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Top Lock & Key offers a Unique Same Day Immediate Response Service to our Clients and new Customers In the Sydney CBD, North Sydney and Lower North Shore suburbs. If you have been locked out of your home or office, had your handbag stolen along with all your Personal details, or just need a service call ASAP due to any unforeseen circumstances this is what we specialize in. Richard Cantor is a Master Locksmith with well over 30 years' experience who is well respected among his colleagues. So just let him put your mind at ease as you are dealing with one of the best in the industry. Top Lock & Key Locksmiths carry $20 million in public Liability and are a fully Master & Security Licenced by The New South wales Police Force. Master Lic.408332287, Security Lic.408332263. We are proud members of the Master Locksmiths Association of Australasia. Master Licence,security licence, Public liability and workers comp COC's and Master locksmith Association Certificate will be emailed on request.
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Got locked out, after hours. Richard came Promptly. He did have a challenging task, as key broke in the lock. He changed the second lock too. A seamless operation in short time frame. Richard is a true professional. Thank you, Claire .
TopLock responded very quickly to my online enquiry via their website providing a very competitive quote over the phone for a new deadlock. Richard was able to fit me in the next day and arrived on time and was very reliable. Richard seamlessly installed the deadlock in no time and was very efficient and respectful … Continue reading Anthony McClenaghan Thanks for your excellent service Richard
Thank you for the quick service to come and unlock our front door when we were locked out
Thank you for coming out so quickly! Only the second day in our new place and we locked the keys inside. Very professional, fast, and friendly too. I will definately recommend you.
I really appreciate you doing this so quickly on Friday.
Thank you Richard for your prompt assistance.It was really appreciated.
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Why author Jon Doust is going To The Highlands
To The Highlands is the second book in Jon Doust's Jack Muir trilogy. The first, Boy on a Wire, was shortlisted for the Miles Franklin award, and told the story of Jack's troubled time at his private boys school in Perth. This time it's 1968, Jack is 19. He's dropped out of school and he's about to set off on an adventure that will change his life.
- Title
- To the Highlands
- Author
- Jon Doust
- Publisher
- Fremantle Press
- Author
- Jon Doust
- Interviewer
- Suzanne Donisthorpe

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- Artist: Hollister Thompson
- Release Date: 02/27/2007
Best Buy is dedicated to always offering the best value to our customers. We will match the price, at the time of purchase, on a Price Match Guarantee product if you find the same item at a lower price at a Designated Major Online Retailer or at a local retail competitor's store.Here's how:
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Exclusions apply including, but not limited to, Competitors' service prices, special daily or hourly sales, and items for sale Thanksgiving Day through the Monday after Thanksgiving. See the list of Designated Major Online Retailers and full details.
- Invisible Girl
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- I'd Like to Be the One
- Love in a Strange World
- Miss Jessica (All I Really Need)
- It's a Lonely Night
- Door Prize (I've Created a Monster)


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U.S. Sailboat Show adds boat prize and sailing lessons
Sailing lessons and a grand prize Beneteau sailboat giveaway are among the new offerings this year at the Oct. 8-12 U.S. Sailboat Show in Annapolis, Md.
The United States Sailboat Show annually attracts more than 50,000 boating enthusiasts worldwide. The in-water show is held on the Annapolis, Md., waterfront in October.
Sailing lessons and a grand prize Beneteau sailboat giveaway are among the new offerings this year at the Oct. 8-12 U.S. Sailboat Show in Annapolis, Md.
For the first time in its decades-long history, sailing lessons will be offered in October at the United States Sailboat Show in Annapolis, Md.
The Annapolis Spring Sailboat Show will be held April 24-26 with nearly 80 new and brokerage sailboats for sale, including catamarans, monohulls, racing boats, family cruisers, daysailers and yachts.
The Boat Village, an online boat management and service coordination platform, is now available as an iPad app for premium subscription users.
The 45th United States Sailboat Show wrapped up Monday in Annapolis, Md., with ticket sales up more than 5 percent from last year, more exhibit space than ever before and nearly two dozen new-model introductions.
Ronstan veteran Alistair Murray was recognized for his contributions to the sailing industry during a launch party at the 45th United States Sailboat Show in Annapolis, Md.
Manufacturers, vendors and sailors from around the globe will gather on miles of docks Thursday in historic Annapolis, Md., to open the 45th United States Sailboat Show.
On the eve of their return, the Annapolis sail and power shows launched a newly designed easy-to-navigate website.
French sail and motoryacht manufacturer Jeanneau, gearing up for its largest display ever at the United States Sailboat Show, plans to exhibit 12 boats at the Maryland event.
The Marine Trades Association of Maryland, the Eastport Yacht Club Foundation and Annapolis Boat Shows are partnering to present Maryland Boating Career Discovery Day, an opportunity for high school students to become familiar with the marine trades industry.
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Bennett DVD - Garmin Colorado Series: 300, 400c, 400i, 400t
Item # 83662
Your Overtons.com Session is About to Expire!
Learn key features of these Garmin units
Covers basics to advanced operation
With all of the features these units include, you will want a training DVD so you can get the most from your Colorado. Learn how to utilize the basemap, coastal charts, US inland lakes, altimeter, picture viewer, exchange tracks, waypoints, routes and geocaches between units, plus many other functions these handhelds offer. Designed for use on land and water.
Share your pictures
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The only thing worse than a disease wherein mysterious microscopic fibers grow out of your arms and legs and cause unbearable itching is the creeping sensation of reading about one of those diseases. Which sort of explains, I think, why the medical community has long dismissed Morgellons disease as a mental illness. Morgellons sufferers get crazy rashes from which they believe they see fibers growing; the doctors see nothing, and the patients get crazier. They report coughing up bugs. They become dependent on cocaine to stay awake. Oh yeah, and almost all sufferers are women, which might be one of the reasons so many doctors have long passed it off as one big hysterical hallucination. But! One doctor finally decided to give it a look. "Send me your fibers!" he posted on a Morgellons website. And in they came. Box after box of identical fibers, all magenta and cobalt blue. He tested them against all 900 materials listed in an American textile database — nothing. He heated them to 700 degrees to determine their chemical makeup — nothing. He held a flourescent light over them. They glowed.
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About the Author
Michelle 's love for writing blossomed when her father gave her a diary. Instead of recounting her daily life, she wrote stories of people who live in her head. Like most of her characters, she believes in Happily Ever After. Naturally, she finds harmony in writing romance. An unabashed, self-proclaimed foodie, Michelle loves to try new food when given the chance. She loves to travel, dislikes the cold and would rather spend money on paperbacks than shoes. She enjoys watching foreign films and reading a great books that make her swoon. Michelle is an active member of RWA and several of its chapters. She lives in Ontario, Canada with her husband, two kids and a morkie pup named Scarlett.


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Folli Follie - Jewellery and Accessories Retailer
Folli Follie
Folli Follie is an international fashion brand of original and fashionable designs of jewellery, watches and accessories.Folli Follie is an international lifestyle fashion brand, which designs, manufactures and distributes jewellery, watches and accessories. Folli Follie creates and offers fashion in 30 markets with more than 650 points of sale worldwide. Today, Folli Follie's core philosophy is to unveil the brightest side of women internationally, by offering a collection of versatile, original and fashionable designs of jewellery, watches and accessories. In addition to its jewellery and watches lines, Folli Follie offers comprehensive assortments in fashion accessories, such as handbags, wallets, small leather goods, belts, pashminas and sunglasses. The exclusively designed pieces add breadth to the company's identity and are now globally recognized amongst accessories brands. The Folli Follie team of designers works restlessly in taking iconic motifs and translating them into unique designs that go through the entire Folli Follie product range, always with impeccable style. The iconic motif approach is yet another aspect that demonstrates the insightful process of the Folli Follie design teams. Over the past few years, the Folli Follie consumer follows the exciting journey of the iconic motifs such as Heart4Heart and Santorini Flower, from a statement necklace translated into an exciting watches collection, into a complete jewellery line with many distinct offerings and into unique bags and purses.
watches, jewellery, bags, accessories
Delivery Information
Domestic: UK
|Click & Collect
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|on orders over £50
|Standard Delivery
|Special Delivery
International: £15.00
* Special Delivery may refer to "Heavy Items", "Express" or "Nominated Day" deliveries; always check the seller's website for full details.
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Discussion in 'General WWE' started by Stopspot, Jun 11, 2015.
Well, if true: Fuck.
Get well soon, Tyson.
The call from Edge & Stone Cold is legit since Nattie tweeted it a couple days ago. Most likely legit.
Cesaro paying tribute to his lil'buddy perhaps?
Sucks for Kidd. He finally got on television again (after being shafted for so long, which is a shame for a guy of his in-ring caliber) in a role that complements him and his talents perfectly and then he ends up being put on the shelf for possibly the next year or more.
Kinda sucks for Joe, too. Not that it'll impact his career negatively or anything since the injury is already being put down as a freak accident, but it must suck seriously hurting a dude in your first official match (dark match or not) with the company.
Damn man. I was really happy that Kidd was getting decent TV time too.
Rough business. Hope he bounces back.
Sad to hear.
Taken outside of Dusty's funeral. Neckbrase confirmed
Gonna miss ya, Tyson. Hope we don't have to wait too long for your return.
I don't mean to criticize, but jesus, great funeral attire Natty lmao
Dayumn, rough business.
Tyson Kidd Injury Update
Jesus Christ.
He's apparently got some really shitty luck too Here's to hoping he can walk after. I thought I saw a news blurb with a picture of his neck post surgery.......
oh yeah
Damn, I hope everything turns out well for him. Hold on and be strong, Tyson!
An absolute shame. Fact.
I'm really hoping Natalya is given time to remain with him. The Total Divas show wasn't appropriate didn't make me feel comfortable at all. It was kind of dirty to me. It would be a sweet ending if Tyson and Natalya grew so much closer over this.
Some surgical notes: Tyson's surgery required 16 staples, 4 screws and the insertion of a metal rod in his neck.
He is Iron Man.


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For bookings /further information, contact:
Tel: 021 783 4545
Email: firstname.lastname@example.com
Opening times
The Café is open every Tuesday, from 9am until 5pm, and every Wednesday through to Sunday from 9am until late.
Where to find us
When you arrive at Imhoff Farm (click here for directions), walk from the parking area through the entrance to the courtyard. You will see the entrance to the restaurant on your right. Continue through to the step and lawn on the other side if you would like to enjoy the views.


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The equine species is very diverse and widely varied. This is largely due to the different breeds within the species. Breed registries have defined standards and traits that are preferred or expected within each category and it is these characteristics that make the breeds unique.
Tail carriage and gait are a couple of these examples. As these standards are sought after, exaggerations of these traits can be overly-promoted. Tail carriage is an example of one of these overly-promoted traits. In western performance horses, a quiet, low-carried tail that doesn't distract from the performance is desired. In some English disciplines, an erect, excited tail to accentuate the performance is preferred. While the breeds of horses used in various disciplines have these tendencies, when it comes to tail carriage, the calm western horse can get irritated and show it by swishing its tail. Likewise the English counterpart may not keep its tail perfectly erect during a performance. Therefore, in some circles, it is has become common place to alter tails to fit the desired look. This might mean deadening the tail so it stays still and quiet, or it may mean "nicking" the tail ligaments and using "tail set" equipment to "train" the tail to be more erect. A more widely known tail alteration is docking the tail of draft animals. Several countries, and even states, have laws banning these procedures, but enforcement and compliance are not always made a priority. Many breed organizations and show circuits have taken a position against these practices, but those positions are only honored when there is a priority put on enforcement.
The practice that has received national attention over the last several years is soring. Soring is an unethical and illegal practice of deliberately inflicting pain to exaggerate the leg motion of horses to gain an unfair advantage in the show ring. The breed most commonly associated with the practice of soring is the Tennessee Walking Horse. While the "big lick" Tennessee Walking Horses are naturally animated and big-stepping, various tactics can and have been used to exaggerate their gaits. These tactics include such things as weighted shoes and ankle chains to caustic agents and painful shoeing practices.
Congress passed legislation in 1970 (The Horse Protection Act) that made soring illegal and punishable by fines and imprisonment. However, enforcement of the Horse Protection Act (HPA) by the U.S. Department of Agriculture (USDA) has been fraught with controversy due to lack of proper funding, expertise and a flawed inspection process and system. Consequently, it has been business as usual for many trainers and exhibitors and therefore, over time, several groups have brought attention to these inhumane practices. Initiatives over the years have attempted to improve the inspection and enforcement of the HPA, but success has been limited and sporadic. In 2012, both the American Veterinary Medical Association (AVMA) and the American Association of Equine Practitioners (AAEP) issued statements in support of providing adequate funding to properly enforce the Horse Protection Act.
The Prevent All Soring Tactics (PAST) Act, in various iterations, has been introduced into previous Congressional sessions (H.R. 3268/S. 1121) and has had wide, bi-partisan support. The PAST Act would make the actual act of soring illegal and require the USDA to be more involved in the inspection process and enforcement. While this legislation is the most direct effort to protect horses from these practices, until it is passed into law and goes through appropriations, the practice continues. Most recently in January of 2017, the USDA released a final rule that strengthens enforcement of the HPA. The AVMA
and the AAEP issued joint comments in support of this final ruling and the USDA adopted many of the suggestions, including prohibition on the use of action devices and non-therapeutic stacks or pads.
Horse Soring and the Past Act, H.R. 1518 & S. 1406 published by the AVMA and AAEP in May 2015.
Literature Review on the Welfare Implications of Horse Tail Modifications published by the AVMA May 12, 2012.
Additional information:
https://www.avma.org/KB/Resources/Reference/AnimalWelfare/Pages/soring-horses.aspx https://aaep.org/position-practice-soring https://www.aphis.usda.gov/aphis/ourfocus/animalwelfare/horse-protection-amendments


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"Crimson Shore" is a highly satisfying addition to the long list of Agent Pendergast thrillers by Douglas Preston and Lincoln Child, and sees the unusual hero and his ward dealing with the locals, including monsters, in Massachusets. Read John Orr's review.
"The Martian," by Andy Weir, is one of our favorite reads in a long time. An astronaut is injured and stranded on Mars, with no working communications and not enough food to last the years it would take a rescue mission to come get him. A very impressive, fascinating book. Read John Orr's review.
See more reviews and interviews in Books.
Review: 'Over the Top: Math Bass & the Imperial Court SF'
Anna Koster photo
Math Bass, center, speaks with a journalist before the exhibition opens to the public. Her apple sculpture "Elizabeth" (ceramic with lacquer and wood, 22 x 22 x 22 inches) and untitled ladder (wood, 67 x 36 x 18 inches) are in the foreground. Both were created in 2017 for this exhibition. Portraits of monarchs from the Imperial Court SF's 62-year history hang on the wall. A selection of Empresses' and Emperors' banners hang above.
"Over the Top: Math Bass & the Imperial Court SF" is a fascinating story that blends modern works by Math Bass with historical artifacts from a 62-year-old LGBTQ society in San Francisco. Anna Koster has seen the show and reports. See her review.
Tony Lacy-Thompson / Regarding Arts
James Reber, Lee Kopp and Keith Pinto, from left, as "The Rude Mechanicals" of Shakespeare's "Midsummer Night's Dream," as performed by ShakesBEERience at Café Stritch in San Jose on Monday, April 17, 2017. Lolling about on the floor are Gendell Hing-Hernandez as Pyramus and Skylar Collins as Thisbe.
"A Midsummer Night's Dream" is usually performed, ya know, with costumes and scenery. At ShakesBEERience in San Jose, they don't bother with that. But they have beer. Lots of beer. And a talented cast. Tony Lacy-Thompson reviews.
TheatreWorks Silicon Valley
Kevin Berne / TheatreWorks Silicon Valley
Jeanne Sakata, left, as Natsuko, and Emily Kuroda as Noriko in "Calligraphy." The TheatreWorks Silicon Valley production runs March 8 through April 2, 2017, at the Lucie Stern Theatre in Palo Alto.
"Calligraphy" has some lovely moments, but the feeling persists that TheatreWorks could have done a better job with it. John Orr saw it almost at the end of its run, and reviews.
Kit Wilder
Courtesy of Kit Wilder
Kit Wilder directs a show at City Lights, circa 2015. His adaptation of "Frankenstein" opens March 25, 2017, and runs through April 23, 2017, at City Lights in San Jose.
Kit Wilder, playwright, director, actor all things theater talks with John Orr about adapting Mary Shelley's "Frankenstein; or, The Modern Prometheus" for the stage. In previews tonight, it opens on Saturday, March 25, 2017, at City Light in San Jose. Read the story.
Cirque du Soleil
Laurence Labat / Costumes: Giovanna Buzzi / 2016 Cirque du Soleil
The acrobatics are amazing in the "Luzia" show staged by Cirque du Soleil.
"Luzia" is the latest powerful extravaganza from Cirque du Soleil, a feast of sight and sound under Le Grand Chapiteau, currently parked in San Jose. Tony Lacy-Thompson reviews.
Keith Pinto
Tracy Martin / Diablo Theatre Company
Melissa WolfKlain, left, and Keith Pinto in "Singin' in the Rain," at Diable Theatre Company in 2013.
Keith Pinto is a song-and-dance man who has been excellent in musicals all across the nation and in the San Francisco Bay Area. He's just finishing up a stellar performance in "Cabaret," is next to direct "Altar Boyz" and there will be more shows to come. Read John Orr's profile of Keith Pinto.
Hillbarn Theatre
Mark & Tracy Photography / Hillbarn Theatre
Entertaining at the Kit Kat Club in "Cabaret" are, from left, Catrina Manahan, Noelani Neal, Gabbi Traub, Melissa Wolfklane, Rachelle Abbey, Jessica Maxey, Jessica Whittemore and Christine Baker. The show runs January 19 through February 5, 2017, at Hillbarn Theatre.
"Cabaret," one of the greatest, most important musicals of the 20th century, is getting a fabulous production with an excellent cast at Hillbarn Theatre. John Orr said he wished he had more eyes in his head to see it all. Read his review.
Valerie Vigoda review
Tony Lacy-Thompson / Regarding Arts
Valerie Vigoda performs a solo show at the home of Kevin Surace and Erica Rogers in Sunnyvale, on Dec 2, 2016.
Valerie Vigoda is well known to Bay Are theater fans, especially for the musicals "Striking 12" and "Sleeping Beauty Wakes," which she performed at TheatreWorks while in the power trio GrooveLily. Recently, she performed a solo show in a house concert and was terrific. Tony Lacy-Thompson reviews.
For ears and eyes
Judy Garland was an amazing talent, unmatched in many ways. Want the proof? Lend eyes and ears to her singing "Somewhere Over the Rainbow" in a poor quality recording from the ancient days of TV. Fabulous.
Some guys singing "Bad Romance." It's so much fun.
Molly Bell is amazing. We have a profile of her here in Regarding Arts, but here's a favorite video of her performing in Divas for Life.
Lake Street Dive is a band formed by Rachael Price, who is a wonderful vocalist. I love this tune, which I heard on A Prairie Home Companion. Then I found this video.
"Laundry Room." Another from The Avett Brothers. Here is another tune that delves deep into emotion and yearning.
"While My Guitar Gently Weeps." Fabulous band performs in 2004 to honor George Harrison upon his posthumous induction into the Rock and Roll Hall of Fame as a solo artist. Tom Petty and the Heartbreakers, Jeff Lynne, Steve Ferrone, Dhani Harrison and Prince. Mike Campbell of the Heartbreakers does the early solo stuff. Prince shows up and takes over.
Tim O'Brien: "Hey, Joe," at Celtic Connections 2009, Glasgow Scotland.
Trucks & Tedeschi Band: "Midnight in Harlem," at the 2010 Guitar Festival.
Asylum Street Spankers: "Monkey Rag," and "If You Want Me to Love You."
OK Go: "This Too Shall Pass." Incredible Rube Goldberg machine video.
Willie Dixon: "I'm Nervous." Funny and charming video of the great songwriter, singer and bassist.
John Lee Sanders: Fabulous musician. Give a listen to "Midnight in New Orleans".
"Let's Go Get Stoned" is the first thing the friend of a friend said when he got off the plane from Vietnam in 1967 or so. It's also the title of this fab song by Ray Charles.


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Can you please tell me what's going on with my face 3 months after having volbella? I have lots of lumps, tenderness. (Photo)
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Doctor Answers 5
Filler reaction to Volbella- HA filler
See your injector
Web reference: http://youtube.com/edelsteincosmetictv
Filler and Reaction to Volbella and Voluma
It is difficult to see from the photos but it is possible that you developed an allergic reaction to the product or it could be poor injection technique. You will probably need to have this dissolved with Hyaluronidase. I would return immediately to your injector to consult a board certified dermatologist who is an expert in cosmetic facial injections for examination. Pleases keep us posted. Best, Dr. Green
Web reference: http://www.michelegreenmd.com/liquid-facelift
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It sounds as though you are experiencing more than one symptom.
Best of Luck
Web reference: http://torontosurgery.ca/Toronto-Fillers-Injections.html
Can you please tell me what's going on?
Thank you for sharing your question and photographs and I am sorry to hear of your filler-related issues. After three months you should not be experiencing these symptoms and I would advocate for you to see your injector for an in-person evaluation. They may need to fully dissolve the filler material and prescribe antibiotics if an infection is thought to be causing the problem. Best wishes.
Web reference: Http://www.nelson-center.com/dermal-fillers.html
These answers are for educational purposes and should not be relied upon as a substitute for medical advice you may receive from your physician. If you have a medical emergency, please call 911. These answers do not constitute or initiate a patient/doctor relationship.


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Sampdoria boss Delio Rossi has named a 24-man squad for their Serie A opener against Juventus on Saturday.
New signing Vasco Regini and Renan Garcia are missing from the party as they are carrying suspensions from the end of last season.
The game, to be played at the Stadio Luigi Ferraris, will kick off at 20.45 local time.
Goalkeepers: Da Costa, Fiorillo, Tozzo.
Defenders: Berardi, Castellini, Costa, Fornasier, Gastaldello, Mustafi, Palombo, Salamon.
Midfielders: De Silvestri, Eramo, Gavazzi, Gentsoglou, Krsticic, Obiang, Rodríguez, Soriano, Wszolek.
Forwards: Eder, Gabbiadini, Pozzi, Sansone.
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Les derniers articles
Tory Burch
Vidéos Beauté/Mode
Tory Burch Happy Birthday! FashionTV loves You! Watch the amazing USA designer interview in The New York Times... Did you know she was listed as the 73rd most powerful woman in the world by Forbes Magazine. Stay in touch with the FashionTV online network: Watch FashionTV New Live Stream : https://youtu.be/A8A1NVZHFtc http://www.fashiontv.com FASHIONTV VOD: http://ftvvod.com FACEBOOK: http://facebook.com/FTV INSTAGRAM: http://www.instagram.com/FashionTV CHANNEL https://www.youtube.com/c/FTVmain GOOGLE PLUS http://plus.google.com/+FashionTV/posts TWITTER: http://twitter.com/FashionTV FashionTV's network brings you fashion in new and imaginative ways every day online! From the front row of fashion's biggest shows and runways, to highlights of all the best fashion stories from around the world, to the gorgeous models that make the industry tick, FashionTV is there to bring them to you first! The total source for worldwide fashion coverage, FashionTV has new uploads every day with 24/7 access to content for all your fashion and style needs. Join our online network and SEE it first on DailyMotion with FTV!


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iPhone Application
This project received 65 bids from talented freelancers with an average bid price of $3029 USD.Get free quotes for a project like this
Project BudgetN/A
Total Bids65
Project Description
This app will allow user to record a video, play it in slow motion, and analyze each frame. The user will also be able to capture pictures in this application and use the phone to analyze the picture. The user will be able to use the phone to calculate angles in the environment which are shown in the frame/picture (example: angle of a doorway, or a tree on the ground). Cropping frame/photo will be necessary.
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When am I supposed to use the lipo foam boards?
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Doctor Answers 6
Foam boards after liposuction
lipo foam boards?
Hello, Lipo Foams should be use as soon as you feel comfortable enough to wear. Lipo foams will prevent burns and markings to skin from Garment the board will keep your abdomen firm at all times allowing your skin to retract and increasing chances for an excellent final result best of luck and thank you for your question.
When am I supposed to use the lipo foam boards?
Best to ask your chosen operative clinic surgeon if you can get a hold of them... In my "private practice" I use these pads immediately. BUT you are NOT my patient so I can not advise....Guess you know the saying about 'what you pay for...'.
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Liposuction and Garments -- Foam Pads
Web reference: https://www.youtube.com/channel/UCa6C2fuS-AgOnvBjr6_VSQg
Liposuction - when to use the foam boards?
When am I supposed to use the lipo foam boards?
Web reference: http://www.nelson-center.com/liposuction.html
These answers are for educational purposes and should not be relied upon as a substitute for medical advice you may receive from your physician. If you have a medical emergency, please call 911. These answers do not constitute or initiate a patient/doctor relationship.


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As Robert Mugabe – the world's oldest head of state – turns 93, an anxious Zimbabwe wonders who's next. However, his name is on the ballot again for next year's election, and he has declared that he would like to live until he's 100 and rule for life. Or even longer, if his wife is to be believed. Grace Mugabe, 51, said that even if he dies, the ruling Zanu-PF party should field his corpsein the 2018 election.
Robert Gabriel Mugabe was born on 21 February 1924 in what was then Southern Rhodesia, a British colony. In the 1960s he fought against the white minority government of Ian Smith, and was held as a political prisoner for more than 10 years. When Zimbabwe won its independence in 1980, Mugabe became prime minister. In 1987, he assumed the office of President of Zimbabwe, giving himself additional powers in the process. He holds this position to this day. He has ruled with an iron fist, crushing all opposition. He has compared himself to Hitler and has been accused of having a racist attitude towards white people.
On Robert Mugabe's 93rd birthday, IBTimes UK looks back at his life in pictures.
Many Zimbabweans follow his health with keen interest, especially after assertions by Wikileaks that he might have prostate cancer – which he denied. In 2015 he read out the wrong speech in parliament, which the opposition seized upon to question whether he was still of sound mind, though the president's spokesman blamed his aides.
In February 2015, the Zimbabwean government denied that President Robert Mugabe fell down the stairs at Harare International Airport. The incident was caught by press photographers, who were later forced to delete images of a tumbling Mugabe.
In the event of the president's death, resignation or incapacity, the first vice president takes over for the remainder of the term, according to the constitution. The catch is that Zimbabwe has two vice presidents. Both belong to bitterly opposing factions and neither is designated as the official first vice president. This could mean a messy succession, say legal experts.
A key figure in the succession talk is Vice President Emmerson Mnangagwa, who is also justice minister and an associate of Mugabe dating to the guerrilla war against minority rule in what was then Rhodesia.
Then there is "G40," short for Generation 40, a group of younger ruling party members that is associated with Mugabe's 51-year-old wife. Grace Mugabe has said she has no plans to be president. But recent statements by the party's youth leader, who is closely associated to her, that Mugabe should only be replaced by a Mugabe have fuelled speculation that she could be positioning herself to take power.
In 2016, a photo allegedly showing a woman picking up cake crumbs that fell from a table during Zimbabwe's President Robert Mugabe's lavish 92nd birthday party caused a stir in the Southern African nation, where nearly a quarter of the population face the risk of starving to death. Mugabe's Zanu-PF spent up to US$1m (£805,000) of taxpayers' money on the celebration, which included a huge cake weighing about 203 pounds (92kg). The festivities were held in the drought-stricken Masvingo province, which also proved particularly controversial.
The country's once-prosperous economy is imploding, bringing more pressure from the opposition and frustration from a restless population. The government has failed to pay salaries on time, public hospital doctors are on strike and cash shortages are driving the economy to the edge. Nationwide protests broke out last year, rallied via social media. Amid these troubles, it is the political uncertainty that has caused the most concern.
Employees in Mugabe's office held a small birthday party for him. A bigger celebration is set for Saturday (25 February) in Matopos, 500km (350 miles) south-west of Harare. The state-owned Herald newspaper carried a 24-page birthday supplement, packed with goodwill messages from government departments.


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Tag Archives: Camp
Camp Update: Big Ben Speaks While Roster Is Tweaked Before Preseason Opener
LATROBE, Pa. (93-7 THE FAN) — Wednesday's full-pad practice was perhaps the most uneventful one of training camp so far, and considering the Steelers are on…
Source: CBS Pittsburgh » Steelers
Steelers Training Camp 2013: A look back over the last three weeks
The work continues after camp ends
The Steelers are packing up and heading out of training camp at St. Vincent College, but the work is far from over. The team still has three preseason games left, starting Monday night against the ……
Source: Pittsburgh Steelers : News
Training Camp: 2013 Steelers Homerun Derby
The Pittsburgh Steelers held their annual Training Camp Homerun Derby Contest at Saint Vincent College. The defending champion, Linebacker Larry Foote, set out to win again this year, but was beat by Long Snapper Greg Warren….
Source: Pittsburgh Steelers : Videos
Photo Gallery: Steelers Gab At Training Camp In Latrobe Part Three
It was a great day Thursday at Steelers Training Camp in Latrobe, and Steelers Gab was on hand for Thursdays session, and here's just some of the pics from the beautiful St.Vincent College, and some of the experience of the events in Latrobe….
Source: Steelers Gab
Competitive spirit continues at camp
It seemed more like a fall evening than a mid-August one at St. Vincent College on Wednesday, but despite the cool temperatures it is still training camp and things are as competitive as ever. "We ……
Source: Pittsburgh Steelers : News
Steelers Training Camp Update: Rough Day For Running Backs
LATROBE, Pa. (93-7 THE FAN/AP) — The routine of another last-week-of-training-camp practice was disrupted in a potentially major wa…
Source: CBS Pittsburgh » Steelers
Training Camp: Foster on protecting Ben
Pittsburgh Steelers Offensive Lineman Ramon Foster talked about protecting Quarterback Ben Roethlisberger, his new contract and Training Camp almost coming to an end….
Source: Pittsburgh Steelers : Videos


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- Product 584564
Yamaha YPT220 61-Key Portable Keyboard
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The Yamaha YPT-220 keyboard features 375 natural sounding voices, including Stereo Grand Piano, 361 XGlite voices, 12 drum kits and a sound effect ki...Click To Read More About This Product
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A keyboard with 61-keys that features 375 natural sound voices.
The Yamaha YPT-220 keyboard features 375 natural sounding voices, including Stereo Grand Piano, 361 XGlite voices, 12 drum kits and a sound effect kit. The YPT-220 also has 100 accompaniment styles and 102 built-in songs. Use the Portable Grand button to instantly call up an authentic stereo grand piano sound. The Yamaha keyboard also has a rich Reverb effect that adds concert-hall ambiance to any performance. The Yamaha Education Suite feature makes learning and practicing music more fun than ever before.
This Yamaha keyboard has 61 regular-sized keys and 32-note polyphony.
Voices and styles:
The Yamaha YPT220 keyboard has a total of 375 high-quality instrument voices (Stereo Grand Piano, 361 XGlite voices, 12 Drum Kits and Sound Effect Kit) and 100 accompaniment styles.
Sound effect kit:
Try out each key on this 61-note keyboard and enjoy the sound of a dog barking, running water, a creaking door and many other unique effects.
Yamaha Education Suite (Y.E.S.)
Yamaha Education Suite (Y.E.S.) is an advanced set of helpful learning tools built into this 61-key keyboard, letting you teach yourself how to play and perform. Y.E.S. helps you master a song with easy lesson steps. Each lesson can be done in isolation with either your left hand or right hand, or both.
Portable grand button:
Playing piano is fast and easy with Yamaha's Portable Grand function. One dedicated button brings up a great sounding piano, stunningly rich and authentic in its sound and exceptionally responsive to your playing touch, as well as setting up the keyboard to play as a piano.
Different reverb types let you add rich, concert-hall ambiance to your performance.
- Total of 375 high-quality instrument voices and 100 accompaniment styles
- Portable grand button lets you instantly call up Yamaha's world-famous grand piano sound
- Yamaha Education Suite (Y.E.S.) feature
- 102 built-in songs for easy learning
YPT220 61-Key Portable Keyboard
- Control interface:
Number of keys: 61
Type: organ style
Display type: custom LCD
Display size: 92mm x 32mm
Display language: English
Panel language: English
Tone generation technology: AWM stereo sampling
Maximum number of polyphony: 32
Preset number of voices: Stereo Grand Piano + 361 XGlite + 13 Drum/SFX/SE Kits
Preset featured voices: sound effect kit
GM compatibility: yes
XGlite compatibility: yes
Reverb types: 9
Panel sustain function: yes (in menu)
Accompaniment styles:
Number of preset styles: 100
Preset fingering: multi
Style control: Intro, Main x 2, Fill-In, Ending
One-touch setting (OTS): yes
Metronome: yes
Tempo Range: 32-280
Transpose: -12 to 0, 0 to +12
Tuning: yes
Piano button: portable grand button
Lesson/Guide: Y.E.S. (Listen & Learn, Timing, Waiting, Chord Dictionary)
Storage and connectivity:
Headphones: x 1
MIDI: In/Out
AUX Pedal: 1 Footswitch (optional)
Amplifiers and speakers:
Amplifiers: 2.5W + 2.5W
Speakers: 12cm x 2
Power supply (included): Adaptor (PA-3C/PA-130), or batteries (six "AA" size, LR6, or equivalent batteries)
Power consumption: 12W
Included accessories: music rest
Number of preset songs: 102
Body color: black
Dimensions: 4-5/8" H x 37-3/16" W x 13-11/16" D
Weight: 9 lb., 7 oz.
Reviewed by 2 customers
this honestly is so worth the price. I was so surprised at how many sounds this keyboard has. The speakers were a little cheap on it and not loud enough to my liking but overall this was worth it. So many features and settings.
if you're looking for top notch piano/keyboard/synth sounds the ypt 220 isn't for you, if you are just starting out or are a casual musician like me and want an affordable addition to experiment with different musical styles and capabilities this is a good lil' unit. i wasn't real impressed with it at first but the more i play around with it the more i like it. some of the sounds&effects are kinda cheesy but it's got some really cool sounds as well. volume wise i've run it thru my stomp boxes and into a warwick blue cab 20 and it's plenty loud, gigging loud? maybe not. it's pretty well made and easy to use. iv'e had a few yamaha items in the past and have always been impressed with the quality and durability. overall i'd definitely recommend the 220 to anyone looking for a decent board to mess around with, the headphone feature is great too, if you wanna play late at night without irritating anyone or embarrasing yourself. there's plenty of good sounds to keep you interested and creative. as far as buying from musician's friend? i got the board, the fc4 sustain pedal(a sustain pedal is a must), the the power adapter and an on stage stand for around $160 and received it within a week. over all a good buy, great price and great service!


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Students volunteered at the American Red Cross Blood Drive for their applied learning projects and met with several patients in the Patients Care Sciences. The results set a record for the Madison West campus.
This quarter's drive brought 41 people signed up to donate and 37 donors who started the process. With a resulting 35 units collected, the drive exceeded the goal along with beating the previous amount collected from last year.
"What an awesome day!" Shared Chad Obright, Academic and Online Coordinator who helped the class schedule the drive. "Many people did their civic duty twice—first by voting and then by giving blood. I appreciate everyone's patience and willingness to give even though there was quite a wait at times. I also want to pay special thanks for Judy Bukstein and her Patient Care Science class. Their hard work promoting the event helped us get one of our highest donation totals ever."
Globe University-Madison West echoes this appreciation to all those who showed their "We Care" attitude and looks forward to hosting future blood drives.
Be sure to check out our campus Facebook page to view more photos.


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So, You're Posted To is a new section by Laura Keller designed to give readers the inside scoop on the places they will go. It's tried and true advice from people who have recently made the move – the information that's NOT in the MFRC package.
So, You're Posted to Ottawa …
People in Ottawa seem to love their neighbourhoods, but the current consensus is to go west. With the future relocation of NDHQ, it will be more convenient to reside in Stittsville, Kanata or Barrhaven. The Queensway can be a bit of a nightmare at rush hour and Ottawa City Transpo get great marks with commuters.
That said, those Orleans folks really love it! And if you don't mind a bit of a drive, there are some really lovely villages on the outskirts of the National Capital Region. Sadly, no one has anything nice to say about the PMQ's in Uplands … hopefully, that's not your only option.
If you are coming from Eastern Canada or the US, you are in for a shock in terms of the cost of things. If you're coming from Alberta or Europe, your shock will be much more pleasant! Kids' sports are pricey in comparison to other parts of the country, but groceries seem to be quite reasonable. And you get to enjoy the abundance of fresh produce that Ontario offers. If you are coming to Ontario for the first time, you may find the taxes high, both property and income.
Some people have difficulty finding a doctor, particularly in the west end, so you might want to get all of your check-ups done before you get here, in case it takes a while. Doctors seem a bit easier to come by in Orleans. Folks seem to have no trouble finding dentists, vets or other healthcare providers though.
One of the big hurdles some spouses face is language. If you have the luxury of time, take advantage of second-language training if you need it. Also, your kids may have to play language catch-up depending on where you are coming from, because children in the English system take Core French right from Junior Kindergarten. If your kids have been in French Immersion or Francophone school, there are an abundance of choices. In terms of employment, language seems to be a factor for most people, but not everyone – there is hope!
Everyone agrees that Ottawa is safe and clean, with loads of fun things to do. MoneySense magazine ranks it as the #1 place to live in Canada! Take advantage of all of the cultural offerings and festivals. Canada Day on Parliament Hill is not to be missed! And sharpen your skates for a day on the Rideau Canal next winter!
We all know that no CF member actually wants to be posted to Ottawa (or so they say), but the quality of life there can be wonderful! Good luck!
Laura Keller spent 17 years married to a military man, who has recently retired from the CF. They live in Guelph, Ontario with their three kids and dog. Laura also writes her own blog at www.HappyCanadianHome.com.


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Right now, thousands of children are battling pediatric cancer and their families are facing mounting bills from expenses you might not think about - gas money to take their child to treatment, meals for mom or dad at the hospital and other everyday essentials. You can help families make sure they can get their child the treatment they need to survive by fundraising for the NCCS.
We are asking our supporters to rally their friends, family, and networks to support The National Children's Cancer Society's (NCCS) work. The NCCS has helped over 63,000 children with cancer and by becoming a NCCS fundraiser, you can help us reach even more.
Click here to join us!
500 North Broadway, Suite 1850, St Louis MO 63102314.241.1600 (phone) 314.241.1996 (fax)Copyright 2016. All Rights Reserved
contact us view our privacy policy, updated June 2015.


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May 26, 2016 Aerovista has a Boeing 737-500 under a lease agreement which has joined the Air Libya's fleet. MSN 25794 is equipped with 108 economy class and 8 business class configuration. The aircraft will operate in the North African region from its operations base in Ben Ghazi.About AerovistaAerovista is ... Read more
Mar 17, 2016 Nordic Aviation Capital (NAC), the world's largest turboprop aircraft lessor announced it is acquiring Jetscape Aviation Group (Jetscape), a leading player in regional jet leasing. The deal will see Nordic Aviation Capital expand into the regional jet arena, bringing 28 owned Embraer E-Jets, commitments ... Read more
Mar 08, 2016 Boeing and China Development Bank Financial Leasing Co., Ltd.(CDB Leasing) celebrated the delivery of the first Next-Generation 737 from the lessor's order book to China Eastern Airlines. It marks the first of 30 Boeing 737NG CDB Leasing has on order. "We are delighted to take delivery of CDB Leasing's first directly purchased Boeing airplane," said Wang Xuedong, ... Read more
Jan 05, 2016 Air Lease Corporation announced long term lease agreements with EVA Air (Taiwan) for four new B787-9s and two new B787-10s. These aircraft are from ALC's Dreamliner order book with Boeing and will deliver from mid-2018 through early 2020. These placements will bring the number of new Boeing widebody ... Read more
Nov 16, 2015 Boeing projects the Latin American commercial aviation market will grow at one of the highest rates in the world over the next 20 years. As a result, Boeing forecasts the region's airlines will need 3,050 new airplanes valued at $350 billion. "The economies of Latin America and the Caribbean will grow faster than the rest of the world over the long term," said Van Rex ... Read more
Nov 04, 2015 FLY Leasing Limited ("FLY"), a global leader in aircraft leasing, today announced that it has acquired a new Boeing 777-200LRF aircraft in a sale and 12-year leaseback transaction with a leading flag carrier. "This is our second B777-200LRF acquisition in the past month as ... Read more
Apr 07, 2015 CIT Group Inc., a global leader in transportation finance has placed a firm order for five more A321ceo aircraft, in effect doubling its most recent commitment for five A321ceo's signed at the 2014 Farnborough International Airshow and firmed up in November 2014. This latest ... Read more
Mar 27, 2015 DUBLIN, Ireland - International aircraft lessor Avolon announces today the delivery of its first Boeing 787-9 to Virgin Atlantic. Today's delivery is the first of four B787-9 aircraft scheduled for delivery to Virgin Atlantic by Avolon. Dómhnal Slattery, Chief Executive Officer, Avolon commented:... Read more
Jan 13, 2015 Toulouse, France - Airbus has officially launched the A321neo with 97 tonnes Maximum Take Off Weight (MTOW) having secured the first commitment from Air Lease Corporation (ALC). The Los Angeles based lessor signed a Memorandum of Understanding (MoU) for 30 more A321neo, upsizing its commitments at the ... Read more
Dec 03, 2014 New York, NY - CIT Group has firmed up its order for 15 A330-900neo aircraft and five A321ceo aircraft. CIT became one of the launch customers of the A330neo after signing its initial agreement in July 2014, at the Farnborough International Airshow. "Given our ... Read more


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Marvel Legends Series: Ben Reilly Spider-Man
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TRANSCRIPTION NOTES These notes relate to the transcriptions of primary witnesses that are given on disk. Some of the notes are more significant than others.
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Curriculum Designers, Inc. 2004 SK1 Notes: Notes: Notes: Dr. Heidi Hayes Jacobs! www.curriculum21.com! Revising teacher and


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- Registry Help Pages:
- At-a-Glance
Transformation Protocol
Printable PDF Protocol
Estimated bench time: 1 hour
Estimated total time: 3 hours (plus 14-18 hour incubation)
Transformations are essential to using the DNA Distribution Kits: resuspend the DNA sample in a well, transform the DNA into competent cells, and select single colonies. However, transformations can also be one of the more fickle laboratory techniques.
At iGEM HQ, we run test transformations of the DNA Distribution Kit with the following protocol. We have found that it is the best protocol to use with the DNA Distribution Kit and ensures high efficiency transformations.
- At iGEM HQ, we make our own stocks of NEB 10b competent cells. Competent cells purchased from vendors will have better efficiency.
- Make sure to test the competency of your cells with the provided Competent Cell Test Kit.
- Read through the entire protocol before starting!
|Resuspended DNA
|Resuspend DNA Distribution Kit well(s) with 10µl dH20. Pipet up and down several times, let sit for a few minutes. Resuspension will be red from cresol red dye.
|10pg/µl Control DNA
|1µl for control transformation. pSB1C3 w/ BBa_J04450, RFP on high-copy chloramphenicol resistant plasmid. Located in the Competent Cell Test Kit.
|Competent Cells
|50µl per transformation. iGEM HQ stores competent cells in aliquots of 260µl (5rxns total) at -80°C.
|2ml Microtubes
|One tube per transformation. Label tubes with part name or well location before starting.
|Floating Foam Tube Rack
|Place 2ml tubes in floating tube rack for better support when working on ice and for the heat shock in the water bath.
|Ice & ice bucket
|Fill bucket with ice, and pre-chill 2ml tubes (5min). Thaw competent cell stock on ice (10-15min).
|Lab Timer
|42°C water bath
|Set water bath to 42°C before starting.
|SOC Media
|200µl per transformation. SOC Media is better than LB Media for higher transformation efficiency. SOC Media should not contain antibiotics, and can be easily contaminated.
|37°C incubator
|Preferably with a rotor/shaker for 2ml tubes. Incubate petri plates overnight (non-agitated).
|Petri plates w/ LB agar and antibiotic
|2 plates per transformation: for 20µl and 200µl platings. Make sure to use appropriate antibiotic. Label with part name or well location before starting.
|Sterile spreader or glass beads
|Used to spread transformation across petri plates. Be sure to use sterile technique in between platings.
|Pipettes and Tips
|10µl, 20µl, 200µl tips and pipettes recommended
Setup & Protocol
When transforming competent cells, both timing and temperature are very important. Use a lab timer, follow the incubation temperatures closely, and keep materials on ice when required.
Resuspend DNA in selected wells in the Distribution Kit. Label 2ml tubes with part name or well location. Fill lab ice bucket with ice, and pre-chill 2ml tubes (one tube for each transformation, including your control) in a floating foam tube rack.
- Thaw competent cells on ice: This may take 10-15min for a 260µl stock. Dispose of unused competent cells. Do not refreeze unused thawed cells, as it will drastically reduce transformation efficiency.
- Pipette 50µl of competent cells into 2ml tube: 50µl in a 2ml tube per transformation. Tubes should be labeled, pre-chilled, and in a floating tube rack for support. Keep all tubes on ice. Don't forget a 2ml tube for your control.
- Pipette 1µl of resuspended DNA into 2ml tube: Pipette from well into appropriately labeled tube. Gently pipette up and down a few times. Keep all tubes on ice.
- Pipette 1µl of control DNA into 2ml tube: Pipette 1µl of 10pg/µl control into your control transformation. Gently pipette up and down a few times. Keep all tubes on ice.
- Close 2ml tubes, incubate on ice for 30min: Tubes may be gently agitated/flicked to mix solution, but return to ice immediately.
- Heat shock tubes at 42°C for 1 min: 2ml tubes should be in a floating foam tube rack. Place in water bath to ensure the bottoms of the tubes are submerged. Timing is critical.
- Incubate on ice for 5min: Return transformation tubes to ice bucket.
- Pipette 200µl SOC media to each transformation: SOC should be stored at 4°C, but can be warmed to room temperature before use. Check for contamination.
- Incubate at 37°C for 2 hours, shaker or rotor recommended:
- Pipette each transformation on two petri plates for a 20µl and 200µl plating: Pipette 20µl and 200µl of the transformation onto appropriately labeled plates. Spread with sterilized spreader or glass beads immediately. This helps ensure that you will be able to pick out a single colony.
- Incubate transformations overnight (14-18hr) at 37°C: Incubate the plates upside down (agar side facing up). If incubated for too long, colonies may overgrow and the antibiotics may start to break down; un-transformed cells will begin to grow.
- Pick single colonies: Pick single colonies from transformations: do a colony PCR to verify part size, make glycerol stocks, grow up cell cultures and miniprep.
- Count colonies for control transformation: Count colonies on the 20μl control plate and calculate your competent cell efficiency. Competent cells should have an efficiency of 1.5x10^8 to 6x10^8 cfu/µg DNA.
Other Resources
Transforming Your Part from iGEM Videos.
- Please note, this video may be outdated.


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Welcome Center
Welcome to the Village of Bourbonnais! We are proud to be the "Village of Friendship". We hope that you will take the time to explore our community and discover all that Bourbonnais has to offer. To assist you with settling in, we have compiled a list of links that we hope you find helpful in learning about local resources.
Bourbonnais Elementary School District - Our district is comprised of six buildings serving approximately 2700 of Bourbonnais' children. Our excellent staff is committed to providing quality learning experiences to all children focusing on both their intellectual and social development.
Bradley-Bourbonnais Community High School - Within a safe and secure environment and in cooperation with parents, students, and the community, BBCHS will provide well-rounded educational opportunities for students of varying abilities, needs, and socio-economic diversities. These educational opportunities will empower students to reach their full potential, to become life-long learners, to acquire subject-specific knowledge and skills, to be effective citizens of the community, to develop creative and critical thinking skills, to communicate their ideas effectively, and to develop a lifestyle that promotes overall health and wellness.
Olivet Nazarene University - A private, Christian, Liberal Arts University–a service of the Church of the Nazarene, theologically grounded in the Wesleyan tradition
Public Library
Bourbonnais Public Library - The purpose of the Bourbonnais Public Library District is to offer a lifelong learning experience for the people in the community it serves by providing access to global information resources and an inviting environment for cultural interaction.
Park District
Bourbonnais Township Park District - park district is responsible for the preservation of open space in a community, development of parks and providing recreation programs for all ages.
Garage Sale
In January of 2000, following a number of public meetings, the Board of Trustees adopted new regulations concerning the size and placement of garage and yard sale signs. (Ord. No. 99-1208)
- Off site garage and yard sale signs shall be allowed on Thursday, Friday and Saturdays only, and must be removed by 7:00 am on the following Monday.
- Off site garage and yard sale signs shall:
- Be no larger than two (2) feet by two (2) feet;
- Shall not be placed on trees or fences, utility poles, street light poles, traffic signals, street signs, stop signs or similar items;
- Contain the address of the property where the garage or yard-sale is being held;
- Not be posted within one hundred (1 00)feet in any direction of the intersection of Routes 45/52 and 102, including the landscape islands therein; and
- Not be posted on any Village property, including the Village Hall, Public Works Buildings, Village Parks, Village flower beds, landscape areas or drainage areas.
- No garage or yard sale sign shall be displayed on any portable device or vehicle parked on any public street or right of way.
- If signs are placed in the right of way, namely that area between a sidewalk and the curb, the person placing the sign shall first have the permission of the owner of the property adjoining the right of way, or that property owner would have the ability to remove and dispose of the signs.
- If the Village has to remove any garage or yard sale sign because the sign(s) do not meet these regulations,-the person or persons responsible for the placement of the sign(s) may be subject to a $50.00 removal fee.
Utility Information
Sanitary Sewer
Village of Bourbonnais
600 Main Street
Bourbonnais, IL
New residents need to call the Village at (815)933-1676 to arrange for sewer bills. Sewer bills are mailed monthly to the more than 6,000 customers in the system.
Residential rates are as follows:
Sewer Rates
The Village of Bourbonnais will raise rates for our customers January 1, 2012. Our overall rate increase of $610,000 per year is related to the capital improvements completed and additional capital improvements committed over the next two years, as well as the escalated cost to process the waste at KRMA. The new rates will appear on the February billing. The capital spending is necessary to maintain and upgrade our infrastructure to protect our environment and provide quality service to our customers.
An example of the charges to a typical customer's monthly sewer bill is broken down below:
Single Family Home: $26.75
Multi-Family Unit: $26.75
Mobile Home: $26.75
Non-Annexed: $28.35
This increase is the first rate increase since January 1997. We are cognizant of the current economic times and have successful cut costs to absorb increased expenses over the past 15 years but must adjust our rates to address needed infrastructure and the reality of the escalating cost of operating the system.
The Village's mission is to provide quality service in an environmentally safe manor at an affordable rate.
Commercial and industrial rates are based on water flow, and are billed on a monthly basis. Commercial and industrial users should contact the Sewer Billing Offices (815.933.1676) for information as to their respective bills.
Direct Debit Program Never worry about forgetting to pay your sewer bill again!
The Village is now offering automatic direct debit for paying your sewer bills. Click here to download the printable ACH to sign up. Once you complete the application, mail to: Sewer Village of Bourbonnais Sewer Billing Department, 600 Main Street, Bourbonnais, IL or bring in to the Village's Administrative Office.
Allied Waste Services
120 East Industrial Dr.
Momence, IL 60954
Aqua Illinois
1000 S Schuyler Avenue
Kankakee, IL
Ph# 815-352-9600
Toll free # 800-851-1305
Com Ed
Ph# 800-334-7661
Ph# 888-642-6748
Chicago Bears Training Camp
The Chicago Bears training camp, located on the campus of Olivet Nazarene University in Bourbonnais. The camp gives fans three weeks of almost daily practices to see their favorite players for free.
With the exception of concessions, everything is still free to the public — free admission and free parking. Only note that to maintain a family-friendly atmosphere, alcohol and smoking are not permitted on the campus.


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Available in multiple colors and in sizes S - 5XL at TeePublic.com
Cell Phone Cases, Mugs, & Other Miscellaneous Wares
Available from Redbubble.com
Available in multiple colors and in sizes S - 5XL at TeePublic.com
Available from Redbubble.com
Second book of Delvers LLC! Now in addition to monsters, Henry and Jason have to deal with…politics!
Want your book here? Advertise directly with DrewHayesNovels.com
Super Powereds Chapter: $250 / $125
Blades & Barriers Chapter: $125 / $125
Next Bonus Chapter: 4/28/2017 (Super Powereds)
How Do Bonus Chapters Work?
Note: We're having some server issues with the SuperPowereds.com site, so access has been erratic. Hope to have to issue fixed soon, thank for your patience.


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Steven Share
Meet Steven Share! Steven spent six years at Lord & Taylor in Philadelphia, NYC, and Washington DC, where he developed his public relations and human resources skills. He then spent six years as Senior Consultant for a private Customer Experience Management firm, where he was a business and Human Resources Consultant, and prided himself on being the "CMO" (Chief Morale Officer.) Steven was also a volunteer for the one of the nation's largest LGBTQ pride events serving on fundraising and special events committees for Capital Pride in DC for 8 years.
Steven joined Tribe 12 as Spectrum Philly's Director in 2014 and is honored to be on the forefront of building a vibrant, exciting LGBTQ Jewish community in Philadelphia. He is also Tribe 12's representative for JProud, a consortium of organizations working to become more LGBTQ inclusive, is on the Young Friends Board and Public Programs Committee at the National Museum of American Jewish History.
When he's not building communities or wandering the gay-bor-hood, Steven can be found spending time with friends and family or practicing yoga, namaste.
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We recently reported a novel anticancer small molecule, designated FL118, which was discovered via high throughput screening (HTS), and followed by hit-lead in vitro and in vivo analysis. FL118 selectively inhibits the expression of four major cancer survival-associated gene products (survivin, Mcl-1, XIAP, and cIAP2) and shows promising antitumor activity in animal models of human cancers when administered using a weekly x 4 schedule (Ling et al., PLOS ONE. 2012, 7: e45571). Here, we compared the antitumor efficacy and therapeutic index (TI) of FL118 in a newly developed Tween 80-free formulation that can be delivered intravenously (i.v.) and intraperitoneally (i.p.) against the previous Tween 80-containing formulation that can only be delivered via an i.p. route. We found that the maximum tolerated dose (MTD) for FL118 in the i.v. formulation increases 3-7 fold in comparison with the MTD of FL118 in the i.p. formulation. FL118 in the i.v. recipe was able to eliminate human tumor xenografts in all three major schedules tested (daily x 5, q2 x 5 and weekly x 5). In contrast, FL118 was able to eliminate human tumor xenografts in the i.p. formulation only with the weekly x 4 schedule previously reported. The TI of FL118 in the i.v. formulation reached 5-6 in the most effective schedule, while the TI of FL118 in the i.p. formulation was only 1.3 - 2. These findings overcome several clinical challenges including FL118 formulation to realize clinically compatible drug administration routes, and expanding effective treatment schedules. The striking improvement of the TI makes FL118 a much safer drug for further development toward clinical trials.
Resistance of cancer cells to treatment is the ultimate cause of cancer relapse due to the failure to eradicate cancer cells that possess multiple survival mechanisms upon treatment. Protein members in the inhibitor-of-apoptosis (IAP) and Bcl-2 families are major cancer-associated survival factors which play critical roles in treatment (drug and radiation) resistance. Specifically, survivin, an IAP member, is a pivotal molecule at the junction of cancer cell survival and division networks [1,2], and an inherent and induced drug/radiation resistance factor for various cancer types during treatment [3-21]. Mcl-1, a Bcl-2 family antiapoptotic protein, also plays important roles in cancer cell survival and resistance to drug/radiation treatment [22-35]. In addition, XIAP [36-45] and cIAP2 [27,46-50], both IAP family members, also play roles in cancer cell resistance and survival.
We have recently reported a novel antitumor small chemical molecule, FL118, which was discovered via high throughput screening (HTS) of compound libraries, followed by hit-to-lead in vitro and in vivo analysis [51]. FL118 selectively inhibits the expression of four cancer-associated gene products (survivin, Mcl-1, XIAP, cIAP2) in the IAP and Bcl-2 families [51]. Consistent with its versatile feature to target multiple cancer survival/proliferation-associated factors, we have shown that in a weekly x 4 schedule using its maximum tolerated dose (MTD) by the intraperitoneal (i.p.) route, FL118 shows striking antitumor activity in both human colon and head-&-neck cancers in animal models [51]. However, the i.p. route is not a clinical conventional route and may only be used for ovarian cancer patients. Instead, the intravenous (i.v.) injection of anticancer drugs is a common route in clinical practice. In this regard, we have developed a new i.v.-compatible formulation for FL118 which is Tween 80 free. In this study, we compared the antitumor efficacy and therapeutic index (TI) of FL118 in the newly developed i.v. formulation with that of FL118 in the previously tested i.p.-compatible formulation containing 10 - 20% of Tween 80. We found that FL118 in the i.v. formulation shows a much lower toxicity, and the MTD of FL118 is strikingly increased (MTD: 1.5 to 10 mg/kg in different schedules) in comparison with that of FL118 in the i.p. formulation (0.2 to 1.5 mg/kg in different schedules). FL118 in the i.v. formulation is able to eliminate xenograft tumors in animal models in all schedules tested, while FL118 in the i.p. formulation is unable to eliminate tumors in most schedules except in the weekly x 4 schedule previously described [51]. Furthermore, FL118 in the Tween 80-free i.v. formulation improved its TI more than 3 fold. These findings indicate that the Tween 80-free i.v. formulation makes FL118 a much safer antitumor drug. This new clinically-compatible i.v. formulation overcomes a big challenge for FL118 in regard to clinical development and now lays a strong foundation for FL118 to be moved into clinical trials in the near future.
Six to 12-week-old female athymic nude mice (nu/nu, body weight 20 - 25 g) were purchased from Charles River Laboratories International, Inc. (Wilmington, MA) or Harlan Sprague Dawley Inc. (Indianapolis, IN). Six to 12-week-old female SCID mice were purchased from Roswell Park Cancer Institute Division of Laboratory Animal Resources (DLAR). Mice were housed at 5 mice per cage with water and food ad libitum. All animal experiments were performed in accordance with our Institute Animal Care and Use Committee (IACUC) approved animal protocols.
FL118 formulation for i.p. administration: FL118 was dissolved in dimethyl sulfoxide (DMSO) to reach a concentration of 1 mg/ml, and the FL118 was further diluted into a solvent containing Tween-80 (10 - 20%) and saline (75 - 85%) to constitute the final formulated solution consisting of 0.05 mg/ml FL118, 5% DMSO (V/V), 10 - 20% Tween-80 (V/V), and 75-85% saline (V/V). Control solution (placebo or vehicle) is 5% DMSO, 10 - 20% Tween-80, and 75 - 85% saline without FL118. The formulated solution with or without FL118 was administered via i.p. injection in animal experiments with different administration schedules.
FL118 formulation for i.v. administration: The Tween 80-free formulation for i.v. administration is described in detail in our pending patent [52]. The i.v. formulation for FL118 in this study used the basic formulation recipe which contains FL118 (0.1 - 0.5 mg/ml), DMSO (5%), and hydroxypropyl-b-cyclodextrin (0.05 - 0.25%, w/v) in saline. The corresponding vehicle solution in the basic formulation recipe contains DMSO (5%) and hydroxypropyl-b-cyclodextrin (0.05 - 0.25%, w/v) in saline without FL118.
FL118 in the formulated solution was administered either by i.p. injection at a dose range of 0.2 - 0.75 mg/kg, or by i.v. injection at a dose range of 1.0 - 10.0 mg/kg in different drug administration schedules. In the i.p. injection, the following schedules were used: 1) once a day for 5 days (daily x 5); 2) every other day for 3 days on days 0, 2, and 4 (q2 x 3 or i.p. x 3); 3) every other day for 5 times (q2 x 5); 4) 2 times a week for 4 weeks (2day/wk x 4). Of note, the schedule of once a week for 4 weeks (weekly x 4) via i.p. routes was evaluated in detail in our previous study [51]. In the i.v. drug administration route, the following schedules were used: 1) only one injection on day 0 (i.v. x 1); 2) daily x 5; 3) q2 x 5; and 4) weekly x 4.
The MTD was defined as the highest drug dose at the defined drug administration schedule and route causing no drug-related lethality in mice with a body weight loss ≤ 20% of original body weight with temporary and reversible toxicities. The kinetics of drug-induced toxicities (e.g. body weight loss, mouse behavior, movement, diarrhea, and lethality) were determined daily for the first two weeks upon treatment or during drug treatment if treatment was more than two weeks. Then, drug toxicity was evaluated every other day. For FL118 formulated in the Tween 80-containing recipe in the i.p. route, we determined the FL118 MTD by starting with 0.1 mg per kg (mg/kg); we escalated doses by 0.1 – 0.25 mg/kg each time, which was dependent on the FL118 schedule, until MTD was achieved. Each dose was tested on a cohort of 5 mice in individual independent experiments. For some doses, experiments were repeated once or twice. For FL118 formulated in the Tween 80-free recipe in the i.v. route, we determined the FL118 MTD by starting with 1.0 mg/kg; we escalated doses by 0.5 – 2.5 mg/kg each time depending on FL118 schedules, until the MTD was achieved. Experiments using 3 mice were further confirmed by repeating the experiment using 5 mice.
All human tumor xenografts in mouse models were established from corresponding human cancer cell lines. Tumor xenografts were initially established from human cancer cell lines by subcutaneously injecting 1 - 3 x 106 cultured cancer cells in athymic nude or SCID mice. The xenografts were then passed several generations by transplanting 30 - 50 mg non-necrotic tumor tissues via a trocar from the passaged tumors. Human tumor xenografts used in this study include human head & neck tumors established from FaDu cells, and human colon cancer tumors established from HCT-8 and SW620 cell lines. Treatment was initiated 7 days after tumor transplantation (designated as day 0) at which time the xenografted tumor sizes were about 100 - 250 mm3, depending on the initial tumor mass used for implantation. Cancer cells used for tumor establishment were tested for mycoplasma before establishment of tumors.
During treatment, tumor size was monitored and documented daily or every other day dependent on the need during the first two weeks; then, three times a week for the following two weeks of post therapy, and twice a week thereafter. Two axes (mm) of a tumor (L, longest axis; W, shortest axis) were measured with a digital vernier caliper. Tumor volume (mm3) was calculated using a formula of tumor volume (mm3) = ½ (L x W2). If a tumor mass disappeared, we maintained the experimental mice for at least 30 days after the completion of drug treatment schedules for observation of tumor relapse.
The definition of therapeutic index (TI) varies in the literature. The standard TI calculation in animal models usually uses the lethal dose of a drug for 50% of the population (LD50) divided by the minimum effective dose for 50% of the population (ED50). From a conservative point of view, this standard method was not chosen to calculate the FL118 TI in this study (see further discussion in the Discussion section). Instead, we used a method that is much closer to the clinical situation which does not involve animal death. The common standard TI calculated in this conservative method was defined as the MTD dose divided by the minimal dose that requires a 100% inhibition of tumor growth during the treatment period (i.e. no tumor growing larger than the tumor size on the treatment day, which is defined as day 0). In this study, a more conservative method was used; the FL118 MTD dose divided by the minimal dose that requires a 100% inhibition of tumor growth (i.e. no tumor growing larger than the tumor size on day 0) during the treatment period, plus the same length period without FL118 treatment. That is, the FL118 TI was calculated as FL118 MTD divided by the FL118 minimal effective dose defined above.
Data analysis and figures were made using Sigma Plot or Microsoft Excel. The mean curves of tumor changes after treatment are presented as mean ± standard error (SE) from five mice. The body weight changes upon treatment in the Tables 2 and and44 are presented as the mean ± standard deviation (SD).
We recently reported the MTD (1.5 mg/kg) of FL118 in a Tween 80-containing formulation using a weekly x 4 schedule [51]. We now extend our studies of FL118 MTD using different drug administration schedules in animal models. Our results show that in the Tween 80-containing i.p. formulation, in contrast to 1.5 mg/kg FL118 MTD for the weekly x 4 schedule, the FL118 MTD in the daily x 5 schedule is only 0.2 mg/kg, and in the every other day for 3 doses (q2 x3) is 0.5 mg/kg. This result, together with other MTD information, is summarized in Table 1. The toxic lethal doses of FL118 in different dose comparisons are summarized in Table 2, and the lethal doses and MTD for the three schedules of daily x 5, q2 x 3, and weekly x 4 are diagramed in Figure 1.
Our goal is to move FL118 into clinical trials. In this regard, the Tween 80-contraining formulation can only be used for i.p. injection, since this recipe appears to be highly toxic to animals via i.v. routes (not shown). We therefore developed a Tween 80-free formulation for FL118 i.v. administration. We then determined FL118 MTD in the Tween 80-free formulation via i.v. injection. We surprisingly found that FL118 in the new Tween 80-free formulation is much less toxic to animals and significantly increases the FL118 MTD. The MTD data from different drug administration schedules are summarized in Table 3. The lethal doses and MTD are also summarized in Table 4, and diagramed in Figure 2. As shown, the MTD for FL118 in the Tween 80-free i.v. formulation increased 3-6 fold in comparison with its MTD in the Tween 80-containing i.p. formulation (Comparing data in Table 3 and Figure 2 with data in Table 1 and Figure 1). This finding suggests significant consequences in terms of potentially improving the FL118 therapeutic index (TI).
We expected that increased MTD for FL118 in the i.v. formulation should significantly improve its anticancer efficacy in comparison with the antitumor efficacy of FL118 in the Tween 80-containing formulation. Our studies indicate that FL118 in the new i.v. formulation effectively eliminates human tumor xenografts in animal models. Specifically, FL118 in the i.v. formulation was able to eliminate tumor mass in the daily x 5 schedule for both FaDu (head-&-neck) and SW620 (colon)-established tumor xenografts in animal models (Figure 3). Furthermore, FL118 in the i.v. formulation with the q2 x 5 schedule showed the best antitumor efficacy by eliminating human xenograft tumors with rare relapse in both FaDu and SW620 xenograft animal models (Figure 4). In contrast to the observation above, we found that FL118 in the i.p. formulation was unable to eliminate human FaDu and HCT-8-established tumor in the schedules of daily x 5, q2 x 3, and 2day/wk x 4 (Figure 6). Given our previous finding that FL118 in the i.p. formulation is able to eliminate xenograft tumors at its MTD (1.5 mg/kg) with weekly x 4 schedules [51], we proposed that the antitumor efficacy of FL118 in the Tween 80-containing i.p. formulation appeared to be highly schedule-dependent.
Together, it appears that the i.v.-compatible formulation of FL118 expanded its schedule scope, and improved antitumor efficacy, especially in the daily x 5 and q2 x 5 schedules (Figures 3, ,4).4). Interestingly, the q2 x 5 became the best schedule for FL118 in the i.v. formulation among three major clinically compatible drug i.v. administration schedules (daily x 5, q2 x 5, weekly x 5). Importantly, FL118 in the Tween 80-free formulation is compatible with both i.v. (a common route in the clinic) and i.p. (a rare route in the clinic) administration of FL118. Thus, the i.v.-compatible formulation would facilitate the efforts to move FL118 into clinical trials.
To alternatively confirm the findings shown in Figures 3, ,4,4, ,55 and and6,6, we expanded the dose range with 5 mice per group for individual dose points, and determined the TI for FL118 in the Tween 80-free i.v. formulation against FL118 in the Tween 80-containing i.p. formulation. Here, we chose the q2 x 5 schedule because it is the most effective schedule among three major schedules tested in this study (Figures 3, ,44 and and5).5). We determined FL118 antitumor efficacy in various sub-MTD doses from both formulations. Since FL118 in the Tween 80-containing formulation could only be injected via i.p. (too toxic for i.v. injection), we therefore chose to use the i.p. route for antitumor efficacy comparison in a series of defined FL118 doses in the experiment. Our studies revealed that for the human FaDu head-&-neck tumors, the minimal dose of FL118 that is required for a 100% inhibition of tumor growth (no growth in comparison with the tumor size on day 0) is 0.2 mg/kg in the i.p. formulation (Figure 7A) and is 0.25 mg/kg in the i.v. formulation (Figure 7B); for the human SW620 colon tumor, the minimal dose of FL118 is 0.3 mg/kg in the i.p. formulation (Figure 7C) and is between 0.25 mg/kg and 0.5 mg/kg in the i.v. formulation (Figure 7D). Based on the formula of TI = MTD/minimal effective dose, the FL118 TI in the i.p. formulation for the FaDu tumor will be 0.4/0.2 (TI = 2); and the FL118 TI in the i.v. formulation is 1.5/0.25 (TI = 6). Similarly, the TI of FL118 in the i.v. formulation is 0.4/0.3 (TI = 1.3) for the SW620 tumor; and the TI of FL118 in the i.v. formulation would be 1.5/0.3 (TI = 5) for the SW620 tumor. In short, the range of FL118 TI in the defined two types of tumor in the Tween 80 containing formulation is 1.3 – 2.0. In contrast, the range of FL118 TI in the same tumor types in the Tween 80-free formulation is 5.0 – 6.0. This would greatly improve the safety for FL118 administration in animal and/or humans.
It has been shown that abrogation of one or more of these four gene products, survivin, Mcl-1, XIAP and cIAP2, inhibits tumor growth, sensitizes drug resistant cancer cells to treatment, and induces apoptosis in various in vitro and in vivo models [53-61], although which one or more of these gene products is playing critical roles in these events may be cancer cell type specific. A great deal of chemopreventive and chemotherapeutic agents were reported to inhibit survivin expression as one of their mechanisms of action [62]. Among these agents, YM155 is very interesting and was shown to be a survivin expression suppressant that shows antitumor activity [63-65]. YM155 was also shown to sensitize cells to radiotherapy [66] or chemotherapy [67,68] in preclinical animal models. YM155 is currently in Phase I/II clinical trials [69-72]. However, based on the outcome from Phase II studies, only modest activity was observed [62,70,72-74]. Nevertheless, we have shown that YM155-mediated abrogation of Sp1 binding on the survivin promoter at -149 to -71 plays a role in its survivin transcription inhibition [75]. Interestingly, recent studies have shown that YM155 and its analog, NSC80467, appear to be DNA damaging antitumor agents, and suppression of survivin transcription could be a secondary event [76].
It is clear that development of additional small chemical molecule survivin inhibitors with high antitumor efficacy and low toxicity are still highly desirable for the treatment of cancer. However, survivin is a multifunctional molecule with unique multi-subcellular localizations in cancer cells. Survivin has been shown to associate with both mitotic spindles [77] and centromeres [78,79] during mitosis, [80] as well as on mitochondria [81]. Its expression is involved in inhibition of apoptosis, [77,81] and regulation of mitotic cell division, [78,79,82,83] as well as in promotion of the G1/S transition, [84-86] and regulation of gene transcription [86,87]. Thus, development of versatile survivin functional inhibitors may technically be more challenging than to develop survivin expression inhibitors. Our research group recently reported the discovery of a novel anticancer small chemical molecule, FL118, which was shown to selectively inhibit the expression of not only survivin, but also Mcl-1, XIAP, and cIAP2 with striking antitumor activity in the schedule of weekly x 4 in animal models [51]. While this is an important discovery, we still have challenges that need to be solved before we can move FL118 into clinical trials. One of our challenges is that although Tween 80 (polysorbate 80) is a FDA-acceptable solvent for drug formulation, 10 - 20% Tween 80 in the finally formulated solution is clearly too high a concentration for clinical application. Therefore, improvement of the current formulation for FL118 by decreasing the percentage of Tween 80 or replacing it with other more acceptable solvents might result in a favorable potential for FL118 to further decrease drug toxicity and increase drug MTD, and thus, improveFL118 antitumor efficacy and TI.
In this context, we have developed a Tween 80-free formulation for FL118 which is compatible with both i.v. and i.p. administration routes of the drug. Specifically, we had tried many solvent combinations in various concentrations and finally found that the cyclodextrin-based formulation, with or without a low percentage of other solvents (PG, PEG 300 or PEG 400), worked fine with FL118 [52]. In the present study, we used the basic Tween 80-free formulation containing hydroxypropyl-β-cyclodextrin without other solvents (refer to Methods section), which is the simplest recipe that can be used for i.v. injection of FL118. As we showed in this study, we surprisingly found that FL118 in this Tween 80-free new formulation exhibited much lower toxicity, and thus, significantly increased FL118 MTD in various drug administration schedules (see the data shown in Figure 2 and Table 3 versus Figure 1 and Table 1). This is a breakthrough finding because FL118 in the i.v. formulation showed outstanding antitumor activity in various drug administration schedules (Figures 3, ,44 and and5).5). This is in striking contrast to the antitumor outcome resulted from FL118 in the Tween 80-containing i.p. formulation (Figure 6). Nevertheless, we observed an interesting phenomenon that while FL118 in the Tween 80-free formulation shows very low toxicity to animals when delivered through i.v. routes, FL118 in this i.v. formulation showed a higher toxicity when injected through i.p. routes. In contrast, the i.p. route is the only route for FL118 in the Tween 80-containing formulation to be administrated, since the Tween 80 formulation solution itself was shown to be highly toxic when injected via the i.v. route. This phenomenon may not be significant in terms of FL118 in the Tween 80-free formulation which results in superior antitumor activity and low toxicity when injected via the i.v. route, since the i.v. route is the clinically compatible route for most anticancer drug delivery in hospitalized cancer patients with ovarian cancer patients the exception.
Previous studies have shown that mice-derived tumors with the exact same genetic background exhibit much different topotecan resistant behavior (i.e. some tumors show very sensitive, but others show very resistant responses to topotecan from the beginning), when the isolated tumors were sub-implanted on 20 individual mice and treated with topotecan [88]. Consistent with this phenomenon, we found that in some cases, the variation of tumor inhibition by FL118 could be significantly different among individual mice (i.e., Data in Figure 5). However, in most cases, the variation is within a reasonable range as shown in Figures 6 and and7.7. Of note, in Figures 6 and and7,7, we show some typical examples of the variation derived from five mice. Alternatively, the data from individual mice were shown for the readers to observe the real variation of tumor after FL118 treatment with various schedules (Figures 3, ,44 and and55).
It is known that the antitumor efficacy of a drug at its sub-MTD level is a foundation and gold standard for predicting the potential of a drug for its further development toward clinical application. This gold standard decides TI levels, which reflect the anticancer drug potential. Therefore, in the present study, we have compared in detail the TI of FL118 in the i.v. formulation versus FL118 in the i.p. formulation (Figure 7). We found that the Tween 80-free i.v. formulation decreases FL118 toxicity, and increases its MTD and anticancer efficacy (compare Figures 3, ,44 and and55 with Figure 6). Given the two types of human tumors used, the TI of FL118 in the Tween 80-free i.v. formulation is 5-6, but only 1.3-2 in the old Tween 80-containing i.p. formulation. We noted that the standard TI calculated in animal models usually uses the lethal dose of a drug for 50% of the population (LD50) divided by the minimum effective dose for 50% of the population (ED50) as mentioned in the Methods section. We did not choose this method to calculate TI for at least two reasons. First, different definitions of the minimum ED50 would derive much different TI. Second, using LD50 is less safe than using MTD in our view, since LD50 involves animal death, while using MTD, animal death would not be involved. In this regard, the FL118 TI derived in this study is a conservative number. It is possible that using other calculation methods may derive a much higher TI value. Furthermore, in clinical trials, toxicity in 50% of the population (TD50), rather than LD50, should be used. Therefore, the calculation method used in this study appears to be much closer to the situation used in clinical trials, since animal death was not involved for the calculation of FL118 TI in this study. We understand that since FL118 is highly effective to inhibit human tumor growth, we were able to get a very favorable TI number using our conservative calculation method. In the case of if a drug could only delay tumor growth rates during treatment period, the TI calculation method used in this study may not fit those types of drugs, since if using our defined method to calculate TI, the TI for such types of drugs will be smaller than 1, which would not lead to further development. In the case of such type of drugs, the LD50/ED50 may be a better choice for calculating the TI. Finally, we should mention that in order to have a comparison in the same condition during TI determination studies, and because i.p. formulation could not be used for i.v. administration, we chose i.p. routes to compare the antitumor efficacy of FL118 in i.v. formulation versus i.p. formulation (Figure 7). We expect that if FL118 in the i.v. formulation was delivered through i.v. administration, the TI could be even better. Nevertheless a TI at 5-6 is already high enough for safe delivery of the drug in vivo.
An additional interesting observation is that our previous studies demonstrated that FL118 at its MTD is able to eliminate human primary head-and-neck tumors in the schedule of weekly x 4 via the i.p. route [51]. However our present studies demonstrated that FL118 in the new formulation at either sub-MTD or MTD is unable to 100% eliminate FaDu-established head-&-neck tumors in the schedule of weekly x 5 (Figure 5). Whether this suggests that FL118 may be more effective for head-&-neck cancer directly from cancer patients than those from cancer cell line-derived tumors would be an intriguing question worthy of further investigation. If the future studies would derive positive results, the potential and the value of FL118 for clinical application to treat cancer patients would be further increased.
In summary, given the unique feature and new findings for FL118 shown in this study, plus the findings presented in our previous studies [51], it is clear that FL118 is a highly promising and potential anticancer agent. The findings described in this report overcome several challenges (e.g. FL118 formulation, clinically compatible route, expanded schedules and improved TI) on the way to moving FL118 toward clinical trials and beyond.
This work was sponsored in part by grants from the US Army Department of Defense (DOD, PC110408), Mesothelioma Applied Research Foundation (Alexandria, VA), and the Roswell Park Alliance Foundation to FL, and by shared resources supported by NCI Cancer Center Support Grant to Roswell Park Cancer Institute (CA016056). Of note, SC was partially paid by grants from FL during this work. We thank Dr. Shousong Cao (SC) for his help in some of animal experiments in this work. The authors would like to thank the Faculty Writing Group from the Pharmacology & Therapeutics Department of Roswell Park Cancer Institute for critically reading and commenting on this manuscript. These authors would also like to thank Dr. Suzanne M. Hess (Research Support Services, Roswell Park Cancer Institute, Buffalo NY) for critically reading and revising this manuscript. Finally, we would like to thank the Drug Synthesis and Chemistry Branch, Developmental Therapeutics Program (DTP), Division of Cancer Treatment and Diagnosis, National Cancer Institute (NCI) for providing chemical libraries and relevant hit analogs in the public domain they collected and/or synthesized as major compound sources during the process of drug screening and characterization.
FL118 will be further developed in Canget BioTekpharma LLC (www.canget-biotek.com), a Roswell Park Cancer Institute (RPCI) spinoff company. FL is the founder of Canget BioTekpharma. Otherwise, there is no other conflict of interest.
PubMed Central Canada is a service of the Canadian Institutes of Health Research (CIHR) working in partnership with the National Research Council's national science library in cooperation with the National Center for Biotechnology Information at the U.S. National Library of Medicine(NCBI/NLM). It includes content provided to the PubMed Central International archive by participating publishers.


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FEATURED: Voter Registration Among Young People in 2008
The new CIRCLE fact sheet "Voter Registration Among Young People in 2008" presents detailed information on registration rates among young people, broken down by racial and ethnic groups, differences in educational background, married and unmarried individuals, urbanicity, and state-by-state information. In 2000, voter registration among young people reached its lowest level (55%). Since then, young voters' registration has been higher, and the rate stayed about the same in 2004 (60%) and 2008 (61%.) Registration is important because registering to vote is sometimes more difficult than the act of voting itself.
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