Therapy

Probing the α-helical structural stability of stapled p53 peptides using replica exchange molecular dynamics.

Zoujun Guo, Udayan Mohanty, Justin Noehre, Tomi Sawyer, Woody Sherman, and Goran Krilov.

Background Biology:
Mdm2 is a negative regulator of the p53 tumor suppressor protein. A helical portion of p53 binds to mdm2 and recent studies have shown that the helical propensity of peptide fragments as measured by circular dichroism (CD) is correlated with inhibitory mdm2 activity. A new synthetic chemistry technology to staple peptides is a way to increase the helical nature of a peptide.

The Aim:
Stapled peptides have been shown to have increased helical characteristics in solution and also increase binding activity to mdm2. Predicting the effect of a staple on helical stability could aid in the understanding and design of therapeutic agents. We aim to see if the helical stabilizing properties of the staple can be reproduced using computer simulations.

Simulation Details:
Replica exchange molecular dynamics (REMD) was run on a wild type p53 peptide and a stapled variant. A total of 64 replicas were run across 64 processors with a temperature range of 300-600 K, for a cumulative simulation time of 320 ns for each peptide.

Comments:
Stapled peptide has increased helical stability. The staple is shown in cyan color. Wild type (unstapled) peptide has decreased helical stability. Residues Leu, Trp and Phe are critical for high affinity peptide binding. They are highlighted in CPK representation. Even after 5 ns of REMD with 64 replicas ranging from 300-600 K, the stapled peptide maintains its helical structure.

Software:
Schrodinger Suite 2009 and PyMOL
(www.schrodinger.com)

Duration : 0:2:14

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Music by Johnnie Cash and Willie Nelson
Chemtrails over Richmond, Indiana.Just shows how they continue to spray us with who knows what and what for.
PUBLIC LAW 105—85—NOV. 18, 1997: USE OF HUMAN SUBJECTS FOR TESTING OF CHEMICAL OR BIOLOGICAL AGENTS

SEC. 1078. RESTRICTIONS ON THE USE OF HUMAN SUBJECTS FOR TESTING OF CHEMICAL OR BIOLOGICAL AGENTS.

(a) PROHIBITED ACTIVITIES.—The Secretary of Defense may not conduct (directly or by contract)

(1) any test or experiment involving the use of a chemical agent or biological agent on a civilian population; or
(2) any other testing of a chemical agent or biological agent on human subjects.

(b) EXCEPTIONS.—Subject to subsections (c), (d), and (e), the prohibition in subsection (a) does not apply to a test or experiment carried out for any of the following purposes:

(1) Any peaceful purpose that is related to a medical, therapeutic, pharmaceutical, agricultural, industrial, or research activity.
(2) Any purpose that is directly related to protection against toxic chemicals or biological weapons and agents.
(3) Any law enforcement purpose, including any purpose related to riot control.

PROTECTED UNDER FREEDOM OF SPEECH IN THE US CONSTITUTION.
This is Freedom of Speech at it’s best!
As Protected and Guaranteed to me in The US Constitution!

Keywords: American Militia, American Resistance Movement, American Revolution, Revolution, Revolt, American Militia Movement, A.R.M, Alex Jones, New World Order, Illuminati, NWO, Skull and Bones, Bush, 911 Conspiracy, The Civilians Military, Militia, American Resistance Movement, Revolt, Bilderberg, CFR, Alex Jones, Jordan Maxwell, Loose Change, End Game, Terrorstorm, Patriot Act, HR 1955, 911 was an inside job, truth, iraq war, black water, free masons, Ron Paul, New World Order carbon tax CO2 Global Warming is a fearmongering scam. The sun is getting hotter. Alex Jones is just one source. Police State is just making some X-military clones. MK Ultra mind control. Income. John F. Kennedy or JFK CIA FBI international bankers Rothschild David Rockefeller. Chemtrails chemical trails from jets. Air Force United States Army Navy Marines National Guard. NORAD stood down. Fake war in Iraq and Afghanistan but the human deaths are real. Corporations own a market for every physical item on this Earth. Immortal Technique is trying to push the revolution into the streets. I don’t know if I can agree with that. People go to work all day Jedi Mind Tricks are alright. Vinnie Paz in shit. Paris is OK. Sick Since and Ill Bill all good. 911 or September 11, 2001 was the greatest world scam to take place in a very long time, no matter what your take on the conspiracy theorist or theories America American Turn off the TV and the news. Project Paper Clip Operation Northwoods George W H Bush Bill Skull and Bones Bohemia Grove secrete societies Freemasons mason Masonic Temple Mormon. Government in schools. Mercury Vaccines. Nazi Hitler Every one is in a rush. Drugs marijuana blunt alcohol tobacco National ID Cards in May 2008. Elections are rigged. Real ID Act congress president. Obama and Mccain are clones. Republicans and Democrats are the same. Council on Foreign Relations. Club of Rome. Trilateral Commission. Federal Reserve illusion money dollar fall. Graph and carts. Round Table. Cocaine Mushrooms Crack Heroin Meth. 666 Mark of the Beast Christian Catholic Muslim Jewish Jew inside job protest fight Last Days Jesus Christ God. The second coming. North American Union. South American Union. APEC. European Union. All Seeing Eye. Devil Lucifer. Traffic cams cameras intersection cops clowns jesters. CFR is weak. NAU One World Government

Duration : 0:5:19

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Lysergic acid diethylamide, LSD, LSD-25, or acid, is a semisynthetic psychedelic drug of the ergoline family. Its unusual psychological effects, which include visuals of colored and crawling geometric patterns, and a sense of time distortion have made it one of the most widely known psychedelic drugs. It has been used mainly as a recreational drug, an entheogen, and as a tool to supplement various practices for transcendence, including in meditation, psychonautics, art projects, and illicit (formerly legal) psychedelic therapy. Formally, LSD is classified as a hallucinogen of the psychedelic type.[1]

LSD was first synthesized by Albert Hofmann from ergot, a grain fungus that typically grows on rye. The short form LSD comes from its early code name LSD-25, which is an abbreviation for the German “Lysergsäure-diethylamid” followed by a sequential number.[2][3]

LSD is sensitive to oxygen, ultraviolet light, and chlorine, especially in solution, though its potency may last for years if it is stored away from light and moisture at low temperature. In pure form it is colorless, odorless, and mildly bitter.[3]

LSD is typically delivered orally, usually on a substrate such as absorbent blotter paper, a sugar cube, or gelatin. In its liquid form, it can be administered by intramuscular or intravenous injection. The threshold dosage level needed to cause a psychoactive effect on humans is between 20 and 30 µg (micrograms).[4]

Introduced by Sandoz Laboratories as a drug with various psychiatric uses, LSD quickly became a therapeutic agent that appeared to show great promise. However, the extra-medicinal use of the drug in Western society during the mid-twentieth century led to a political firestorm that resulted in the banning of the substance.[5] A number of organizations—including the Beckley Foundation, MAPS, Heffter Research Institute and the Albert Hofmann Foundation—exist to fund, encourage and coordinate research into its medicinal uses.[6]

The European Monitoring Centre for Drugs and Drug Addiction reports that LSD retail prices range between €5 and €11 per unit in most European countries.[7]

Duration : 0:1:3

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Please read this. It will take 2 minutes and it is very important.
TITLE 50 > CHAPTER 32 > § 1520a
Restrictions on use of human subjects for testing of chemical or biological agents

(a) Prohibited activities
The Secretary of Defense may not conduct (directly or by contract)—
(1) any test or experiment involving the use of a chemical agent or biological agent on a civilian population; or
(2) any other testing of a chemical agent or biological agent on human subjects.
(b) Exceptions
The prohibition in subsection (a) of this section does not apply to a test or experiment carried out for any of the following purposes:
(1) Any peaceful purpose that is related to a medical, therapeutic, pharmaceutical, agricultural, industrial, or research activity.
(2) Any purpose that is directly related to protection against toxic chemicals or biological weapons and agents.
(3)!!!!!!!!!!!!!!!!!!!! Any law enforcement purpose, including any purpose related to riot control.!!!!!!!!!!
“Biological agent” defined
In this section, the term “biological agent” means any micro-organism (including bacteria, viruses, fungi, rickettsiac, or protozoa), pathogen, or infectious substance, and any naturally occurring, bioengineered, or synthesized component of any such micro-organism, pathogen, or infectious substance, whatever its origin or method of production, that is capable of causing—
(1) death, disease, or other biological malfunction in a human, an animal, a plant, or another living organism;
(2) deterioration of food, water, equipment, supplies, or materials of any kind; or
(3) deleterious alteration of the environment.

SO THERE IT IS. A police officer has the legal authority to pull you over and kill you with a bilogical weapon. Or if you are a striking teacher or a civil rights marcher they can KILL YOU WITH A BIOLOGICAL OR CHEMICAL WEAPON LEGALY.

http://www4.law.cornell.edu/uscode/html/uscode50/usc_sec_50_00001520—a000-.html
"Trollbust…" read the "biological agent defined" or go to the cornell law link and read the U.S code for yourself. It doesnt mean pepper spray.

Here–protect yourself:

http://www.zapatopi.net/afdb/

They’re talking about pepper spray and that genre of agent.

sheeeeeeesh.

what are their uses or definitions? pls.. help me, it’s my report..give me some sure information about all of it and how it’s process takes place in general…thanks a lot..

http://magegame.ru/?rf=53756e736574

TITLE 50–WAR AND NATIONAL DEFENSE

CHAPTER 32–CHEMICAL AND BIOLOGICAL WARFARE PROGRAM

Sec. 1520a. Restrictions on use of human subjects for testing of
chemical or biological agents

(a) Prohibited activities

The Secretary of Defense may not conduct (directly or by contract)–
(1) any test or experiment involving the use of a chemical agent
or biological agent on a civilian population; or
(2) any other testing of a chemical agent or biological agent on
human subjects.

(b) Exceptions

Subject to subsections (c), (d), and (e) of this section, the
prohibition in subsection (a) of this section does not apply to a test
or experiment carried out for any of the following purposes:
(1) Any peaceful purpose that is related to a medical,
therapeutic, pharmaceutical, agricultural, industrial, or research
activity.
(2) Any purpose that is directly related to protection against
toxic chemicals or biological weapons and agents.
(3) Any law enforcement purpose, including any purpose related
to riot control.

http://www.skyhighway.com/~chemtrails/docs/U_S_%20Code_Title_50_Chapter_32_Section_1520a.html

Duration : 0:10:59

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OK. On Sept. 1 I met a guy from Spain while vacationing with my friends in Mexico. There was instant chemistry. I had a boyfriend at the time, so all me and Mr. Spain did was talk. From that moment forward I have thought about him every day. And I mean every day. I have tried to forget about him and let it be, but I can’t. While in MX, we exchanged contact info and have been chatting via IM ever since, which is 4 & 1/2 months now. In Oct. I became single, which allowed me to explore the feelings I was having for Mr. Spain. However, how do you explore your feelings with someone who lives in another country? So instead I held my feelings in and continued to talk with him on IM as before. Then recently he proposed that the two of us go on holiday together. That was a very exciting moment for me. I talked with my travel agent, and she found me some good deals on all inclusive trips. I told Mr. Spain about the trips, and he said they sounded great but didn’t indicate anything further like, "Lets book it." It was two days ago that this happened. Then yesterday I wrote an email as if I was writing it to him that told him what I was feeling, that I thought about him a lot and that seeing him again might help me determine if what I am feeling is legit. I didn’t say those words, but that was the overall tone of the email. It was therapeutic (I am a writer at heart, so writing is therapy) to get it all out, but I didn’t hit send. As I was talking to him on IM yesterday evening I mentioned the email, and he asked me to send it. I said that I was scared, and he said never to be scared with him. So I sent it. He said he would read it while at work today. Well, he is now off work as it is almost 10pm in Spain. He has not signed in to IM nor has he emailed me back. I don’t know what to do! I allowed myself to be vulnerable, and now I am sitting here in agony wondering what he thought about what I said. It’s killing me. I just want him to say something about it, even if that something is, "No, I don’t think about you all the time and don’t really care if we see each other again." Yes, it would hurt, but at least I would know. I could then get over it and focus on guys that are here…like the one I am going on a date with tonight. We had our first date two days ago, and he is soooo sweet and funny and charming. But on my drive home I couldn’t get Mr. Spain out of my head. Until I know how he feels, it’s like I can’t give myself to someone else. I am just so afraid that if I didn’t make my feelings known and put effort into seeing Mr. Spain again then I would always wonder "what if." So because of that I don’t regret sending that email, but I’m still dying over here waiting to know what he’ll say or if he’ll ever talk to me again. Anyone have any advice?

Sending the email off to him was a good idea because if nothing else comes of it, a least you won’t have to wonder what if. This fantasy you have…this insatiable desire for him, it is preventing you from functioning as well as you could be in your real, here, now, and available world. Sure it hurts not hearing that he feels the same but it should no way keep you from moving forward (enjoying dating others). Get out your emotions about it and then move on. The whirlwind of emotions had swept you up and overtaken you; don’t let it take your common sense…and don’t let it make you miss out on something special that is waiting for you hear and now.

If I could not read my whole world would be a very dismal and dark place. And I feel sorry for those people who have no interest no desire to read. Reading takes me to a different place, world and time. Reading makes me forget about everything and focus on what the main character is going through and how is he or she going to get out of their troubling dilemma. In a lot of ways reading is very much therapeutic as it helps you forget about a stressful day. It is educational as a nonfiction account of a particular subject, like a war, will teach readers things they did not know before like how cold weather can affect tanks and ultimately the war. Out of the millions upon millions subjects to read about, I personally like to read about the Vampire Chronicles written by Anne Rice and any books by African-American Authors.

I enjoy these types of books mainly because I love the story line to them and how they can keep me wrapped up for hours at a time. I have read all of the Vampire Chronicles which follows a vampire named Lestat around the world, through time and all of the obstacles he faces as both a protagonist and antagonist. I enjoy reading about him because he is so personal and you really see things from his perspective even if it is wrong. The author is also very talented because there are times in which the book isn’t told through Lestat’s perspective but rather another vampire. For example, the first book in the Vampire Chronicles is told from Louis’ (another vampire) perspective and his writing style and views are much different than Lestat. Because Anne Rice is so talented in the way that she writes, all of the vampires have a unique voice and it’s as if the books are written by six to seven different vampires.

The same goes for E. Lynn Harris, who is an accomplished African- American writer. For a long time he wrote books about a character named John Basil Henderson who was a very famous sports agent who was bi sexual but lived a secret life as a gay man. Throughout the books you can see how Basil deals with his sexuality, the people in his life and the haunting of his sexual abuse by his uncle when he was younger. He is very much like a Lestat in the way he goes through life as being both a good and bad guy. Also, like in the Vampire Chronicles certain chapters in these books are told from other characters. The difference in their tone and voice is written and executed. Again, it is another well written book that is simply amazing and keeps me turning the pages.

I enjoy books that keep me in suspense. Books that are not just told from same person from page one to page five hundred fifteen. I like it to be diverse in the narration, the time, and maybe even the place. I like being able to put two and two together to figure what is going to happen next and being surprised. Most of all I just like books that are well written that makes me feel like I am right next to the main character, that I can feel what he or she is feeling, thinking and going through.

Don’t start sentences with "And."
Comma after "world."
The forth sentence isn’t clear. Replacing the first "and" with because I or something similar would make it better.
"He or she" is awkward, change the sentence so you can use they instead.
I personally don’t like "very much."
"It is educational" because. Not as. This sentence is also a run on, and you might want to break it up.
No dash between "African" and "Americans," and "Authors" should be lowercase. The meaning of this sentence isn’t clear. You’re saying you like to read books that mention The Vampire Chronicles and books by African Americans.

Storyline is one word, and no "to them."
Break up the second sentence so you don’t have to use "which." No comma.

Is not, not isn’t. No contractions in a formal essay.
Maybe use since, instead of "because."
No contractions again.

I’d get rid of "who is."
No dash in African American.
The second sentence is a run on. I’d break it up at "who was."
Comma after "people in his life."
Comma after "Vampire Chronicles"
You need a positive word after "executed."

"I like" them. Not "it"
Phrases like "two and two together" are too informal for a formal essay, but it depends what teacher you are writing for.
The last sentence is another run on. The "that" needs to be and.

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Duration : 0:7:29

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currently enrolling in a pharmacology course, and i am struggling with this one question:

Acyclovir is a new potent and selective anti-viral agent.When administered to human beings,most of the drug is eliminated from the body unchanged,via glomerular filtration and tubular secretion.Due to its large therapeutic index,the maximum plasma level after administration can be 1.3mg/L without causing any side effect,whereas the clinical effective plasma concentration needs to be higher than 0.06mg/L.The bioavailability of the orally administered Acyclovir is low(20%),and dosing is required 2-5times a day.Acyclovir.For a 70kg adult,the elimination rate constant is 0.28hr and apparent volume of distribution is 56liters approx.The oral dose is considered to be formulated as 200mg or 400mg.Due to a limitation of sustained release capsule,the absorption rate constant of oral dosing form can be controlled as 0.167hr,or 0.083hr.Design a possible once-a-day oral dosing form(the best D and Ka)

This question is really more appropriate for the engineering or math sections. Consider the human body as a box. Drug is going in and drug is coming out. Your ultimate goal for this question is to figure out what the concentration of the drug is inside the box at any given time (and you will want it to be in the range of 0.06-1.3 mg/L). The only info you have are the rates at which things are going in and coming out. These won’t tell you what the concentration is, but they will tell you how it is changing over time–and you can figure out the concentration based on this since you know the starting condition.

First, what is going into the box at any given time?
(1) D * ba * exp(-ka * t) / V
where D is the dosage (either 200 or 400 mg), ba is the bioavailability (20%), ka is the absorption constant (either 0.167/hr or 0.083/hr), t is time, and V is volume of distribution (56 L).

Second, what is coming out of the box at any given time?
(2) C * ke
where C is the concentration, and ke is the elimination constant (0.28/hr).

The change in concentration with time is equal to [stuff going in] – [stuff coming out].
(3) dC/dt = [D * ba * exp(-ka * t) / V] – [C * ke]

rearrange to:
dC + ke*C*dt = D * ba * exp(-ka * t) / V * dt

If you have been assigned this problem, then you must know how to solve differential equations. Analytically, you can solve this first-order linear differential equation using an integrating factor of exp(ke*t).

(4) dC*exp(ke*t) + ke*C*dt*exp(ke*t) = D*ba*exp(-ka*t)/V*dt*exp(ke*t)

The left side of the equation (4) is the differential of C*exp(ke*t) (that’s the whole trick behind the use of integrating factors). So when you integrate both sides of the equation and you get:

(5) C*exp(ke*t) = A + Int{ D*ba*exp(-ka*t)/V *dt*exp(ke*t)}
where A is a constant of integration and Int{ denotes the integral operator.

Solve this to get
(6) C = {A + D*ba*exp[(ke-ka)*t] / V / (ke-ka)} / exp(ke*t)
You could also solve equation (3) computationally, but why bother?

You can solve for A using either the initial condition of C(0) = 0 or C(0) = 0.06. Just make sure to specify which one you used.

Now you have the function C(t). You can plot it using the two possible values for D and the two possible values of ka over a time period of 24 hours. You should find that D=200 mg and ka=0.167/hr are the only values that keep the plasma concentration within the therapeutic range.