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Down the Line Rooftop is perched along the first base line in right field, just 448 from home plate. You'll have a stunning view of Wrigley Field and can mill about between two different levels that are home to bars, large-screen TVs and climate-controlled spaces. Picture windows in the bar just below the rooftop give you floor-to-ceiling views of Wrigley Field.
The Quarry Cable Park and Grille
The Quarry Cable Park & Grille is located on the 32-acre North Lake of Three Oaks Recreation Area in Crystal Lake. Enjoy wakeboarding at this next-generation cable wake park complete with a Full-Size Six-Tower cable system with jumps and features for experienced riders and two System 2.0 Two-Tower cable systems for beginners. Stay a little longer and enjoy the lakefront tap & grille, fire pits, live entertainment, sand volleyball, baggo, and open-air yoga. While promoting recreation and relaxation, The Quarry aims to provide a new approach to staying active for visitors near and far and invites everyone to unearth their potential.
CITY:Crystal Lake
Apple Orchard Golf Course is a nine hole, par three, public course located at 692 W. Stearns Rd. about 3/4 mile east of Route 59 on Stearns Road. Other features include a clubhouse equipped with snacks, beverages, beer, restrooms, golf accessories and indoor/outdoor sitting areas. Rental golf clubs and pull carts are available for a slight fee.
Catch a Cubs game from one of the original Wrigley rooftops. Skybox on Sheffield is perched just inside Wrigley Field's right field foul pole and offers spectacular views of the field just across the street. Renovated in 2011, Skybox on Sheffield offers four luxurious levels, including a three-tier outdoor roof deck, a lavish indoor clubhouse and 150 stadium seats. Guests will also enjoy a three-course menu served with an extensive beer selection from Goose Island.
Northwestern University Soccer
Enjoy a soccer game right next to Lake Michigan, played at Lakeside Field.
All day long, and both prior to and after United Center events, people from all over the world come to visit and have their picture taken in front of one of Chicago's most famous and recognizable landmarks.
This 18-hole course features a practice range, pro shop, snack shop and banquet facilities. Bartlett Hills Golf Club & Banquets is also an award-winning wedding venue that can accommodate up to 230 of your friends and family.
DuPage County, Chicago's Western Suburbs - Brunswick Zone offers bowling, billiards, Laser Tag, an arcade/game room plus meeting space for corporate parties, team-building and special events.
CITY:Carol Stream
Located down the right field line, Wrigley Field Rooftop Club is one of the closest rooftops to home plate, and even closer than some seats in the ballpark. Built in 2008, this is one of the largest rooftop facilities overlooking Wrigley Field, offering over 9,000 square feet of space on three levels: the Rooftop Level, the Stadium Club Level and the exclusive MVP Suites, with a clear view of the game from each seat.
The Willow Glen Golf Club is home to a picturesque 18-hole layout that provides an enjoyable challenge for all skill levels. The new clubhouse is home to Buckley's Restaurant and Pub making Willow Glen one of the finest golf and dining experiences on the North Shore. Open to the public!
CITY:Great Lakes
Deerpath Golf Course in Lake Forest opens for play in March and closes for the season on or about December 15. This 18-hole public course, measures 6,255 yards with a par 70 and 5,487 yards with a par 72 for women. The course has spectacular mature trees, high quality naturalized areas and beautiful water features including ponds and streams. The Deerpath Golf Academy offers the finest golf instruction on the North Shore. Golfers of all abilities will realize immediate and sustainable improvement for a lifetime of better golf.
CITY:Lake Forest
This beautiful 30,000-square-foot clubhouse features an upscale restaurant with patio seating and 18 holes of championship golf. Our scenic 18 hole Dick Nugent designed golf course, state of the art electric carts, beautiful clubhouse, outstanding food and exceptional service are sure to make your outing a success.
CITY:Buffalo Grove
Trackside Waukegan offers a casual, comfortable setting to wager on horse racing from around the world, broadcast on 250 television monitors. Watch and bet on races in the Finish Line Restaurant and Lounge, Grandstand Bar, Teletheater or Backstretch Deli.
This 9-hole, par-35 course stretches over 3,000 yards. The well-maintained fairways and greens, along with sand and water hazards, offer a unique and challenging golf experience. The newly remodeled clubhouse is a picturesque location for a special event.
The Big Ten Experience features a collection of 13 interactive exhibits showcasing conference notables dating back to 1896, the year the conference was founded. Highlights include the Big Ten Theater which gives patrons a behind-the-scenes, immersive audio and video experience looking at student-athletes and traditions, along with radio and television features of notable accomplishments on and off the field of play.
Located just left of the third-base line, this rooftop offers a unique view of Wrigley Field. Your vantage point gives you a clear site line to home plate and a sweeping view of the bleachers and historic scoreboard in centerfield. Guests have access to four areas of this facility: Wrigley View Lounge, Stadium Club, Stadium Buffet and the outdoor Sky Deck where you're rewarded with panoramic views of not just Wrigley Field, but also the city.
Pinecrest Golf Club, Restaurant and Banquet Facility
Pinecrest Golf Club, Restaurant and Banquet Facility is open to the public and operated by the Huntley Park District. Pinecrest Golf Club features 18 holes of championship golf for all skill levels, driving range, sand/chipping area and putting green.
This brand-new Wrigley rooftop was built from the ground up in 2010 to take advantage of the stunning views while also offering guests unparalleled comfort during the game. Five levels, the most of any Wrigley rooftop, provide many different ways to enjoy the game—from outdoor stadium-style seating atop the rooftop to three levels of indoor lounges. Each one is accessible by elevator and features its own restrooms, full-service bars with premium draft beers and wine, as well as their own food service.
Enjoy the delightful rural atmosphere at this semi-private facility located near the banks of the Fox River in lovely McHenry. Accept the challenge to play the longest hole in Illinois, measuring over 700 yards.
Kristof's Entertainment Center
Complete entertainment for all ages and interests. Bowling, mini golf, Go Karts, redemption arcade, batting cages, birthday parties and a haunted house. Lunch and dinner served daily. Bar and billards with various night time entertainment. A safe and fun environment for all members of the family. Kristof's is a smoke-free facility.
CITY:Round Lake Beach
This brand-new rooftop facility features over 9,000 square feet of space when enjoying the Cubs game across the street. The rooftop offers stadium-style seating that gives you a complete view of Wrigley Field. Outside you'll also find a large covered bar, umbrella-covered tables and plenty of plasma TVs. Large groups can also enjoy the game from two other levels: the stadium club and All-Star suite where you'll find state-of-the-art amenities and upgraded food menus.
DuPage County, Chicago's Western Suburbs - North Central College offers a 5,000 seat football stadium with lights, and Olympic-size championship track, a multi-use 25,000 sq. ft.Fieldhouse, baseball and softball fields and tennis courts.
Itasca Country Club is rich in tradition and offers a cost-effective solution for golf outings, corporate entertaining and special events in a picturesque setting. Enjoy beautiful surroundings, spectacular views, and the service of a fine country club-for your wedding reception or other banquet event. Amidst the elegant grounds and facilities, our skilled professional staff will put you at ease and ensure your special occasion is unforgettable.
A Big Ten school and one of the leading universities in the U.S. Its Evanston campus is on the shores of beautiful Lake Michigan. Founded in 1851, this renowned educational institution is rich in stunning architecture. More than 150 historically significant and interesting sites on campus are featured in various walking tours, each taking approximately 30 minutes to complete. Highlights include the Arch, University Hall and the Arts Circle.
The Chicago Sports Museum combines hi-tech interactive experiences—including skill challenges and simulated experiences—with unique sports memorabilia and an impressive collection of game-used treasures and other artifacts.
The Norge Ski Club features a 70-meter ski jumping scaffold situated high on a hill overlooking Fox River Grove. There are also four smaller scaffolds for ski jumping training, member cottages and a clubhouse.
CITY:Fox River Grove
The top sports complex in Northern Illinois which features 14 outdoor soccer fields including a lighted synthetic turf Championship Field and 4 softball diamonds with lights. A perfect place to host tournaments and events.
Highland Park Country Club is an immaculately maintained 18-hole public golf course offering an unforgettable challenge for players of all skill levels. Located just 25 minutes north of Chicago, Highland Park's scenic beauty and world-class amenities make it the perfect locale for golf outings, weddings, banquets and fundraising events.
CITY:Highland Park
Come and play right in your backyard! Visit Maple Meadows for outings, leagues, tournaments, individual play, and the great food in our restaurant. 27 holes, no reservations required and a beautiful public course!
CITY:Wood Dale
Upscale nightclub newly renovated to create a spectacular nightlife experience. Available for corporate, social and philanthropic occasions. Let us work with you to make your event a success.
18-hole public golf course and golf shop. Restaurant open for lunch daily; Wednesday, Thursday and Friday for dinner. Meeting rooms and banquet facilities for up to 250.
CITY:Glendale Heights
DuPage County, Chicago's Western Suburbs - Located on 25 acres, with woods, lakes and rolling hills, the course offers 9 holes of challenging golf for beginners and advanced golfers. Reduced rates available for golfers 55 and over. Clubhouse seats 60+ and has a variety of foods.
Boone Creek consists of three unique 9-hole courses that can be combined to make up three different 18-hole courses, allowing you to play a different course while visiting the same location. Boone Creek Golf Club has a natural setting with a number of wetlands and creeks that are home to a variety of wildlife including frogs, beavers, snapping turtles, wood ducks, deer, cranes, and red-tail hawks. Our golf course has large and undulating greens that provide some of the best putting surfaces in McHenry County.
Beyond the Ivy offers three rooftop experiences for watching a Cubs game—each with its own vibe. The 1010 Waveland Avenue location is their largest rooftop, holding as many as 100 guests—perfect for group outings. Beyond the Ivy at 1038 Waveland Avenue has a modern décor that feels more like a nightclub. Beyond the Ivy at 1048 Waveland Avenue has a classic vibe with a bar-like setting that's decked out with plenty of Cubs memorabilia—perfect for longtime Cubs fans.
Playing this unique, well-conditioned and spectacularly-designed 18-hole course will surely make you want to come back. Full service premier meeting and banquet facility provides outstanding culinary offerings and personal service.
CITY:West Chicago
This Killian/Nugent-designed course features five water holes. An Olympic-size pool is available for free to golfers, along with sand volleyball, tennis, a softball area and more.
Make Salt Creek Golf Club your golfing "home course". When you select a facility to patronize regularly, you want the facility that offers the full gamut of a private club without the dues. Our 18-hole executive style golf course will challenge golfers of all skill levels. Set amidst gently rolling terrain, mature tree, and beautiful ponds, Salt Creek's 3895 yard, par 63 course challenge players of all skill levels with tree-lined fairways and strategically placed sand bunkers.
CITY:Wood Dale
HeatherRidge Golf Course is a beautiful and challenging full length nine hole layout that is enjoyable for players of all skill levels. Adding to its beauty are the flowing creeks and ponds that come into play on seven of the nine holes. Also enjoy the unique outside Cabana Bar and Grill. Great food, cold drinks, outstanding atmosphere and friendly staff will complete your HeatherRidge golfing experience. Golf clubs available for rent. Located on Northern Illinois' favorite 9-hole golf course, The HeatherRidge Clubhouse is a beautiful venue for just about any occasion. If you are planning a weddings, banquets or party we are the place.
Built on the well-known Cuneo Estate in Vernon Hills, White Deer Run Golf Club is an 18-hole public course sprawling over 240 acres of rolling terrain and picturesque lakes with bent grass greens and fairways. Able to accommodate small and large group outings and banquets.
CITY:Vernon Hills
The folks at Brixen Ivy pride themselves on catering to your group as you catch the Cubs game across the street. Their rooftop facility was built from the ground up specifically with group events in mind. The result is a state-of-the-art facility that offers your group a chance to watch the game, socialize in a climate-controlled bar or on private decks—all while taking in the game outside, through soaring windows, or on one of the many big-screen TVs.
This championship 18-hole golf course with 6,950 yards offers bent grass fairways, and beautiful rolling hills and vistas. Power carts are required Friday through Sunday and holidays.
This 18-hole championship golf course has been rated 4 stars by Golf Digest, 4-1/2 stars by Chicagoland Golf, and has been voted one of the best values in all of Illinois.
CITY:Crystal Lake
18-hole golf course with driving range, restaurant and pro shop. Oak Brook Golf Club is a classic playing experience in a spectacular natural setting where every hole calls for solid shot-making from tee to green. Unlike boring daily-fee courses of cookie-cutter municipal courses, this is a thinking person's course that rewards sound play for players at any skill level.
CITY:Oak Brook
Enjoy hockey, figure skating or recreational skating at this ice arena in Skokie.
Bowes Creek delivers a private club experience to the public golfer! It offers annual memberships for a day, or just enjoy Porter's Pub - an English inspired eatery.
Championship 9-hole course. Water comes into play on all 9 holes -- a challenge for any golfer. Full-service pro shop. The club house has a beautiful central fireplace and exterior patio.
Come for business, stay for golf. The Glen Club has 21 overnight rooms featuring unique layouts and elegant fixtures including historic photographs from Chicago's famous Golf Clubs. Dine on delicious American fare at "The Grill" or host your corporate events in our elegant ballroom seating up to 230, or our stately meeting rooms. Visit the Illinois Golf Hall of Fame. Designed by renowned golf course architect Tom Fazio, the Glen Club's golf course features rolling terrain with dramatic elevation changes, meandering lakes and streams and stunning vistas.
With undulating and quick greens, the course's front nine rolls and winds through 200-year old oak trees, while the back side is longer, with more water and strong winds.
CITY:West Dundee
The Highlands of Elgin Golf Course
This collection of eighteen holes now provides golfers with an adventure through a variety of unique golf holes in a beautiful setting. The prairie style clubhouse features an expanded golf shop, locker rooms, event rooms with expansive ceilings and a full scale food and beverage operations. Enjoy dining at the Hickory Stick Bar & Grill and experience stunning golf course views.
Eat. Drink. Play. Watch. Over 40,000 square feet of fun!! With more than 200 games in the Million Dollar Midway. Win tickets playing the games and turn them in for great prizes in the Winner's Circle. Grab an appetizer at the bar, or head into the dining room for awesome dishes. With a full menu featuring burgers, steaks, seafood, pasta, salads and more, everyone will find something that satisfies. Watch sports on big screens and enjoy great deals on signature cocktails, beer and wine. Specials: 1/2 Price Games Wed - open to close. Eat & Play is $16.99 at this location, restrictions apply. House Policies: Under 18 need a parent or guardian. 6 minors per adult. Kiddie call 11pm.
CITY:Vernon Hills
A state-of-the-art ice training facility featuring figure skating, hockey for every age and skill level, goalie training, meeting rooms and concessions.
CITY:West Dundee
This 18-hole championship golf course, featuring wildflowers and elevated tees, offers spectacular views of the Fox Valley region.
Brae Loch Banquets and Golf Club
The golf course has 18-holes and it is a par-70 course. Brae Loch Banquets feature a bright space in a country setting overlooking the fairways at the Lake County Forest Preserves Brae Loch Golf Club. A fine balance of food, location and people are the three ingredients that an event at Brae Loch brings together for a truly memorable experience. The banquet facility comfortably seats up to 165. The menu includes appetizers, entrees, and desserts that are almost too beautiful to eat, but too wonderful to skip.
At Countryside Golf Club, play two challenging, award-winning 18-hole golf courses. The Prairie course, with bentgrass tees, wide-open greens and sand bunkers offers golfers a chance to challenge their game. The Traditional course, with bentgrass tees and tree-lined fairways, offers golfers scenic and challenging rounds of golf. Also try out the driving range.
Nestled on the banks of the Fox River and used annually by tens of thousands of people, the 9-hole regulation Pottawatomie Golf Course, which is owned and operated by the St. Charles Park District, is certainly the most beautiful golf course in the Fox Valley area offering scenic views with lush landscapes along the shore of the Fox River.
CITY:St. Charles
With five elegant banquet rooms that serve the needs of groups from thirty to six hundred guests including a championship eighteen hole golf course, driving range, all suites hotel with a pool/ fitness center, and a state-of-the-art nightclub, Midlane is uniquely outfitted to suit any of your banquet needs. Don't gamble on the outcome of your special event - come to the golf, banquet and wedding experts.
GameWorks is the perfect place for your next event. You can eat, drink and play all under one roof! GameWorks has an awesome catering menu, private rooms and lounge areas, pool tables and state of the art video games. GameWorks provides options for groups of all sizes from 10 to 1200 guests.
This indoor sports facility offers soccer, lacrosse, floor hockey and basketball.
CITY:St. Charles
Featured on The Golf Scene with Steve Kashul and Heralded as one of Chicagoland's best buys for 18 holes, Settler's Hill is a favorite in Kane County and beyond. Here links, parkland and water holes combine to create a truly varied and memorable golf experience. Quirky greens, deep bunkers and colorful seasonal wildflower displays add to the course's charm. Superb conditioning and a casual atmosphere make Settler's Hill welcoming and enjoyable for all levels of golfers. The course's west-central location in Batavia near the Fox River makes Settler's Hill a natural choice for meeting friends for a round or planning an outing.
The Chicago Bandits are a women's professional softball team based in Rosemont, Illinois. Since the 2005 season, they have played as a member of National Pro Fastpitch (NPF). The Bandits won the 2008 NPF championship, defeating the Washington Glory in the final game of the championship series. The team won their second NPF championship following the 2011 season when they won the championship series two games to none over the USSSA Pride. Following the 2015 season the team won its third NPF championship defeating the USSSA Pride two games to none. They play their home games at Rosemont Stadium in Rosemont, Illinois.
If you enjoy challenging greens and a not too overbearing of a course, you have come to the right place. Bloomingdale Golf Club offers an enjoyable challenge for golfers of all levels.
Makray Memorial Golf Club is a premier 18-hole championship caliber courses in Illinois, 7,000 yards with four sets of tees; lots of water, strategic bunkers, bent grass tees, fairways and greens, blue grass roughs and spectacular views. The course re-opened for play June 8, 2004.An Enchanting Experience begins the moment you enter Makray Memorial Golf Club. Our brand new 24,000 sq. ft. Clubhouse has the charm of an old world manor and spectacular views of the golf course.
Built in 1965 and purchased by the village in 1977, the Buffalo Grove Golf Club is one of the finest municipal facilities in the area. The course features bent grass greens that are complemented with bluegrass fairways and tees. A mix of mature trees, sand and water will challenge shot-making abilities of all skill levels. Buffalo Grove Golf Club can be played from 6883 yards to as short as 5983 yards. The course offers three sets of tees; the choice is up to you. Course amenities include a driving range, chipping green, putting green, locker rooms, and a full service restaurant.
CITY:Buffalo Grove
A phenomenal golf course playing to 7,047 yards from the tips, Foxford Hills tests golfers' stamina and shot-making savvy with intriguing 60 MacKenzie style bunker complexes and strategically placed water. Five tee placements per hole create a truly flexible, dynamic layout, while expansive bentgrass fairways and generous greens ensure all golfers can have fun here.
Recently redesigned by renowned golf architect Dick Nugent Indian Boundary is a track suited for all levels of golfers. With its heavily-wooded layout and strategically placed water and sand the course is both scenic and challenging. Conveniently located in Chicago's Northwest side Indian Boundary is Forest Preserve Golf's most popular course.
Situated on land that once held the World's Columbian Exposition of 1893; the golf course opened six years later in 1899. The only eighteen hole golf course in the CPD Golf portfolio, the course meanders through the overall footprint of the 500 acre Jackson Park site. This includes mature trees, some newly renovated tee boxes, and large greens that all offer a challenging golf experience.
Burnham Woods, named after Daniel Burnham, who is credited with developing much of the structure of the City of Chicago, has some of the biggest cottonwood trees in the state. Located in southeastern Cook County this course's small greens, mature trees, and meandering streams makes for an excellent golfing experience.
Come see all the Cary Country Club has to offer from our rolling hills to our magnificent vistas! Come enjoy the spacious deck while enjoying lunch, dinner or a beverage of your choice. Cary Country Club offers golfers an array of shots and beautiful backdrops.Looking forward to seeing you soon!
Harborside International Golf Center
Harborside International Golf Center, home to both the Port & Starboard Courses, has been Chicago's home for golf since 1995. Located only minutes from Chicago's Loop, Harborside offers the premier golf experience in the Chicagoland area. As the only facility with two of Golfweek's "Best Courses You Can Play in Illinois" and the home to the most expansive driving range and practice facility.
The Highlands of Elgin Golf Course
The Highlands of Elgin has become a premier destination for thousands of golfers throughout the region. Nine new holes reclaim an old stone quarry, and take maximum advantage of the unique and dramatic landforms that were left behind, including a twelve acre quarry lake. Four holes hug the top of the bluff thirty to forty feet above the water providing golfers with incredible views and numerous shot options on each hole.
In 1919, when the North Shore Channel was new, and the area surrounding it was largely unusable, some progressive and creative leaders of Evanston and Wilmette joined together with a vision for a golf course — not just any golf course, but one tailored to wind through our communities and provide a unique public golf experience.
Whether it be for your wedding reception, a round of golf, fine dining, quick lunch or Sunday brunch, Carriage Greens Country Club is one of the finest entertainment and banquet facilities in the Chicago area. Boasting an ever expanding wine list, paired with any of the delicious menu items, and great service makes The Sandtrap Grill a unique dinning experience in Darien, Westmont, Lemont and the surrounding western suburbs.
Lake Park Golf Course is perfect for the young golfer who wants to play a shorter course with real bunkers and excellent greens. For the more experienced golfer, Lake Park is where you'll want to practice your all-important short game. The 18-hole, par 3-course is 1,515 yards in length with holes ranging from 50 to 115 yards.
CITY:Des Plaines
Fox Lake Country Club is a beautiful 18-hole golf course that is open to the public and nestled in the rolling terrain in the Village of Fox Lake, IL. Rated in the top 50 golf courses in Illinois. Fox Lake Country Club is convenient to the Chain O' Lakes that border Illinois and Wisconsin and is a popular summer vacation location. Fox Lake Country Club offers full banquet and grill services and is the perfect wedding and special event location.
CITY:Fox Lake
Featuring plenty of "breathing room" between holes, and given its appeal to a broad spectrum of golfing abilities, Tanna Farms is a fabulous outing venue. Combine great golf and a beautiful natural atmosphere with the award-winning onsite restaurant T.F. Boonie's and The Pavilion, a three-season venue that accommodates up to 200, and this is an unparalleled choice for your next event.


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Official: New Ford Focus Powertrain Technologies & Videos
The reveal of the next-generation Ford Focus at the 2010 North American International Auto Show includes the first in a series of powertrain technology developments coming from Ford that give its new global C-segment leader a combination of power, exhilarating performance and unsurpassed fuel economy.
Ford has disclosed that North American models of the new Focus will be equipped with a responsive, fuel-efficient combination of a 2.0-liter I-4 engine with Twin Independent Variable Camshaft Timing (Ti-VCT) and direct injection (DI) plus a dual-clutch PowerShift transmission.
"Combining a direct-injected engine and the dual-clutch PowerShift transmission will help Focus redefine fuel economy and flexibility in the C-car segment," said Barb Samardzich, vice president for Ford's global powertrain development. "The refinement and sheer fun-to-drive nature of the new Focus will surprise a lot of drivers."
The new engine is designed to deliver an estimated 155 horsepower and 145 ft.-lb. of torque to give customers ample performance and a refined driving experience.
The 2.0-liter Ti-VCT I-4 also serves as another example of Ford delivering fuel economy leadership by using advanced technologies to produce surprising power from minimal displacement. The engine can deliver outstanding fuel economy and emissions along with the throttle response, performance and flexibility expected from a world-class engine.
"Using direct injection and Ti-VCT, and coupling that to a dual-clutch transmission, we've been able to make a quantum leap in fuel economy and performance," said Derrick Kuzak, group vice president, Global Product Development. "We're meeting the goals of our global powertrain strategy, and we now have another key powertrain for use around the world."
Core engine technologies
As a DOHC design, the 2.0-liter I-4 uses two camshafts: one to open the intake valves and one to open the exhaust valves. Traditionally, camshafts have only been able to open the valves at a fixed point, defined during engine design and manufacture. But with modern variable cam timing systems, the camshafts can be rotated slightly relative to their initial position, allowing the cam timing to be advanced or retarded.
Ti-VCT takes this technology and applies it to both the intake and exhaust camshafts of its DOHC design, using electronic solenoid valves to direct high-pressure oil to control vanes in each of the camshaft sprocket housings. By using one oil control solenoid per camshaft, controlled by the Electronic Control Module, each intake and exhaust cam can be advanced or
retarded independently of the other as engine operating conditions change, providing an exceptional degree of valve timing control.
"The overlap control via Ti-VCT helps us eliminate compromises in the induction and exhaust systems," said Jamie Hanshaw, Ford VCT technical specialist. "Drivers will notice improved low-end power and better fuel economy. And there are benefits they won't notice too, like reduced emissions overall, especially at part-throttle."
Fuel metering duties on the 2.0-liter I-4 are handled by a DI system that precisely delivers a fine mist of fuel directly into each cylinder for optimal performance, economy and emissions. Unlike port fuel injection (PFI) engines that spray fuel into the intake system, the direct injection system puts the fuel in the combustion chamber, exactly where it needs to be for combustion. Thanks to DI, the engine can safely operate at a high 12:1 compression ratio (compared with the current engine's 10:1 ratio), further enhancing power and efficiency. And unlike most competitive direct injection systems, the engine will be E85 flex fuel-capable.
The high-pressure fuel injectors are positioned to the side of each cylinder, aiming the fuel directly into the cylinder adjacent to a high-intensity spark plug and alongside the intake and exhaust valves. Fuel is sprayed into the cylinders at pressures of up to 2,150 pounds per square inch, which is about 35 times more intense than PFI injection.
"The DI system creates an incredibly fine spray of gasoline that's injected directly into the combustion chamber at the precise moment it's needed, eliminating a lot of the compromises on traditional fuel systems," explains Scott Makowski, I-4 engine manager. "It sounds simple, but months of testing and computer simulation went into finding the exact injector spray pattern, where in the cylinder to aim the spray, and even the piston dome design."
The Denso high-pressure fuel injectors use internal solenoids to precisely switch the flow of fuel on and off. Fuel flows through six tiny outlets – like pinholes – in each injector, and each spray is positioned to provide benefits in fuel economy and emissions. A sophisticated electronic control system varies the timing and intensity of the fuel delivery according to engine operating conditions.
Attention to detail yields fuel economy improvements
Complementing the efficiencies introduced by Ti-VCT and DI, every aspect of the proven 2.0- liter I-4 was examined to identify ways fuel economy could be improved. Key strategies focused on reducing internal engine friction and reducing overall weight.
Computer modeling indicated areas where friction reduction strategies would pay the most dividends. The valvetrain received a fine surface treatment to present the smoothest surface possible. Piston skirts are treated with a special low-friction coating, and the oil pump and its drive ratio are sized for the exact capacity requirements of the new 2.0-liter engine.
Accessory drive friction was also reduced through a series of actions. Electric Power Assist Steering eliminates the drag of an engine-driven power steering pump, while the use of so-called stretchy belt technology removes friction in the form of a belt tensioner on the air-conditioning compressor drive system.
Additionally, an overriding alternator decoupler – essentially a special pulley that reduces certain types of vibrations – allows the alternator and water pump drive belt to operate at a much lower tension than is typically used, further reducing frictional losses.
To keep overall powertrain weight as low as possible, the block, cylinder head and oil pan – traditionally the heaviest engine components – are aluminum castings. To increase rigidity, these elements are ribbed for additional strength and durability. Pistons are cast aluminum as well, with the light weight helping to reduce reciprocating mass.
Composite material is employed to keep intake manifold weight to an absolute minimum, while allowing for induction routing to increase thermal efficiency and improve low-end torque characteristics.
PowerShift: A different kind of automatic
An all-new PowerShift six-speed automatic transmission that combines the responsive performance and fuel economy of a manual gearbox with the convenience of a traditional automatic transmission promises to be another key Focus powertrain technology.
"PowerShift is a transmission that changes the game," said Samardzich. "Our fuel economy leader is now a PowerShift automatic. Previously, a C-segment driver needed a manual transmission and a clutch pedal to enjoy the greatest fuel efficiency."
Twin internal clutches keep the PowerShift in constant mesh, continuously optimizing for maximum responsiveness and fuel efficiency, depending on engine speed, vehicle speed and input from the driver's foot on the accelerator pedal. The new technology provides significant uel economy improvement, and for the driver, it retains the operational ease of an automatic ith noticeably quicker and smoother shift quality.
PowerShift is a dual dry clutch transmission, operating with sealed internal lubrication, reducing riction and contributing to Focus fuel economy improvements. The lack of pumps and hoses educes complexity, saves weight nd contributes to fuel efficiency.
An additional feature is Hill Start Assist functionality. This sensor-based system will "hold" the rakes for an instant (2.5 seconds) to prevent rollback when stopping or starting from rest on an ncline. Employing a digital accelerometer to measure slope incline, the system activates
automatically when the incline exceeds 3 percent.
Simpler, more responsive and more fuel-efficient than a conventional automatic transaxle, owerShift represents an innovative small car reakthrough.
Continuing refinement on the global stage
Using the 2.0-liter Ti-VCT engine and PowerShift dual-clutch transmission in the North merican market, combined with state-of-the-art common-rail diesels for global customers, ocus is poised to claim a leadership role in fuel economy from the moment t's launched. This owertrain will not be marketed in Europe.
The global powertrain lineup for the new Focus also will include a range of state-of-the-art Ford EcoBoost™ four-cylinder turbocharged direct injection engines – including the 1.6-liter unit in urope and a choice of advanced and improved Duratorq TDCi common-rail diesel engines, all f which offer reductions in fuel consumption of between 10 and 20 percent compared to the utgoing models.
"When the new Focus launches in late 2010, it will be among the global eaders in fuel economy nd CO2 emissions," said Kuzak. "We will continue to pioneer new technologies beyond launch, ncluding a true zero-emission model launching in North America in 2011. Throughout its life cycle, Focus in all forms, in all regions, will demonstrate the Ford commitment to deliver unsurpassed fuel economy on a truly global scale."
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GO Green
Good post time...I wanted to add a few things, not strictly powertrain but will be a huge difference regarding it over previous models. To also get the best fuel economy Ford has implemented start stop technology into the car, the first of its kind here in the US on a non hybrid car. Should be interesting, and will definitely be something that will take time to getting used too...unless you already drive a hybrid.
My 2003 Ford Focus ZX3 - Finally realized it's a 4cyl
Excellent information!
Disciple of the "Push harder, suck less" school of autocross.
gumpcrew #6
Focus Fanatic
The tranny idea
Yes I posted this in another thread but its how i feel
So it take one of the fun factors away....being able to control a manaul and to fpick when you shift.......
I like to be "connected" to the car in as many ways as possible ....
no actual clutch= FAIL
I dont care if it helps with econ-factor....it take away the FUN factor
Focus Fanatic
Are you all SURE there is no manual? I would have sworn I either read or maybe it was an interview that there is a traditional 6-speed manual option. The PowerShift is the 'automatic', but it's not a traditional (torque converter) type.
Steeda SRI w/CAI intake. Trubendz SS 2.5" . FR Susp/Struts. Tune by Tom (FocusPower). Rota Grids. SAP rear spoiler. Custom front air dam, rocker panel bits and Rear valance.
Last of the Hatches #28
Focus Enthusiast
We never get any of the goodies they have in Europe. :(
I would give my left lugnut for an RS (not a green one)
Just keep driving...
Focus Addict
Don't worry, you'll get manual and ST/RS versions but the name could be SVT I guess
V8, 4.0 L, 420 hp, 6 speed manual, rear wheel drive, coupe, REDLINE AT 8400 rpm = 2007 BMW M3 E92 - new will be turbo, shame
Visit http://zinteractive-fordfocus.webs.com/ for all informations about ford focus! / UPDATED at 27/07/2012
Focus Addict
Actually I saw http://www.youtube.com/watch?v=DjmyTw0JS0k
and he says: and for those who want be able to have flexability of shifting their transmission themselfs we will have a 5 speed manual transmission available!
So YES!!!!
V8, 4.0 L, 420 hp, 6 speed manual, rear wheel drive, coupe, REDLINE AT 8400 rpm = 2007 BMW M3 E92 - new will be turbo, shame
Visit http://zinteractive-fordfocus.webs.com/ for all informations about ford focus! / UPDATED at 27/07/2012
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Property to let in Church Road, Little Berkhamsted, Hertford SG13 - 5 bedrooms
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St. Marys Lane, Hertingfordbury, Hertford SG14Detached house to rent - 5 bedrooms
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A beautifully presented five bedroom detached family home located in the popular village of Hertingfordbury. Set within 17 acres of grounds, this Victorian property features five bedrooms, four bathrooms, Lounge, kitchen/breakfast room, utility room, ...
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Anesthesiologist (pain control)
11 years of experience
11 years of experience
804 Scott Nixon Memorial Dr
Augusta, GA 30907 Phone number & directions
804 Scott Nixon Memorial Dr
Augusta, GA 30907 Phone number & directions
License & Identifications
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text:
My son turned one yesterday and we started the weaning process about a week ago, and he's also cut out one of his nursing sessions on his own. I work FT and I've stopped pumping at work so my supply has dropped.
He refuses to take a bottle from us, and his nanny said that when she started to give him all whole milk he resists but would finally give in and only drink like 4-6oz, he previous was drinking 7-8oz of breastmilk from a bottle. With us he just won't take a bottle and will just suck his thumb to pacify and eventually start crying.
Any advice? We have also tried to give him milk in his sippy but he won't drink it like that either. The main reason we're switching to whole milk is because I'm starting to travel for work again now that he's a year old and I have my first trip without him this weekend.
Help! People are telling us to not give in a nurse him and he'll eventually realize there's no more breast, but I feel awful doing that I and I haven't.


text:
|Publication number
|Publication type
|Application number
|Publication date
|Jan 31, 1984
|Filing date
|May 17, 1982
|Priority date
|May 17, 1982
|Fee status
|Publication number
|Jean E. F. Rivier, Wylie W. Vale, Jr., Marvin R. Brown
|Original Assignee
|The Salk Institute For Biological Studies
|Export Citation
|BiBTeX, EndNote, RefMan
|Referenced by (15), Classifications (17), Legal Events (4)
|External Links: USPTO, USPTO Assignment, Espacenet
This invention was made with Government support under Grant Nos. AM20917 and AM26741 awarded by DHHS(NIH). The Government has certain rights in this invention.
This invention is directed to peptides related to the tetradecapeptide somatostatin and to methods for pharmaceutical treatment of mammals using such peptides. More specifically, the invention relates to methods of treatment of mammals using somatostatin analogs which increase electrolyte absorption in the gut and also to certain analogs of somatostatin and to pharmaceutical compositions containing such analogs.
The tetradecapeptide somatostatin was characterized by Guillemin et al. and is described in U.S. Pat. No. 3,904,594 (Sept. 9, 1975). The tetradecapeptide has the formula: ##STR2## wherein there is a bridging bond between the sulfhydryl groups of the two cysteinyl amino acid residues. The tetradecapeptide in its linear form (sometimes referred to as dihydrosomatostatin), as well as analogs wherein this bridging bond is not present and is replaced by hydrogen, are for purposes of this application considered to be included in the definition "somatostatin analogs" as they appear to have substantially the same biological activity.
Somatostatin and many analogs of somatostatin exhibit activity in respect to the inhibition of growth hormone(GH) secretion from cultured, dispersed rat anterior pituitary cells in vitro and also in vivo, and with respect to the inhibition of insulin and glucagon secretion in vivo in the rat and in other mammals. Somatostatin has also been found to inhibit the secretion of gastrin and secretion by acting directly upon the secretory elements of the stomach and pancreas respectively. Its ability to inhibit the secretion of such hormones, allows somatostatin to be therapeutically employed in clinical conditions for the treatment of acromegaly, pancreatic islet cell tumors, diabetes mellitus and gastrointestinal bleeding. Because somatostatin has these properties, they must be taken into consideration whenever it is administered in vivo. The search has continued for somatostatin analogs which are potent in their effect in the gut but which are less potent than somatostatin in their inhibitory functions.
It has been found that diarrhea and the like can be effectively treated by the administration of analogs of the peptide somatostatin that have been prepared and purified (i.e., substantially free of related synthetic replicates) and which increase electrolyte absorption in the gut but which are very substantially less potent than somatostatin in inhibiting the release of GH, glucagon and/or insulin. This is referred to as having dissociated biological activity with respect to SS-14. The analogs have the formula: ##STR3## wherein: R is hydrogen or an acylating agent selected from the group consisting of amino acids, dipeptides, tripeptides and aliphatic, aromatic and cyclic organic acids having from 1 to 10 carbon atoms; R1 is Ala or des R1 ; R2 is Gly or des R2 ; R4 is Lys or D-Lys or des R4 ; R5 is Asn or des R5 ; R6 is Phe or D-Phe or Ala; R10 is Thr or Ala or des R10 ; R11 is Ala, Arg, Trp, Val, Ile, Ser, Thr, Glu, His, β-Nal, Lys, Pro or des R11 ; R12 is Thr or Ala or des R12 ; and R13 is Ser or D-Ser or des R13 ; provided that not more than two of R10, R11, R12 and R13 are deleted and provided that if R4 is deleted, either R12 or R13 is deleted.
Pharmaceutical compositions in accordance with the invention include specific of these analogs, or nontoxic addition salts thereof, dispersed in a pharmaceutically acceptable liquid or solid carrier. The administration of such somatostatin analogs or pharmaceutically acceptable addition salts thereof to mammals in accordance with the invention may be carried out to increase the absorption of electrolytes and thereby effectively treat diarrhea in patients with endocrine tumors and short bowel syndrome.
The nomenclature used to define the peptides is that specified by Schroder & Lubke, "The Peptides", Academic Press (1965) wherein, in accordance with conventional representation, the amino group appears to the left and the carboxyl group to the right. Where the amino acid residue has isomeric forms, it is the L-form of the amino acid that is represented unless otherwise expressly indicated. By β-Nal is meant 3-(naphthyl)-Ala.
The invention provides analogs of having the following formula: ##STR4## wherein: R is hydrogen or an acylating agent selected from the group consisting of amino acids, dipeptides, tripeptides and aliphatic, aromatic and cyclic organic acids having from 1 to 10 carbon atoms; R1 is Ala or des R1 ; R2 is Gly or des R2 ; R4 is Lys or D-Lys or des R4 ; R5 is Asn or des R5 ; R6 is Phe or D-Phe or Ala; R10 is Thr or Ala or des R10 ; R11 is Ala, Arg, Trp, Val, Ile, Ser, Thr, Glu, His, β-Nal, Lys, Pro or des R11 ; R12 is Thr or Ala or des R12 ; and R13 is Ser or D-Ser or des R13 ; provided that not more than two of R10, R11, R12 and R13 are deleted and provided that if R4 is deleted, either R12 or R13 is also deleted. Although not specifically shown herein, the formula should be understood also to include the linear form thereof wherein the bridge between the sulfhydryl groups of Cys residues is not present and is replaced by hydrogen. Of particular interest are the analogs where R11 is Trp, Arg, His, β-Nal or Glu, with the first four being preferred.
The peptides are synthesized by a suitable method, such as by exclusively solid-phase techniques, by partial solid-phase techniques, by fragment condensation or by classical solution addition. For example, the techniques of exclusively solid-state synthesis are set forth in the textbook "Solid-Phase Peptide Synthesis", Stewart & Young, Freeman & Co., San Francisco, 1969 and are exemplified by the disclosure of U.S. Pat. No. 4,105,603, issued Aug. 8, 1978 to Vale et al. The fragment condensation method of synthesis is exemplified in U.S. Pat. No. 3,972,859 (Aug. 3, 1976). Other available syntheses are exemplified by U.S. Pat. No. 3,842,067 (Oct. 15, 1974) and U.S. Pat. No. 3,862,925 (Jan. 28, 1975).
Common to such syntheses is the protection of the labile side chain groups of the various amino acid moieties with suitable protecting groups which will prevent a chemical reaction from occurring at that site until the group is ultimately removed. Usually also common is the protection of an alpha-amino group on an amino acid or a peptide fragment while that entity reacts at the carboxyl group, followed by the selective removal of the alpha-amino protecting group to allow a subsequent reaction to take place at that location. Accordingly, it is common that, as a step in the synthesis, an intermediate compound is produced which includes each of the amino acid residues located in its desired sequence in the peptide chain with various of these residues linked to the side-action protecting groups.
Also considered to be within the scope of the present invention are intermediates of the formula:
X1 -R1 -R2 -Cys(X2)-R4 (X3)-R5 (X4)-Phe-Phe-Trp-Lys(X3)-R10 (X5)-R11 (X6)-R12 (X5)-R13 (X5)-Cys(X2)-X7
wherein: the R-groups are as hereinbefore defined except for R11 which is Trp, Arg, His, Glu or β-Nal and wherein:
X1 is either hydrogen or an α-amino protecting group. The α-amino protecting groups contemplated by X1 are those known to be useful in the art in the step-wise synthesis of polypeptides. Among the classes of α-amino protecting groups covered by X1 are (1) acyl-type protecting groups, such as formyl, trifluoroacetyl, phthalyl, p-toluenesulfonyl(Tos), benzenesulfonyl, nitrophenylsulfenyl, tritylsulfenyl, o-nitrophenoxyacetyl, chloroacetyl, acetyl, and γ-chlorobutyryl; (2) aromatic urethan-type protecting groups, such as benzyloxycarbonyl(Z) and substituted Z, such as p-chlorobenzyloxycarbonyl, p-nitrobenzyloxycarbonyl, p-bromobenzyloxycarbonyl, p-methoxybenzyloxycarbonyl; (3) aliphatic urethan protecting groups, such as t-butyloxycarbonyl (BOC), diisopropylmethoxycarbonyl, isopropyloxycarbonyl, ethoxycarbonyl, allyloxycarbonyl; (4) cycloalkyl urethan-type protecting groups, such as cyclopentyloxycarbonyl, adamantyloxycarbonyl, and cyclohexyloxycarbonyl; (5) thiourethan-type protecting groups, such as phenylthiocarbonyl; (6) alkyl-type protecting groups, such as triphenylmethyl(trityl), benzyl(Bzl); (7) trialkylsilane groups, such as trimethylsilane. The preferred α-amino protecting group is BOC.
X2 is a protecting group for Cys preferably selected from the class consisting of p-methoxybenzyl(MeOBzl), p-methylbenzyl, acetamidomethyl, trityl and Bzl. The most preferred protecting group is p-methoxybenzyl. X2 can also be hydrogen, meaning that there is no protecting group on the sulfur.
X3 is hydrogen or a protecting group for the side chain amino substituent of Lys. Illustrative of suitable side chain amino protecting groups are Z, 2-chlorobenzyloxycarbonyl(2-Cl-Z), Tos, t-amyloxycarbonyl and BOC. The selection of a side chain amino protecting group is not critical except that it must be one which is not removed during deprotection of the α-amino groups during the synthesis. Hence, the α-amino protecting group and the side chain amino protecting group cannot be the same.
X4 is hydrogen or a protecting group for the amido group of Asn and is preferably xanthyl(Xan).
X5 is a protecting group for the hydroxyl group of Thr or Ser and is preferably selected from the class consisting of acetyl(Ac), benzoyl(Bz), tert-butyl, trityl, tetrahydropyranyl, benzyl ether(Bzl), 2,6-dichlorobenzyl and Z. The most preferred protecting group is Bzl. X5 can be hydrogen, which means there is no protecting group on the hydroxyl group.
X6 may be a protecting group for the guanidino group of Arg, if Arg is employed, preferably selected from the class consisting of nitro, Tos, Z, adamantyloxycarbonyl and BOC, or is hydrogen. Tos is most preferred. Otherwise, X6 is a side chain protecting group for Glu or His, such as 2,6 dichlorobenzyl or Tos, respectively, if either of these residues is employed.
X7 is selected from the class consisting of OH, OCH3, amides, hydrazides and esters, including a benzyl ester or a hydroxymethyl ester anchoring bond used in solid phase synthesis for linking to a solid resin support, represented by the formulae:
--O--CH2 --polystyrene resin support
O--CH2 --benzyl-polystyrene resin support
The polystyrene polymer is preferably a copolymer of styrene with about 0.5 to 2% divinyl benzene as a cross-linking agent, which causes the polystyrene polymer to be completely insoluble in certain organic solvents.
In the formula for the intermediate, at least one of X1, X2, X3, X4, X5, X6 and X7 is a protecting group. In selecting a particular side chain protecting group to be used in the synthesis of the peptides, the following rules are followed: (a) the protecting group must be stable to the reagent and under the reaction conditions selected for removing the α-amino protecting group at each step of the synthesis, (b) the protecting group must retain its protecting properties and not be split off under coupling conditions and (c) the side chain protecting group must be removable, upon the completion of the synthesis containing the desired amino acid sequence, under reaction conditions that will not alter the peptide chain.
The peptides are preferably prepared using solid phase synthesis, such as that described by Merrifield, J. Am. Chem. Soc., 85, p 2149 (1964), although other equivalent chemical syntheses known in the art can also be used as previously mentioned. Solid-phase synthesis is commenced from the C-terminal end of the peptide by coupling a protected α-amino acid to a suitable resin. Such a starting material can be prepared by attaching α-amino- and S-protected Cys to a chloromethylated resin or to a hydroxymethyl resin. The preparation of the hydroxymethyl resin is described by Bodansky et al., Chem. Ind. (London) 38, 1597-98 (1966). Chloromethylated resins are commercially available from Bio Rad Laboratories, Richmond, Calif. and from Lab. Systems, Inc. The preparation of such a resin is described by Stewart et al., "Solid Phase Peptide Synthesis" (Freeman & Co., San Francisco 1969), Chapter 1, pp 1-6.
Cys protected by BOC and by p-methoxybenzyl is coupled to the chloromethylated polystyrene resin according to the procedure of Monahan and Gilon, Biopolymer 12, pp 2513-19, 1973. Following the coupling of BOC-(p-methoxybenzyl) (Cys) to the resin support, the α-amino protecting group is removed, as by using trifluoroacetic acid(TFA) in methylene chloride, TFA alone or with HCl in dioxane. Preferably 50 weight % TFA in methylene chloride is used with 0-5 weight % 1,2 ethane dithiol. The deprotection is carried out at a temperature between about 0� C. and room temperature. Other standard cleaving reagents and conditions for removal of specific α-amino protecting groups may be used as described in Schroder & Lubke, "The Peptides", 1 pp 72-75 (Academic Press 1965).
After removal of the α-amino protecting group of Cys, the remaining α-amino- and side chain-protected amino acids are coupled step-wise in the desired order to obtain the intermediate compound defined hereinbefore. As an alternative to adding each amino acid separately in the synthesis, some of them may be coupled to one another prior to addition to the solid phase reactor. The selection of an appropriate coupling reagent is within the skill of the art. Particularly suitable as a coupling reagent is N,N'-dicyclohexyl carbodiimide (DCCI).
The activating reagents used in the solid phase synthesis of the peptides are well known in the peptide art. Examples of suitable activating reagents are:
(1) carbodiimides, such as N,N'-diisopropyl carbodiimide, N-ethyl-N'-(3-dimethylaminopropyl)carbodiimide; (2)cyanamides such as N,N'-dibenzylcyanamide; (3) keteimines; (4) isoxazolium salts, such as N-ethyl-5-phenyl isoxazolium-3'-sulfonate; (5) monocyclic nitrogen-containing heterocyclic amides of aromatic character containing one through four nitrogens in the ring, such as imidazolides, pyrazolides, and 1,2,4-triazolides. Specific heterocyclic amides that are useful include N,N'-carbonyl diimidazole, N,N'-carbonyl-di-1,2,4-triazole; (6) alkoxylated acetylene, such as ethoxyacetylene; (7) reagents which form a mixed anhydride with the carboxyl moiety of the amino acid, such as ethylchloroformate and isobutylchloroformate and (8) nitrogen-containing heterocyclic compounds having a hydroxy group on one ring nitrogen, such as N-hydroxyphthalimide, N-hydroxysuccinimide and 1-hydroxybenzotriazole(HOBT). Other activating reagents and their use in peptide coupling are described by Schroder & Lubke, supra, in Chapter III and by Kapoor, J. Phar. Sci., 59, pp 1-27 (1970).
Each protected amino acid or amino acid sequence is introduced into the solid phase reactor in about a two- to fourfold excess, and the coupling is carried out in a medium of dimethylformamide(DMF):CH2 Cl2 (1:1) or in DMF or CH2 Cl2 alone. In instances where the coupling is carried out manually, the success of the coupling reaction at each stage of the synthesis is monitored by the ninhydrin reaction, as described by E. Kaiser et al., Anal. Biochem. 34, 595 (1970). In cases where incomplete coupling occurs, the coupling procedure is repeated before removal of the α-amino protecting group prior to the coupling of the next amino acid. The coupling reactions can be performed automatically, as on a Beckman 990 automatic synthesizer, using a program such as that reported in Rivier et al., Biopolymers, 1978, 17, pp.1927-1938.
After the desired amino acid sequence has been completed, the intermediate peptide is removed from the resin support by treatment with a reagent, such as liquid hydrogen fluoride or an equivalent, which not only cleaves the peptide from the resin but also cleaves all remaining side chain protecting groups X2, X3, X4, X5 and X6 and the α-amino protecting group X1, to obtain the peptide in its linear form. The cyclic form of the peptide is obtained by oxidizing using a ferricyanide solution, preferably as described Rivier et al., Biopolymers, Vol. 17 (1978), 1927-38, or by air oxidation, or in accordance with other known procedures.
As an alternative route, the intermediate peptide may be separated from the resin support by alcoholysis after which the recovered C-terminal ester is converted to the acid by hydrolysis. Any side chain protecting groups may then be cleaved as previously described or by other known procedures, such as catalytic reduction (e.g., Pd on BaSO4) using conditions which will keep the Trp moiety intact. When using hydrogen fluoride for cleaving, anisole and methylethyl sulfide are included in the reaction vessel for scavenging.
The following Example sets forth the preferred method for synthesizing analogs of somatostatin by the solid-phase technique.
The synthesis of the analog [Trp11 ]-SS having the formula: ##STR5## is conducted in a stepwise manner on a chloromethylated resin, such as LS-601 available from Lab Systems, Inc., containing 0.9 Meq Cl/gm. resin. Coupling of BOC-(p-methoxybenzyl)Cys to the resin is performed by the procedure set forth by Horiki et al., in Chemistry Letters (Chem. Soc. of Japan) (1978) pp. 165-168, and it results in the substitution of about 0.35 mmol. Cys per gram of resin. All solvents that are used are carefully degassed, preferably by sparging with an inert gas, e.g., nitrogen, to insure the absence of oxygen that might undesirably oxidize the Trp residue.
After deprotection and neutralization, the peptide chain is built step-by-step on the resin. Generally, one to two mmol. of BOC-protected amino acid in methylene chloride is used per gram of resin, plus one equivalent of 2 molar DCCI in methylene chloride, for two hours. When BOC-Trp or BOC-Arg(Tos) or BOC-Asn(Xan) is being coupled, a mixture of 10% DMF and methylene chloride is used. Bzl is used as the hydroxyl side-chain protecting group for Ser and Thr. P-nitrophenyl ester(ONp) is used to activate the carboxyl end of Asn, and BOC-Asn(ONp) is coupled overnight using one equivalent of HOBt in a 50% mixture of DMF and methylene chloride. 2-Cl-Z is used as the protecting group for the Lys side chain. The amido group of Asn is protected by Xan. At the end of the synthesis, the following composition is obtained (BOC)Ala-Gly-Cys(MeOBzl)-Lys(2-Cl-Z)-Asn(Xan)-Phe-Phe-Trp-Lys(2-Cl-Z)-Thr(Bzl)-Trp-Thr(Bzl)-Ser(Bzl)-Cys(MeOBzl)-O-CH2 -benzyl-polystyrene resin support.
In order to cleave deprotect the resulting protected peptide-resin, it is treated with 1.5 ml. anisole, and 15 ml. hydrogen fluoride(HF) per gram of peptide-resin, first at -20� C. for 20 min. and then at 0.� C. for one-half hour. After elimination of the HF under high vacuum, the resin-peptide is washed alternately with dry diethyl ether and chloroform, and the peptides are then extracted with de-gassed 2 N aqueous acetic acid and separated from the resin by filtration.
The cleaved and deprotected peptide is then and added dropwise to a potassium ferricyanide solution to form the disulfide bond between the Cys residues, as described by Rivier et al. in Biopolymers, Volume 17 (1978) pp. 1927-1938. After cyclization, the peptide is chromatographed on both anion- and cation-exchange resins using the methods described in the Rivier et al. article and then lyophilized.
The peptide is then purified by gel permeation followed by semi-preparative HPLC as described in Rivier et al., Peptides: Structure and Biological Function (1979) pp. 125-128. The chromatographic fractions are carefully monitored by HPLC, and only the fractions showing substantial purity were pooled.
Specific optical rotation of the SS analog, which was synthesized and purified in the foregoing manner, was measured on a Perkin Elmer Model 141 as [α]D 22� =-34.5� (c=1 in 1% acetic acid) and had a purity of about 95%. To check whether the precise sequence was achieved, the analog was hydrolyzed in sealed evacuated tubes containing 4 N methanesulfonic acid and 0.2% tryptamine for 24 hours at 110� C. Amino acid analyses of the hydrolysates using a Beckman 121 MB amino acid analyzer showed that the 14-residue peptide structure had been obtained.
The other analogs listed in Table I are also synthesized and purified using the same method as set forth above.
TABLE I______________________________________No. Composition______________________________________1 [Trp11 ]--SS2 [Arg11 ]--SS3 des-AA1,2,[Trp11 ]--SS4 des-AA1,2,4,5,12,[D-Trp8,Trp11 ]--SS5 [Ala11 ]--SS6 des-AA1,2,4,5,12,[D-Trp8 ]--SS7 des-Thr12 --SS8 des-Phe11 --SS9 des-Ala1,Gly2 --SS10 [His11 ]--SS11 des-AA1,2,[β-Nal11 ]--SS12 [Glu11 ]--SS13 des-Asn5 --SS14 des-Ser13 --SS15 [D-Lys4 ]--SS16 [D-Phe6 ]--SS17 [D-Cys14 ]--SS______________________________________
To determine the effectiveness of the peptides to inhibit the release of growth hormone, in vitro radioimmunoassays are carried out using the SS analogs in side-by-side comparison with equimolar concentrations of somatostatin-14 having a known effectiveness to inhibit the release of growth hormone induced by the application of isobutyl methyl xanthine to pituitary cells. Cultures are used which include cells of rat pituitary glands removed some four to five days previously in a system that minimizes enzymatic degradation, generally following the procedure set forth in Vale et al., Methods in Enzymology, Hormones and Cyclic Nucleotides (1975) Vol. 37, p. 82. Both cultures of a defined standard medium and cultures which are considered optimal for the secretion of growth hormone, as a result of having additions of either 2% or 10% of serum from a foetal calf, are used for the comparative testing. The result of this comparative testing is that analog No. 1 shows a potency for the inhibition of GH less than about 1% of that of SS-14.
In vivo experiments are carried out with the analogs, using the procedure described in Brown et al., Metabolism (1976) Vol. 25, pp. 1501-1503, to determine the potency, relative to somatostatin-14, to inhibit the secretion of glucagon and insulin stimulated by the administration of arginine to groups of six rats. Analog No. 1 exhibits a potency to inhibit basal and stimulated insulin and glucagon secretion in mammals, including humans and dogs, less than about 1% and 1% respectively, compared to SS-14. The remaining peptide analogs have similar significantly reduced effects upon the inhibition of GH, insulin and glucagon release.
The analogs are tested in vitro in isolated rabbit ileum using the modified Ussing chamber technique, as described in Amer. J. of Physiol., 225:776-780 (1973). Unidirectional chloride fluxes are determined and used to characterize bi-directional fluxes following the addition of an SS-analog. Changes are measured with varying concentrations, and the potency to inhibit ion transport is quantitated and expressed as a percentage of the potency of SS-14. For example, analog No. 1 shows a potency about 249% of that of SS-14 which is indicative of its effectiveness in increasing electrolyte absorption in the gut. All of the analogs either show a very substantial increase in electrolyte absorption in the gut without increasing the inhibition of other secretions, or show a far greater decrease in the inhibition of the secretion of insulin, glucagon and/or GH than in its biological activity in the gut. These results are summarized in Table II.
______________________________________Peptide Insulin Glucagon GH Ion Transport______________________________________SS-14 100 100 100 1001 <1 <1 <1 2492 142 <1 2913 4054 375 <10 3 526 70 20 45 2577 <1 <1 2 218 <1 <1 2 349 61 60 23110 <1 <1 4811 10712 <1 <1 913 10 <1 4 1114 <1 <1 2 915 1 1 22 13916 <1 <1 5 1017 20 310 270 336______________________________________
The administration to mammals of an effective amount of these analogs (or a nontoxic, pharmaceutically aceptable addition salt thereof) can be used to very substantially increase electrolyte absorption and decrease gut motility in mammals and may be employed in the treatment of diarrhea, in the same general manner as somatostatin is presently being administered for inhibiting gastric secretion, particularly in patients with carcinoid tumors and short bowel syndrome. Likewise, administration of these peptides to mammals in effective amounts can be used to increase the absorption of electrolytes in the gut without significantly inhibiting the release of growth hormone, insulin or glucagon and can be used for this purpose, under the guidance of a physician, generally along the lines and in accordance with clinical procedures heretofore developed using somatostatin-14 for the purpose of decreasing gastric acid secretion.
It was very surprising to discover that certain of these analogs exhibited such a substantial increase in electrolyte absorption, in comparision with SS-14, while having very significantly less effect upon the inhibition of GH, insulin and glucagon secretion. As a result, these peptide analogs are particularly valuable for the treatment of diarrhea which can be carried out without undesirable side effects that would accompany treatment with larger dosages of SS-14 for this purpose.
These analogs or the nontoxic addition salts thereof, combined with a pharmaceutically acceptable carrier to form a pharmaceutical composition, may be administered to mammals, including humans, either intravenously, subcutaneously, intramuscularly, intranasally or orally. The administration may be employed by a physician to treat diarrheal syndrones. The required dosage will vary with the particular condition being treated, with the severity of the condition, with the duration of desired treatment and with the method of administration. Intravenous administration is preferred because it has about the same effect as a dose given orally one thousand times greater or a dose given intranasally one hundred times greater.
The peptides should be administered under the guidance of a physician, and pharmaceutical compositions will usually contain the peptide in conjunction with a conventional, sterile liquid pharmaceutically-acceptable carrier. Usually, the intravenous administration for a patient of normal body weight will be from 25 to 300 μg/hr. for as long as necessary to alleviate the diarrheal syndrone, e.g., for a 24-hour period. Overall, treatment of subjects with these peptides is generally carried out in the same manner as the treatment for gastric ulcers is presently carried out using somatostatin itself.
Such peptides are often administered in the form of pharmaceutically acceptable nontoxic salts, such as acid addition salts or metal complexes, e.g., with zinc, iron, calcium, barium, magnesium, aluminum or the like (which are considered as addition salts for purposes of this application). Illustrative of such acid addition salts are hydrochloride, hydrobromide, sulphate, phosphate, tannate, pamoate, oxalate, fumarate, gluconate, alginate, maleate, acetate, citrate, benzoate, succinate, malate, ascorbate, tartrate and the like. If the active ingredient is to be administered in tablet form, the tablet may contain a binder, such as tragacanth, corn starch or gelatin; a disintegrating agent, such as alginic acid; and a lubricant, such as magnesium stearate. If administration in liquid form is desired, sweetening and/or flavoring may be used, and intravenous administration in isotonic saline, phosphate buffer solutions or the like may be effected.
Although the invention has been described with regard to its preferred embodiments, which constitute the best mode presently known to the inventors, it should be understood that various changes and modifications as would be obvious to one having the ordinary skill in this art may be made without departing from the scope of the invention which is set forth in the claims appended hereto. For example, substitutions and modifications at positions in the somatostatin peptide chain which are indicated as being presently subject to deletion, as well as in the 6-position, can be made with other naturally occuring amino acids without detracting from the potency of the analogs, and such peptides are considered as being within the scope of the invention. As earlier indicated, the linear form as well as the preferred cyclic form of the analogs is considered to be within the scope of the invention, and the two-member tail (i.e., Ala-Gly) can be deleted, substituted, modified or substantially added to without adversely affecting the potency of the analogs, as set forth in Guillemin et al. U.S. Pat. No. 3,904,594 which describes the addition of an acylating agent.
Various features of the invention are emphasized in the claims which follow.
|Citing Patent
|Filing date
|Publication date
|Sep 17, 1985
|Mar 28, 1989
|Todaro George J
|Biologically active polypeptides
|Jun 12, 1987
|Jun 13, 1989
|Eastman Kodak Company
|Polypeptide compounds having growth hormone releasing activity
|May 22, 1987
|Sep 5, 1989
|Todaro George J
|Biologically active polypeptides
|Apr 10, 1987
|Nov 14, 1989
|Eastman Kodak Company
|Combinations having synergistic growth hormone releasing activity and methods for use thereof
|Dec 9, 1991
|Aug 31, 1993
|Todaro George J
|Transforming growth factor (TGF) peptides
|Apr 21, 1994
|Jul 9, 1996
|Polygen Holding Corporation
|Polypeptide compounds having growth hormone releasing activity
|Dec 26, 1995
|Jan 13, 1998
|Biomeasure Incorporated
|Cyclic peptide analogs of somatostatin
|Oct 18, 1995
|May 12, 1998
|The Salk Institute For Biological Studies
|Receptor-selective somatostatin analogs
|Jan 13, 1998
|Dec 14, 1999
|Biomeasure, Inc.
|Cyclic peptide analogs of somatostatin
|Jun 14, 2011
|The Salk Institute For Biological Studies
|Receptor(SSTR2)-selective somatostatin antagonists
|Jun 13, 2011
|Aug 6, 2013
|Jean E. F. Rivier
|Receptor(SSTR2)-selective somatostatin antagonists
|Apr 16, 2008
|Apr 8, 2014
|Jean E. F. Rivier
|Somatostatin receptor 2 antagonists
|Oct 15, 2007
|Oct 23, 2008
|The Salk Institute For Biological Studies
|Receptor(sstr2)-selective somatostatin antagonists
|Apr 16, 2008
|Dec 4, 2008
|Salk Institute For Biological Studies Universitat Bern University Hospital Basel
|Somatostatin receptor 2 antagonists
|Sep 4, 1996
|Aug 26, 1998
|Biomeasure, Inc.
|Cyclic peptide analogs of somatostatin
|U.S. Classification
|International Classification
|Cooperative Classification
|European Classification
|May 17, 1982
Owner name: SALK INSTITUTE FOR BIOLOGICAL STUDIES THE, SA DIEG
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST.;ASSIGNORS:RIVIER, JEAN E. F.;VALE, WYLIE W. JR.;BROWN, MARVIN R.;REEL/FRAME:004002/0558;SIGNING DATES FROM 19820510 TO 19820511
Owner name: SALK INSTITUTE FOR BIOLOGICAL STUDIES THE, SA DIEG
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:RIVIER, JEAN E. F.;VALE, WYLIE W. JR.;BROWN, MARVIN R.;SIGNING DATES FROM 19820510 TO 19820511;REEL/FRAME:004002/0558
|Feb 12, 1987
|Fee payment
Year of fee payment: 4
|Feb 27, 1991
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TIMBERLINE LODGE, Ore. (AP) - Nine climbers fell into a crevasse Thursday near the summit of Mount Hood in an accident that killed three and critically injured two others. Rescue efforts took a dramatic turn when a helicopter trying to reach the survivors crashed nearby, tumbling down the snowy mountainside.
The four crew members escaped the battered helicopter, but at least two were seriously injured, said Chris Bernard, an Air Force Reserve rescue specialist.
The injured climbers and helicopter crew members were taken to hospitals in Portland, about 50 miles away, said Angela Blanchard, spokeswoman for the Clackamas County Sheriff's Department. By late evening, the rescuers were working to recover the three bodies.
The Pave Hawk helicopter was attempting to bring up a climber on a gurney attached to a cable when it started to lose altitude. A crew member released the cable just before the pilot pulled away from the ridge.
Its refueling probe jutted into the snow, and the helicopter careened sideways down the mountain. Its rotor blades sheared off, and it rolled about 1,000 feet before coming to a rest at the base of Crater Rock.
Three separate groups of climbers were ascending the 11,240-foot mountain and were about 800 feet from the summit when the accident occurred about 9 a.m. A climber who was beneath the crevasse used his cell phone to call for help.
The chain reaction began when two climbers at the front of the pack slipped, falling into climbers behind them. They all crashed into the next group of climbers, and everyone tumbled into the crevasse, said Cleve Joiner, who called for help.
"Everybody was sliding on the ice, and then they disappeared."
Cleve Joiner, climber
"The only thing I can compare it to is hockey players who throw themselves on the ice to block a shot," Joiner said. "Everybody was sliding on the ice, and then they disappeared."
Joiner, the assistant fire marshall at the Tualatin Valley Fire & Rescue department, was among five people from the department who were climbing. His 14-year-old son was among the climbers who fell in the crevasse, but he wasn't seriously injured.
"When I found out he was alive, it was an emotional moment," Cleve Joiner said. "I just kind of fought back the tears and carried on."
The helicopter went down nearly five hours after the climbers fell. Rescue teams who were on their way up to the crevasse on foot and in snow vehicles made their way to the crash site.
The weather was sunny and winds were calm, easing the task of helicopter crews, but officials said any high-altitude operation is risky.
Pave Hawk helicopters can operate at altitudes up to 14,200 feet. The Pave Hawk is a modified version of the Army's Black Hawk helicopter used for search-and-rescue missions.
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What Are Good Kitchen Tools for Cooks with Arthritis?
more about it here.) If your aunt has arthritis in her fingers, this might help her out when peeling fruit and vegetables. That's just one small suggestion. Readers, what are the most useful kitchen gadgets and tools for cooks with arthritis? Gadget: Rotato Express


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|Boxing Champions | Boxing Schedule | Boxing Video | Boxing History | Pound For Pound | Lounge | The Wire | Arcade
|View Poll Results: Better Resume?
|Voters: 125. You may not vote on this poll
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Why do i read the "everyone thought Moreno would beat Mares" in every Mares thread?
Mares was a BETTING FAVORITE. He had more backing than Moreno.
Selective memory perhaps?
Donaire have a better overall resumé, but i have ZERO respect for him right now. I hope Rigo or Mares knocks his head off if he ever fights them.
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i dont even know why this is somewhat close when it really should'nt be...
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Donaire but Mares really isn't far behind, Mares' run of opposition in the last 2 years has been amazing Donaire has taken on and beaten the best in basically each division he has been in. I mean guys like Darchinyan, Montiel and Nichioka were the best in their weight class at the time and were even given some pound for pound consideration by some when Donaire basically steamrolled them.
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You know, I hadn't seen the Mathebula/Caballero fight before because I couldn't find it. I went by what other people had said about it. I just found it on youtube today and it was it was pretty amazing. An honest to god argument can be made that Mathebula won every single round. Even the Panamanian commentators thought Mathebula won. I personally only gave Caballero the last two rounds when both were tired. There were some competitive rounds that could go either way, but I thought Mathebula edged those rounds too.
It was actually a pretty fun fight and worth watching.
Last edited by DoktorSleepless; 02-02-2013 at 05:14 AM.
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Donaire & Donaire.
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Can't believe this poll is pretty much a 50/50.
In brief - Donaire beat the far superior version of Darchinyan.
Mares hasn't fought nevermind beat a top Super Bantam.
Morel was shot & it was also at a catchweight - still a decent win. Moreno was a very good win! Draw with Perez & two wins over Agbeko who I think is a good fighter but a little bit overrated tbh
Nishioka whilst old & inactive still deserves credit.
Hernan Marquez, Sydorenko deserve credit.
Montiel was a nice win & the way he won made it more impressive IMO
Destroyed a prime Darchinyan who was knocking guys dead.
Arce was done, Vasquez Jr was coming off a beating but both top 10.
I don't like Donaire but for me its not even close, Donaire easily especially at 122 where Mares hasn't no real resume.
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Donaire has the better resume. Has fought more current and former world champs. I honestly don't think it's even close.
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Yeah, blame fighters based Africa for that. They pad their records even worse than European fighters do. The most recent African fighters that have found little success in the states have been Clottey, Funeka, and Fana. There's a reason they don't get opportunities... genius.
Don't care at all about that, but it's on par if not better than Donaire's 2012.
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Skip to comments.(TIME FOR A RESPONSE) DFU Letter to Howard Dean - stop lying about me OR ELSE!
Posted on 05/11/2007 8:29:17 PM PDT by doug from upland
click here to read article
Well done.
Congressman Billybob
Latest article: "Jeffrey Has Escaped, and Other Tales of Divorce"
You crack me up. You're a treasure.
That is a great slogan. DEMOCRATS: NOT QUITE AMERICAN
Loved the music. That's something we should do is find a song that is liked by a lot of people and have a message of the republican party with it. Because liking the song people can get behind the message. Something through a grass roots movement. You know so many people REALLY believe that the republican party is made up of rich people for rich people. They really do. And I can tell ya this family is so far from rich we might just be called poor. lol
My take is that comparing Dean to Hitler is both correct and appropriate, but an entire thread devoted to a Photoshop(tm) image of Dean as Hitler did FR more harm than good.
Note that I included a link in my Post #18 to a web page with just such a Photoshopped image of Dean, but didn't in-line the image in this thread. That was deliberate.
One of the problems with Photoshop is that our enemies (both the left and the jihadists) use Photoshopped images as one tool in their arsenal of weapons against us, against what's good and true. They are then more than happy to provide cover for their deceptive images by pointing out where we use Photoshop as well.
That is, Photoshop is a weapon, just like guns and bombs. We should use our weapons with restraint, but not hesitate to use them as necessary.
Since the primary battleground on which the war against the left is being fought is not military, but propaganda and lies, we need to be especially careful to minimize aiding the enemies efforts to spread deceit and lies by doing the same ourselves.
I also do not like the Nazi references. If anyone today in the U.S. is compared to the Nazis, it devalues the horror of the Nazis.
There really is a valid comparison today. It is the Islamofascists. Give them time and they are this century's Nazis, or worse.
Though, if one considers the modern day left to be the butt boys and useful idiots of the Marxists, and if one counts up the murders committed by the Marxists, such as Stalin and Mao and Pol Pot, then one can make a good case that the Marxists and fellow travelers are far worse than the Nazi's and their close descendants, the Jihadists.
For a damning look into how the left serves as the useful idiots of the Marxists, do a YouTube search for Bezmenov. You will find several 5 or 10 minute snippets from an interview of a KGB agent who defected. For example, he explains how the leading voices of the Left be the first to be lined up and shot if the Marxists gain even brief control. He spells out how the lies, deceits, moral degeneration and social collapse caused by our modern leftists are the intentional first stage in destroying America.
For a damning look into the evils of the Chinese Communist Party, see the "Nine Commentaries on the Communist Party", either read aloud by a fine narrator with appropriate images found in a YouTube search for Nine Commentaries on the Communist Party, or in online text at The Epoch Times, or in book form at Amazon.com They make the case that the Chinese Communist Party (CCP) has been responsible for more "premature deaths" than all the other Communists, Nazis and Jihadists combined.
For a humorous, but deadly serious, look into the Mind of the Liberal, see Evan Sayet's speech to the Heritage Foundation How Modern Liberals Think, on YouTube.
And so that no one protests that I am not giving our Islamic Jihadist colleagues equal time, see perhaps the best exposition on the world war they are engaging against civilization, in six parts at YouTube again, as Obsession: Radical Islam's War Against the West
Totally agree about the communists. They killed multiple times the number of people the Nazis killed. One of the great films I've seen is IN THE FACE OF EVIL. It was Reagan's lifelong battle to bring down that evil system. He is one of the great men of all time.
Yes - Reagan was a great one.
I wish I were a younger man, so that I could father and raise many children, steeped in the morals and values of our declining civilization, and so do my little part to carry on our traditions.
Unfortunately, I was a damn liberal in my youth. Fortunately I only sired and raised one child during those times.
"One of the problems with Photoshop is that our enemies (both the left and the jihadists) use Photoshopped images as one tool in their arsenal of weapons against us, against what's good and true."
Not at all the same. The enemy (both DUmocrats and terrorists) use photochopped images to pass off as the truth.
We use the images to make fun of the enemy or to make a point, but never making the attempt to pass off a fabricated image as the real deal.
But the Leftist Liberal Liars can't, or won't, see that, and will gladly take the opportunity to shout "See -- they do it too!".
The other side, devoid of morals and intellect honesty, always does it. They certain believe what the communists believe -— the end justifies the means. They believe they are the ones who should decide for everyone, they are right, and it doesn't matter how they lie, cheat, or steal to achieve their noble cause.
Some of them have compared an affair Gingrich had to the Lewinsky affair, as if there was anything to compare other than sex. Gingrich did not give an aide top secret clearance at the Pentagon. Gingrich did create a hostile work environment. Gingrich did not commit perjury or suborn perjury. Gingrich did not have thugs intimidate witnesses. Gingrich did not hide evidence. Gingrich did not try to fix a federal trial and, as the chief law enforcement officer, deny a woman her day in court. Gingrich did not turn in a false affidavit to the court. Yes, they both had sex with someone other than their wife. But that's where it ends.
To those on the left, a parking ticket by a Republican is equivalent to Kennedy driving off the bridge and leaving a young woman to die. They each violated the vehicle code.
This is explained nicely, with good humor, in Evan Sayet's speech to the Heritage Foundation How Modern Liberals Think, on YouTube.
That is just so they can disarm us when parody has been quite effective in exposing the LIEberals....just ask Rush:
Well done Doug!
Nailed it I say!
Wow! Can I use some of that in my effort to bombard Harry Reid once a week? </ sarc >
I've decided to be a thorn in his side. I email him once a week or 10 days, just to remind him he doesn't speak for all Nevadans. Just the stupid ones who are willing to buy into his treasonous claptrap.
Thanks for taking on another doo-doo head in the name of Freedom!
Mocking Harry Reid on YouTube — http://youtube.com/watch?v=yqMoe7u7Qdc
He needs to be *itch-slapped a time or two, but he's so power hungry, I don't think anything will stop him but a ZOT!
Darn, I should have remembered. Sorry.
Way to shoot from the hip, Doug.
in case you didn't see this ping
Well done.
Wow Doug! Saw Hank Aaron looking skyward...said you knocked this one clear out of the ball park! Way to go from FRiends you haven't met in other parts of this great country.
The story will have legs if someone in Brownback's office, the purported source, will go on record. I can't see Howard Dean being foolish enough to try to push this. Or, maybe I can. They really do worry about the free flow of information that they cannot control.
There, fixed it.
QUINN AND ROSE - The Warroom — http://www.warroom.com/
And I find this by means of News Busters.
Going to clean off the computer srreen now.
My Marine son sends this to Howard The Duck: NUTS!
I salute you FRiend. Truly excellent. BRAVO.
Semper Fi to your son.
Thanks for the kind words.
Lets correct the error: Gingrich did NOT create a hostile work environment.
HERE IS THE LATEST. THE GOV AND THE DNC HAVE BEEN ASKED TO RELEASE PHONE RECORDS http://www.freerepublic.com/focus/f-news/1833389/posts
GREAT job, Doug!
I think he's trying to commit sushi.
No word yet from Dean. Maybe he has been busy with electroshock therapy.
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Perfect for Needle felting!
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Great earthy tones, fast shipping and easy to felt! This is a great product and I highly recommend Wilde Wool for beginners as well as experts. The texture makes it easy to felt for larger things (gnome bodies) as well as fine detail. The Ocean Blue is my favorite; very rich and unique. Really, you can't go wrong with any of these colors, (I have ordered them all). They are very close in person to the pictures online. And the price.... can't be beat!
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I am so pleased with this wool, for its beautiful colors, versatility in both wet and needle felting, and affordability. We purchased several colors to try out for different homeschool projects and they will last us a while. Colors are very true to photos on the website.
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