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Property to let in North Luton Place, Cardiff CF24 - 2 bedrooms
£475 pcm (£110 pw)
Howard Gardens, Cardiff CF24
Flat to rent - 2 bedroomsA ground floor, 2 bedroomed flat in a traditional house in walking distance to the City Centre. The flat has its own entrance and comprises of lounge/kitchen with appliances, two double bedrooms and bathroom (no shower). The property is alarmed and ...
Marketed by Burnett Davies Lettings, CF62. Call 01446 361099
£500 pcm (£115 pw)
Cumnock Terrace, Cardiff CF24
Property to rent - 2 bedroomsTerraced two bedroom house, unfurnished available immediately. Housing Benefit considered.
Marketed by Thomas Joseph, CF14. Call 029 2168 0141
£550 pcm (£127 pw) Just added
Constellation Street, Cardiff CF24
Flat to rent - 2 bedroomsSuperb 2 bedroom ground floor apartment situated in a very convenient location just a few minutes walk from Cardiff city centre and Queen St railway station. Benefitting from a modern kitchen and bathroom, and having a double and single bedroom, being ...
Marketed by South Wales Estates, CF24. Call 029 2227 0016
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Flat to rent - 2 bedroomsSpacious 2 bedroom ground floor flat located in the sought after area of Adamsdown.
Marketed by Ashi Properties, CF24. Call 029 2168 0189
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Moira Place, Adamstown CF24
Terraced house to rent - 2 bedrooms*** spacious 2 bedroom flat close to city centre ***
Marketed by Issa Estates, CF24. Call 029 2227 9541
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text:
Analysis of the buzz about Social Media Week 2013
by Braulio Medina, Co-Founder / Latam Manager at Vortio.com.br / uberVU.com on Oct 07, 2013
- 7,031 views
Featured in: Business & Mgmt, Technology
This is a social media analysis report about Social Media Week 2013. ...
This is a social media analysis report about Social Media Week 2013.
We have monitored mentions on social media containing the following keywords "social media week", "socialmediaweek" or "smw13" between september 23rd and 27th.
We have done a deep analysis of tweets in the english language using Vortio´s clustering methodology.
Vortio´s clustering engine automatically detects topics and clusters of conversations and influencers. This helps one understand the most important topics around any subject (brands, market terms, events etc.) in a matter of minutes.
Not only retweets and exact matches are identified but mentions that are closely related to each other are grouped together as well.
After analyzing a couple of clusters, we are able to deliver more comprehensive metrics (influence, sentiment, engagement) without having to analyze thousands of mentions by reading each one.
- Total Views
- 7,031
- Views on SlideShare
- 6,432
- Embed Views
- Likes
- 15
- Downloads
- 35
- Comments
- 2
Upload Details
Uploaded via SlideShare as Adobe PDF
Usage Rights
© All Rights Reserved

subset: commoncrawl


text:
Sustain Pedal/Switch for Bass Guitar? Do they make such an item? |
Depends on exactly what you mean. The sustain pedal/switch for a keyboard is totally unrelated to bass guitar. If you want just a bit more sustain, a compressor can do that. If you want a lot more sustain and don't mind being compressed intensely, there are heavy squishing sustainers like the Pigtronix Philosophers. If you want infinite synthetic sustain, check out the EHX Freeze. |
Yep that's what I meant....just simply sustain a note.....nothing else.... Thanks for the EXH Freeze reference.......... I don't really want anything in the way of effects......except for the sustain option..... Thanks.... |
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Earlier this month, Shane Battier of the Miami Heat uploaded a video of himself dressed like a ship's captain, singing the theme to 'The Love Boat.' It was the worst THE BEST, advertised his second annual "South Beach Battioke" celebrity karaoke event, and allowed me to make a joke about LeBron James singing Pretty Ricky.
- Happy International Women's Day! This Female Comedian Just Got Bumped For Being A Woman
- Texans Gear Up For The 56th Rattlesnake RoundUp In The Most Texas Story Ever
- Watch Tara Lipinski And Johnny Weir Give Their Olympic Commentary For Amateur Skaters On 'Late Night'
- 'Banshee' GIF Recap: Hospitals Are Death Traps


text:
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You missed it This great deal for Paintball Depot is over. But don't despair, we've got more great deals every day.
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One hundred supporters are expected to pluck down $40,000 a head to attend the bash in Chelsea netting the commander in chief a cool $4 million. In a message to supporters Beyonce wrote she's "met the president and its an opportunity you don't want to miss."
She also invited donors to contribute $25,000 for a chance to win an trip to New York and tickets to the fundraiser. Beyonce has supported the first family before singing at one of the President's inaugural balls.
The President has a full schedule in the city and his motorcade is expected to generate gridlock in a number of areas. He is slated to arrive at John F. Kennedy International Airport just after 3 p.m. The president then visits David Letterman at the Ed Sullivan Theater on Broadway at 4:40.p.m. At 7:40 p.m., Mr. Obama will attend a fundraiser at the Waldorf Astoria Hotel. He is then scheduled to make remarks at the 40/40 Club at about 9:45 p.m.
Republican candidate Mitt Romney is due in town for a fundraiser on Friday.


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Saturday, January 19, 2013
QPR boss Harry Redknapp hopes to combine his record signing of Loic Remy with Bobby Zamora, who could return from injury next week.
The perpetrator of that strike against the run of play was Remy, who was played in by Adel Taarabt, the playmaker with whom he linked well throughout.
"It was good to see him score in his first game," Redknapp said.
"I thought at that stage of the game he and Taarabt were going to do a bit of damage today.
"He (Remy) will do that. He's got great movement off the ball and if you can get people to slide him in when he makes those runs, he will get in because he's got lightning pace and he will score some goals. He'll do okay.
"We haven't had any pace up front. If I can get Bobby fit, next week he could be around and ready to play, I think Zamora and Remy could be a real good partnership."
Tottenham boss Tim Sherwood hopes his side can ruin as many of their rivals' Champions League qualification dreams as possible.
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Business Matters: Why Spotify Bought The Echo Nest
Beats Music Opens API To Public
7Digital's music service is coming to Tizen OS and Samsung's new Gear 2 smartwatches
Spotify launches a new SDK to tap its music-streaming service for iOS apps
Here at The Orchard, we take pride in delivering the music of our artists and labels to all of the places around the world where it can be purchased or listened to. Once it's delivered, we use our charm and relationships to get front-and-center placement so that our clients' music gets the attention it deserves, and the royalties, too.
We figure that everyone enjoys pretty pictures, so we created the graphic below to highlight some of the outlets we market to. There's a lot — which is why we have a global team located in major music markets to do the heavy lifting.
Thanks to Airene Resurreccion for the graphic.
Good to know that you guys are on top of your game! We appreciate our partnership with you here at Rymatica Recordings! Thank you!
Keep up the great work you guy are doing over there.
We at Unknown Source Music know's the importance
of consistency and foresight ,that experience really shows.
Thank you
Awesome job ! Great ideas ! Always i believed that Cretan music can be world famous but through your team Orchard i saw it with my own eyes ! Keep going !


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Late Night Hosts React to Jimmy Fallon's 'Tonight Show' Debut
UPDATED: David Letterman, Jimmy Kimmel, Conan O'Brien and Seth Meyers had words of support and congratulations for Jay Leno and his replacement.
Jimmy Fallon took to the airwaves for the first time hosting The Tonight Show on Monday in his highly anticipated debut, and while Hollywood stars such as Robert DeNiro, Will Smith, U2, Lady Gaga, and former New York mayor Rudy Giuliani helped him get off to an explosive start, other late night hosts also took notice.
During Monday's monologue on the Late Show on CBS, David Letterman referred to the absence of his longtime late night rival, Jay Leno, from NBC, saying, "First thing this morning, I get a call from my mom. She says 'David, did something happen to Jay?' What am I gonna do?" he asked the audience.
PHOTOS: Jimmy Fallon: From Early 'SNL' to Movie Star to 'Late Night'
There has long been animosity between the pair of TV greats, after many assumed that Letterman would take the hot seat of The Tonight Show in 1992 when Johnny Carson retired but Leno got the spot instead.
However, Letterman expressed his respect for Leno earlier this month when he said, "He was a host on The Tonight Show for 22 years and now retiring," he said. "Congratulations on a wonderful run."
Fallon's former competitor, Craig Ferguson, who hosts CBS' Late Late Show, also made a couple of jokes in his monologue about the late-night shift at NBC.
After a few Presidents' Day remarks, in which he joked that all of the former presidents live together in a clubhouse, Ferguson said that all of the late-night hosts also live together in a clubhouse.
"I haven't seen Leno recently, though," Ferguson continued. "Although, one of his cars is still in the driveway, so maybe he's coming back."
Ferguson also alluded to NBC's previous decision to have Conan O'Brien succeed Leno as host of The Tonight Show, which ended up being short-lived, with O'Brien leaving to go to TBS and Leno returning to the Tonight Show job.
Referring to Bob Costas returning to host NBC's primetime Olympics coverage after a bout with an eye infection that forced Matt Lauer and Meredith Vieira to fill in, Ferguson said, "I'm surprised NBC let him back. Usually when they replace a host, they stick with their decision."
STORY: Inside Jimmy Fallon's Star-Filled 'Tonight Show' Debut
Jimmy Kimmel didn't mention Fallon's debut in his own opening monologue of Jimmy Kimmel Live! that began 30 minutes earlier, but he did tweet his support on Monday morning:
congratulations @jimmyfallon -- I look forward to doing this side-by-side until our suits look funny and our hair turns white #FalPals
— Jimmy Kimmel (@jimmykimmel) February 17, 2014
VIDEO: Jimmy Fallon's 10 Best 'Late Night' Moments
While his own show was a rerun on Monday, O'Brien was quick to congratulate Fallon on Twitter:
As the only man alive who's hosted The Tonight Show & Late Night, I want to congratulate @JimmyFallon & @SethMeyers. They'll both do great!
— Conan O'Brien (@ConanOBrien) February 17, 2014
Seth Meyers, who will debut as host of Late Night With Seth Meyers on Feb. 24, congratulated his former Saturday Night Live costar by reminding his Twitter followers to tune in for Fallon's first night on the job:
Don't forget, @FallonTonight starts tonight!
— Seth Meyers (@sethmeyers) February 17, 2014
Prince Takes Over the 'Arsenio Hall Show,' Debuts New Funky Song A Train, a Trestle and 60 Seconds to Escape: How 'Midnight Rider' Victim Sarah Jones Lost Her Life 'Divergent' Star Shailene Woodley: The Next Jennifer Lawrence? 'Noah' Banned in Several Middle Eastern Countries Lindsay Lohan's OWN Series Gets First Official Trailer (Video) -
- 1
President Obama to Introduce 'Cosmos'
- 2
Harvey Weinstein at UCLA: Hillary Clinton Benghazi Flap 'Complete Bull---'
- 3
Charlie Sheen No-Shows Delay 'Anger Management' Production (Exclusive)
- 4
Veronica Mars: SXSW Review
- 5
A Train, a Narrow Trestle and 60 Seconds to Escape: How 'Midnight Rider' Victim Sarah Jones Lost Her Life
- 6
Neighbors: SXSW Review
- 7
'Noah' Banned in Several Middle Eastern Countries
- 8
'Divergent' Star Shailene Woodley: The Next Jennifer Lawrence?
- 9
Oscars 2014 Winners: The Complete List
- 10
SXSW: 'Veronica Mars' Delights Diehards at World Premiere


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I think the way we talk about cancer has really evolved. I remember the way my grandmother used to talk about it, like a death sentence, no-one would even mention the word.
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Note: Select a region before finding a country.
Mostly sunny and pleasant
A t-storm in the afternoon
A thunderstorm Wednesday afternoon
Mar 10, 2014; 5:00 PM ET On Wednesday, snow and cold will produce major travel delays over New England in the US.
Rises at 6:45 AM with 11:56 of sunlight, then sets at 6:41 PM
Rises at 1:58 PM with 13:12 of moolight, then sets at 3:10 AM
7:10pm CST


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Top Apps
- Audio & Video
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- Communications
- Development
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- Games
- Graphics
- Science & Engineering
- Security & Utilities
- System Administration
Showing page 3 of 9.
TriGrid - FE Triangular Grid Builder Two dimensional (2D) fine mesh finite element (FE) grid editing system. Includes constrained Delaunay triangulation, and automated grid resolution changes based on local attributes. Win32 and Motif GUIs. Mature application, now going open source.
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General Knowledge Machine Project The volume of actual knowledge prevents people from applying it, because even the cleverest persons can not learn everything they need. Try to overturn this with idea of Just-In-Time Knowledge. Intelligent e-knowledge base engine provided.
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g2 graphical library g2 is an easy to use, portable and powerful 2D graphics library. It provides a comprehensive set of functions for simultaneous generation of graphical output on different types of devices.
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ProgPorts ProgPorts is an administrative and easy user interface to hundreds of proteomics, molecular dynamics, and protein crystallography programs. It is a hybrid of the prog/setup system, developed at Johns Hopkins University, and GNU-Darwin ports system.
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MCCCS Towhee Towhee is a Monte Carlo molecular simulation code originally designed for the prediction of fluid phase equilibria using atom-based force fields and the Gibbs ensemble with particular attention paid to algorithms addressing molecule conformation sampling.
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COSTA; PSE for data assimilation Problem Solving Environment (PSE) for Data Assimilation and Model Calibration
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2-D inviscid flow and adjoint solver A 2-D inviscid flow and adjoint solver on unstructured triangular grids. It makes use of a vertex-centroid finite volume scheme which is second order accurate. The adjoint solver is developed using the automatic differentiation tool called TAPENADE. Code has been moved to https://github.com/cpraveen/euler2d
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cundctex Ein Projekt zur mathematischen Betrachtung moderner kryptographischen Verfahren und von Laplaceschen Fraktalen mit Fraktionellen Ableitungen. Das Projekt ist für die Forschung und nicht für kommerziellen Einsatz gedacht.
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libcgi Common Gateway Interface Library.
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Open FMM Open FMM ( http://www.openfmm.net ) is and open source EM software project. It consist of a fast parallel two-dimensional TM/TE solver called Nero2d.
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NOSE NOSE is a package for simulation of linear and non-linear optical and infrared spectra, including absorption, fluorescence, circular dichroism, pump-probe, photon echo and other.
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Visual FUPROLAN Visual FUPROLAN (Futured Programming language )Is a programming language for programming in multiple paradigms, such procedural programming, object-oriented programming, and generic programming. But which is characterized by a clear syntax, rigorous and
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SEACAS The Sandia Engineering Analysis Code Access System (SEACAS) is a suite of preprocessing, postprocessing, translation, and utility applications supporting finite element analysis software using the ExodusII database file format.
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hybrid model optimization/identification hybopt is a set of libraries to solve the identification and optimal control problems for hybrid (mechanistic/empirical) dynamic (ODE and DAE) models.
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NexPower NexPower - a suite of tools for transient and harmonic analysis of electric power distribution and transmission systems.
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Thermal-Tempest Tempest is a "Temperature Estimator" that runs on any Linux based system with LMSensors configured. Tempest provides a thermal profile of an application and correlates temperature data to source code. Tempest also regulates the temperature within stipu
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CGNU project CGNU (Clean GNU) aims to use modern documentation technologies to clean the GNU project of bitrot and outdated build technology.
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STAR-MPI The STAR-MPI (Self-tuned adaptive routines for MPI collective routines) project is an on-going research and development effort to apply the adaptive software approach to develop efficient MPI collective routines across platforms and applications.
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MIR A High-Order Multi-Variate Approximation Scheme for Arbitrary Data Sets, C implementation of the method described in http://web.mit.edu/qiqi/www/paper/interpolation.pdf, with Python and Fortran interfaces.
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VectTens A library for handling vectors, tensors, and more.
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Central Silicon Experimental ESL Compiler from C to Verilog
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RegCM3 Utilities A set of utilities for manipulating ICTP's RegCM3 input and output data.
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Suprangen - pseudorandom numbers Suprangen is a system of libraries for pseudorandom number generation
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GNUPinch GNU Pinch is a tool for the analysis of the energy consumptions of industrial processes. Given a process involving energy requirements, the program delivers a report of the most efficient heat exchanger network in terms of consumption and fixed costs.
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NearTree function library efficiently solving the Nearest Neighbor Problem (also know as the post office problem).
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Your search for Computer and Video Games in Defense and Military Forces returned 33 articles
Video Game Uses Japanese War Criminals as Targets
The game, unveiled by People's Daily Online Weibo, a microblog affiliated with the newspaper of the ruling Chinese Communist Party, is titled Shoot the Devils.
February 27, 2014, ThursdaySpies Infiltrate a Fantasy Realm of Online Games
American and British spies have infiltrated online fantasy games, fearing that militants could use them to communicate, move money or plot attacks, documents show.
December 10, 2013, TuesdayNorth Korean Propaganda Video Imagines a Brighter World, Without Manhattan
When North Koreans dream of taking revenge on the United States, it appears that American video games and music figure heavily.
February 05, 2013, TuesdayA Soldier in a Skeleton Scarf in Mali
The similarities to a killer character from an online warfare game to a news agency's recent photograph of an actual soldier with French forces in Mali is called unacceptable by a military spokesman in France.
January 24, 2013, ThursdayIn Defense of Offense: Why We Gamers Shoot
Superior video games, like the new Call of Duty: Black Ops II and Halo 4, are more like chess with added firepower than mere violent mayhem.
November 13, 2012, TuesdayGame On: A 19th-Century Approach to Photographing Modern Warfare
Karl Burke's eerie war images recall Mathew Brady or Roger Fenton's work of the 19th century, but Mr. Burke has never set foot on a battlefield.
May 24, 2012, ThursdayOops! Documentary Mistakes Video Game for Battle Footage
A British broadcaster admitted to erroneously using footage from a video game in a documentary about arms sales by Col. Muammar el-Qaddafi to the Irish Republican Army.
September 27, 2011, TuesdayA War Training Platform From an Unlikely Source
A game called VBS 2, used by militaries around the world to simulate battlefield conditions in training, owes its existence to an Australian heavy metal song.
May 02, 2011, MondayCombat Game Goes Too Far for Military
Air Force and Navy bases said they would refuse to sell a soon-to-be-released combat-simulation game, Medal of Honor.
September 10, 2010, FridayUrban Tool in Recruiting by the Army: An Arcade
The Army is hoping that new "experience centers," complete with video games that simulate battle, will increase enlistment among young people.
January 05, 2009, MondaySEARCH 33 ARTICLES ABOUT DEFENSE AND MILITARY FORCES:
- Reaching My Autistic Son Through Disney
- Well: Gadgets to Boost Bike Safety
- Books of The Times: The Jews, a History in So Many, Many Words
- Well: The Monitored Man
- Op-Ed Columnist: The Leaderless Doctrine
- Well: Do Brain Workouts Work? Science Isn't Sure
- Editorial: The Democrats Stand Up to the Kochs
- Well: Every Dog Has Its Data
- Opinion: The Fat Drug
- Even Before Fort Lee Lane Closings, Port Authority Was a Christie Tool
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text:
If a red-faced slaphead lumbers wearily past you, all words of encouragement will be most welcome"
Selfies have caught the imagination of pop stars, politicians and even the Pope, who posed with young visitors to the Vatican last August."
It has been a torrid time for Blues' fans since and they will be hoping the mess left by Carson Yeung can be cleared up sooner rather than later."
Carson Yeung's incarceration, you would imagine, should focus his mind on just what to do with Blues"
The plastic macs handed out as we went in were an indication that this was no ordinary show"
It's easy to see the appeal for people taking up the habit with no restrictions on where they can smoke."
The agent rings with news of that one job you've been hanging on for - and it clashes with the job you've just signed up for."
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Criminal lawyers across the region are to stage a mass exodus in anger at Justice Minister Chris Grayling's latest cutbacks
Nine-hour Redditch bridge drama causes major disruption as man threatens to jump
A jobless man has been remanded in custody on wounding and theft charges after a Kidderminster store guard sustained serious head injuries
Robert Coulson, of Quarry Bank died in collision with tanker on Tuesday
Appeal for witnesses after man arrested over security guard assault in Kidderminster's Weavers Wharf complex
Man charged with possessing gun and cannabis after being pulled over in Wolverley
A Marks & Spencer security guard was airlifted to hospital in Birmingham after town centre incident
A van driver was killed when his vehicle was in collision with a tanker on the A449 on the outskirts of Kidderminster
The Grade II-listed buildings in Horsefair, Kidderminster, date back 300 years, and are believed to be the last surviving examples of domestic carpet-weaving premises in 'Carpet Town'
Our resident fish and chip shop expert gives the lowdown on the West Midlands most sizzling friers
The three men struck at stores in Birmingham, Staffordshire and the Black Country in a brazen ten-month crime spree
Vikram Thakur, from Solihull, helps ophthalmologist mum with surgery in rural village near Raipur
This café has plenty of chairs and tables right on the canalside.
Fraud trial here's how Simon Drew and David Griffiths tricked people into believing InspireGLG was a hugely successful animation company
Ian Clarkson talks to Brian Halford about the demise of West Midlands football
Michelle Clifton was discharged after being treated in hospital for a broken arm and bruising but collapsed and died at home two days after the Christmas Day collision
Michelle Clifton was injured in collision near Kidderminster but died days later after collapsing at home
Collision in Kidderminster later claimed life of driver who died from his injuries
Officers trying to piece together last movements of Paul Humphries early on Boxing Day morning
Police yet to identify man found dead in Chaucer Street.
Highlights include Black Sabbath: LG Arena/The NIA, Birmingham, and Wolf Hall, Swan Theatre, Stratford upon Avon
Jonathan O'Brien, aged 55, convicted of attacking pupils under his care in Worcestershire during the 1980s
Baggies star Jesse Pennington was approached to help throw a game - but defender went to club and police
Knife attack was so frenzied two blades broke, court told
What is a reasonable price to pay to see Santa? Catherine Lillington looks into the growing cost of trips to grottos.
This week's Birmingham Children's Hospital Charity Champions are runners, Richard, Fay, Maddie, Aylah and Oscar, from Kidderminster.
Richard Larkin was killed along with three fellow soldiers when the Snatch Land Rover they were travelling in hit a landmine in Afghanistan
Court told a catalogue of health and safety blunders led to woman not being reported missing for 12 hours after walking out of fire door
Alan Evans, 35, showed no emotion as he was jailed for life at Worcester Crown Court after a judge described the murder of his wife Louise as a "callous" and deliberate killing
Alan Evans, 35, broke down in the dock and held his head in his hands at Worcester Crown Court after being unanimously convicted of killing his wife Louise
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He has over 30 years experience as a journalist in the West Midlands including editorships on the Coventry Telegraph and Sunday Mercury.


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I have a plist which is an array, the file name is called startups.plist. I tried to read it into an array by the following code:
NSString *path = [[NSBundle mainBundle] pathForResource:@"startups" ofType:@"plist"];
NSMutableArray * wordList = [[NSMutableArray alloc] initWithContentsOfFile:path];
However, wordList is always 0 here. Printed the path when testing on device, and it gives me:
Here's what the structure looks like of the plist:
the size of the array is 0. What am I doing wrong here?


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Come on in! Join Pinterest today...it only takes like a second or so.
"I just thought he was really quiet."
Or any number of emails for that matter-hysterical....just sounded like something I would actually say
bring on the crayons!
Driving a Real Muscle Car With Led Zepplin Playing on your 8 Track Tape Deck and Sitting at a Red Light at 2am and Hoping another Muscle Car would Pull up for a Drag Race Cool Times


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A collection of news and information related to Peyton Manning published by this site and its partners.
Top Peyton Manning Articles
Displaying items 100-110
Michael Jordan ranks as most likable athlete today, Dwight Howard No. 45
Story | Sep 17, 2010 | 4:35 PMSo, I'm sure some of you have read about the "Q scores" which found that LeBron James is almost considered as unlikeable as Kobe Bryant. If you thought that was surprising, the top 10 list of "likeable" sports personalities is even more intriguing with... -
Former Tennessee coach Phil Fulmer predicts victory in Florida footballâs SEC opener
Story | Sep 13, 2010 | 4:35 PMDespite Florida's early hiccups against USF Saturday, they shouldn't have any problems knocking off SEC foe Tennessee on the road Saturday, says former Tennessee coach and CBS college football analyst Phil Fulmer.... -
Florida State coach Jimbo Fisher, quarterback Christian Ponder meet the press
Story | Aug 30, 2010 | 4:32 PMFlorida State coach Jimbo Fisher, quarterback Christian Ponder meet the press... -
Peyton Manning is not a fan of Lane Kiffin
Story | Aug 23, 2010 | 4:33 PMPeyton Manning not a fan of Lane Kiffin The former Volunteers and current Indianapolis Colts quarterback was on the The Dan Patrick Show this morning and he was asked what he would say to former Tennessee coach Lane Kiffin is he saw him on the street.... -
Tim Tebow will haunt Jacksonville into eternity
Story | Jul 30, 2010 | 4:32 AMTim Tebow just wonât go away, reminding the Jacksonville Jaguars of their monumental fail during the NFL Draft. See Tebow posing as a pitchman for Jockey underwear. See him lead the league in jersey sales. Tebow is the most recent league-leader in... -
Florida State QB Christian Ponder joins star-studded cast at 2010 Manning Passing Academy
Story | Jun 1, 2010 | 4:33 PMFlorida State quarterback Christian Ponder will be one of 25 college quarterbacks to attend the Manning Passing Academy, according to NewOrleans.com. The academy, of course, is the most prestigious of its kind and is considered a must-attend for college... -
Report: Indianapolis Colts interview Jim Tressel
Story | Jan 21, 2012 | 4:36 PMReport: Indianapolis Colts interview Jim Tressel... -
Jay Gruden: Tim Tebow in spread offense will work in the NFL
Story | Nov 8, 2011 | 4:35 AMBengals Jay Gruden: Tim Tebow in a college spread offense will work in the NFL... -
Heisman Trophy Watch: Marcus Lattimore bolts ahead
Story | Sep 22, 2011 | 4:35 AMHeisman Trophy Watch: Marcus Lattimore bolts ahead... -
Chris Johnson: Titansâ Chris Johnson says he canât play for $550,000
Story | Jun 17, 2010 | 4:34 PMFor the second time in the NFL offseason, Chris Johnson has voiced his concerns about being slighted. The most recent being his paycheck from the Tennessee Titans. Chris Johnson signed a five-year contract with the Titans as a rookie for $12 million.... -
Peyton Manning: Derek Dooley needs time
Story | Jun 22, 2010 | 4:33 PMPeyton Manning says Derek Dooley needs time with the Vols....


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The Care Quality Commission (CQC) is the health and social care regulator for England. The organisation's aim is to ensure that everyone receives better care, whether they are in hospital, in a care home or at home.
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Every Vote Counts! Voting for the St. Patrick's Day Showdown is ON!
Voting Home / Primrose Dallas
Nominated for: BEST Day Care
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Hi, guys! We just voted for you. Please vote for us! Absinthe Lounge. Nightlife category - Trendy Bars. Thanks!
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text: beautiful, beauty, color, colorful, cute, fashion Added: July 16, 2011 | Image size: 720 x 564 px | More from: www.facebook.com | Source: link No comments Please log in or sign up to post a comment. add to set Views: 963 Likes (**who?): 2 Comments: 0Tagged with:beautiful 118080beauty 24630color 9058colorful 8462cute 204216fashion 167049milk 782model 31924photography 126050polaroid 1416pretty 92956rachel lynch 23retro 4302vintage 49395Log in or Sign upLog In or Sign Up


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This was my first time ever trying Hamantaschen. In fact, when my boyfriend came by the office with these treats, I had no idea what they were. 176 more words
Tags » Cookies
Cookie Crush
Cookie Casa
8116 Beverly Blvd, Los Angeles, CA 90048, PH: 310.922.6396
Pricing: $/$$-Inexpensive/Moderate
Hi Friends,
We are so sorry we did not have a post for you all last week. 358 more words
Purim is rolling in again, which is the Jewish equivalent of Halloween. Okay, admittedly, Purim is the celebration of the story of Esther, who rescued the Jewish people from essentially being assassinated. 1,134 more words
Recipe of the day:
Chocolate Chip Cookies
-Soft and chewy in the center crispy on the outside-
1 cup of butter
3/4 cup of white sugar
1 cup of brown sugar… 108 more words
Galletas "Eat me" de Alicia en el País de las Maravillas
"Que le cooooooooorten la cabezaaaa!!"
Como me ha gustado siempre esta película. Me recuerda siempre a mi y mis mundos de colorines y locura!
Tenía muchísimas ganas de hacer alguna receta con una temática en concreto, no solo experimentos raros y recetas sin sentido. 706 more words
Teff Peanut Butter Cookies (gluten free)
Hello! Double post today, I know! But we will be busy with family from out of town and rebuilding our living room this week-end so I figured I'd share now a new recipe! 360 more words
Francis Rustico Bakery Spring is in the Air Market
Francis Rustico Bakery will be at the Old town market place in Huntington Beach with lots of cookies! Saint Patricks day being the next day there will be a lot of celebrating. 103 more words


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If the game freezes, just click inside it (games can get unresponsive if you click elsewhere on the page).
i luv this game its my fav
i`m a boy but i like this
Yes |
No |
Go clean the laundry.
This game is played with the mouse only.
Add this game to your web page!
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Houses for sale in Gorsley
£375,000 Just added
3 bedroom bungalow for sale
Gorsley, Ross-On-Wye HR9Six bedroom detached chalet style house in need of updating together with ample off road parking, swimming pool in need of updating, plot measuring approximately third of an acre and offered with no onward chain.
Marketed by Steve Gooch, GL18. Call 01531 577014
3 bedroom bungalow for sale
Gorsley, Ross-On-Wye HR9Three bedroom detached bungalow in need of updating having the added benefit of off road parking, garage, workshop being set in a total plot approaching 1/3 of an acre the property details you are about to view are awaiting vendor approval and ...
Marketed by Steve Gooch, GL18. Call 01531 577014
4 bedroom bungalow for sale
Gorsley, Ross-On-Wye HR9A four bedroom detached bungalow with two bathrooms. Benefits include double glazing, double garage and enclosed rear gardens.
Marketed by Bidmead Cook, HR9. Call 01989 569053
Offers in region of £425,000
4 bedroom detached house for sale
Manse Lane, Gorsley, Ross On Wye HR9A large and individual Executive style four bedroom detached House with Double Garage, ample parking and private rear garden, located in a popular village location. Energy Performance rating 'C'
Marketed by Smiths of Newent, GL18. Call 01531 888380
3 bedroom semi-detached new house for sale
Gorsley, Ross-On-Wye HR9** coming soon** currently under construction - specification to be clarified three/four bedroom semi-detached country style homes built of reclaimed gorsley stone having character features and a slate roof.
Marketed by Steve Gooch, GL18. Call 01531 577014
Guide price £1,485,000
7 bedroom detached house for sale
Gorsley, Ross-On-Wye, Herefordshire HR9An imposing country house surrounded by mature grounds - The house which was built in 1888, lies at the end of a tree-lined drive where it sits proudly looking out over its garden & paddocks with a wooded backdrop beyond. A 2 bed cottage lies to the ...
Marketed by Knight Frank - Hereford, HR4. Call 01432 367333
4 bedroom detached house for sale
Gorsley, Ross-On-Wye HR9Lilly hall is an attractive stone built residence with parts dating back to 1760. The property has been sympathetically renovated by the present owners and enjoys delightful landscaped gardens measuring in excess of three acres.
Marketed by Steve Gooch, GL18. Call 01531 577014
Latest Gorsley houses for sale
Zoopla is one of the UK's leading property portals, helping you to find property for sale and to rent and make smarter decisions when buying and renting homes in the UK. Discover information on homes in Gorsley by researching Gorsley property values, Gorsley house prices paid, our Gorsley property market overview and find Gorsley agents.


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Photo Flash: First Look at the Minnesota Opera's Production of MACBETH with Greer Grimsley and Brenda Harris
Minnesota Opera is pleased to announce its first production of 2014. Verdi's dark-hued Macbeth examines the corrosive consequences of tyranny. At the urging of his wife, Macbeth murders the king to claim the crown. His desperate and deadly reign of terror devastates his country and hastens his doom in this masterwork based upon Shakespeare's classic thriller. The Show Premieres Saturday, January 25th, and runs through February 2nd at Ordway, 345 Washington Street, Saint Paul, MN 55102. The show is sung in Italian with English surtitles projected above the stage.
Bass-baritone Greer Grimsley (The Flying Dutchman) makes his long-awaited return as the ambitious and sinister King of Scotland with soprano Brenda Harris (Nabucco) as his scheming wife, Lady Mac- beth. American bass-baritone Alfred Walker (The Magic Flute) returns to Minnesota Opera as Banquo, the one-time ally Macbeth betrays in his lust for power, and tenor Harold Meers (La bohe?me) is Macduff, Lord of Fife and foil to Macbeth. Joel Ivany (Nabucco) directs a new Minnesota Opera production with costumes by Camellia Koo (debut), lighting by Jason Hand (debut) and projections by Sean Nieuwenhuis (debut). Michael Christie conducts the Minnesota Opera Orchestra.
Saturday, January 25, 7:30pm Tuesday, January 28, 7:30pm Thursday, January 30, 7:30pm Saturday, February 01, 8pm Sunday, February 02, 2pm
Tickets: $20 - $200. Call the Minnesota Opera Ticket Office at 612.333.6669, Monday-Friday, 9am-6pm, or purchase online at mnopera.org.
Photo Credit: Michal Daniel
Greer Grimsley
Greer Grimsley and AlFRed Walker
Greer Grimsley and Brenda Harris
Greer Grimsley and Brenda Harris
Greer Grimsley and Brenda Harris
More On: F, Red Walker, Brenda Harris,
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Analog semiconductor sales to hit nearly $62B by 2015
- Patrick O'Grady
- Managing Editor- Phoenix Business Journal
- Email | Twitter | Google+
Analog semiconductors are looking to outpace the full semiconductor market at least this year, and potentially through the next four years.
Semico Research in Phoenix released a report this week that the analog market will grow to $61.9 billion through 2015 and have growth rates that will top 10 percent in two out of the next three years.
This comes as the overall semiconductor market is slowing down as demand for chips is following demand for products in a global economy that appears to be waning.
The growth will be driven by needs in computing, consumer uses and communication markets -- particularly smartphones.
Those numbers could provide a boost for two Valley firms. On Semiconductor Corp. (Nasdaq: ONNN) and Microchip Technology Inc. (Nasdaq: MCHP) both are heavily invested in analog devices.
Semiconductor sales, which grew sharply in 2010, have slowed considerably but are still growing slightly. According to the Washington-based Semiconductor Industry Association, the global industry grew by 2.2 percent in August to $25 billion.
Patrick O'Grady is managing editor of the Phoenix Business Journal.
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One of the professors at Central Seminary gave a talk last night about Biblical geography (specifically the Shepelah hills west of the mountains), and gave some fascinating insight into Solomon's marriage to Pharaoh's daughter. Ever notice how he built her a palace away from the Temple, as she was a pagan? Dr. Beacham noted a real reason for the marriage; Pharaoh captured Gezer, along the strategic road to Joppa, for Solomon as a dowry for her.
In short, Solomon effectively posted a personals ad saying "wanted; woman with truck. Please send picture of truck." Pharaoh gave him the truck, and a nice one it was, too.
In "very sad" news, I believe it's mere days until my television will no longer receive broadcast TV programs. Not that I'll notice. I was thinking today that a great part of the lack of thinking might have a lot to do with our dependence on the idiot box. If you're wondering how to improve your thinking, turn it off for a while and see what happens. You just might be very surprised.
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Prince Stops By 'The View' Unannounced
VIDEO: The singer surprised the co-hosts when he gave each of the co-hosts a pair of tickets to his Dec. 18 concert.
NEW YORK -- You know that you are truly a rockstar when you can just walk onto a talk show without letting the host, or hostesses in this case, know you're coming. Prince showed that he doesn't need to make appointments -- not even with Barbara Walters -- when he showed up for a surprise visit on The View on Thursday.
The singer appeared on the show to promote his Welcome 2 America concert dates at Madison Square Garden, giving each of the ladies a pair of tickets to his Dec. 18 show.
Barbara Walters couldn't help but mention that she'd interviewed Justin Bieber recently and that the teen sensation had said he'd love to be like Prince one day -- the ultimate consummate performer. Prince looked grateful for the compliment and advised Bieber that learning every aspect of music that you can is the key to longevity, and that he hopes the young star will "pick up an instrument and get a good teacher." Prince may have missed the memo -- Bieber already plays four instruments: guitar, piano, drums and a little saxophone.
Although we are well aware that just the mention of Bieber gets the girls' hearts racing, Prince showed that he is far more practiced in the art of melting a woman. Hostess Sherri Shepherd could hardly contain herself! She first requested Prince declare his love for her and, after being chastised by Whoopi Goldberg for trying to take the singer's gloves, declared that she had wanted to make love to Prince her entire life.
Probably a little TMI, Sherri. Prince couldn't handle the heat and had to leave the stage before giving Shepherd a response, but Whoopi had his back and explained that the singer is just really shy -- sure Whoopi, sure.
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- Humble, TXenvironmentPrevious experience with Customer Relationship Management (CRM) systems is a plusHigh level of integrityDesire to help others, and earn a competitive incomeAbility to...
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- Houston, TXTX. Responsibilities:Deliver excellent service to our customers by listening to ... Diploma or GED is requiredPrevious sales and customer service experience is preferredHigh...
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Publications (24)168.91 Total impact
Article: Calcium influx through Cav1.2 is a proximal signal for pathological cardiomyocyte hypertrophy.
[show abstract] [hide abstract]
ABSTRACT: Pathological cardiac hypertrophy (PCH) is associated with the development of arrhythmia and congestive heart failure. While calcium (Ca(2+)) is implicated in hypertrophic signaling pathways, the specific role of Ca(2+) influx through the L-type Ca(2+) channel (I(Ca-L)) has been controversial and is the topic of this study. To determine if and how sustained increases in I(Ca-L) induce PCH, transgenic mouse models with low (LE) and high (HE) expression levels of the β2a subunit of Ca(2+) channels (β2a) and in cultured adult feline (AF) and neonatal rat (NR) ventricular myocytes (VMs) infected with an adenovirus containing a β2a-GFP were used. In vivo, β2a LE and HE mice had increased heart weight to body weight ratio, posterior wall and interventricular septal thickness, tissue fibrosis, myocyte volume, and cross-sectional area and the expression of PCH markers in a time- and dose-dependent manner. PCH was associated with a hypercontractile phenotype including enhanced I(Ca-L), fractional shortening, peak Ca(2+) transient, at the myocyte level, greater ejection fraction, and fractional shortening at the organ level. In addition, LE mice had an exaggerated hypertrophic response to transverse aortic constriction. In vitro overexpression of β2a in cultured AFVMs increased I(Ca-L), cell volume, protein synthesis, NFAT, and HDAC translocations and in NRVMs increased surface area. These effects were abolished by the blockade of I(Ca-L), intracellular Ca(2+), calcineurin, CaMKII, and SERCA. In conclusion, increasing I(Ca-L) is sufficient to induce PCH through the calcineurin/NFAT and CaMKII/HDAC pathways. Both cytosolic and SR/ER-nuclear envelop Ca(2+) pools were shown to be involved.Journal of Molecular and Cellular Cardiology 03/2011; 50(3):460-70. · 5.15 Impact Factor - [show abstract] [hide abstract]
ABSTRACT: Activation of prosurvival kinases and subsequent nitric oxide (NO) production by certain G protein-coupled receptors (GPCRs) protects myocardium in ischemia/reperfusion injury (I/R) models. GPCR signaling pathways are regulated by GPCR kinases (GRKs), and GRK2 has been shown to be a critical molecule in normal and pathological cardiac function. A loss of cardiac GRK2 activity is known to arrest progression of heart failure (HF), at least in part by normalization of cardiac β-adrenergic receptor (βAR) signaling. Chronic HF studies have been performed with GRK2 knockout mice, as well as expression of the βARKct, a peptide inhibitor of GRK2 activity. This study was conducted to examine the role of GRK2 and its activity during acute myocardial ischemic injury using an I/R model. We demonstrate, using cardiac-specific GRK2 and βARKct-expressing transgenic mice, a deleterious effect of GRK2 on in vivo myocardial I/R injury with βARKct imparting cardioprotection. Post-I/R infarct size was greater in GRK2-overexpressing mice (45.0±2.8% versus 31.3±2.3% in controls) and significantly smaller in βARKct mice (16.8±1.3%, P<0.05). Importantly, in vivo apoptosis was found to be consistent with these reciprocal effects on post-I/R myocardial injury when levels of GRK2 activity were altered. Moreover, these results were reflected by higher Akt activation and induction of NO production via βARKct, and these antiapoptotic/survival effects could be recapitulated in vitro. Interestingly, selective antagonism of β(2)ARs abolished βARKct-mediated cardioprotection, suggesting that enhanced GRK2 activity on this GPCR is deleterious to cardiac myocyte survival. The novel effect of reducing acute ischemic myocardial injury via increased Akt activity and NO production adds significantly to the therapeutic potential of GRK2 inhibition with the βARKct not only in chronic HF but also potentially in acute ischemic injury conditions.Circulation Research 10/2010; 107(9):1140-9. · 11.86 Impact Factor - [show abstract] [hide abstract]
ABSTRACT: Myocardial infarction (MI) leads to heart failure (HF) and premature death. The respective roles of myocyte death and depressed myocyte contractility in the induction of HF after MI have not been clearly defined and are the focus of this study. We developed a mouse model in which we could prevent depressed myocyte contractility after MI and used it to test the idea that preventing depression of myocyte Ca(2+)-handling defects could avert post-MI cardiac pump dysfunction. MI was produced in mice with inducible, cardiac-specific expression of the β2a subunit of the L-type Ca(2+) channel. Myocyte and cardiac function were compared in control and β2a animals before and after MI. β2a myocytes had increased Ca(2+) current; sarcoplasmic reticulum Ca(2+) load, contraction and Ca(2+) transients (versus controls), and β2a hearts had increased performance before MI. After MI, cardiac function decreased. However, ventricular dilation, myocyte hypertrophy and death, and depressed cardiac pump function were greater in β2a versus control hearts after MI. β2a animals also had poorer survival after MI. Myocytes isolated from β2a hearts after MI did not develop depressed Ca(2+) handling, and Ca(2+) current, contractions, and Ca(2+) transients were still above control levels (before MI). Maintaining myocyte contractility after MI, by increasing Ca(2+) influx, depresses rather than improves cardiac pump function after MI by reducing myocyte number.Circulation Research 09/2010; 107(6):800-9. · 11.86 Impact Factor - [show abstract] [hide abstract]
ABSTRACT: Hypertension occurs with higher prevalence and morbidity in black Americans compared with other groups. Alterations in the signal transduction pathways of 7-transmembrane spanning receptors are found in hypertensive patients. G protein-coupled receptor kinases (GRKs) play an important role in regulating this receptor signaling. The 2 most abundantly expressed GRKs in the cardiovascular system are GRK2 and GRK5, and each has unique substrates. Understanding changes in expression may give us insight into activated receptors in the pathophysiological progression of hypertension. In heart failure and white hypertensives, increased GRK2 expression arises because of neurohormonal stimulation of particular receptors. GRK2 subsequently desensitizes specific receptors, including beta-adrenergic receptors. In blood pressure control, beta-adrenergic receptor desensitization could lead to increased blood pressure. GRK2 and GRK5 mRNA were evaluated in lymphocytes of black Americans via quantitative real-time PCR. GRK2 mRNA expression directly correlated with systolic blood pressure and norepinephrine levels. GRK2 was elevated >30% among those with systolic blood pressure > or =130 mm Hg. No significant correlation between GRK5 mRNA expression and blood pressure or catecholamines was observed. Diabetic status, age, sex, and body mass index were also compared with GRK2 expression using univariate and multivariate analyses. GRK2 protein expression was elevated 2-fold in subjects with higher blood pressure, and GRK activity was increased >40%. Our data suggest that GRK2, but not GRK5, is correlated with increasing blood pressure in black Americans. Understanding the receptors stimulated by increased neurohormonal activation may give insight into the pathophysiology of hypertension in this at-risk population.Hypertension 07/2009; 54(1):71-6. · 6.87 Impact Factor - [show abstract] [hide abstract]
ABSTRACT: Chronic ventricular pressure overload states, such as hypertension, and elevated levels of neurohormones (norepinephrine, angiotensin II, endothelin-1) initiate cardiac hypertrophy and dysfunction and share the property of being able to bind to Gq-coupled 7-transmembrane receptors. The goal of the current study was to determine the role of endogenous cardiac myocyte Gq signaling and its role in cardiac hypertrophy and dysfunction during high blood pressure (BP). We induced renal artery stenosis for 8 weeks in control mice and mice expressing a peptide inhibitor of Gq signaling (GqI) using a 2 kidney, 1 clip renal artery stenosis model. 8 weeks following chronic high BP, control mice had cardiac hypertrophy and depressed function. Inhibition of cardiomyocyte Gq signaling did not reverse cardiac hypertrophy but attenuated increases in a profile of cardiac profibrotic genes and genes associated with remodeling. Inhibition of Gq signaling also attenuated the loss of cardiac function. We determined that Gq signaling downstream of angiotensin II receptor stimulation negatively impacted beta-adrenergic receptor (AR) responses and inhibition of Gq signaling was sufficient to restore betaAR-mediated responses. Therefore, in this study we found that Gq signaling negatively impacts cardiac function during high BP. Specifically, we found that inhibition of AT1-Gq signaling augmented betaAR mediated effects in a renal artery stenosis model of hypertension. These observations may underlie additional, beneficial effects of angiotensinogen converting enzyme (ACE) inhibitors and angiotensin receptor antagonists observed during times of hemodynamic stress.Journal of Molecular and Cellular Cardiology 10/2008; 46(1):100-7. · 5.15 Impact Factor - [show abstract] [hide abstract]
ABSTRACT: G protein-coupled receptor (GPCR) kinases (GRKs) are critical regulators of cellular signaling and function. In cardiomyocytes, GRK2 and GRK5 are two GRKs important for myocardial regulation, and both have been shown to be up-regulated in the dysfunctional heart. We report that increased levels and activity of GRK5 in failing myocardium may have unique significance due to its nuclear localization, a property not shared by GRK2. We find that transgenic mice with elevated cardiac GRK5 levels have exaggerated hypertrophy and early heart failure compared with control mice after pressure overload. This pathology is not present in cardiac GRK2-overexpressing mice or in mice with overexpression of a mutant GRK5 that is excluded from the nucleus. Nuclear accumulation of GRK5 is enhanced in myocytes after aortic banding in vivo and in vitro in myocytes after increased G alpha q activity, the trigger for pressure-overload hypertrophy. GRK5 enhances activation of MEF2 in concert with Gq signals, demonstrating that nuclear localized GRK5 regulates gene transcription via a pathway critically linked to myocardial hypertrophy. Mechanistically, we show that this is due to GRK5 acting, in a non-GPCR manner, as a class II histone deacetylase (HDAC) kinase because it can associate with and phosphorylate the myocyte enhancer factor-2 repressor, HDAC5. Moreover, significant HDAC activity can be found with GRK5 in the heart. Our data show that GRK5 is a nuclear HDAC kinase that plays a key role in maladaptive cardiac hypertrophy apparently independent of any action directly on GPCRs.Proceedings of the National Academy of Sciences 09/2008; 105(34):12457-62. · 9.74 Impact Factor - [show abstract] [hide abstract]
ABSTRACT: Hypertension is a prevalent condition in the developed world and disease severity is directly correlated with additional cardiovascular complications. It is estimated that 30% of the adult population in the United States has hypertension, which is classified as a systolic blood pressure > or =140 mmHg and/or a diastolic blood pressure > or =90 mmHg. A prolonged increase in afterload ultimately leads to congestive heart failure in the majority of cases. Currently, medication designed to treat hypertension is inadequate, thus new therapies need to be explored. Blood pressure is tightly regulated by blood vessel radius, which is established by hormones and/or peptides binding to GPCRs (G-protein-coupled receptors). Catecholamines and peptide hormones, such as AngII (angiotensin II), are elevated in hypertension and, therefore, signalling by these GPCRs is increased. Their signalling is tightly controlled by a class of proteins, the GRKs (GPCR kinases). Elevated levels of either GRK2 or GRK5 in both the lymphocytes and VSM (vascular smooth muscle) are associated with human hypertension and animal models of the disease. The focus of the present review is on the role GRKs, and their regulation of GPCRs, play in high blood pressure.Clinical Science 09/2008; 115(3):79-89. · 4.86 Impact Factor - [show abstract] [hide abstract]
ABSTRACT: G protein-coupled receptor kinase 2 (GRK2) is a serine/theorinine kinase that phosphorylates and desensitizes agonist-bound G protein-coupled receptors. GRK2 is increased in expression and activity in lymphocytes and vascular smooth muscle (VSM) in human hypertension and animal models of the disease. Inhibition of GRK2 using the carboxyl-terminal portion of the protein (GRK2ct) has been an effective tool to restore compromised beta-adrenergic receptor (AR) function in heart failure and improve outcome. A well-characterized dysfunction in hypertension is attenuation of betaAR-mediated vasodilation. Therefore, we tested the role of inhibition of GRK2 using GRK2ct or VSM-selective GRK2 gene ablation in a renal artery stenosis model of elevated blood pressure (BP) [the two-kidney, one-clip (2K1C) model]. Use of the 2K1C model resulted in a 30% increase in conscious BP, a threefold increase in plasma norepinephrine levels, and a 50% increase in VSM GRK2 mRNA levels. BP remained increased despite VSM-specific GRK2 inhibition by either GRK2 knockout (GRK2KO) or peptide inhibition (GRK2ct). Although betaAR-mediated dilation in vivo and in situ was enhanced, alpha(1)AR-mediated vasoconstriction was also increased. Further pharmacological experiments using alpha(1)AR antagonists revealed that GRK2 inhibition of expression (GRK2KO) or activity (GRK2ct) enhanced alpha(1D)AR vasoconstriction. This is the first study to suggest that VSM alpha(1D)ARs are a GRK2 substrate in vivo.AJP Heart and Circulatory Physiology 09/2008; 295(4):H1695-704. · 3.63 Impact Factor - [show abstract] [hide abstract]
ABSTRACT: Abnormal L-type Ca(2+) channel (LTCC, also named Cav1.2) density and regulation are important contributors to depressed contractility in failing hearts. The LTCC agonist BAY K 8644 (BAY K) has reduced inotropic effects on failing myocardium. We hypothesized that BAY K effects on the LTCC current (I(CaL)) in failing myocytes would be reduced because of increased basal activity. Since support of the failing heart with a left ventricular assist device (LVAD) improves contractility and adrenergic responses, we further hypothesized that BAY K effects on I(CaL) would be restored in LVAD-supported failing hearts. We tested our hypotheses in human ventricular myocytes (HVMs) isolated from nonfailing (NF), failing (F), and LVAD-supported failing hearts. We found that 1) BAY K had smaller effects on I(CaL) in F HVMs compared with NF HVMs; 2) BAY K had diminished effects on I(CaL) in NF HVM pretreated with isoproterenol (Iso) or dibutyryl cyclic AMP (DBcAMP); 3) BAY K effects on I(CaL) in F HVMs pretreated with acetylcholine (ACh) were normalized; 4) Iso had no effect on NF HVMs pretreated with BAY K; 5) BAY K effects on I(CaL) in LVAD HVMs were similar to those in NF HVMs; 6) BAY K effects were reduced in LVAD HVMs pretreated with Iso or DBcAMP; 7) Iso had no effect on I(CaL) in LVAD HVMs pretreated with BAY K. Collectively, these results suggest that the decreased BAY K effects on LTCC in F HVMs are caused by increased basal channel activity, which should contribute to abnormal contractility reserve.AJP Heart and Circulatory Physiology 06/2008; 294(5):H2257-67. · 3.63 Impact Factor - [show abstract] [hide abstract]
ABSTRACT: S100A1, a Ca(2+)-binding protein of the EF-hand type, is known to modulate sarcoplasmic reticulum Ca(2+) handling in skeletal muscle and cardiomyocytes. Recently, S100A1 has been shown to be expressed in endothelial cells (ECs). Because intracellular Ca(2+) ([Ca(2+)](i)) transients can be involved in important EC functions and endothelial NO synthase activity, we sought to investigate the impact of endothelial S100A1 on the regulation of endothelial and vascular function. Thoracic aortas from S100A1 knockout mice (SKO) showed significantly reduced relaxation in response to acetylcholine compared with wild-type vessels, whereas direct vessel relaxation using sodium nitroprusside was unaltered. Endothelial dysfunction attributable to the lack of S100A1 expression could also be demonstrated in vivo and translated into hypertension of SKO. Mechanistically, both basal and acetylcholine-induced endothelial NO release of SKO aortas was significantly reduced compared with wild type. Impaired endothelial NO production in SKO could be attributed, at least in part, to diminished agonist-induced [Ca(2+)](i) transients in ECs. Consistently, silencing endothelial S100A1 expression in wild type also reduced [Ca(2+)](i) and NO generation. Moreover, S100A1 overexpression in ECs further increased NO generation that was blocked by the inositol-1,4,5-triphosphate receptor blocker 2-aminoethoxydiphenylborate. Finally, cardiac endothelial S100A1 expression was shown to be downregulated in heart failure in vivo. Collectively, endothelial S100A1 critically modulates vascular function because lack of S100A1 expression leads to decreased [Ca(2+)](i) and endothelial NO release, which contributes, at least partially, to impaired endothelium-dependent vascular relaxation and hypertension in SKO mice. Targeting endothelial S100A1 expression may, therefore, be a novel therapeutic means to improve endothelial function in vascular disease or heart failure.Circulation Research 05/2008; 102(7):786-94. · 11.86 Impact Factor - [show abstract] [hide abstract]
ABSTRACT: A salient characteristic of dysfunctional myocardium progressing to heart failure is an upregulation of the adenylyl cyclase inhibitory guanine nucleotide (G) protein alpha subunit, G alpha(i2). It has not been determined conclusively whether increased Gi activity in the heart is beneficial or deleterious in vivo. Gi signaling has been implicated in the mechanism of cardioprotective agents; however, no in vivo evidence exists that any of the G alpha subunits are cardioprotective. We have created a novel molecular tool to specifically address the role of Gi proteins in normal and dysfunctional myocardium. We have developed a class-specific Gi inhibitor peptide, GiCT, composed of the region of G alpha(i2) that interacts specifically with G protein-coupled receptors. GiCT inhibits Gi signals specifically in vitro and in vivo, whereas Gs and Gq signals are not affected. In vivo expression of GiCT in transgenic mice effectively causes a "functional knockout" of cardiac G alpha(i2) signaling. Inducible, cardiac-specific GiCT transgenic mice display a baseline phenotype consistent with nontransgenic mice. However, when subjected to ischemia/reperfusion injury, GiCT transgenic mice demonstrate a significant increase in infarct size compared with nontransgenic mice (from 36.9+/-2.5% to 50.9+/-4.3%). Mechanistically, this post-ischemia/reperfusion phenotype includes increased myocardial apoptosis and resultant decreased contractile performance. Overall, our results demonstrate the in vivo utility of GiCT to dissect specific mechanisms attributed to Gi signaling in stressed myocardium. Our results with GiCT indicate that upregulation of G alpha(i2) is an adaptive protective response after ischemia to shield myocytes from apoptosis.Circulation 04/2008; 117(11):1378-87. · 15.20 Impact Factor - [show abstract] [hide abstract]
ABSTRACT: More than 30% of the US population has high blood pressure (BP), and less than a third of people treated for hypertension have it controlled. In addition, the etiology of most high BP is not known. Having a better understanding of the mechanisms underlying hypertension could potentially increase the effectiveness of treatment. Because G(q) signaling mediates vasoconstriction and vascular function can cause BP abnormalities, we were interested in determining the role of vascular smooth muscle (VSM) G(q) signaling in two divergent models of hypertension: a renovascular model of hypertension through renal artery stenosis and a genetic model of hypertension using mice with VSM-derived high BP. Inhibition of VSM G(q) signaling attenuated BP increases induced by renal artery stenosis to a similar extent as losartan, an ANG II receptor blocker and current antihypertensive therapy. Inhibition of G(q) signaling also attenuated high BP in our genetic VSM-derived hypertensive model. In contrast, BP remained elevated 25% following treatment with losartan, and prazosin, an alpha(1)-adrenergic receptor antagonist, only decreased BP by 35%. Inhibition of G(q) signaling attenuated VSM reactivity to ANG II and resulted in a 2.4-fold rightward shift in EC(50). We also determined that inhibition of G(q) signaling was able to reverse VSM hypertrophy in the genetic VSM-derived hypertensive model. These results suggest that G(q) signaling is an important signaling pathway in two divergent models of hypertension and, perhaps, optimization of antihypertensive therapy could occur with the identification of particular G(q)-coupled receptors involved.AJP Heart and Circulatory Physiology 12/2007; 293(5):H3072-9. · 3.63 Impact Factor - [show abstract] [hide abstract]
ABSTRACT: Calcineurin, a Ca(2+)-regulated protein phosphatase, links myocardial Ca(2+) signaling with hypertrophic gene transcription. Calcineurin abundance increases in pressure-overload hypertrophy and may reduce agonist-mediated phospholamban (PLB) phosphorylation to underlie blunted beta-adrenergic receptor (beta-AR) responsiveness in hypertension. This hypothesis was tested by measuring the effects of calcineurin inhibition on changes in cardiac contractility caused by beta-adrenergic stimulation in spontaneously hypertensive rats (SHR). Female SHR (age: 7 mo) and age-matched female Wistar-Kyoto rats (WKY) were studied. Heart weight-to-body weight ratio (P < 0.01) and systolic blood pressure (P < 0.01) were greater in SHR compared with WKY and were associated with increased myocardial calcineurin mRNA (CnAbeta) and activity (P < 0.05). beta-AR stimulation with isoproterenol (Iso) increased calcineurin activity (P < 0.05) in both WKY and SHR hearts, and this activity was suppressed with cyclosporin A (CsA) treatment. In SHR, CsA improved left ventricular whole heart and isolated myocyte beta-AR responsiveness by normalizing PLB phosphorylation at Ser(16) and Thr(17) (P < 0.05). These CsA-induced, PLB-mediated effects were associated with an augmentation in cardiomyocyte peak Ca(2+) and a reduced rate (time constant of isovolumic pressure relaxation, tau) and magnitude of diastolic Ca(2+) during beta-AR stimulation. In conclusion, CsA normalized the blunted beta-AR responsiveness associated with hypertension, in part, by mitigating calcineurin activity while improving PLB phosphorylation and subsequent sarcoplasmic reticulum Ca(2+) regulation.AJP Heart and Circulatory Physiology 11/2007; 293(5):H3122-9. · 3.63 Impact Factor - [show abstract] [hide abstract]
ABSTRACT: Recent studies suggest that rather than being terminally differentiated, the adult heart is a self-renewing organ with the capacity to generate new myocytes from cardiac stem/progenitor cells (CS/PCs). This study examined the hypotheses that new myocytes are generated during adolescent growth, to increase myocyte number, and these newly formed myocytes are initially small, mononucleated, proliferation competent, and have immature properties. Ventricular myocytes (VMs) and cKit(+) (stem cell receptor) CS/PCs were isolated from 11- and 22-week feline hearts. Bromodeoxyuridine incorporation (in vivo) and p16(INK4a) immunostaining were measured to assess myocyte cell cycle activity and senescence, respectively. Telomerase activity, contractions, Ca(2+) transients, and electrophysiology were compared in small mononucleated (SMMs) and large binucleated (LBMs) myocytes. Heart mass increased by 101% during adolescent growth, but left ventricular myocyte volume only increased by 77%. Most VMs were binucleated (87% versus 12% mononucleated) and larger than mononucleated myocytes. A greater percentage of SMMs was bromodeoxyuridine positive (SMMs versus LBMs: 3.1% versus 0.8%; P<0.05), and p16(INK4a) negative and small myocytes had greater telomerase activity than large myocytes. Contractions and Ca(2+) transients were prolonged in SMMs versus LBMs and Ca(2+) release was disorganized in SMMs with reduced transient outward current and T-tubule density. The T-type Ca(2+) current, usually seen in fetal/neonatal VMs, was found exclusively in SMMs and in myocytes derived from CS/PC. Myocyte number increases during adolescent cardiac growth. These new myocytes are initially small and functionally immature, with patterns of ion channel expression normally found in the fetal/neonatal period.Circulation Research 03/2007; 100(4):536-44. · 11.86 Impact Factor - [show abstract] [hide abstract]
ABSTRACT: Hypertrophy and failure (H/F) in humans and large mammals are characterized by a change from a positive developed force-frequency relationship (+FFR) in normal myocardium to a flattened or negative developed force-frequency relationship (-FFR) in disease. Altered Ca(2+) homeostasis underlies this process, but the role of intracellular Na(+) concentration ([Na(+)](i)) in H/F and frequency-dependent contractility reserve is unclear. We hypothesized that altered [Na(+)](i) is central to the -FFR response in H/F feline myocytes. Aortic constriction caused left ventricular hypertrophy (LVH). We found that as pacing rate was increased, contraction magnitude was maintained in isolated control myocytes (CM) but decreased in LVH myocytes (LVH-M). Quiescent LVH-M had higher [Na(+)](i) than CM (LVH-M 13.3 +/- 0.3 vs. CM 8.9 +/- 0.2 mmol/l; P < 0.001) with 0.5-Hz pacing (LVH-M 14.9 +/- 0.5 vs. CM 10.8 +/- 0.4 mmol/l; P < 0.001) but were not different at 2.5 Hz (17.0 +/- 0.7 vs. control 16.0 +/- 0.7 mmol/l; not significant). [Na(+)](i) was altered by patch pipette dialysis to define the effect of [Na(+)](i) on contraction magnitude and action potential (AP) wave shape at slow and fast pacing rates. Using AP clamp, we showed that LVH-M require increased [Na(+)](i) and long diastolic intervals to maintain normal shortening. Finally, we determined the voltage dependence of contraction for Ca(2+) current (I(Ca))-triggered and Na(+)/Ca(2+) exchanger-mediated contractions and showed that there is a greater [Na(+)](i) dependence of contractility in LVH-M. These data show that increased [Na(+)](i) is essential for maintaining contractility at slow heart rates but contributes to small contractions at fast rates unless rate-dependent AP shortening is prevented, suggesting that altered [Na(+)](i) regulation is a critical contributor to abnormal contractility in disease.AJP Heart and Circulatory Physiology 02/2007; 292(2):H1129-38. · 3.63 Impact Factor - Journal of Cardiac Failure - J CARD FAIL. 01/2007; 13(6).
- Journal of Cardiac Failure - J CARD FAIL. 01/2007; 13(6).
- [show abstract] [hide abstract]
ABSTRACT: Physiological hemodynamic stress, such as aerobic exercise, is intermittent and requires an increase in Ca2+ -dependent contractility through sympathetic nervous system activation. Pathological hemodynamic stress, such as hypertension, is persistent and requires sustained increases in cardiac function. Over time, this causes left ventricular hypertrophy (LVH)-reduced responsiveness to sympathetic stimulation. In this study, we examined the hypothesis that blunted in vivo adrenergic contractile responsiveness in pressure overload (PO)-induced cardiac hypertrophy is caused by abnormalities in the abundance and/or basal phosphorylation state of Ca2+ regulatory proteins. PO, induced by aortic constriction, caused concentric LVH or dilated LVH. Only animals with dilation exhibited a decrease in baseline left ventricle function [fractional area change (FAC); measured with echocardiography]. All PO animals had a reduced contractile response to adrenergic agonists (increase in FAC with 40 microg.kg(-1).min(-1) dobutamine, control 0.30 +/- 0.04, n = 5 vs. banded 0.10 +/- 0.03, n = 10; P < 0.01). PO animals had reduced phospholamban (PLB) protein abundance (P = 0.07, not significant) and increased PLB phosphorylation at the calmodulin-dependent kinase II (CaMKII)-specific site (PLB-Thr17, P < 0.05) but not at the protein kinase A-specific site (PLB-Ser16). PLB-Thr17 phosphorylation was inversely correlated with dobutamine-induced increases in contractility in PO animals (r2 = 0.81, P < 0.05). Continuous induction of Ca2+ transients in isolated ventricular myocytes for 24 h increased phosphorylation at PLB-Thr17 and diminished inotropic responsiveness and PLB-Ser16 phosphorylation after exposure to isoproterenol (P < 0.05). These data show that reduced adrenergic responsiveness in feline PO hypertrophy and failure involves increases in basal PLB-Thr17 phosphorylation, suggesting that activation of CaMKII in PO hypertrophy contributes to defective adrenergic reserve in compensated LVH and early heart failure.AJP Heart and Circulatory Physiology 07/2006; 291(1):H61-70. · 3.63 Impact Factor -
Article: Galphaq and its Aktions.
Journal of Molecular and Cellular Cardiology 06/2006; 40(5):589-92. · 5.15 Impact Factor - [show abstract] [hide abstract]
ABSTRACT: Bacterial diarrheagenic heat-stable enterotoxins induce colon cancer cell cytostasis by targeting guanylyl cyclase C (GCC) signaling. Anticancer actions of these toxins are mediated by cyclic guanosine 3',5'-monophosphate (cGMP)-dependent influx of Ca2+ through cyclic nucleotide-gated channels. However, prolonged stimulation of GCC produces resistance in tumor cells to heat-stable enterotoxin-induced cytostasis. Resistance reflects rapid (tachyphylaxis) and slow (bradyphylaxis) mechanisms of desensitization induced by cGMP. Tachyphylaxis is mediated by cGMP-dependent protein kinase, which limits the conductance of cyclic nucleotide-gated channels, reducing the influx of Ca2+ propagating the antiproliferative signal from the membrane to the nucleus. In contrast, bradyphylaxis is mediated by cGMP-dependent allosteric activation of phosphodiesterase 5, which shapes the amplitude and duration of heat-stable enterotoxin-dependent cyclic nucleotide accumulation required for cytostasis. Importantly, interruption of tachyphylaxis and bradyphylaxis restores cancer cell cytostasis induced by heat-stable enterotoxins. Thus, regimens that incorporate cytostatic bacterial enterotoxins and inhibitors of cGMP-mediated desensitization offer a previously unrecognized therapeutic paradigm for treatment and prevention of colorectal cancer.Cancer Research 01/2006; 65(23):11129-35. · 8.65 Impact Factor
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Thomas Jefferson University
- • Center for Translational Medicine
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Philadelphia, Pennsylvania, United States
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- • Independence Blue Cross Cardiovascular Research Center (CVRC)
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Duke University Medical Center
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Durham, NC, United States


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M&A Roundup: KentuckyOne Health forms $1.4B JOA
The healthcare sector got a little more concentrated last week with the announcement out of Louisville that University Hospital and James Graham Brown Cancer Center have signed a joint operating agreement with KentuckyOne Health.
Officials say KentuckyOne Health will invest about $1.4 billion in infrastructure improvements, research, and program development over the next 20 years.
The joint announcement was made by leaders from the University of Louisville and University Medical Center, which are the parent organizations for University Hospital and the Brown Cancer Center, and from KentuckyOne Health.
"Our Joint Operating Agreement ensures that we not only maintain our current academic and medical services, but that we have the financial resources and statewide network to continue to expand and innovate those services for the future," UMC President and CEO Jim Taylor said in prepared remarks. "This venture will put us at the forefront in our field to create an aligned organization that has both the breadth and depth to address the coming challenges of healthcare reform."
Comments are moderated. Please be patient.
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