Source: http://news.feedzilla.com/en_us/stories/politics/top-stories/258419604?client_source=feed&format=rss
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Friday, October 26, 2012
GAMBLING: Lack of law spells end to California Online Poker Assoc ...
Posted on | October 25, 2012 |
(Bloomberg News)
After spending two years trying unsuccessfully to legalize online poker, a group that included an Inland casino-owning tribe, has dissolved.
Tribes, including Inland tribes, were not united behind the effort to legalize online poker ? a factor that certainly didn?t make the failed attempt any easier.
From the San Manuel Band of Mission Indians: Effective October 12, 2012, the San Manuel Band of Mission Indians has withdrawn from the 29 tribe California Tribal Intrastate Poker Consortium, LLC, which was formed in 2009 to further the interests of California tribes in intrastate Internet poker. The consortium is one of two members of the California Online Poker Association (COPA). The other member is a consortium of major
California card rooms. San Manuel?s withdrawal from the tribal consortium automatically removes it as one of that organization?s delegates on the COPA board.
?Our tribe?s withdrawal was made after careful deliberation and with the greatest of respect for, and gratitude to, our tribal co-members in the consortium,? said San Manuel Band of Mission Indians
Chairperson Carla Rodriguez. ?Our collective effort was a meaningful step toward bringing the benefits of intrastate Internet poker that is safe and well-regulated to the public, the state government, and the
gaming industry in California. We look forward to continuing the cooperative efforts in the future.?
San Manuel?s decision to withdraw was based, she said, on the realization that, ?The politics over Internet poker over the last two years simply has not caught up with modern technology?s inroads into California gaming economics, and it was unclear how soon in the future that would change. We decided it was time to step back for awhile and assess the situation.?
From Ryan Hightower, the association?s spokesperson: ?The California Online Poker Association?s Board of Managers has announced it is dissolving the association. The decision was based upon insufficient progress within the legislature toward the passage of an online poker [sic] bill.
When the California Online Poker Association (COPA) was formed two years ago, the COPA operating agreement contemplated that the organization might be dissolved if state online poker legislation had not passed by January 2, 2013.
COPA?s members continue to believe that the authorization of intrastate Internet poker would provide California with hundreds of millions in new state revenue, thousands of new jobs and vital protections for players.?
Check back for more information as this story develops.
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China calls on all sides to abide by Syria ceasefire
BEIJING (Reuters) - China called on Thursday for all sides in the Syrian conflict to observe U.N.-Arab League peace envoy Lakhdar Brahimi's proposal for a Muslim holiday ceasefire.
The ceasefire for the Muslim 'Eid' holiday is due to start on Friday and Chinese Foreign Ministry spokesman Hong Lei said he welcomed the move.
"We are happy with the positive reaction to the proposal from relevant sides in Syria," he told a daily news briefing.
"We hope that all the relevant parties in Syria can take a sincere attitude and concrete action to support and cooperate with U.N. envoy Brahimi's proposal and his mediation efforts and seize the opportunity to earnestly implement promises to cease fire and stop the violence."
China also hoped this would be a chance "to put in place a long-term and effective ceasefire to create conditions to relieve the Syrian people's hardship and start political dialogue and the political transition process as soon as possible", he said.
China and Russia have vetoed three U.N. resolutions condemning Syrian President Bashar al-Assad's government for the violence.
But China has been keen to show it does not take sides in Syria and has urged the government there to talk to the opposition and take steps to meet demands for political change. It has also said a transitional government should be formed.
(Reporting by Reuters Television; Writing by Ben Blanchard; Editing by Nick Macfie)
Source: http://news.yahoo.com/china-calls-sides-abide-syria-ceasefire-094057271.html
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Thursday, October 25, 2012
7 Truths About Social Media and Online Relationships
We are both active on a ton of social media networks including Facebook, Twitter, Instagram and LinkedIn to name a few. You name it, we've tried them. In fact, we actually first met and grew our relationship on Twitter and Facebook. We are grateful for social media because if it was not for Twitter, we never would have met. Imagine one of us living in the Philippines and the other living thousands of miles away in Connecticut. It all started for us as a simple tweet that grew into phone calls and video chats and on to meeting in person and being together. It all culminated in us getting married this past summer.
While our story had a happy outcome, not everyone is so lucky. We have heard many personal horror stories of built-up expectations that were never realized. Love is something all people crave. Why do you think a lot of hit songs, books and movies are about love? People long to be loved and long for the day of finding that one special person they can't live without.
Here are seven truths we've learned about social media and relationships as well as from people who have found themselves in bad situations. We hope these "truths" will help you avoid heartaches and create meaningful and positive relationships:
Truth 1: Social media sites are not dating sites.
We are elated when we see people find love on social media but if that is the only purpose of joining a social network, you may be disappointed. If you are looking for love online, it may be a better idea to consider using a dating website designed specifically to help people meet compatible partners and hopefully form meaningful and lasting relationships. We were both active on Facebook and Twitter long before we first met so it was never our initial intention to find love through social media.
Truth 2: Not everyone is truthful about who they say they are on social media.
Don't fall into the trap of believing everything you see on social media. Don't fall in love with people's avatars and bios. People will often stretch the truth to hide their perceived flaws and build up their positives to get people to follow or friend them. The biggest letdown is if you get into an intimate relationship right away based only on what the other person says in their profile or an attractive profile photo. Before falling head over heels for someone, make sure you get to know the real person first. There is nothing wrong with asking questions and really getting to know who the person is in real life before committing to a more serious relationship.
Truth 3: People will and can hurt you.
Relationships on social media may be great in the beginning, but once you take the next step and meet in person you may be in for a surprise. People may take more liberties engaging on social media than in real life. The fact is some think they can stretch the truth online and hide behind the shield of anonymity. Be careful!
Truth 4: The same process must be followed for both online and offline relationships.
Social media is a great tool to meet interesting people and create relationships, but you must be smart about it. Spend plenty of quality time with each other offline to find out if you really click. No matter how you met, your soul mate is someone who should bring out the best in you. It is through experiencing the ups and downs of a relationship beyond the world of social media that you will find out if you're meant to be together.
Truth 5: Follow your heart but take your brain with you too.
There will be people who will question your choices especially for those who meet online. No matter what people say, it is still your choice. Just make sure you use common sense and always be on the lookout for your safety. Sometimes we don't see everything objectively when we are in love. Be on the lookout for red flags when you are beginning your online relationship:
- They should be willing to talk with you on the phone and meet with you in person and in public.
- They should be willing to talk with you on stream, not just through private messages (PMs) or direct messages (DMs.)
- They should not ask you for money as a perquisite to meeting you. This is a big red flag!
- They should be willing to back-up claims and statements they make publicly online and to you privately. Remember, anyone can say anything online. It doesn't make it true!
Truth 6: Following your instincts is a must.
There are many awesome people in social media but there are still those who may take advantage of you and your vulnerability. Just because they are active and share a lot doesn't mean they are particularly trustworthy. If your instincts tell you to stop, investigate further before continuing to interact. Matters of the heart are emotional experiences that should not be taken lightly especially if it turns ugly. Break-ups can take a nasty turn and become amplified on social media.
Truth 7: Honesty is the best policy.
Be yourself! Whatever your reason for joining any social media network, it is always a good practice to be honest. It's never been an issue for us meeting our online friends in person because we are no different offline than how we represent ourselves online. Some people find it hard to connect offline because they're afraid of being exposed as not who they say they are.
Being honest is important if you want to build trust and authentic relationships with people beyond social media. If you see someone is falling in love with you and you do not feel the same way, be honest and firm. Tell them exactly how you feel. Never play with anyone's feelings and never pretend to like someone. Remember those avatars represent real human beings who can get hurt.
Bonus Truth: Safety first!
When it comes to the matters of the heart, there is certainly nothing wrong with meeting and falling in love with someone you meet through social media. We have met many people like us who have been successful in finding their partners online. When we see people find true happiness it really put a smile in our hearts although not everyone is so lucky. Just make sure you use common sense and take extra measures to keep yourself safe when engaging with people online:
- Go ahead and meet up in person but do it in a public place. If you're still unsure, bring a friend along or go on a double date.
- Take it slow and easy. Be friends first and get to know the person before getting really serious.
- Don't feel bad about asking questions and seeking answers. If the person your building a relationship with is reluctant or not forth coming, have the courage to move on. Putting your safety and reputation at risk is not worth the short term pain and sadness of ending the relationship.
Did you meet your partner through social media? Tell us your story.
Check out our blog here: http://PodJam.tv
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Follow Marty McPadden on Twitter: www.twitter.com/MartyMcPadden
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Source: http://www.huffingtonpost.com/marty-mcpadden/7-truths-about-social-media_b_2009105.html
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Judge to decide fate of West Penn investor talks
NEW YORK (Reuters) - The outcome of a court hearing set to begin on Thursday will determine whether a major regional healthcare system in Pennsylvania is driven into bankruptcy or will be allowed to seek other suitors after a $475 million merger deal with insurer Highmark Inc crumbled.
At stake is the fate of the nonprofit West Penn Allegheny Health System and nearly $740 million of municipal debt it issued in 2007. In an era of growing hospital consolidation across the country, West Penn's case is also an unusual one - a merger suddenly gone wrong.
The two initially announced their agreement in June, saying Highmark would take control of West Penn in exchange for a cash infusion that would allow West Penn, which had already shuttered some facilities, to avoid more layoffs and closures.
But the partnership imploded amid demands by Highmark that before it would consummate the transaction, West Penn must declare bankruptcy in order to reduce its burdensome debt load, according to court documents.
Allegheny County Judge Christine Ward will hear arguments on Thursday and Friday about whether she ought to grant a request from Highmark, filed October 1, to block West Penn from talking to other potential buyers and investors.
"If they're not allowed to potentially align themselves with someone else, they're out on an island by themselves," said Tom Metzold, co-director of municipal investments at Eaton Vance Management. "I don't see how they can survive otherwise."
Some attribute the change of tenor to the April departure of former Highmark CEO Kenneth Melani, who had resisted ideas that West Penn file for bankruptcy. He was fired after a fight with his girlfriend's husband led to an assault charge.
New CEO William Winkenwerder appeared at a West Penn board meeting on August 30 for the first time and said he wanted to renegotiate the terms of the agreement to include debt reduction, even bankruptcy, West Penn said in its countersuit.
POTENTIAL DOWNGRADES ON HORIZON
The heated dispute and the abrupt end to the planned alliance caused concern among all three major credit rating agencies. On September 28, the same day the public learned of the collapsed deal, the agencies warned that they might downgrade West Penn.
"We view this agreement as providing a strong path forward for them," Martin Arrick, senior nonprofit healthcare analyst for Standard & Poor's Ratings Services, told Reuters. "Without a Highmark merger, it's a much more difficult situation."
S&P rates West Penn at Caa1, already a speculative grade. West Penn has about $1.2 billion in assets but $1.4 billion in liabilities.
The first nine months of West Penn's fiscal year were strained, with the system's expenses exceeding revenues by nearly $76 million, according to the most recent data.
Net patient revenue was down 2.2 percent, or $25 million, from the same period in 2011. The system is now run by interim CEO Keith Ghezzi of the turnaround firm Alvarez & Marsal.
Pittsburgh-based Highmark, one of the 10 largest health insurers in the United States, has already provided $225 million to West Penn under the terms of their agreement. How much of that money constitutes a loan, which must be repaid, rather than a grant is also likely to be a contentious issue as the court case unfolds.
SOME DEBT REDUCTION STILL LIKELY
West Penn has also lost some business to its main regional rival, University of Pittsburgh Medical Center, rated A-plus by S&P. In a continuing lawsuit, West Penn accuses UPMC of stifling competition.
West Penn has also suffered financially from regional demographic changes, including an aging population and increasing Medicare patients, Arrick said.
West Penn, which is highly leveraged, has been trying to find a way out of its difficult financial bind for several years. It has lost patients and has significant pension expenses, he said.
West Penn could still find other potential investors if the judge allows it, according to Alan Schankel, head of fixed income research at Janney Montgomery Scott LLC.
"There's always suitors," he said. "There's always a chance that even somebody not from that area, looking to expand or grow, would come into the market."
But the terms offered by another partner would likely still require some debt reduction, or bankruptcy. That could even push West Penn back into discussions with Highmark if West Penn sees that "just about every road they could possibly go down leads to the same thing," Schankel said.
"I think West Penn's future is pretty dim," he said. "I'm not sure how they can avoid some kind of bankruptcy."
Some of West Penn's doctors on Wednesday wrote an open letter to Governor Tom Corbett, asking him to intervene and seeking to get negotiations with Highmark reopened.
The system's municipal bonds, which mature in November 2040, sold at about 70 cents on the dollar as of October 19, according to Municipal Market Data, a unit of Thomson Reuters. On the day West Penn announced that the merger was off, they had been selling for as much as 86 cents on the dollar.
(Reporting by Hilary Russ; Edited by Tiziana Barghini and Lisa Shumaker)
Source: http://news.yahoo.com/judge-decide-fate-west-penn-investor-talks-110716519--finance.html
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93% Looper
All Critics (228) | Top Critics (41) | Fresh (213) | Rotten (15)
The reasoning behind all this may not reward prolonged inspection, but Johnson is smart enough to press onward with his plot, leaving us with neither the time nor the desire to linger over the logic ...
Writer-director Rian Johnson establishes himself as an original talent who clearly believes storytelling must prevail.
A mind-bending ride that is not afraid to slow down now and again, to explore themes of regret and redemption, solitude and sacrifice, love and loss. It's a movie worth seeing and, perhaps, going back to see again.
Looper has more heart than Brick and the 2008 con-man flick The Brothers Bloom. Both fine achievements, they could also be described as viscerally cerebral.
I'm a sucker for time-travel movies.
Looper felt to me like a maddening near-miss ...
While it sometimes feels like it's trying to do much, Looper manages to be a creditable and exciting sci-fi flick that homages the past while carving out a unique identity.
Much as he did in Brick, Johnson creates a carefully drawn world in Looper that exists by its own particular set of rules.
... has an irresistible energy and a don't-give-a-damn unpredictability ...
Beautifully crafted, acted and written.
Anchors high-concept thrills and captivating ideas in a world of challenging morality and intricate personal consequences.
Truly imaginative but all the twists and turns make the overall film difficult to follow. Plus Gordon-Levitt has not reached leading man status yet.
Kind of a reverse-"Terminator" without any of James Cameron's wit (or wisdom),
An endlessly creative mind-blowing film that captures everything right about the movie going experience. Johnson conjures up the most imaginative action/science fiction film since 'Inception.'
Part science fiction, part mob movie, and with a nice infusion of dark comedy at just the right moments, Looper is Johnson's best movie yet, and manages to be hugely entertaining, affecting, and thought-provoking.
takes us far beyond the film's high-concept premise into the kind of emotional terrain that too often escapes even the best genre filmmakers
Doesn't quite reach the heights of the lofty ideals that it so ardently seeks to expound, but makes up for this with the sheer thrill of the journey Rian Johnson takes us on.
Ingenious with a fine performance by Emily Blunt, but far too much cold-blooded violence.
Engaging, exciting, and successfully cross-breeding elements of Terminator and even Pet Sematary, Looper is a solid work of palatable science-fiction.
Looper's super. An action-thriller that bothers to have a brain.
Looper may not take us back to the future as satisfyingly as Robert Zemeckis' Marty McFly trilogy or James Cameron's Terminator franchise, but writer-director Rian Johnson does enough right to all but guarantee that he has a future cult film on the books.
The best time travel films play on emotion rather than logic, and once Looper realises this and drops all the tail-chasing about how time travel works it settles into the engrossing action/drama about destiny it should have been from the get go.
Has more depth, smarts, and heart than the usual sci-fi bluster.
A just about brilliant sci-fi crime-drama-thriller mostly set in the years 2044 and 2074. Rian Johnson is a rare director who creates entertainment with depth.
The key to enjoying the gruesome violence mixed with a healthy potion of emotional depth rarely found in this genre is to not dwell on the fiction in the science.
Sometimes time travel is just used a cheap device in movies to make them seem different; this is not one of those films. It's genuinely unique and fresh.
More Critic ReviewsSource: http://www.rottentomatoes.com/m/looper/
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Wednesday, October 24, 2012
Baseball: Giants oust reigning champs to reach World Series
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SAN FRANCISCO, USA - Rising from the brink of elimination, the San Francisco Giants reached the World Series by beating St. Louis 9-0 on Monday, October 22, ousting the reigning champions from the Major League Baseball playoffs.
The Giants captured the best-of-seven National League Championship Series 4-3 after having trailed the Cardinals 3-1. For the second playoff series in a row, San Francisco advanced by winning the last three games.
San Francisco will face the Detroit Tigers, who swept the New York Yankees in the American League final, when the best-of-seven World Series championship series starts Wednesday, October 24 in the Giants' ballpark.
The Giants seek their second World Series crown in three seasons while the Tigers, who lost to St. Louis in 2006 in their most recent World Series, have not won the championship since 1984.
Giants dominate
Winning pitcher Matt Cain pitched 5 2/3 scoreless innings for the Giants, striking out four Cardinals while surrendering five hits and a walk, and aided his own cause by knocking in a run in the second inning.
San Francisco opened the scoring in the first when Angel Pagan singled, took third base on a Marco Scutaro single and crossed home plate on Pablo Sandoval's ground out to the pitcher.
The Giants took a 2-0 lead when Gregor Blanco singled, advanced on Brandon Crawford's ground out to first base and scored on a Cain single up the middle.
San Francisco pounded in five runs in the third inning to seize command.
Hunter Pence blasted a bases-loaded double to centerfield to drive in two runs and a fielding error on the play by Jon Jay allowed a third run to score.
Pence advanced to third on Brandon Belt's single and scored when Crawford hit into a bases-loaded fielder's choice. Belt scored from third when Pagan hit into a fielder's choice and the Giants took a 7-0 edge.
Blanco scored from third base in the seventh inning when Aubrey Huff grounded into a double play and Belt blasted a solo home run in the eighth for the Giants' final runs.
St. Louis threatened in the eighth with runners at second and third and one out, but David Freese grounded out to the pitcher and Giants relief pitcher Javier Lopez struck out pinch-hitter Tony Cruz to end the inning.
The Cardinals put runners on second and third again in the ninth inning with two outs but Matt Holliday flew out to second baseman Scutaro to end the game in heavy rain. - Agence France-Presse
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Central Dauphin's Allison Cooper, Carlisle's J.D. Hughes earn top-7 finishes in PIAA golf championships
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Central Dauphin sophomore Allison Cooper finished sixth in the state in the PIAA AAA girls' tournament. - (JOHN C. WHITEHEAD, The Patriot-News)
YORK - After a rough first day in the PIAA boys? and girls? state golf championships at Heritage Hills Golf Resort, the Mid-Penn Conference contingent put on their rally caps and produced a pair of top-10 finishers on Tuesday. Central Dauphin sophomore Allison Cooper, the two-time conference champ and reigning District 3 runner-up, shot a 75 and earned a sixth-place finish in the girls? AAA field. And Carlisle junior J.D. Hughes, who survived a playoff in the Eastern Regionals just to make States, shot a 72 and finished alone in seventh place in the boys? AAA division.
HOT HORNBERGER
Manheim Twp. senior Craig Hornberger shot a 1-under 70 on Tuesday and had a 1-over 143 total and won the AAA boys? crown by a shot over Peters Twp.?s Tommy Nettles and Slippery Rock?s Brian Rinker. That?s three wins in the last three postseason events for Hornberger, who won his third District 3 championship in a row, followed that up with a win in the Eastern Regionals last week and pocketed an individual state title on Tuesday. On Wednesday he?ll try and help the Blue Streaks defend their PIAA team title back at Heritage Hills. Hornberger became the first Manheim Twp. boys? player to win an individual state title since PGA Tour vet and U.S. Open winner Jim Furyk won in 1987. Furyk sent Hornberger an email Tuesday morning wishing him luck in the state finals.
MID-PENN CREW
Hughes, who had a double-bogey on his very first hole of the tournament, and took a 2-stroke penalty for hitting the wrong ball on Monday, finished with a 76-72?148 for his seventh-place medal. He was the low Mid-Penn man in the bunch. Conference champ Jake Reilly from Hershey, the top Mid-Penn finisher in Districts and Regionals, finished 75-79?154 and tied for 16th. Mid-Penn runner-up Tyler Shank from Palmyra shot back-to-back 79s and finished at 158, tied for 22nd. Reilly played in the same foursome with his cousin, Zach Herr from Council Rock North, who shot a 3-under 68 Tuesday and finished alone in fourth.
HOT FINISH FOR COOPER
Cooper carded a 3-over 75 Tuesday to nab a sixth-place finish. That?s the good news. The not-so-good news: She was standing on the 18th tee at even par for the day before making a triple-bogey on her final hole. Still, a two-day 81-75?156 was good for sixth, up from her 13th-place finish in her breakout freshman season last fall. Cooper finished 16 shots behind Council Rock North junior Erica Herr, who successfully defended her girls? AAA crown with a blistering 4-under 68 on Tuesday to finish 72-68?140 for her second gold in a row.
GRAHAM CAPS UNFORGETTABLE RUN
Boiling Springs sophomore Rebecca Graham, the first Bubblers? girls? player to ever make the PIAA finals, improved on her first-round 109 with a 96 on Tuesday. She finished with a 205 ? 18th in the girls? AA division. Villa Maria sophomore Cara Basso shot 78-72?150 to win the girls? AA title by 10 shots. The boys? AA title went to District 3 golfer Isaiah Logue from Fairfield; he shot 74-71?145 and won gold by two shots.
QUOTABLE
?I just wanted to go out and play my game and see what happened. Overall I?m happy, but I know I could have done a lot better. But I?ll definitely take it. I know I?ll be ready to get going next year. I?ll be working on my game and trying to improve all the time.? ? Allison Cooper.
?I played really well but my putting wasn?t all that great. I knew I could play wiht all of these guys; it came down to some little things that I had to do, and I just didn?t do them. But it was an excellent experience.? ? J.D. Hughes
?? ?
JEFF REINHART: jreinhart@pnco.com
ON TWITTER: @JeffReinhartPN
Source: http://highschoolsports.pennlive.com/news/article/-3654280553775006401
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Arrest made in dismemberment killing of Colo. girl
Authorities in Colorado announce that a 17-year-old male has been arrested and charged with the murder of 10-year-old Jessica Ridgeway.
By Sevil Omer, NBC News
Updated at 3:32 p.m. ET:?Police in Westminster, Colo., say they have made an arrest in the dismemberment killing of 10-year-old Jessica Ridgeway.
Police said the suspect is a 17-year-old Westminster resident.
NBC News is not identifying the suspect because he is a juvenile.
Police received a call late Tuesday evening that led them to a home near the Ketner Lake Open Space in Westminster, a Denver suburb, according to police.
Jessica was abducted on her way to school on Oct. 5. Her dismembered body was found Oct. 10 in a nearby field.?
"This morning the Ridgeway family was notified of this arrest," Westminster Police Chief Lee Birk said. "We hope and pray this arrest gives them some measure of closure in dealing with their horrible loss and tragedy."
The teen will be charged with two counts of murder in the first degree, authorities said.
Reached by phone Wednesday, the teen's mother told The Associated Press he surrendered to authorities. "I made the phone call, and he turned himself in. That's all I have to say," the mother told the AP. She broke down in tears and hung up.
Police said authorities will also file charges against the teen in connection with a?May 28 attempted abduction of a female jogger at Ketner Lake.?The lake is located near Witt Elementary School in Westminster where Jessica was headed on the day she vanished, police said.
In the May 28 case, a 22-year-old woman told police she fought off a stranger who grabbed her from behind and put a rag over her mouth. She told police the rag smelled of chemicals.
The suspect is to appear in court on Thursday morning.
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Tuesday, October 23, 2012
Fitness Yoga for Ballroom Dancers | Tango Rouge Ballroom Blog
Dancemasters Studio Dallas is now offering a Fitness Yoga class at 6 pm every Wednesday evening beginning November 7, 2012.? This class will be taught by certified Yoga instructor and professional ballroom dancer, Marcy Lambert.? She will be using a series of? flowing yoga poses which guarantees an energetic workout and offers basic challenges that can be done even by beginners in Yoga.
You can release stress, build strength, increase flexibility, detox, stimulate
weight loss, generate balance, reverse the aging process?.and?.just plain ?feel? good!Prepare to work hard and work up a sweat in these classes. Don?t forget your yoga mat, towel, and water bottle.? While there is no one who should be excluded, check with your doctor before you begin any new activity.? Check our? schedule for?a full list of?classes, or contact us with any questions.? Follow us on Twitter and Facebook to keep up to date with all our events and activities.
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Competitive Ballroom Dancer, Golfer, Grandmother, EntrepreneurSource: http://tangorougeballroomblog.com/2012/10/23/fitness-yoga-for-ballroom-dancers/
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Video: A Technical Slice of Apple
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Source: http://video.msnbc.msn.com/cnbc/49504029/
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3D structure of an unmodified G protein-coupled receptor in its natural habitat
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Public release date: 22-Oct-2012[ | E-mail |
Share ] Contact: Stanley Opella
scinews@ucsd.edu
858-822-4820
University of California - San Diego
Scientists have determined the three-dimensional structure of a complete, unmodified G-protein-coupled receptor in its native environment: embedded in a membrane in physiological conditions.
Using NMR spectroscopy, the team mapped the arrangement of atoms in a protein called CXCR1, which detects the inflammatory signal interleukin 8 and, through a G protein located inside the cell, triggers a cascade of events that can mobilize immune cells, for example.
Because G protein-coupled receptors are critical for many cellular responses to external signals, they have been a major target for drugs. More precise knowledge of the shapes of these receptors will allow drugmakers to tailor small molecules to better fit specific targets, avoiding collateral hits that can cause detrimental side effects.
"This finding will have a major impact on structure-based drug development since for the first time the principal class of drug receptors can be studied in their biologically active forms where they interact with other proteins and potential drugs," said Stanley Opella, professor of chemistry and biochemistry at the University of California, San Diego who led the work, which Nature published online October 21st in advance of the print edition.
Protein structures are most often determined by reading the diffraction patterns of X-rays beamed at their crystalline form, but crystallizing such large, unwieldy molecules is a challenge often met with strategies such as snipping off floppy ends.
Those changes can alter the shape of critical regions of the protein. "Our approach was to not touch the protein," Opella said. "We are working with molecules in their active form."
Their strategy has revealed a new view of these receptors. Previous reports have all noted seven helices weaving through the membrane. Opella's group sees an eighth lying on the membrane surface, a trait that at least some other G protein-coupled receptors must share.
And the loops inside and outside of the cell are structured. "For years people thought the loops were mobile. They're not," Opella said. "The signals we get from the loops aren't any weaker than the other parts of the protein as they would be if they were waving about."
CXCR1 has been implicated in the progression of several types of cancer. In one example, preclinical studies have shown that blocking this receptor inhibits the undifferentiated stem cells within breast cancer tumors, leading to the death of all tumor cell types and stopping them from seeding new tumors.
Opella and colleagues hope this finding along with continuing studies of changes in this receptor's configuration as it binds to interleukin 8 and drug candidate will lead to more effective and less harmful cancer treatments.
###
Additional authors include Sang Ho Park, Bibhuti Das, Fabio Casagrande, Ye Tian, Henry Nothnagel and Mignon Chu of UC San Diego; Hans Kiefer of HBS Hochschule Biberach in Germany; Klaus Maier and Anna De Angelis of Membrane Receptor Technologies in San Diego, California; and Ye Tian and Francesca Marassi of Sanford Burnham Medical Research Institute in La Jolla, California. The National Institutes of Biomedical Imaging and Bioengineering through Biomedical Technology Resource Center and Bioengineering Research Partnership grants.
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Public release date: 22-Oct-2012[ | E-mail |
Share ] Contact: Stanley Opella
scinews@ucsd.edu
858-822-4820
University of California - San Diego
Scientists have determined the three-dimensional structure of a complete, unmodified G-protein-coupled receptor in its native environment: embedded in a membrane in physiological conditions.
Using NMR spectroscopy, the team mapped the arrangement of atoms in a protein called CXCR1, which detects the inflammatory signal interleukin 8 and, through a G protein located inside the cell, triggers a cascade of events that can mobilize immune cells, for example.
Because G protein-coupled receptors are critical for many cellular responses to external signals, they have been a major target for drugs. More precise knowledge of the shapes of these receptors will allow drugmakers to tailor small molecules to better fit specific targets, avoiding collateral hits that can cause detrimental side effects.
"This finding will have a major impact on structure-based drug development since for the first time the principal class of drug receptors can be studied in their biologically active forms where they interact with other proteins and potential drugs," said Stanley Opella, professor of chemistry and biochemistry at the University of California, San Diego who led the work, which Nature published online October 21st in advance of the print edition.
Protein structures are most often determined by reading the diffraction patterns of X-rays beamed at their crystalline form, but crystallizing such large, unwieldy molecules is a challenge often met with strategies such as snipping off floppy ends.
Those changes can alter the shape of critical regions of the protein. "Our approach was to not touch the protein," Opella said. "We are working with molecules in their active form."
Their strategy has revealed a new view of these receptors. Previous reports have all noted seven helices weaving through the membrane. Opella's group sees an eighth lying on the membrane surface, a trait that at least some other G protein-coupled receptors must share.
And the loops inside and outside of the cell are structured. "For years people thought the loops were mobile. They're not," Opella said. "The signals we get from the loops aren't any weaker than the other parts of the protein as they would be if they were waving about."
CXCR1 has been implicated in the progression of several types of cancer. In one example, preclinical studies have shown that blocking this receptor inhibits the undifferentiated stem cells within breast cancer tumors, leading to the death of all tumor cell types and stopping them from seeding new tumors.
Opella and colleagues hope this finding along with continuing studies of changes in this receptor's configuration as it binds to interleukin 8 and drug candidate will lead to more effective and less harmful cancer treatments.
###
Additional authors include Sang Ho Park, Bibhuti Das, Fabio Casagrande, Ye Tian, Henry Nothnagel and Mignon Chu of UC San Diego; Hans Kiefer of HBS Hochschule Biberach in Germany; Klaus Maier and Anna De Angelis of Membrane Receptor Technologies in San Diego, California; and Ye Tian and Francesca Marassi of Sanford Burnham Medical Research Institute in La Jolla, California. The National Institutes of Biomedical Imaging and Bioengineering through Biomedical Technology Resource Center and Bioengineering Research Partnership grants.
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AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.
Source: http://www.eurekalert.org/pub_releases/2012-10/uoc--3so102212.php
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Monday, October 22, 2012
Rice agriculture accelerates global warming: More greenhouse gas per grain of rice
ScienceDaily (Oct. 19, 2012) ? More carbon dioxide in the atmosphere and rising temperatures cause rice agriculture to release more of the potent greenhouse gas methane (CH4) for each kilogram of rice it produces, new research published in this week's online edition of Nature Climate Change reveals.
"Our results show that rice agriculture becomes less climate friendly as our atmosphere continues to change. This is important, because rice paddies are one of the largest human sources of methane, and rice is the world's second-most produced staple crop," said Dr Kees Jan van Groenigen, Research Fellow at the Botany Department at the School of Natural Sciences, Trinity College Dublin, and lead author of the study.
Van Groenigen, along with colleagues from Northern Arizona University and the University of California in Davis, gathered all published research to date from 63 different experiments on rice paddies, mostly from Asia and North America. The common theme in the experiments was that they measured how rising temperatures and extra carbon dioxide in the atmosphere affect rice yields and the amount of methane that is released by rice paddies.
The research team used a technique called meta-analysis, a statistical tool for finding general patterns in a large body of experimental data. "Two strong patterns emerged when we analysed all the data: first, more CO2 boosted emissions of methane from rice paddies, and second, higher temperatures caused a decline in rice yields," explained Professor Bruce Hungate of Northern Arizona University and co-author of the study.
Methane in rice paddies is produced by microscopic organisms that respire CO2, like humans respire oxygen. More CO2 in the atmosphere makes rice plants grow faster, and the extra plant growth supplies soil microorganisms with extra energy, pumping up their metabolism. Increasing CO2 levels will also boost rice yields, but to a smaller extent then CH4 emissions. As a result, the amount of CH4 emitted per kilogram of rice yield will increase. Rising temperatures were found to have only small effects on CH4 emissions, but because they decrease rice yield, they also increase the amount of CH4 emitted per kilogram of rice. "Together, higher CO2 concentrations and warmer temperatures predicted for the end of this century will about double the amount of CH4 emitted per kilogram of rice produced.," explained Professor Chris van Kessel of the University of California in Davis and co-author of the study.
"Because global demand for rice will increase further with a growing world population, our results suggest that without additional measures, the total CH4 emissions from rice agriculture will strongly increase..."
However, the authors point out that there are several options available to reduce CH4 emissions from rice agriculture. For instance, management practices such as mid-season drainage and using alternative fertilizers have been shown to reduce CH4 emissions from rice paddies. Moreover, by switching to more heat tolerant rice cultivars and by adjusting sowing dates, yield declines due to temperature increases can largely be prevented, thereby reducing the effect of warming on CH4 emissions per yield. "These findings, together with our own results really stress the need for mitigation and adaptation measures to secure global food supply while at the same time keeping greenhouse gas emissions in check." van Groenigen concluded.
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The above story is reprinted from materials provided by Trinity College Dublin, via AlphaGalileo.
Note: Materials may be edited for content and length. For further information, please contact the source cited above.
Journal Reference:
- Kees Jan van Groenigen, Chris van Kessel, Bruce A. Hungate. Increased greenhouse-gas intensity of rice production under future atmospheric conditions. Nature Climate Change, 2012; DOI: 10.1038/nclimate1712
Note: If no author is given, the source is cited instead.
Disclaimer: Views expressed in this article do not necessarily reflect those of ScienceDaily or its staff.
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'Walking Dead': Five 'Sick' Questions
Killing zombies is one thing, but how about killing humans? That's one of the many questions at the heart of the latest episode of 'Walking Dead.'
By Josh Wigler
Daryl Dixon in "Walking Dead"
Photo: AMC
Source: http://www.mtv.com/news/articles/1695968/walking-dead-zombies-episode-2.jhtml
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What's Donald Trump's October Surprise?
Could ladies be as cheating-prone as their husbands? Could this be because of "gender equality"? There's some recent research indicating that "unfaithfulness among wives may be approaching that of husbands"?that, as Anna Breslaw writes in a post on Jezebel, more married ladies may be "Turning Into Unfaithful, Aloof Donna Drapers."?This research, as reported in a piece over the weekend in the Wall Street Journal, is not as new or shocking as one might find it at first glance. ...
Source: http://news.yahoo.com/blogs/ticket/trump-announcement-obama-133419054--election.html
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Sunday, October 21, 2012
Derek Jeter has surgery on broken left ankle
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Source: http://news.yahoo.com/derek-jeter-surgery-broken-left-ankle-211429906--mlb.html
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Iran | The Aussie Digger : Home of all Australian Veterans ex ...
Herman Rosenblatt and his wife Roma, smirking contentedly after having conned the world into accepting their fake Holocaust memoir Angel at the Fence. TV celeb Oprah Winfrey was taken in by their touching concentration camp romance and gushed breathlessly, ?This is the single greatest love story we?ve ever told on the air!? Asked why he had lied, Mr Rosenblatt explained, ?I wanted to bring happiness to people.? Despite the book being a proven fake, a $25 million blockbuster movie is now being made by Jewish producer Harris Salomon.
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This week the US, UK, France, and a few Middle Eastern countries are conducting naval exercises in the Gulf of Persia to practice clearing mines that Iran, or other groups may place around the Straits of Hormuz in an attempt to disrupt the movement of oil tankers in the region.
Mohammed Ali Jafari, the commander of the Islamic Revolutionary Guard Corps, said that the ?exercise is a defensive exercise and we don?t perceive any threats from it. We are not conducting exercises in response.?
?
Israeli lobby groups have reportedly contacted two communications satellite service providers to force them to take Iranian radio and television channels off the air following a recent ban on the broadcasters in Europe, Press TV reports.
The lobbies have recently approached International Telecommunications Satellite Organization (Intelsat) and Hispasat ? a group of Spanish communication satellites ? and called on them to stop the broadcast of Iranian channels.
Source: http://theaussiedigger.com/site/2012/10/iran-405/
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Questions for Medicare in meningitis outbreak
FILE - In this May 15, 2012 file photo, Health and Human Services Secretary Kathleen Sebelius speaks in Bethesda, Md. Medicare, overseen by Sebelius' department, is coming under scrutiny in the meningitis outbreak that has rekindled doubts about the safety of the nation?s drug supply. (AP Photo/Jose Luis Magana, File)
FILE - In this May 15, 2012 file photo, Health and Human Services Secretary Kathleen Sebelius speaks in Bethesda, Md. Medicare, overseen by Sebelius' department, is coming under scrutiny in the meningitis outbreak that has rekindled doubts about the safety of the nation?s drug supply. (AP Photo/Jose Luis Magana, File)
WASHINGTON (AP) ? Medicare is coming under scrutiny in the meningitis outbreak that has rekindled doubts about the safety of the nation's drug supply.
The giant health insurance program for seniors long ago flagged compounded drugs produced for the mass market without oversight from the Food and Drug Administration as safety risks. In 2007, Medicare revoked coverage of compounded inhaler drugs for lung disease.
But Medicare doesn't seem to have consistently used its own legal power to deny payment, and critics say that has enabled the compounding business to flourish.
Now program officials are scrambling to find out how many Medicare beneficiaries are among the more than 270 people sickened in 16 states in a still-growing outbreak that has claimed 21 lives.
The illnesses have been linked to an injectable steroid used to treat back pain, made by the New England Compounding Center, a Massachusetts specialty pharmacy. The medication was contaminated with a fungus.
A senior lawmaker and consumer advocates are raising questions about Medicare's role, including an apparent lack of coordination between Medicare and the FDA, the two most powerful agencies within the federal Health and Human Services Department.
In response, a department spokesman says Congress needs to provide the FDA with stronger powers.
The meningitis outbreak has called attention to the role of compounding pharmacies in supplying medications routinely used by hospitals and doctors to treat patients. Regulated primarily by states, the pharmacies specialize in customizing doses for individual patients who have allergies to ingredients in an FDA-approved drug, or who might need a smaller dosage than what's available commercially. But some pharmacies have pushed into full-scale manufacturing.
Medicare has long been aware of the risks.
"By compounding drugs on a large scale, a company may be operating as a drug manufacturer within the meaning of (federal law), without complying with requirements of that law," Medicare's coverage manual, a reference for contractors that handle payments, says in a section dealing with compounded drugs.
That situation, adds the manual, fails Medicare's basic standard, that treatments must be "reasonable and necessary" in order to be covered. "This means, in the case of drugs, the FDA must approve them for marketing," says the manual.
It goes on to say that billing contractors should wait for instructions from Medicare before cutting off payment in specific cases where the FDA has determined that a company is producing compounded drugs in violation of the law.
"Medicare indicates in its own policy documents that it can cut off payments for compounded drugs produced under manufacturing-like conditions," said Sen. Charles Grassley, R-Iowa, who over the years has pushed for stronger government oversight of the pharmaceutical industry.
"Medicare should explain whether it uses this step, and if not, why not. Every avenue for explaining how this health crisis occurred and preventing others like it needs exploration," he added.
Joyce Lovelace of Albany, Ky., says she doesn't understand how the outbreak could have happened. Eddie Lovelace, her husband of 55 years, died of a stroke after receiving injections of the steroid implicated in the outbreak as a treatment for pain from an auto accident.
"I'm 100 percent behind not paying ... whether it's Medicare, Blue Cross, or whatever," she said. "Somebody dropped the ball and as a result my husband is gone." Eddie Lovelace, 78, a long-serving judge, was still working at the time of his death and Medicare was not his primary insurance.
Medicare officials are looking into whether the program paid for drugs that have sickened patients.
"If the FDA determines a company is producing compounded drugs in violation of (federal law), Medicare will not reimburse for drugs produced in that facility," said HHS spokesman Tait Sye. "The FDA's regulatory authority over compounding pharmacies is more limited by statute than it is for typical drug manufacturers. We urge Congress to strengthen the FDA's authority."
FDA records show that in 2006 the agency issued a warning letter to the New England Compounding Center for producing anesthetic creams, but officials were unable to say if Medicare was alerted.
In a separate case, Medicare seems to have taken sweeping action on its own without much prodding from the FDA. In 2007, Medicare stopped coverage for compounded inhalation drugs used to treat lung disease.
"Compounded drugs are not considered interchangeable with FDA-approved products," said an information bulletin at the time from Noridian, a major Medicare payment contractor. "The absence of testing for safety and effectiveness has the potential of putting a patient at increased risk of injury, illness or death."
Michael Carome, deputy director of Public Citizen's health research group, says Medicare's policy on compounded drugs seems "internally contradictory."
"They do appear to have a policy for which the default setting is that Medicare does not cover drugs that have not been approved by the FDA," said Carome. "That essentially applies to many, if not all, drugs made by compounding pharmacies."
Medicare's defenders say the agency may be reluctant to act for a number of reasons. Cutting off compounding pharmacies could aggravate drug shortages. Also it could open Medicare to a political counterattack from industry, even charges of rationing.
But Carome, a physician who once served in an HHS regulatory office, says the alternative is that compounding will continue with little federal oversight and recurring outbreaks.
If Medicare had expanded its compounding crackdown beyond just lung disease medications, "that might have prevented the widespread use of these drugs," Carome said. "Without coverage, things don't get used."
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Saturday, October 20, 2012
22 Tools Every Internet Marketer Must Have To Make Money Online ...
Posted on October 20, 2012
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Source: http://andreabolder.com/2012/22-tools-every-internet-marketer-must-have-to-make-money-online/
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No. 18 Texas Tech pulls 3-OT win at TCU, 56-53
FORT WORTH, Texas (AP) ? Seth Doege tossed a touchdown pass in each of the three overtime periods, giving him seven for the game and helping No. 18 Texas Tech beat TCU 56-53 on Saturday after blowing a late 10-point lead.
The game-winning pass was an 8-yarder to Alex Torres, which came four plays after freshman Jaden Oberkrom's Big 12-record sixth field goal had put TCU ahead. Both teams scored touchdowns in the first two overtime periods.
TCU (5-2, 2-2), the Big 12 newcomer, has lost consecutive home games in a single season for the first time since it dropped its final two home games of 1998. Two weeks ago, the Horned Frogs lost their first Big 12 home game to Iowa State.
Doege hit Torres in the middle of the end zone to end the game with the most combined points ever for Texas Tech, and the second-most for TCU. He threw a 6-yard TD pass to Eric Ward in the first overtime, and a 25-yarder to Jakeem Grant on the first play of the second extra period.
Doege completed 30 of 42 passes for 318 yards and Texas Tech (6-1, 3-1) quickly became bowl eligible a year after its first losing season since 1992. The Red Raiders were coming off an impressive 49-14 victory over then-No. 5 West Virginia.
After upsetting third-ranked Oklahoma last season, Texas Tech followed with five losses in a row that ended a Big 12-record streak of 18 consecutive seasons of bowl eligibility.
It almost let this game slip away.
Tech led 36-26 when Kenny Williams busted loose for a 47-yard touchdown run with 4:06 left in regulation. That came after TCU was held to a three-and-out following Doege's 8-yard TD pass to Torres and 2-point conversion.
Trevone Boykin threw a 60-yard TD pass to LaDarius Brown with 2:25 left before the Frogs failed to recover an onside kick. But they held to Tech to 1 yard before a punt, setting up a nine-play, 56-yard drive capped by Oberkrom's 42-yard field goal with 18 seconds left.
Boykin, the redshirt freshman who this month replaced second-year starter Casey Pachall, was 26 of 44 for 332 yards with four touchdowns and two interceptions.
TCU had the first shot in overtime, and Boykin threw an 8-yard TD pass to Josh Boyce on the fourth play. Ward's third TD catch, a 6-yarder, tied the score again.
Tech lined up in a wildcat formation to start the second overtime, but the ball was then pitched to Doege, who threw it to Grant for the score. Boykin responded with a 7-yard TD pass to B.J. Catalon.
Ward had six catches for 61 yards.
Skye Dawson had 10 catches for 154 yards and a touchdown for TCU, a 19-yarder less than 2? minutes into the game.
After falling behind 17-7, the Red Raiders went ahead with two touchdowns in a span of just over 3 minutes in the second quarter. They recovered an onside kick and got the second score in that span after a replay review overturned an official's ruling of incomplete pass.
Moore had a 33-yard touchdown catch even with defender Kevin White right with him. That was only three plays after Moore was called for offensive pass interference when he pushed off the same cornerback to make a catch, the penalty wiping out a nearly 25-yard gain to the TCU 22.
Tech then caught TCU by surprise with an onside kick it recovered at midfield.
That led to Ward's 29-yard TD catch, when he was initially ruled out of bounds after making a leaping grab and then falling down on the far side of the end zone. But officials reviewed the play, which showed Ward's right elbow had landed in the end zone before the rest of his body came down on the line for a score that made it 21-17.
Source: http://news.yahoo.com/no-18-texas-tech-pulls-3-ot-win-235302955--spt.html
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