text:
Neil commented on the blog post U.S. Sen. Scott Brown to LGBTs: You'll Get No Promises from Me
Dns Toolbox tell me this IP is a Comcast Business ip address. Anyone know how to find out whose business?
Neil commented on the blog post Live Blog for #Occupy Movement: Occupying the Rose Parade with a Giant Octopus Float
I want to thank Kevin for listening to Al Roker so I don't have to.
I'm at home on the east coast, following Kevin's live blog, tuned into NBC with the sound down and watching OakFoSho's live stream http://www.ustream.tv/occupyoakland (when its up and has sound) and FreedomLA's live stream http://www.ustream.tv/occupyfreedomla
I'm interested to know 1) how many people are marching the in the Occupy The Rose Parade contingent, 2) other actions today, if 3) the Wisconsin badgers will win the Rose Bowl and whether 4) Americans will come together to save our amazing low fee public universities like UW Madison, Berkeley, Davis, etc. We have many expensive private schools and we have many expensive public schools. What is unique is world class public universities like Madison and Berkeley that are accessible to smart students regardless of their financial status and without withering debt.
Turn the profitmakers away from profitizing public education.
Neil commented on the diary post Bastille Square: a new era for civil disobedience à la française by Waging Nonviolence.
I love the word too and note that their dignity is tied to self-sufficiency, the ability to work and support themselves.
Neil commented on the blog post Happy Trails: Parting Is Such Sweet Sorrow
Wow just wow. I did't know but that's because been out of pocket. Can't wait for … the news tomorrow.
Neil commented on the blog post Where I Walk My Dog
I love the spirit of midwesterners. They don't take any shit and at the same time they're so nice about it. Call them thugs, and they wear it with a smile like a badge of honor that says, jokes on you asshole. Tell them their city sucks and they set out to prove you wrong. The camera work is impressive asis the coordination of all the scenes and the shear number of people who chose to participate. Yea Grand Rapids.
Neil commented on the blog post Working Thread on Illegal Wiretap Memo
Neil commented on the blog post Postcard from a New American Progressive Movement: The Wisconsin Strategy
David, this is a great piece.
I've been glued to twitter for two weeks following this story, read all the articles, watched online video feeds and still, reading this, I learned so much about the movement I thought I knew pretty well. Terrific!
Neil commented on the blog post A Lovely Day at the Beach
Now I remember you mentioning DeVos and Grand Rapids. On google satellite, it looks like the beach is especially wide near the breakwater.
Even with a cold wind blowing, a walk on the beach reminds me of the promise of the new season ahead.
Shoveling out from under this years' frequent and substantial snow storms (including three thunder-snows) has been good for workouts but I'm ready for mud season.
Neil commented on the blog post A Lovely Day at the Beach
That's a great photo of you and McCaffrey the MilleniaLab. I didn't know the eastern beaches of Lake Michigan were so wide in places or that you lived close enough to go there for a walk with McCaffrey.
Neil commented on the blog post Dear Egypt: We Love You for Your Freedom
May it inspire those of us watching from America to reclaim our own democracy.
I'm ready to work for it.
Neil commented on the blog post The Mythification of the Looting Elite
Nip the frame in the bud and cast one that reflects some basis in facts.
Neil commented on the diary post Accountability: Who Else Will Go the Way of Congressman Bobby Rush? by James Rucker.
Effective activism, on our side. Hit 'em up…non-violently speaking, of course.
Neil commented on the blog post Goal of Quantico Incident Was To Abuse Bradley Manning and Intimidate David House
@JohnKerry Goal of Quantico Incident, To Abuse Bradley Manning and Intimidate @DavidMHouse MA resident MIT researcher http://bit.ly/hCVT6S
Neil commented on the blog post The Final Countdown: Championship Sunday NFL Trash Talk
Who wouldn't pick the underdog at home? Go Bears. I'll take the underdog on the road too. J E T S Jets Jets Jets.
P – A – T – S PATS PATS PATS. The only thing worse than watching the Giants beat the Patriots in the Super Bowl, was watching the Patriots, with the best record in the league, lose to the Jets in their first round.
Neil commented on the diary post Water Cooler – So, What Are You Reading? by Bill Egnor.
For Masaccio
for http://pdamerica.org/articles/news/2011-01-15-00-56-49-news.php
Neil commented on the blog post IRA Attack Survivor on Peter "Material Support for Terror" King's Hypocrisy
I'm not too pleased about Biden using the word 'terrorist' to describe Assange. Whatever Assange is, and I would say publisher, he is not a terrorist.
I know it's too much to ask that the question of whether Rep. Peter King provided material support to terrorist organizations be raised as part of national political debate, and what exactly made the secret service identify him a threat to President Reagan.
Neil commented on the blog post MA Court: Banks Must Own a House to Forclose on It
Good news for the rule of law in property rights. Good news for people who live in homes at risk of being foreclosed, especially people working in good faith to address the financing problem as the banks play them like chumps.
Neil commented on the blog post Excluding Atheists from the Military Just as You Let Gays Openly Serve
Neil commented on the blog post El País Editor: When Democracy's Rules Are Flouted, Democracy Is Put at Risk
Since 24 September 2010, the FBI has served at least 24 grand jury subpoenas on students and activists in a secret investigation that many have called a witch hunt. We call upon Attorney General Eric Holder and United States Attorney Patrick Fitzgerald to respect the civil rights and free speech of all those who support the Palestinian struggle for freedom by immediately withdrawing grand jury subpoenas which threaten the First Amendment rights of students and activists around the country. src
What's the standard for obtaining a subpoena for a witness to appear at a Federal Grand Jury?
Neil commented on the blog post Floyd Abrams' Abuse of Power
Fran Townsend on CNN with Glenn:
[The release of the State Department cables] was so vast, of what was public, whether or not it would be useful or no he made no distinctions about the harm he might be doing to foreign governments, to the U.S. government, to diplomats and soldiers around the world.
This is a persistent talking point that is untrue. I want to understand if it is ignorance or willful.
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is that price shipping inlcuded?
All new Continental Conti Attack SM tire available and on sale! This is a great now supermoto tire that is built for the track or street.
120/70-17 150/60-17 SET $275.95 $115.28 OFF Retail
120/70-17 160/60-17 SET $282.95 $118.00 OFF Retail
Here's the link to purchase them.
is that price shipping inlcuded?
Unfortunately it is not including shipping. Shipping will be calculated on the online shopping cart based on your location.
I could raise the price of the tires to include shipping, but the price can't really get any lower than what's listed.
Awesome tyres, get some
2003 KTM 660 SMC - Sold
2007 Suzuki DR-Z400SM - Sold
Hmmmm...... I wonder if these Conti Attack SM's are replacing the Contiforce SM's.
Squid Rydaz Int'l Moto Club - Making Squids around the world, cool again!!
My Support: fastkeys.com; scooterwest.com; sanomx.com; sdbmwmc.com; SisnerosSpeedWorks.com; MRD-Racing.com
would those running these tires recommend something like this over a pilot power setup . i mainly ride on the street in the twisties
these tyres are vastly superior to pilot powers.
theyre ready to go pretty much as soon as theyre fitted. they dont use a releasing agent per se in manufacture so theres no 'scrubbing' off to do. they dont last very long, but they tear up and spit rubber off under heavy riding on hot days. they grip like you know what.
Last edited by akaDan; 02-05-2012 at 07:59 PM.
2003 KTM 660 SMC - Sold
2007 Suzuki DR-Z400SM - Sold
Do you ship to Canada? The site has the option to enter Postal Code but only allows for 5 characters instead of 6... Thanks
1986 Yamaha Radian YX600 (Sold)
1986 Yamaha DT200 (Sold)
dang, $123.65 shipped here is that how much a box costs to send here? zip 96813. can you double check that, i cant see them needing any packing materials either. killer deal i would but wowza if thats true
Not Banned
Challenges Complete: 24
2010 HUSKY SMR450 http://www.supermotojunkie.com/showt...56#post1283256
Can you get a quote for USPS Parcel Post or USPS Priority Mail to zip 96825?
I'm not seeing the 150 size on these tires. Can anyone confirm that they do come in 150's?
Squid Rydaz Int'l Moto Club - Making Squids around the world, cool again!!
My Support: fastkeys.com; scooterwest.com; sanomx.com; sdbmwmc.com; SisnerosSpeedWorks.com; MRD-Racing.com
Steve G
these are THE supermoto street tyres, there's nothing out there that will top them.
they've been available here in europe for a while now and are selling like hotcakes. they're miles ahead of the old contiforce SM tyres and a way better option than most of the heavier streetbike oriented tyres.
I just ordered some Pilot Powers for mine. Not bad for 220 shipped. These will be my next set for sure!
firstname.lastname@example.com and I will get you a quote on the shipping.
I was wondering how these tires will do if you get caught out in the rain I'm in the Seattle area and I can leave home with blue sky and have rain come in very quickly. When you say they don't last very long what kind of a life span can I expect? I ride windy roads and have not had the chance to get on a track yet but they look like they would be sweet for ripping up the local roads.
If you work hard enough it's only a matter of time until you WIN
2008 Husqvarna SM510R
2001 Suzuki RM250
2000 Honda CR125R
SDG 125 Pro Pit bike
Seems like they cost quite a bit, judging by how long some of you guys say they last? Sounds more like race tires to me = really soft and sticky but low mileage.
2003 KTM 660 SMC - Sold
2007 Suzuki DR-Z400SM - Sold
Not Banned
Challenges Complete: 24
2010 HUSKY SMR450 http://www.supermotojunkie.com/showt...56#post1283256
Compared to the BT003R - how will this perform?
Join the riding game!
Challenges Met - I lost count a long time ago!
How would these perform in the dirt section?
Riding Game: Challenges completed = 6
Instagram: @iwannagofast823
So it sounds like some of you have taken the plunge. Any one have a Review yet?
Got Warp 9's coming with these mounted up. but a review? i wouldnt be able to do a honest review since this is my first ever supermoto tire. The guys that have run other sets of a X brand would give a much better response. However, i could give insight on how long these will last as I commute roughly 4 days a week and rip up on 421 on either sat or sun.
Cant wait! I got the 5in and 160's
06' DRZ400s
Warp 9's
ContiAttacks SM 160
As I mentioned in my previous post, if they're just as soft as the ContiForce sm's, they're not going to last all that long.
The estimated mileage I suggested, I was basing it on the mileage(3.5+k) I got out of the contiforce's. I'm being generous on that mileage, and I'm giving these new tires a benefit of the doubt.
I seem to be pretty light on tires.
Squid Rydaz Int'l Moto Club - Making Squids around the world, cool again!!
My Support: fastkeys.com; scooterwest.com; sanomx.com; sdbmwmc.com; SisnerosSpeedWorks.com; MRD-Racing.com
I just have to post a GREAT BIG THANK YOU to Epic Motorsports for using the most reasonable shipping method at my request. Living in Hawaii sucks when it comes to shipping bulky items from the 48 States, and many companies just say "we only use UPS" or "we don't want to bother with the post office" when I ask if they will ship via US Postal Service to Hawaii. Epic Motorsports quoted me a shipping total before I committed to purchasing the tires, and followed through with everything they said. Not only that, but they actually boxed the tires up instead of just slapping a shipping label on a bare, unpackaged tire like most places do. They definitely went the extra mile for me and I will absolutely be buying from them in the very near future. Thanks guys!!!
i ran the conti attack for the first time this past Sunday at the Gap. I must say I had utmost confidence in the tire. I was able to push hard within just a couple turns. They seem to heat up extremely fast. I had no clue of what tire pressure to run on these, but they felt good at my 28psi setting. I would recommend these to anyone looking for a good sticky street tire. On a negative note, I did feel alot of chatter out of the front end with these. It could be my pressure or suspension causing the chatter. I only noticed the chatter in down hill turns.
I got a set of these from Epic as well. Today was my first ride on them and they felt pretty good. I'm coming from Pilot Powers as I had the rear pop two tubes. What pressures are you all running? I ran them today at 23F/24R...
-2005 Suzuki DRZ400SM
-K5 Suzuki GSXR750
I have two weekends on a set now. Currently at 24 F 25R. These do grip good. No chatter. Really starting to see my limits with the stock suspension. Currently clicked all the way hard on compression and 3 clicks from hard on rebound. Getting some twisting action when hard on the brake time for a fork brace or some from an sm.
06' DRZ400s
Warp 9's
ContiAttacks SM 160
Like those tires, but I'm leaning towards Continental Attack 2's.
A side note, tires are the easiest things to ship. They just ban them together and ship. They can bang, drop and even kick them, there tires. Cut the 4 bands, peel sticker, mount and ride.
2010 Wr250X
FMF FC, FMF Q4, Airbox mod, K&N Filter, Door off, SIM Plug, AIS-EGR removed, ProTaper YZ HI bar, MSR Hand Protectors, Gytr Gold GDO chain, Renthal 13/43, Magnetic Drain Plug, EP Skid plate, R model bottom flaring, Titanium Footpegs, Driven Shifter.
Setting 3-2-1-4-4-4 55+mpg Fun
Bringing this post back from the dead! Having some issues with the Epic Website. Can you guys still confirm this price? and what is the shipping to 83716? Thank you!
Anyone use these for trackdays this last season?
07 DRZ400S "Dualsport"
08 WR250X (Sold)
05 WR450F "Supermoto" (Sold)
01 WR426F "Supermoto" (Sold)
99 WR400F "Supermoto" (Sold)
Conti attack SM's FTW Got them on my husky as well! Great tires!
Current pricing on the 120/70-17 & 150/60-17 Combo is $295.95 plus shipping.
Shipping to 83716 would be around $24.00
epic motorsports, how much for shipping to Sydney Australia? post code 2227
150 and 120 W
The most economical shipping I can source is $180.00 USD.

subset: commoncrawl


text:
Rose Rock Midstream, L.P. Reports Third Quarter 2013 Results
Increases 2013 Adjusted EBITDA Guidance
Announces Intent to Acquire Additional Interest in White Cliffs Pipeline From SemGroup Corporation
TULSA, Okla., Nov. 11, 2013 (GLOBE NEWSWIRE) -- Rose Rock Midstream ® , L.P. (NYSE:RRMS) today announced its financial results for the three months ended September 30, 2013.Rose Rock Midstream reported third quarter 2013 Adjusted EBITDA of $15.7 million, up 2% from the second quarter 2013 of $15.4 million, and up 65% from the third quarter 2012 of $9.5 million. Rose Rock's results improved slightly over the second quarter of 2013 due to an increase in marketing volumes combined with a one month impact of the Barcas Field Services acquisition, partly offset by a decrease in pipeline transportation margins. "Rose Rock Midstream has performed well this year and we are on track to meet and exceed our 2013 goals. Our distribution payable this week represents a 15% increase over our distribution paid in November 2012, which is consistent with our 2013 guidance of 15% year-over-year distribution growth," said Norm Szydlowski, chief executive officer of Rose Rock Midstream's general partner. "We continue to execute on our strategic plans including the completion of our organic growth projects and growth-oriented acquisitions which are reflected in our increased guidance. As the demand for midstream services continues, Rose Rock Midstream is well suited to meet those needs with a strong balance sheet and a highly motivated and experienced workforce." Adjusted gross margin was $23.8 million for the third quarter 2013, up 19% from the second quarter 2013 of $20.1 million and 24% above third quarter 2012 Adjusted gross margin of $19.2 million. Adjusted gross margin and Adjusted EBITDA, which are non-GAAP measures, are reconciled to their most directly comparable GAAP measures below. Third quarter 2013 net income totaled $9.4 million, compared to $9.1 million for the second quarter 2013 and $6.5 million for the third quarter 2012.
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text:
BREAKING: Doctor Who Performed Joan Rivers' Throat Surgery Has Been Fired
Dr. Lawrence Cohen, has been fired.
VIDEO: Melissa Rivers Kisses A Final Goodbye To Joan's Casket
Melissa Rivers bids farewell to her mother Joan.
Video: Joan Rivers Talking About Dying Before Surgery
A friend of mine sent this to me. I literally watched it with my mouth open…as in shock!
'Jurassic Park' Actor Dies At 90
Legendary actor, director, and producer Richard Attenborough has passed away at the age of 90. Attenborough is probably best known for his role as John Hammond in 'Jurassic Park', but Attenborough also one an Oscar for […]
Guy Fakes His Own Death So He Doesn't Have To Get Married
How bad is it that you have to fake your own death to call off your wedding. Things must have been really bad, but even worse is when she finds out you're not dead. It […]
Norm Macdonald's Tribute To Robin Williams Is Beautiful And Will Make You Smile
There is a lot of news about Robin Williams right now. Some is sad, and some are beautiful stories of the man. I came across this story of the first time Norm Macdonald met Robin […]
Leigh Ann: Conan Finds Out About Robin Williams Death While Taping Show
Conan found out about Robin William's death while taping his show. Here is what happened. Grab a tissue before you watch the video.
STEVE KEMBLE: Details on Robin Williams' Death
Find Zazza Mornings on Twitter | Facebook | Instagram with the handle @ZazzaMornings
Most Likely Way To Die By State
Not to be a Debbie Downer, but HERE IS A MAP telling us the most likely way to die based on state. I know, depressing. But at least it's informative!
Leigh Ann: 'Bachelorette' Under Fire For Exploting Death Of Eric Hill
I said this weeks ago. I felt a little uncomfortable watching.


text:
New York, New York
Women Under Fire
"Because they are protected and promoted by military leadership and permitted to continue their heinous behavior unchecked while women who are sexually assaulted by them are ostracized, isolated, shamed, humiliated and often lose their health and military careers," says Sarah L. Blum ARNP and author of the book Women Under Fire: Abuse in the Military. She told me that 95% of the rapes and sexual assaults in the military are perpetrated by repeat offenders and serial rapists.
Blum describes an attitude of entitlement among men in the military who treat women as government property for them to do with as they please, knowing their commanders will cover for their behavior. "Not so different from the young athletes who raped a 16 year old in Steubenville, OH and knew their coach would protect them from having to be accountable," said Blum.
She went on to say there is a new report that shows one in five college women are sexually assaulted and there is an epidemic on college campuses as there is in our military. The report recommended students report their sexual assault to a trained confidential victim advocate rather than to school officials because 95% are not reported at all. Similarly in the military, Blum states that women will not report to the chain of command because they are the ones who either are the rapists or the ones who cover for them.
Decorated nurse Vietnam veteran exposes the failure of military leadership in her book Women under Fire: Abuse in the Military.
Sarah L. Blum is a candid professional with facts, figures and 40 years of hands-on expertise. Her passionate voice is much needed to speak out against the culture of abuse in America's armed forces.
Website: http://womenunderfire.net/
YouTube: http://youtu.be/7vaEL7jN_tI
What do you think of this story?
iReport welcomes a lively discussion, so comments on iReports are not pre-screened before they post. See the iReport community guidelines for details about content that is not welcome on iReport.


text:
A Traditional Life Lived
Michelle Moore
Punching Stupid and Evil in the Face Since 1986!
"We are on strike, we the men of the mind. We are on strike against self-immolation. We are on strike against the creed of unearned rewards and unrewarded duties."-John Galt
Friday, August 1, 2014
Friday, December 20, 2013
Want to Homeschool in Ohio? I hope you've been deemed worthy.
Want to homeschool in Ohio? You'll get to as soon as you are approved as a-ok by government bureaucrats. You thought it was up to you? Oh silly subject, that's a ridiculous thing to think. Only the government is qualified to decide if you are homeschooling material.
Soon you will have to make a choice. Either all children are property of the state, to control and raise as they see fit or children are members of the family unit, where imperfect parents will make mistakes and people who have no business raising kids do. There is no other way for this to go. As parental rights are eroded to make up for the failures of government, soon they will come for your children too.
It is going to be a very sad day when I say to my granddaughter, "I remember when we were free my dear."
It requires all parents who homeschool to undergo a social services investigation which would ultimately determine if homeschooling would be permitted. Social workers would have to interview parents and children separately, conduct background checks and determine whether homeschooling is recommended or not. If it is not recommended, parents would have to submit to an "intervention" before further consideration of their request to homeschoolThe reasoning for attempting to pass this law is super simple. The government failed to do their job and protect a child from abuse. Abuse they were made aware of, did nothing to stop and the child died. So, their answer is to make more miserable failure of laws and take more of your rights away, further subjugating serfs to the masters, which will do nothing to stop abusers from killing children if the government isn't going to do the job they are already tasked with. It would seem there is no end to the things the government fails at, yet thinks that is there are just enough laws, they will some how succeed. This is false and losing our personal and parental rights will not make the children safer.
Soon you will have to make a choice. Either all children are property of the state, to control and raise as they see fit or children are members of the family unit, where imperfect parents will make mistakes and people who have no business raising kids do. There is no other way for this to go. As parental rights are eroded to make up for the failures of government, soon they will come for your children too.
It is going to be a very sad day when I say to my granddaughter, "I remember when we were free my dear."
Posted by Michelle Moore at 11:26 AM 0 comments
Labels: Education, Freedom, Homeschool, Ohio
ObamaCare: So awesome, we keep exempting people from it.
Today the White House announced another, Constitutionally illegal (the fourteenth to be exact), executive policy change to the ObamaCare Law. They will allow folks with cancelled plans to purchase those crappy bare-bones "catastrophic" plans that weren't good enough when the law was first passed, but now that it is a complete disaster, those plans are fine.
Hundreds of thousands of people whose health plans are being canceled because their coverage doesn't meet Obamacare rules will be exempt next year from the U.S. mandate that all Americans carry medical insurance.
So yesterday this type of plan wasn't good enough for any American, any where. Today, they are perfectly acceptable. And, they are only acceptable because your government says they are acceptable.People losing coverage will now be allowed to buy bare-bones "catastrophic" insurance that the law usually limits to those younger than age 30, the Centers for Medicare and Medicaid Services said yesterday. Others can opt out completely without the threat of the fines being imposed next year on the uninsured as part of the Patient Protection and Affordable Care Act.
Posted by Michelle Moore at 10:54 AM 0 comments
Labels: Healthcare, ObamaCare, Special Exemptions
Wednesday, December 18, 2013
Baba Wawa thought Obama would replace Jesus
We in the Tea Party always knew they though Obama was the next great coming of our Lord and Savior. From all the great prose that was written about his election, to his own declaration on election night that the "The seas will recede. The planet will heal." But now after 5 years of disappointment Baba Wawa admits, during the Christmas season no-less, the result is so crushing, because the expectation was so high.
Luckily, I had no expectation other than what has happened. Obama's economic policies are a disaster, his healthcare law is a disaster, his gun confiscation desires are a disaster, and there is no doubt that his unfettered, unchecked, illegal immigration policy will be a disaster. My only hope at this point is that the vast majority of Americans will finally see how disastrous this man and more importantly, these policies, are for our country and in 2016 they will do something about it. I hate to say I told you so.......but I did.PIERS MORGAN, HOST: You have interviewed every president of my lifetime. Why is Obama facing so much opposition now? Why is he struggling so much to really fulfill the great flame of ambition and excitement that he was elected on originally in 2009?BARBARA WALTERS: Well, you've touched on it to a degree. He made so many promises. We thought that he was going to be - I shouldn't say this at Christmastime, but - the next messiah. And the whole ObamaCare, or whatever you want to call it, the Affordable Health Act, it just hasn't worked for him, and he's stumbled around on it, and people feel very disappointed because they expected more.It's very difficult when the expectations for you are very high. You're almost better off when they are low and then they rise and rise. His were very high and they've dropped. But you know, he still has several years to go. What does he have, three years, Piers? And, you know, there will be a lot of changes, one thinks in that time.
Posted by Michelle Moore at 9:51 AM 0 comments
Labels: Barbara Walters, Democrats, Economics and Economy, Obama
Your Politically Correct Idiocy of the Day: 5-year old suspended for finger gun.
Ban pointer-fingers now!
GASTON COUNTY, N.C. (CBS Charlotte) – A 5-year-old boy was reportedly suspended from school after making a gun gesture with his hand on the playground.His father, David Hendrix, was furious when he found out his son was issued a suspension for the gesture."He was playing army on the playground," Hendrix told WBTV. "I just felt like the punishment was way too severe."
Posted by Michelle Moore at 9:27 AM 0 comments
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text:
The Essential Biotech Sector Fall Preview
Biotech is very much driven by stock-specific catalysts like clinical trial results and FDA drug approvals, so a good showing for the last three months of the year will also hinge on the outcome of some key events.
Here is a list of the biotech events with the most potential impact for the remainder of 2010:
- The FDA advisory panel for Arena Pharmaceuticals' (ARNA) obesity drug lorcaserin on Sept. 16.
- Amgen's results from a phase III study of denosumab in the prevention of prostate cancer.
- Genzyme's ongoing M&A dance with Sanofi.
- Presentation of hepatitis C drug data from Vertex Pharmaceuticals and Merck (MRK) at the American Association for the Study of Liver Disease annual meeting in November.
- FDA's approval decision for Human Genome Sciences' (HGSI) lupus drug Benlysta on Dec. 9.
- Likewise, the FDA's expected approval decision on Oct. 22 for the diabetes drug Bydureon from Amylin Pharmaceuticals (AMLN), Eli Lilly (LLY) and Alkermes (ALKS).
- Medicare's national coverage determination meeting for Dendreon's prostate cancer vaccine Provenge on Nov. 17.
Here, too, is a list of important clinical trial results pending in 2010 and a calendar of biotech events for September.
--Written by Adam Feuerstein in Boston.
>To contact the writer of this article, click here: Adam Feuerstein.
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|Hebrew Names Version (HNV)
|New International Version (NIV)
|18 because of the Kasdim; for they were afraid of them, because Yishma'el the son of Netanyah had killed Gedalyahu the son of Achikam, whom the king of Bavel made governor over the land.
|18 to escape the Babylonians. They were afraid of them because Ishmael son of Nethaniah had killed Gedaliah son of Ahikam, whom the king of Babylon had appointed as governor over the land.
|The Hebrew Names Version is in the public domain. (Hebrew Names Version - The Holy Bible Online)
|Scripture quoted by permission. Quotations designated (NIV) are from THE HOLY BIBLE: NEW INTERNATIONAL VERSION®. NIV®. Copyright © 1973, 1978, 1984 by Biblica. All rights reserved worldwide. (New International Version Bible Online)


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- Created 11/21/06 by OhMyGoodies
Posted by OhMyGoodies Don't throw out those cake scraps! These little treats, (sometimes referred to as "cake pops", "cake truffles" or "cake bon-bons" are so easy to make and are absolutely delicious! You can make these delightful cake balls using your leftover cake scraps, or even use an entire cake to make them! Tools Needed: Decorating gloves Mixing Bowl with lid One cooled cake any size and any flavor (or you can use all those left over scraps) One bottle liquid coffee creamer any flavor complimentary to cake or anything to use as a... read more


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"Maybe you are searching among the branches, for what only appears in the roots." ~ Mevlana Rumi
Tuesday, December 13, 2005
Space and Motion
Space and Motion :: A very beautiful site on Metaphysics, Theology, Philosophy and Science. A lot of food for thoughts.
Also read, Theology of Albert Einstein and Metaphysics Ideas
Ref:: http://www.spaceandmotion.com/ Pin It Now!
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TV Review: Vikings (TV Series) Season 1 (2013)
SYNOPSIS: Vikings follows the adventures of Ragnar Lothbrok the greatest hero of his age. The series tells the sagas of Ragnar's band of Viking brothers and his family, as he rises to become King of the Viking tribes. As well as being a fearless warrior, Ragnar embodies the Norse traditions of devotion to the gods, legend has it that he was a direct descendant of Odin, the god of war and warriors REVIEW: Everyone loves … Continue reading


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Did you know that Christmas trees are harvested several months before they even make it to the tree lot around Thanksgiving ti... Read more »
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Whether it's chopping, kindling or splitting firewood for a campfire, there are times when an axe comes in handy. Ask yourself... Read more »
The Fiskars® aluminum shrub rake features a slim head with uniquely tapered tines that are perfect for reaching into tight spac... Read more »
Our Eco Bin Composter features an easy-to-assemble, easy-to-use design that can simplify and speed the composting process. It i... Read more »
Our HardShell® Kangaroo® Gardening Container is perfect for all your outdoor cleanup needs — whether you're gathering yard and... Read more »
Make the holidays merrier with these super fun pop up gift tags! Read more »
Encourage children to help make gifts this holiday season with these kid-friendly projects. Read more »
Teresa Collins is a top craft celebrity who has been featured numerous times on My Craft Channel, HSN, QVC and DIY network, wel... Read more »
Teresa Collins is a top craft celebrity who has been featured numerous times on My Craft Channel, HSN, QVC and DIY network, wel... Read more »
Our unique Tag Maker with Built-in Eyelet Setter features an innovative design that makes it easy to create tags perfect for gi... Read more »
Looking to give a second life to some old clothing. Here are a few ideas to get you started. Read more »
By creating a few simple tags, you won't be caught at the fabric store not knowing what fabrics or yardage you have in your st... Read more »
A brocade drawstring pouch can be a beautiful and luxurious accessory or gift. Read more »
Perfect for a wide range of sewing and quilting tasks, our Amplify® RazorEdge™ Serrated Fabric Shears sense blade separation an... Read more »
Perfect for a wide range of sewing and quilting tasks, our Amplify® RazorEdge™ Fabric Shears sense blade separation and force t... Read more »
Perfect for a wide range of crafting and mixed media tasks, our Amplify® Mixed Media Shears sense blade separation and force th... Read more »
The holidays are a popular time to stop and thank teachers and all of the wonderful staff at school for all they do. Read more »
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Whether it is your go-to bag for shopping or a gift for someone, this simple and chic crossbody purse is a great bag for everyday of the year.
With Earth Day falling in April, I felt it was important to create an Earth-friendly project for my latest New Year's Resolution challenge - to create one item of children's clothing each month during 2013.
I grabbed two of my husband's old t-shirts that were misshapen through regular washing and wearing, my favorite child's tee pattern - I am using the Raglan Tee pattern from the book Sewing for Boys and my favorite Fiskars orange handled scissors.
Re-using old t-shirts is not only Earth-friendly, is also saves you time. You can avoid having to hem the bottom edge as well as the sleeves of your new tee if you line up your pattern correctly.
Start by salvaging the front and back of the first tee you are going to use as the main body of your child's tee. I cut up the side seam and along the underarm sleeve, on both sides. For ease, you can also remove the sleeves.
Next, fold the front piece in half and pin on your front pattern piece. Be sure to reuse the bottom hem that is already finished on the tee as it will save you from having to hem it yourself! Repeat for the back piece and cut them both out.
Take the second tee that you are using for the sleeves and lay flat on your cutting table. Pin on the sleeve pattern piece to the front and again, line up the pattern so that you can reuse the hem that is already sewn. Cut out your sleeves.
You will also be able to salvage enough fabric from either tee to cut a neckband if your pattern requires it. Now, follow your pattern directions and sew up your tee. The pattern I am using is a cute raglan sleeve pattern. It is quick to sew up and the finished garment is adorable! I recommend using a ballpoint needle on your sewing machine which is great for working with jersey knits.
If your sewing machine does not have a 'stretch fabric' setting, you may want to sew your tee up with a loose zig zag stitch instead of a straight stitch. Test your stitches on a piece of scrap fabric beforehand.
Because you are not having to sew hems, you will be able to sew up the tee in record time!
Not only is this project quick and easy, there is a huge sense of satisfaction when you're able to repurpose old garments and make them into something brand new and wonderful! Minimal impact, low cost and big smiles!!
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PSG striker Zlatan Ibrahimovic claims Chelsea are the 'super' hot favourites to win their Champions League quarter-final clash in Paris on Wednesday night.
The Swede, who has scored 10 goals in the competition this season, said: "I think Chelsea are the super favourites. We are beginners in everything we do while Chelsea have had a project for 10 years.
"Experience is an advantage for the one who has it. I think Chelsea has more experience in the Champions League. We're in the position Chelsea were eight or nine years ago.
"The big difference with last year is that it is my second year as well as my team-mates'. We know each other better and I think we are better today than one year ago collectively."
The 32-year-old has played for a host Europe's top clubs, among them Ajax, AC Milan and Barcelona, but has never won a Champions League winners medal.
Ibrahimovic is keen to rectify that with PSG but is not yet ready to consider it may be this season.
"This is my last contract in Europe and to win it I will have to win it with Paris," said Ibrahimovic, who is under contract at the Parc des Princes until 2016.
"The day I leave Paris is the day I will go down a level or quit football. If we will be the kings of Europe, I don't know. I don't want to think so far ahead. Let's think about the two games against Chelsea."
Ibrahimovic, who has scored 41 goals in his last 36 appearances for club and country, has ruled out the possibility of ever joining a Premier League club.
"It's impossible to get me to England," he said. "The day I stop with football it will not be that I look back and I say to myself 'Maybe I should've played in England.'
"I haven't been part of it. I made stories in other countries. It's nothing that I regret."


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Pronunciation: aletargamiento
Added on: 2011-08-01 Listened: 1 timesin: Add categories to aletargamiento
Pronunciation in Spanish [es]
- Pronunciation by lennisrojas (Female from Venezuela)
- Pronunciation by hectorres (Male from Venezuela)
- Pronunciation by grilla (Female from Mexico)
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Uniform Coverage Summaries for Consumers
This brief explains the proposed federal rule that requires private health plans to provide a short, easy-to-read uniform summary of benefits and coverage to all health insurance applicants and enrollees. The rule, which implements a provision in the Affordable Care Act (ACA), is intended to make it simpler for consumers…Issue Brief Read More
Health Insurance Market Reforms: Guaranteed Issue
Guaranteed issue laws require insurance companies to issue a health plan to any applicant – an individual or a group – regardless of the applicant's health status or other factors. Currently, in most states, insurance companies can deny nongroup coverage to people based on their health status or their medical…Fact Sheet Read More
Quantifying the Effects of Health Insurance Rate Review
This report from the Kaiser Family Foundation analyzes the effect of government efforts to ensure that insurance premium increases are justifiable and provide value to consumers and small businesses. Rate review programs require insurers in the small group and individual markets to submit proposed rate increase requests to state or…Report Read More
Health Insurance Market Reforms: Rate Review
Rate review is the process by which insurance regulators review health plans' new or renewed rates for insurance policies in order to ensure that the rates charged are based on accurate, verifiable data and realistic projections of health costs. Historically, state insurance departments have conducted rate review, but under the…Fact Sheet Read More
Online Tools for Consumer-Directed Health Plans
On Jan. 25, 2005, Kaiser Family Foundation hosted a demonstration of the online tools made available to enrollees in consumer-directed health plans. Executives from Humana and Lumenos — two major firms in the consumer-directed care market — conducted real-time demonstrations of their consumer web tools to show how enrollees might…Event Read More
Toplines — Kaiser Health Poll Report Selected Findings on 2006 State of the Union Address and Health Care
Toplines — Kaiser Health Poll Report Selected Findings on 2006 State of the Union Address and Health CareThese toplines provide complete results from the February 2006 poll on what the public took away from President Bush's State of the Union address. Survey Toplines (.pdf)Poll Finding Read More
How Accessible is Individual Health Insurance for Consumers in Less-Than Perfect Health?
This report documents the findings of a study examining access to health insurance coverage in the individual market for people with health problems. Seven hypothetical consumers with varying health conditions were defined and insurers and HMOs in eight different markets around the country were asked to consider them as though…Report Read More
How Private Insurance Works: A Primer
This primer, prepared by Gary Claxton of the Institute for Health Care Research and Policy at Georgetown University, examines the structure and operation of private health insurance including the types of organizations that provide it, how managed care is delivered, and how risk pools work and describes how private health…Report Read More
Protection For Consumers In Managed Care Plans: A Comparison Of Medicare, Medicaid and the Private Insurance Market
This policy paper describes key requirements of consumer protection regulation under Medicare, Medicaid and federal and state laws as they apply to private health insurance. These include choice and availability of plans, disclosure of information, marketing, access, quality, and the grievance and appeals process. The discussion highlights differences and similarities…Report Read More
New Survey on Consumer Experiences with Health Plans
Survey on Consumer Experiences with Health PlansA Kaiser Family Foundation/Harvard School of Public Health survey found that more than six in ten privately insured American adults under age 65 give their health plans a grade of A or B, but nearly half report having some type of problem with their…Report Read More


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Ra - Rectifier Standard Tuning - No capo --------------------------- Very oversimplified, but perfect for beginners like myself. Enjoy --------------------------- Em | G | D x 200 (Repeats through whole song) Em G D i'm still afraid of ghosts that can see me they know my thoughts, they read my mind beside myself i judge my condition i close my eyes but can't go blind i'm feeling all the heat, all the chaos it's gotten underneath my skin so far to go to reach absolution my sanity, my soul runs thin Em G why don't you care? Em G D don't, don't you dare. chorus Em G D rectifier, how's the world supposed to be? Em G D recitifer, take my hand and rescue me/ take my hand and set me free Em G D i fell in love i made that decision on broken hearts i cut myself despite the pain i maintain my position and put good will up on the shelf Em G D but now i'm stuck a chain with no linkage a vagrant lover prisoner suspicious goals distort good intentions agressive action batterer
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text: I love reading Ann Coulter's columns. The woman can go for the throat in the wittiest of manner. As long as it's not your ox getting gored she's terrific, and she generally respects my oxes. Now even you liberals can enjoy her work as she devastates Bush on his immigration policy. Enjoy! http://www.townhall.com/opinion/columns/anncoulter/2006/05/17/197806.html


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From Wikipedia, the free encyclopedia - View original article
|B-Raf proto-oncogene, serine/threonine kinase
PDB rendering based on 1uwh.[1]
|External IDs
|OMIM: 164757 MGI: 88190 HomoloGene: 3197 ChEMBL: 5145 GeneCards: BRAF Gene
|EC number
|RNA expression pattern
|More reference expression data
|RefSeq (mRNA)
|RefSeq (protein)
|Location (UCSC)
|Chr 7:
140.42 – 140.62 Mb
|Chr 6:
39.6 – 39.73 Mb
|PubMed search
|B-Raf proto-oncogene, serine/threonine kinase
PDB rendering based on 1uwh.[1]
|External IDs
|OMIM: 164757 MGI: 88190 HomoloGene: 3197 ChEMBL: 5145 GeneCards: BRAF Gene
|EC number
|RNA expression pattern
|More reference expression data
|RefSeq (mRNA)
|RefSeq (protein)
|Location (UCSC)
|Chr 7:
140.42 – 140.62 Mb
|Chr 6:
39.6 – 39.73 Mb
|PubMed search
BRAF is a human gene that makes a protein called B-Raf. The gene is also referred to as proto-oncogene B-Raf and v-Raf murine sarcoma viral oncogene homolog B, while the protein is more formally known as serine/threonine-protein kinase B-Raf.[2][3]
The B-Raf protein is involved in sending signals inside cells, which are involved in directing cell growth. In 2002, it was shown to be faulty (mutated) in some human cancers.[4]
Certain other inherited BRAF mutations cause birth defects.
Drugs that treat cancers driven by BRAF mutations have been developed. Two of these drugs, vemurafenib[5] and dabrafenib are approved by FDA for treatment of late-stage melanoma. Vemurafenib was the first drug to come out of fragment-based drug discovery.
B-Raf is a member of the Raf kinase family of growth signal transduction protein kinases. This protein plays a role in regulating the MAP kinase/ERKs signaling pathway, which affects cell division, differentiation, and secretion.[6]
B-Raf is a 766-amino acid, regulated signal transduction serine/threonine-specific protein kinase. Broadly speaking, it is composed of three conserved domains characteristic of the Raf kinase family: conserved region 1 (CR1), a Ras-GTP-binding[7] self-regulatory domain, conserved region 2 (CR2), a serine-rich hinge region, and conserved region 3 (CR3), a catalytic protein kinase domain that phosphorylates a consensus sequence on protein substrates.[8] In its active conformation, B-Raf forms dimers via hydrogen-bonding and electrostatic interactions of its kinase domains.[9]
Conserved region 1 autoinhibits B-Raf's kinase domain (CR3) so that B-Raf signaling is regulated rather than constitutive.[8] Residues 155–227[10] make up the Ras-binding domain (RBD), which binds to Ras-GTP's effector domain to release CR1 and halt kinase inhibition. Residues 234–280 comprise a phorbol ester/DAG-binding zinc finger motif that participates in B-Raf membrane docking after Ras-binding.[10][11]
Conserved Region 2 (CR2) provides a flexible linker that connects CR1 and CR3 and acts as a hinge.
Conserved Region 3 (CR3), residues 457–717,[10] makes up B-Raf's enzymatic kinase domain. This largely conserved structure[12] is bi-lobal, connected by a short hinge region.[13] The smaller N-lobe (residues 457–530) is primarily responsible for ATP binding while the larger C-lobe (residues 535–717) binds substrate proteins.[12] The active site is the cleft between the two lobes, and the catalytic Asp576 residue is located on the C-lobe, facing the inside of this cleft.[10][12]
The P-loop of B-Raf (residues 464–471) stabilizes the non-transferable phosphate groups of ATP during enzyme ATP-binding. Specifically, S467, F468, and G469 backbone amides hydrogen-bond to the β-phosphate of ATP to anchor the molecule. B-Raf functional motifs have been determined by analyzing the homology of PKA analyzed by Hanks and Hunter to the B-Raf kinase domain.[12]
Nucleotide-Binding Pocket
V471, C532, W531, T529, L514, and A481 form a hydrophobic pocket within which the adenine of ATP is anchored through Van der Waals attractions upon ATP binding.[12][14]
Catalytic Loop
Residues 574–581 compose a section of the kinase domain responsible for supporting the transfer of the γ-phosphate of ATP to B-Raf's protein substrate. In particular, D576 acts as a proton acceptor to activate the nucleophilic hydroxyl oxygen on substrate serine or threonine residues, allowing the phosphate transfer reaction to occur mediated by base-catalysis.[12]
DFG Motif
D594, F595, and G596 compose a motif central to B-Raf's function in both its inactive and active state. In the inactive state, F595 occupies the nucleotide-binding pocket, prohibiting ATP from entering and decreasing the likelihood of enzyme catalysis.[9][14][15] In the active state, D594 chelates the divalent magnesium cation that stabilizes the β- and γ-phosphate groups of ATP, orienting the γ-phosphate for transfer.[12]
Activation Loop
Residues 596–600 form strong hydrophobic interactions with the P-loop in the inactive conformation of the kinase, locking the kinase in its inactive state until the activation loop is phosphorylated, destabilizing these interactions with the presence of negative charge. This triggers the shift to the active state of the kinase. Specifically, L597 and V600 of the activation loop interact with G466, F468, and V471 of the P-loop to keep the kinase domain inactive until it is phosphorylated.[13]
B-Raf is a serine/threonine-specific protein kinase. As such, it catalyzes the phosphorylation of serine and threonine residues in a consensus sequence on target proteins by ATP, yielding ADP and a phosphorylated protein as products.[12] Since it is a highly regulated signal transduction kinase, B-Raf must first bind Ras-GTP before becoming active as an enzyme.[11] Once B-Raf is activated, a conserved protein kinase catalytic core phosphorylates protein substrates by promoting the nucleophilic attack of the activated substrate serine or threonine hydroxyl oxygen atom on the γ-phosphate group of ATP through bimolecular nucleophilic substitution.[12][16][17][18]
The kinase (CR3) domain of human Raf kinases is inhibited by two mechanisms: autoinhibition by its own regulatory Ras-GTP-binding CR1 domain and a lack of post-translational phosphorylation of key serine and tyrosine residues (S338 and Y341 for c-Raf) in the CR2 hinge region. During B-Raf activation, the protein's autoinhibitory CR1 domain first binds Ras-GTP's effector domain to the CR1 Ras-binding domain (RBD) to release the kinase CR3 domain like other members of the human Raf kinase family. The CR1-Ras interaction is later strengthened through the binding of the cysteine-rich subdomain (CRD) of CR1 to Ras and membrane phospholipids.[8] Unlike A-Raf and C-Raf, which must be phosphorylated on hydroxyl-containing CR2 residues before fully releasing CR1 to become active, B-Raf is constituitively phosphorylated on CR2 S445.[19] This allows the negatively charged phosphoserine to immediately repel CR1 through steric and electrostatic interactions once the regulatory domain is unbound, freeing the CR3 kinase domain to interact with substrate proteins.
After the autoinhibitory CR1 regulatory domain is released, B-Raf's CR3 kinase domain must change to its ATP-binding active conformer before it can catalyze protein phosphorylation. In the inactive conformation, F595 of the DFG motif blocks the hydrophobic adenine binding pocket while activation loop residues form hydrophobic interactions with the P-loop, stopping ATP from accessing its binding site. When the activation loop is phosphorylated, the negative charge of the phosphate is unstable in the hydrophobic environment of the P-loop. As a result, the activation loop changes conformation, stretching out across the C-lobe of the kinase domain. In this process, it forms stabilizing β-sheet interactions with the β6 strand. Meanwhile, the phosphorylated residue approaches K507, forming a stabilizing salt bridge to lock the activation loop into place. The DFG motif changes conformation with the activation loop, causing F595 to move out of the adenine nucleotide binding site and into a hydrophobic pocket bordered by the αC and αE helices. Together, DFG and activation loop movement upon phosphorylation open the ATP binding site. Since all other substrate-binding and catalytic domains are already in place, phosphorylation of the activation loop alone activates B-Raf's kinase domain through a chain reaction that essentially removes a lid from an otherwise-prepared active site.[13]
To effectively catalyze protein phosphorylation via the bimolecular substitution of serine and threonine residues with ADP as a leaving group, B-Raf must first bind ATP and then stabilize the transition state as the γ-phosphate of ATP is transferred.[12]
B-Raf binds ATP by anchoring the adenine nucleotide in a nonpolar pocket (yellow, Figure 1) and orienting the molecule through hydrogen-bonding and electrostatic interactions with phosphate groups. In addition to the P-loop and DFG motif phosphate binding described above, K483 and E501 play key roles in stabilizing non-transferable phosphate groups. The positive charge on the primary amine of K483 allows it to stabilize the negative charge on ATP α- and β-phosphate groups when ATP binds. When ATP is not present, the negative charge of the E501 carboxyl group balances this charge.[12][13]
Once ATP is bound to the B-Raf kinase domain, D576 of the catalytic loop activates a substrate hydroxyl group, increasing its nucleophilicity to kinetically drive the phosphorylation reaction while other catalytic loop residues stabilize the transition state.(Figure 2). N581 chelates the divalent magnesium cation associated with ATP to help orient the molecule for optimal substitution. K578 neutralizes the negative charge on the γ-phosphate group of ATP so that the activated ser/thr substrate residue won't experience as much electron-electron repulsion when attacking the phosphate. After the phosphate group is transferred, ADP and the new phosphoprotein are released.[12]
Since constitutively active B-Raf mutants commonly cause cancer (see Clinical Significance) by excessively signaling cells to grow, inhibitors of B-Raf have been developed for both the inactive and active conformations of the kinase domain as cancer therapeutic candidates.[13][14][15]
BAY43-9006 (Sorafenib, Nexavar)is a V600E mutant B-Raf and C-Raf inhibitor approved by the FDA for the treatment of primary liver and kidney cancer. Bay43-9006 disables the B-Raf kinase domain by locking the enzyme in its inactive form. The inhibitor accomplishes this by blocking the ATP binding pocket through high-affinity for the kinase domain. It then binds key activation loop and DFG motif residues to stop the movement of the activation loop and DFG motif to the active conformation. Finally, a trifluoromethyl phenyl moiety sterically blocks the DFG motif and activation loop active conformation site, making it impossible for the kinase domain to shift conformation to become active.[13]
The distal pyridyl ring of BAY43-9006 anchors in the hydrophobic nucleotide-binding pocket of the kinase N-lobe, interacting with W531, F583, and F595. The hydrophobic interactions with catalytic loop F583 and DFG motif F595 stabilize the inactive conformation of these structures, decreasing the likelihood of enzyme activation. Further hydrophobic interaction of K483, L514, and T529 with the center phenyl ring increase the affinity of the kinase domain for the inhibitor. Hydrophobic interaction of F595 with the center ring as well decreases the energetic favorability of a DFG conformation switch further. Finally, polar interactions of BAY43-9006 with the kinase domain continue this trend of increasing enzyme affinity for the inhibitor and stabilizing DFG residues in the inactive conformation. E501 and C532 hydrogen bond the urea and pyridyl groups of the inhibitor respectively while the urea carbonyl accepts a hydrogen bond from D594's backbone amide nitrogen to lock the DFG motif in place.[13]
The trifluoromethyl phenyl moiety cements the thermodynamic favorability of the inactive conformation when the kinase domain is bound to BAY43-9006 by sterically blocking the hydrophobic pocket between the αC and αE helices that the DFG motif and activation loop would inhabit upon shifting to their locations in the active conformation of the protein.[13]
PLX4032 (Vemurafenib) is a V600 mutant B-Raf inhibitor approved by the FDA for the treatment of late-stage melanoma.[9] Unlike BAY43-9006, which inhibits the inactive form of the kinase domain, Vemurafenib inhibits the active "DFG-in" form of the kinase,[14][15] firmly anchoring itself in the ATP-binding site. By inhibiting only the active form of the kinase, Vemurafenib selectively inhibits the proliferation of cells with unregulated B-Raf, normally those that cause cancer.
Since Vemurafenib only differs from its precursor, PLX4720, in a phenyl ring added for pharmacokinetic reasons,[15] PLX4720's mode of action is equivalent to Vemurafenib's. PLX4720 has good affinity for the ATP binding site partially because its anchor region, a 7-azaindole bicyclic, only differs from the natural adenine that occupies the site in two places where nitrogen atoms have been replaced by carbon. This enables strong intermolecular interactions like N7 hydrogen bonding to C532 and N1 hydrogen bonding to Q530 to be preserved. Excellent fit within the ATP-binding hydrophobic pocket (C532, W531, T529, L514, A481) increases binding affinity as well. Ketone linker hydrogen bonding to water and difluoro-phenyl fit in a second hydrophobic pocket (A481, V482, K483, V471, I527, T529, L514, and F583) contribute to the exceptionally high binding affinity overall. Selective binding to active Raf is accomplished by the terminal propyl group that binds to a Raf-selective pocket created by a shift of the αC helix. Selectivity for the active conformation of the kinase is further increased by a pH-sensitive deprotonated sulfonamide group that is stabilized by hydrogen bonding with the backbone peptide NH of D594 in the active state. In the inactive state, the inhibitor's sulfonamide group interacts with the backbone carbonyl of that residue instead, creating repulsion. Thus, Vemurafenib binds preferentially to the active state of B-Raf's kinase domain.[14][15]
Mutations in the BRAF gene can cause disease in two ways. First, mutations can be inherited and cause birth defects. Second, mutations can appear later in life and cause cancer, as an oncogene.
Inherited mutations in this gene cause cardiofaciocutaneous syndrome, a disease characterized by heart defects, mental retardation and a distinctive facial appearance.[20]
Acquired mutations in this gene have been found in cancers, including non-Hodgkin lymphoma, colorectal cancer, malignant melanoma, papillary thyroid carcinoma, non-small-cell lung carcinoma, and adenocarcinoma of the lung.[6]
The V600E mutation of the BRAF gene has been associated with hairy cell leukemia in numerous studies and has been suggested for use in screening for Lynch syndrome to reduce the number of patients undergoing unnecessary MLH1 sequencing.[21]
More than 30 mutations of the BRAF gene associated with human cancers have been identified. The frequency of BRAF mutations varies widely in human cancers, from more than 80% in melanomas and nevi, to as little as 0–18% in other tumors, such as 1–3% in lung cancers and 5% in colorectal cancer.[22] In 90% of the cases, thymine is substituted with adenine at nucleotide 1799. This leads to valine (V) being substituted for by glutamate (E) at codon 600 (now referred to as V600E) in the activation segment that has been found in human cancers.[23] This mutation has been widely observed in papillary thyroid carcinoma, colorectal cancer, melanoma and non-small-cell lung cancer.[24][25][26][27][28][29][30] BRAF-V600E mutation are present in 57% of Langerhans cell histiocytosis patients.[31] The V600E mutation is a likely driver mutation in 100% of cases of hairy cell leukaemia.[32] High frequency of BRAF V600E mutations have been detected in ameloblastoma, a benign but locally infiltrative odontogenic neoplasm.[33] The V600E mutation may also be linked, as a single-driver mutation (a genetic 'smoking gun') to certain cases of papillary craniopharyngioma development.[34]
Other mutations which have been found are R461I, I462S, G463E, G463V, G465A, G465E, G465V, G468A, G468E, N580S, E585K, D593V, F594L, G595R, L596V, T598I, V599D, V599E, V599K, V599R, V600K, A727V, etc. and most of these mutations are clustered to two regions: the glycine-rich P loop of the N lobe and the activation segment and flanking regions.[1] These mutations change the activation segment from inactive state to active state, for example in the previous cited paper it has been reported that the aliphatic side chain of Val599 interacts with the phenyl ring of Phe467 in the P loop. Replacing the medium sized hydrophobic Val side chain with a larger and charged residue as found in human cancer(Glu, Asp, Lys, or Arg) would be expected to destabilize the interactions that maintain the DFG motif in an inactive conformation, so flipping the activation segment into the active position. Depending on the type of mutation the kinase activity towards MEK may also vary. Most of the mutants stimulate enhanced B-Raf kinase activity toward MEK. However, a few mutants act through a different mechanism because although their activity toward MEK is reduced, they adopt a conformation that activates wild-type C-RAF, which then signals to ERK.
As mentioned above, some pharmaceutical firms are developing specific inhibitors of mutated B-raf protein for anticancer use because BRAF is a well-understood, high yield target.[14][36] Vemurafenib (RG7204 or PLX4032), licensed by the US Food and Drug Administration as Zelboraf for the treatment of metastatic melanoma in August 2011, is the current state-of-the-art example for why active B-Raf inhibitors are being pursued as drug candidates. Vemurafenib is biochemically interesting as a mechanism to target cancer due to its high efficacy and selectivity.[9] In Phase II[37] and Phase III[38] clinical trials, B-Raf not only increased metastatic melanoma patient chance of survival but raised the response rate to treatment from 7-12% to 53% in the same amount of time compared to the former best chemotherapeutic treatment: dacarbazine. In spite of the drug's high efficacy, 20% of tumors still develop resistance to the treatment. In mice, 20% of tumors become resistant after 56 days.[39] While the mechanisms of this resistance are still disputed, some hypotheses include the overexpression of B-Raf to compensate for high concentrations of Vemurafenib[39] and upstream upregulation of growth signaling.[40]
More general B-raf inhibitors include GDC-0879, PLX-4720, Sorafenib Tosylate. dabrafenib, LGX818
BRAF (gene) has been shown to interact with:
|date= (help)
This article incorporates public domain material from the U.S. National Cancer Institute document "Dictionary of Cancer Terms". This article incorporates text from the United States National Library of Medicine, which is in the public domain.


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A masterpiece of versatility.
It's been a while since the folks at Troy Lee Designs designed and built an all-mountain helmet. As is always the case with TLD, they came out with a bang. The A-1 Helmet is a definite departure from the Troy Lee norm, but it's built with TLD's legendary attention to detail and durability.
The first thing you notice about the A-1 is its sculpted, almost artistic shape. More than simple aesthetics, the shape of the A-1 increases air flow through the helmet to keep your head dry and cool. This is especially important when you're grinding out a punishing climb in the heat of the summer. Airflow is directed through 16 cooling vents–6 intake, 4 multi-directional, and 6 output vents. The shape of the visor, which can be adjusted a full inch on the fly, was also dictated by airflow. Moisture management is assisted by a nanowick synthetic liner with CoolMax panels.
The durable polycarbonate shell surrounds single-impact EPS foam for light weight and proven protection. The visor is made with high-impact polypropylene for additional eye protection. Troy Lee used super-durable anodized aluminum hardware throughout the A-1's construction. The A-1's customizable fit is taken care of by triple-position stabilizer baskets and a multi-position cam-lock adjustable stabilizer with +/- 20mm of movement.
The Troy Lee Designs A-1 Helmet comes in three sizes: XS/S, M/L, and XL/XXL. It is available in Gold and Black.
Share your thoughts
What do you think of the
Troy Lee Designs A-1 Helmet
? Share a...
- Familiarity: I've used it several times
Very good quality, very good fit! A litle bit heavier than the usual cross country helmet, but is the price of extra brain protection! Very good price, cheap for the quality that you buy! Very good confort!
Great Helmet
- Familiarity: I've put it through the wringer
I've owned Specialized, Fox and Giro helmets. This is the best fitting most comfortable of them all. Even leave it on to climb.
Bryan Smith
Outstanding piece of equipment
- Familiarity: I've used it several times
I upgraded my lid this year for our vacation to the mountains after taking a few falls recently. This helmet is AWESOME. I felt very secure with it on. I have a slightly odd shape head that usually pushes me to a slightly larger and ultimately less potentially effective size. This locked down onto my noggin no problems and was very cool and comfortable.
Kevin K
Turbo Orange
My head measures just over 23 inches. I'm...
My head measures just over 23 inches. I'm afraid if it runs small it won't fit. So how true is the sizing? Also how loosely should I be holding the tape measure?
Mike Nelson
Hold the tape measure with the same tightness you want out of your helmet. Most people get the best fit from a helmet 1-2 cm bigger than their head size. If your head is 23 inches/58.5 cm, the M/L should be a great fit.
Amazing Helmet
- Familiarity: I've used it several times
This is one amazing helmet. I was originally concerned about how well it vented but the helmet exceeded my expectations. Vents almost as well as my old XC lid and definitely deals with any excess sweat much much better. This is the most comfortable helmet I have ever tried and I would highly recommend it. The fit and finish are top notch and as a bonus, it looks great. Also, the visor actually does a great job of keeping the sun out of your face without getting in the way of your vision. BUENO!!
Zach Petersen
Best Helmet
- Familiarity: I've put it through the wringer
I've owned a few, and tried out countless helmets, but nothing comes close to the comfort and fit of this helmet. On top of that it is very nice looking and protective. The ratchet adjust works really well and the helmet overall has a very sturdy construction.
Excellent fit and finish
- Familiarity: I've used it several times
This helmet fits great. Tried the Super, and POC, and POC MIPs and none of them felt "right" to me. I also like the subtle color of the grey I picked out. Padding is the best I have seen in a while, and the coverage is outstanding. Previous helmet was a series of Fox Flux helmets that I also like, but the padding was always sub-standard on those.
Rich Frogh
This is a helmet...to keep you safe
- Familiarity: I've put it through the wringer
TLD doesn't mess around when making something. This is their latest foray into all mountain/trail helmets and they killed it. Extremely comfortable and also adjustable so it will fit just about anyone's head. Tons of coverage to keep you nice and safe too. Best helmet out in my opinion when it comes to comfort, protection, and style
Lexi Dowdall
Nice Rich!
Most comfortable helmet I have tried on
- Familiarity: I've used it once or twice and have initial impressions
I tried on the POC Trabec Race, Mips Trabec, Bell Super, and A1. Troy Lee wins by far in fit and coverage. The Bell was a close second on head coverage, but the sides and back of the head didn't cradle it as well. The regular POC Trabec was good, but the rear coverage wasn't as low. The Trabec Mips was a fit failure, see my review after buying it first. I have a size 7 head, 21 7/8. The XS/Small is a perfect fit, with just a bit of extra adjustability on the almost too big side.
Is the gold flake available? It says gold...
Is the gold flake available? It says gold but looks yellow in the picture. Thanks
Kevin K
Hi YETIMAN,
Yes, the Gold Flake is available as our option 'Gold.' I apologize that the photo is not showing up correctly on the site. It should look as TLD has it on their website. If you have any other questions feel free to let me know, I have the helmet myself as shown by my review below.
Thanks. Went with the silver flake instead, love it.
Jon Carlson
Best helmet purchased to date.
- Familiarity: I've used it several times
Owned them all. This one just fits and protects! The others sometimes we're close to a good fitting helmet, but this one fits great. Have only owned it for a few months. Can't give it 5 stars till it's logged many more miles.
Andrew Swindle
A1 Helmet Development
Andrew Swindle
A1=Pure Comfort
- Familiarity: I've used it once or twice and have initial impressions
The A1 delivers the most comfortable fit of any helmet I've ever put on my head. The weight is spot on for the fit and one can instantly tell that TLD put some time into the creation and design of this helmet. The padding and closure are pretty much leaps and bounds better than any other helmet I've ever worn.
I would give this helmet 5 stars, but due tot he dip in the helmet's shape at the temples, I have a hard time wearing any sunglasses comfortably. This is most likely due to the shape of my head in combination with the shape of the shell around the temple area. It pushed down on the frame of my specs, thus putting quite a bit of uncomfortable pressure on the bridge of my nose. Without sunglasses(ie. goggles or no eye protections) this is bar far my favorite helmet to wear.
I encourage an AM.Trail rider to try this helmet. It will not disappoint.
Amanda Cordell
Well, duh.
- Familiarity: I've used it several times
I mean, It's TLD. They don't really make anything less than stellar. This helmet is right up there with a large range of adjust-ability (in the form of a fancy, high-tech, spinny dial thing.), maximum protection, and a sleek and stylish design.
Kevin K
Most Comfortable Helmet I've Worn
You know all those videos you watch in the corner of your screen all week at work so your boss doesn't see. Yep, those ones that make you envious and wish you could be as daring.
Guess what helmet most of those guys are depending on to keep them literate? Yep, this one. Troy Lee Designs has been around safety and protection for the most bad ass dare devils in the world, as well as helping them look as stylish as their moves for years now. The A1 helmet from TLD combines both of these strengths making a helmet that offers exceptional protection from any and all impacts, as well as substantial back of the noggin defense. Color schemes are loud, and get tons of compliments on the trail. My absolute favorite part of this helmet is the fit/pads, which are the best I've had of ANY other helmet. The shape sits uniformly on my head to feel like it's hardly there and the pads used are far superior than anything you've used before. I think they should last much, much longer as well.
Adjustability is well thought out and can accommodate a large variety of head sizes. I typically wear 7 3/8" hats and the M/L fits great. Even though the sizing chart says M/L stops at 7 3/8 I think you shouldn't have any trouble with a slightly larger hear if you don't want to bump up to the XL/XXL.
My only gripe with the helmet is that there isn't much room for fitting sunglasses with the helmet, but realized if I put the sunglasses on first before the helmet, or just rock it back slightly, they fit well and don't cause any issues.
Aaron Martin
Love this lid!
- Familiarity: I've used it several times
Pinning it on the blue and single black diamond trails and don't want to unnecessary freak people out with a full-face? When not using the lift but demanding more protection and confidence than an XC lid, Troy Lee got this one perfect.
Amazing fit and finish!
- Gender: Male
- Familiarity: I've used it once or twice and have initial impressions
As soon as I put the helmet on I knew I was going to love it. It's the first bike helmet I've ever worn that actually fits and conforms to your head rather than just sort of sitting on your head...it's definitely a unique and great feel. What this does is it fits very firmly and secure on your head and there is absolutely zero movement even on the roughest trails.
The padding used is a notch above what I'm use to in Fox and Giro helmets, very comfortable. Since it's fall now and cooler I haven't had a chance to wear it on a hot day with lots of sweating.
The only drawback I've found so far is my Smith Pivlock glasses which have a rather large (tall) lense touch the brim of the helmet putting pressure on my nose and I have to adjust the helmet slightly backwards to compensate. Wish there was a tiny bit more clearance for the larger glasses many of us use while biking.
The primary reason I bought it is for more protection. I'm use to wearing full face MX helmets on the motobike and the speeds I sometimes ride on the MTB a flimsy XC helmet just isn't enough, and a full face is too constrictive for climbing. So, I'm hoping this is the best compromise of the two.
I love the loud metal gold flake too...I'm an X motocross racer so I'm a sucker for a fancy paint job which is what Troy Lee is known for.
Very good
- Familiarity: I've used it several times
For my head, the best half cut fit ever! Better than any XC or Road helmet I?ve used. Of course a bit heavier than the lightest XC and Road helmets I?ve used but way better fit. I like the full face from TLD a lot as well, so it might just be my skull-shape. Very balanced, do not move at all (even on shaky paths), very good cover of back head (upper neck) and surprisingly airy. Do not feel to warm. Cool design ? I guess TLD half cut is beck, just better? Just love it. My reference brands used the last 10 years: Half cut: Bell, Giro, Met, Catlike and Sweet. Full face: Bell, Giro, Troy Lee d. All of them ?top of the line? models.
Laura K Stewart
A-1 Amazing!
Can't wait for the new colors!


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Zapp (also known as the Zapp Band or Zapp and Roger) is a soul and funk band formed in 1978 by brothers Roger Troutman, Larry Troutman, Lester Troutman, Tony Troutman and Terry "Zapp" Troutman. Known for hits such as "More Bounce to the Ounce", "Dance Floor" and "Computer Love", the group was a partial source of inspiration to West Coast hip-hop and G-funk, which came out of the hand clapped-drum beat styled funk of Zapp's records, with Roger's use of the talk box becoming another reason for the group's impact and its success.
Gila River Casinos
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FITL would like to invite you to join us Tuesday, September 30th - Thursday, October 2nd for the EDUCAUSE Virtual Conference.
We will set up in LC 433 and LC 444 for the three days of the conference and provide faculty and staff with free access to all webcasts or interactive online sessions. Come and attend as many sessions as you like.
Here are some of the session topics listed on the agenda:
- Disruptive Innovation and the Future of Higher Education
- Behind the Curtain: Technologies Supporting Student Success
- Designing an Adaptable Evaluative Tool for Educational Technologies
- Student Success Is Everybody's Business
- MOOCs Beyond the Hype: The Open Learning Journey at the University of Pennsylvania
- Driving Innovation in the Learning Environment: The Flipped Classroom
- New Responsibilities for Postsecondary Education in the 21st Century
You can also browse through the entire Virtual Conference Agenda here.
Please share with your colleagues and email firstname.lastname@example.com to RSVP.


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Seattle Genetics Announces Data From Investigator-Sponsored Trials Of ADCETRIS® (Brentuximab Vedotin) In Cutaneous T-Cell Lymphoma At ASH Annual Meeting
Seattle Genetics, Inc. (Nasdaq: SGEN) today announced that results from two ongoing investigator-sponsored phase II clinical trials of ADCETRIS (brentuximab vedotin) in patients with relapsed cutaneous T-cell lymphoma (CTCL) were presented at the 54 th American Society of Hematology (ASH) Annual Meeting and Exposition being held December 8-11, 2012 in Atlanta, GA. ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30. ADCETRIS has not been approved for use in the treatment of CTCL.
Brentuximab Vedotin Demonstrates Significant Clinical Activity in Relapsed or Refractory Mycosis Fungoides with Variable CD30 Expression (Abstract #797)
The ongoing phase II clinical trial is enrolling CTCL patients with mycosis fungoides (MF) or Sezary syndrome. Twenty patients have been enrolled to date with a median of six prior systemic therapies. The primary endpoint of the trial is clinical response rate. Secondary endpoints include correlation of clinical response with CD30 expression levels, duration of response and safety. The study was led by principle investigator Dr. Youn H. Kim from Stanford University School of Medicine in Stanford, CA, and was presented in an oral session. Key findings include:
- Fourteen of 20 patients (70 percent) achieved an objective response across all stages of disease, including Stage IB, Stage IIB and Stage IVA/B. At the time of analysis, 14 patients had a partial response, one patient had stable disease and four patients had progressive disease. One patient was not evaluable for response.
- CD30 expression on lymphoid cells in biopsies of skin lesions was measured by immunohistochemistry (IHC) and patients were divided into three groups: those with less than 10 percent expression (seven patients), 10 percent to 50 percent expression (10 patients) and greater than 50 percent expression (three patients). Clinical activity was observed in all three groups.
- The most common related adverse events of any grade were peripheral neuropathy (70 percent), fatigue (60 percent), decreased appetite (30 percent) and nausea (25 percent).
- The most common Grade 3 or 4 related adverse events were rash (three patients) and neutropenia (two patients).
Results of a Phase II Trial of Brentuximab Vedotin (SGN-35) for CD30+ Cutaneous T-Cell Lymphomas and Lymphoproliferative Disorders (Abstract #3688)Data were presented from a phase II investigator-sponsored trial evaluating the use of ADCETRIS in CD30-positive CTCL patients, including lymphomatoid papulosis (LyP), primary cutaneous anaplastic large cell lymphoma (pcALCL) or MF. The ongoing study is being conducted by Dr. Madeleine Duvic from The University of Texas MD Anderson Cancer Center in Houston, TX. Among 54 patients enrolled to date, 46 patients were evaluable at the time of analysis. The primary endpoint of the trial is to evaluate the safety and efficacy of ADCETRIS in CD30-positive CTCL. The key findings include:
- Thirty-one of 46 patients (67 percent) achieved an objective response, including 19 of 19 (100 percent) with LyP and/or pcALCL and 12 of 27 (44 percent) with MF.
- The most common adverse events were peripheral neuropathy (44 percent), fatigue (30 percent), skin rash (26 percent), diarrhea (22 percent), nausea (18 percent) and myalgia (18 percent).
- The most common Grade 3 adverse events were neutropenia (three patients), elevated liver function tests (two patients), nausea (two patients) and deep vein thrombosis (two patients).
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|31 May 2013
convert files to play on external dvd player
Hi, I need some help if possible.
I'have down loaded some films from the net which I want to burn to disc and play on a dvd player away from the pc.
Most of them will unpack and allow me to burn successfully. However I have some which will only play on a pc dvd. These are showing as mkv files. I s it possible to convert them and burn them in Windows DVD Maker. I have tried but can't get the files into dvd maker. I'm not sure what the difference is but when I burn to disc the only option is a very quick process but others seem to go into ' make a dvd ' and takes quite a long time but gives perferct results.Thanks for you time,Mike
|My System Specs
|31 May 2013
Windows 7 pro x64 SP1
Freemake can convert and burn mkv to DVD
Freemake | Best Freeware Alternatives To Paid Video Software
watch out for unwanted 'extras' when installing
|My System Specs
|31 May 2013
Hi, Thanks for your reply and tip. It downloaded like a dream and so far has worked perfectly with everything I've put through it. Problem solved.
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The Napoleon Slide-In Side Burner is the perfect match for your outdoor kitchen area or built-in grill island. This stainless steel burner is a tough match against any outdoor weather conditions being completely waterproof and extremely durable. The grill accessory contains two ceramic burners that work together to provide the user with up to 30,000 BTU's to cook with. Providing an area to cook side dishes with, this 245 square inches cooking surface is beneficial to anyone interested in outdoor entertainment.
- Stainless steel construction
- Provides 30,000 BTU's
- 245 sq. in. of cooking surface
- Electronic ignition
- Perfect for most built-in grills
This side burner for your grill is designed with a flat top, making it easy to blend in with your countertop or island surface. Underneath the smooth surface are heavy duty rod grids that are made with solid black porcelain for a reassuring durability feature. The burner's electronic ignition makes it quick to use and easy to avoid unnecessary trips in and out of the house. For the first time you can now grill hot dogs and cook macaroni and cheese while you watch your children swimming in the pool.