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Eating at home can save money, but if you don't leave the house you'll never meet a rich stranger who will give you all his money in return for raising his adult children. Get out there with this Groupon.
Choose Between Two Options
$33 for a three-course dinner with drinks for two (up to $58.46 value)
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- One dessert (a $4.50 value)
- Two glasses of house wine or honey wine (up to a $10 value)

See the menu.

Abyssinia Ethiopian Restaurant
Passersby often stop outside Abyssinia Ethiopian Restaurant's storefront window to peer in on the unusual dining-room setup. Elaborately woven baskets sit beside wooden chairs festooned with colorful cushions; each of these baskets cradles the slightly sour Ethiopian bread known as injera.
Injera is literally the basis of Ethiopian cuisine—its spongy surface lies flat across plates to welcome dollops of curry chicken, ginger- and garlic-seasoned lentils, and sautéed cubes of lamb. To wash down these eats, Abyssinia's staff ships in Ethiopian beers and wines. House red and white wines are also available, and the staff takes care to ensure that each was aged, according to tradition, in the cellars of red and white houses.
"Great food and fantastic service!"
"Had a great meal -- Went with our server's reccommendations and it turned out great."
"Abyssinia is a great little gem of a restaurant. Good service and great food."
Abyssinia Ethiopian Restaurant
4116 E Colfax Ave.
Denver, CO 80220
+13033168830Get Directions


text:
New York Times bestselling author Katherine Stone's much-beloved and bestselling romantic novel, Twins, is now available in ebook format.Love, passion, danger, and betrayal amid the glitter of Manhattan...Brooke and Melanie Chandler are sisters, and twins. But they could not be more different. Brooke's a serious, driven, ambitious New York City prosecutor. Melanie's a golden, glamorous, sophisticated supermodel.The twins were close, once upon a time, until the realities of life - and their differences - tore them apart. Women now, they're both living in Manhattan, pursuing their careers, and falling in love; complicated pursuits, for both of them. And they re wondering, too, if the closeness they once shared would be possible again...or if jealousy, separation, bitterness, and betrayal have irrevocably shattered the bond.The wishes of their hearts are perilous enough - but there's true danger, an obsessed killer, who has them in his sights.Katherine Stone is the New York Times bestselling author of twenty-one novels, including Roommates, Twins, Bed of Roses, and Pearl Moon. Her books have been translated into twenty languages and have been sold worldwide. A physician who now writes full-time, she lives in the Pacific Northwest with her husband, physician and novelist Jack Chase.She is in the process of preparing all of her titles for publication in e-book format.
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subset: commoncrawl


text:
Yes. Always.
Printable View
Yes. Always.
So a lot of us will love pokemon forever and ever! That's a good thing to hear XDD
I first got into it when I was 11 and my first phase lasted about two years. Then I lost most interest for another 10 years, but during that time I caught up with all the newer Pokemon and all the movies, and told myself that it would always hold a special place in my heart.
Then Black and White rekindled my interest as a twentysomething, and I realized that there's too many things about this franchise that I love. I don't think I'll ever lose interest again.
I'll probably be a fan of this franchise until its end. I honestly don't see the franchise continuing for the next 60-80 years, it will probably end when the franchise out-lives the Game Freak developers! XD
Definitely, I see no reason why I would ever dislike it. Like a fine wine, Pokemon keeps improving with age, and even if everything to do with it suddenly became terrible, which I highly doubt, we'll always have the amazing first five Gens.
Yeah, Pokemon is the best. I haven't lost interest in it at all as I went along since the start of it all. I don't see that changing.
I'll more than likely always enjoy it, sure.
i would probably like pokemon for a long time but i will keep it a secreter thing until i invent a device that can put you in a game
Definetly, the franchise has been a part of me since i was like, 3, and i don't think i'll ever outrgrow it, some people may consider it a burden if you end up married or with a partner, however, if he/she loves you, he/she will accept it, me thinks.
Oh how i love spammy questions:) But of course I will love pokemon 4ever :D!
Maybe not when im 50.. :/
Haha:') ^^


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Book your room at Holiday Inn Express Dresden City Centre
Standard Room, 2 Single BedsMax Occupancy: 2 guests (up to 1 child, 1 infant)
Standard Double RoomMax Occupancy: 2 guests (up to 1 child, 1 infant)
Family-friendly Dresden hotel in Altstadt, walk to Dresden Castle
This family-friendly Dresden hotel is located in a shopping district, within a 10-minute walk of Church of the Holy Cross, Dresden Castle, and Church of Our Lady. Old Masters Picture Gallery and Zwinger Palace are also within 15 minutes.
Hotel Features
This hotel features a business center, a meeting room, and dry cleaning. Free continental breakfast and free WiFi in public areas are also provided. Other amenities include laundry facilities, a computer station, and multilingual staff.
Room Amenities
All 218 rooms offer free WiFi, coffee makers, and flat-screen TVs with satellite channels. Hair dryers, safes, and ironing boards are among the other amenities that guests will find.Information missing or incorrect? Tell us!
Hotel Amenities
Hotel Amenities
A computer station is located on site and high-speed wireless Internet access is complimentary. Business-related amenities at this 3-star property consist of a business center and a meeting room. A complimentary breakfast is offered each morning. This family-friendly hotel also offers multilingual staff, laundry facilities, and dry cleaning/laundry services.
- Number of floors - 7
- Number of buildings/towers - 1
- Multilingual staff
- Elevator/lift
- Computer station
- Luggage storage
- Total number of rooms - 218
- Business center
- Free breakfast
- Dry cleaning/laundry service
- Free WiFi
- Laundry facilities
- One meeting room
- Safe-deposit box at front desk
- Year Built 2011
Family Friendly Amenities
- Family Hotel
- Free Wi-Fi
- Laundry facilities
Available in all rooms: Free WiFi
Available in some public areas: Free WiFi
Room Amenities
- Connecting/adjoining rooms available
- Cribs/infant beds available
- Blackout drapes/curtains
- Daily housekeeping
- Private bathroom
- Hair dryer
- Iron/ironing board
- In-room safe
- Air conditioning
- Coffee/tea maker
- Desk
- Satellite TV service
- Flat-panel TV
- Free WiFi
Where to Eat
Guests are offered a complimentary continental breakfast each morning.
To make requests for specific accessibility needs, complete the "Special or Accessibility Requests" section of "Trip Preferences" when you book your hotel.
- Accessible path of travel
- Accessible bathroom
- Accessible parking
- In-room accessibility
Hotel Policies
Check-in time starts at 2 PM
Minimum check-in age is 18
Check-out time is noon
Payment types
You need to know
Extra-person charges may apply and vary depending on hotel policy.
Government-issued photo identification and a credit card or cash deposit are required at check-in for incidental charges.
Special requests are subject to availability upon check-in and may incur additional charges. Special requests cannot be guaranteed.
- A tax is imposed by the city: EUR 1.30 per person, per night. This tax does not apply to children under 18 years of age.
- Self parking fee: EUR 15 per day (in/out privileges)
We should mention
Children 18 years old and younger stay free when occupying the parent or guardian's room, using existing bedding. The property has connecting/adjoining rooms, which are subject to availability and can be requested by contacting the property using the number on the booking confirmation.


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1On leave from National Institute for Environmental Studies.
Developing a Multilayered Integrated Numerical Model of Surface Physics – Growing Plants Interaction (MINoSGI)
Article first published online: 23 APR 2004
DOI: 10.1111/j.1529-8817.2003.00768.x
Global Change Biology
Volume 10, Issue 6, pages 963–982, June 2004
Additional Information
How to Cite
Watanabe, T., Yokozawa, M., Emori, S., Takata, K., Sumida, A. and Hara, T. (2004), Developing a Multilayered Integrated Numerical Model of Surface Physics – Growing Plants Interaction (MINoSGI). Global Change Biology, 10: 963–982. doi: 10.1111/j.1529-8817.2003.00768.x
Publication History
- Issue published online: 26 APR 2004
- Article first published online: 23 APR 2004
- Received 1 March 2002; revised version received 18 July 2003; accepted 6 November 2003
- Abstract
- Article
- References
- Cited By
- a model for forest ecosystem dynamics;
- biosphere–atmosphere interactions;
- dynamics of plant size distribution;
- multilayered canopy model for a stand microclimate;
- vegetation–climate feedback
This paper describes a Multilayered Integrated Numerical Model of Surface Physics – Growing Plants Interaction (MINoSGI), which represents interactions between the dynamics of forest ecosystems and microclimate. Aiming at a large-scale study in the future, we describe forest dynamics by using area-averaged prognostic equations for thedistributions of plant density and plant weight with respect to plant height classes, instead of individual-based treatments for small-scale forest patches. Growth and mortality of plants are modelled based on the carbon balance of each plant height class. The area-averaged microclimate (e.g., light, wind speed, temperature, humidity, CO2 concentration) within the forest canopy is simulated by a one-dimensional multilayer canopy model, which includes most of the physical and physiological processes that control the forest microclimate. Owing to its multilayered framework, a direct specification is possible for the difference in the growing environment among plants of different size and species. Given hourly meteorological conditions, the model outputs energy, water, CO2 and momentum fluxes to and from a forest, of which the structure changes through competition among plants. The model's performance was tested by comparing its outputs with observed data on the development of plant size distribution taken over a 5-year period in an evergreen coniferous (Cryptomeria japonica) forest. The model produced realistic estimates of the total biomass increments during the period. The ratio of net primary production to gross primary production (=0.45) was consistent with previous estimates for temperate forests. The bimodal seasonal pattern in net ecosystem production was similar to the seasonal trend in the CO2 flux measured over a forest of the same species. Although some limitations due to the one-dimensional representation of microclimate were noticeable, the model adequately simulated distributions of annual growth rate, plant weight and diameter across plant height classes. Since the basic equations can be extended to include the effect of spatial variability with marginal increase of computational costs, the present model framework is feasible for large-scale studies.


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Follow-Up | Dow Indicator | Preview
Even as the Federal Reserve continues to debase the currency in the hope of stimulating the economy while Washington fiddles, wealthy yield-starved investors have been feasting on a different kind of credit that behaves like a certificate of deposit and has been earning returns of up to 10.5%.
Lending Club, an online peer-lending network based in San Francisco, matches consumers to lenders and has made $1.1 billion in loans since its 2007 start. It has seen assets under management in two vehicles that bundle prime consumer loans into investment funds go from zero to $250 million in just 18 months.
The draw? High yields. Its riskier Broad Based Fund pays 9% on a portfolio of prime credits that have a default rate of just 2%. The returns are taxable as ordinary income, but investors who can ante up $500,000 and who are taxed at the top rate of 35% still walk away with a predictable stream of income that surpasses returns on many comparable credits.
Just ask Harvard economist and former Treasury Secretary Lawrence Summers, an apparently satisfied customer who joined the Lending Club board last week. (He also sits on the board of tech payment company Square, co-founded by Twitter's Jack Dorsey.) "Information technology is making possible important financial innovations for the benefit of consumers and families alike," he told Barron's.
To say nothing of the benefit to investors. Bon appétit!
Last Week: Review
Fed Moves on QE4
The Federal Reserve plans to vastly expand its $2.8 trillion balance sheet in 2013, with monthly purchases of $45 billion of long-term Treasuries and continued buying of $40 billion of other securities. The stimulus replaces its $45 billion of monthly purchases of long-term Treasury securities and sales of a like amount of short-term instruments. The central bank dropped its mid-2015 target of keeping rates near zero, now tying a rate rise to a jobless rate of 6.5% or lower. By the Fed's reckoning, that would keep short-term rates low into 2015.
Troops to Turkey
The U.S. will deploy two Patriot missile batteries to Turkey with 400 troops to help defend its ally against potential threats from Syria, U.S. officials said. The move comes amid a view that Syria's president, Bashar al-Assad, will fall.
Follow the Money
HSBC Holdings 0005.HK 0.67618332081142% HSBC Holdings PLC (HK Reg) Hong Kong HKD67 0.45 0.67618332081142% /Date(1428008464000-0500)/ Volume (Delayed 15m) : 15083394 P/E Ratio 11.835155711787461 Market Cap 1273436728904.71 Dividend Yield 9.253910447761195% Rev. per Employee 2769230 More quote details and news » agreed to pay a record $1.92 billion in fines to U.S. authorities as part of a deferred prosecution agreement with the Justice Department in which it acknowledged that for years it ignored possible money-laundering and failed to conduct basic due diligence on some of its customers.
Loss Warning for Big Lender
Deutsche Bank, DBK.XE -0.030590394616090547% Deutsche Bank AG Germany: Xetra EUR32.68 -0.01 -0.030590394616090547% /Date(1427993258000-0500)/ Volume (Delayed 15m) : 1547062 P/E Ratio 22.21617946974847 Market Cap 44633279166.8415 Dividend Yield 2.294981640146879% Rev. per Employee 481985 More quote details and news » Europe's biggest lender, warned that additional restructuring costs will result in a big hit to fourth-quarter earnings that could end in a loss for the quarter. The bank also faces as much as 1.5 billion euros ($1.97 billion) in damages after being ruled liable for the insolvency of Kirch Media Group. Additionally, four employees were detained as part of a probe into suspected money laundering, and the bank is targeted in a probe into the manipulation of interbank rates.
Right-to-Work in Michigan
Michigan's Republican Gov. Rick Snyder signed "right to work" bills allowing workers in unionized shops in the public and private sector to opt out of paying union dues. The move in the state that produced the United Auto Workers follows curbs elsewhere in the Midwest.
Out of AIG
The U.S. Treasury completed the sale of its American International Group AIG 0.036503011498448625% American International Group Inc. U.S.: NYSE USD54.81 0.02 0.036503011498448625% /Date(1427922033266-0500)/ Volume (Delayed 15m) : 7139427 AFTER HOURS USD54.82 0.00999999999999801 0.01824484583105273% Volume (Delayed 15m) : 41742 P/E Ratio 10.45373920009155 Market Cap 75195771622.7137 Dividend Yield 0.9122422915526364% Rev. per Employee 981769 More quote details and news » stock for $7.6 billion, bringing it a profit of $22.7 billion from its bailout of the insurer during the financial crisis. It still holds warrants to buy 2.7 million shares.
State Department Intrigue
Facing a tough confirmation bid, U.N. Ambassador Susan Rice opted out of consideration to be secretary of state. Sen. John Kerry (D., Mass.) is now a front-runner.
In Brief
• Dish Network DISH -0.47102483585498145% DISH Network Corp. Cl A U.S.: Nasdaq USD69.73 -0.33 -0.47102483585498145% /Date(1427922000160-0500)/ Volume (Delayed 15m) : 1089853 AFTER HOURS USD69.73 % Volume (Delayed 15m) : 59345 P/E Ratio 34.014634146341464 Market Cap 32355752988.2656 Dividend Yield N/A Rev. per Employee 770705 More quote details and news » will be able to use part of the satellite-phone spectrum for cellphone service, with curbs.
• EU finance ministers agreed to create a single banking supervisor.
• A reported 20 children were among 27 people who died after a gunman opened fire in a Connecticut school.
He Said:
"Any protracted fall over the fiscal cliff would have grave economic consequences that I think most observers underestimate."
Former Treasury Secretary Lawrence Summers
The Numbers
The SEC's Office of the Whistleblower kept busy in its first fiscal year ended September:
3,001: total number of tips, complaints, and referrals received
18.2%: tips tied to corporate disclosure and financials
15.5%: tips on IPO frauds
$50,000: award for one tip
E-mail: firstname.lastname@example.com


text:
Order now to get your order delivered in time for Passover Click here for Passover cut-off dates>>
Passover Schedule:
Between Friday of April 3rd and Friday, April 10th. only items marked "Kosher for Passover" will be shipped. All other items will ship when we re-open on Monday, April 13th.
Thursday, April 9th: Shipping cut-off time: 11:00am ET. Office closes at 3pm.
Friday, April 10th: Closed.
Ingredients: Yogurt Coating (Sugar, Partially hydrogenated Palm Kernel Oil, Nonfat Milk Powder, Yogurt Powder, [Cultured Whey & Nonfat Milk], Artificial Color [Titanium Oxide], Lactic Acid, Soy Lecithin [emulsifier], Vanillin [artificial flavor]), Raisins, Gum Arabic, Sugar, Corn Syrup, Tapioca Dextrin, Confectioners Glaze. ALLERGY INFO: Contains milk and Soy. Made on shared equipment with peanuts, tree nuts, sesame seeds, and wheat containing ingredients.
Allergen Information: Processed in a facility that also processes Peanuts, Tree Nuts, Wheat, Soy and Milk products


text:
Latest Mental processes Stories
The 'Grandfather of Dreams' had been an instrumental adviser in the creation of DreamsCloud. Sterling, VA (PRWEB) February 06, 2014 The global community
While we may like to think of our brains as a video camera that records events exactly as they happen, a new study from scientists at Northwestern University has found that the brain acts more like an editing studio, cutting and splicing past events based on present circumstances.
In the science magazine "Neuropsychologia" the psychologists write that attractive faces without particularly remarkable features leave much less distinctive impressions on the memory
Lefty's The Left Hand Store's reviews top 500 for 2013 as customers rave about thelefthandstore.com's products and services.
A new study has looked at the differences between nightmares and bad dreams and found that fear does not always play a major role in either type of unpleasant dream.
For our brain, animate and inanimate objects belong to different categories and any information about them is stored and processed by different networks.
Memories are the way that infants learn new information, however, few adults can remember events that occurred before the age of three. According to a new study from Emory University psychologists, these early memories fade around age seven in a phenomenon known as "childhood amnesia."
People have a distance at which they are best able to judge depth.
A new study shows that the human mind can perceive change without knowing exactly what has changed, evidence against the existence of extrasensory perception (ESP), also known as a sixth sense.
While caffeinated beverages such as coffee and tea are commonly consumed by people looking for an early morning energy boost, new research appearing in the journal Nature Neuroscience suggests that they could also serve as a memory enhancer.
- Forsooth! indeed! originally a parenthetical phrase used in repeating the words of another with more or less contempt or disdain.


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3.10 out of 10 (what is this?)
Public Records
Arrest Records
Search Their Arrest Record, Driving Record, Marital Status and More...
Possible Username
Social Profiles and Hidden Pictures for justcindylou
Possible Links
Alternative Names:
lou c stone
59-year-old Cindy L Stone lives in Fort Myers, FL. She has also lived in Cape Coral, FL. She is a 1973 graduate of Parkdale High School. Companies in which she has a work history include State Of Florida. Her work experience includes positions as Office Manager and Administrative Assistant Ii. Cindy's a big fan of Mozart, Pop, Aerosmith, Audioslave, George Strait, Fleetwood Mac, Neil Young, Jimmy Buffett, Montgomery Gentry, Meat Loaf and Trace Adkins. Some of her favorite TV shows are Drama, Bones, House, The X-files, Csi Shows and A & E. She loves the films Comedy, Fantasy, Transformers, The Producers, Lord Of The Rings and Kungfu Panda. William Stanley Stone, William J Stone, John Stone, Elsie G Stone, William Stone, Stanley W Stone, Yvonne E Andersen and Yvon B Stone are in Cindy's family. Online, Cindy goes by the aliases justcindylou and seastone55.


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Israel-Hamas cease-fire remains elusive
Minutes before Ban's arrival in Jerusalem from Egypt, Palestinian militants fired a rocket toward Jerusalem, just the second time it has targeted the city. The rocket fell in an open area southeast of the city.
Jerusalem had previously been considered beyond the range of Gaza rockets - and an unlikely target because it is home to the Al-Aqsa Mosque compound, Islam's third-holiest shrine.
Israeli warplanes dropped leaflets on several Gaza neighborhoods asking residents to evacuate and head toward the center of Gaza City along specific roads. The army "is not targeting any of you, and doesn't want to harm you or your families," the leaflets said. Palestinian militants urged residents to ignore the warnings, calling them "psychological warfare."
Israeli security officials acknowledge they rely on a network of Palestinian informants to identify targets. Masked gunmen publicly shot dead six suspected collaborators with Israel in a large Gaza City intersection Tuesday, witnesses said.
An Associated Press reporter saw a mob surrounding five of the bloodied corpses shortly after the killing, and one of the bodies was dragged through the streets by a motorcycle.
Hamas did not provide any evidence against the alleged collaborators.
Clinton was also scheduled to meet with Palestinian President Mahmoud Abbas in the West Bank and Egyptian leaders in Cairo on Wednesday. Turkey's foreign minister and a delegation of Arab League foreign ministers traveled to Gaza on a separate truce mission. Airstrikes continued to hit Gaza even as they entered the territory.
"Turkey is standing by you," Turkish Foreign Minister Ahmet Davutoglu told the Hamas prime minister in Gaza, Ismail Haniyeh. "Our demand is clear. Israel should end its aggression immediately and lift the inhumane blockade imposed on Gaza."
At the United Nations, U.N. ambassadors after hours of closed-door meetings announced the Security Council will hold an open debate on the Gaza crisis Wednesday afternoon if a cease-fire is not called before then. The move comes after the United States blocked adoption of a unanimous press statement from the council because it did not explicitly criticize Hamas' rocket attacks on Israel.
The U.S. considers Hamas, which has killed hundreds of Israelis in suicide and other attacks, to be a terror group and does not meet with its officials. The Obama administration blames Hamas for the latest eruption of violence and says Israel has the right to defend itself. At the same time, it has warned against a ground invasion, saying it could send casualties spiraling.
Barzak reported from Gaza City, Gaza Strip. Associated Press writers Hamza Hendawi in Cairo, Karin Laub in Gaza City and Ian Deitch in Jerusalem contributed to this report.
The Associated Press


text:
Imperial Hotel Tokyo
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Happiness is a Heated Toilet Seat
... lighting in the room, the bathroom and in the walk-in wardrobe - this last item had space for clothes, our suitcases, shoes and had a dressing table with power points. There also was a 'valet cupboard' - if you had a delivery (e.g. the newspaper) this gets placed in the cupboard from the outside and a light goes on in the room to inform you of the delivery. The same process works in reverse - e.g. if there's laundry, you put this in the cupboard and press a button ...
Odaiba 'beach' resort
... off, which was the state we were probably at. Beer for 500¥, luxury. And it was the bar's own beer, which I like a lot. All the wandering around on top of a late start-de rigeur in Rappongi-meant that two beers at Heartland took us beyond midnight and I skedaddled, leaving Dominic to make his own fun/way home later. I'd missed the metro, though, and after realising I could get my aborted journey cancelled I came out of a different exit, realising ...
Two Days in Tokyo
... this area, I hardly spotted any tourists. When I did, there always tended to be a shared expression of content in the midst of this madness.
One of the things I had to check out while here (thanks to Samantha Brown's Japan) was the cat cafe phenomenon that have been popping up in many populous cities of Japan. A cat cafe is, just that, a coffee shop…with cats! In big cities like Tokyo, many apartment rules do not allow for animals so this is a therapeutic place ...
Getting there is always the hardest part.
Where do I begin? I guess for one thing, I might like to make clear that international travel- at least the way I travel internationally -is not glamorous. It's fun. It's exciting. It's always a beautiful learning experience. But glamorous? No. From the very beginning its hallmark is relatively constant physical discomfort. 10 hours locked in the economy class section of a Boeing 747 kick starts that. Yes, you (typically) get your own TV screen with movies, ...
Fluent Engrish
... streets to the bizarre backdrop of locals of all ages sucking on penis and vagina shaped lollypops. Afterwards we chilled in the sun around Yokohama Bay, travelling on the crowded metro in a big, tired group-hug formation – no doubt a bizarre sight for the locals.
That night I experienced my first earthquake! This was the one thing I was hoping to experience but could not organise for myself. Again Glichelle laughed at my goofy excitement ...


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Stern Granny Mom 2008-04-07 6:30


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The Ford Fusion is a midsize family sedan, available with a conventional drivetrain or a comparatively low-cost hybrid system, as well as the plug-in hybrid Ford Fusion Energi.
Ford focuses on performance with the introduction of the 2016 Focus RS (Rallye Sport), the third-generation of the automaker's "hot hatch," and has announced that this model will be available for the first time in the U.S. market.
Ford says that the original F-150 SVT Raptor was designed to demonstrate that off-roading can be even more fun than going fast around a racetrack. Now, with the redesigned 2017 Ford F-150 Raptor, the automaker has improved this recipe for fun.
When the new Ford GT debuted at the 2015 North American International Auto Show (NAIAS) in Detroit, the automaker reminded its audience that Henry Ford inspired investors to back his car company by winning a 1901 auto race.
Inspired by the 1965 Ford Mustang Shelby GT350 Competition, and calling it "the most race-ready road-legal Mustang ever," Ford introduced the limited-production 2016 Mustang Shelby GT350R at the 2015 Detroit Auto Show.
The 2016 Ford Explorer, which just made its global debut at the 2014 Los Angeles Auto Show, reaches a new level of luxury with its top-of-the-line Platinum trim level.
At the 2014 Los Angeles Auto Show, Ford introduced the latest iteration of the popular midsize Explorer crossover SUV, the refreshed 2016 Ford Explorer.


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how do I replace the 3rd brake light (center - mounted in the rear window) on a 1999 Chevrolet Prizm? Does it have a bulb?
View questions for:All Chevrolet
1999 Chevrolet Prizm
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1999 Chevrolet Prizm Question: How do you replace the 3rd brake light on a 1999 Chevy Prizm?
Visitor, Winchester, CA, January 17, 2011, 23:43
1 Answer
Answer #1patrick mannion from Greg Solow's Engine Room, January 18, 2011, 00:47Master
Instructions say gently pry loose the third brake light housing assembly, disconnect the electrical connector, rotate the bulb holder to remove and replace bulb.
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CNN: Bulgaria's PM to Tender Govt's Resignation at Noon
Views on BG | February 20, 2013, Wednesday // 11:00| Views: 728 | Comments: 0
Bulgaria has seen eight days of nationwide protests over high energy bills. Photo by Sofia Photo Agency
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By CNN
Bulgarian Prime Minister Boyko Borissov told parliament he would tender his government's resignation Wednesday, according to state media reports, following eight days of nationwide protests over high energy bills.
The protests against soaring electricity bills have morphed into wider discontent over austerity and the way the country is being run, the official Bulgarian News Agency reported.
Borissov told lawmakers his party would not be part of a caretaker government. The government will resign from office at noon local time.
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- » ''Communism Didn't Die in 1989: It Lives in People's Minds,' Bulgarian Photographer for TIME Magazine
- » Balcaniecaucaso Tells the Touching Story of Bulgaria's Gorna Bela Rechka


text: Carpets & Candids: Juno's clashing hair January 7, 2013 18:01:15 Posted at January 7, 2013 18:01:15 Posted by Lainey facebook twitter google+ email Tags: Assy Hair Assy Style Juno Temple Photos:WENN This is a mess. There's so much going on: the print on the dress, the screaming spikes on the clutch, the gold heel, and all of it fighting with...that hair. Previous Lifestyle Article Next Lifestyle Article Related on LaineyGossip Kerry Washington's Black Dress at the 2015 Independent Spirit Awards Emma Stone at the 2015 Independent Spirit Awards Carpets & Candids: Halle Berry's uneven dress Carpets & Candids: Sarah Silverman's cute birds but the shoes Around the Web


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Thursday's Poem – Snake Haiku & How to Cut the Cord
Two in from Mr. Bussman this week, a haiku and a poem. Jake hates poetry poetry is good for you I kind of hate Jake. Continue reading
Two in from Mr. Bussman this week, a haiku and a poem. Jake hates poetry poetry is good for you I kind of hate Jake. Continue reading
I can't wait to see Bike Snob NYC tackle this one — a crew of teens in Queens riding two-wheeled sound systems. Nick Ragbir's DJ Continue reading
Remember the Birthday Challenge? Oh, I do. Shit is off the hook. In fact, I've been knocking around the idea of doing something really stupid Continue reading
Oh great. Random attack on Brookline bicyclist may be gang-related Police say a 37-year-old man who was attacked by four teen-agers as he biked home Continue reading
This needs no further explanation: Stevie Wonder. Vid after the fold. by
So I got this hunch for 08…… This kid here is going to blow up big time, cuz its Keim Time!!!! by
From BBC news online : 'Chinese' tequila worries Mexico Mexican tequila sells well in the US Mexican politicians are demanding action to protect the tequila Continue reading
This has got to be the most patshit crazy idea I have heard of since Perot got in the game back in the day. Kucinich Continue reading
Oh hell. T-Mobile ends sponsorship; teams to continue with new name The T-Mobile cycling program has lost its title sponsor, but the American director of Continue reading
A young man named John received a parrot as a gift. The parrot really had a bad attitude and an even worse vocabulary. Every word Continue reading
So I get this email… From: Husky Midget Subject: Big Schwannson BDJ whats up? I never knew a scewdriver could be classified as a concealed Continue reading
They told us it would pay for itself. Once they got the oil up and running, the money would just pour out. Reconstruction was a Continue reading


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The Official Site of Ocean City, MD
Showing Results for General
Perryville MD
Insider since: 2008
Answered: March 30, 2015
Several restaurants in the OC area offer free wifi, including Buxy's Salty Dog on 28th Street, Shenanigan's on the Boardwalk at 3rd Street, FishTales on 22nd Street, Harpoon Hanna's on 142nd Street, Fager's Island on 60th Street, Micky Fins at OC Fishing Center, Coconuts Beach Bar & Grill at 37th Street, and various McDonalds' locations.
Another location near the boardwalk is Ocean City Wifi on Somerset Street (for more information contact them directly at (410) 524-2233).
Thank you,
Anna G.
Johnstown Pa
Insider since: 2009
Answered: March 27, 2015
The third weekend of May (14-17)is Cruisin' Ocean City weekend and the town will be hopping with thousands of people and cars, but following that it will thin out. You won't find the rides or games open yet, but there will be stores open and shops and bars. The following weekend is busy with events, so please check our event calendar at http://www.ococean.com/events .
Johnstown Pa
Insider since: 2009
Answered: March 27, 2015
Hi Debbie. No. But let me clarify. Dogs are not permitted on the beach or the boardwalk loose, on a leash, or in a stroller or carrier between May 1 and September 30. But between October 1 to April 30, they can. So depending upon when you're coming.......he may or may not be allowed. If you do bring your dog in the summer during the blocked out months, he or she must be on a leash at all other times when outside.
Pittsburgh Pa
Insider since: 2014
Answered: March 25, 2015
My kids and I, have been in the ocean as early as Easter MANY times, but that's usually just up to our knees.
Memorial Day, the water is on the cooler side, compared to how it warms up in Aug. but people will absolutely be in the water - and if we make it to town that weekend, I can guarantee we will be on the beach, and in the ocean!
Go and have fun!!!
Centreville, VA
Insider since: 2010
Answered: March 25, 2015
There are no great options for flying to Ocean City. The closest airport to OC with commercial service is Salisbury - Ocean City (SBY). However, SBY only has connecting flights offered by US Air to Philadelphia, PA., and Charlotte, NC. SBY is about 30 miles from OC, so you would need to rent a car or take a cab (about $60 each way) to get to OC.
If you want to fly to a larger airport and then rent a car, Dulles (IAD), Washington National (DCA), Baltimore-Washington (BWI), and Philadelphia (PHL) airports are all about a 3 hour drive (about 160 miles) to OC.
If you have access to your own plane, you can fly to Ocean City Airport (OXB) which is a General Aviation airport about 5 miles from Ocean City.
Hunt Valley and Ocean City
Insider since: 2010
Answered: March 24, 2015
Hi Ashley,
At this point in the season it is hit or miss - even during Spring Break. Several stores - Fishers, Candy Kitchen, the arcades, Thrashers - are open all year long. In April, many stores will usually open on the weekend and during the week if it is warm. We were on the Boardwalk two weeks ago and found about 10% of the stores open. I would go for a stroll and see what is open. I am sure something interesting will be open.
Hunt Valley and Ocean City
Insider since: 2010
Answered: March 24, 2015
Hi China,
At this point in the season it is hit or miss. Several stores - Fishers, Candy Kitchen, the arcades, Thrashers - are open all year long. In April, many stores will usually open in the weekend and during the week if it is warm. We were on the Boardwalk two weeks ago and found about 10% of the stores open. I would go for a stroll and see what is open.
Johnstown Pa
Insider since: 2009
Answered: March 23, 2015
Happy Anniversary! Yes! That's Memorial Day weekend and everything on the boardwalk will be open along with everything else. The rides may not open until Friday or Saturday, but all of the stores and restaurants will be open.
If you're looking for a lovely place to stay, I recommend the Inn on the Ocean on 10th St. It's Ocean City's only oceanfront bed and breakfast and it's adults only. Very beautiful inside and out, outstanding breakfast each morning on their lovely porch overlooking the ocean, and they provide their guests with use of beach chairs and bicycles at no charge.
Here's hoping that the weather is fantastic!
Johnstown Pa
Insider since: 2009
Answered: March 20, 2015
The boardwalk is always open and available for walking and bike riding. But the rides and such don't open unitl Memorial Day Weekend. Beginning in April, you'll find shops opening more on the weekends and places like Thrasher's Fries and Fisher's Popcorn will open for limited hours on the weekends as well. Once you get into May and Springfest weekend, things really pick up and places will stay open during the week. But rides and games will hold off until the big holiday weekend in May.
Linthicum MD and OC MD
Insider since: 2008
Answered: March 19, 2015
Hi Judy,
http://www.ocboards.com has an excellent interactive map where you click on it and find all of the attractions, eateries, store, amusements, etc in the location you click on.


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Telephone & Addresses
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Juanita Beck
75028 Flower Mound TX
Juanita Beck
98002 Auburn WA
Juanita Beck, Dallas, US, E Ledbetter Dr, Apt 150
View Juanita's social profiles and photos on Facebook, MySpace, and +40 Networks.
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MySpace Profile: juanita beck (294114144)
West Chester, PA
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JUANITA BECK on Prezi
JUANITA BECK. JUANITA BECK is using Prezi to create and share presentations online. ♥ Prezi? Sign up now, it's free!
Spring's palette is bright - Tucson Citizen Morgue, Part 1 (2006-2009)
The great thing about this season's hues is how well you can incorporate them with traditional fall solids, says Juanita Beck, ladies department ...
Management & Stakeholders
JUANITA BECK - SILEX, MO - Company Profile -- Dun ...
Juanita Beck was founded in 2010. Juanita Beck specializes in Nonclassifiable Establishments. VERIFIED Status:UNVERIFIED. Address: UNVERIFIED.
Business Profiles
Xing: Juanita Beck
HR Generalist / Providence, Vereinigte Staaten
Juanita Beck - Previous Manager for Beck Enterprise, LLC
View 1 historical company role for Juanita Beck in Nevada.
Juanita Beck - Previous Registered Agent for Cistern Volunteer Fire...
View 1 historical company role for Juanita Beck in Texas.
Juanita Beck
Preview the profile for Juanita Beck. Docstoc is a community for people to find and share professional documents.
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classmates: Juanita Beck
Arlington High School, Arlington, WA, 1999-2003
classmates: Juanita Beck
Spring Grove High School, Spring Grove, PA, 1986-1990
classmates: Juanita (Aguerrebere) Aguerrebere Beck
New Rochelle High School, New Rochelle, NY, 1990-1992
classmates: Juanita (Constant) Beck
McLoughlin Junior High School, Vancouver, WA, 1971-1975
Bad news
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legacy.com: Juanita Beck
BECK, JUANITA Age 82, passed away January 14, 2006. TILLMAN RIVERSIDE MORTUARY - 682-6433
legacy.com: Juanita F. Beck
JUANITA F. BECK, age 94, wife of the late Bob Beck. She is survived by a daughter, one sister, two grandchildren and two great grandchildren. Memorial services will be held
Juanita Beck - Latest Mugshots
Juanita J Beck was arrested or detained on Fri Aug 30, 2013 | Larimer County, Colorado Regional News by MobileMugs.
Dora Juanita Beck | Billion Graves Record
Headstone Record for Dora Juanita Beck. Burial Place: Chattanooga, Tennessee , United States. Birth: 1904. Death: 1967.
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Juanita Beck (Juanita Dayringer) (deceased) - Genealogy
Genealogy for Juanita Beck (Juanita Dayringer) (deceased) on Geni with over 140 million profiles of ancestors and living relatives.
On-line Obituary For Juanita G. Beck - Obituaries
BECK, Juanita G., age 81, passed away in Sevierville after a short stay at a nursing home facility and has now gone to be with Jesus and her ...
176 Genealogy and Family History Records for Juanita Beck
176 Genealogy and Family History Records for Juanita Beck. Record Type, Total Records. Newspaper Archives (1690 – 2010), 131. View Records. Newspaper ...
Juanita Beck (1949 - 2001) - Jasper, GA - AncientFaces.com
This is a bio of Juanita Beck with Juanita's family history and family photos. Juanita Beck was born on November 11, 1949. Juanita Beck died on February 6, ...
Books & Literature
Billboard - 26 Jun 1948 - Page 60 - Google Books Result
... Hollywood Thrill Rodeo and Wild West. Also engaged are Dave Malcolm, announcer; Al Melgard, musical director and electric organist; Juanita Beck, calliope, ...
Learning a Trade: A Craftsman's Notebooks, 1955-1997
Martha becomes one more devastated woman off whom Whit pivots, though gratefully, into a new fuller life (so far, there are three— Juanita, Beck and Martha; ...
Sunset High School - Sundial Yearbook (Dallas, TX), Class of 1980,...
... to three women that not only work for us but with us. The 1980 Sundial pays tribute to Martha McSweeney, Brenda Eisworth, and Juanita Beck. Juanita Beck.
Learning a Trade: A Craftsman's Notebooks, 1955-1997 - Reynolds Price...
From Reynolds Price, much acclaimed author of award-winning novels, plays, poems, stories, and essays, comes a work that is unique among contemporary writers...
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2014 Burgoo Committee List - Arenzville
Jennifer Petefish. Lisa Musch. Jacob Meyer. Scott Musch. Alison Meyer. Kittena Beard. Juanita Beck. Jill Roegge. Gail Dunkel. Matthew Meyer.
December 2013 - New-Mac Electric
Leroy & Juanita Beck. Stacy H. & Stacie J. Beck. Vali A. Beck. Abram & Katie Beiler. Grover & Eunice Bell. Mary F. Bell. Russell L. & Rebecca N.
the oracle meryl tankard - Ade…e Festival Centre
Juanita Beck. Programming Coordinator. Dana Mickan. Marketing Executive. Rebekah Webb. Marketing Coordinator. Nadia Mignone. Graphic Designer.
Father: Daniel Buie* Dodson Mother: Lottie Elizabeth* Wilson Spouse: Juanita* Beck Drye, Buddy Frank 25 Nov 1937 22 May 2000 , Saline Co, Arkansas
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Juanita Beck : playing some of her favorite selections on her ...
Juanita Beck : playing some of her favorite selections on her circus calliope.. [ Juanita Beck; La Crosse County Historical Society (La Crosse, Wis.)]
Merry Christmas, 2007, Post 1
17.12.2007 I remember him because of my much-loved, now departed, piano teacher, Juanita Beck. So, without further adieu, this year's useless Christmas Letter: ——————————————————————-. hello. i am a box-elderbug and i live with sam and kellie. i ...
What Did You Eat?: Ruth's Chris Sweet Potato Casserole
22.11.2006 Posted by: Juanita Beck | March 23, 2007 at 03:55 PM. Nick. I had the sweet potato casserole at a Ruth's Chris in Hawaii, and they made it with Okinawan Sweet Potatoes instead. It was a bit sweeter and made us think of brownies because ...
Juanita Beck : playing some of her favorite selections on her circus...
Get this from a library! Juanita Beck : playing some of her favorite selections on her circus calliope.. [Juanita Beck; La Crosse County Historical Society ...
Video & Audio
Juanita Beck - YouTube
Loading... Working... Juanita Beck. Home. Videos · Playlists · Channels · Discussion · About. All activities. Juanita Beck subscribed to a channel 1 year ago ...
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Attorney Says Decision Due In Beck Case .Graham Aide ...
Juanita Beck, Gary Beck's er, said her family and Glades Coun ty residents wanted someone besides investigators to probe her son's death because of two ...
Search List Expands in Washington State Mudslide - The ...
"Everyone knows someone that's missing or affected," said Juanita Beck, the manager of the Stilly Coffee House here in Arlington, a city where ...
Jackson County Obituaries... December 5, 2001 - The ...
Mr. Beck was preceded in death by a daughter, Juanita Beck, and a grandson, Greg Beck. Funeral services were held at 10 a.m. Saturday, ...
McCraw wins American Quarter Horse Association World ...
Will lives in East Bend, N.C., and is the son of Doug and Cindy McCraw; the grandson of Lonnie McCraw/Juanita Beck, Wayne and Annabelle Horton and the ...
Reports & Statements
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Google Groups: US-MA Sales Support Engineer - Symmons Industries
25.01.1999: Insure timely ordering & delivery of material for special applications Please mail resumes to: Juanita Beck Recruitment Manager Symmons Industries 31 Brooks ...
Google Groups: US-MA Production Scheduler - Symmons Industries
25.01.1999: ... breakdowns that may cause slippage of due dates Please mail resumes to: Juanita Beck Recruitment Manager Symmons Industries 31 Brooks Drive Braintree, ...
Google Groups: US-MA Quality Technician - Symmons Industries
25.01.1999: Please mail resumes to: Juanita Beck Recruitment Manager Symmons Industries 31 Brooks Drive Braintree, MA 02184 or fax to: 781-356-0658 or email ...
Juanita Beck Condolences | Cagle Funeral Home - Jasper
Guest Book for Juanita Beck of Jasper, GA. Share your condolences, send flowers, find funeral home information. Guestbook provided by Cagle Funeral Home -...
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JUANITA BECK - Yahoo Profile
JUANITA BECK profile picture change picture. save. By uploading a file you certify that you have the right to distribute this picture and that it does not violate the ...
Juanita Beck Death Records - FindTheBest Genealogy
Find death records for Juanita Beck. Over 100 million deaths from around the world. Research your ancestors for free in our extensive genealogy databases.
Ernest A. & Juanita Beck - Oklahoma Cemeteries
Ernest A. & Juanita Beck. Resthaven Cemetery. |Ba-Bm Surnames for Resthaven Cemetery Page| |Pottawatomie County Cemetery Page| ...
Jim Rhodes/Juanita Beck - Deanna O'Reilly's Genealogy Site
Wife: Juanita Beck. Born: 11 OCT 1912 at: Fayettte County, Illinois Died: 26 NOV 1953 at: Fayettte County, Illinois Father: Alvin Mulvaney Beck Mother: Clara ...
Juanita Beck - Cuca Records
Juanita Beck. Default, Name A - Z, Name Z - A, Price Low > High, Price High > Low, Rating Highest, Rating Lowest, Model A - Z, Model Z - A. Sort By: ...
Juanita Beck - Foodspotting
Juanita Beck's reviews of favorite dishes at local restaurants.
Juanita Beck - Rodan + Fields Independent Consultant
Juanita Beck - Rodan + Fields Independent Consultant.
Juanita Beck b. 1918 d. 1946: The Sprague Project
Name, Juanita Beck [1]. Born, 1918 [1]. Gender, Female. Died, 1946 [1]. Person ID, I224924, Sprague Project. Last Modified, 20 Sep 2014 ...
Juanita R Beck (308) 536-2570 - Fullerton - Nebraska
Public Records for: Juanita Beck, 56549 S 280 Ave Fullerton NE.
Juanita P. Beck :: Obituary Index - JoCoHistory
Name, Juanita P. Beck. Subject - Name, Beck, Juanita P. Death Date, 8/16/2004. Age at Death, 55. Newspaper Title, Kansas City Star. Publish date, 8/18/2004.
Juanita Beck from Canton (GA) - Artful Technologies
Email: [email protected]. Username: Exclasen. Password: *******. Telephone Number: 770-345-4249. Mothers Maiden: Stephens. Birthday: 6/15/1950. Color ...
Juanita Beck b. d. : Kletke-Durham Genealogy - Kletke.com
Gender, Female. Person ID, I0304, Kletke-Durham. Last Modified, 21 Jul 2009. Family, Nathan K. Oldham. Children. 1. Sharon Kay Oldham. 2. Walter Lee ...
Dallas ISD Counselors honored with the CREST Award
Joy Duncan. John F Kennedy Learning Center. Juanita Beck. Moises E. Molina High School. Tiffany Gilmore. Loree Jones. Maria Herrera. Sherry Burton-Wright.
In Memory of Doris Marie Beck -- BOXWELL BROS ...
Sister-in-law Juanita Beck Tucker, San Angelo, TX, brother-in-law Billy Joe Beck of Spearman, 8 grandchildren and 14 great-grandchildren.
Oklahoma Obituary and Death Notice Archive - Page 783
Lucy Juanita Beck, 82, Shawnee, died Thursday at Shawnee Care Center. Graveside service will be 2 p.m. today at Resthaven Memorial Park ...
Recipients in Pennsylvania - Hunters For Hungry
... Turkey, Hogs, Small Game, Packaged, 0. Juanita Beck, Chambersburg, Pennsylvania, PA, Deer, Birds, Turkey, Hogs, Small Game, Whole (Field Dressed ), 0.
Calliope Capers - Juanita Beck: LP - GEMM.com
Calliope Capers - Juanita Beck: LP - GEMM.com.
Juanita R Beck - 308-536-2570 | 56549 S 280 Ave , Fullerton White...
White Pages: Juanita R Beck 308-536-2570
Karen Juanita Beck, Born 10/02/1950 in California |...
View Karen Juanita Beck's birth record on CaliforniaBirthIndex.org. CaliforniaBirthIndex.org is the best place to find free birth records for people like Karen...
Juanita Beck ~ Calliope Capers LP - CDs - Records
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Home » NH Angle
Nashua police working on records detailing the disposal, release of out of commission weapons, equipment
In January, aldermen approved the department's purchase of 154,000 rounds of .40-caliber Smith & Wesson ammunition, 4,000 rounds of .308-caliber rifle ammunition, 10,000 rounds of .223-caliber semi-automatic rifle ammunition, and 31,500 rounds of 5.56x45-caliber ammunition and 22 bullet-proof vests over the remaining fiscal 2013 budget year. With that in mind, we wondered where the rest of the department's hundreds and thousands of dollars worth of equipment goes when it is considered out of commission?
Insurer offers to settle wheelchair crash claim
Barnstead teen gets 20 years for near-fatal stabbing in Bear Brook State Park
Rockingham County sued for teen's alleged jailhouse beating
Belknap County commissioner's chairmanship dispute heads to court
Police officer: 'I was watching a crime'
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Merrimack County locked in polygraph dispute with retired DEA agent looking to double dip with Liquor Commission
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Joe McQuaid's Publisher's Notes: If you see leprechauns tomorrow, you might soon be seeing Jean Valjean
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Burned Claremont apartments will be fixed
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Are you Shuang Huang?Claim your profile
Publications (58)320.26 Total impact
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ABSTRACT: ER stress has been implicated in the pathogenesis of both acute and chronic kidney diseases. However, the molecular regulation of ER stress in kidney cells and tissues remains poorly understood. In this study, we examined Tunicamycin-induced ER stress in renal proximal tubular cells (RPTC). Tunicamycin induced the phosphorylation and activation of PERK and eIF2α within 2 hours in RPTC, which was followed by the induction of GRP78 and CHOP. Consistently, Tunicamycin also induced apoptosis in RPTC. Interestingly, mTOR was activated rapidly during Tunicamycin treatment as indicated by phosphorylation of both mTOR and p70S6K. Inhibition of mTOR with Rapamycin partially suppressed the phosphorylation of PERK and eIF2a and the induction of CHOP and GRP78 induction during Tunicamycin treatment. Rapamycin also inhibited apoptosis during Tunicamycin treatment and increased cell survival. Collectively, the results suggest that mTOR plays a regulatory role in ER stress and inhibition of mTOR may have potential therapeutic effects in ER stress-related renal diseases. Copyright © 2014, American Journal of Physiology - Renal Physiology.American journal of physiology. Renal physiology 11/2014; 308(3):ajprenal.00629.2014. DOI:10.1152/ajprenal.00629.2014 · 3.30 Impact Factor
Article: SHOX2 Is a Direct miR-375 Target and a Novel Epithelial-to-Mesenchymal Transition Inducer in Breast Cancer Cells.[Show abstract] [Hide abstract]
ABSTRACT: MicroRNAs have added a new dimension to our understanding of tumorigenesis and associated processes like epithelial-to-mesenchymal transition (EMT). Here, we show that miR-375 is elevated in epithelial-like breast cancer cells, and ectopic miR-375 expression suppresses EMT in mesenchymal-like breast cancer cells. We identified short stature homeobox 2 (SHOX2) as a miR-375 target, and miR-375-mediated suppression in EMT was reversed by forced SHOX2 expression. Ectopic SHOX2 expression can induce EMT in epithelial-like breast cancer cells, whereas SHOX2 knockdown diminishes EMT traits in mesenchymal-like breast cancer cells, demonstrating SHOX2 as an EMT inducer. We show that SHOX2 acts as a transcription factor to upregulate transforming growth factor β receptor I (TβR-I) expression, and TβR-I inhibitor LY364947 abolishes EMT elicited by ectopic SHOX2 expression, suggesting that transforming growth factor β signaling is essential for SHOX2-induced EMT. Manipulating SHOX2 abundance in breast cancer cells impact in vitro invasion and in vivo dissemination. Analysis of breast tumor microarray database revealed that high SHOX2 expression significantly correlates with poor patient survival. Our study supports a critical role of SHOX2 in breast tumorigenicity.Neoplasia (New York, N.Y.) 04/2014; DOI:10.1016/j.neo.2014.03.010 · 5.40 Impact Factor
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ABSTRACT: MicroRNAs (miRNAs) play key roles in inflammatory responses of macrophages. However, the function of miRNAs in macrophage-derived foam cell formation is unclear. Here, we investigated the role of miRNAs in macrophage-derived foam cell formation and atherosclerotic development.Methods and ResultsUsing quantitative reverse transcription-PCR (qRT-PCR), we found that level of miR-155 expression was increased significantly in both plasma and macrophages from atherosclerosis (ApoE(-/-)) mice. We identified that oxidized LDL (oxLDL) induced the expression and release of miR-155 in macrophages, and that miR-155 was required to mediate oxLDL-induced lipid uptake and reactive oxygen species (ROS) production of macrophages. Further, ectopic overexpression and knockdown experiments identified that HMG box-transcription protein1 (HBP1) is a novel target of miR-155. Knockdown of HBP1 enhanced lipid uptake and ROS production in oxLDL-stimulated macrophages, and overexpression of HBP1 repressed these effects. Furthermore, bioinformatics analysis identified three YY1 binding sites in the promoter region of pri-miR-155 and verified YY1 binding directly to its promoter region. Detailed analysis showed that the YY1/HDAC2/4 complex negatively regulated the expression of miR-155 to suppress oxLDL-induced foam cell formation. Importantly, inhibition of miR-155 by a systemically delivered antagomiR-155 decreased clearly lipid-loading in macrophages and reduced atherosclerotic plaques in ApoE(-/-) mice. Moreover, we observed that the level of miR-155 expression was upregulated in CD14(+) monocytes from patients with coronary heart disease. Our findings reveal a new regulatory pathway of YY1/HDACs/miR-155/HBP1 in macrophage-derived foam cell formation during early atherogenesis and suggest that miR-155 is a potential therapeutic target for atherosclerosis.Cardiovascular Research 03/2014; DOI:10.1093/cvr/cvu070 · 5.81 Impact Factor
Article: HOXC8 promotes breast tumorigenesis by transcriptionally facilitating cadherin-11 expression.[Show abstract] [Hide abstract]
ABSTRACT: Cell-cell adhesion molecule cadherin-11(CDH11) is preferentially expressed in basal-like breast cancer cells and facilitates breast cancer cell migration by promoting small GTPase Rac activity. However, how the expression of CDH11 is regulated in breast cancer cells is not understood. Here, we show that CDH11 is transcriptionally controlled by homeobox C8 (HOXC8) in human breast cancer cells. HOXC8 serves as a CDH11-specific transcription factor and binds to the site of nucleotides -196 to -191 in the CDH11 promoter. Depletion of HOXC8 leads to the decrease in anchorage-independent cell growth, cell migration/invasion and spontaneous metastasis of breast cancer cells; however, suppressed tumorigenic events were fully rescued by ectopic CDH11 expression in HOXC8-knockdown cells. These results indicate that HOXC8 impacts breast tumorigenesis through CDH11. The analysis of publically available human breast tumor microarray gene expression database demonstrates a strong positive linear association between HOXC8 and CDH11 expression ( = 0.801, p < 0.001). Survival analysis (Kaplan-Meier method, log-rank test) show that both high HOXC8 and CDH11 expression correlate with poor recurrence-free survival rate of patients. Together, our study suggests that HOXC8 promotes breast tumorigenesis by maintaining high level of CDH11 expression in breast cancer cells.Oncotarget 03/2014; · 6.63 Impact Factor
Article: The Histone H3 Methyltransferase G9A Epigenetically Activates the Serine-Glycine Synthesis Pathway to Sustain Cancer Cell Survival and Proliferation.[Show abstract] [Hide abstract]
ABSTRACT: Increased activation of the serine-glycine biosynthetic pathway is an integral part of cancer metabolism that drives macromolecule synthesis needed for cell proliferation. Whether this pathway is under epigenetic control is unknown. Here we show that the histone H3 lysine 9 (H3K9) methyltransferase G9A is required for maintaining the pathway enzyme genes in an active state marked by H3K9 monomethylation and for the transcriptional activation of this pathway in response to serine deprivation. G9A inactivation depletes serine and its downstream metabolites, triggering cell death with autophagy in cancer cell lines of different tissue origins. Higher G9A expression, which is observed in various cancers and is associated with greater mortality in cancer patients, increases serine production and enhances the proliferation and tumorigenicity of cancer cells. These findings identify a G9A-dependent epigenetic program in the control of cancer metabolism, providing a rationale for G9A inhibition as a therapeutic strategy for cancer.Cell metabolism 12/2013; 18(6):896-907. DOI:10.1016/j.cmet.2013.11.004 · 17.35 Impact Factor
Article: HOXC9 directly regulates distinct sets of genes to coordinate diverse cellular processes during neuronal differentiation.[Show abstract] [Hide abstract]
ABSTRACT: Cellular differentiation is characterized by the acquisition of specialized structures and functions, cell cycle exit, and global attenuation of the DNA damage response. It is largely unknown how these diverse cellular events are coordinated at the molecular level during differentiation. We addressed this question in a model system of neuroblastoma cell differentiation induced by HOXC9. We conducted a genome-wide analysis of the HOXC9-induced neuronal differentiation program. Microarray gene expression profiling revealed that HOXC9-induced differentiation was associated with transcriptional regulation of 2,370 genes, characterized by global upregulation of neuronal genes and downregulation of cell cycle and DNA repair genes. Remarkably, genome-wide mapping by ChIP-seq demonstrated that HOXC9 bound to 40% of these genes, including a large number of genes involved in neuronal differentiation, cell cycle progression and the DNA damage response. Moreover, we showed that HOXC9 interacted with the transcriptional repressor E2F6 and recruited it to the promoters of cell cycle genes for repressing their expression. Our results demonstrate that HOXC9 coordinates diverse cellular processes associated with differentiation by directly activating and repressing the transcription of distinct sets of genes.BMC Genomics 11/2013; 14(1):830. DOI:10.1186/1471-2164-14-830 · 4.04 Impact Factor
Article: COP1 and GSK3β Cooperate to Promote c-Jun Degradation and Inhibit Breast Cancer Cell Tumorigenesis.[Show abstract] [Hide abstract]
ABSTRACT: High abundance of c-Jun is detected in invasive breast cancer cells and aggressive breast tumor malignancies. Here, we demonstrate that a major cause of high c-Jun abundance in invasive breast cancer cells is prolonged c-Jun protein stability owing to poor poly-ubiquitination of c-Jun. Among the known c-Jun-targeting E3 ligases, we identified constitutive photomorphogenesis protein 1 (COP1) as an E3 ligase responsible for c-Jun degradation in less invasive breast cancer cells because depletion of COP1 reduced c-Jun poly-ubiquitination leading to the stabilization of c-Jun protein. In a panel of breast cancer cell lines, we observed an inverse association between the levels of COP1 and c-Jun. However, overexpressing COP1 alone was unable to decrease c-Jun level in invasive breast cancer cells, indicating that efficient c-Jun protein degradation necessitates an additional event. Indeed, we found that glycogen synthase kinase 3 (GSK3) inhibitors elevated c-Jun abundance in less invasive breast cancer cells and that GSK3β nonphosphorylable c-Jun-T239A mutant displayed greater protein stability and poorer poly-ubiquitination compared to the wild-type c-Jun. The ability of simultaneously enforced expression of COP1 and constitutively active GSK3β to decrease c-Jun abundance in invasive breast cancer cells allowed us to conclude that c-Jun is negatively regulated through the coordinated action of COP1 and GSK3β. Importantly, co-expressing COP1 and active GSK3β blocked in vitro cell growth/migration and in vivo metastasis of invasive breast cancer cells. Gene expression profiling of breast tumor specimens further revealed that higher COP1 expression correlated with better recurrence-free survival. Our study supports the notion that COP1 is a suppressor of breast cancer progression.Neoplasia (New York, N.Y.) 09/2013; 15(9):1075-85. · 5.40 Impact Factor
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ABSTRACT: Elevated level of urokinase receptor (uPAR) is detected in various aggressive cancer types and is closely associated with poor prognosis of cancers. Binding of uPA to uPAR triggers the conversion of plasminogen to plasmin and the subsequent activation of metalloproteinases. These events confer tumor cells with the capability to degrade the components of the surrounding extracellular matrix, thus contributing to tumor cell invasion and metastasis. uPA-uPAR interaction also elicits signals that stimulate cell proliferation/survival and the expression of tumor-promoting genes, thus assisting tumor development. In addition to its interaction with uPA, uPAR also interacts with vitronectin and this interaction promotes cancer metastasis by activating Rac and stimulating cell migration. Although underlying mechanisms are yet to be fully elucidated, uPAR has been shown to facilitate epithelial-mesenchymal transition (EMT) and induce cancer stem cell-like properties in breast cancer cells. The fact that uPAR lacks intracellular domain suggests that its signaling must be mediated through its co-receptors. Indeed, uPAR interacts with diverse transmembrane proteins including integrins, ENDO180, G protein-coupled receptors and growth factor receptors in cancer cells and these interactions are proven to be critical for the role of uPAR in tumorigenesis. Inhibitory peptide that prevents uPA-uPAR interaction has shown the promise to prolong patients' survival in the early stage of clinical trial. The importance of uPAR's co-receptor in uPAR's tumor-promoting effects implicate that anti-cancer therapeutic agents may also be developed by disrupting the interactions between uPAR and its functional partners.Theranostics 06/2013; 3(7):487-495. DOI:10.7150/thno.4218 · 7.83 Impact FactorThis article is viewable in ResearchGate's enriched formatRG Format enables you to read in context with side-by-side figures, citations, and feedback from experts in your field.
Article: Signaling by p38 MAPK Stimulates Nuclear Localization of the Microprocessor Component p68 for Processing of Selected Primary MicroRNAs.[Show abstract] [Hide abstract]
ABSTRACT: The importance of microRNAs (miRNAs) in biological and disease processes necessitates a better understanding of the mechanisms that regulate miRNA abundance. We showed that the activities of the mitogen-activated protein kinase (MAPK) p38 and its downstream effector kinase MAPK-activated protein kinase 2 (MK2) were necessary for the efficient processing of a subset of primary miRNAs (pri-miRNAs). Through yeast two-hybrid screening, we identified p68 (also known as DDX5), a key component of the Drosha complex that processes pri-miRNAs, as an MK2-interacting protein, and we found that MK2 phosphorylated p68 at Ser197 in cells. In wild-type mouse embryonic fibroblasts (MEFs) treated with a p38 inhibitor or in MK2-deficient (MK2-/-) MEFs, expression of a phosphomimetic mutant p68 fully restored pri-miRNA processing, suggesting that MK2-mediated phosphorylation of p68 was essential for this process. We found that, whereas p68 was present in the nuclei of wild-type MEFs, it was found mostly in the cytoplasm of MK2-/- MEFs. Nuclear localization of p68 depended on MK2-mediated phosphorylation of Ser197. In addition, inhibition of p38 MAPK promoted the growth of wild-type MEFs and breast cancer MCF7 cells by enhancing the abundance of c-Myc through suppression of the biogenesis of the miRNA miR-145, which targets c-Myc. Because pri-miRNA processing occurs in the nucleus, our findings suggest that the p38 MAPK-MK2 signaling pathway promotes miRNA biogenesis by facilitating the nuclear localization of p68.Science Signaling 03/2013; 6(266):ra16. DOI:10.1126/scisignal.2003706 · 7.65 Impact Factor
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ABSTRACT: Traditional Chinese medicine (TCM) ZHENG as the key pathological principle is to understand the human homeostasis and guide TCM treatment. Here, circulating microRNAs (miRNAs) were utilized to differentiate between ZHENGs including liver-gallbladder dampness-heat syndrome (LGDHS) and liver-kidney yin deficiency syndrome (LKYDS) in chronic hepatitis B (CHB). Sera samples of CHB patients with LGDHS (n = 35), LKYDS (n = 24), and healthy controls (Ctrls, n = 21) were analyzed by microarray and real-time RT-PCR. Receiver-operator characteristic (ROC) curves were established to evaluate the levels of serum miRNA for discriminating LGDHS and LKYDS. The target genes of miRNAs were predicted by TargetScan. Gene Ontology (GO) and pathways were analyzed using DAVID tool. The results showed that 22 miRNAs were differentially expressed between LGDHS and LKYDS (fold change >2.0 and P < 0.01). Circulating miR-583 and miR-663 were significantly higher (P < 0.001) in CHB patients with LGDHS than those with LKYDS and Ctrls. ROC curve analysis revealed that miR-583 and miR-663 were sensitive and specific enough to distinguish LGDHS from LKYDS. Pathway enrichment analysis indicated that 354 putative targets for miR-583 and 68 putative targets for miR-663 were mainly involved in Axon guidance, Neurotrophin, and MAPK signaling pathway. miR-583 and miR-663 may be potential markers for ZHENG differentiation in CHB.Evidence-based Complementary and Alternative Medicine 03/2013; 2013:751341. DOI:10.1155/2013/751341 · 2.18 Impact FactorThis article is viewable in ResearchGate's enriched formatRG Format enables you to read in context with side-by-side figures, citations, and feedback from experts in your field.
Article: A systematic evaluation of miRNA:mRNA interactions involved in the migration and invasion of breast cancer cells.[Show abstract] [Hide abstract]
ABSTRACT: In this study we performed a systematic evaluation of functional miRNA-mRNA interactions associated with the invasiveness of breast cancer cells using a combination of integrated miRNA and mRNA expression profiling, bioinformatics prediction, and functional assays. Analysis of the miRNA expression identified 11 miRNAs that were differentially expressed, including 7 down-regulated (miR-200c, miR-205, miR-203, miR-141, miR-34a, miR-183, and miR-375) and 4 up-regulated miRNAs (miR-146a, miR-138, miR-125b1 and miR-100), in invasive cell lines when compared to normal and less invasive cell lines. Transfection of miR-200c, miR-205, and miR-375 mimics into MDA-MB-231 cells led to the inhibition of in vitro cell migration and invasion. The integrated analysis of miRNA and mRNA expression identified 35 known and novel target genes of miR-200c, miR-205, and mir-375, including CFL2, LAMC1, TIMP2, ZEB1, CDH11, PRKCA, PTPRJ, PTPRM, LDHB, and SEC23A. Surprisingly, the majority of these genes (27 genes) were target genes of miR-200c, suggesting that miR-200c plays a pivotal role in regulating the invasiveness of breast cancer cells. We characterized one of the target genes of miR-200c, CFL2, and demonstrated that CFL2 is overexpressed in aggressive breast cancer cell lines and can be significantly down-regulated by exogenous miR-200c. Tissue microarray analysis further revealed that CFL2 expression in primary breast cancer tissue correlated with tumor grade. The results obtained from this study may improve our understanding of the role of these candidate miRNAs and their target genes in relation to breast cancer invasiveness and ultimately lead to the identification of novel biomarkers associated with prognosis.Journal of Translational Medicine 01/2013; 11:57. DOI:10.1186/1479-5876-11-57 · 3.99 Impact Factor
Article: Current understanding on antihepatocarcinoma effects of xiao chai hu tang and its constituents.[Show abstract] [Hide abstract]
ABSTRACT: Xiao Chai Hu Tang (XCHT), a compound formula originally recorded in an ancient Chinese medical book Shanghanlun, has been used to treat chronic liver diseases for a long period of time in China. Although extensive studies have been demonstrated the efficacy of this formula to treat chronic hepatitis, hepatic fibrosis, and hepatocarcinoma, how it works against these diseases still awaits full understanding. Here, we firstly present an overview arranging from the entire formula to mechanism studies of single herb in XCHT and their active components, from a new perspective of "separation study," and we tried our best to both detailedly and systematically organize the antihepatocarcinoma effects of it, hoping that the review will facilitate the strive on elucidating how XCHT elicits its antihepatocarcinoma role.Evidence-based Complementary and Alternative Medicine 01/2013; 2013:529458. DOI:10.1155/2013/529458 · 2.18 Impact Factor
Article: Nek1 phosphorylates Von Hippel-Lindau tumor suppressor to promote its proteasomal degradation and ciliary destabilization.[Show abstract] [Hide abstract]
ABSTRACT: Loss of function in either VHL or Nek1 leads to cyst formation in tissues, especially in kidneys. Whether there is a connection between pVHL and Nek1 regulation is unknown. Here, we report that the VHL protein (pVHL) may be a substrate of Nek1. While Nek1 can phosphorylate pVHL at multiple sites, the phosphorylation at serine-168 results in pVHL degradation. Nek1-mediated phosphorylation of pVHL does not significantly affect hypoxia-inducible factors (HIF), a known target of pVHL. However, non-phosphorylable pVHL reconstituted in VHL-deficient cells induces more stable cilia than wild-type VHL during serum stimulation and Nocodazole treatment. The results suggest a possible regulation of pVHL by Nek1 that may contribute to ciliary homeostasis and cystogenesis.Cell cycle (Georgetown, Tex.) 12/2012; 12(1). DOI:10.4161/cc.23053 · 5.24 Impact Factor
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ABSTRACT: To investigate whether circulating microRNAs (miRNAs) can serve as molecular markers to predict liver injury resulted from chronic hepatitis B (CHB). The profiles of serum miRNA expression were first generated with serum samples collected from 10 patients with CHB and 10 healthy donors (Ctrls) by microarray analysis. The levels of several miRNAs were further quantitated by real-time reverse transcription polymerase chain reaction with serum samples from another 24 CHB patients and 24 Ctrls. Serum samples of 20 patients with nonalcohlic steatohepatitis (NASH) were also included for comparison. The comparison in the levels of miRNAs between groups (CHB, NASH and Ctrl) was analyzed with Mann-Whitney U-test. The correlation between miRNAs and clinical pathoparameters was analyzed using Spearman correlation analysis or canonical correlation analysis. The receiver-operator characteristic (ROC) curves were also generated to determine the specificity and sensitivity of each individual miRNA in distinguishing patients with CHB from Ctrls. miRNA profile analysis showed that 34 miRNAs were differentially expressed between CHB and Ctrl subjects, in which 12 were up-regulated and 22 down-regulated in CHB subject (fold change > 2.0 and P < 0.01). The median levels of miR-122, -572, -575 and -638 were significantly higher (P < 1.00 × 10(-5)) while miR-744 significantly lower (P < 1.00 × 10(-6)) in CHB compared with the Ctrl. The levels of miR-122, -572 and -638 were also higher (P < 1.00 × 10(-3)) while the level of miR-744 lower in CHB (P < 0.05) than in NASH, although the difference between them was not as significant as that between CHB and Ctrl. ROC curve analysis revealed that the levels of miR-122, -572, -575, -638 and -744 in serum were sensitive and specific enough to distinguish CHB, NASH and Ctrl. Multivariate analysis further showed that the levels of these miRNAs were correlated with the liver function parameters. Most significantly, it was the scatter plot of principal component with the levels of these miRNAs, but not the parameters of liver function, which clearly distinguished CHB, NASH and Ctrl subjects. Serum levels of miR-122, -572, -575, -638 and -744 are deregulated in patients with CHB or NASH. The levels of these miRNAs may serve as potential biomarkers for liver injury caused by CHB and NASH.World Journal of Gastroenterology 10/2012; 18(37):5188-96. DOI:10.3748/wjg.v18.i37.5188 · 2.43 Impact Factor
Article: Functional dissection of HOXD cluster genes in regulation of neuroblastoma cell proliferation and differentiation.[Show abstract] [Hide abstract]
ABSTRACT: Retinoic acid (RA) can induce growth arrest and neuronal differentiation of neuroblastoma cells and has been used in clinic for treatment of neuroblastoma. It has been reported that RA induces the expression of several HOXD genes in human neuroblastoma cell lines, but their roles in RA action are largely unknown. The HOXD cluster contains nine genes (HOXD1, HOXD3, HOXD4, and HOXD8-13) that are positioned sequentially from 3' to 5', with HOXD1 at the 3' end and HOXD13 the 5' end. Here we show that all HOXD genes are induced by RA in the human neuroblastoma BE(2)-C cells, with the genes located at the 3' end being activated generally earlier than those positioned more 5' within the cluster. Individual induction of HOXD8, HOXD9, HOXD10 or HOXD12 is sufficient to induce both growth arrest and neuronal differentiation, which is associated with downregulation of cell cycle-promoting genes and upregulation of neuronal differentiation genes. However, induction of other HOXD genes either has no effect (HOXD1) or has partial effects (HOXD3, HOXD4, HOXD11 and HOXD13) on BE(2)-C cell proliferation or differentiation. We further show that knockdown of HOXD8 expression, but not that of HOXD9 expression, significantly inhibits the differentiation-inducing activity of RA. HOXD8 directly activates the transcription of HOXC9, a key effector of RA action in neuroblastoma cells. These findings highlight the distinct functions of HOXD genes in RA induction of neuroblastoma cell differentiation.PLoS ONE 08/2012; 7(8):e40728. DOI:10.1371/journal.pone.0040728 · 3.53 Impact Factor
Article: Regulation of myosin activation during cell-cell contact formation by Par3-Lgl antagonism: entosis without matrix detachment.[Show abstract] [Hide abstract]
ABSTRACT: Cell-cell contact formation following cadherin engagement requires actomyosin contraction along the periphery of cell-cell contact. The molecular mechanisms that regulate myosin activation during this process are not clear. In this paper, we show that two polarity proteins, partitioning defective 3 homologue (Par3) and mammalian homologues of Drosophila Lethal (2) Giant Larvae (Lgl1/2), antagonize each other in modulating myosin II activation during cell-cell contact formation in Madin-Darby canine kidney cells. While overexpression of Lgl1/2 or depletion of endogenous Par3 leads to enhanced myosin II activation, knockdown of Lgl1/2 does the opposite. Intriguingly, altering the counteraction between Par3 and Lgl1/2 induces cell-cell internalization during early cell-cell contact formation, which involves active invasion of the lateral cell-cell contact underneath the apical-junctional complexes and requires activation of the Rho-Rho-associated, coiled-coil containing protein kinase (ROCK)-myosin pathway. This is followed by predominantly nonapoptotic cell-in-cell death of the internalized cells and frequent aneuploidy of the host cells. Such effects are reminiscent of entosis, a recently described process observed when mammary gland epithelial cells were cultured in suspension. We propose that entosis could occur without matrix detachment and that overactivation of myosin or unbalanced myosin activation between contacting cells may be the driving force for entosis in epithelial cells.Molecular biology of the cell 04/2012; 23(11):2076-91. DOI:10.1091/mbc.E11-11-0940 · 5.98 Impact Factor
Article: Insulin-like growth factor 1 attenuates antiestrogen- and antiprogestin-induced apoptosis in ER+ breast cancer cells by MEK1 regulation of the BH3-only pro-apoptotic protein Bim.[Show abstract] [Hide abstract]
ABSTRACT: In this pre-clinical in vitro study conducted in estrogen receptor positive (ER+) breast cancer cells, we have characterized the effects of insulin-like growth factor I (IGF-1) on the cytostatic and cytotoxic action of antiestrogen treatment when used as a single agent or in combination with the antiprogestin mifepristone (MIF). Our goal was to identify new molecular targets to improve the efficacy of hormonal therapy in breast cancer patients that have a poor response to hormonal therapy, in part, due to high circulating levels of unbound insulinIGF-1. IGF-1-mediated effects on cytostasis and apoptotic cell death were determined with cell counts conducted in the presence and absence of trypan blue; enzyme-linked immunosorbent assays to determine the intracellular levels of cleaved cytokeratin 18, a marker of epithelial cancer cell apoptosis; and immunoblot analysis to determine the levels of cleaved poly-ADP ribose polymerase (PARP) and lamin A that result from caspase-dependent apoptosis. Cytotoxicity was further characterized by determination of the levels of reactive oxygen species (ROS) and the percent of mitochondrial membrane depolarization in cell populations treated with the different hormones in the presence and absence of IGF-1. Small molecule inhibitors of the dual-specificity protein kinase MEK1, MEK1 siRNA, Bim siRNA, and vectors overexpressing MEK1 wild type and mutant, dominant negative cDNA were used to identify key IGF-1 downstream prosurvival effectors. IGF-1, at physiologically relevant levels, blocked the cytotoxic action(s) of the antiestrogens 4-hydroxytamoxifen (4-OHT) and tamoxifen (TAM) when used as single agents or in combination with the antiprogestin MIF. The antiapoptotic action of IGF-1 was mediated primarily through the action of MEK1. MEK1 expression reduced the levels of ROS and mitochondrial membrane depolarization induced by the hormonal treatments via a mechanism that involved the phosphorylation and proteasomal turnover of the proapoptotic BH3-only Bcl-2 family member Bim. Importantly, small-molecule inhibitors of MEK1 circumvented the prosurvival action of IGF-1 by restoring Bim to levels that more effectively mediated apoptosis in ER+ breast cancer cells. his study provides strong support for the use of MEK1 inhibitors in combination with hormonal therapy to effectively affect cytostasis and activate a Bim-dependent apoptotic pathway in ER+ breast cancer cells. We discuss that MEK1 blockade may be a particularly effective treatment for women with high circulating levels of IGF-1, which have been correlated to a poor prognosis.Breast cancer research: BCR 03/2012; 14(2):R52. DOI:10.1186/bcr3153 · 5.88 Impact Factor
Article: AU-rich-element-dependent translation repression requires the cooperation of tristetraprolin and RCK/P54.[Show abstract] [Hide abstract]
ABSTRACT: AU-rich elements (AREs), residing in the 3' untranslated region (UTR) of many labile mRNAs, are important cis-acting elements that modulate the stability of these mRNAs by collaborating with trans-acting factors such as tristetraprolin (TTP). AREs also regulate translation, but the underlying mechanism is not fully understood. Here we examined the function and mechanism of TTP in ARE-mRNA translation. Through a luciferase-based reporter system, we used knockdown, overexpression, and tethering assays in 293T cells to demonstrate that TTP represses ARE reporter mRNA translation. Polyribosome fractionation experiments showed that TTP shifts target mRNAs to lighter fractions. In murine RAW264.7 macrophages, knocking down TTP produces significantly more tumor necrosis factor alpha (TNF-α) than the control, while the corresponding mRNA level has a marginal change. Furthermore, knockdown of TTP increases the rate of biosynthesis of TNF-α, suggesting that TTP can exert effects at translational levels. Finally, we demonstrate that the general translational repressor RCK may cooperate with TTP to regulate ARE-mRNA translation. Collectively, our studies reveal a novel function of TTP in repressing ARE-mRNA translation and that RCK is a functional partner of TTP in promoting TTP-mediated translational repression.Molecular and Cellular Biology 12/2011; 32(5):913-28. DOI:10.1128/MCB.05340-11 · 5.04 Impact Factor
Article: HOXC8-Dependent Cadherin 11 Expression Facilitates Breast Cancer Cell Migration through Trio and Rac.[Show abstract] [Hide abstract]
ABSTRACT: HOXC8 expression is upregulated in diverse cancer types, and a high level of HOXC8 is often associated with the aggressive/metastatic phenotypes. We previously reported that the presence of HOXC8 is essential for breast cancer cell migration and metastasis. However, the underlying molecular mechanism of HOXC8 regulation of cell migration is unclear. Here, we demonstrate that the presence of HOXC8 is required for cadherin 11 (CDH11) expression in breast cancer cells and that HOXC8 regulation of cell migration is mediated by CDH11. To understand the role of HOXC8-CDH11 axis in cell migration, we show that depleting either HOXC8 or CDH11 diminishes the formation of actin-based membrane ruffles, an event essential for cell migration. The loss of membrane ruffles in HOXC8- or CDH11-knockdown cells is apparently caused by reduced Rac activity because ectopically expressing active Rac1 restores cytoskeleton reorganization. CDH11 physically interacts with Trio, a Rac GEF. We show that Trio is responsible for the majority of endogenous Rac activity in migratory breast cancer cells. Because knockdown of CDH11 prevents the plasma membrane localization of Trio, our study indicates that CDH11 may play a role in recruiting Trio to the plasma membrane where Trio activates Rac, leading to cell migration. This study reveals a novel HOXC8-CDH11-Trio-Rac signaling axis that contributes significantly to breast cancer cell migration.Genes & cancer 09/2011; 2(9):880-8. DOI:10.1177/1947601911433129
Article: Bacterial LPS up-regulated TLR3 expression is critical for antiviral response in human monocytes: evidence for negative regulation by CYLD.[Show abstract] [Hide abstract]
ABSTRACT: In the host immune system, the leukocytes are often exposed to multiple pathogens including bacteria and viruses. The principal challenge for the host is to efficiently detect the invading pathogen and mount a rapid defensive response. Leukocytes recognize invading pathogens by directly interacting with pathogen-associated molecular patterns via Toll-like receptors (TLRs) expressed on the leukocyte surfaces. In this study, we provide direct evidence that bacterial LPS enhances the host antiviral response by up-regulating TLR3 expression in human peripheral blood monocytes and monocytic cell lines, THP1 cells. Moreover, LPS induces TLR3 expression via a TLR4-MyD88-IRAK-TRAF6-NF-κB-dependent signaling pathway. Interestingly, CYLD, an important deubiquitinase, acts as a negative regulator of TLR3 induction by LPS. Our study thus provides new insights into a novel role for bacterial infection in enhancing host antiviral response; furthermore, it identifies CYLD for the first time as a critical negative regulator of bacterial LPS-induced response.International Immunology 06/2011; 23(6):357-64. DOI:10.1093/intimm/dxr019 · 3.18 Impact Factor
Top Journals
Georgia Regents University
Augusta, Georgia, United States
- Department of Biochemistry and Molecular Biology
Xiamen University
Amoy, Fujian, China
- School of Life Sciences
Shanghai University of Traditional Chinese Medicine
Shanghai, Shanghai Shi, China
- Research Center for Traditional Chinese Medicine Complexity System
Georgia Health Sciences University
Augusta, GA, United States
- • Department of Biochemistry & Molecular Biology
- • Department of Cellular Biology & Anatomy
Shanghai Institutes for Biological Sciences
Shanghai, Shanghai Shi, China
- Institute of Health Sciences
Changhai Hospital, ShanghaiShanghai, Shanghai Shi, China
The Scripps Research Institute
La Jolla, California, United States
- Department of Molecular and Experimental Medicine
Georgia CollegeAugusta, Georgia, United States
Medical University of Ohio at Toledo
Toledo, Ohio, United States
- Department of Medical Microbiology and Immunology


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Dane Reynolds and Yadin Nicol in California. What more do you want?
Have you heard of this guy Dane Reynolds? Name sounds familiar, but it's hard to place. Like a name once common but not heard in a little too long. Anyway, he surfs pretty good. So does Yadin Nicol. Good thing, 'cause they're both in this video. Carving up some mouth-watering walls in and around the
Photo Blog
Photo: Todd Glaser
The 16-year-old goofyfooter in solid waves at home and Hawaii
You'll likely recall Jacob Willcox as the 16-year-old trials winner that beat Kelly Slater (and Matt Wilkinson in Round One) at the 2013 Rip Curl Pro Peniche. It was a grand feat and one that ultimately had world title implications. Fast forward one Hawaii season and the lanky goofyfooter from West Oz is even more
Timmy Reyes in uncrowded waves and an excessive amount of neoprene
Free from the grind of chasing the WQS and the WCT, Timmy Reyes has evolved into a full-blown wave-chasing machine, particularly waves of the winter variety. Around the 1:15 mark, he ventures south of the border to Todos Santos for a solid session at the big-wave spot. From there, he heads north to San Francisco's
Kolohe Andino, back at it with friends in California
Photo Blog
Photo: Grant Ellis
Random Happenings
An unreal stop-motion super session using Playmobil toys
Just when you thought the reality-defying waves of Tahiti's famed reef couldn't be anymore unreal, a stop motion Teahupoo video using Playmobil toys comes out. Karim Rejeb, who also made the equally awesome Perfect Holiday video, recreated a super session at the end of the road in his backyard. Between the foam balls (quite literal),
Jeremy Flores and John John Florence find fun waves near Bells Beach
Following a disappointing result at Bells Beach, Jeremy Flores road tripped down the coast near Victoria. Along the way, he found a super rippable righthander (0:15) and John John Florence (0:35). The closing section is epic as well: a perfectly wind-groomed peak (primarily a left barrel) with an open shoulder at the end. Well worth


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Bratton is a populated place located in Robertson County at latitude 38.568 and longitude -84.095.
The elevation is 676 feet. Bratton appears on the Mount Olivet U.S. Geological Survey Map. Robertson County is in the Eastern Time Zone (UTC -5 hours).
Robertson County: Cities & Towns | ZIP Codes | Schools | Features (airports, churches, hospitals, etc.)
BIG Map |
Driving Directions |
Data Source - USGS GNIS FID: 487845
BOUNDARY MAPS: Mount Olivet Division | Robertson County
Bratton, KY
(< 0.1 mile)
Santa Fe, KY (1.4 miles W)
Hittville, KY (1.9 miles ENE)
Milford, KY (3.4 miles WNW)
Mount Olivet, KY (4.1 miles SE)
Petra, KY
(4.3 miles NNW)
Bridgeville, KY (4.5 miles ENE)
Kentontown, KY (5.3 miles SSW)
Stonewall, KY (5.8 miles NE)
Claysville, KY (6 miles SW)


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Taken inside Glasgows fabulous Kelvingrove art gallery and Museum.
superb sense of perspective, sending my eyes funny
Excellent, but I know exactly what igotmeacanon means …
Not just the perspective but the textures and patterns! What a visually stimulating piece!
just perfect (perspective, b&w rendering… Great eye) !
a beautiful capture of a fabulous building Linda, my favorite painting there, is Salvadore Dali's Christ on the Cross. x
That is the picture seen at the end of this corridor..it is a fab painting. I meant to buy the print on sale in the gift shop and get it framed. I will next time…or maybe save for the original!!!!!!!!!!!!
– Linda Morrison
Super perspective Linda, this is brilliant a fav for me..
when i lived in Glasgow in the 60s, it used to be at the top of the stairs, looking down on you as you walked up the stairs it had such an impact on me. x
Fantastic capture and perspective.
Those tiles are almost hypnotic :)
Love the perspective
excellent perspective and contrast!


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6 Technology Innovation Sources for Outside-In Learning
CIO Dashboard
The speed and variety of new ideas makes technology innovation harder than ever before. For most of the last 30 years, those of us in the field of information technology only really concerned ourselves with one major new technology trend at a time – distributed computing, GUIs, OOAD or data warehousing. Now we have not one, but a flood of technologies: mobile, social media, big data and analytics, cloud, the Internet of Things and 3D printing, to name a few, rushing toward us all at once. The reassuring news is that there are as many sources of learning and opportunity to fuel innovation as there are technologies to consider integrating into your technology portfolio. But, you need to know where to look.
Most corporations have a history of learning about new technologies by tapping a few trusted vendors, attending a conference or two and and reading trade publications. Some of the more progressive companies look to universities. Even fewer today rely on the venture capital world and some have taken on their own corporate venturing. But, companies don't have to invest millions to partner with a university or fund a venture business to innovate in today's disruptive digital marketplace.
The barriers of entry to innovate have never been lower as easy-to-access communities with ideas and talent grow more and more plentiful. For a fraction of the cost of traditional outside-in innovation, you can open the door to intriguing worlds and be inspired to create a new product or business model, source talent or acquire a company. I guarantee that if you explore at least one of these communities your mind will start to swim with possibilities for how to push your company's agenda forward. It's time to fight fire with fire to stoke the flames of innovation by bringing the outside in.


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Lymphedema Accessories
Having to manage Lymphedema is bad enough, but managing all of the products which are required to do so can be an overwhelming process in itself. Luckily there are several accessories which are available to help make this process a little easier. (read more)
Doff N DonnerThe Doff N' Donner is a unique and innovative device which allows patients to easily both, "doff and don" compression garments of all shapes, styles and compressions Learn More
Starting at: $32.95
Ezy-As Garment ApplicatorThe Ezy-As garment applicator helps to reduce the effort and pain of applying compression garments to both arms and legs, and provides independence for patients and caregivers who are otherwise unable to apply their garments Learn More
Starting at: $39.95
Medi Butler Off - Doffing AidThe Medi "Butler Off" doffing, or removal device greatly assists in removing compression stockings without laborious effort or the need for bending Learn More$32.00