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Labyrinth (Anniversary Edition) (Sous-titres français) [Import]
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Relive the magic! This newly restored, 2-disc anniversary edition of Jim Henson's LABYRINTH contains an all-new commentary and bonus features that are guaranteed to captivate as never before. David Bowie and Jennifer Connelly invite you into a magical universe where nothing is what it seems! Babysitting infant stepbrother Toby on a weekend night isn't young Sarah's (Connelly) idea of fun. Frustrated by his crying, she secretly imagines the Goblins from her favorite book, LABYRINTH, carrying Toby away. When her fantasy comes true, a distraught Sarah must enter a maze of illusion to bring Toby back from a kingdom inhabited by mystical creatures and governed by the wicked Goblin King (Bowie).
Sarah (a teenage Jennifer Connelly) rehearses the role of a fairy-tale queen, performing for her stuffed animals. She is about to discover that the time has come to leave her childhood behind. In real life she has to baby-sit her brother and contend with parents who don't understand her at all. Her petulance leads her to call the goblins to take the baby away, but when they actually do, she realizes her responsibility to rescue him. Sarah negotiates the Labyrinth to reach the City of the Goblins and the castle of their king. The king is the only other human in the film and is played by a glam-rocking David Bowie, who performs five of his songs. The rest of the cast are puppets, a wonderful array of Jim Henson's imaginative masterpieces. Henson gives credit to children's author and illustrator Maurice Sendak, and the creatures in the movie will remind Sendak fans of his drawings. The castle of the king is a living M.C. Escher set that adults will enjoy. The film combines the highest standards of art, costume, and set decoration. Like executive producer George Lucas's other fantasies, Labyrinth mixes adventure with lessons about growing up. --Lloyd Chesley --This text refers to an out of print or unavailable edition of this title.
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This edition has quite a number of excellent special features. All the featurettes are excellent and are a half-hour or longer (where most DVDs have 15 segments). There is lots to learn about how the puppets were done, technical contruction, casting, writing, etc. Full of interesting tidbits for the die-hard Labyrinth fan.
The commentary with Brian Froud is entertaining and despite Froud having to carry the commentary by himself, he keeps the viewer engaged as he reminisces about the film and tells cute stories. Plus he has a very jovial voice and truly loved making the film, which helps alot.
My one critique is the lack of reflection from Jennifer Connelly and David Bowie. Playing the two main characters (and certainly two very defining ones in my childhood) I was hoping for a commentary with the two of them. Sadly I was disappointed.
It would be BRILLIANT if in the next issue of this movie they included a commentary from them - together. I am eager to hear from both their perspectives on this AMAZING film.
And Sony, I PROMISE I will purchase the release! You have my word.
Beautiful film, beautiful transfer, excellent special features (though lacking Connelly and Bowie).
The world of the Labyrinth world was what I found so creepy as a child, as an adult I appreciated how Henson created such an atmosphere. Like with many Henson shows, this movie combines muppets and live actors. The best part of the movie by far is the music. This movie was actually my first introduction to David Bowie and the lyrics/ music he created for this soundtrack should have been given more credit. Some of the most well known singles include "Magic Dance", "As the world falls down" and "within you", they have spectacular lyrics and music and fit perfectly into the movie although could be singles on their own.
Jeniffer Conolly is superp as Sarah, and David Bowie even more superb as Jareth, The Goblin King. The casting couldn't have been more perfect, as both artists became legends in their own right in that their appeal has lasted through the decades, and so, has the film. It remains a cult classic.
If anything, the lack of special effects has made it's appeal even more undeniable, as it cannot be dated. Too many times has it occured with films that as speical effects develop, the films lose their appeal. As the film relies on the fantastic nature of not only the genre, but the spectacular muppetry, the film retains it's beauty, despite it's simplistic cinematics...
A must see for all lovers of the fantsy genre...and of course Jim Henson or David Bowie fans...
The story centres around Sarah, a teenager, who resents her stepmother and Toby, her baby stepbrother and 'wishes' for the goblins to take him away. When they do Sarah finds herself journeying through the labyrinth of the goblin king (Bowie) in order to save him.
She befriends an assortment of creatures such as Hoggle, a grumpy dwarf type being and Ludo, a massive, hairy beast who has a gentle nature. They accompany and help Sarah on her way to the goblin king's castle where Toby is being held.
Jim Hensons workshop has worked it's usual magic and the film is littered with songs written and performed by David Bowie.
This film is pure entertainment for any age group, well worth watching.
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malheureusement seulement en espagnol et en anglais alors que j`ai vu ce film en français avant.Published 2 months ago by Client d'Amazon
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GOS Awardee Casa Libre en la Solana – Lidia Yuknavitch at the Fair Weather Reading Series, photo by Michael Dauphinais
The Tucson Pima Arts Council is pleased to announce its General Operating Support (GOS) Awardees for FY 2015-2016. Thirty local non-profit arts and cultural organizations received funding to support their ongoing contributions to the quality of life in the city. A total of $130,000 total were allocated through a highly competitive application process.
GOS 2015-2016 Awardees

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text: Army's Top Sex Assault Prosecutor Accused of Sexual Assault, SuspendedTaylor Berman3/06/14 4:40pmFiled to: armysexual assault1371EditInvite manuallyPromoteDismissUndismissHideShare to KinjaToggle Conversation toolsGo to permalink Last month, the Army prosecutor in charge of investigating sexual assault cases was reportedly suspended after a subordinate accused him of sexually assaulting her at a legal conference two years ago.Lt. Col. Joseph "Jay" Morse supervised more than 20 Army special victim prosecutors—the lawyers in charge of prosecuting sexual abuse cases, as well as domestic and child abuse cases—before he was suspended in February, according to Stars and Stripes. Sources told Stars and Stripes that the Army lawyer alleged that Morse attempted to kiss and grope her against her will. The alleged assault reportedly took place in a hotel room at a 2011 sexual assault legal conference attended by special victims prosecutors in Alexandria, Va., before he was appointed as chief of the Trial Counsel Assistance Program.The lawyer reported the incident in mid-February and Morse was suspended shortly thereafter, according to one source. "We can confirm that this matter is currently under investigation and that the individual in question has been suspended from duties pending the outcome of the investigation," an Army official who wasn't authorized to speak publicly told Stars and Stripes. "Given that this is still an open case, we are precluded from providing any additional information at this point." Advertisement This marks the third time in nine months a military officer in charge of sexual assault prevention has been accused of sexual assault: In May, the head of the Air Force's Sexual Assault Prevention and Response Program was arrested for sexual assault. Just eight days later, the Army sergeant in charge of sexual assault prevention at Ft. Hood was investigated on sexual assault charges, including allegations that he forced subordinates into prostitution. [h/t Mediaite/Image via AP] Sponsored Reply137 repliesLeave a reply


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Governor's Executive Orders
MoDOT Transportation Library
WHEREAS, the State of Missouri has been severely impacted by high winds, floodwater and severe storms; and
WHEREAS, on or about April 29, 1996, the Governor of the State of Missouri declared a State of Emergency existed in the State of Missouri, pursuant to his authority under Chapter 44, RSMo; and
WHEREAS, the Missouri Department of Natural Resources is charged by law with protecting and enhancing the quality of Missouri's environment and with enforcing a variety of environmental rules and regulations; and
WHEREAS, in a prompt effort to respond to the emergency and also to expedite the cleanup and recovery, it is necessary to adjust certain environmental rules and regulations on a temporary and short-term basis.
NOW, THEREFORE, I, Mel Carnahan, Governor of the State of Missouri, by virtue of the authority vested in me by the Constitution and laws of the State of Missouri, do hereby issue the following order:
The Director of the Missouri Department of Natural Resources is vested with full discretionary authority to temporarily waive or suspend the operation of any statutory or administrative rule or regulation currently in place under his purview in order to best serve the interest of public health and safety during the period of the emergency and the subsequent recovery period. The authority granted by this Order shall remain in effect for the duration of the emergency.
[Rebecca McDowell Cook's signature]SECRETARY OF STATE
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600 West Main Street Jefferson City, MO 65101 Main Office: (573) 751-4936 firstname.lastname@example.com Branch Offices


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Main Entry: mono�logue Variant(s): also mono�log /'m�-n&l-"og, -"�g/Function: nounEtymology: Middle French monologue, from mon- + -logueDate: 15491 a : SOLILOQUY 2 b : a dramatic sketch performed by one actor c : the routine of a stand-up comic2 : a literary composition written in the form of a soliloquy3 : a long speech monopolizing conversation
So how's that Kingsway stock doinf for ya now!
The fact that you, personally, are agitated enough to respond is enough for me. I'm happy!


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Non Tech Project Manager III Location:. This person will work with a virtual team of sales, operations, technical, legal and marketing resources to transition...
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Direct/Manage/Supervise software quality analysts, technicians, and test engineers. May act as liaison between software developers and software quality analysts...
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III.*. We are looking for both entry level and experienced On-Line Marketing Analysts. The Online Marketing Analyst is responsible for executing, reporting and...


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by Lauren C. Williams Jul 4, 2016
Hundreds more were injured by a car bomb that coincided with the end of Ramadan.
by Laurel Raymond Jun 28, 2016
Turkey has been hit with 8 devastating attacks in the past year. This latest is on a major transit hub.
by Laurel Raymond Jun 7, 2016
Over 200 people have been killed in terrorist attacks in Turkey's main cities in the past year.
by Beenish Ahmed Mar 23, 2016
As ISIS loses ground in Iraq and Syria, some experts believe it'll focus more on attacks across Europe.
by Esther Yu-Hsi Lee Mar 22, 2016
It's always easy to blame refugees.
by Judd Legum Mar 22, 2016
A deadly attack in Belgium.
by Erica Hellerstein Mar 19, 2016
The explosion hit part of Istiklal Street, a long and busy street lined with cafes, shops, and restaurants.
by Justin Salhani Mar 18, 2016
All the attackers identified are European nationals.
by Beenish Ahmed & Laurel Raymond Mar 14, 2016
"We don't know when and where there will be another attack, but it's apparent now that they can't be prevented, and everyone is on edge."
by Beenish Ahmed Feb 18, 2016
French school administrators are being forced to decide if smoking outside -- and risking attack -- is a greater concern than smoking indoors.


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Fulfilling the Sustainable Development Goals and Paris Climate Agreement will depend on how they are translated into action by governments, and the extent to which they spur complementary action by actors like businesses, financial institutions, cities and the academic community. As a new WRI commentary explains, achieving both sets of objectives by 2030 will require more than just doing more of the same, faster. It will require new approaches and ways of doing business.
Insights: WRI's Blog
Insights offers WRI experts' timely analysis and commentary on crucial issues at the nexus of environment and human development.
For cross-post requests and other inquiries, please contact Online Editor Sarah Parsons.
Leading Topics
More and more companies are profiting through the "circular economy," or an economic model by which waste is not just avoided, but completely re-envisaged.
The Sustainable Development Goals aim to halve food waste by 2030, but there had been no consistent guidance on how to get there. The new Food Loss and Waste Accounting and Reporting Standard offers help.
Florida's Treasure Coast has turned toxic this summer, as a foul-smelling algae bloom resembling guacamole has made some of the Sunshine State's beaches untouchable. One cause is the controlled release of water from an over-full Lake Okeechobee into local rivers that flow east to the Atlantic and west to the Gulf of Mexico.
The Science-Based Targets initiative to cut corporate greenhouse gas emissions has met and exceeded its first goal, with more than 165 companies committed to use the best climate science to inform their carbon reduction decisions. SBTs are succeeding because they take the guesswork out of the process of shrinking businesses' carbon footprints.
The new Fire Risk Map on Global Forest Watch shows where dry conditions increase fire risk in Indonesia and Malaysia. The tool can help decision-makers take action to prevent forest fires before they ignite.
Making our infrastructure cleaner and more sustainable could add as little as 5 percent to upfront costs, which could be fully offset by lower operating costs. WRI Board member and former President of Mexico Felipe Calderón reveals four ways to unlock capital for low-carbon infrastructure.
Natural infrastructure, strategically managed natural and open spaces like forests or wetlands, can direct more clean water to cities by controlling water flows, preventing sediment buildup and absorbing pollutants before they flow into waterways.
People watched closely when China launched the Asian Infrastructure Investment Bank (AIIB) last year, with a mandate to be "lean, clean and green." After its first annual general meeting and seminars this week, it appears that the AIIB is starting to move in a positive direction.
Leaders of the United States, Mexico and Canada heralded a new phase in continent-wide collaboration on climate and energy at the June 29 North American Leadership Summit in Ottawa. For the first time, President Barack Obama, President Enrique Peña Nieto and Prime Minister Justin Trudeau have put together an aligned and comprehensive set of climate and energy priorities.


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Engine Mechanical problem
1988 Mercury Tracer 4 cyl Two Wheel Drive Automatic
I lost the valve keeper - that goes inside the valve spring.
Is this a universal part?
There aren't any other old Mercury Tracer's in our area.
Are there other types of vehicles that have the same part?
Thank you,
Gina Peters
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Friday, January 1st, 2010 AT 6:24 PM


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Dune series
Group DescriptionGames based on the Frank Herbert novels of the same name.
Cancelled Atari 2600 gameAtari began (and then terminated) development on a Dune game in 1984 for a film tie-in on the VCS (Atari 2600). Only an early prototype has surfaced, revealing a game not dissimilar to Warren Robinett's Adventure for the 2600.
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Game group created by Anonymous User, additional games added to group by Lance Boyle (1334), Rola (7766), Patrick Bregger (156079), Sciere (373759) and Foxhack (12623)
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An inverse remote-sensing procedure is presented for reconstructing the spatial waveform of the lightning return stroke current throughout a numerical-field synthesis procedure, based on working regularization methods. The approach uses as input data the acquisition of time-domain recordings of the electric and/or magnetic field generated by the lightning current, at various locations on the ground and converts these signals into harmonics by Fourier decomposition. This combination between the proposed solving procedures and harmonic filtering yields numerical results that are in good agreement with the testing functions.
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PLEASE READ THE DESCRIPTION! The Punch doesn't come in until 1:30 First I have background info until then. ...
PLEASE READ THE DESCRIPTION! The Punch doesn't come in until 1:30 First I have background info until then. I was laughing and enjoying it way too much. it was a lot better than dealing with the pain I experienced stretching my scar tissued ear. Don't get me wrong it hurt, but oddly I enjoyed it way too much. Hey, it's been 5 months since I got my left earlobe punched. and I've been a lot more careful about my stretching habits since my scaring problem. no scar tissue has reappeared since I did it. I had my ear punched at a 0. it was immediately stretched with a 00 taper. since then I've stretched my ears to 5/8" which is 4 sizes bigger than 00, but then I've gone down 3 sizes to 7/16" because of trying to stay somewhat professional for work purposes. 5/8" I also felt was just too large for my ears. ANYWAY. No scar tissue has resurfaced. a few things I would have liked to of done different though are: I would have preferred to have my left ear scalped instead of punched, so I wouldn't have lost any tissue. My right ear for the most part was fine, but If I had to again I think I would have punched both. I've taken them out and not had anything in my ear for days/weeks at a time. There is still a visible hole in my left ear, while my right ear has a small slit, instead of a gaping hole compared to my right ear. And if I were to bunch both ears, I would have punched them at the smallest size possible just to get rid of scar tissue. Because I can feel a difference when touching, and feeling the lower part of my lobes. Visibly you can't tell, but when feeling them you can. which can be detrimental to further stretching, or for your ears to close up. If you live in Florida, I HIGHLY recomend Shamrock tattoo.


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ATLANTIC CITY — As the state orchestrates an unprecedented intervention in Atlantic City's casino industry and government, Atlantic County officials have quietly been discussing their own strategies for running parts of the city.
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WASHINGTON, DC-In the last week of 2012 Cassidy Turley closed on a significant acquisition, its merger with CLW Real Estate Services Group in Tampa, GlobeSt.com has learned exclusively. Cassidy Turley and CLW were set to make the announcement internally Wednesday morning.
The combined firm will represent a major advance for Cassidy Turley in several markets, starting with, of course, CLW's home base of Tampa and the state of Florida, Cassidy Turley CEO Joe Stettinius tells GlobeSt.com. However, some 50% of CLW's activity is outside of Florida, giving Cassidy Turley valuable exposure to such markets as Boston, New York and Southern California. CLW counts about 18 or so national corporate accounts as well as another dozen of property management accounts in Florida. In addition, "the merger gives both firms the ability to provide better and broader service to clients and as well as providing us with the ability to provide better career opportunities," Stettinius says.
Terms of the deal are not public. CLW is now wholly owned by Cassidy Turley, and its shareholders are now shareholders in Cassidy Turley. CLW Principals Doug Rothschild and Lou Varsames will be executive managing directors, located in Cassidy Turley's newly expanded Tampa office, which will incorporate CLW's 20 brokerage professionals and approximately 100 total employees.
From CLW's perspective, Cassidy Turley's current trajectory made the deal a no brainer, Rothschild tells GlobeSt.com. "Cassidy Turley is in growth mode and we feel we can have an impact on that growth."
Also, Varsames notes, CLW's strong senior housing group is complementary to Cassidy Turley's own capital markets operation. Cassidy Turley has some senior housing capabilities on the West Coast and has been involved in certain transactions "episodically" in other markets, Stettinius says.
"This acquisition will provide us with leadership in the senior housing space," he says. CLW also has a strong property management portfolio—a space where Cassidy Turley is already very strong. Indeed, about half of its recurring revenues can be attributed to property and building management. In this case, Stettinius says, Cassidy Turley is not necessarily looking to just boost its recurring revenues but rather gain entrance to new markets. "For property management, the deal is more a growth story than it is about straight revenue," he says.


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|Mailing address:
|University of Alberta, Augustana Campus
|4901 46 Avenue
|Camrose, AB T4V 2R3
Dr. Mohr has completed his term as Chair of Science and is on leave for the 2015-16 academic year.
Check Digits
Generating Random Numbers in Sorted Order
Generating a Random Ordering of Numbers in Some Range
Computer music analysis/synthesis
Genetic algorithms, swarm intelligence, ant colony optimization
The University of Alberta's Augustana Campus enrolls about 1000 students in baccalaureate degree programs on a picturesque residential campus in the city of Camrose, 90 km southeast of Edmonton. Augustana is committed to building on its reputation for rigorous, high-quality teaching in the tradition of the liberal arts and sciences, and, in doing so, providing a distinctive undergraduate academic experience for students within one of Canada's leading universities.


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Listen to free music played by Jenny2485
Blip.fm is internet radio made social. It's easy to search for, play, and discover free music recommended by real people. Join today to create your own free station and start listening to @Jenny2485.
Jenny2485 Why this song is in my head right now I have no idea.
Heatwave – Boogie Nights| play
Kyle Hollingsworth – Way That It Goes| play
Jan 10, 2011 at 6:12 pm via YouTube | AMAZON | ITUNES
Childish Gambino – Fuck It All| play
Jan 5, 2011 at 8:45 pm via YouTube | AMAZON | ITUNES
AM – Leavenworth| play
Jenny2485 This popped into my head for some reason.


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#31 - freemonkeyballs
Reply +2(08/23/2013) [-]
Ok why is he kissing him on the lips though on the ellen show thats just awkward even if its your parent.
#45 to #31 - spankyy
Reply +3(08/23/2013) [-]
One of my closest friends kisses his father on the lips I believe, and his dad made a comment about how when he found it his father had terminal cancer it seemed so minor to worry about something as silly as kissing him on the lips. Some people just do it. They're your parents so I don't see the big deal, but I am a very calm, non-outwardly emotional guy, and my dad is the same way. So we don't do that, but I see it all the time.
#50 to #45 - trollchildxyMy dad used to kiss me on the head, until i got too tall... O ,oss ot/
Reply +4(08/23/2013) [-]
#51 to #50 - trollchildxy
Reply +1(08/23/2013) [-]
The last bit was supposed to say "I miss it."


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This Friday (25 November) sees the last LeftLion Presents of 2005 at the Malt Cross.
Over the course of the last year we have brought you performances from the likes of The Magic Heroes, The Silver Tongues, Computerman, The Henry Road and many more of the best upcoming acts from the Nottingham music scene.
This month, we have the indie riffs of Love Ends Disaster (lead singer Matt is pictured left), who cite Sonic Youth and The Flaming Lips among their influences. Also along for the ride are the sonic wall that is Public Display of Affection, who we think sound a bit like a Rocks-era Primal Scream crossed with Spiritualised. Brendan Randall (dead_fly) will be on the decks.
Not only that, but we also have a magic show from Jack Curtis. Like a teenage Tommy Cooper, Jack is one of the latest products of the Nottingham-based Central drama school, which has seen the likes of Hollywood starlet Samantha Morton (...and the guy who played Peter Barlow in Corro) tread it's boards.
We're not doing a LeftLion Presents at the Malt Cross in December and in the new year we'll be changing the format and dates of our events to launch LeftLion Unplugged. This will be a new acoustic night featuring the best of local musical talent and we're currently looking for acts to book. If you'd like to put yourself forward please email email@example.com
So, if you've always wanted to make it to a LeftLion night at one of the best venues in Nottingham, this is your last chance for this year. It's the usual deal. Doors from 7pm. Music and magic starts at 8.45pm. Entrance is Free! Get there early if you want a table…
LeftLion Presents at the Malt Cross - 7-11pm Friday 25 November 2005
Last LeftLion Presents of 2005
Come and join us at the last LeftLion Presents of 2005
This Friday (25 November) sees the last LeftLion Presents of 2005 at the Malt Cross.
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Event Listings
The Portland Miniatures 20/03
Venue: The Harley Gallery
Ends: 31/08/16
Price: Free
Intersections, commission #3 Emma Smith 01/04
Venue: Primary
Ends: 28/02/17
Venue: Filthy's Nottingham
Ends: 19/12/16
Price: 1 Class - £5 / £4, 2 Classes - £8 / £6
Samba dance (14+) medium to high impact 19/04
Venue: City Arts - Nottingham
Ends: 19/04/20
Price: £5 in advance £30 for 6 weeks, £7 OTD
Grand Tourists and Others: Travelling Abroad Before the 20th Century 29/04
Venue: Weston Gallery
Ends: 07/08/16
Price: Free
Exhibition: Grand Tourists and Others: Travelling Abroad before the Twentieth Century 29/04
Venue: Lakeside Arts Centre
Ends: 07/08/16
Price: Admission Free
Maxine Hunt 09/06
Venue: Patchings Art Centre
Ends: 31/07/16
Sarah Danays' Arms of the Portland Vase 18/06
Venue: The Harley Gallery
Ends: 14/08/16
Price: Free
Made in China by Clare Twomey 18/06
Venue: The Harley Gallery
Ends: 14/08/16
Price: Free


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Cotswold Wildlife Park has a series of events – take a look at what we've got planned over the next few months below.
July 23rd - August 21st 2016
Cotswold Falconry Flying Displays
Cotswold Falconry Flying Displays will be at the Park every weekend from 23rd July through to 21st August including the August Bank Holiday weekend.
August 1st - August 31st 2016
Rhino Month
Our keepers will be doing a daily talk throughout August at 2pm near the Rhino Paddock about these magnificent animals, the threats and the conservation work that is going on to try and protect them for future generations.
August 6th - August 7th 2016
Rhino Weekend
Rhino Weekend is aimed at helping raise awareness and funds for Rhino Conservation work in Africa through fun activities and competitions. The Park supports Tusk Trust and has done for many years, and we hope to generate more interest, awareness and support through this fund raising activity weekend.
August 27th - August 29th 2016
Cotswold Falconry Flying Displays
See a variety of Birds of Prey, all of which are free flying. As they fly close by you will witness their speed and grace. The Cotswold Falconry will endeavour to show you Vultures, Owls, Falcons and Eagles.
September 3rd - September 4th 2016
Cotswold Falconry Flying Displays
The Cotswold Falconry display will be at the Park and will show a variety of Birds of Prey, all of which are free flying.


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Nov 9
May 24
Feb 26
Feb 8
Lucky Five - Pete Adams w/ Lucky Five
Feb 2
Sounds Like: 70's Stevie Wonder meets Dave Matthews band
Manager: Jim Jervis
Bio: About Us
Early collaborators Marques Nash (Vocals, Piano and Song Writer), Shago Elizondo (Guitar and Backing Vocals) and Andy Morimoto (Bass) formed the original foundation in December, 2006….it wasn't until the addition of Jesse Williams (Drums) and Jonny Fung (Guitar, Piano, and Backing Vocal...See Full Bio
"Lucky Five "La Resistance" The album comes out of the corner swinging with the upbeat "Something In Your Head." The songs are propelled by the vocals of singer Marques Nash, but that's not to downplay the instrumental talents contained here. Guitar work by Shago Elizondo and Jonathan Fung harmonize well — whether tearing through riffs, sparking rhythm or trading solos, such as on "LA Live." Andy Morimoto's bass drives the back end while Jesse Williams isn't afraid to expand on a simple beat without overwhelming the song. Nash also plays keys to give an added element and some depth to what might be a typical rock band otherwise. The band fuses its rock base with elements of jazz, funk and blues to form an amalgam that's melodic without being overly pop. You can easily hear in the album's eight tracks that these guys put on a helluva live show"


text: David Henningsson schreef op vr 10-02-2012 om 17:44 [+0100]: > It was decided not to drop the non-pae kernel flavour until 12.10, so > that non-pae computers would still be supported for five years. > > I happen to have one of these, I use it on a daily basis for IRC and a > few other things. So now I want to test 12.04 on that laptop, but when I > try to boot the daily live-CD, I get an error saying that my CPU is > missing the pae feature. https://bugs.launchpad.net/ubuntu/+source/linux/+bug/930447 We have 5 or 6 Thinkpad R51 (bought in 2005 by one of our sponsors, and donated to us a couple of years ago) capable of running Unity 3D in the event boxes of our locoteam, which will become obsolete or at least difficult to use because of this, so I feel your pain... :-/ -- Jan Claeys


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Hotels near U. S. Consulate
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- Most bookedSofitel Mumbai BKC
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"Very nice rooms and courteous staff good breakfast spread only pool is a little small. Overall a good stay really relaxed."
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"Very clean, staffs are great and always helpful but breakfasts could be better, Foods and drinks are very expensive. Good swimming pool. "
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"Excellent. Service and location.very helpful staff"
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"Stated as a get away with my partner. Couldn't have had a better time. Will be returning soon"
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"it was pleasant & satisfactory service we found , we hope when we come to america we are sure to stay at your hotel once again.and we also tell my relative and friend to visit the hotel."
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"I,m not sure what some people experienced at this place but our stay was wonderful.if you don't want to pay for two bedrooms it is a shared apartment, to us that just meant that on top of your normal hotel room you get to share a lounge kitchen and dinning area what a deal! the bed was the most c..."
A Traveller, Nov 2015, GB
14 people looked at this hotel in the last hour
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"Everything is nice except for free internet, don't count on it, it is for 24 hours only and the connectivity is quite spotty...food variety, quality, availability is awesome."
A Traveller, May 2016, US
- OYO Premium Sion Railway StationNo Guest Reviews yet
4 people looked at this hotel in the last hour
- OYO Rooms Chembur Swastik ChambersNo Guest Reviews yet
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- High Street Phoenix Mall
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- Powai Lake
- Bombay Hospital
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Best Cheap U. S. Consulate, Mumbai Hotels
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If you're visiting U. S. Consulate with the family or in a large group, be sure to check out the room options and facilities we list for each hotel to ensure we help find you the perfect hotel. Right now, our most popular hotel in Mumbai is Maxxvalue Hotels & Hospitality Pvt. Ltd..
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Things To Do Near U. S. Consulate - Mumbai Travel Guides
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The fee that they collected from CHA upon filing the IND should be in the bank now, and I imagine it will be in the next PR. The more milestone we achieve, the more we obtain in fees. The total in fee based incentives is $1.9M
Here's a link, as ACT's website is giving me trouble...http://www.thefreelibrary.com/Advanced+Cell+Technology+Provides+Single+Blastomere+Technology+To+CHA...-a0199662483*****The license between ACT and Cha Bio is a part of continuing cooperation and collaboration between the two companies, including a joint venture regarding hemangioblast technology. In March, the Company also announced that it licensed its retinal pigment epithelium (RPE) technology, for the treatment of diseases of the eye, to CHA Bio for development and commercialization exclusively in Korea. ACT is eligible to receive up to a total of $1.9 million in fees based upon the parties achieving certain milestones, including ACT making an IND submission to the FDA to commence clinical trials in humans using the technology, which ACT currently plans to do during the second half of 2009.*****


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Pebble Beach Systems launched Marina, an enterprise-level automation system to address the business requirements of broadcasters who have a variety and ever-changing set of content delivery requirements.
Marina is scalable up to hundreds of channels. It offers its users an almost infinite variety of configuration options, but it does so using a single central database, allowing coordinated applications and resources to operate in a distributed architecture across multiple servers.
A new playlist engine, designed from the ground up, is coupled with a fully distributed architecture and leverages the manufacturer's experience in developing drivers for a huge variety of delivery devices from leading industry manufacturers. Pebble Beach is entirely independent, and offers solutions with any mix of equipment to meet customer requirements. This allows broadcasters to maximize the benefit they get from investing in new technology whatever the source.
Marina is fully interoperable with Anchor, Pebble Beach's media and workflow management system. Broadcasters can create end-to-end workflows in order to manage content through all stages of the process, from ingest through to delivery via many channels, in many formats, using rules-based logic to carry out automatically processes such as transcoding.
The system is Unicode-compliant, allowing it to operate in all languages including Chinese, Japanese and Arabic. The entire system can be instantly toggled between languages, making it easy for operators to manage the system in their own language but also overcoming potential problems a support engineer would face.
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Toolkit: August 2016
Baz Luhrmann on Making a Netflix Series That Was Too Epic for a Movie
Field Guides: Shooting with SmallHD's 502 Monitor and Sidefinder EVF System


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Cashman's Burden
Being the general manager of the Yankees is his dream job. So why does he seem to want out?
Being the general manager of the Yankees is his dream job. So why does he seem to want out?
Sandy Alderson needed to dump salary, and rebuild from scratch, anyway. Being broke, for now, might actually be a good thing.
Don't be fooled by his low-key vibe. Carmelo Anthony has brought excitement, and hope for a title, back to the Knicks.
Contrary to his hapless image, baseball's chief is the most effective commissioner in sports.
Whether the Mets keep or trade their superstar shortstop this season will say a lot about where the team is headed.
Reyes conquers clichéd haplessness in Flushing.
Why the Rex Ryan show keeps getting renewed.
When will a gay professional athlete finally come out?
The Yankee manager's calm, even boring, style is perfect for getting the team to the playoffs. Now, can they win?
Blaming the NBA owners.
Penn State's anachronistic fans.
It's been a fun run, but the end of the Ryan era has arrived.
The champ fights at Barclays on Saturday night.
A tournament's magical run.
Unless you're a college student.
Unwinding after practice with the Knicks' new hipster center and resident photography enthusiast.
Last week's online uprising made it official: Hollywood rules the culture no more.
Coughlin: adequate, brilliant.


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NEW YORK (AP) Ś With its playful mingling of fantasy and reality, James Thurberĺs beloved short story ôThe Secret Life of Walter Mittyö has seemed the stuff of movies since its initial publication in 1939.
But it has proved a tough nut to crack, having been made into an unloved 1947 film with Danny Kaye that Thurber himself decried and having led to numerous attempts that fizzled before they got started.
Whether Ben Stiller has finally succeeded was greeted as a matter of debate.
Stiller premiered his contemporary version of ôWalter Mittyö at the New York Film Festival on Saturday. The film screened for press and film industry members ahead of its evening red carpet premiere at Lincoln Center. The centerpiece of the NYFF, it was a hometown launch for the New York-native Stiller, whose film is also set in the Big Apple.
While the festival platform offered a prestigious debut for ôWalter Mitty,ö the movie started on rocky ground with critics. The film, which Stiller directed and stars in, was met by decidedly mixed reviews that partly diffused the assumed Oscar hopes of the film. 20th Century Fox will release the movie in the heart of awards season on Dec. 25.
Stiller stars as Mitty, a daydreaming Life magazine photo editor (ôa negative asset managerö is his official title) whoĺs uneventful, workaday life is contrasted by his vivid imagination. When the magazine is bought and moved online, Mitty is forced to pursue an intrepid photographer (Sean Penn) and grow closer to a colleague heĺs long admired from afar (Kristen Wiig).
In one memorable dream sequence, he imagines a reverse-aging future like ôBenjamin Button,ö another hard-to-adapt short story from the early 20th century. But his flights of fantasy gradually give way to actual adventures in Greenland, Iceland and the Himalayas.
Stiller wrestled over balancing the storyĺs many daydreaming sequences throughout the process, he said in a Q&A following the screening Saturday.
ôWhen you have fantasies that stop the story, an audience naturally wants to see the story unfold,ö said Stiller, who previously directed the comedies ôZoolanderö and ôTropic Thunder.ö ĹĺSo itĺs very challenging to keep the momentum going and have the fantasies play out.ö
ôOriginally, we had envisioned these much more elaborate fantasies that went on a lot longer,ö he continued. ôAs we developed the script and worked on the script, we realized that we had to keep paring them down. That process sort of continued through the editing of the movie, finding that balance of how you could keep the momentum of the story going, but also having enough of the fantasies in there to give you a sense of whatĺs going on inside Walter and just have fun.ö
Some more elaborate daydreams had to be cut before production started. One began in the mold of ôLawrence of Arabiaö before culminating in a song-and-dance routine from ôGrease,ö Stiller said.
ôI donĺt know why we cut that,ö said Stiller, before remembering the hard realities of a shooting budget. ôIt was money, basically.ö
Follow AP Film Writer Jake Coyle on Twitter at: http://twitter.com/jake_coyle
Caption 1:
This film image released by 20th Century Fox shows Ben Stiller in ôThe Secret Life of Walter Mitty.ö Running Sept. 27 through Oct. 13, the 51st New York Film Festival will feature the world premieres of Paul Greengrassĺ ôCaptain Phillips,ö Spike Jonzeĺs ôHerö and Ben Stillerĺs ôThe Secret Life of Water Mitty.ö (AP Photo/20th Century Fox, Wilson Webb)


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Endurance exercise and metabolism are linked to transcriptional activation of human telomeres, researchers propose.
Sperm Shadows
January 1, 2013|
Tracking the shadows cast by sperm reveals their precise 3-D movements.
January 1, 2013|
Tracking the shadows cast by sperm reveals their precise 3-D movements.
December 20, 2012|
Comparing gene transcripts from different species reveals surprising splicing diversity.
December 20, 2012|
After undergoing untested cosmetic surgery that uses stem cells to rejuvenate skin, a woman grew bone fragments in the flesh around one of her eyes.
December 18, 2012|
A roundup of species that made their scientific debut in 2012, and a few that said goodbye as well
December 14, 2012|
The science images and videos that captured our attention in 2012
December 13, 2012|
Tumor cells can exhibit different behaviors despite being genetically indistinguishable.
December 6, 2012|
Scientists engineer a spectrum of artificial pigments to understand how animals see in color.
December 1, 2012|
Certain immune cells keep adipose tissue in check by helping to define normal and abnormal physiological states.
December 1, 2012|
A hormone called jasmonate mediates plants' responses to touch and can boost defenses against pests.
December 1, 2012|
A precision microfluidic system enables single-cell analysis of growth and division.


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Call us now: 530-275-5510 | Shasta Lake, CA
Depending on how many people are attending, you have the option of renting out the full ranch or half of the ranch.
You can even rent single homes. Call us first for the best rates!
No schedules! No forced planned events! Bring your own food, or we have caterers available. We have an extra large kitchen for large family meals. All activities are available all day long...you decide! Your vacation, your way!
You'll never get bored at Coram Ranch.
We have a variety of different on-site activities and local attractions to keep you and your guests entertained. We will help plan your entire vacation!
For large scale events like weddings or corporate retreats, Coram Ranch is a perfect selection. You'll have a wonderful experience that you and your guests will never forget.
Mornings and evenings at Coram Ranch can be very cool, so plan accordingly.
The terrain is also very steep if you choose to hike the higher elevations, so hiking boots are recommended.
Dress is casual unless you plan to go out to dinner in Redding or in Mt Shasta.
We have mountain bikes and fishing poles available on a limited basis.
Please no pets.
*All rentals must be a two night stay minimum*
"We absolutely loved our stay at Coram Ranch. It was perfect for our family, as we don't like to go to places
where they have a lot of preplanned activities.
I would highly recommend your ranch for other families."
Best Regards,


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Current drug discovery is dominated by label-dependent molecular approaches, which screen drugs in the context of a predefined and target-based hypothesis in vitro. Given that target-based discovery has not transformed the industry, phenotypic screen that identifies drugs based on a specific phenotype of cells, tissues, or animals has gained renewed interest. However, owing to the intrinsic complexity in drug–target interactions, there is often a significant gap between the phenotype screened and the ultimate molecular mechanism of action sought. This paper presents a label-free strategy for early drug discovery. This strategy combines label-free cell phenotypic profiling with computational approaches, and holds promise to bridge the gap by offering a kinetic and holistic representation of the functional consequences of drugs in disease relevant cells that is amenable to mechanistic deconvolution.
Early drug discovery is achieved mainly through two strategies, target-based and phenotypic approaches (Hart, 2005; Swinney and Anthony, 2011). Target-based screens use high-throughput and label-dependent molecular assays to measure the effect of compounds on a specific target protein in vitro, while phenotypic screen use unbiased phenotypic assays to examine the effect of compounds on a specific phenotype of cells, tissues or animals. Target-based approaches have been dominating early drug discovery in the past quarter of century, which is coincident with the continuous decline in productivity of pharmaceutical research and development (Paul et al., 2010; Pammolli et al., 2011; Scannell, 2012). Several factors contribute to this productivity crisis. First, there have been increasing efforts in high-risk projects for unmet therapeutic needs and associated with unexploited biological mechanisms in the past decades (Kamb et al., 2007; Hopkins, 2008; Rask-Andersen et al., 2011). Second, the target chosen in a screen may be not essential to disease pathogenesis or induce undesired toxicity, and the molecular mechanism of action (MMOA) investigated may be unable to produce therapeutic benefits (Hopkins, 2008; Swinney and Anthony, 2011). The MMOA describes the interaction between a drug and its target (or targets) that creates a specific response. Third, many, if not all, drugs display clinically relevant polypharmacology – the specific binding of a drug to more than one target (Roth et al., 2004; Yildirim et al., 2007; Hopkins, 2008; Rask-Andersen et al., 2011), suggesting that single target-based screen may de facto be ineffective. Fourth, molecular assays for target-based screens generally rely on the use of labels, which may cause artifacts in results (Beher et al., 2009; Pacholec et al., 2010; Hu et al., 2012). Lastly, traditional phenotypic approaches suffer disadvantages associated with low-to-moderate throughput, and difficulty in target deconvolution and in governing medicinal chemistry optimization (Kenakin, 2009; Swinney and Anthony, 2011).
In the past years, phenotypic screens have gained renewed interest in discovering first-in-class or best-in-class medicines (Lee et al., 2012; Eggert, 2013). Comparing to traditional phenotypic approaches, label-free cell phenotypic profiling techniques afforded by optical or electric biosensors offer clear advantages in rich information content, real-time kinetics, highly flexible assay formats, and high-throughput, beside wide pathway coverage and ability in multi-target profiling and screening that are common to all phenotypic assays (Fang, 2013). Optical biosensors such as resonant waveguide grating (RWG) measure drug-induced dynamic mass redistribution (DMR) signals, while electric biosensors measure drug-induced impedance signals (Fang, 2010). In parallel, similarity analysis based on two-dimensional structures of compounds has been used to predict drug–target interactions (Keiser et al., 2007, 2009; Lounkine et al., 2012), while molecular docking using ever increasing numbers of three-dimensional protein structures are also productive (Carlsson et al., 2011; Koutsoukas et al., 2011; Shoichet and Kobilka, 2012; Stevens et al., 2012).
Herein, I propose a label-free strategy combining label-free cell phenotypic profiling techniques with computational approaches for early drug discovery (Figure Figure11). Essential to this strategy is that label-free cell phenotypic profiling techniques are used for multi-target screening, target identification, MMOA determination, and lead selection. Bioinformatics analysis of the label-free profiles of compounds is used to provide analytical support for target identification, and chemical similarity analysis is used to expand compound library for lead optimization and selection. Of note, the principles and applications of label-free biosensors for cell analysis have been widely reviewed in literature (Fang, 2006,2011b; McGuinness, 2007), and thus not included in the present review.
As the basic unit of life cells have been widely used for drug discovery, mostly because the functional responses of drugs in cells provide better understanding of receptor physiology and drug pharmacology than in vitro binding studies. Target-based approaches often use recombinant cell lines expressing a specific target implicated in a disease, while cell phenotypic approaches often use native cells including immortalized cell lines, primary cells, and stem cells. As surface sensitive and non-invasive techniques label-free biosensors can examine drug-induced minute changes in a confluent layer of eventually all types of cells (Fang, 2010, 2011a), including primary (Hennen et al., 2013) or stem cells (Bagnaninchi and Drummond, 2011; Abassi et al., 2012; Pai et al., 2012). Compared to recombinant cell lines, primary or stem cells retain many functions seen in vivo and express endogenous targets of interest in their native signaling circuitry, thus permitting drug profiling using more physiologically and clinically relevant cell phenotypes (Kenakin, 2009; Eglen and Reisine, 2011). Owing to its spatially resolved capability the recently developed RWG imager enables drug profiling using partially confluent cells (Ferrie et al., 2010) or even single cells (Ferrie et al., 2012), and thus opens an unique opportunity to screen drugs using primary or stem cells when homogeneous cell populations are difficult to obtain (Pai et al., 2012).
Disease relevant cellular phenotypes can be structural, morphological, or physiological abnormalities involving cells or cell components. Structural abnormalities can be classified based on cellular component hierarchy, whereas abnormal morphology phenotypes is either the (abnormal) absence of required cellular parts, the (abnormal) presence of additional cellular parts, or abnormal qualities of cellular parts, and abnormal physiology of a cell component refers to abnormal functionality of a cell component (Hoehndorf et al., 2012). Thus, drug profiling and screening can be performed using a great number of cellular phenotypes such as angiogenesis, cell death, cell division, and inflammation; depending on the MMOA of interest one or more specific cellular phenotype may be examined (Welsh et al., 2009; Kepp et al., 2011). For label-free cell phenotypic screening, two common approaches developed are endpoint and kinetic based screens (see below). Given that label-free biosensors are sensitive to cell numbers, cell signaling and morphological changes, these biosensors permit screening and profiling compounds in the context of a great number of cellular phenotypes ranging from cell adhesion to cell life cycle (cell cycle progression, division, and growth), receptor signaling, cell death, viral infection, cell migration and invasion, and cell-cell communication (Figure Figure22).
The endpoint screens leverage the ability of a biosensor to record and encode the signaling events of a specific receptor in a population of cells (typically confluent cells) into an integrated and kinetic biosensor response for identifying active molecules specific to the receptor (Fang, 2010). Here, once the biosensor profile of a receptor cognate agonist in the cells is obtained, its response at a specific time point is monitored and used as the readout to fish out ligands for the receptor of interest from a compound library. In order to identify distinct classes of ligands screening can be performed using different formats. For instance, one-step assay may be useful for discovering agonists, wherein the cells are stimulated with compounds, each individually. Considering the wide presence of compensatory pathways in cell signaling, the one-step agonist screen may result in relatively high false positives for the receptor of interest. Such false positives can be minimized using two-step endpoint screens, wherein the cells are stimulated with compounds first, followed by stimulation with a cognate agonist specific to the receptor. Compounds that are active in the first step and also desensitize the second agonist stimulation would be agonists for the receptor, while compounds that are inactive in the first step but block the second agonist stimulation would be antagonists for the receptor (Tran and Fang, 2008; Deng et al., 2011a). In addition, a three-step assay wherein a compound washout step is introduced between compound and receptor cognate agonist stimulation steps can be useful for identifying long-acting antagonists or agonists (Goral et al., 2011; Deng et al., 2012b).
Receptor signaling is encoded by the coupling of temporal dynamics with spatial gradients of signaling activities (Kholodenko, 2006), and may come in multiple pathways and waves (Ferrie et al., 2013; Lohse and Calebiro, 2013). Consequently, label-free biosensors as a non-invasive recorder mirror the dynamics of receptor signaling, and the biosensor signature arising from the activation of a receptor could contain multiple phases. Therefore, multi-parameter profiling and screening may be feasible and offer additional information regarding to the specificity and mechanisms of action of hits to a receptor, a signaling protein, or a pathway.
For label-free cell phenotypic screens, real-time kinetic measurements of drug action would be more informative but with lower throughput than end-point screens. The kinetic profiling of compounds may be performed in the context of a specific cellular process such as cell adhesion, cell growth and death, or cell signaling. Label-free biosensors allow for interrogating drug molecules with wide coverage in targets and pathways of native cells (Figure Figure33; Fang, 2011b, 2013). The modulation of many classes of targets including G protein-coupled receptors (GPCRs), receptor tyrosine Kinases (RTKs), transporters, Toll-like receptors (TLRs), immune receptors, enzymes, cell structural proteins, and kinases can directly lead to rapid biosensor responses. The most popular is to profile compound-induced cell signaling in confluent cells, given that the cells once reach confluency start to enter a new growth cycle or a quiescent state and the compound-induced response is almost exclusively due to cell signaling (Fang, 2010, 2011a). Alternatively, the long-term impacts of compounds on cell growth can also be used to screen compound library (Abassi et al., 2009; Fu et al., 2011). Of note, this approach may be able to identify ligands for other classes of targets such as nuclear receptors whose activation by themselves may not result in rapid signaling-related biosensor responses.
Large panels of disease relevant cell lines annotated with both genetic and pharmacological data are powerful tools for drug discovery (Barretina et al., 2012; Garnett et al., 2012). For instance, NCI60 consists of 60 (now 59) human cancer cell lines from nine different tissues introduced in 1990 by the US National Cancer Institute (NCI) in Bethesda, Maryland, and has been widely used for discovering new anticancer drugs (Shoemaker, 2006). For label-free profiling, cell panels may consist of multiple cell lines for a disease, a parental cell line and its recombinant counterparts, or a stem cell and its differentiated cells. Each cell line has unique expression pattern of functional receptors and signaling circuitry. Thus, the use of cell panels not only expands the number of addressable targets/pathways, but also offers confirmative information regarding to the potential mechanism of action of active compounds identified in label-free cell phenotypic screens (Verdonk et al., 2006; Morse et al., 2011, 2013; Pai et al., 2012; Ferrie et al., 2014). For instance, using the DMR assay we profiled a library of sixty-nine ligands of adrenergic receptor (AR) with a cell panel consisting of the parental HEK-293 and four β2-AR-stably expressed cell lines, and found that HEK-293 endogenously expresses functional Gi-coupled α2-AR and Gs-coupled β2-AR, and these ligands displayed divergent label-free cell phenotypic pharmacology (Ferrie et al., 2014).
Identifying the target for a specific phenotype is vital to guide lead optimization and to understand the potential toxicity for the target (Hart, 2005). Common to classic phenotypic approaches for determining target engagement is to first generate target hypotheses using pattern recognition to compare small molecule phenotypic profiles to those of known reference molecules, followed by confirmation using direct proteomic approaches (Young et al., 2008; Schenone et al., 2013). However, classical phenotypic approaches mostly rely on descriptive, empirical, and end-point measurements, which, by themselves, generally offer little insights about the biological mechanisms of action of drugs (Feng et al., 2009). In contrast, label-free cell phenotypic approaches all measure real-time kinetic responses of compounds in cells, which contain target- and pathway-specific information (Fang, 2011a). For label-free endpoint and multi-parameter screens, target hypothesis is predefined by the reference agonist cognate to the receptor of interest, so target engagement can be confirmed using direct binding assays or counter profiling using another cell line that does not express the target receptor. For instance, using the DMR signal at 25 min post-stimulation with methacholine in CHO-M3 cells as the readout, screening a library of 83,000 compounds led to identification of 49 novel muscarinic M3 receptor ligands that had pIC50 values between 4.8 and 6.3 and were further confirmed using radiobinding assays (Dodgson et al., 2009). Here, methacholine is used as the reference agonist for the M3 receptor. Of note, these novel ligands were found to be false negatives in a calcium flux assay.
For label-free kinetic profiling, target hypothesis can be generated using several approaches. First, target/pathway deconvolution may be directly achieved through investigating the impact of chemical probes and/or genetic manipulations (e.g., RNAi) on the kinetic response of a compound itself (Fang et al., 2005; Deng et al., 2011b; Verrier et al., 2011). Second, counter profiling between a recombinant cell line expressing the receptor of interest and its parental cell line without the receptor is also effective to confirm the target specificity (Ferrie et al., 2014). Third, multiple assays including agonist, antagonist, desensitization, and antagonist reversal assays when respective pharmacological tools are available can be used to ascertain the specificity of a compound to the receptor of interest (Ferrie et al., 2013). Fourth, pattern recognition based on label-free profiles of compounds can be used to generate target hypothesis through comparison of their profiles with databases of the activity profiles of other reference molecules with known targets (Abassi et al., 2009; Fu et al., 2011). Traditional approaches including proteomics-, genetics-, and bioinformatics-based approaches can then be used for determining target engagement (Ziegler et al., 2013). Fifth, computational approaches based on similarity analysis of known probe molecules (Keiser et al., 2007, 2009; Lounkine et al., 2012) or molecular docking (Carlsson et al., 2011; Shoichet and Kobilka, 2012) can be used to predict the probability of the binding of small molecules to a specific target.
For label-free endpoint screens, hits are selected based on the label-free profile arising from the activation of the receptor of interest, similar to classical target-based screens (Dodgson et al., 2009). For label-free kinetic profiles, hits are selected based on a specific phenotypic response in the context of a specific cellular process, such as the increase in label-free profile of cell adhesion, alteration of the label-free profile of cell growth, or a specific label-free profile of cell signaling. For instance, screening a library of 660 compounds led to identification a characteristic DMR signal in HT-29 cells for a subset of compounds (Deng et al., 2011b). Combining DMR antagonist/desensitization assays with GPR35 knockdown with interference RNA, receptor internalization, and Tango β-arrestin translocation assays revealed that two novel series of chemical compounds, 2-(4-methylfuran-2(5H)-ylidene)malononitrile and thieno[3,2-b]-thiophene-2-carboxylic acid derivatives, are GPR35 agonists.
Once hits are identified and confirmed, searching similar compounds from commercial and public databases can quickly expand compound library for generating structure-activity relationship (SAR) analysis. These databases include PubChem (Wang et al., 2009), ChemBank (Seiler et al., 2008), DrugBank (Knox et al., 2011), ChemBL (Gaulton et al., 2012), and ZINC (Irwin and Shoichet, 2005). With the ever-increasing number of compounds annotated with biological and pharmacological activities in these databases, it is highly possible to quickly identify lead-like compounds with high specificity and potency to the target receptor. For instance, according to the similarity of tyrphostins to 2-(4-methylfuran-2(5H)-ylidene)malononitrile compounds, we hypothesized and confirmed that a group of tyrphostins such as tyrphostin-51 are GPR35 agonists with moderate potency (Deng et al., 2011a). Given that tyrphostins, the first generation of tyrosine kinase inhibitors, are tyrosine analogs (Levitzki and Mishani, 2006), we hypothesized and confirmed that multiple tyrosine metabolites are GPR35 agonists (Deng and Fang, 2012b; Deng et al., 2012a). From these SAR studies, we further expanded the chemical library by searching public databases and identified a group of nitrophenols as GPR35 agonists, among which 4,4'-(2,2-dichloroethene-1,1-diyl)bis(2,6-dinitrophenol) displays high potency with an EC50 of 6nM (Deng and Fang, 2012a).
Drug toxicity/safety assessment is essential to drug discovery and development, and may be studied using several label-free cell phenotypic profiling approaches. First, the recently developed high frequency electric impedance biosensor system can be used to monitor the impact of drugs on the beating patterns of primary or stem cell-derived cardiomyocytes; and this system can recapitulate known effects of various known modulators of cardiac function (Abassi et al., 2012). Cardiac toxicity is one of the major concerns in drug development, and accounts for one-third of all drug withdrawals from the market (Wilke et al., 2007). Second, potential adverse drug reactions (ADRs) of compounds can be assessed using a panel of cells consisting a parental cell line and a number of recombinant cell lines, each expressing a specific target receptor that is known to be associated with and prone to cause ADRs. ADRs are the second leading cause for attrition of drug candidates in clinical trials, behind lack of efficacy (Arrowsmith, 2011). Factors that cause ADRs include the primary target of the drug itself, non-specific interactions of reactive metabolites of the drug, or unintended activity at off-targets. The number of off-targets that is known to be associated with ADRs is relatively small (~75; Bender et al., 2007; Campillos et al., 2008; Lounkine et al., 2012), almost all of which can be directly examined using label-free profiling. Practically, these recombinant cell lines can be made readily to be profiled as cell bank (e.g., frozen cell batches), or transitly transfected in situ using classical viral or plasmid DNA-based approaches. Third, computational approaches based on chemical structures or molecular docking can be used to calculate the probability of drug candidate molecules binding to these ADR-related targets (Lounkine et al., 2012).
Elucidating the MMOA of drug candidate molecules is a critical step in drug discovery. Label-free biosensor such as surface plasmon resonance and RWG is well-known for its ability to determine the affinity and kinetics of drugs binding to their primary target (Schuck, 1997; Fang, 2012). Label-free cell phenotypic profiling also can provide information regarding to the MMOA of compounds. This is done through leveraging the sensitivity of the label-free profiles of compounds to their polypharmacology (Wermuth, 2004), functional selectivity (or biased agonism; Kenakin, 2012), binding kinetics (Deng et al., 2013a), binding orientation (Bock et al., 2014), cell membrane permeability (Ferrie et al., 2013), and transport mechanisms (Deng et al., 2013b; reviewed in Fang, 2013).
The biased agonism describes ligand-dependent selectivity for a specific signal transduction pathway over others downstream the same receptor, and is common to ligands for GPCRs and potentially other classes of receptors (Fang, 2013). Owing to its integrative nature in measurement (Fang et al., 2006), label-free cell phenotypic profiling, by de facto, is not ideal for directly assessing biased agonism (Morse et al., 2013). However, several label-free approaches may be useful to manifest biased agonism. First, multi-parameter kinetic analysis may sort ligands for a specific target into different clusters. For instance, profiling of a set of β2-adrenergic receptor (β2-AR) ligands in A431 cells using DMR assays revealed that multiple kinetic parameters extracted from their responses allow fine classification of these ligands based on their efficacy and biased agonism (Fang and Ferrie, 2008; Fang, 2010). Second, the recent developed integrative pharmacology ontarget (iPOT) approach can classify ligands based on their specificity, pathway selectivity, and efficacy for the target receptor of interest (Ferrie et al., 2011; Morse et al., 2011, 2013). The iPOT approach leverages distinct sensitivity of the label-free profiles of different drugs acting through the same receptor in different cell lines, or the same cell line but with different preconditioning. The cell preconditioning can be achieved using specific probe molecules to impair or alter specific pathways, or genetic tools to alter the expression of a specific signaling protein. Using this approach, we had obtained a pharmacological heatmap of all adrenergic receptor drugs approved by the US Food and Drug Administration that correlates well with their in vivo indications (Ferrie et al., 2011).
The functional consequence of different binding kinetics of a family of ligands for a specific receptor can also be assessed using label-free biosensor ligand washout assay. The onboard microfluidics is the most effective means to control the duration of a ligand exposed to the cells, so it is possible to determine whether the effect of the ligand is short or long acting. For instance, using microfluidics to control the agonist stimulation duration we found that the activation of the β2-AR in A431 with a pulse of its agonist as short as 1 min is sufficient to trigger a sustained response, whose sustainability is dependent on the type and concentration of agonists, and the stimulation duration (Goral et al., 2011; Ferrie et al., 2013). In another study, combining radiobinding results with electric biosensor profiling results revealed that the efficacy of adenosine A2A receptor agonists is positively correlated to their receptor residence time (the reciprocal of off rate; Guo et al., 2012). Almost identical trend was found for a family of agonists for endogenous muscarinic M3 receptors in six different cell lines (Deng et al., 2013a).
The cell membrane permeability and transport mechanism are important mostly for the efficacy of drugs acting at intracellular targets. A recent DMR study of three inhibitors for epidermal growth factor receptor (EGFR) in A431 and HT-29 showed that the recovery of EGFR signaling after inhibitor removal from the extracellular buffer was faster in HT-29 than in A431, and also dependent on the duration of inhibitor removal (Deng et al., 2013b). Furthermore, the potency of three inhibitors including gefitinib, erlotinib, and AG1478 was generally higher in A431 than HT-29 cells. The most possible mechanism for this is that the drug uptake and retention paly a dominating role in determining the whole cell efficacy of these kinase inhibitors. The cellular retention of these inhibitors is a function of cell uptake and effluxing via efflux transporter such as breast cancer resistance protein (BCRP/ABCG2). All three inhibitors tested are ABCG2 substrates; A431 cells express little ABCG2, while HT-29 expresses high amount of ABCG2.
Effective lead selection and prioritization is essential for getting the cost of early drug discovery under control. In a typical screening campaign, tens of thousands of hits are often identified. After optimization, about one hundred lead-like molecules are selected for animal testing. The iPOT approach, label-free profiling techniques in general, are useful to classify these lead-like molecules into distinct clusters, each of which may share a common MMOA (Ferrie et al., 2011). Representative lead-like molecules from each cluster can then be selected for in vivo testing (Morse et al., 2013). Computational approaches, in particular chemical similarity analysis against the ADR-related receptor panel, would also be beneficial to lead selection process.
In the recent years, there has been a renaissance in phenotypic approaches for drug discovery. Label-free cell phenotypic profiling and screening holds great promise in discovering disease-modifying activities of drug molecules via validated or previously undescribed targets, or by acting simultaneously on more than one target. Combining computational approaches, in particular similarity analysis based on chemical structures and molecular docking based on three-dimensional structures of target proteins, with label-free approaches would greatly facilitate early drug discovery by permitting target engagement determination, compound library expansion, MMOA deconvolution, safety and toxicity assessment, and lead optimization and selection.
Ye Fang is a research director/fellow of Corning Incorporated. DMR technology is patented by Corning Incorporated.
PubMed Central Canada is a service of the Canadian Institutes of Health Research (CIHR) working in partnership with the National Research Council's national science library in cooperation with the National Center for Biotechnology Information at the U.S. National Library of Medicine(NCBI/NLM). It includes content provided to the PubMed Central International archive by participating publishers.


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I am in China right now. Try to locate their operation in China, I went to the price they had address in Shanghai, I could not find the office.
It looks like a residential area for me.
Anyway, If anyone could find their telephone number or address, please posted here.
I will be in China for another month. Would like to find what is PV's 100 million operation in China really all about.
Invested over 30K on CCTR/New Market. I still have the stocks, but there are worth less then $1 combines.
I will spend my money and make sure this scam go to jail.
Need to see this
There was no trip to China. It is just a scam like most things bashers write.
bump. This guy is my new hero.
Can we assume that no one posting here has been to China? And can we
assume that no one knows whether They have an office?
You must have gone to the wrong place.
Their Shanghai office looks like a doctor or dentist's office.
It is not in a residential area, but an area with many small companies.
You can see a photo of the office here:
If you put the address info into Google Maps it will display the area to you and the satellite view shows plainly that it isn't a residential area.
It is two blocks West of The Haiyatt Hotel Shanghai and about 4 blocks East of Kensaku Sharon Tennis
Stadium that is at where Qinjiang Rd dead ends at Guiguo Rd.
In reality they probably just rent a room in that building. They only pay $527 month to month.
Anyone could provider the telephone number for so called operation in China, so every one can go and check if you get the chance.
I don't need to go to China to know this is bogus.
Need to read this.
Just an afterthought to my reply, you may also want to share your findings with the local Media in Dallas, Texas. I am sure it will make a very compelling special interest story.
email@example.com channel-8-wfaa-tv-abc-dallas
email@example.com The Texas Tribune
Anyone could find their phone number in China.Big operation might not have a telephone. Maybe they are too busy with the Wi-fi deal.
Good day. It's morning in China. The price I went yesterday had address:
Shanghai Office
2F No. 123 Qinjiang Rd.
Shanghai, 200233, P.R. China
From CCTR's web Site. For some reason, they don't have the Telephone Number(Is it a joke) or a fax number. If they have a telephone, I will double check the address.
Now I understand the problems: They don't even have operation in China. The management should go to jail. They don't have any personal in China.
Hope other Chinese national could verify the same thing for me.
The address I have is: Shanghai Office
2F No. 123 Qinjiang Rd.Shanghai, 200233, P.R. China
Since you are there maybe a call to Investor Relations at, (214) 722-3060, will provide the information you need. Since your are in China they may want you to talk with Dr. James Jiang,President and Chief Executive Officer of the Company. I am pretty sure they he will want to hook you up with a guided tour and roll out the red carpet.
I understand the phones are pretty busy and sometimes it is difficult to get through. The email for Investor Relations at China Crescent Enterprises, Inc.
is: email@example.com
This is very exciting actually having a shareholder in China. I hope you have sufficient time to visit all their holdings and regale your fellow shareholders with detailed information of your findings.
Please keep us informed of your "progress."
I will keep searching for additional information that may be beneficial for your quest. Thank you!
Not even a fake office front?
Shocking...No business in China.
Thanks for your post ,and all your time and work . I just want this p o s stopped .
please see if you can find local listings for phone numbers. i've tried and cannot find anything:
● Clipper Technology, Ltd. ("CLPTEC"): A Wholly Owned Foreign Entity ("WOFE") registered in Shanghai, China, which provides consulting, development, implementation, and maintenance of technology systems
● Clipper Huali Co., Ltd. ("Clipper-Huali"). Clipper-Huali was originally formed as a collaborative business enterprise between ClpTec and a consortium of Chinese technology firms called The Huali Group, Ltd. ("Huali"). Clipper-Huali is registered in the City of Ningbo, China. Effective April 1, 2009, Clipper-Huali is owned 76% by ClpTec and 24% by Huali. Clipper-Huali is engaged in the sales, distribution and integration of IT products
● Dalian Aoyuan Electronic Technology Services Co., Ltd. ("DAETS"). DAETS is a wholly-owned subsidiary that was acquired by CLPTEC in December 2009 from Aoyuan Electronic Company, Ltd., located in Dalian, China, which was established in March 1995. Aoyuan is one of the top 500 computer hardware suppliers in China and is listed as one of the "Top 100 Northeast Regional Computer Suppliers" by First Chinese Computer Vendors. ● Shenzhen Newbao Technology Co., Ltd. ("Newbao"). Newbao is a wholly-owned subsidiary that was acquired by CLPTEC in December 2009 from China Radio Technology Co., Ltd., an Original Design Manufacturer located in Shenzhen, China, that designs and manufactures a wide range of wireless products specified by customers throughout Asia.


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Mi Amigo
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It was a great time spent with great people. You should buy this movie if for no other reason than to support the awesome people that put so much time and effort into making it a reality.
It's not that the acting is horrible - although it isn't spectacular. It's pretty much all about the awful writing and lack of a plot - or more accurately, too many competing plots to the point of not knowing what the story is really supposed to be about. It's quite confusing and just not well written.
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not a good movie..not really bad though. I just bought it fir Josh Holloway. I knew his was a miniscule role, but i still bought it. Its kinda bore. Read morePublished on March 17, 2011 by saurabh
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I am sick and tired of these people complaining about this movie! You know what, it may not be the Best movie in the world, but it was (atleast for me) Fun to watch. Read morePublished on January 22, 2010 by Ghoste Kruegar x
THIS MOVIE IS A WASTE OF A DVD. Do not buy this movie, even if just for the Josh Holloway footage. It is the story of 2 Amigos, but after the first 20 minutes, the movie "fast... Read morePublished on July 25, 2008 by Julia Ann Miracle


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Also, our Annual Dahlia Show is coming up Saturday, Aug. 20 and Sunday, Aug. 21. Here is a link to the show schedule and entry cards.
Chapter 11 - The Firebolt


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The Democratic Caucus of the Committee on Oversight and Government Reform named the ranking members of the seven subcommittees on Thursday, according to a release from Rep. Elijah E. Cummings (D-Md.), the committee's ranking member.
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MELBOURNE, Jan 14 Order of play on the main showcourts at the Australian Open on Wednesday (play starts at 0000 GMT on all courts, prefix denotes seeding): Rod Laver Arena 4-Li Na (China) v Belinda Bencic (Switzerland) 1-Serena Williams (U.S.) v Vesna Dolonc (Serbia) Leonardo Mayer (Argentina) v 2-Novak Djokovic (Serbia) From 0800 17-Sam Stosur (Australia) v Tsvetana Pironkova (Bulgaria) Matthew Ebden (Australia) v 28-Vasek Pospisil (Canada) - - Hisense Arena 7-Tomas Berdych (Czech Republic) v Kenny De Schepper (France) Adrian Mannarino (France) v 3-David Ferrer (Spain) Casey Dellacqua (Australia) v 18-Kristen Flipkens (Belgium) - - Margaret Court Arena Monica Niculescu (Romania) v 15-Sabine Lisicki (Germany) 28-Flavia Pennetta (Italy) v Monica Puig (Puerto Rico) 9-Angelique Kerber (Germany) v Alla Kudryavtseva (Russia) Sam Querrey (U.S.) v 23-Ernests Gulbis (Latvia) From 0800 8-Stanislas Wawrinka (Switzerland) v Alejandro Falla (Colombia) (Compiled by Greg Stutchbury; Editing by Patrick Johnston)
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Allergies Health Center
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Eleven million people are allergic to cats alone. About 15% of us are allergic to animals.
People who love pets and don't have allergies should not become complacent. "You can develop an allergy at any time," Derek K. Johnson, MD, director of allergy and immunology at Temple University Children's Medical Center, tells WebMD. "That's why it's important to know what causes pet allergies. It's the flakes from the animal's skin, called dander, not the fur. So even if it's a bald cat, you can be allergic."
The animal's saliva on the fur from cleaning itself or on your skin from slobbery kisses can also incite a reaction. Pet urine can also be a culprit.
"To be exact," Pamela A. Georgeson, MD, a board-certified allergist at the Kenwood Allergy and Asthma Center in Chesterfield Township, Mich., tells WebMD, "a lot of people are allergic to a cat protein called FEL-d1 found in dander and saliva."
Allergies are more commonly caused by cats, says Dean C. Mitchell, MD, a board-certified allergist in practice in New York.
"I have had people come to me from all walks of life," he continues. "Some people can't even go to Thanksgiving at a house with a pet. I see veterinarians with allergies, pet groomers."
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Walking on Water - The Invisible Surfboard
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Ruched One-Shoulder Chiffon Gown
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Ruched silk chiffon defines the fitted one-shoulder bodice of an elegant silk gown wrapped with a soft, removable sash at the waist before floating away to the long skirt.
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