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That's a 29er?! Chris Doney Jumping, Trials Riding, and Backflipping His Charge Cooker 10
Chris Doney shows us just what is possible on board his Charge Cooker 29er Single Speed. The bike he is riding in the video is a stock single speed 29er Charge Cooker frame in size small with some specially shortened (60mm travel) Rockshox Reba forks. This is one of a fleet of bikes that were made last year for the Red Bull / Charge Bikes Weavers slalom event. After the event we handed a few of these custom bikes out to a select few of the talented riders that attended... Chris was one of them!Credit: Charge Bikes / Alex Rankin
bturman 4/29/2013 12:53 PM
10 comments newest first
10960 emersonfnogueira http://p.vitalmtb.com/photos/users/10960/avatar/c50_SORRISO.jpg?1317226825 http://www.vitalmtb.com/community/emersonfnogueira,10960/all 09/28/11 72 1
emersonfnogueira 4/30/2013 4:38 PM
15963 Bill.Ning http://p.vitalmtb.com/photos/users/15963/avatar/c50_fb_picture_1385808091.jpg?1338818909 http://www.vitalmtb.com/community/Bill-Ning,15963/all 06/04/12 2
Bill.Ning 4/30/2013 9:12 AM
he is really cool
21660 mrpowerjd http://p.vitalmtb.com/photos/users/21660/avatar/c50_fb_picture_1574198553.jpg?1360382891 http://www.vitalmtb.com/community/mrpowerjd,21660/all 02/08/13 2 22 342 1
mrpowerjd 4/29/2013 11:57 PM
Beauty! Great edit with chill tunes. Well done.
931 scriz http://p.vitalmtb.com/photos/users/931/avatar/c50_Screen_Shot_2012_10_03_at_3.13.04_PM.jpg?1349302478 http://www.vitalmtb.com/community/scriz,931/all 09/22/09 6 266
scriz 4/29/2013 9:42 PM
Cool edit and a mega talented rider, but the strengths *and* weaknesses of 29'er are pretty visible in this video, so enough with the sensationalism eh?
6865 s.sheline /images/default/avatar/c50.png http://www.vitalmtb.com/community/s-sheline,6865/all 02/20/11 3 91 1
s.sheline 4/29/2013 8:01 PM
gah! why must you complicate my view on 29ers??
10866 cofattire http://p.vitalmtb.com/photos/users/10866/avatar/c50_IMG_2342.jpg?1316791237 http://www.vitalmtb.com/community/cofattire,10866/all 09/23/11 9 25 114 1 4
cofattire 4/30/2013 8:31 AM
killing it!
Have you seen the video of Mike Montgomery back flipping a road bike with drop bars? I'm no 29 hater, but I'm not overly impressed when an uber-talented rider kills it on a 29. One day a company will hire Danny Mac to advertise their 29. Then he'll go back to riding 24".
Have you seen the video of Mike Montgomery back flipping a road bike with drop bars? I'm no 29 hater, but I'm not overly impressed when an uber-talented rider kills it on a 29. One day a company will hire Danny Mac to advertise their 29. Then he'll go back to riding 24".
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- HankTheTank
94 iceman2058 http://p.vitalmtb.com/photos/users/94/avatar/c50_johan_1385064431.jpg?1385063576 http://www.vitalmtb.com/community/iceman2058,94/all 08/01/09 636 47 684 1463 http://www.vitalmtb.com/community/iceman2058,94/setup 16 197 2748 59 23
iceman2058 4/29/2013 2:41 PM
23373 todd.margeson.9 http://p.vitalmtb.com/photos/users/23373/avatar/c50_fb_picture_583868002.jpg?1365187053 http://www.vitalmtb.com/community/todd-margeson-9,23373/all 04/05/13 9
todd.margeson.9 4/29/2013 1:31 PM
Hope that singletrack in the first half was private trail. A whole lot of destructive skidding going on there...
27787 HankTheTank http://p.vitalmtb.com/photos/users/27787/avatar/c50_image_1423452219.jpg?1423451407 http://www.vitalmtb.com/community/HankTheTank,27787/all 10/05/13 1
HankTheTank 10/5/2013 8:32 PM
Skidding? Destructive? Better let the rain, snow and other weather conditions know that they aren't allowed on this track. LOL
23373 todd.margeson.9 http://p.vitalmtb.com/photos/users/23373/avatar/c50_fb_picture_583868002.jpg?1365187053 http://www.vitalmtb.com/community/todd-margeson-9,23373/all 04/05/13 9
todd.margeson.9 4/14/2014 11:16 PM
Wow. Go talk to your local trail building/maintenance organization or IMBA chapter and try to argue your viewpoint. Who really believes skidding on the trail isn't destructive??? And as for the weather, that is in fact the main reason that trail maintenance is necessary due to erosion, but it's unavoidable and uncontrollable, so it doesn't really counter my argument. Rider behavior, however, IS controllable. Huge difference. Sounds like you're the type that also goes out and ride trails after rain (and snow and other weather conditions) and tears up the trails even more than skidding. Trails don't just get built and take care of themselves. Go volunteer for a trail day sometime...


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I have a point layer, that I'd like to return the Longitude, latitude using the qgis api. I assume I need to use QgsPoint
Take the 2-minute tour ×
Geographic Information Systems Stack Exchange is a question and answer site for cartographers, geographers and GIS professionals. It's 100% free, no registration required.
This works on the latest release 'Tethys'.
The point layer that I am interested in is the first layer in my layer list. The coordinate values will be in the units of the spatial reference system of the layer. If your layer is in lat/lon, remember that x=lon and y=lat...
Open the Python Console and type this:
This requires your layer to be in a projection using lat/lon to return geographic coordinates:
(taken from Points2One Plugin by Pavol Kapusta & Goyo Diaz)

subset: commoncrawl


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Construction of a new bus barn
From Jim Stalker • Creston | I apologize for maybe jumping the gun a bit when I last wrote about moving the bus barn, although it was hard to imagine the original bus barn was in such horrible condition when the only visible damage was the loss of a little tin sheeting.
Not having gone through the details of running a school system and having to comply with seemingly idiotic rules and regulations regarding schools or any level that receives funding in some form, from the government, I may have been wrong to suggest that a building that was thrown together by volunteer labor and held strong since before the new high school was built, could be done once more, not by volunteers, but by professionals on the same location as before. I hope, at least, the doors, that were obviously not damaged by the storm, were saved to use again, when a new structure is finally decided upon and built, hopefully before winter strikes.
I don't know whether the current plan to acquire the AEA property is worth the effort the board is going through, when the property the schools are sitting on right now is large enough to place 10 bus barns on property that is already paid for. But again, I am not on the school board and not up on the compliance rules.


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Comments On Mar 24, 2015:durable product and looks good
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Comments On Sep 23, 2014:Easy to install. Provides great protection. I regularly ride extremely rocky trails in very remote locations and the disc guard has taken a beating. Has definitely done its job to date.
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Comments On Nov 08, 2013:GREAT PRODUCT.Cant beat the price or shipping
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Comments On Mar 06, 2013:Great item that offer amazing protection. My only complaint is I had to add a washer between the brake holder and the swing arm to get the clearance needed to stop the rotor bolts from rubbing on the holder. I ride enduros mostly and this is a key protection item.
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Comments On Dec 15, 2012:Love this heavy duty aluminum rear disc protection. Not too heavy works like a champ! Must have for trail riding. It's been on my bike for a full season and has worked great, a few dings & nicks in it which indicates to me it is doing its job.
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Comments On Dec 02, 2012:it is in great shape. Worth every penny, wish I put a guard on the front.
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Comments On Jul 07, 2012:I bought this to help protect my WR250f when I race an enduro or ride a 100+ mile dual sport. and what do you know, after the first ride having this thing on, its full of huge dings and nick. surly saved my rotor. great buy!
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Comments On Apr 27, 2012:I bought this guard for my 03 cr250 and it fits on great and look sweet. The actually guard itself is thick and seems like it will hold up to anything thrown at it.
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Comments On Apr 05, 2012:You cant hurt this thing and your disc will never get bent.
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Comments On Dec 11, 2011:Installation is straightforward. The only issue I had was I had to file my rear brake rotor screw heads down slightly - they were scraping against the guard. I haven't taken a big hit to it yet, but I like the idea of being able to replace the lower section of the guard.
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Vincent T DeVita, Jr, MD
Amy and Joseph Perella Professor of Medicine (Medical Oncology) and Professor of Epidemiology (Chronic Diseases)
Research Interests
Hodgkin Disease; Lymphoma; Molecular Biology; Health Care
Public Health Interests
Cancer; Health care delivery
Research Organizations
Cancer Center, Yale: Developmental Therapeutics
Internal Medicine: Medical Oncology: Subset Medical Oncology Faculty
Research Summary
Primary interest in the mechanisms cancer cells use to develop resistance to cancer drugs. The molecular switches.
Extensive Research DescriptionInterest in how cancer cells manipulate molecular pathways to circumvent drug resistance. Aimed at identifying appropriate molecular targets for combination targeted treatment.
Writing a lay history of the war on cancer.
Selected Publications
- DeVita VT, Lawrence TS, Rosenberg SA, (Eds) DeVita, Hellman, and Rosenberg's Cancer: Principles & Practice of Oncology, 10th Edition. Philadelphia: Lippincott Williams & Wilkins, 2014.
- DeVita VT, Eggermont AMM, Hellman S, Kerr D. NRCO 10 Year Viewpoint Anniversary: Clinical cancer research: the past, present and the future. NRCO 11(11) Nov. 2014 (in press)
- Canellos GP, Rosenberg SA, Friedberg JW, Lister TA, DeVita VT. Treatment of Hodgkin's Lymphoma: A 50-Year Perspective. JCO 32(3) Jan 20, 2014.
- Oncology in Primary Care. eds Rose M, DeVita VT, Lawrence TS, Rosenberg SA. Lippencott Williams and Wilkens, Philadelphia, PA, May 2013.
- Physicians' Cancer Chemotherapy Drug Manual. eds DeVita VT, Chu E. Jones and Bartlett, Sudbury, MA, 2013.
- DeVita VT, Rosenberg SA. Two Hundred Years of Cancer Research. NEJM 366 (23) June 2012.


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latest episodes
Jack & Amanda Get Married
Jack Porter & Amanda Clarke renew the vows they took on the beach as kids.
The End of Revenge
Amanda and Jack sail off into the sunset.
Victoria & Amanda are Shot
Victoria is shot...but not by Amanda.
David Clarke Passes Away
David Clarke takes his last breath with Amanda by his side.
White Gold Stabs Jack
White Gold stabs Jack in the stomach.
Jack & Amanda Make Love
Amanda & Jack can't resist each other any longer.
Louise Changes Sides
Louise tells Amanda where to find Victoria.
Nolan Takes Down White Gold
Nolan takes down White Gold (Courtney Love) & Margaux turns herself in.
SNEAK PEEK: Will Amanda Shoot Victoria?
Amanda finally has her chance to kill Victoria.
David is Dying
David breaks the news to Amanda that he only has a few months to live.
Amanda Chokes Margaux
Margaux doesn't cooperate so Amanda takes things into her own hands.
Victoria Grayson is Alive!
Victoria Grayson is alive & Ben Hunter is killed by Courtney Love.
Charlotte Isn't Attending Victoria's Funeral
Louise finds out how much Charlotte despises Victoria.
Amanda & Jack Together at Last
Four years in the making, Amanda & Jack are finally a couple.
Louise's Evidence Changes Everything
Louise has evidence that Amanda was framed by Victoria.
Margaux is Arrested
Margaux is arrested...with a little help from Jack.
about the show
When Emily Thorne arrived in the Hamptons, she appeared to be nothing more than the friendly, sophisticated "girl next door." But Emily is more than what she seems. When she was a child, her father was framed then murdered by the people he trusted most, leaving her to be consumed by loss, betrayal and rage. Since then, Emily's every social overture has been carefully planned to bring the opulent lives of her enemies crashing down around them. But now, having achieved her goal of taking the Graysons down, a new truth has come to light... her father is ALIVE! How will she continue when the biggest motive behind her revenge is no longer true?? Watch full episodes of Revenge with WATCH ABC.
Emily Thorne
Played by Emily VanCamp
Victoria Grayson
Played by Madeleine Stowe
Daniel Grayson
Played by Josh Bowman
Jack Porter
Played by Nick Wechsler
Nolan Ross
Played by Gabriel Mann
Charlotte Grayson
Played by Christa B. Allen
Margaux LeMarchal
Played by Karine Vanasse
David Clarke
Played by James Tupper


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The Ironstone Nest is a home decor, furniture refinishing, DIY blog with a little lifestyle thrown in for good measure. I specialize in refurbishing antique furniture, re-purposing vintage found … read more
Copyright © 2015 · The Ironstone Nest · Website Development By Launch Creative Studio


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Just in time for the holidays…
The word is out. Top designers are all saying that seasonal décor this year is not just about tree trimming and table top. It's all about the walls.
"It may have started as a trend, but now my clients are pulling out art from holiday storage year after year – same as they would the garlands and wreathes and their other little treasures."
Seriously – Picture this: It's late Saturday afternoon and it's cold outside – too cold to go out. You're lounging in your comfiest chaise in front of a roaring fire with a yummy cashmere throw and an even yummier mug of mulled wine. Perhaps you're still wearing your pajamas. You've forgotten the book on your lap because you're transfixed by a fresh fir tree sparkling with tiny white lights. But how does last summer's sunflower or beach print fit in? Indeed, it's jarring. The tableau is simply not complete without seasonal art.
Gallery Direct makes it possible for you to decorate in style this winter with festive imagery from your favorite artists – Sia – Paul – Saris – Abbott – Gjevukaj – Graham – plus our colorful photography. From trees to stars to lights to nature's curiosities, and even a sweet little deer, this imagery is available on numerous media to select from, including traditional framed paper for a classic touch, light weight canvas that's easy-to-hang, sophisticated aluminum or acrylic for a modern spin and unique birchwood for a rustic feel. Plus all the red you need to turn your space into a warm and cozy holiday home.
Hinners advises canvas precisely because it's lightweight, durable, and easy to hang and move around.
"It's perfect for seasonal décor for all those reasons, but it also has the feel of an original, especially framed canvas."
As this year's designers will tell you and savvy home makers get it: It's not just about the tree or the table this year, it's about the holistic experience. And there's no better way to create that than to surround yourself with cheery wall décor!
And don't forget that Valentine's Day is right around the corner!


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When it comes to men's underwear, guys today have just as many options as the ladies—everything from everyday basics to sexy men's underwear. Gone are the days when your choices were limited to tighty whiteys or boxy shorts, nowadays guys can find everything from sexy men's bikinis to super hot men's underwear like men's thongs, men's jocks and men's g-strings. Of course, there are classic briefs, men's boxer briefs and trunks, men's undershirts and even shape enhancers.
Let's start with the most basic of men's underwear styles: briefs. This classic cut fits close to the body and offers comfort and just the right amount of coverage. Calvin Klein®, UnderGear® and Contour offer some of the best everyday basic briefs in soft stretch knits with special contouring for comfort and support. Briefs also come in fashion colors and fabrics. Some of the best are offered by C-IN2®, 2(x)ist® or Body Tech®, and combine bold details and trendy colors with comfortable coverage.
If you like a bit more coverage, you'll want to check out trunks and boxer briefs. The longer length and smooth fit of trunks is great when you want support, and with their muscle-hugging contours they can be a surprisingly sexy underwear option too. Check out Unico®, N2N® or Man Zone®. For those who prefer something looser, boxer briefs offer length with fit that's a little roomier. Top sellers from Ken Wroy® and Good Devil® continue to be customer favorites.
If you're looking for sexy underwear some of the hottest looks in men's underwear are from brands like Andres Velasco®, which combines fashion trends with a touch of Latin flavor. Up the drama with edgy styles from Doreanse and Extreme Collection®. So how bare will you dare to go? For starters, men's bikinis, like the designs from Body Tech® and Male Power®, offer the perfect balance of coverage and exposure, many are specifically designed with no-show waistbands which offer a sleek look under tight low-rise jeans and pants. Thongs are another great option, as the barely-there back and front pouch are virtually invisible under clothes. We're hearing really great things about the super-sleek, modern thong from Clever®. Some of the best men's thongs offer enhancement which will give your whole look a major boost. Get a load of the forward-thinking designs from brands like Joe Snyder, Cocksox™, Intymen®.
These days jocks have stepped out of the gym and entered into seriously sexy territory. You'll be amazed at the variety of materials and styles available—everything from faux suede and leather to the clingiest spandex. They still offer support and keep your jewels safe, plus these hot men's underwear styles from Pistol Pete® or Pikante will definitely bring the attention front and center.
When is less more? When it's a men's g-string. This minimal style delivers maximum exposure and is the next best thing to being bare.
Shape enhancers can really help you accentuate the positive, hide the negative and will do wonders for how you look and feel. If you're looking to boost your bottom line, Shape Enhancers® is exactly what you're looking for. Want to tone and tighten faster than the gym? Shape-enhancing undershirts from Naughty Boy® and 2(x)ist® will have you looking buff instantly.


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BST. LOUIS — The oil and gas drilling technique known as "fracking," once trumpeted as a job-creating boon for southern Illinois, is off to a feeble start in the state as slumping oil prices and the rigors of Illinois' new regulations have energy interests cautiously waiting on the sidelines.
Mike Krzyzewski earned his 1,000th career win Sunday, making him the first NCAA Division I men's coach to reach the milestone, when No. 5 Duke surged past St. John's in the second half for a 77-68 victory at Madison Square Garden.
New York City Mayor Bill de Blasio says the snowstorm bearing down on the Northeast could be among the worst the city has ever seen.
Seizing on their personal bond, President Barack Obama and Indian Prime Minister Narendra Modi said Sunday they had made progress on nuclear cooperation and climate change, with Obama declaring a "breakthrough understanding" in efforts to free U.S.
Supporters of Egypt's ousted Islamist President fought street battles with police in Cairo and other cities on Sunday, the fourth anniversary of the country's 2011 uprising, as clashes left at least 13 people dead and dozens injured. Another two...
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A system of about 100 billion stars. Our Sun is a member of the Milky Way Galaxy. There are billions of galaxies in the observable universe. Exactly when and how galaxies formed in the Universe is a topic of current astronomical research.
Jupiter's four largest moons: Io, Europa, Ganymede and Callisto; discovered independently by Galileo Galilei in 1610.
A substance, such as oxygen or hydrogen, that has no fixed shape and that can expand without limit.
The outer solar system planets: Jupiter, Saturn, Uranus, and Neptune, composed mostly of hydrogen, helium and methane gas, and have a density less than 2 grams per cubic centimeter.
An ellipsoid or sphere-shaped "net" that is used as a type of base-map or control to correlate co-ordinates on a flat image with their actual location on the spherical planetary body in order to obtain accurate measurements from images.
The expression of the internal and external processes and events that affect a planetary body.
The time extending from the end of the formative period of the Earth to the beginning of human history.
A body of rock (or ice, in Europa's case) that has a distinct origin and consists of dominant, unifying features that can be easily recognized and mapped.
A direct, circular, low inclination orbit in which the satellite's orbital velocity is matched to the rotational velocity of the planet; a spacecraft appears to hang motionless above one position of the planet's surface. In other words, the satellite and planet move at the exactly the same speed.
A depressed segment of the crust of the earth or a celestial body (as the moon) bounded on at least two sides by faults.
The acceleration produced by the mutual attraction of two masses, and of magnitude inversely proportional to the square of the distance between the two centers of mass.
Refers to the difference in the acceleration of gravity from one side of an object to another, because gravity is a force that changes with distance between two points.
The line of intersection of the surface of a sphere and any plane which passes through the center of the sphere.
Increase in temperature caused when incoming solar radiation is passed but outgoing thermal radiation is blocked by the atmosphere (carbon dioxide and water vapor are the major factors). Very important on Venus and Earth but very weak on Mars.
The on-site gathering of data at a particular location, for the purpose of calibrating and interpreting remotely acquired data.


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Book your room at Bay Gardens Beach Resort
Deluxe Room, 2 Queen Beds, Garden ViewMax Occupancy: 4 guests (up to 3 children, 2 infants)
Deluxe Room, 2 Queen Beds, Pool ViewMax Occupancy: 4 guests (up to 3 children, 2 infants)
Deluxe Room, 2 Queen Beds, BeachsideMax Occupancy: 4 guests (up to 3 children, 2 infants)
Standard Room, 1 Bedroom, Pool ViewMax Occupancy: 4 guests (up to 3 children, 2 infants)
Suite, 1 Bedroom, BeachsideMax Occupancy: 4 guests (up to 3 children, 2 infants)
Suite, 2 Bedrooms, Pool ViewMax Occupancy: 6 guests (up to 5 children)
Suite, 2 Bedrooms, BeachsideMax Occupancy: 6 guests (up to 5 children)
Get an overview of this hotelCondo with private beach, full-service spa
+VIP Access™ Hotel
We carefully hand-picked this hotel based on its dedication to service and excellent guest reviews.
Expedia +gold members receive free room upgrades and +gold and +silver members get other perks upon availability at check-in.See details
Located in Rodney Bay, this beachfront condo is in the entertainment district and within 1 mi (2 km) of Baywalk Shopping Mall and Reduit Beach. Rodney Bay Marina and Bonne Terre Tropical Gardens are also within 2 mi (3 km).
Property Features
Catch some rays on Bay Gardens Beach Resort's private white sand beach or spend the day relaxing at the full-service spa. Then enjoy a meal at one of the condo's 2 restaurants.
Room Amenities
All 75 condos boast deep soaking tubs and offer free WiFi and balconies or patios. Sitting areas and DVD players are standard, as are TVs with cable channels.Information missing or incorrect? Tell us!
Hotel Amenities
Hotel Amenities
Step outside to feel the sun on your face and the sand in your toes on the white sand beach. For a free ride to the surf and sand, catch the condo's complimentary beach shuttle. Pamper yourself with a treatment at the full-service spa and enjoy amenities at Bay Gardens Beach Resort like an outdoor pool and a children's pool.
Dining is available at one of the condo's 2 restaurants and guests can grab coffee at the coffee shop/café. The property also has a snack bar/deli. Guests can unwind with a drink at one of the condo's bars, which include 3 bars/lounges and a poolside bar. A computer station is located on site and high-speed wired and wireless Internet access is complimentary. This Colonial condo also offers an outdoor tennis court, a spa tub, and a fitness center. Onsite self parking is complimentary.
- 24-hour front desk
- Arcade/game room
- Babysitting or childcare (surcharge)
- Free beach shuttle
- Beach sun loungers
- Pool umbrellas
- Breakfast available (surcharge)
- Business center
- Children's pool
- Coffee shop or café
- Computer station
- Conference center
- Conference space
- Conference space size (feet) - 12551
- Conference space size (meters) - 1166
- Dry cleaning/laundry service
- Express check-in
- Fitness facilities
- Free self parking
- Free WiFi
- Free wired high-speed Internet
- Full-service spa
- Garden
- Gift shops or newsstand
- Laundry facilities
- Library
- Limo or Town Car service available
- Meeting rooms
- Number of bars/lounges - 3
- Number of floors - 3
- Number of restaurants - 2
- On private beach
- Outdoor pool
- Outdoor tennis court
- Poolside bar
- Porter/bellhop
- Shopping on site
- Snack bar/deli
- Spa services on site
- Spa treatment room(s)
- Spa tub
- Terrace
- Total number of rooms - 75
- Tours/ticket assistance
- Wedding services
- Year Built 2007
Family Friendly Amenities
- Arcade/game room
- Babysitting or childcare (surcharge)
- Children's pool
- DVD player
- Free Wi-Fi
- In-room childcare (surcharge)
- Laundry facilities
- Microwave
- On private beach
- Outdoor pool
- Outdoor tennis court
- Refrigerator
- Rollaway/extra beds available
- Snack bar/deli
Available in all rooms: Free WiFi
Available in some public areas: Free WiFi , Free wired high-speed Internet
Free self parking
Room Amenities
- Access via exterior corridors
- Air conditioning
- Balcony or patio
- Bathrobes
- Cable TV service
- Ceiling fan
- Coffee/tea maker
- Cribs/infant beds available
- Daily housekeeping
- Deep soaking bathtub
- Desk
- DVD player
- Free WiFi
- Hair dryer
- In-room childcare (surcharge)
- In-room massage available
- In-room safe
- Iron/ironing board
- Microwave
- Phone
- Premium bedding
- Premium TV channels
- Private bathroom
- Refrigerator
- Rollaway/extra beds available
- Room service
- Room service (limited hours)
- Separate bathtub and shower
- Separate sitting area
- Slippers
- Television
- Turndown service
Where to Eat
Hi Tide Restaurant - This beachfront restaurant serves breakfast, brunch, lunch, and dinner. Guests can enjoy drinks at the bar. A children's menu is available.
Trios Caribbean Fusion - This theme restaurant serves dinner only. Reservations are required. Open daily.
Room service (during limited hours) is available.
Nearby Things to Do
A private beach and an outdoor tennis court are featured at the condo. An outdoor pool, a children's pool, and a spa tub are on site. Other recreational amenities include a fitness center.
The recreational activities listed below are available either on site or nearby; fees may apply.
- Golfing nearby
- Bicycle rentals nearby
- Scooter/moped rentals nearby
- Hiking/biking trails nearby
- Aerobics on site
- Pilates classes on site
- Sailing on site
- Scuba diving on site
- Snorkeling on site
- Water skiing on site
- Windsurfing on site
- Yoga classes/instruction on site
- Ecotours nearby
- Golf lessons available nearby
Spa Services
La Mer Spa has 5 treatment rooms including rooms for couples and outdoor treatment areas. Massages are available on the beach and in the spa; other services include facials, body wraps, and body scrubs. The spa is equipped with a mud bath and a spa tub.
- Number of treatment rooms 5
- Outdoor treatment areas
- Couples treatment rooms
- Massages on beach
- Manicures and pedicures
- Body wraps
- Body scrubs
- Mud bath in spa
- Spa tub in spa
- Massages
- Body treatments
- Facial treatments
To make requests for specific accessibility needs, complete the "Special or Accessibility Requests" section of "Trip Preferences" when you book your hotel.
- Accessible bathroom
- Accessible path of travel
- Accessible parking
- In-room accessibility
- Roll-in shower
Hotel Policies
Check-in time starts at 4 PM
Minimum check-in age is 18
Check-out time is 11 AM
Payment types
Children and extra beds
- Children are welcome.
- Rollaway/extra beds are available.
- Cribs (infant beds) are available.
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.
No elevators
Optional extras
- Breakfast fee: USD 22.00 per person (approximately)
We should mention
Only registered guests are allowed in the guestrooms.
Summer/Fall Sale
Book a stay in a Garden View room category, for travel May 11, 2015 - December 19, 2015 and receive the following:
- 40% discount on the Garden View room rate at time of booking, or
- 30% discount on the Pool or Beach Front room rate at time of booking
- Stay 5-nights and receive a $150 resort credit and free buffet breakfast for 2 persons(or 4 if when booking a Two Bedroom Suite Pool View or Two Bedroom Suite Beach Front)
Family Promotion
Book a 5-night minimum stay in a Deluxe Beach Front of higher room category and receive the following:
- Free breakfast for 2 persons (or 4 if booking a Two Bedroom Suite)
- $150 resort credit per room/stay
- Free meals for up to 2 kids under age 13 when ordering from the kid's menu
- Free babysitting for 2 kids for up to 4 hours per room/stay
- 2 free motorized watersports adventures for up to 2 children per stay (children under age 14 years)
Half Term Offer - UK Residents Only
Book a minimum 7-night stay in any room and rate category for travel September 1 - November 30, 2015 and receive the following:
- 6 one-hour Splash Island Water Park passes per room, per stay
- For guests booking a One Bedroom Suite, 2 children up to 12 years of age can eat free from the kids menu (must be the same meal plan basis as adults; children must dine with adults)


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statelinetack.com > Wormers > Rotational Paste, Gel & Pellets > Item # SLT151412
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Crosley Record Storage Case
Crosley's classic vinyl-wrapped record carry case is completely portable, too.
Virtually identical to the LP storage box you had in the 60s, Crosley's Record Carrying Case from Brookstone® neatly stores 30 albums and protects them from wear and tear.
Remember the summer when almost every dollar you earned was spent on your record collection? You probably learned then that proper storage and handling can mean the difference between warped, ruined records and an impeccable, long-lasting collection. Times have changed since then, but the need to store and protect your albums hasn't—and this carrying case is still exactly what you need.
The sturdy, vinyl-wrapped case keeps 30 or more albums neat and tidy, and guards against dampness, bumps, knocks and other mishaps of everyday life.
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Comments about Crosley Record Storage Case:
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Freedom Flix
Free the Vendors: Hialeah, Florida Attacks Mobile Vendors
In October 2011, the newly created Institute for Justice Florida Chapter filed a lawsuit in state court on behalf of street vendors. These vendors are challenging a law passed by the city of Hialeah, Fla. (located near Miami), that not only makes vendors' work more dangerous by forcing them to constantly be on the move rather than vend in one location, but also is purposefully anticompetitive—making it impossible for vendors to compete against politically powerful brick-and-mortar businesses. The heart of the Institute for Justice's challenge is that, under the state of Florida's constitution, the government must protect the rights of individuals to pursue an honest living free from unnecessary and arbitrary government-imposed restrictions. Likewise, it is not the government's place to put in place anticompetitive restrictions that arbitrarily protect one business while harming another. Street vendors are a core part of the American Dream. Whether it is selling newspapers in New York City or hot dogs in Chicago or cheesesteaks in Philadelphia, the image of a hard-working street vendor climbing his way up the economic ladder is familiar to Americans from coast to coast. Vending provides a perfect means of entering the economic mainstream, especially for the poor and newcomers to our nation, because vending doesn't require a great deal of financial capital or formal education; it merely requires a dream for a better life and hard work. Unfortunately, local governments are making it all but impossible for street vendors to earn an honest living. That is what is happening in Hialeah. Although street vending is legal in Hialeah, city laws designed to protect brick-and-mortar businesses from competition make it illegal to be an effective street vendor. In an effort to fight these anticompetitive laws, local vendors are teaming up with the Institute for Justice's new Florida chapter to stand up for their economic liberty.Read more
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Freedom Flix
The Institute for Justice is always looking for new ways to promote the message of freedom. To that end, IJ produced the following videos in-house to tell the stories of our clients and their fight for individual liberty.
None of this — the cases or these videos — would be possible without the continued generosity of our donors. We hope you enjoy them and share them with those who need a little inspiration.
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Ozzy Osbourne, Drug Relapse: Rocker Admits He Struggled With Addiction Again, Addresses Divorce Rumors
Recently, Ozzy Osbourne and wife Sharon have filled headlines with divorce rumors, but this time, it's Ozzy who's ready to do the talking.
In a Facebook post, Ozzy updated his fans on what's been going on and also addressed his continued struggle with addiction.
"For the last year and a half I have been drinking and


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By Nate Rau
The Tennessean
The CMA Music Festival enjoyed its best year ever in 2013, breaking all-time attendance records and bringing in more direct spending to the Nashville economy than ever before.
This year's festival saw $31.5 million in direct spending, according to new data from the Nashville Convention and Visitors Corp. That's a $1.5 million increase from 2012.
The CMA Music Fest attracted more than 80,000 people to downtown, also a record, and its prime-time broadcast on ABC, which was filmed during the June event and then broadcast on Aug. 12, achieved its best ratings since 2005. The special had 8.3 million viewers, a 45 percent increase from the previous year.
It's against that backdrop of growth and record-setting revenue that the Country Music Association launched a search for a new CEO. Though the association has had just five CEOs since its formation in 1958, it will soon be hiring its third chief in the past seven years.
Continue reading


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Senator Portman Photos
FPFW Dem Gallery
CIA Award Ceremony
12.11.12 DNI Award Lieberman
Homeland Threats and Agency Responses
Moving from Scandal to Strategy: The Future of the General Services Administration
Labor-Management Forums in the Federal Government
Homeland Security Hearing: Evolving and Emerging Threats
Cybersecurity Press Conference 8.2.12
Committee Markup 6/27/12
DHS Demonstration on Hacker Methods and Defensive Strategies
Chairman Lieberman talks cybersecurity with Bloomberg staff
Chairman McCaskill Holds Hearing on Veterans Employment
Subcommittee Witnesses at Veterans Employment and Government Contractors Hearing on June 5, 2012
Secret Service on the Line: Restoring Trust and Confidence
May 15, 2012 Mark up, Domestic Partners bill
STOCK Act Press Conference
Senators Lieberman, Collins, Gillibrand and Scott Brown held a press conference shortly after Senate passage of the Stop Trading on Congressional Knowledge (STOCK) Act.
DHS Budget Under the Microscope
Retooling Government for the 21st Century
Photos from the March 21 hearing, "Retooling Government for the 21st Century: The President's Reorganization Plan and Reducing Duplication"
Witnesses were Dan Werfel, Controller, Office of Federal Financial Management at the Office of Management and Budget and Patricia Dalton, Chief Operating Officer of the U.S. Government Accountability Office
McCaskill Moves to Protect Contracts for Small Businesses
An investigation spearheaded by Senator Claire McCaskill has targeted the various loopholes, oversight failures, and tangled regulations which have resulted in contracts intended for small businesses being performed, instead, by large corporations. On July 26, 2011, Chairman McCaskill held a hearing to continue the Subcommittee on Contracting Oversight's efforts to examine small business contracting issues. Since 2005, the Inspector General of the Small Business Administration has listed as one of the agency's top management challenges the fact that large firms are obtaining small business contracts, as well as agencies counting contracts performed by large corporations toward their small business contracting goals.
McCaskill Looks at Whistleblower Protections for Federal Contractors
On December 12, 2011, Chairman McCaskill held a Subcommittee on Contracting Oversight hearing to review the "Non-Federal Employee Whistleblower Protection Act," a bill that was introduced by Senator McCaskill to bolster whistleblower protections for government contractors and other non-federal employees. The hearing also reviewed whether current whistleblower protections for contractors working under Defense Department and Recovery Act contracts have been effective in encouraging reports of waste, fraud, and abuse.
Zachary Chesser report cover
McCaskill, Webb Introduce Comprehensive Contracting Reform Legislation
Wednesday, February 29, 2012
On Wednesday, February 29, 2012, Senators Claire McCaskill and Jim Webb introduced legislation to overhaul the federal government's planning, management, and oversight of wartime contracting. The Senators' comprehensive reform legislation (S. 2139) builds on the recommendations of the U.S. Commission on Wartime Contracting in Iraq and Afghanistan – an independent, bipartisan panel that Senators McCaskill and Webb created through legislation they introduced in 2007.
McCaskill Looks at Next Steps for Arlington National Cemetery
At a recent Subcommittee on Contracting Oversight hearing that assessed the need for continuing improvements at Arlington National Cemetary, Senator McCaskill cited a successfully managed Missouri cemetery as an example.
Where Were the Watchdogs: Financial Regulatory Lessons from Abroad
Gulf Coast Catastrophe: Assessing the Nation's Response to the Deepwater Horizon Oil Spill
The Committee examined both the governmental and business community's response to the Gulf Coast oil spill.
Nomination Hearing for Robert Groves
The D.C. Opportunity Scholarship Program: Preserving School Choice for All
Iran Sanctions: Why does the U.S. government Do Business With Companies Doing Business in Iran?
The hearing scrutinized the status of government contracts with companies doing business with Iran, especially those violating U.S. sanctions.
The Homeland Security Department's Budget Submission for Fiscal Year 2010
Nomination Hearing for Cass Sunstein
Terrorists and Guns Hearing
The hearing examined how to prevent and protect against terrorists using firearms to attack the United States.
Swine Flu: Coordinating the Federal Response
Nominations Hearing for Ivan K. Fong and Timothy W. Manning
Business Meeting042809
Cyber Security: Developing a National Strategy
Follow the Money: State and Local Oversight of Stimulus Funding
Nomination Hearing for John T. Morton
Nomination Hearing for W. Craig Fugate
Lessons and Implications of the Christmas Day Attack: Securing the Visa Process
Witnesses were: Janice Jacobs, Assistant Secretary, Bureau of Consular Affairs, State Department; David Heyman, Assistant Secretary, Office of Policy, Homeland Security Department; John Morton, Assistant Secretary, Immigration and Customs Enforcement, Department of Homeland Security
Border Security: Moving Beyond the Virtual Fence
The hearing focused on the federal government's plans for securing the Southwest border and the potential for spillover violence from the Mexican drug cartel battles.
Ft Hood Press Conference
April 15, 2010, Chairman Lieberman and Ranking Member Collins held a press conference to announce they would subpoena the Departments of Defense and Justice if they continued to withhold information critical to the Committee's independent investigation of the Ft. Hood massacre.
STOCK Act markup
U.S. Postal Service in Crisis: Proposals to Prevent a Postal Shutdown
Protecting Cyberspace: Assessing the White House Proposal
The hearing to assessed the White House cybersecurity proposal in relation to legislation introduced by Senators Lieberman, Collins, and Carper, D-Del. Lieberman, Collins, and Carper have led efforts to secure the nation's most critical cyber infrastructure and are partnering with Majority Leader Harry Reid and others to pass legislation this year.
Ten Years After 9/11: Improving Emergency Communications
Witnesses told the Homeland Security and Governmental Affairs Committee the ability of first responders to communicate with one another across jurisdictions and agencies has improved significantly since 9/11 but will remain incomplete without dedicated broadband spectrum that can transmit large caches of data .
Federal Regulation: A Review of Legislative Proposals, Part II
The hearing featured outside experts and advocates discussing the regulatory reform bills currently before Congress. This was a continuation of the Committee's June 23 hearing, at which senators with regulatory reform legislation and Office of Information and Regulatory Affairs head Cass Sunstein testified.
Ten Years After 9/11: Preventing Terrorist Travel
Homeland Security and Governmental Affairs Committee Chairman Joe Lieberman, ID-Conn., and Ranking Member Susan Collins, R-Maine, pressed Administration officials about continuing gaps in our defenses against terrorist travel, including inadequate security in visa processing, a large backlog of visa overstays in this country, and our failure to implement biometric information-sharing programs with our allies.
Federal Regulation: A Review of Legislative Proposals
The first panel consisted of several senators discussing their own regulatory reform bills, and the second panel looked at how reform efforts would impact the regulatory process.
See Something, Say Something, Do Something: Next Steps for Rail and Transit
Witnesses: John Pistole, TSA Administrator Peter Boynton, Commissioner for the CT Department of Emergency Management and Homeland Security Dr. Stephen Flynn, President of the Center for National Policy
Transforming Lives Through Diabetes Research
This was the seventh biennial hearing held in conjunction with the Juvenile Diabetes Research Founadation and focused on the JDRF's work and efforts to find a cure.
How to Save Taxpayer Dollars: Case Studies of Duplication in the Federal Government
The hearing, sparked by a recent report by the Government Accountability Office, examined how the federal government can save taxpayer dollars by reducing duplication and fragmentation in agencies and programs.
Ten Years After 9/11: Is Intelligence Reform Working? Part II
This was the third in a year-long series of hearings to assess the progress made since 9/11 and the work still left to be done to protect the American people from terrorist attacks. The hearing measured the headway made in intelligence reforms proposed by the 9/11 Commission and enacted by Congress in 2004.
May 18 Markup
The Committee passed legislation to reform the Federal Protective Service and reauthorize three fire grant programs.
Ten Years After 9/11 Part II
The hearing was the second in a year-long series assessing the progress made and the work still left to be done to protect the American people from terrorist attacks. The hearing measured the headway made in intelligence reforms proposed by the 9/11 Commission and enacted by Congress in 2004.
May 11 Markup
Securing the Border: Progress at the Federal Level
The hearing was the third in a series examining the progress made in securing our borders and what still needs to be done to lay the groundwork for comprehensive immigration reform.
Federal Regulation: How Best to Advance the Public Interest
April 13 Business Meeting
Securing our Borders: Progress at the Local Level
The hearing was the second in a series examining the progress made in securing our borders and what may still need to be done.
Rafael Borras Nomination Hearing
Recovery and Reinvestment
Securing the Border: Building on the Progress Made
The hearing was the first in a series that is examining what it means to secure the border, how to measure gains that reflect a comprehensive picture of the facts on the ground, and ways to forge a pragmatic policy grounded in facts and results.
Southern Border Violence
Robert Harding Nomination
Catastrophic Preparedness: How Ready Is FEMA for the Next Big Disaster?
The hearing examined progress made by the Federal Emergency Management Agency since Hurricane Katrina and steps it must still take to respond effectively to catastrophes
Christmas Day Attack Reform
David Heyman Nomination
Information Sharing in the Age of Wikileaks Hearing
Homeland Security and Governmental Affairs Committee Chairman Joe Lieberman, ID-Conn., and Ranking Member Susan Collins, R-Me., urged the federal government to resist the chilling effect of the disclosure of vast amounts of classified information by Wikileaks and, instead, find ways to protect shared information.
Christmas Day Attack Watchlisting
Nomination Hearing for Heather Higginbottom to be Deputy Director of OMB
Chemical Security
Hearing on Eliminating the Bottlenecks--Nominations Reform
The hearing examined proposals to move Executive Branch nominees through the confirmation process more swiftly.
DHS Budget
Hearing on DHS Budget Request
The Homeland Security and Governmental Affairs Committee heard testimony Thursday, February 17 from Secretary Janet Napolitano about the Department of Homeland Security's Fiscal Year 2012 budget.
GAO Unveils Newest High Risk Program Report
Fort Hood Hearing and Meeting with Victims and Families
The hearing examined the findings and recommendations of the Senators' bipartisan report on the failures of the U.S. government to prevent the November 5, 2009, massacre that killed 13 people and wounded 32 others.
The Value of Education Choices: Saving the DC Opportunity Scholarship Program
The hearing examined the value of continuing the D.C. voucher program as part of an initiative that includes additional funding for public and charter schools.
A Ticking Time Bomb Press Conference
Senators Joe Lieberman and Susan Collins released their bipartisan report on the failures of the U.S. government to prevent the November 5, 2009, shooting at the Fort Hood Army base that killed 13 people and wounded 32 others.
Senators Lieberman and Collins release Northern Border Security Report
The Senators unveiled a GAO report detailing gaps in security along the 4,000-mile-long U.S.-Canadian border.
Intelligence Reform (Part 2)
Intelligence Reform (Part 1)
Markup of DHS Authorization Bill, Part I
This was the Senate's first Department of Homeland Security reauthorization bill since the Department launched operations in 2003.
Ten Years After 9/11: Are We Safer?
The hearing examined the current terrorist threat against the United States, how the threat has evolved, and what steps are needed to further strengthen our defenses. National Counterterrorism Center Director Olsen testified before Congress for the first time since his confirmation.
Defending the Nation Since 9/11: Successful Reforms and Challenges Ahead at DHS
Ten years after the 9/11 terrorist attacks, the Department of Homeland Security (DHS) has matured to the point where it has significantly contributed to the nation's security, said Homeland Security and Governmental Affairs Committee Chairman Joe Lieberman, ID-Conn., and Ranking Member Susan Collins, R-Maine.


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The ultimate in recycling and reuse! Our reusable insulated lunch tote with zipper closure and adjustable strap is made from recycled plastic bottles and will keep your lunch cold or hot for hours. Inside pocket for an ice pack, bamboo utensil and cotton napkin. Durable and machine-washable, this designer bag is perfect for adults and kids. Keep lunches cold at work or at school, and ideal for picnics and travel.
The inside pocket, adjustable strap and insulated fabric make this stylish tote very versatile while traveling with kids. Wear over your shoulder, hang on your stroller, or wear messenger-style and keep your hands free. Add an ice pack in the inside pouch, and our insulted fabric keeps baby food and baby bottles cold while on the go.
BPA-free, PVC-free, phthalate-free and lead-free!
Pharmaca Integrative Pharmacy is your source for natural health products. Browse our online selection of products from all of the best natural brands, or visit one of our pharmacy locations and talk with one of our licensed practitioners. From natural beauty products and cosmetics to vitamins, herbs and supplements, we offer high-quality natural wellness products for the whole family! Start exploring—shop by brand or by condition to find the perfect natural health products for your body, skin, home and more.
The products and claims made about specific products on this site have not been evaluated by Pharmaca.com or the United States Food and Drug Administration and are not approved to diagnose, treat, cure or prevent disease. The information on this site is for educational purposes only and is not intended as a substitute for advice from your physician or other health care professional or any information contained on or in any product label or packaging. You should not use the information on this site for diagnosis or treatment of any health problem or for prescription of any medication or other treatment. You should consult with a healthcare professional before starting any diet, exercise or supplementation program, before taking any medication, or if you have or suspect you might have a health problem. Pharmaca Integrative Pharmacy will not assume liability for any cross-contamination of ingredients, misprints, or adverse reactions to any ingredients in the products we carry. The products sold here may contain lead and other substances that are known to the state of California to cause cancer and birth defects and other reproductive harm. Prices and promotions are subject to change without notice. All content on this web site is copyrighted by Pharmaca Integrative Pharmacy unless otherwise stated. All online offers and prices are valid for online purchases only, and may be different from those in our retail stores. Free shipping offer may not apply to all orders and all states; see shipping policy for full details. Copyright © 2009 – 2015 by Pharmaca Integrative Pharmacy. All rights reserved.


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#24 - Josiah Glafenhein
|2004-05 Baseball
6' 0"
Knoxville, Tenn.
Winthrop Univ.
2005 Season: Josiah played in 38 games last season, starting 29 ... He started 15 games in left field, 10 at designated hitter, two at second base and two at shortstop ... He batted .252 on the season with 24 runs scored, five doubles, one triple, one homer and 10 RBIs ... He batted .406 (13-for-32) against left-handed pitching and .571 (4-for-7) with a runner on third and less than two outs ... Also had nine multiple-hit games on the year and two multi-RBI games ... Went 2-for-3 with a run scored and two RBIs against Xavier on Feb. 26 ... Was 3-for-4 with a run scored and three RBIs against Georgia Southern on Mar. 18. 2004 Season: Josiah was one of three Buccaneer players to play in and start all 58 games last season ... Batted .286 with five home runs and 32 RBIs ... Also scored 41 runs, hit 14 doubles and was successful on seven-of-eight stolen base attempts ... Had a season-high four hits against The Citadel in the Southern Conference Tournament on May 26, going 4-for-4 with two RBIs ... Also had three hits on four occasions ... Went 3-for-4 with two runs scored and three RBIs on Mar. 14 at Georgia Southern ... Was 3-for-4 with two runs scored and three RBIs on Apr. 4 against Western Carolina ... Was named the TIAA-CREF Southern Conference Student-Athlete of the Week on Apr. 7 after batting .636 over the previous week with two home runs, five RBIs and three runs scored. Prior to ETSU: Josiah played one season at Winthrop and batted .287 for the Eagles. High School: Set school records at Gibbs High School in Knoxville, Tenn., with 50 single-season hits and a .462 career batting average ... Josiah was an all-state selection following the 1999 and 2000 seasons. Personal: Born on Dec. 27, 1982, Josiah is the son of Steve and Lydia Glafenhein ... His brother Caleb is also a member of the ETSU Baseball team.
|Copyright ©2015 East Tennessee State Athletics. All Rights Reserved.


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On Trello, I have my notifications set to instantly, but I'm not receiving email updates in my Gmail. Is there a bug or problem I am unaware of?
Take the 2-minute tour ×
Web Applications Stack Exchange is a question and answer site for power users of web applications. It's 100% free, no registration required.
Perhaps the issue is that you are not subscribed to any cards. Trello does not send email notifications of all changes that are made to your board. Try subscribing to a card, and then ask someone else to comment on that card, and see if you get an email.
More information from their blog: http://blog.trello.com/introducing-subscribe-get-notifications-for-any-card/


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HEAD Swimming has signed a two year partnership with Vansbrosimningen, the largest open- water swim event in the world with over 14.000 participants annually. The 60th edition of the event will take place July 8-10 in the beautiful northern part of Sweden, Dalarna.
The swim weekend contains 8 different races with Vansbrosimningen as the main event on the Sunday. Totally 3.000 meters in two different rivers, 2.000 meters with the current and 1.000 meter against. The fastest swimmers will accomplish the distance under 35 minutes while the average exerciser need around 1 hour. The race attracts participants from all around the world and has grown every year.
For more info: http://www.vansbrosimningen.se


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Sorry there are no shows for Uriah Heep right now.
What people are saying about Uriah Heep
This area is intended for discussion only. If you have a question about your order you can get in touch via our Customer Service Area. Comments about existing orders, or with questions will be deleted.


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Ex-Guns N' Roses Drummer Steven Adler Splits With Band Member, Announces New Project
David Livingston, Getty Images
Bassist Chip Z'Nuff has split with ex-Guns N' Roses drummer Steven Adler's band Adler's Appetite and the skinsman has taken to Twitter to address the dissolved partnership. Z'Nuff and Adler played together for six years. Adler revealed some interesting details behind the rhyt


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When I moved from Wisconsin to New York City by myself right after college, I learned quickly how expensive east coast living really was. My entry level graphic design paycheck hardly covered the rent, so I had to get a weekend job. Even though a 7-day workweek was going to be a difficult adjustment, I didn't have a choice. I applied for weekend shifts at a museum gift shop, which appealed to me for several note-worthy reasons:
1) It would (in theory) be less pressure-filled than my day job
2) I could actually put to use all the things I learned in Art History class
3) This job would be like getting paid to learn priceless information, and I knew it! An assemblage of famous artist fun facts makes a boring party better instantly. Nothing says icebreaker quite like sharing the knowledge that Andy Warhol's first attempt at film making was called Sleep, and featured 6 hours of a man--you guessed it-- sleeping; or the fact that the title of Marcel Duchamp's last painting was "You Bore Me"!
4) Since I wouldn't have time to socialize like a normal person, I'd need as many opportunities to make new friends as possible, and the people at work were going to be my best chance.
A few months into my back-breaking schedule, I met the latest addition to our museum shop crew. Like me, she worked full time somewhere else but needed a second income. We clicked immediately; both of us having braved The Big Move-- from the midwest to New York City-- around the same time, both supporting ourselves and feeling the stress of real world pressures, both interested in similar things. We decided to get together and do something fun, outside of work. The problem with a non-stop work week (a schedule that can start at 8a.m. on Monday and drag on through 10pm on Sunday night, only to start all over again at 8a.m. on Monday) is that it barely pauses long enough for you to eat & sleep, let alone socialize.
Finally, one Saturday night after closing, we hit a little bar nearby, fittingly called The Office. I figured the owners decided to name it as such in case their customers needed a good excuse for coming home with whiskey breath, and "I was at The Office!" might just do the trick. The Office is where we'd spend the most of what little off-the-clock time we had during those East Coast years; opting against dinner entrees in favor of budget-friendly (and delicious) salsa & chips just so we could afford margaritas. We'd sit at the bar and swap stories of our lives before The Big Move. We discussed all-things-art and reminisced on days when we didn't have to spend every waking moment working.
We were in our 20's; exhausted from the pace, constantly adjusting to the miles between ourselves and our loved ones, but were truly exhilarated by the city. On that very first night out together, we both said, "This place just FEELS like home" at the same time; which the bartender confused as a compliment to his place of employment. We meant that New York City felt like home, even with all of the challenges. Especially with all of the challenges. We understood every bit of what the other was going through in a way our friends & family back home couldn't. I said we should toast to being friends for a very long time, and that's exactly what we did.
Though our schedules never let up, she became my one of my closest friends. I would joke about her love for Lip Smackers™ (gloss of choice for the 10-year-old and under set) until she presented me with my own root beer flavored tube, and I was hooked (to this day I have 2 different flavors floating around in my bag at all times). In those rare instances when we took time off of work, she was the person I did most of my city adventuring with. We went to museums, window-shopped along Fifth Avenue, drank beer at Irish pubs, snuck into movies. We would laugh about our own life contradictions, like:
1) my steadfast belief that Van Gogh was overrated (my exact words were that I'd rather EAT paint than see his "Sunflowers" or "The Starry Night" ever again), yet I coveted his multi-canvas "Olive Grove" series; and
2) her apartment was filled with vintage furniture, yet her full time job as the manager for a fancy home furnishing store allowed for a deep discount on anything she wanted.
A handful of years later, I'd had enough of burning the candle at both ends. It was time to move to back to Chicago, near my family. Coincidentally, Nic got a huge job promotion and transfer to Chicago shortly thereafter. By then, I was freelancing and was looking for more work. The first thing she did upon reporting to her new job was to hire me as the display designer for the museum store windows, which meant that she could expense pricey dinners at nice restaurants to the company if we took the time to talk business. There were some very pressing business-y things that needed discussion, like what color polish would look best on her short nails and which of those multi-million dollar Olive Grove paintings would fit in with the furniture we'd circled in the IKEA catalog.
If all these things and more were the backbone of our friendship, the heart of it was laughter. There was never enough free time and there never was enough pocket change to scrape together back then, but there was always laughter.
There are so many memories that stand out in my mind, especially now. She was the kind of person who would finally, after months of badgering, rent a certain movie starring a certain actor and would then call to say, "Why didn't you TELL me he was in it? You did? Well, why didn't you tell me LOUDER?!". She was the kind of person who came up with the idea to stay on the phone with each other the entire 5 hours it took us to drive (very slowly) 40 miles in separate cars and opposite directions during a blizzard, just so one of us could get help for the other if we needed it. She was the kind of person who made a habit of sending her friends Wonder Woman™ cards, because she thought we were all Wonder Women.
Remarkable moments with my remarkable friend.
She was the kind of person who, while going through radiation treatments and chemotherapy and seizures and massive headaches and nausea, made me earrings with flat silver beads that simply say, "LAUGH" on them; during a time when she had every reason to feel like doing the opposite. The medical experts gave her 6 months to live, but she defied them all and battled it out longer than anyone thought possible. She worked through the intense challenges that come along with brain cancer, the treatments prescribed and every complication imaginable.
She kicked cancer's ass for two whole years from the exact day of her diagnosis, and she fought to the very end without the use of bulletproof bracelets, a golden lasso or the ability to get away in an invisible plane. She was a real life superhero, and I was lucky enough to be her sidekick for awhile.
She didn't want a funeral, it wasn't her style. This was her wish: an evening in a central location where Nic's husband Tim, various family members and friends from all different stages in her life get to finally meet each other, swap stories, look through photos, laugh together and help each other choke back the tears as we celebrate her life. In a few weeks, we're all descending upon Atlanta from every direction for what we've come to call Nikki Night. We'll all be able to toast to our sweet friend Nic, with her very favorite margaritas. It'll be just as she wanted it.
I'll be thinking about the first of many margaritas we had together at The Office.
I'll be talking about the time she overheard me say to someone in casual conversation that I'd always wanted to go to an opera.*
I'll be wearing my little silver "LAUGH" earrings, and I can't wait.
*A couple of weeks later, she handed me The Metropolitan Opera schedule. When I asked her why, she said, "Pick one, we'll save up the money and go!", and that's exactly what we did.


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Each week TimesNews.net will work with the Kingsport Animal Shelter in Kingsport, TN, to spotlight adoptable animals available at the shelter. The new video of the week's animals will publish on timesnews.net every Thursday by 11 A.M. Check back each week to meet the new Furry Friends!
Also, each week on Fridays by 11 A.M. we will post the new Furry Friends from the Sullivan County Animal Shelter in Blountville, TN. So check back tomorrow!
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EUR-USD ranged between 1.1233 and 1.1281 through the bulk of the session, never giving much thought to the overnight high of 1.1330 posted in London. The softer EU PMI data was responsible for the euro giving back the 1.13 handle, though risk-off limited dollar gains through the session. The pairing did poke to 1.1313 highs as Wall Street hit its lowest levels, though two-way risk lays ahead in the overnight session, depending on what China ... Read More ►
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Chemical optimization of in vitro pharmacology and DMPK properties of the highly selective mAChR 4 (M4) Positive Allosteric Modulator (PAM) Series with Greatly Improved Human Receptor Activity (rM5 CounterScreen)
To date, five muscarinic acetylcholine receptor (mAChR) subtypes have been identified (M1-M5) and play important roles in mediating the actions of ACh in the peripheral and central nervous systems (Langmead et al. 2008). Of these, M1 and M4 are the most heavily expressed in the CNS and represent attractive therapeutic targets for cognition, Alzheimer's disease, and schizophrenia (Felder et al. more ..
Related BioAssays
Related BioAssays
Tested Compounds:
Related Experiments
To date, five muscarinic acetylcholine receptor (mAChR) subtypes have been identified (M1-M5) and play important roles in mediating the actions of ACh in the peripheral and central nervous systems (Langmead et al. 2008). Of these, M1 and M4 are the most heavily expressed in the CNS and represent attractive therapeutic targets for cognition, Alzheimer's disease, and schizophrenia (Felder et al. 2000; Clader and Wang 2005; Wess et al. 2007; Langmead et al. 2008). For example, clinical trials with xanomeline, a M1/M4-preferring orthosteric agonist, demonstrated efficacy as both a cognition-enhancing agent and an antipsychotic agent (Bodick et al. 1997a; Bodick et al. 1997b; Shekhar et al. 2008). However, a long standing question concerns whether or not the antipsychotic efficacy or antipsychotic-like activity in animal models is mediated by activation of M1, M4, or a combination of both receptors. Data from mAChR knockout (KO) mice led to the suggestion that a selective M1 agonist would be beneficial for cognition, whereas an M4 agonist would provide antipsychotic activity for the treatment of schizophrenia (Gomeza et al. 1999; Gomeza et al. 2001; Anagnostaras et al. 2003; Tzavara et al. 2004). This proposal is further supported by recent studies demonstrating that M4 receptors modulate the dynamics of cholinergic and dopaminergic neurotransmission and that loss of M4 function results in a state of dopamine hyperfunction (Tzavara et al. 2004). These data, coupled with findings that schizophrenic patients have altered hippocampal M4 but not M1 receptor expression (Raedler et al. 2007), suggest that selective activators of M4 may provide a novel treatment strategy for schizophrenia patients.
Unfortunately, xanomeline lacks true M1/M4 specificity and also has significant affinity and efficacy at M2 and M3 mAChRs. Thus xanomeline, like many other cholinergic agents including acetylcholinesterase (AChE) inhibitors, displays significant adverse effects including bradycardia, GI distress, excessive salivation, and sweating, which are thought to be primarily due to activation of peripheral M2 and M3 mAChRs (Bymaster et al. 2003; Wess et al. 2007; Langmead et al. 2008). Due to the high sequence homology and conservation of the orthosteric ACh binding site among the mAChR subtypes, development of chemical agents that are selective for a single mAChR subtype has been largely unsuccessful, and in the absence of highly selective activators of M4, it has been impossible to test the role of selective M4 activation. However, in recent years, we have been highly successful in the identification of multiple highly selective allosteric activators for M1 (Bridges et al. 2008; Jones et al. 2008; Ma et al. 2009; Marlo et al. 2009; Shirey et al. 2009; Bridges et al. 2010) and M4 (Brady et al. 2008; Shirey et al. 2008; Kennedy et al. 2009). Though we are encouraged by these results, unfortunately, highly selective centrally penetrant activators of either M1 or M4 remain unavailable, making it impossible to determine the in vivo effects of selective activation of these receptors. Future compounds developed should exhibit sufficient potency, efficacy, and pharmacokinetic properties, including brain penetration, to make useful probes to progress M4 biology, which will undoubtedly allow the intense study of M4 activation in multiple areas of neuroscience.
Potency and efficacy of compounds will be determined by performing concentration-response curves (CRCs, 10 points, ranging from approximately 30 uM-1 nM at 0.3% final DMSO concentration) at human M4 using a calcium assay in which the cells also express the chimeric G protein Gqi5 to couple M4 to calcium mobilization (Brady et al. 2008; Shirey et al. 2008; Kennedy et al. 2009). PAMs with EC50 values < 1 uM versus human M4 will next be evaluated for potency versus rat M4 in an analogous calcium assay utilizing Gqi5. Following potency evaluation at human and rat M4, PAMs with EC50 values less than 1 uM at rat M4 will be evaluated for their ability to left-shift the CRC of acetylcholine (ACh) for rat M4 in a calcium assay and will be examined for their selectivity for M4 relative to other mAChR subtypes (Brady et al. 2008; Shirey et al. 2008; Kennedy et al. 2009). PAMs with a fold-shift of the ACh CRC of > 5 will then be evaluated for Tier 1 DMPK assays including plasma protein binding (PPB), intrinsic clearance (Obach 1997; Obach 1999), and inhibition of cytochrome p450 enzymes (CYP) (Youdim et al. 2008; Engers et al. 2009; Lebois et al. 2011; Jones et al. 2012). Next, compounds demonstrating PPB > 0.01 fraction unbound (Fu), a clean CYP profile, and moderate clearance will be evaluated for CNS exposure and Plasma:Brain levels using an in vivo snapshot PK paradigm (Frick et al. 1998; Engers et al. 2009; Lebois et al. 2011; Jones et al. 2012). Novel M4 PAMs showing a CNS exposure > PAM EC50, a Brain:Plasma ratio of >0.5, and at least a 10-fold or greater selectivity versus other mAChR subtypes will next be evaluated in a preclinical model of antipsychotic drug action: amphetamine-induced hyperlocomotion (AHL) (Brady et al. 2008; Jones et al. 2008). M4 PAMs demonstrating activity in AHL will have their ancillary pharmacology fully evaluated and those compounds that show no significant off-target activity and suitable solubility will be declared an MLPCN probe. The ultimate goal of this project from the PI's perspective is to generate compounds which should exhibit sufficient potency, efficacy, and pharmacokinetic properties, including brain penetration, to make useful probes to progress M4 biology.
1. Anagnostaras, S. G., G. G. Murphy, et al. (2003). "Selective cognitive dysfunction in acetylcholine M1 muscarinic receptor mutant mice." Nat Neurosci 6(1): 51-8.
2. Bodick, N. C., W. W. Offen, et al. (1997a). "Effects of xanomeline, a selective muscarinic receptor agonist, on cognitive function and behavioral symptoms in Alzheimer disease." Arch Neurol 54(4): 465-73.
3. Bodick, N. C., W. W. Offen, et al. (1997b). "The selective muscarinic agonist xanomeline improves both the cognitive deficits and behavioral symptoms of Alzheimer disease." Alzheimer Dis Assoc Disord 11 Suppl 4: S16-22.
4. Brady, A. E., C. K. Jones, et al. (2008). "Centrally active allosteric potentiators of the M4 muscarinic acetylcholine receptor reverse amphetamine-induced hyperlocomotor activity in rats." J Pharmacol Exp Ther 327(3): 941-53.
5. Bridges, T. M., A. E. Brady, et al. (2008). "Synthesis and SAR of analogues of the M1 allosteric agonist TBPB. Part I: Exploration of alternative benzyl and privileged structure moieties." Bioorg Med Chem Lett 18(20): 5439-42.
6. Bridges, T. M., J. Phillip Kennedy, et al. (2010). "Chemical lead optimization of a pan Gq mAChR M1, M3, M5 positive allosteric modulator (PAM) lead. Part II: development of a potent and highly selective M1 PAM." Bioorg Med Chem Lett 20(6): 1972-5.
7. Bymaster, F. P., P. A. Carter, et al. (2003). "Role of specific muscarinic receptor subtypes in cholinergic parasympathomimetic responses, in vivo phosphoinositide hydrolysis, and pilocarpine-induced seizure activity." Eur J Neurosci 17(7): 1403-10.
8. Clader, J. W. and Y. Wang (2005). "Muscarinic receptor agonists and antagonists in the treatment of Alzheimer's disease." Curr Pharm Des 11(26): 3353-61.
9. Engers, D. W., C. M. Niswender, et al. (2009). "Synthesis and evaluation of a series of heterobiarylamides that are centrally penetrant metabotropic glutamate receptor 4 (mGluR4) positive allosteric modulators (PAMs)." J Med Chem 52(14): 4115-8.
10. Felder, C. C., F. P. Bymaster, et al. (2000). "Therapeutic opportunities for muscarinic receptors in the central nervous system." J Med Chem 43(23): 4333-53.
11. Frick, L. W., K. K. Adkison, et al. (1998). "Cassette dosing: rapid in vivo assessment of pharmacokinetics." Pharmaceutical Science & Technology Today 1(1): 12-18.
12. Gomeza, J., L. Zhang, et al. (1999). "Enhancement of D1 dopamine receptor-mediated locomotor stimulation in M(4) muscarinic acetylcholine receptor knockout mice." Proc Natl Acad Sci U S A 96(18): 10483-8.
13. Gomeza, J., L. Zhang, et al. (2001). "Generation and pharmacological analysis of M2 and M4 muscarinic receptor knockout mice." Life Sci 68(22-23): 2457-66.
14. Jones, C. K., A. E. Brady, et al. (2008). "Novel selective allosteric activator of the M1 muscarinic acetylcholine receptor regulates amyloid processing and produces antipsychotic-like activity in rats." J Neurosci 28(41): 10422-33.
15. Jones, C. K., M. Bubser, et al. (2012). "The metabotropic glutamate receptor 4-positive allosteric modulator VU0364770 produces efficacy alone and in combination with L-DOPA or an adenosine 2A antagonist in preclinical rodent models of Parkinson's disease." J Pharmacol Exp Ther 340(2): 404-21.
16. Kennedy, J. P., T. M. Bridges, et al. (2009). "Synthesis and structure-activity relationships of allosteric potentiators of the m(4) muscarinic acetylcholine receptor." ChemMedChem 4(10): 1600-7.
17. Langmead, C. J., J. Watson, et al. (2008). "Muscarinic acetylcholine receptors as CNS drug targets." Pharmacol Ther 117(2): 232-43.
18. Lebois, E. P., G. J. Digby, et al. (2011). "Development of a highly selective, orally bioavailable and CNS penetrant M1 agonist derived from the MLPCN probe ML071." Bioorg Med Chem Lett 21(21): 6451-5.
19. Ma, L., M. A. Seager, et al. (2009). "Selective activation of the M1 muscarinic acetylcholine receptor achieved by allosteric potentiation." Proc Natl Acad Sci U S A 106(37): 15950-5.
20. Marlo, J. E., C. M. Niswender, et al. (2009). "Discovery and characterization of novel allosteric potentiators of M1 muscarinic receptors reveals multiple modes of activity." Mol Pharmacol 75(3): 577-88.
21. Obach, R. S. (1997). "Nonspecific binding to microsomes: impact on scale-up of in vitro intrinsic clearance to hepatic clearance as assessed through examination of warfarin, imipramine, and propranolol." Drug Metab Dispos 25(12): 1359-69.
22. Obach, R. S. (1999). "Prediction of human clearance of twenty-nine drugs from hepatic microsomal intrinsic clearance data: An examination of in vitro half-life approach and nonspecific binding to microsomes." Drug Metab Dispos 27(11): 1350-9.
23. Raedler, T. J., F. P. Bymaster, et al. (2007). "Towards a muscarinic hypothesis of schizophrenia." Mol Psychiatry 12(3): 232-46.
24. Shekhar, A., W. Z. Potter, et al. (2008). "Selective muscarinic receptor agonist xanomeline as a novel treatment approach for schizophrenia." Am J Psychiatry 165(8): 1033-9.
25. Shirey, J. K., A. E. Brady, et al. (2009). "A selective allosteric potentiator of the M1 muscarinic acetylcholine receptor increases activity of medial prefrontal cortical neurons and restores impairments in reversal learning." J Neurosci 29(45): 14271-86.
26. Shirey, J. K., Z. Xiang, et al. (2008). "An allosteric potentiator of M4 mAChR modulates hippocampal synaptic transmission." Nat Chem Biol 4(1): 42-50.
27. Tzavara, E. T., F. P. Bymaster, et al. (2004). "M4 muscarinic receptors regulate the dynamics of cholinergic and dopaminergic neurotransmission: relevance to the pathophysiology and treatment of related CNS pathologies." FASEB J 18(12): 1410-2.
28. Wess, J., R. M. Eglen, et al. (2007). "Muscarinic acetylcholine receptors: mutant mice provide new insights for drug development." Nat Rev Drug Discov 6(9): 721-33.
29. Youdim, K. A., R. Lyons, et al. (2008). "An automated, high-throughput, 384 well Cytochrome P450 cocktail IC50 assay using a rapid resolution LC-MS/MS end-point." J Pharm Biomed Anal 48(1): 92-9.
rM5 Muscarinic Receptor CounterScreen
Cell line creation and culture of the rat M5/CHO line
Rat M5 (rM5) in pCD was a gift from T.I. Bonner at the NIH. rM5 was subcloned from pCD into pcDNA3.1 (+) (Invitrogen Corp., Carlsbad, CA) and stably transfected into Chinese hamster ovary (CHO K1) cells purchased from the ATCC (www.atcc.org). rM5 CHO cells were cultured in Ham's F-12; 10% heat-inactivated fetal bovine serum (FBS), 20mM HEPES, and 500 ug/mL G418 (Mediatech, Inc., Herndon, VA). All cell culture reagents were purchased from Invitrogen Corp. (Carlsbad, CA) unless otherwise noted.
Potency determinations
Assays were performed within the Vanderbilt Center for Neuroscience Drug Discovery's Screening Center. CHO cell lines expressing muscarinic acetylcholine receptors were plated (15,000 cells/20 uL/well) in black-walled, clear-bottomed, TC treated, 384 well plates (Greiner Bio-One, Monroe, North Carolina) in Ham's F-12, 10% FBS, 20 mM HEPES. The cells were grown overnight at 37 degrees C in the presence of 5% CO2. The following day, plated cells had their medium exchanged to Assay Buffer (Hank's balanced salt solution, 20 mM HEPES and 2.5 mM Probenecid (Sigma-Aldrich, St. Louis, MO)) using an ELX405 microplate washer (BioTek), leaving 20 uL/well, followed by addition of with 20 uL of 4.5 uM Fluo-4, AM (Invitrogen, Carlsbad, CA) prepared as a 2.3 mM stock in DMSO and mixed in a 1:1 ratio with 10% (w/v) pluronic acid F-127 and diluted in Assay Buffer for 45 minutes at 37 degrees C. The dye was then exchanged to Assay Buffer using an ELX405, leaving 20 uL/well and the plates were incubated at room temperature for 10 min prior to assay. Test compounds were transferred to daughter plates using an Echo acoustic plate reformatter (Labcyte, Sunnyvale, CA) and then diluted into Assay Buffer to generate a 2x stock in 0.6% DMSO (0.3% final). Acetylcholine (ACh) EC20 and EC80 were prepared at a 5X stock solution in assay buffer prior to addition to assay plates. Calcium mobilization was measured at 37 degrees C using a Functional Drug Screening System 6000 or 7000 (FDSS6000 or FDSS7000, Hamamatsu, Japan) kinetic plate reader according to the following protocol. Cells were preincubated with test compound (or vehicle) for 144 seconds prior to the addition of an EC20 concentration of the agonist, ACh. 86 seconds after this addition, an EC80 concentration of ACh was added. Control wells also received a maximal ACh concentration (1 mM) for eventual response normalization.
Data analysis
The signal amplitude was first normalized to baseline and then as a percentage of the maximal response to ACh. Microsoft XLfit (IDBS, Bridgewater, NJ) was utilized for curve fitting and EC50 value determination using a four point logistical equation.
Compounds showing dose-dependency were assigned 'Outcome' = 'Active', EC50='Value', and % ACh max='Value'.
Categorized Comment - additional comments and annotations
From PubChem:
Assay Test Type: In vitro
Result Definitions
* Activity Concentration. ** Test Concentration.
Additional Information
Grant Number: MH077607-1
Data Table (Concise)


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Everyone who was in the original "Star Trek" TV series eventually came to terms with its pop-cult status, starting with the fact that "Star Trek" is a life sentence.
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