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It's Free Stuff Thursday!Mar 22nd, 2012 | 100 Comments
Crush The Composition DVD Scott Kelby's hugely popular Crush The Composition class is now available on DVD! Filmed under the stars in front of a live audience in Downtown Tampa, Scott shares the secrets to nailing your composition in a way no other photographer has done. Pick up your copy at the Kelby Training Store. LeaveContinue…
It's Guest Blog Wednesday featuring Scott Strazzante!Mar 21st, 2012 | 16 Comments
When I was a kid, in lieu of hiring a babysitter, my mom would just plop me down in front of the television. I think I learned more about life from Mike and Carol Brady than my own parents. In fact, at the time, I looked a lot like Cousin Oliver, who was brought onContinue…
The Vinnie Award at Photoshop WorldMar 15th, 2012 | 5 Comments
We just got the crazy list of prizes that will be awarded to the winner of The Vincent Versace Award for Excellence in Digital Photography (or, as we like to call it, "The Vinnie") at Photoshop World in Washington DC! Vincent has managed to put together a list of prizes that individually would make anyContinue…
Printing 101 Notebook from Ron MartinsenMar 15th, 2012 | 4 Comments
Internationally renowned commercial photographer Ron Martinsen has just released Printing 101 Notebook: An Introduction to Fine Art Photography Printing, an eBook that is designed to help frustrated ink jet printer users get the most out of their investment by educating them on everything they will need to make great prints. With interviews and advice from industry legends like Vincent Versace,Continue…
It's Free Stuff Thursday!Mar 15th, 2012 | 60 Comments
NAPP Member Webinar with Fay Sirkis Next Tuesday, March 20th, NAPP (the National Association of Photoshop Professionals) is hosting an exclusive members-only webinar entitled A Stroke of Genius Photoshop Art Studio. Fay Sirkis will show you how to take your photographs and turn them into gorgeous paintings using Photoshop. If you're not a member ofContinue…
It's Guest Blog Wednesday featuring Dean Bradshaw!Mar 14th, 2012 | 27 Comments
Think like a digital ninja. First of all I'd like to thank Scott and Brad for inviting me to write – I'm a big fan of what they do and how they empower the world to be better creators. Without people like them spreading the amazing wealth of information we have at our fingertips itContinue…
Posts by Brad Moore


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about me
Grow a friendship through shared experiences
I am a succesful and strong person, who would like to share the experiences that life brings. Experiences are great alone, but when they are shared they can mean so much more.
I am relaxed amongst my true friends, able to have converstions at any level, any time, and just as happy to discovering a new place to eat, or wine to drink, as I am sitting home and just "being" with someone.
Enjoy a good laugh, and am able to find fun in a lot of things.
So firstly looking for a friend, then through sharing experiences a relationship may develop!
At a glance
|JR64's details
|JR64's ideal partner
|51 years old
|45 - 52 yrs old
|Adelaide - North & North Eastern Suburbs, SA
|Within 10km of his
|Body type
|Average, Athletic, A bit overweight
|6'3/190 cm
|5'6/167 cm - 6'2/188 cm
|Smoking habits
|Don't smoke
|Don't smoke
|Relationship status
|Separated, Single, Widowed, Divorced
|Have children
Yes, have children who don't live at home
|Yes, have children living at home sometimes, No, have no children, Yes, have children living at home, Yes, have children who don't live at home
|Wants children
|Don't want any (more) of my own ask me about yours
|Don't want any (more) of my own or anyone else's, Don't want any (more) of my own ask me about yours, Don't want any (more) of my own but yours are fine
|Average, Social
|Eye colour
|Hair colour
|Dark Brown
|Ethnic/cultural background
|Other Caucasian
|Political persuasion
|No strong beliefs
|Sign of the Zodiac
|Capricorn Check compatibility »
|Drinking habits
|Occasionally / socially
|Occasionally / socially, Often
|No special diet
|No special diet
|Have pets
|No, like pets but do not have any
|Education level
|Some college
|HR/Employment / Training
|Job role
What I'm looking for
I would like to find someone who is seeking companionship and friendship, and use that as a base for a relationship. Someone like minded who can go out and enjoy what life has to offer. Fun, loving and affectionate, with self respect and confidence.
- Female, for dating, friendship or companionship
My interests
- Music
- Like most types of music live in small venues
- Reading
- I like to read and do enjoy stories with some factual or real basis. I read a lot at work and this is an chance to relax and clear the the mind a little
- Movies & TV
- Enjoy a story well told
- Sport
- enjoying being envolved competitively
- Other Interests
- Wine and finding out about new things
My groups
Contact JR64
- Send a kiss to flirt and see if there is an initial attraction
- Open up a 30-day contact period* to send unlimited messages
- During the contact period you can also chat if JR64 is online now.
- Get to know JR64 safely and securely before you exchange your personal contact details
* One RSVP stamp is required per contact period.
- Last online:
- 28 Jun '15

subset: commoncrawl


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CHICAGO, Oct. 15 /PRNewswire/ -- The NFL and National Dairy Council (NDC) today launch Fuel Up to Play 60, a new initiative aimed at tackling childhood obesity by giving youth a voice in changing the school nutrition and physical activity environment. The program will reach 36 million youth in 60,000 elementary, middle and high schools during the 2009/2010 school year.
The youth-led program empowers children and teens to take charge of their health and work with school leaders to create more opportunities for 60 minutes of daily physical activity and to make more healthy foods available, such as low-fat and fat-free dairy foods, fruits, vegetables and whole grains. Since more than 50 percent of a student's daily calories are consumed at school, the school environment is an ideal setting for teaching these healthy behaviors so they become lifelong habits.(1)
"NFL is a proud partner of Fuel Up to Play 60. It is an important component of our overall NFL Play 60 campaign," says NFL Commissioner Roger Goodell. "Our goal is to raise awareness about the importance of staying fit and eating right, especially for America's young people. This partnership is a powerful alliance to address childhood obesity and emphasize the role of daily physical activity in a healthy lifestyle."
"National Dairy Council is honored to work together with the NFL on Fuel Up to Play 60," said Thomas P. Gallagher, chief executive officer of Dairy Management Inc., the managing organization for National Dairy Council. "Child nutrition, particularly in schools, has been a cornerstone of National Dairy Council for nearly a century. This program centers on youth taking the lead in changing the school environment through increasing opportunities for eating healthier and getting more physical activity."
How the Fuel Up to Play 60 Works
Schools and youth enroll for the program at FuelUp
|SOURCE National Dairy Council
Copyright©2009 PR Newswire.
All rights reserved


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Folks, there is no accident that Bloomberg posted this new video today.
I predict that we will be seeing this new UST money (U S Treasury) money in the banks next week or sooner! This UST money is gold backed - no more Federal Reserve fiat money.
Without a plan, without priorities in living, it's difficult - perhaps impossible - to achieve traction in experiencing your progress in a fulfilling life. I do believe life is meant to be fun, working your plan by living your priorities keeps you up to speed with all you can be, do and have.
Wednesday, June 12, 2013
(Another Sign) Bloomberg News posts video on new Treasury Bill - has US Constitution on front and is gold colored!
Posted by Steu Mann at 10:13 AM
Labels: UST bills
Subscribe to: Post Comments (Atom)


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Open Tuesday- Saturday 9 a.m.* - 5 p.m.
$7.00 per person
Free for children 12 months & under
201 E. Congress St. Lafayette, LA 70501 337.232.8500
*Summer hours for June and July
Memberships are available for museum visitors.
Membership levels consist of Individual Family,
Basic Family, Family Plus, and Senior Citizens.
Interested in a CMA Membership? Click Here.
|Join the CMA at "Uncle Sam's Jam"
July 4th ~ 3 pm to 10 pm
Arts, Crafts, Bubbles, Chalk Art
Food, Drinks, great Music and FIREWORKS!
Reading with Ringling
Ringling Bros. performars will host an exclusive book reading of "If I ran the Circus" by Dr. Seuss
Tuesday, July 7th - 11:30 am
Included with paid admission
Open for play at 9:00 am
Scrapbook Camp - Register NOW!
July 21-23
9 am - 12 pm
Click here for Camp Information
Work with our staff to plan the perfect field trip!
We can help to reinforce the subjects you are already teaching in your classrooms.
Want to see more special field trips?
|Book a Field Trip Today
© Copyright 2015, Childrens Museum of Acadiana. All rights reserved.


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On Tap for Today: An enlightened Wednesday
So, we're going to get some answers today -- about world peace, the future, the meaning of art and how to use LinkedIn.
First, consider that Palestinian novelist Samier El-Youssef will talk about the prospect of peace tonight at the Boswell Book Company. A Palestinian refugee now living in London, he will discuss one the most vexing political questions of the age: Is it possible to find a middle ground in the Israeli-Palestinian conflict? »Read Full Blog Post
Orwell meets animation in Youngblood's challenging 'Cartoon'
Asylums and hospitals. Circus cages and suburban cul-de-sacs. Tiny apartments, cramped submarines and the antechamber to hell.
Youngblood Theatre Company's plays regularly feature nightmarish, confined spaces in which a lost generation dreams forlornly of liberation. »Read Full Article
Martina McBride brings Christmas glow to Milwaukee Theatre
Saturday night's outdoor temperatures and drizzle belied a calendar that had already turned over to December.
Inside the Milwaukee Theatre, a multigenerational audience of revelers was greeted with all the trappings of the Christmas season as Martina McBride crafted a classic holiday extravaganza. »Read Full Article


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Flamingo Hotel By The Beach
Flamingo Hotel By The Beach
Hotel Guest Rating: 6.7/10
Jalan Tanjung Bungah
Tanjung Bungah, Penang 11200
Hotel Freebies Available*
• Generic Agoda Promotion show dates
• Free Internet in Room show dates
Flamingo Hotel By The Beach
Set in a prime location of Penang, Flamingo Hotel by the Beach puts everything the city has to offer just outside your doorstep. Featuring a complete list of amenities, guests will find their stay at the property a comfortable one. Service-minded staff will welcome and guide you at the Flamingo Hotel by the Beach. Guestrooms are fitted with all the amenities you need for a good night's sleep. In some of the rooms, guests can find internet access - wireless (complimentary), internet access - wireless, non smoking rooms, air conditioning, balcony/terrace. Entertain the hotel's recreational facilities, including fitness center, outdoor pool, spa, massage, children's playground. Discover all Penang has to offer by making Flamingo Hotel by the Beach your base. ...read more
Flamingo Hotel By The Beach Amenities
- 24-Hour Front Desk
- 24-Hour Room Service
- Air Conditioning
- American Express
- Balcony/Terrace
- Bar
- Business Center
- Car Hire
- Car Park
- Children's Playground
- Coffee/Tea Maker
- Complimentary Bottled Water
- Concierge
- Currency Exchange
- Daily Newspaper
- Desk
- Elevator
- English
- Facilities For Disabled Guests
- Family Room
- Fitness Center
- Free Wi-Fi In All Rooms
- Garden
- Hair Dryer
- In Room Safe
- Inhouse Movies
- Internet Access - Wireless
- Internet Access - Wireless (Complimentary)
- Ironing Facilities
- Jcb
- Kids Club
- Laundry Service
- Malay
- Massage
- Mastercard
- Meeting Facilities
- Mini Bar
- Newspapers
- Non Smoking Rooms
- Outdoor Pool
- Pool (Kids)
- Poolside Bar
- Restaurant
- Room Service
- Safety Deposit Boxes
- Salon
- Satellite/Cable Tv
- Shops
- Shower
- Smoking Area
- Spa
- Television Lcd/Plasma Screen
- Tours
- Visa
- Water Sports (Motorized)
- Water Sports (Non-Motorized)
- Wi-Fi In Public Areas
Hotel Guest Reviews of the Flamingo Hotel By The BeachOur hotel ratings and reviews are from real hotel guests. Priceline.com ensures that its reviews are guests-only by proactively sending hotel surveys to customers after they've completed their hotel stays. In the post-stay surveys, priceline.com hotel customers are asked a number of questions about their stay and the hotel. On a scale of 1-10 with 10 being the best, the survey asks guests to rate their overall experience and specifically rate the hotel's cleanliness, staff and location. Priceline.com does not allow site visitors to post unsolicited hotel reviews.
Lee from Nepean, Canada
February 8, 2012
Solo Traveler
February 8, 2012
Solo Traveler
on 2 different occasions the front desk gave my room number to people who could identify me by only my first name and nationality. not smart.
The hotel is clean and nicely maintained. I arrived (unknowingly) on a holiday weekend so it was packed with families - large noisy families - but they were enjoying themselves!
Reviews of Flamingo Hotel By The Beach
(1 - 1 of 1 review)
(1 - 1 of 1 review)
from $55


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PVC welded wire mesh roll is an ideal material for various fences, its PVC coating is attached with a strong adhesive which prolongs its working life drastically. besides, this kind of welded mesh roll could resist allali, acid, rust and UV greatly. But the installation of PVC welded wire mesh roll could be a little difficult without the aid of concrete which helps keep the fence posts vertical. Therefore, we would like to offer an easier way to install a PVC coated welded fence without concrete.
·Step 1
Measure and calculate the total perimeter of the fence area so that you could know how much welded mesh roll you need.
·Step 2
Dig a post hole at each of the corners whose diameter should be about 3 inches larger than that of the post. Put the corner post into the hole. Make sure the post is vertical enough, you may need a level or plumb to help you. Scrap some soil into the holes until they are full and tamp the soil to make it tightly.
·Step 3
Attach one end of the welded mesh roll with staples, make the corner of the fence roll the center of the nail and fix a staple every 6 inches to fasten the roll firmly into the post. Pay attention to make the width of the roll parallel to the post. You'd better start from the top and work your way downward to the end. Then unravel the roll and
·Step 4
When finishing a roll, you should cut the end to stop on the center of the fence post. Stapling the end of the second roll with that of the first with 16-gauge staples to make the joint well-knit. Then continue installing the fence until all the four sides are encompassed with the fence roll.


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- Brasserie Red-Banded Porcelain Cups & Saucers, Set of 4 $59.95
- Monogrammed Champagne Flute, Set of 4 $59.95
- Vintage Etched Champagne Flutes, Set of 4 $51.95
- Somerset Champagne Flutes, Set of 4 Sugg. Price: $75.95 Sale $53.99
- Dorset Champagne Coupe, Set of 2 $59.95
- Riedel Grape Champagne Coupes, Set of 2 Sugg. Price: $72 Our Price: $64
- Riedel Grape Champagne Flutes, Set of 2 Sugg. Price: $72 Our Price: $64
- Riedel Sommeliers Champagne Flute $68
- Riedel Vinum Champagne Flute, Set of 2 Sugg. Price: $65.90 Our Price: $54.95
- Schott Zwiesel Pure Champagne Flutes, Set of 6 $84
- Monogrammed Glass Ice Bucket $69.95
- Presidio Silver-Plated Ice Bucket $99.95
- Waring Commercial Electric Wine Opener $99.95
- Beeswax Candles $29.95 – $59.95
Valentine's Day Tabletop
Start Valentine's Day off with your favorite coffee or hot tea in our Valentine glasses and mugs. Or toast your loved one in the evening with our Valentine glassware such as our monogrammed champagne flutes. Find Valentines Day mugs and bar glasses online and at your local Williams-Sonoma store.
We've designed our classic flutes to be utilitarian yet beautiful, so they're great for both casual entertaining and everyday use. This well priced European stemware is made of brilliant, lead free crystal for a timeless look with exceptional durability. ...
Elevate the pleasures of sparkling wine with our special setperfect for entertaining or gift giving. Designed to bring out the best in your bubbly, Riedel's stemless tumblers echo the graceful silhouettes of classic Champagne flutes. Use them for serving ...
Perfect for the bride and groom on their wedding day, these toasting flutes feature one of Waterfords most treasured patterns. Lismore stemware was inspired by Irelands spectacular Lismore Castle, once home to Sir Walter Raleigh. Waterfords master artisans hand ...


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You can now invite anyone to meet at your favorite Starbucks.
Limited-time feature
28 year old woman | Hopkins, MN, USA | Seeking men 25-33 within 20 miles
Active within 5 days
Looking for a good match who makes me laugh!
Things to know about me: - I love my faith, family, and friends - My family is very close and does a lot together...I have the cutest niece and nephews! - I love to laugh and have mastered the art of sarcasm:) - Lifelong Minnesotan - Never met a dog I don't like (especially my 4 year old yellow lab Molli) - Fall days are my favorite especially when spent outside - I like to stay active and do a fair amount of running...which is good because I have a terrible sweet tooth! - Love new restaurants and happy hours - Summer nights playing softball - My second home in the summer is my family's cabin in Nisswa, MN - I would eat breakfast food for every meal if I could! - What else do I like: camping, being a homeowner, being on the lake, holiday traditions, coffee, white wine, coffee, dessert, sushi...did I mention coffee (I drink way too much coffee!), country music, traveling, road trips, and the list goes on!! I would love to find someone who enjoys laughing with me. Someone who likes to go out and try new restaurants or get a drink...but enjoys a night at home with a good movie or friends as well. Someone who is kind and finds their faith important. Motivated in their career but puts their family and friends first. All gentlemen and romantics welcomed too:)
Camping , Coffee and conversation , Business networking , Cooking , Dining out , Music and concerts , Exploring new areas , Playing cards , Playing sports , Religion/Spiritual , Travel/Sightseeing , Volunteering , Watching sports , Wine tasting
Baseball, Cycling, Golf, Running, Skiing, Soccer, Swimming, Walking / Hiking
I exercise 5 or more times per week.
I have Dogs
I have a 4 year old yellow lab named Molli!
Some other viewpoint
West End, D.C., Baltimore, Cabin up North, the lakes in Uptown
University of St. Thomas, St. Paul, MN
Favorite Show: Castle Favorite Music: Country (but i listen to it all) Favorite Color: Purple (Go Tommies...Go Ravens!) Favorite Flower: Tulips...just in case you ever need to know;) Favorite place I've been: Greece
For fun i enjoy going out with friends and trying new restaurants, or staying in and attempting to cook up something new! I love to spend time with my niece and nephews, who always provide tons of laughter.
Gone Girl
Z{{Cta}} {{#if HasMoreInfo}} ?{{CtaSecondary}} {{/if}}
|What she is looking for
|5'6" (167cms)
|5'8" (172cms) to 6'7" (200cms)
|Body type:
|Athletic and toned
|About average, Athletic and toned
|No preference
|Light brown
|Black, Light brown, Dark brown, Blonde, Dark blonde
|No Way
|No Way
|Social Drinker
|No preference
|Financial / Accounting / Real Estate
|No preference
|I'll tell you later
|No preference
|Never Married
|Never Married
|Have kids:
|Wants kids:
|Definitely, Someday
|White / Caucasian
|No preference
|Christian / Catholic
|Christian / Catholic, Christian / Protestant, Christian / Other
|No preference
|Bachelors degree
|No preference
I loved being a Tommie! I am now a gopher close to finishing up my masters degree!


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ClarkConnect Is Now ClearOS: Enterprise 5.1 Available
ClearOS, formerly known as the ClarkConnect distro, with firewall, content filter and fileserver, is now in version 5.1.
A new module in ClearOS should protect users from phishing attacks. Developers also upgraded the core system from CentOS 5.3 to 5.4 and replaced the apt package manager with yum. Samba 3.4.3 provides support for Windows 7. Details are in the project release notes.
Apart from the name change, a new feature named ClearSDN was introduced. The service currently in beta provides ClearOS users with free software updates, backups and DNS management. Upgrades for filters, antispam and antivirus programs, support and other services do require a paid subscription, however.
ClearOS 5.1 is available for free download of ISO images, source code and even a VMware image. Upgrades from ClarkConnect 4.x and later are also available.
ClarkConnect is Now ClearOS - Dec 24, 2009 ArticleI work for Open Invention Network "http://www.openinventionnetwork.com" a community of parties with a mission to protect and promote Linux. I'm having difficulty locating a contact email address and/or phone number for Peter Baldwin, Chief Technical Officer, for the Clear Foundation. Can you help??
Thank you.
Pete Montano
email: firstname.lastname@example.com
Office Phone: 704-341-5888
Issue 177/2015
Buy this issue as a PDF
NoScript Flaw
Mozilla's script blocker add-on could be putting malware sites on the whitelist.
RIP SSLv3
The Internet community officially banishes the notoriously unsafe Secure Sockets Layer protocol.
Mate 1.1 Arrives
Popular desktop environment continues the Gnome 2 legacy – with new support for the Gnome 3 toolkit.
US Government Requires HTTPS
The Obama White House has issued a memorandum telling all US government agencies they must use HTTPS for all websites and web communication.
Mozilla Signs Firefox Add-Ons
New program will dial up security for the Firefox browser.
Fedora 22 Arrives
Red Hat's community distro embraces the cloud.
Code.org and College Board Team Reach Out for Talented High School Coders
New partnership will bring more and better CS training to US schools
A Peek Inside TeslaCrypt Ransomware
Criminals offer online help over Tor network
Mumblehard Still Spams
Sophisticated malware is still present on Joomla and WordPress sites around the world.
Launchpad Gets Git
Future versions of Ubuntu's code service will support the popular Git version control system used with Linux and other open source projects.


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'Talent' Tops Tuesday for NBC
NBC earned a 7.0 rating/12 share for the night, comfortably beating
In the adults 18-49 demographic, NBC's 3.5 rating snagged the top spot over ABC's 2.8. CBS, 2.0, came in third, followed by FOX, 1.7, and The CW, 0.6.
"America's Got Talent" drew a 7.0/13 at 8 p.m., holding off an
NBC stayed in front at 9 p.m. as "America's Got Talent" improved to 7.9/13. Game 3 of the NBA Finals between San Antonio and Cleveland posted a 5.1/9. "The Unit," 4.6/7, was third for CBS, beating out a
At 10 p.m., a "Law & Order: SVU" rerun completed an NBC sweep of the night with a 6.1/11. ABC's NBA coverage improved a little to 5.7/10, while CBS' "48 Hours Mystery" scored a 5.1/9.


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Cock in all of her holes she can take it easy
Cute foxy hoe is so nasty and wild most cant take it
Sexy ex-GF pussy nailed till she cant take it
Fuck that white pussy big cock nutsher..she cant handle it
See Tory Lane get fucked hard in all holes It starts with her sucking his cock until she deepthroats it and gags on it She then sits on his huge cock
horny brunette would take it all day in the ass if she could
All Rebecca wanted for her big day was a big cock...so she
Chrystine pours water all over herself and stuffs a big corn cob inside her pussy. She gets so excited that she pees all over the floor. Oops
This slut is out to prove she can take it all
so horny because she hadn't got a great fuck in months so she plays with her toys starting with her dildo sucking it like a real cock and riding
Ebony stud Justyn Blade whips out his hard cock so his white friend can suck on it then take it in his ass
Its big cock day for her so she gets right to it
Barbie Blaze is cum hungry so she takes it all
Bustylicious bitch receives fucked so good she cant wait to reach her big O
Big Booty Ayana Angel getting so drilled doggystyle she cant wait to get cummed
Jules cant fit it all in her mouth
Big butt Ayana Angel getting so fucked from behind she cant wait to get cummed
Sexy big assed Alanah Rae gets fucked so good she cant wait to get gooed
Saana has traveled to Porn Valley all the way from Finland so she can get some big cock
Sheena Shaw has a big ass made for cock so she is gets it hard
2 She-males 1 man suck cock, fuck and take it in the ass...
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Although advanced-stage cervical cancer can benefit from current treatments, approximately 30% patients may fail after definitive treatment eventually. Therefore, exploring alternative molecular therapeutic approaches is imperatively needed for this disease. We have recently shown that activation of AMP-activated protein kinase (AMPK), a metabolic sensor, hampers cervical cancer cell growth through blocking the Wnt/β-catenin signaling activity. Here, we report that activated AMPK (p-AMPK) also inhibits cervical cancer cell growth by counteracting FOXM1 function.
Effect of the activation of AMPK on FOXM1 expression was examined by hypoxia and glucose deprivation, as well as pharmacological AMPK activators such as A23187, AICAR and metformin. RT Q-PCR and Western blot analysis were employed to investigate the activities of AMPK, FOXM1 and AKT/FOXO3a signaling.
Consistent with our previous findings, the activation of AMPK by either AMPK activators such as AICAR, A23187, metformin, glucose deprivation or hypoxia significantly inhibited the cervical cancer cell growth. Importantly, we found that activated AMPK activity was concomitantly associated with the reduction of both the mRNA and protein levels of FOXM1. Mechanistically, we showed that activated AMPK was able to reduce AKT mediated phosphorylation of p-FOXO3a (Ser253). Interestingly, activated AMPK could not cause any significant changes in FOXM1 in cervical cancer cells in which endogenous FOXO3a levels were knocked down using siRNAs, suggesting that FOXO3a is involved in the suppression of FOXM1.
Taken together, our results suggest the activated AMPK impedes cervical cancer cell growth through reducing the expression of FOXM1.
Keywords:AMPK; FOXM1; FOXO3a; Cervical cancer
Cervical cancer results from uncontrolled growth of malignant cells started within the uterine cervix and is one of the most common malignancies in women worldwide [1-3]. Although this disease is almost preventable with routine genetic screening and vaccination, more than 80% of cervical cancers with a majority in the advanced stage are currently found in developing countries including China, leading to a high risk of recurrence and poor survival [2,4]. Thus, there is a compelling need to explore novel therapeutic interventions for this disease.
Emerging evidence suggests that targeting cancer cell metabolism is a promising therapeutic approach in human cancers. AMP-activated protein kinase (AMPK) is a known cellular metabolic sensor and plays an important role in the control of energy homeostasis in response to external stresses [5-8]. Recent studies have documented that pharmacological activation of AMPK is able to block cancer cell growth in various human cancers [8-11]. Indeed, we have previously reported that pharmaceutical AMPK activators such as AICAR (ATP-dependent) and A23187 (ATP-independent) could suppress cervical cancer cell growth in the presence or absence of LKB1, an upstream kinase of AMPK [10]. We also proposed mechanistic evidence showing that metformin, AICAR and A23187 suppress cervical cancer cell growth through reducing DVL3, a positive effector of Wnt/β-catenin signaling cascade which has been shown to be constitutively active during cervical cancer development [12]. Yet, it is still believed that there are other molecular mechanisms by which these pharmaceutical AMPK activators suppress cancer cell growth. The understanding of these mechanisms will assist in exploring better therapeutic regimes when using these drugs.
Forkhead Box M1 (FOXM1) is a member of the Forkhead Box transcription factors which is essential for cell proliferation and apoptosis in the development and function of many organs [13-17]. We previously reported that aberrant upregulation of FOXM1 is associated with the progression and development of human cervical squamous cell carcinoma (SCC) [18]. Biochemical and functional studies confirmed that FOXM1 is critically involved in cervical cancer cell growth through upregulating cyclin B1, cyclin D1 and cdc25B and downregulating p27 and p21 expressions. These findings suggest that FOXM1 plays a vital role in cervical cancer cell growth and oncogenesis.
In this study, we reported that the activated AMPK inhibits the cell growth by reducing FOXM1 expression in human cervical cancer cells upon treatments with hypoxia, glucose deprivation and pharmaceutical AMPK activators. We provided both biochemical and functional evidence to support our findings that the repression of FOXM1 expression of AMPK is dependent on the AKT/FOXO3a/FOXM1 signaling cascade.
Cell lines and reagents
Cervical cancer cell lines HeLa, CaSki, C33A and SiHa (American Type Culture Collection, Rockville, Md., USA) (cell line authentication was done by in-house STR DNA profiling analysis) were employed in this study. They were maintained in Dulbecco's Modified Eagle Medium (DMEM) (Invitrogen, Carlsbad, CA) supplemented with 10% (v/v) fetal bovine serum (Gibco), 100 units/ml penicillin/streptomycin (Gibco) at 37°C in an incubator with humidified atmosphere of 5% CO2 and 95% air. AMPK activators AICAR, A23187 and metformin and AKT inhibitor LY294002 were obtained from Tocris Bioscience (Bristol, UK). FOXM1 inhibitor Thiostrepton was purchased from Calbiochem (La Jolla, CA, USA).
Plasmids and cell transfection
To study the effects of enforced FOXM1 expression, the FOXM1c-expressing plasmid pcDNA3–FOXM1c was used because the c isoform has higher transactivating activity and is expressed dominantly in cells as well as tissues. Whereas, the pcDNA3 empty vector was used in mock transfections as control. Besides, the vector-based shRNA plasmid pTER–FOXM1 was used to knockdown endogenous FOXM1. All of these plasmids had been described previously [18]. As controls in knockdown assays, the p-super GFP and pcDNA3 vectors were used in mock transactions. To knockdown human FOXO3a, the TriFECTa RNAi Kit which contains three siRNAs targeting human FOXO3a was purchased from IDT (Integrated DNA Technologies, Inc., Iowa, USA). Cell transfection was carried out using LipofectAMINETM 2000 (Invitrogen) according to the manufacturer's instructions. Expression patterns were analyzed by Western blotting. The parental vector pEGFP-C1 was used as empty vector control.
Cell proliferation assay
Cell proliferation kit (XTT) (Roche, Basel, Switzerland) was used to measure cell viability according to the manufacturer's protocol. Three independent experiments were performed in triplicates.
RNA extraction and quantitative reverse transcriptase–PCR (Q-PCR)
According to the instruction of the manufacturer, total RNA was extracted using TRIzol reagent (Invitrogen). Complementary DNA (cDNA) was subsequently synthesized using a reverse transcription reagent kit (Applied Biosystems, Foster City). The expression level of FOXM1 was then evaluated by q-PCR in an ABI PRISM™ 7500 system (Applied Biosystems) using Taqman® Gene expression Assays; human FOXM1 (Assay ID: Hs00153543_m1). The human 18S rRNA (Assay ID: Hs99999901_m1) was used as an internal control.
Western blot analysis
Proteins in cell lysates were separated by 10% SDS-PAGE and transferred to polyvinylidene-difluoride (PVDF) membranes. The membranes were blotted with 5% skimmed milk and subsequently probed overnight at 4°C with primary antibodies specific for p-AMPKα, AMPKα, p-AKT, AKT, p-FOXO3a, FOXO3a (Cell Signaling, Beverly, MA, USA), FOXM1 (Santa Cruz Biotechnology, Inc., Santa Cruz, CA, USA) and β-actin (Sigma-Aldrich, St. Louis, MO, USA) and then incubated with horseradish peroxidase conjugated goat anti-rabbit or anti-mouse secondary antibody (Amersham, Uppsala, Sweden). Immunodetection was performed with enhanced chemiluminescent reagent solution (AmershamTM ECLTM) and visualized using medical X-ray film.
Data analysis
Student's t test was applied to the data analysis. All data were expressed as mean ± SEM. P-value of less than 0.05 was considered as significant.
Increased AMPK activity inhibits cervical cancer cell growth by suppressing FOXM1 expression
Consistent with our previous findings [12], this study also showed that the cell growth of cervical cancer cell lines such as Caski and SiHa was significantly inhibited by the AMPK activator metformin on a time and dose dependent manner (Figure 1A). Similarly, other AMPK activators such as AICAR and A23187 displayed remarkable inhibitory effect on cervical cancer cells (data not shown), confirming that activation of AMPK is able to reduce cervical cancer cell growth.
Figure 1. Activation of AMPK by pharmaceutical AMPK activators suppresses expression of FOXM1. (A) XTT cell proliferation assay showed that the growth rates of cervical cells; Caski and SiHa, were significantly reduced in a dose and time dependent manner upon the treatment of metformin (10 mM and 20 mM) when compared with the control medium. (B) Western blot analysis showed that the level of p-AMPKα was increased, while the level of FOXM1 was reduced in cervical cancer cells (Caski, C33A and Hela) when treated with AICAR (1 mM), A23187 (2 μM) and metformin (25 mM) for various time points. (C) RT-Q-PCR analysis demonstrated that the FOXM1 mRNA level of C33A and SiHa cells was remarkably reduced when treated with metformin (25 mM) and A23187 (2 μM) from 16 hrs to 24 hrs. The 18S gene was used as an internal control.
As FOXM1 is a master regulator of cancer cell growth, it is of interest to examine whether increased AMPK activity has any functional impact on FOXM1 in cervical cancer oncogenesis. Upon treatment of AICAR (1 mM), A23187 (2 μM), metformin (25 mM), glucose deprivation and hypoxia on the cervical cancer cell lines Caski, C33A and HeLa, we found that FOXM1 expression was drastically decreased while AMPK activity [p-AMPK (Thr172)]was elevated concomitantly (Figure 1B and Figure 2). Interestingly, Q-PCR analysis also demonstrated that the mRNA level of FOXM1 in C33A and SiHa cells was remarkably reduced upon treatment of metformin (25 mM) and A23187 (2 μM) in a time dependent manner (Figure 1C). This finding indicates that AMPK activated by these pharmaceutical activators could suppress FOXM1 expression at both protein and mRNA levels.
Figure 2. Activation of AMPK by glucose deprivation and hypoxia inhibits cell growth in cervical cancer cells. Caski cells treated by glucose deprivation and hypoxia at various time intervals showed an increased of p-AMPKα but a reduction of FOXM1.
Activated AMPK represses FOXM1 expression through blocking the AKT/FOXO3a signaling pathway
FOXO3a is well known to be one of the FOXO transcription factors that functions downstream of PI3K-PTEN-AKT (PKB) signaling in modulating cell growth [19]. Along the signaling cascade, FOXO3a is a negative regulator of FOXM1 expression [20]. To investigate whether the suppressive effect of AMPK on FOXM1 is mediated via FOXO3a, we first examined the intensity of FOXO3a dephosphorylation by metformin. Upon treatment of metformin (25 mM) on the cervical cancer cell line C33A, not only FOXM1 expression diminished remarkably but also the phosphorylation of AKT and the AKT-specific phosphorylation of FOXO3a (Ser253) (Figure 3A). We then examined whether the PI3K/AKT inhibitor LY294002 could reduce FOXM1 expression in cervical cancer cells. As expected, C33A cells exhibited decreased intensity of AKT-specific phosphorylation of FOXO3a (Ser253) as well as FOXM1 expression upon the treatment of LY294002 (10 μM) (Figure 3B). To further assess whether FOXO3a is primarily involved in the reduction of FOXM1 induced by AMPK activation but not an off-target pharmaceutical effect, siRNA-based knockdown of FOXO3a in C33A cells was carried out. Western blot analysis revealed that cervical cancer cells with depletion of endogenous FOXO3a did not show altered FOXM1 expression even when AMPK was activated subsequently by metformin (25 mM) (Figure 3C). Taken together, our data support that inhibition of FOXM1 by AMPK activation is attributed to the repression on AKT and its downstream, AKT-specific phosphorylation of FOXO3a (Ser253) in cervical cancer cells.
Figure 3. Activation of AMPK represses FOXM1 expression through inhibiting the AKT/FOXO3a signaling pathway. (A) Upon treatment of metformin (25 mM) in cervical cancer cells (C33A), the expression of FOXM1 diminished remarkably and the phosphorylation of AKT and AKT-specific phosphorylation of FOXO3a (Ser253) decreased concomitantly. (B) Co-treatment of PI3K/AKT inhibitor, LY294002 (10 μM), inhibited p-AKT and concomitantly reduced the levels of FOXO3a (Ser253) and FOXM1 in C33A cells. (C) Depletion of endogenous FOXO3a in C33A cells using siRNAs showed that FOXO3a expression is required for the suppression of FOXM1 by metformin (25 mM) treatment.
Ectopic expression of FOXM1 rescues AMPK-mediated cell growth inhibition
Given that activation of AMPK leads to growth inhibition of cervical cancer cells through reduction of both the mRNA and protein levels of FOXM1, we sought to determine whether enforced expression of exogenous FOXM1 could counteract the AMPK-induced suppressive effect. C33A and SiHa cells were transiently transfected with FOXM1c-expressing plasmid and treated with metformin (20 mM). Consistent with our previous findings [18], XTT cell proliferation analysis showed that enforced expression of FOXM1c significantly promoted cell proliferation in both C33A (P = 0.00007) and SiHa (P = 0.0004) cells as compared with the vector control (Figure 4A). Importantly, C33A and SiHa cells with ectopic expression of FOXM1c could significantly reduce the effect of AMPK-mediated cell proliferation inhibition as compared with their vector controls upon treatment of metformin (20 mM) (Figure 4A). Such counteracting effect of ectopic FOXM1c was particularly evident in SiHa cells (Figure 4A). Indeed, Western blot analysis confirmed that there was no reduction in the expression of FOXM1 in FOXM1c-transfected SiHa cells upon treatment of metformin (25 mM) for 24 hrs (Figure 4B). Collectively, these findings confirm that activation of AMPK by hypoxia and glucose deprivation, as well as pharmacological AMPK activators inhibits cervical cancer cell growth, and this effect is dependent on the endogenous expression level of FOXM1.
Figure 4. Ectopic expression of FOXM1c could rescue AMPK mediated cell growth inhibition in cervical cancer cells. (A) XTT cell proliferation assay showed that the growth rates of C33A and SiHa cells with ectopic expression of FOXM1c (OE) were significantly increased as compared with empty vector control (VC). C33A and SiHa cells with ectopic expression of FOXM1c showed a less inhibitory effect on cell growth rate as compared with the vector controls upon treatment of metformin (20 mM). (B) Western blot analysis showed that the level of FOXM1 (including exogenous FOXM1c) could not be reduced in SiHa cells when treated with metformin (25 mM) for 24 hrs. (C) The level of p-AMPKα remained constant when C33A cells were treated with FOXM1 specific inhibitor, thiostrepton (5 μM). (D) Depletion of the endogenous FOXM1 by shRNA knockdown approach could not affect the level of p-AMPKα. Both sh1 and sh2 represent two independent pTER–FOXM1 transfections, while C1 and C2 represent the vector controls.
FOXM1 acts as an AMPK downstream effector
Previous experiments have demonstrated that reduction of FOXM1 is a common scenario when AMPK is activated in cervical cancer cells. As FOXM1 is a key transcription factor, we sought to determine whether alteration of FOXM1 levels causes a feedback control on AMPK activity. To this end, we treated C33A cells with the FOXM1 specific inhibitor thiostrepton to suppress FOXM1 expression. Upon treatment of thiostrepton (5 μM), FOXM1 expression was significantly suppressed, whereas the expression of p-AMPKα (Thr172) was unchanged (Figure 4C). Similarly, knockdown of endogenous FOXM1 using shRNAs did not reveal any discernible change on the expression level of p-AMPKα (Thr172) in C33A cells (Figure 4D). Taken together, p-AMPKα activity per se is not altered by FOXM1 suppression induced by thiostrepton treatment or shRNA knockdown, implying that AMPK is acting upstream of FOXM1 and there is no feedback loop. Our analysis strongly supports that increased AMPK activity down-regulates FOXM1 through the AKT/FOXO3a/FOXM1 signaling cascade (Figure 5).
Figure 5. A schematic diagram to illustrate AMPK/AKT/FOXO3a/FOXM1 as the proposed molecular mechanism by which activated AMPK down-regulates FOXM1 expression.
Recent studies have suggested that targeting cancer cell metabolism is an alternative therapeutic approach in cancer treatment. AMPK is a pivotal energy sensor governing normal and cancer cell metabolism. Our previous research has shown that pharmaceutical AMPK activators are able to repress cervical cancer cell growth through targeting DVL3 in the Wnt/β-catenin signaling pathway [12]. In this study, we report another molecular mechanism by which AMPK can retard cervical cancer cell growth: inhibition of FOXM1 function via AMPK/AKT/FOXO3a signaling. We demonstrated that AMPK activated by either micro-environmental stresses or pharmaceutical AMPK activators could reduce FOXM1 expression through blocking the AKT/FOXO3a signaling pathway, that in turn impaired cervical cancer cell growth.
The Forkhead box transcription factor FOXM1 regulates a number of key cell cycle regulators that control the G1 to S and the G2 to M transitions [21-26]. Accumulating evidences have shown that the upregulation of FOXM1 is often involved in the development of various human cancers [27-32]. We previously reported that there is a progressive increase in FOXM1 level in the progression of human cervical cancer [18]. The inhibition of FOXM1 by genetic or pharmaceutical approach significantly impairs tumor growth of this cancer in vitro and in vivo[18,25,27,33], suggesting that targeting FOXM1 is an appealing and potential approach for anticancer therapeutics. On the other hand, we and others have proved that activation of AMPK is able to inhibit the growth of various human cancers including cervical cancer [10,34-36]. The pharmacological activation of AMPK using AICAR or metformin has been shown to inhibit cell growth and induce cell apoptosis of a wide spectrum of cancer cells through modulation of p53 [37], p27 [38,39], or p21 [18,40], or DVL3 in Wnt/β-catenin signaling in cervical cancer [12]. Herein, we demonstrated that the activation of AMPK by various AMPK activators or hypoxia and glucose deprivation stresses induces a remarkable reduction of FOXM1 which in turn leads to a remarkable decrease of cervical cancer cell growth in both HPV positive (Caski, Hela and SiHa) and HPV negative (C33A) cell lines. On the other hand, ectopic expression of FOXM1c could counteract the suppressive effect of activated AMPK. These findings indicate that FOXM1 is a key oncogenic factor associated with cervical cancer cell growth, while activated AMPK inhibits cervical cancer cell growth through downregulation of endogenous FOXM1.
In fact, we demonstrated that reduction of FOXM1 occurred at both the mRNA but and protein levels in cervical cancer cells. This is suggestive of a transcriptional suppression of FOXM1 by its upstream effectors. Previous studies have reported that FOXM1 is transcriptionally suppressed by FOXO3a, which is a critical downstream effector of the PI3K/AKT/FOXO signaling pathway [19,20]. For example, it has been reported that FOXO3a represses estrogen receptors α (ERα) activity in breast cancer cells through an alternative mechanism by which FOXO3a interacts and downregulates the expression of FOXM1 [29,41]. These evidences imply that the reduction of FOXM1 at both the mRNA and protein levels is due to the presence of FOXO3a in cervical cancer cells. In fact, our data using siRNA-mediated FOXO3a knockdown showed that FOXO3a expression is required for FOXM1 reduction upon activation of AMPK.
How do activated AMPK leads to FOXO3a accumulating in the nucleus and blocking the transcription of FOXM1 mRNA? FOXO3a, which belongs to the class O of Forkhead/winged helix box (FOXO) transcription factors, is a key tumor suppressor involved in different cellular processes [42]. FOXO3a is modified by phosphorylation, acetylation and ubiquitination, which in turn affect its nuclear/cytoplasm shuttling, transcriptional activity and stability [43-46]. It is known that the PI3K/AKT signaling is the main regulatory pathway of FOXO3a [44,47,48]. When PI3K/AKT signaling is activated, FOXO3a is not only inactivated and phosphorylated at Thr32, Ser253 and Ser315 residues, but is also exported out from the nucleus to the cytoplasm where it is ubiquitinated and subjected to proteasome-dependent degradation [43,48]. Therefore, nuclear FOXO3a functions as transcriptional regulator, whereas cytoplasmic FOXO3a is considered inactive [46]. On the other hand, AKT is a signaling kinase known to be inactivated by activated AMPK [49,50]. In our study, treatment of either AMPK activator (metformin) or PI3K/AKT inhibitor (LY294002) showed significant inhibition of p-AKT and a remarkable reduction of p-FOXO3a (Ser253), an AKT-specific phosphorylation site, suggesting that suppression of FOXO3a is reduced. As a result, FOXO3a will be more nuclear-localized and activated to inhibit FOXM1 mRNA expression in cervical cancer cells.
Aforementioned, AMPK activation can commonly inhibit FOXM1 expression in cervical cancer cells. However, whether there exists a feedback loop on the activity of AMPK is still unknown. To test this notion, cervical cancer cells were treated with the FOXM1 inhibitor thiostrepton to investigate the effect on AMPK activation. Results showed that treatment of thiostrepton only reduced expression of FOXM1 but not the activity of AMPK. In addition, depletion of endogenous FOXM1 using shRNAs gave similar findings as the treatment of thiostrepton, implying that FOXM1 is acting downstream of AMPK without any feedback regulation.
In summary, our findings here prove that activation of AMPK frequently inhibits cervical cancer cells. More importantly, we demonstrated that activated AMPK reduces FOXM1 by counteracting the AKT/FOXO3a/FOXM1 signaling axis. Our findings shed light on the application of AMPK activators in the treatment of human cervical cancer.
Competing interests
The authors declare that they have no competing interests.
Authors' contributions
MY and DC designed research; MY, DC and VL performed the experiments; DC, VL and KY contributed new reagents-analytic tools; MY, DC and HN analyzed and interpreted data; MY and DC wrote the manuscript. All authors were involved in editing the manuscript and had final approval of the submitted and published versions.
This study was supported by Wong Check She Charitable Foundation.
Yang HJ, Liu VW, Tsang PC, Yip AM, Tam KF, Wong LC, Ng TY, Ngan HY: Quantification of human papillomavirus DNA in the plasma of patients with cervical cancer.
Int J Gynecol Cancer 2004, 14(5):903-910. PubMed Abstract | Publisher Full Text
Robinson-Bennett BL, Deford J, Diaz-Arrastia C, Levine L, Wang HQ, Hannigan EV, Papaconstantinou J: Implications of tyrosine phosphoproteomics in cervical carcinogenesis.
J Carcinog 2008, 7:2. PubMed Abstract | BioMed Central Full Text | PubMed Central Full Text
Parkin DM, Bray F, Ferlay J, Pisani P: Global cancer statistics, 2002.
CA Cancer J Clin 2005, 55(2):74-108. PubMed Abstract | Publisher Full Text
Nishio S, Katsumata N, Matsumoto K, Tanabe H, Yonemori K, Kohno T, Shimizu C, Ando M, Kasamatsu T, Fujiwara Y: Analysis of the clinicopathological prognosis of stage IVb cervical carcinoma.
Oncol Rep 2008, 19(2):497-503. PubMed Abstract | Publisher Full Text
Witczak CA, Sharoff CG, Goodyear LJ: AMP-activated protein kinase in skeletal muscle: from structure and localization to its role as a master regulator of cellular metabolism.
Cell Mol Life Sci 2008, 65(23):3737-3755. PubMed Abstract | Publisher Full Text
Carling D: AMP-activated protein kinase: balancing the scales.
Biochimie 2005, 87(1):87-91. PubMed Abstract | Publisher Full Text
Hardie DG: AMPK: a key regulator of energy balance in the single cell and the whole organism.
Shackelford DB, Shaw RJ: The LKB1-AMPK pathway: metabolism and growth control in tumour suppression.
Nat Rev Cancer 2009, 9(8):563-575. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Kuhajda FP: AMP-activated protein kinase and human cancer: cancer metabolism revisited.
Yu SY, Chan DW, Liu VW, Ngan HY: Inhibition of cervical cancer cell growth through activation of upstream kinases of AMP-activated protein kinase.
Tumour Biol 2009, 30(2):80-85. PubMed Abstract | Publisher Full Text
Fay JR, Steele V, Crowell JA: Energy homeostasis and cancer prevention: the AMP-activated protein kinase.
Cancer Prev Res (Phila) 2009, 2(4):301-309. Publisher Full Text
Kwan HT, Chan DW, Cai PC, Mak CS, Yung MM, Leung TH, Wong OG, Cheung AN, Ngan HY: AMPK activators suppress cervical cancer cell growth through inhibition of DVL3 mediated Wnt/beta-catenin signaling activity.
PLoS One 2013, 8(1):e53597. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Wierstra I, Alves J: FOXM1, a typical proliferation-associated transcription factor.
Biol Chem 2007, 388(12):1257-1274. PubMed Abstract | Publisher Full Text
Wang X, Kiyokawa H, Dennewitz MB, Costa RH: The Forkhead Box m1b transcription factor is essential for hepatocyte DNA replication and mitosis during mouse liver regeneration.
Proc Natl Acad Sci USA 2002, 99(26):16881-16886. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Katoh M: Human FOX gene family (Review).
Int J Oncol 2004, 25(5):1495-1500. PubMed Abstract | Publisher Full Text
Kim IM, Ramakrishna S, Gusarova GA, Yoder HM, Costa RH, Kalinichenko VV: The forkhead box m1 transcription factor is essential for embryonic development of pulmonary vasculature.
J Biol Chem 2005, 280(23):22278-22286. PubMed Abstract | Publisher Full Text
Yoshida Y, Wang IC, Yoder HM, Davidson NO, Costa RH: The forkhead box M1 transcription factor contributes to the development and growth of mouse colorectal cancer.
Gastroenterology 2007, 132(4):1420-1431. PubMed Abstract | Publisher Full Text
Chan DW, Yu SY, Chiu PM, Yao KM, Liu VW, Cheung AN, Ngan HY: Over-expression of FOXM1 transcription factor is associated with cervical cancer progression and pathogenesis.
J Pathol 2008, 215(3):245-252. PubMed Abstract | Publisher Full Text
Wilson MS, Brosens JJ, Schwenen HD, Lam EW: FOXO and FOXM1 in Cancer: The FOXO-FOXM1 Axis Shapes the Outcome of Cancer Chemotherapy.
Curr Drug Targets 2011, 12(9):1256-1266. PubMed Abstract | Publisher Full Text
Zhao F, Lam EW: Role of the forkhead transcription factor FOXO-FOXM1 axis in cancer and drug resistance.
Front Med 2012, 6(4):376-380. PubMed Abstract | Publisher Full Text
Leung TW, Lin SS, Tsang AC, Tong CS, Ching JC, Leung WY, Gimlich R, Wong GG, Yao KM: Over-expression of FoxM1 stimulates cyclin B1 expression.
FEBS Lett 2001, 507(1):59-66. PubMed Abstract | Publisher Full Text
Fung TK, Poon RY: A roller coaster ride with the mitotic cyclins.
Semin Cell Dev Biol 2005, 16(3):335-342. PubMed Abstract | Publisher Full Text
Wang IC, Chen YJ, Hughes D, Petrovic V, Major ML, Park HJ, Tan Y, Ackerson T, Costa RH: Forkhead box M1 regulates the transcriptional network of genes essential for mitotic progression and genes encoding the SCF (Skp2-Cks1) ubiquitin ligase.
Mol Cell Biol 2005, 25(24):10875-10894. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Laoukili J, Kooistra MR, Bras A, Kauw J, Kerkhoven RM, Morrison A, Clevers H, Medema RH: FoxM1 is required for execution of the mitotic programme and chromosome stability.
Nat Cell Biol 2005, 7(2):126-136. PubMed Abstract | Publisher Full Text
Lok GT, Chan DW, Liu VW, Hui WW, Leung TH, Yao KM, Ngan HY: Aberrant activation of ERK/FOXM1 signaling cascade triggers the cell migration/invasion in ovarian cancer cells.
PLoS One 2011, 6(8):e23790. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Lam AK, Ngan AW, Leung MH, Kwok DC, Liu VW, Chan DW, Leung WY, Yao KM: FOXM1b, which is present at elevated levels in cancer cells, has a greater transforming potential than FOXM1c.
Front Oncol 2013, 3:11. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Chan DW, Hui WW, Cai PC, Liu MX, Yung MM, Mak CS, Leung TH, Chan KK, Ngan HY: Targeting GRB7/ERK/FOXM1 signaling pathway impairs aggressiveness of ovarian cancer cells.
PLoS One 2012, 7(12):e52578. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Teh MT, Wong ST, Neill GW, Ghali LR, Philpott MP, Quinn AG: FOXM1 is a downstream target of Gli1 in basal cell carcinomas.
Cancer Res 2002, 62(16):4773-4780. PubMed Abstract | Publisher Full Text
Madureira PA, Varshochi R, Constantinidou D, Francis RE, Coombes RC, Yao KM, Lam EW: The Forkhead box M1 protein regulates the transcription of the estrogen receptor alpha in breast cancer cells.
J Biol Chem 2006, 281(35):25167-25176. PubMed Abstract | Publisher Full Text
Kim IM, Ackerson T, Ramakrishna S, Tretiakova M, Wang IC, Kalin TV, Major ML, Gusarova GA, Yoder HM, Costa RH, et al.: The Forkhead Box m1 transcription factor stimulates the proliferation of tumor cells during development of lung cancer.
Cancer Res 2006, 66(4):2153-2161. PubMed Abstract | Publisher Full Text
Douard R, Moutereau S, Pernet P, Chimingqi M, Allory Y, Manivet P, Conti M, Vaubourdolle M, Cugnenc PH, Loric S: Sonic Hedgehog-dependent proliferation in a series of patients with colorectal cancer.
Surgery 2006, 139(5):665-670. PubMed Abstract | Publisher Full Text
Kalinichenko VV, Major ML, Wang X, Petrovic V, Kuechle J, Yoder HM, Dennewitz MB, Shin B, Datta A, Raychaudhuri P, et al.: Foxm1b transcription factor is essential for development of hepatocellular carcinomas and is negatively regulated by the p19ARF tumor suppressor.
Genes Dev 2004, 18(7):830-850. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Ahmad A, Wang Z, Kong D, Ali S, Li Y, Banerjee S, Ali R, Sarkar FH: FoxM1 down-regulation leads to inhibition of proliferation, migration and invasion of breast cancer cells through the modulation of extra-cellular matrix degrading factors.
Breast Cancer Res Treat 2010, 122(2):337-346. PubMed Abstract | Publisher Full Text
Kim YH, Liang H, Liu X, Lee JS, Cho JY, Cheong JH, Kim H, Li M, Downey TJ, Dyer MD, et al.: AMPKalpha modulation in cancer progression: multilayer integrative analysis of the whole transcriptome in Asian gastric cancer.
Cancer Res 2012, 72(10):2512-2521. PubMed Abstract | Publisher Full Text
Guan TJ, Qin FJ, Du JH, Geng L, Zhang YY, Li M: AICAR inhibits proliferation and induced S-phase arrest, and promotes apoptosis in CaSki cells.
Acta Pharmacol Sin 2007, 28(12):1984-1990. PubMed Abstract | Publisher Full Text
Din FV, Valanciute A, Houde VP, Zibrova D, Green KA, Sakamoto K, Alessi DR, Dunlop MG: Aspirin inhibits mTOR signaling, activates AMP-activated protein kinase, and induces autophagy in colorectal cancer cells.
Gastroenterology 2012, 142(7):1504-1515.
e1503PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Karuman P, Gozani O, Odze RD, Zhou XC, Zhu H, Shaw R, Brien TP, Bozzuto CD, Ooi D, Cantley LC, et al.: The Peutz-Jegher gene product LKB1 is a mediator of p53-dependent cell death.
Mol Cell 2001, 7(6):1307-1319. PubMed Abstract | Publisher Full Text
Liang J, Shao SH, Xu ZX, Hennessy B, Ding Z, Larrea M, Kondo S, Dumont DJ, Gutterman JU, Walker CL, et al.: The energy sensing LKB1-AMPK pathway regulates p27(kip1) phosphorylation mediating the decision to enter autophagy or apoptosis.
Nat Cell Biol 2007, 9(2):218-224. PubMed Abstract | Publisher Full Text
Short JD, Houston KD, Dere R, Cai SL, Kim J, Johnson CL, Broaddus RR, Shen J, Miyamoto S, Tamanoi F, et al.: AMP-activated protein kinase signaling results in cytoplasmic sequestration of p27.
Cancer Res 2008, 68(16):6496-6506. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Tiainen M, Vaahtomeri K, Ylikorkala A, Makela TP: Growth arrest by the LKB1 tumor suppressor: induction of p21(WAF1/CIP1).
Hum Mol Genet 2002, 11(13):1497-1504. PubMed Abstract | Publisher Full Text
Zou Y, Tsai WB, Cheng CJ, Hsu C, Chung YM, Li PC, Lin SH, Hu MC: Forkhead box transcription factor FOXO3a suppresses estrogen-dependent breast cancer cell proliferation and tumorigenesis.
Breast Cancer Res 2008, 10(1):R21. PubMed Abstract | BioMed Central Full Text | PubMed Central Full Text
Schmidt M, Fernandez de Mattos S, van der Horst A, Klompmaker R, Kops GJ, Lam EW, Burgering BM, Medema RH: Cell cycle inhibition by FoxO forkhead transcription factors involves downregulation of cyclin D.
Mol Cell Biol 2002, 22(22):7842-7852. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Myatt SS, Lam EW: The emerging roles of forkhead box (Fox) proteins in cancer.
Nat Rev Cancer 2007, 7(11):847-859. PubMed Abstract | Publisher Full Text
Fernandez De Mattos S, Villalonga P, Clardy J, Lam EW: FOXO3a mediates the cytotoxic effects of cisplatin in colon cancer cells.
Mol Cancer Ther 2008, 7(10):3237-3246. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Brunet A, Bonni A, Zigmond MJ, Lin MZ, Juo P, Hu LS, Anderson MJ, Arden KC, Blenis J, Greenberg ME: Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor.
Cell 1999, 96(6):857-868. PubMed Abstract | Publisher Full Text
Motta MC, Divecha N, Lemieux M, Kamel C, Chen D, Gu W, Bultsma Y, McBurney M, Guarente L: Mammalian SIRT1 represses forkhead transcription factors.
Cell 2004, 116(4):551-563. PubMed Abstract | Publisher Full Text
Chiacchiera F, Simone C: The AMPK-FoxO3A axis as a target for cancer treatment.
Cell Cycle 2010, 9(6):1091-1096. PubMed Abstract | Publisher Full Text
Link W, Oyarzabal J, Serelde BG, Albarran MI, Rabal O, Cebria A, Alfonso P, Fominaya J, Renner O, Peregrina S, et al.: Chemical interrogation of FOXO3a nuclear translocation identifies potent and selective inhibitors of phosphoinositide 3-kinases.
J Biol Chem 2009, 284(41):28392-28400. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Rattan R, Giri S, Hartmann LC, Shridhar V: Metformin attenuates ovarian cancer cell growth in an AMP-kinase dispensable manner.
J Cell Mol Med 2011, 15(1):166-178. PubMed Abstract | Publisher Full Text
Li C, Liu VW, Chan DW, Yao KM, Ngan HY: LY294002 and metformin cooperatively enhance the inhibition of growth and the induction of apoptosis of ovarian cancer cells.
Int J Gynecol Cancer 2012, 22(1):15-22. PubMed Abstract | Publisher Full Text
Pre-publication history
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Gordon Young, editor of The Drum, offers his insight and opinion on various matters relating to media and marketing.
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Much of this material is the sort of stuff which inspired many of those journalists reared on films like 'All the President's Men' to get into this profession in the first place.
Now The Drum is not really in the business of holding the political classes to account. But even we can't help stubbing our toe on the odd forgotten issue lying hidden in the long grass. Very often it's the sort of stuff that would have been picked up by the old investigation teams of the past who once tended our public interest landscape.
A few examples spring to mind. The story of former newspaper executive Steve Sampson for example. He was the man who persuaded Scottish Enterprise to invest £1m in his start up Talent Nation only to be accused of transferring much of this cash into his own personal account shortly afterwards, leaving staff unpaid, a bankrupt business and much acrimony behind. Since other investors in Talent Nation – which was placed into liquidation by Scottish Enterprise - included Premier League football players and other sports stars you would have expected to see this story appear across the Scottish press, despite Sampson's denials that he had done anything wrong. Apart from in The Drum, it hardly merited a mention elsewhere.
Another example of where the Scottish media were surprisingly mute was in reporting the resignation of high-flying Glasgow City Council leader, Steven Purcell back in 2010.
He shocked the political establishing by suddenly resigning – citing a nervous breakdown.
But it wasn't long before rumours of drug abuse and allegations of patronage surfaced, fuelled by the fact that he received a visit from police warning him of potential blackmail.
To put this in context, it is the equivalent of the career of Boris Johnson suddenly going up in a puff of cocaine; Purcell was seen as a potential Scottish First Minister.
The saga was covered unconvincingly. The Herald, for example, initially carried surprisingly little comment about the scandal.
Perhaps Purcell was simply really good at crisis PR. And he certainly had some good advisers. They included Jack Irvine – once an editor of The Scottish Sun (and colleague of Steve Sampson) - who is now seen as a Scottish Max Clifford. His business is called Media House.
Meanwhile he received legal advice from Irvine's friend and business associate Peter Watson of Levy & McRae (who also at one stage advised Steve Sampson).
Levy & McRae were certainly well placed to advise on media matters. His team also worked (and still does) for many newspapers including the Herald, advising them on what could and could not, be published.
The arrangement struck The Drum as strange, which is why we wrote to every newspaper which was represented by Levy & McRae asking if they thought that the set up – where they were running stories on somebody also represented by the firm – might add up to a conflict of interest.
The Sunday Herald eventually carried a full page editorial which read: "There have been hints that some Scottish newspapers have pulled their punches because editors have been too close to Steven Purcell or worse have been cowed in submission by Peter Watson and PR firm Media House."
Herald MD Tim Blott confirmed: "We are currently reviewing our relationship with Levy & McRae in the light about our editors' concerns about any current or future conflict of interests."
Adding impetus to this process was the fact that one arm of Levy & McRae had demanded a right of reply for a piece another arm of the firm had cleared for publication in a Herald title.
However, despite the public posturing the group re-appointed Levy & McRae, albeit with a new set of safeguards.
Levy & McRae were also well placed to advise Purcell on criminal law. Strathclyde Police, which investigated the Purcell resignation, sought advice from the Crown Office on how to proceed.
Watson acts for the Strathclyde Police Federation and has advised the Crown Office and its head honcho the Lord Advocate in the past.
The Drum has first-hand experience of this, because in 2009 the then Lord Advocate, Elish Angiolini, instructed Levy & McRae to take action against our company.
Our then sister title The Firm had published allegations that while Angiolini was Procurator Fiscal in Aberdeen, her office had failed to handle an investigation into an alleged paedophile ring properly.
In the end she dropped her defamation claim and a referral to the Press Complaints Commission was settled without an adjudication being made.
In the aftermath The Drum wanted to find out who had paid for her action – because in a defamation case the only recourse an individual can hope for is compensation which would be paid to them personally.
So did she pay her own bills? As the Lord Advocate she employs more lawyers than anybody else in Scotland, so you would have thought she would have been able to get advice for free. Or did the Government pay for outsourcing this to a private firm?
And there was another point too. The victim at the heart of the original allegations – a Down Syndrome child – received £15,000 as part of the criminal compensation scheme. Angiolini's costs could have amounted to more than this. So did she spend more public money defending her reputation than this young girl received for being raped?
Of course there is also a bigger picture here. If a government starts using its vast resource to sue journalists it will inevitably compromise the ability of media to do its jobs and call politicians and their political appointees to account.
That was why we lodged a Freedom of Information Request with the Crown Office. And I suspect it was also why it was simply denied. To this day we do not know who footed Angiolini's bill.
Now in itself none of this is hard evidence of wrongdoing. But it is evidence of all the untold stories lying submerged in the murk of Scottish public life. At the moment it is, in my view, short sighted commercial pressures that are stopping media owners doing their jobs. But in the future they could be further muzzled by McLeveson.
I have to say the composition of the Leveson advisory panel the Scottish Government are proposing doesn't fill me with confidence.
It includes one Peter Watson of Levy & McRae. Perhaps it might adopt a paragraph the firm had on its website as its credo: "With a low profile, we aim to keep clients off the front page and take swift and effective action where required. Being networked at the highest levels and having access to major decision makers is key to our success."
Levy & McRae have been in touch on behalf of Elish Angiolini asking me to set the record straight in one important respect; which I am happy to do. Originally I wrote that the Press Complaints Commission rejected her complaint against The Firm. In actual fact they never adjudicated on the matter as The Firm and Levy & McRrae reached an agreement (which involved no admission of liability on The Firm's part and both sides paid their own costs). It was after this that The Drum lodged its Freedom of Information request to find out if Angiolini had received a form of 'Scottish Legal Aid' to cover her costs. Our report on this matter led to another Press Complaints Commission referral by Levy & McRae which was ultimately rejected. I have amended the above blog accordingly. So sorry Elish, we all make the odd mistakes from time to time.
Gordon Young is editor of The Drum
Glad someone is actually telling it like it should be......truthfully! Great piece
How exactly will MacLeveson law impact on Scottish journalism? You never explained that at all in this fairly bland opinion piece. The Scottish and British media are selective about trashing their erstwhile pals in politics and business: more to do with media ownership issues than anything else. But give us a better case why media self-regulation should not have statutory underpinning. Perhaps with examples of how the Irish system works or not...
Ironically, referring to possible new legislation-backed press regulation in Scotland as "Alex Salmond's Leveson law" is just the kind of misleadingly pejorative language that has contributed greatly to bringing "Scottish" newspapers into disrepute. As is the tendency to mindlessly condemn everything the Scottish government does; proposes to do; is merely imagined to be contemplating; or is dishonestly portrayed as having done in the past.
More thoughtful readers will wonder how it is possible to bemoan legislation which hasn't even been drafted yet. They will wonder, especially given their experience of the generalised political bias and blatant dishonesty in the nominally Scottish media, what exactly it is about journalists as a group which makes them worthy of the special status that they demand.
If they are possessed of sensible caution and a measure of the open-mindedness we all might aspire to, people will await the advisory panel's recommendations before commenting. And they will be extremely wary of the special-pleading of a clique they have learned to regard as just another self-serving interest group, no matter how plaintive the protestations of journalistic dedication to the public interest.
The Hollie Greig case has been proven to be based on a great number of lies, please see website http://www.theholliegreigcoverup.net/
28. 03. 2012We believe, beyond reasonable doubt, that Hollie Greig was abused and has been badly let down by the Scottish justice system and that this same system has treated Robert Green disgracefully.We are very angry and upset that the words and actions of a number of misguided people who think of themselves as supporters of Hollie and Robert, have created the present situation where this gravely serious case has been reduced to a farce.
Sarah McLeod
I notice that no one has enlightened us about the awful Irish legislation which Salmond has hinted at as being a possible model to follow. We still get framed in the context of London-centric press views.
Where is the evidence that strengthening post-publication redress for those unfairly treated in the press will impact on risk-taking in what editor's publish? If the argument above is that Scottish papers are too timid (quite possibly true) under the current PCC regime it suggests that fear of retribution isn't the cause and that the two are probably not linked. It follows that it should be perfectly possible to both strengthen papers risk taking AND subjects' avenues for redress at the same time...
CICA have numerous historical cases of false payments -
http://tinyurl.com/8u5eoyj http://tinyurl.com/d22yk37 http://tinyurl.com/95hdypv
and should you enquire they will tell you any payment by them is not an admission of a crime or proof of anything.
Also, as you have pointed out at the very beginning of "Hollie Demanding Justice" Angiolini was not the PF - which started in 2009.....but as the internet was swarming with all manor of false allegations, i would have thought that Angiolini had every right to take proper precautions.
You also stated "If she had won, she could have picked up more for damage to her reputation than the original victim did for being raped. The key issue is whether or not this sets a bad precedent."
Need i remind you that there remains no proof Hollie was raped - none whatsoever. No witnesses, no material evidence and most certainly no medical evidence - nothing. I am bound to suggest then, that this sets a bad precedent of reporting....
However i would agree the public have an interest in knowing who was paying for Angiolini's legal action, and i wish you good luck with that.
@Gordon Young Your headline did - but you also stated "than the original victim did for being RAPED"
You have no evidence for rape - yet you are telling people she was.....perhaps you should have used the word "allegedly."
CICA were convinced by her testimony - her mothers testimony - a correspondence from D.I.Ally saying that on the balance of probabilities Hollie was abused (because they did not know about her boyfriend, nor Anne's mental breakdown) and forensic medical evidence saying Hollie was not a virgin (again because they did not know about her boyfriend)
There has NEVER been any evidence that Hollie was the victim of a paedophile ring for 14 years, as claimed by her mother Anne, Robert Green, Brian Gerrish, Lou Collins and David Icke.
When something cannot be proved, people are found innocent - in this case, not only can nothing be proved, (yet people are still found guilty) we have shown an intolerable amount of lies and misrepresentations that clearly point to an alternative agenda. What that agenda is we leave you to decide.
@Gordon Young Your knocking on an open door there Gordon - but i still can't see past the fact that the article is still misleading by stating the individual was raped when there is no evidence for such.
Perhaps it's me - perhaps i have read it wrong, so i will agree to disagree as i do agree with you on other issues also like no legislation on the press - even given the excellent points peterabellfb makes.
You have a rather rose-tinted view of the activities - if not the ideal role - of the "Scottish" press. I reckon I'm far from being alone in saying that what I see is not some band of honourable scribblers valiantly holding to account the bastions of power and privilege. Rather, I see a coterie of shallow, venal hacks dutifully serving their corporate masters and the British establishment without a moment's thought for a public interest which can only be served by the kind of unwavering honesty and analytical rigour which are all but totally absent from mainstream journalism.
In demanding extraordinary privilege for these journalists you ask us to set aside all that was revealed by the Leveson inquiry and disregard our own experience of what we see in the "Scottish" press every day. Why would we do that? Why would it be in our interests to do that? What gives you the right to insist that we simply turn a blind eye to the myriad faults and failings of the media?
Of course, you will hold up the bogey-man of "unchecked government" as if there were an imminent threat from some kind of totalitarian power. You will exaggerate this menace, just as you will massively overstate the threat of regulation, even as you hyperbolise the willingness of journalists to defend us against all this evil. But we have an unregulated press now and it is patently failing to defend us from the vested interests of the British state. It is not draconian regulation that is preventing the press from properly serving the people of Scotland. It is the fact that the preponderance of newspapers and those who make their living from them are servants of that state rather than its inquisitors.
You want the public's help in preserving journalistic privilege. But how do you go about getting that help? By assaulting us with the same mix of scaremongering sensationalism, self-righteous superiority and supercilious sense of entitlement that contributed to you losing the public's respect in the first place.
I value a free press as much as anybody else. But the press has to earn the right to the the social licence that we afford it. Having failed to do so, we are perfectly justified in seeking to amend the terms of that licence. Let's wait and see what our democratically elected representatives come up with in that regard. Let's trust the people to decide whether they have gone too far. The press has forfeited the right to be its own judge and jury.
@peterabellfb "Of course, you will hold up the bogey-man of "unchecked government" as if there were an imminent threat from some kind of totalitarian power." You mean there isn't such a threat? I beg to differ...more and more of our rights and freedoms are being eroded away as we see ever more legislation...but in the main i agree with you.
Gordon Young is one of the few journalists who has simply assessed irrefutable facts, and come to the courageous decision to highlight these facts to the public, and to hopefully ascertain the truth surrounding these facts. He is not defaming anyone. If he was he would have to stump up £185,000 or £125,000.
If the public were made aware of the substance of http://holliedemandsjustice.org campaign website they would demand action by the government. The website contains voluminous details, any number of which could be addressed by any one of the appropriate authorities, and if proven false would mortally discredit the HDJ campaign.
To date this has not happened. Highly unusual given the high profile of a number of these public servants. Common sense produces the conclusion that facts and truths are being covered up.
The jailing of Robert Green for 1 year, the result of being en-route to hand out leaflets in Aberdeen as part of the HDJ campaign. The fact that he experienced 18 different court appearances at a cost to the public purse of £500,000 should have been all over the mainstream media. By any consideration this is a matter that is in the public interest. Not a squeek from msm - this can only happen when the press is controlled.
Freedom of speech, and freedom of the press are under relentless attacks by the UK and Scottish Governments. When government denies the people the truth and denies them the right to speak openly and freely we have dictatorship.
Recent history has shown us that if we do not support those trying to expose truths, we permit dictatorship to develop and grow. No-one is safe in a dictatorship, even those supporting it.
We need more courageous journalists to stand up and speak out on what they know. This is probably their last chance.
Well done Gordon, Hold Fast,
Jim Graham.
@aloca17614 Yes- please do look at the official website http://holliedemandsjustice.org - and then look at ours http://www.theholliegreigcoverup.net/ you will see the complete lack of real and verifiable evidence on the official site as it is full of hearsay. If you want to believe it, that is exactly what you have to do - BELIEVE because all that's there is opinion and conjecture.
The same can be said for Robert Green's £500,000 court case - anyone seen any evidence for that? Oh and please don't start again with the line "he was arrested for giving out leaflets" - he was arrested for sending letters to the neighbours of Wyn & Sylvia telling them they were surrounded by paedophiles causing them harm and distress....BoP don't you know! I know Robert told you all that he was arrested for leafleting, but that's because he lies you know! He did it about the Autopsy - he said Roy had a fractured skull - he didn't, it was a tiny bump on the head! Even Stuart Usher (Scotland against crooked lawyers) admitted the Autopsy didn't say what Anne and Robert said it did - how much more do you need to know?
What about the accused that don't exist? What about the house where both Anne and Robert said most of the abuse took place? Oh, haven't you heard? It didn't exist either!! What about the other children named as victims? They have made public statements saying they have never been abused! The list is endless - but of course it HAS to be a conspiracy because the authorities are involved!! Yeah right!
As the authorities addressing any of the details on the HDJ website, its been done! Did you not read the PCCS report where Hollies testimony was discredited? It's also been done on our website where we show you the evidence in full!!
I vote @peterabellfb comments to be the funniest.
There is another issue that worryingly underpins some of the original blog. And it is this. Scotland is now sadly lacking any credible newspaper-led investigations that properly shine a light into the darker recesses of Scottish life. An example of this is Craig Whyte's purchase of Rangers Football Club. The Scottish press were asleep at the wheel while this takeover was going on. A simple check at Companies House would have revealed the background to Whyte's previous business dealings and the fact he had been banned from being a director. Instead, it was only when the BBC documentary was broadcast - with all its flaws and foibles - that most newspapers hopped aboard the train. Because it revealed that one irrefutable nugget - that he was banned from being a director of a company. It was hardly Woodward and Bernstein but it was enough to set in motion a sequence of events that took saw the story lurch forwards. Yes, some papers did try to get on top of the story, notably The Record re Ticketus etc. But the feeling persists that others were slow to react. So have newspapers sacrificed solid investigations on the altar of showbix pap and X Factor drivel? Sometimes, it looks that way.
I should just make it clear that the Hollie Greig campaign is based on the complete failure of Grampian Police to question a single person named to the force by Hollie on 8th September 2009, despite overwhelming support for Hollie`s allegations by expert witness statements, including that of Grampian Police`s forensic medical officer and the aforementioned CICA award.
Thus, the whole issue revolves around the police`s failure to conduct even the most cursory investigation, not whether those named can be found guilty in law or even arrested
One fact that may be of some interest to the observer was that during my trial, no complaint about me was made by the two individuals against whom the evidence was strongest.
From the said expert witness evidence, on which I largely relied, there is absolutely no question that Hollie Greig was the victim of sexual abuse. There can be no possible argument about that
Alex Salmond and the SNP are just like ALL the other political parties and have a lot to hide just like them. There are already laws that exist that can be used to deal with the press so WHY the rush by Salmond like ALL the other party leaders to bring forward government control of the press.
Is Salmond and the SNP being blackmailed or are they controlled by the BANKERS and GLOBALISTS like the Labour, Lib-Dems and Tory parties? www.paisleyexpressions.blogspot.com
do doctors not ask victims of sex crimes if they have had sex anymore ?
Opinion, blogs and columnists - call them what you like - this is the section where people have something to say. You might agree or you might not - whatever opinion you have make your views known in comments. Views of writers are not necessarily those of The Drum. If you would like to contribute a comment piece, email your idea to firstname.lastname@example.com.


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Join us for Summer School at Tate Modern
28 Jul 2014 – 1 Aug 2014
Event times
10:30 - 17:00
Cost of entry
£300 per person. Half price for teacher trainers
- Bankside
- London
- United Kingdom
- www.tate.org.uk/modern/
Travel Information
- Bus: 45, 63, 100, 344, 381, RV1
- Tube: Southwark/Blackfriars
- Train: London Bridge
AboutSummer School is week-long opportunity to actively reflect on current connections between contemporary practice and art education, each year a new programme of practical and discussion-based workshops, curators' talks and artist interventions, explore the possibilities for using Tate Modern as an exceptional resource for teachers. Join artists, students, architects, physicists, specialists and non-specialists in the production of a live and continually changing resource; a generative, chaotic system that draws people, things and ideas to it.
Have you been to this event? What do you think? Join the discussion here!
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I have the M3 and an M6, but no M2. The M3's viewfinder is better for 50mm than anything else, the M6 included. As pointed out by numerous posters above, the M3 lacks 35mm and 28mm viewfinder lines. I find the M6's 28mm lines almost unusable, because they are so far toward the outer edges, and I use Leica's 21mm-28mm adjustable viewer for 28mm and 21mm lenses. I also use a Voitlander 35mm viewer with my M3, and I shoot 35mm a lot, probably as much as I shoot 50mm. I don't find the external viewfinders to be much of a problem. I guess I've shot enough with my IIIc not to mind switching back and forth for rangefinder and viewfinder. If I had to get rid of one of my M bodies, it would be the M6.
Others here are doubtless more knowledgable than I, but I have also read that the M3's viewfinder is much better, but mechanically more complicated than the cheaper-to-manufacture mechanism that Leica began using with the M2 and has continued to use to date. It also has a .92 magnification vs. the .72 magnification in the M2 and most successors; thus, is more precise in focusing 50mm and longer focal lenths because of the higher effective rangefinder distance. I am sure that the M2 is no slouch either, so it probably comes down to whether having the 35mm framelines is important to you.
Regarding cleanup of the viewfinder in the M3, I saw a recommendation for Sherry Krauter, which I can second. I bought my first M3 from her, which she had overhauled, and she does excellent work.


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June 13th
Past, Present, & Future Fashion Show
September 26th
Family Picnic
July 4th
Old fashioned 4th of July
September 10th
Exhibit Opening "Hello Dolly"
The Wichita County
Heritage Society is celebrating 40 years and was
founded in 1974 by a group of visionaries who gave
the society the mission of promoting the heritage of
Wichita County.
From its inception
the Society has strived to be a strong influence in
the community in the name of historic preservation.
While our
accomplishments are many, such as The Kemp-Kell
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our future goals are just as great.
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Wichita County
Heritage Society and its membership strive for
excellence in all of these areas.
Please join us in
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July 9, 2015 | 9:00 am MST - 11:00 am MST
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Information on Small business development programs.
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July 9, 2015 | 9:00 am PST - 10:00 am PST
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July 9, 2015 | 9:00 am PST - 12:00 pm PST
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Governement wide procurement goals encourage opportunities for small businesses. This workshop will provide information on each program to become a successful entrepreneur in the contracting arena. ...
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OK, so you're finally getting ready to hire someone to develop your company's website. Or, you already have a site, and it's a mess. What do you need to know about creating functionality to ...
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This workshop will cover general business legal issues as well as entity information.
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Originally written on Football Nation | Last updated 1/4/13
Tim Tebow is not for everyone, he is a limited passer and needs to be with a coach and team that will work with him and build around his limitations. The kid is a winner and a nightmare for modern NFL defensive coordinators to prepare for. Think about the 1st Playoff game Tebow played in and the DC he was against…. Dick Lebeau, From the Powerhouse Pittsburgh Steelers. A man who is a Hall of Famer and has made many great NFL QBs look like fools. Tebow beat him with the help of his Broncos teammates, throwing for over 300 yards while rushing for 50. With the right type of personnel around him, #15 can win in this league. It was proven in 2011. The Arizona Cardinals and Tim Tebow are a marriage made in heaven.The 2012 Arizona Cardinals were a terrible offensive team that failed to get production out of both the running and passing game, ranking 32(Out of 32 teams) in most statistics. The team had injuries along the offensive line and the quarterbacks were beaten and battered because o...
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Narrow your search
Sun should at least make the old college try to display some enthusiasm about products that are proven and bringing in real revenues.
Sun Microsystems and Fujitsu announce a quad-core Sparc64 VII processor that puts all processing cores in one chip.
Harnessing more than 82,000 processors on the world's fourth-ranked supercomputer, scientists run an experiment that represents 1 percent of human brain activity.
The fastest got faster, as the K Computer topped its own record on the twice-yearly supercomputer speed test by scoring 10.51 quadrillion calculations per second.
CEO Larry Ellison today will tout a SuperCluster system based on the Sparc T4 processors, which take a step back toward traditional chip designs.
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The Hot Chips conference is focusing on high-end chips for server computers, with IBM's upcoming Power7 as a standout.


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Baileys Holiday Martini
2 oz. Baileys Irish Cream
1/4 oz. Smirnoff Vodka
1/4 oz. Godiva Chocolate Liquer
1 raspberry
Mix Baileys Irish Cream, Smirnoff Vodka, and Godiva Chocolate Liqueur to an ice-filled shaker. Shake with ice and pour into martini glass. Garnish with raspberry. Recipe courtesy of Baileys.com.
S'more Martini at The Blue Martini
No exact recipe for this one, but you can get it at the Blue Martini in Westshore. Enjoy this inventive cocktail with Grey Goose Vodka, ChocoVine, a splash of cream in a graham cracker rimmed Glass with a skewer of marshmallows.
Hot Apple Cider with Run
1 apple
2 teaspoons whole cloves
1 orange, thinly sliced
2 quarts apple cider
1/2 cup light brown sugar
1 teaspoon allspice
Pinch grated nutmeg
1 cup dark rum
Cinnamon sticks, garnish
Stud an apple with the cloves. In a pot, mix the studded apple and other ingredients excluding the rum. Bring to a simmer over low heat for 10 minutes. Remove from the heat, add rum, and discard the apple. Ladle into mugs and garnish each with a cinnamon stick. Recipe courtesy of FoodNetwork.com.
Snowcap at Whiskey North
Head to Whiskey North, one of the biggest nightclubs in North Tampa, for this classic holiday drink made with Patron XO Coffee Liquer and Baileys Irish Cream. Enjoy a variety of other holiday drinks, dancing, and more at this premier nightlife spot in Tampa.


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The fundamentals of delay and modulation effects and how to apply these effects, technically and creatively, to improve the sound of a mix.
Explains one of the most essential ingredients in audio mixing, reverb—the time it takes for sound to bounce, echo, and decay during a live performance or recording.
Shows how to properly apply equalization (EQ) to improve the sound of a mix.
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"My biggest problem is figuring out what I want to watch next. Just when I think I'm all set, I find something ELSE that is fascinating." —John O.
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On Nov. 2nd, 2013, activists partned with the Illuminator, an artist collective using a projector, hit the streets of Portland, Oregon to magnify the people's message, End Coal!
Coal companies are spending millions trying to build export facilities in the Pacific Northwest. These coal export terminals would not only harm the health of the people living near them, but also exasperate climate change.
This short video features two of the most majestic creatures, the humpback whale and pygmy killer whale. The humpback whale is one of the largest creatures on Earth. The pygmy killer whale is fairly small and not commonly seen. It is part of the...
Greenpeace Greenwire is an online community that fosters real world connections and activities.
Enjoy the view from above Glacier National Park. It is a truly beautiful place.
Saint Paul Island is nestled in the heart of the Bering Sea. It's scenery and wildlife is gorgeous. In this video, there are bountiful puffins and seals.
Most of the footage in this video was taken on Saint Paul Island. Full disclosure, the...
Take a peak into an Indonesian peatland forest. We hope this video brings you a moment of peace.
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The Message audio Bible is now available on Bible Gateway! Click to learn more.
The books of the Old Testament are written almost entirely in the Hebrew language. It is a branch of the Shemitic language, one of the three great divisions into which all languages have been reduced. It is one of the earliest of known languages, and some suppose that it was the original language of man.


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The Havens Winter Sale of China Tableware, Glassware, Housewares and Cutlery is now on.
China Dinner Sets from Maxwell and Williams, Villeroy and Boch, Portmeirion, Wedgwood, Royal Worcester, Spode and Jamie Oliver tableware with up to 50% off.
Our famous Glassware Sale features Dartington Glass, Waterford Crystal, Royal Scot Crystal, Rockingham Glass along with the best selling Villeroy and Boch Maxima glasses, again with savings of up to 50%
In the Housewares department we have Canteens of Cutlery, Saucepan Sets and Cookware.
The Havens sale starts online on Christmas Day and in the Store on Monday the 26th December 2010.
Prices are greatly reduced but never the quality.
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