresis of charged drug and change the shape of hydrogel to release the drug

##### Ethylene-vinyl alcohol hydrogel

Untralsound irradiation is used to increase the temperature to cause the hydrogel to swell to release the drug.

# Reference

Zhang, Liangfang. "Controlled Drug Delivery Systems." CENG 207 Lecture 11. University of California, San Diego, La Jolla. 10 May 2012. Lecture.
# Super Mario World/Donut Plains/Donut Plains 2

This is an underground level. Lots of Buzzy Beetles and Swoopers. The secret exit that leads to the Green Switch Palace can be reached by entering the green pipe that's after the green block among the rising yellow stones. You need to be able to fly, either with Yoshi or a cape. The four yellow blocks that form a staircase lead to a chamber that holds the key. The last block has a vine in it, directly above is the entrance to the chamber. Flying in just with the cape can be tricky since the entrance is narrow, so it's better to let the vine grow and grab it.
# Super Mario World/Donut Plains/Donut Plains 4

At the beginning there is a "Tornado Shell", bring Yoshi and eat it up!
# Super Mario World/Donut Plains/Donut Secret 1

Donut Secret 1 :
| Level type | Underwater |
| Entrance | Donut Plains 1 |
| Exit | Donut Ghost House |
| Secret Exit | Donut Secret House |
| Time at start | 300 |
| Difficulty | Easy |
Donut Secret 1 is the first underwater stage in Super Mario World. It can be accessed using the secret exit in Donut Plains 1.
It is full of all the three kinds of fishes: Blurp, Rip Van Fish and Cheep Cheep. It's highly helpful to enter this level with Fire Mario. If not, a Fire Flower can be found not far from the start. The first purple pipe leads to a bonus level, which can be navigated with P-Balloons. After taking the first balloon head left, a second balloon is inside a ? block. Then head for the middle and a yellow block will have a 1-up mushroom. Then to the right collect a Dragon Coin and fall to collect another Fire Flower. To take the secret exit grab the P-Switch and swim with it until you see the key hole. Press the switch and inside the ? block is the key.
# Super Mario World/Donut Plains/Morton's Castle

Morton's Castle is the second castle level in Super Mario World. It is where Morton Koopa is fought. To defeat Morton, Mario must stomp on him three times, but must also make sure to avoid his traps.
# Super Mario World/Donut Plains/Donut Plains 3

This a very easy level that takes place on the air and has lots of revolving plataforms. It's even easier if you have Yoshi. The R Button can let you see ahead. This helps a lot.--Pikminkid 13:55, 3 July 2006 (UTC)
# Super Mario World/Donut Plains/Donut Secret 2

Donut Secret 2 can be accessed using the secret exit in Donut Secret House. It's an underground level, made mostly out of ice. Lots of Spike Tops and Koopas. After clearing two Jumpin' Pirahna Plants a green pipe will lead to an above ground bonus level. YOu can pass that level with or without the P-Ballon that's inside the ? block. With the ballon you will be able to get more coins.
# Super Mario World/Donut Plains/Donut Secret House

Donut Secret House :
| Level type | Ghost house |
| Entrance | Donut Secret 1 |
| Exit | Donut Secret 2 |
| Secret Exit | Star World 1 |
| Time at start | {{{time_at_start}}} |
| Difficulty | {{{difficulty}}} |
Donut Secret House is one of two ghost houses in Donut Plains. After transversing the first "room" left-to-right, and entering the second room, there will be a circular arrangement of Boo Buddies. There will then be a small platform with five coins on it. In order to get to the normal exit, these coins must first be taken, and then the P-switch obtained from the leftmost end of the room, brought back to the small platform, and activated. A blue door will then appear, through which is the non-secret goalpost.
In order to get to the secret exit, obtain the P-switch, bring it to the arrangement of yellow blocks in the center, and activate it. A row of question-mark blocks will appear, making it possible to stand on what was previously empty space. Stand on the center question-mark block and hit the yellow block immediately above. A vine will appear, which must be climbed. At the top is a long platform extending to the right, and there is a blue door at the rightmost end. (The P-switch must not have timed out in order for the door to still be there.) The door leads to a battle-room, where there is one Big Boo and three Boo Buddies. The Big Boo must be defeated by throwing at it the gray blocks that make up the floor. Be careful not to create a hole in the floor and fall through it. After the Big Boo is hit three times, it will be defeated, leading to Star Road.
# Super Mario World/Enemies

There are many enemies in Super Mario World. Some can be defeated simply by jumping on them. Some require more complicated moves, while some cannot be defeated at all.
Descriptions and methods of defeating an enemy are listed on the page about the enemy.
A
B
* Ball 'n' Chain
* Banzai Bill
* Blargg
* Blurp
* Bob-omb
* Bony Beetle
* "Boo" Buddy
* The Big "Boo"
* Bullet Bill
* Buzzy Beetle
C
D
* Dino-Rhino
* Dino-Torch
* Dry Bones
E
F
* Fishbone
* Fishin' Boo
* Fishin' Lakitu
G
* Goomba
* Grinder
H
J
* Jumpin' Piranha Plant
* Jumpin' Pumpkin Plant
K
L
* Lakitu
* Lil' Sparky
M
* Magikoopa
* Mask Koopa
* Mechakoopa
* Mega Mole
* Monty Mole
N
P
* Para-bomb
* Para-koopa
* Para-goomba
* Pidgit Bill
* Pokey
* Porcu-Puffer
R
* Rex
* Rip Van Fish
S
* Spiny
* Spike Top
* Sumo Brother
* Super Koopa
* Swooper
T
* Thwimp
* Thwomp
* Torpedo Ted
U
V
W
Bosses:
* Bowser
* Iggy Koopa
* Larry Koopa
* Lemmy Koopa
* Ludwig von Koopa
* Mechakoopa
* Morton Koopa
* Reznor
* Roy Koopa
* Wendy O. Koopa
# Super Mario World/Donut Plains/Green Switch Palace

You start out in a room with a P Switch, a Tornado Shell, brown blocks, coins, and Koopas. Hit the switch and run across the coins that changed into blocks. The Tornado Shell will hit all the Koopas and get you a 1up! Then get it in between two coins before the switch runs out. This will trap it. Go through the pipe and press the Green Switch. Now you will find green blocks. These give you a cape if hit, and they make it easy to unlock DONUT SECRET 1. You need them to get past STAR WORLD 4 along with red blocks, and you need them to enter the Special World.
# Super Mario World/Donut Plains/Top Secret Area

The Top Secret Area can be accessed through Donut Ghost House on the second island of Super Mario World. The Top Secret Area contains 5 yellow boxes. The first 2 are Fire Flowers and the second 2 are Feathers. The middle box contains Yoshi. If you go to the Top Secret Area and are small, the first box you hit will be a Mushroom (with the exception of the middle box). If you go to the Top Secret Area and already have Yoshi, you will get a one up mushroom when you hit the middle box. If you think you need to skip this part of the game... Don't! It's very handy where you're running low on lives or need a cape/flower power. (Repeatedly enter this Secret Area when you have Yoshi to aquire more lives). This basically is the coolest part of the game.
When you leave this level in 2-Player mode, it's still your turn!
# Structural Biochemistry/Salt Effects

With one negative charge per connective phosphate, RNA is considered a polyelectrolyte. In order to achieve neutrality, RNA attracts cations, creating a counterion atmosphere. While weak, this cation bonding is crucial to maintain both secondary and tertiary structures. For this reason, the structure, stability, and reactivity are heavily dependent on external ionic conditions. Salt, usually in the form of Mg(2+), has been found to have profound kinetic effects on the folded and unfolded states of RNA (Li, Vieregg, Tinoco Jr, 85). The addition of salt causes a higher kinetic barrier between the folded and unfolded states, but does not effect the point at which the transition between the two states occurs.
The aforementioned statement was confirmed by a study by Li, Vieregg, and Tinoco Jr titled "How RNA Unfolds and Refolds." The study examined the effect of increasing levels of Mg(2+) on RNA hairpins and a three-helix junction. As predicted, the addition of the salt resulted in higher energy unfolding and refolding, meaning that the higher concentration of cations stabilizes secondary structures. This increase in stability was found to be the result of a slight decrease in the unfolding rate and a larger increase in the folding rate of the RNA (87). Monovalent cations were also studied, and where found to have the same effect as divalent salts, but to a much lesser extent (86).
Metal ions, like Mg(2+), have an even stronger effect on RNA tertiary structure than on secondary structure, due to a higher dependence on ionic conditions. The addition of metal ions greatly slows the process of undoing tertiary structure, but has little effect on tertiary folding rates (88). For example, loop-loop interactions, which rely on a "kissing" interaction, becomes highly stabilized with the addition on a mere mM of Mg(2+)(88).
Work Cited: Li, Pan T.X., Jeffrey Vieregg, and Ignacio Tinoco. "How RNA Unfolds and Refolds." Annual Review of Biochemistry 77.1 (2008): 77-100. Print.
# Structural Biochemistry/Salt Effects on Mechanical Folding

With one negative charge per connective phosphate, RNA is considered a polyelectrolyte. In order to achieve neutrality, RNA attracts cations, creating a counterion atmosphere. While weak, this cation bonding is crucial to maintain both secondary and tertiary structures. For this reason, the structure, stability, and reactivity are heavily dependent on external ionic conditions. Salt, usually in the form of Mg(2+), has been found to have profound kinetic effects on the folded and unfolded states of RNA (Li, Vieregg, Tinoco Jr, 85). The addition of salt causes a higher kinetic barrier between the folded and unfolded states, but does not effect the point at which the transition between the two states occurs.
The aforementioned statement was confirmed by a study by Li, Vieregg, and Tinoco Jr titled "How RNA Unfolds and Refolds." The study examined the effect of increasing levels of Mg(2+) on RNA hairpins and a three-helix junction. As predicted, the addition of the salt resulted in higher energy unfolding and refolding, meaning that the higher concentration of cations stabilizes secondary structures. This increase in stability was found to be the result of a slight decrease in the unfolding rate and a larger increase in the folding rate of the RNA (87). Monovalent cations were also studied, and where found to have the same effect as divalent salts, but to a much lesser extent (86).
Metal ions, like Mg(2+), have an even stronger effect on RNA tertiary structure than on secondary structure, due to a higher dependence on ionic conditions. The addition of metal ions greatly slows the process of undoing tertiary structure, but has little effect on tertiary folding rates (88). For example, loop-loop interactions, which rely on a "kissing" interaction, becomes highly stabilized with the addition on a mere mM of Mg(2+).

## Reference

Li, Pan T.X., Jeffrey Vieregg, and Ignacio Tinoco. "How RNA Unfolds and Refolds." Annual Review of Biochemistry 77.1 (2008): 77-100. Print.
# Structural Biochemistry/Roger D. Kornberg

Roger David Kornberg was born in April 24th, 1947, and was the Nobel Prize winner of Chemistry in 2006 for his research in eukaryotic transcription.
Transcription is part of the Central Dogma in which DNA is transcribed into RNA and then translated into proteins. In DNA transcription, mRNA is transcribed by an enzyme called RNA polymerase II with the help of other proteins. In Kornberg’s research at Stanford University, yeast was used to determine the three-dimensional structure of a protein cluster of RNA polymerase II and other proteins. Identification of transcription machinery, to Kornberg, was necessary in order to further the study of transcriptional regulation. In addition, yeast was used because it was a unicellular organism that had the same RNA polymerase II system as mammalian systems. Kornberg first accomplished this by creating a technique to form a two-dimensional protein crystal on lipid membranes to produce a low resolution image of the RNA polymerase II. Later, he was able to use this technique to yield larger crystals that could be used in x-ray crystallography to determine the three-dimensional structure of RNA polymerase II on an atomic level. This technique was then applied to find the other accessory proteins that are associated with RNA polymerase II. He then used this information about the proteins to determine the transcription process of yeast by isolating purified forms of certain proteins in transcription. These discoveries in yeast, Kornberg was able to detect an additional protein that transmitted gene regulation signals to the RNA polymerase II that was named “Mediator”. The discovery of the “mediator” was, “a true milestone in the understanding of the transcription process” according to the Nobel Prize committee.

## References

http://www.nobelprize.org/nobel_prizes/chemistry/laureates/2006/kornberg-autobio.html
http://www.nndb.com/people/615/000138201/
# Super Mario World/Enemies/Para-bomb

Para-bombs are tiny bombs that fall from the sky with a parachute. Once they land they walk about until their timer is set and they soon explode.

## Resistance to attacks

* Normal Jump: Prematurely sets timer
* Spin Jump: Ineffective
* Jump with Yoshi: Effective
* Fireballs: Ineffective
* Cape Spin: Effective
* Yoshi's Tongue: Edible (So is the explosion)
* Yoshi's Fireballs: Ineffective

## Locations

* Forest of Illusion 3
* Vanilla Secret 2
* Chocolate Island 5
# Super Mario World/Enemies/Mask Koopa

The same as an ordinary Koopa, but you must go through the special star road in the special zone to get to the Fall, where you will see them instead of koopas. (Some of them change color-like the red ones in Yoshi's Island 2 turned blue) See Koopa page for info!
# Super Mario World/Enemies/Monty Mole

Monty Moles are small creatures that hide in the ground and in mountains, waiting for Mario or Luigi to approach them. Before they pop up out of the ground, they cause the dirt in the ground and on the mountain walls to crumble, giving away their location. They then pop out of the ground, and follow Mario and Luigi wherever they walk until they are outrun or they fall off the stage. Also, if Mario or Luigi outruns a Monty Mole, but then returns to the area where it popped out of, another Monty Mole will spawn from the same hole the first one jumped out of.

## Resistance to attacks

* Normal Jump: A normal jump defeats a Monty Mole in one hit.
* Spin Jump: A spin jump defeats a Monty Mole in one hit.
* Jump with Yoshi: With Yoshi, a normal jump defeats Monty Moles in one hit.
* Fireballs: When hit with a fireball, Monty Moles turn into coins.
* Cape Spin: Spinning with (B) or (R) will defeat a Monty Mole.
* Yoshi's Tongue: Yoshi will swallow and eat Monty Moles.
* Yoshi's Fireballs: Monty Moles turn into coins if you shoot fireballs at them (with Red Yoshi and/or a red shell).
*** You can swallow them with Yoshi when they aren't out of the ground, on a flat surface (where the earth crumbles)***

## Locations

* 5 on Yoshi's Island 2
# Super Mario World/Enemies/Para-goomba

Para-Goombas are similar to regular Goombas, except they have wings and fly around to hit you. One stomp will remove the wings.
# Super Mario World/Enemies/Mechakoopa

Mechakoopas are wind-up toy robots shaped like a Koopa. They're actually quite useful, for example in the final battle against Bowser. Bowser will randomly throw two down at a time. They must be stomped, then thrown back at Bowser. Note that if you have jumped on them, they come back to life in a few seconds, so you need to throw them away as fast as possible.

## Resistance to attacks

* Normal Jump: A single jump will make them shrink, to defeat them, just jump another time on them
* Spin Jump: Very effective, a spin jump will defeat them instantly
* Jump with Yoshi: N/A, you can't jump with Yoshi on them, since they're only in Bowsers Castle.
* Fireballs: Ineffective, it won't harm them
* Yoshi's tongue: N/A, since Yoshi can't enter the castle
* Yoshi's fireballs: N/A, since Yoshi can't enter the castle
* Slow cape landing: It will do the same as when you smash them with your cape by pressing Y in the SNES version, or just by pressing B in the GBA version
* Sliding down a hill: It will defeat the Mechakoopas

## Locations

Bowser's Castle
# Super Mario World/Enemies/Morton Koopa

Morton Koopa Jr. is the second koopa boss in the game, located in his castle in Donut Plains. He is stationed on a platform over a large lava pit confined by two large pillars, he must be hit when he is on the ground three times to be defeated.

## Resistance to attacks

* Normal jump: A normal jump will weaken Morton Koopa Jr,you must hit him three times to defeat him.
* Spin jump: Has the same effect as a normal jump.
* Jump with Yoshi: N/A
* Fireballs: No effect
* Cape spin: No effect
* Yoshi's tongue: N/A
* Yoshi's fireballs: N/A

## Locations

* Morton's Castle
# Super Mario World/Enemies/Ludwig von Koopa

Sort of a mix between Iggy Koopa and Morton Koopa. He will spit fire balls for a main attack, either jump or duck to dodge it. He will then go in his shell and try to hit you.
# Super Mario World/Enemies/Mega Mole

Mega Moles are giant versions of Monty Moles, and they are only found in Valley of Bowser 1.
You cannot defeat them by jumping on them, but you can use them for a ride. Cape spins and aerial diving slams will defeat them, though. Yoshi can also eat them.