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At first glance, the headline makes no sense whatsoever. But contemplate a bit further, and you'll find that it's a perfect summary of what happens when you turn your passion/ hobby into your job. It's taken me a while to figure out where the balance lies – and I admit I nearly gave up a couple of times – but I think we're just about there. Let me explain…
I have to be a professional so I can be an amateur.
Have some stones
Rocks, hard places, stones…mix and match your own metaphor.
Today, a few tangential thoughts on photography and the overall state of marketing strategy these days. Yes, I've done a lot of this kind of work extensively in my previous life as a consultant, but guess what: most of it is really common sense. And sometimes it can be very difficult to see the wood from the trees if you've been lost in the forest for too long. I'll start with two thoughts:
Have some stones and
Social media metrics are not an indicator of fiscal success.
This principles apply equally to both sides of the negotiating table.
Digital posterity: will your images survive you?
An old family photograph: the young man in the center is my grandfather; he passed away 22 years ago in 1992.
Back story: my grandmother's passing last year and sorting of her effects unearthed a number of photographs from a much earlier era; my guess is the mid 1950s; that's the better part of 65 years ago. There weren't that many – about 10 in all. Ostensibly being the authority on all things photographic in the family, they were passed to me for restoration. Combined with a recent SSD failure on my primary machine, it got me thinking on a subject beyond backups: how can we ensure our images survive us? Do we even want them to?
Repost: Basic street photography techniques
Offerings for sale. Sony RX100
Following on from the previous photoessay and numerous emails, I thought it'd be useful to repost this article I wrote previously on street photography techniques. Although it's possible to describe most of them in some detail, full understanding requires both demonstration and practice – this is where the Street Photography video comes in, or alternatively joining one of my workshops. Together with the basic principles of balance, perspective, composition and what makes a good image – these techniques may be used singly or in combination to generate strong street images. In fact, they also apply to documentary and reportage work, too; the only difference between good street photography and photojournalism is that the latter has a consistent theme and subject.
Can you tell the difference?
Following on from an interesting suggestion made by knickerhawk in the comments section of an article a little while back on achieving visual consistency, here's both a little test/ exercise for you and a little more expounding on the idea of sufficiency. Read on if you think you're up for the challenge.
The pre-shot checklist
All of the below applies, even in a situation like this. What you're not seeing is that it isn't a Wild-West quick draw: it's more like the preparation of a sniper.
There are many different types of photographers; all the way from the fully spontaneous use-whatever-falls-to-hand-and-just-hit-the-shutter-so-long-as-I-get-an-image, to the people who only photograph under 100% controlled situations – think still life in a studio, tethered. I'm somewhere in the middle, though definitely much further towards the latter end of the spectrum. The reason I'm writing this article is because during a recent workshop, I was asked by a student if I really kept all of the 'four important things' (and sub things) in my head and under active consideration even in a split-second instant; the answer is yes, and there's quite a bit more on top of that – but I've been doing it for so long that the vast majority of the whole capture process becomes second nature.
A photo reflects the photographer
Escape from yourself: clouds are like thoughts, the clear blue sky is freedom, and the person left behind is your ego. The car represents your way out, and the road is the constraints of your mind, complete with bright areas, order, logic, and dark, unconscionable ones.
I've often been accused of making images that are precise, cold and soulless; the more I look at images from other photographers, I'm inclined to agree. Taken in context with the opening title of this article, that probably doesn't bode well for impressions of me as a person. It did get me thinking, though: since the act of photographing is really one of conscious exclusion in which we eliminate all of the elements that are distracting or unnecessary to the subject/ story, what does this say about us?
Getting over the hump
There comes a point in the growth of every photographer where they reach a 'hump' which appears to be insurmountable in any obvious way: you just don't think you can get any better, no matter what you do. This may be at a very low level, or a very high one; depending on your natural visual aptitude. But it happens to everybody – it's happened to me several times in the past. Today I'd like to talk about things you can do to move past it and up your game. After all, everybody wants to make better images, right?
Questioning the 'art' market
Too commercial, with no artistry required, apparently.
Attempting to make the transition – perhaps augmentation is a more accurate description – from commercial photographer to fine art photographer as a profession in the last six months has not been easy. I suspect there are quite a few reasons for this: firstly, [defining a product] has become a significantly larger challenge since you are not creating to-spec for a client, but creating something you imagine from scratch. That something has to be visually distinctive enough to stand out, aesthetically pleasing enough to elicit desire, and exclusive enough to appeal to the typical art buyer.
And here the conflict begins.
Why I must do all the things I do
I struggled to find an appropriate image to go with this article. I think this works, though: firstly, it was shot with an iPhone, on an occasion I could not foresee doing any photography. But having an open mind and an active eye meant that I saw it; experience/ practice meant that I could make do with the bare minimum, and enjoying cigars meant that I was in the right place at the right time to begin with. All will be explained towards the end of the article…
Don't worry. Despite the slightly off-topic title, it's very much a post about photography. This isn't a moment of existential angst, but rather a clarification of purpose. It isn't quite the same as article on Why We Photograph from some time ago; it's far more personal than that. On reflection, I think it's very important to understand the motivations behind certain things so that a) we might do them better and b) we avoid doing things we don't enjoy. Especially when there's a choice.


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With 2014 winding down its time to launch the 2015 version of the Driver's Roster. Please use the form below to send us your information on plans for 2015. Please include your name and affiliation to the driver/team so we recognize our source properly. Also make sure to check out Hoseheads' The Pits and IBRACN.com for other great "silly season" information.
Updated 10/14/2014
|Brown, Mitch
|10/14/2014: Mitch informed us his team will focus on Ohsweken Speedway on Friday night's and travel more often on Saturday's in 2015.
|Dollansky, Craig
|10/08/2014: Dollansky is teaming up with Destiny Motorsports to run the entire World of Outlaws STP Sprint Car Series in 2015.
|Gravel, David
|10/07/2014: Gravel indicated on Winged Nation he plans on running the World of Outlaws series in 2015 with Roth Motorports. https://twitter.com/WingedNation/status/519523076443504640
|Holtgraver, Danny
|10/14/2014: Holtgraver announced he will drive the Phoenix Racing 59 car for the remainder of 2014 and in 2015. (http://tjslideways.com/2014/10/14/holtgraver-will-leidig-59-for-remainder-of-2014-and-beyond/)
|Kaeding, Tim
|10/14/2014: Kaeding and Phoenix Racing have parted ways and as of now Kaeding is searching for a ride for next season.
|Nouse, Kevin
|09/22/2014: Nouse said on our podcast after his 100th win he is looking for a ride for the 2015 season.
|Saldana, Joey
|10/01/2014: Dan Motter said on the Sprint Car Unlimited Podcast (http://www.pennlive.com/sports/index.ssf/2014/10/drug_testing_in_sprint_car_rac.html) Motter Motorsports plans on doing the same thing with Joey Saldana for 2015 and looking for corporate sponsorship on the car.
Send us your plans for the 2015 season!
© TJSlideways.com

subset: commoncrawl


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Thursday, December 4
Brown Bag Lunch Lecture: Election Wrap-up with Dr. Jay Barth
Sunday, December 7
Holiday Open House
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Brown Bag Lunch Lecture: Arkansas and the Cold War: Titan II Missiles in Cow Pastures
Friday, December 12, Saturday, December 13 and Sunday, December 14
Arkansas Chamber Singers Holiday Concert
Wednesday, December 17
Little Beginnings Toddler Program: Winter Holidays
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text: NEW SEXY: The 30 Hottest Celebrities Under 30 IGGY AZALEA Age: 21 Profession: Rapper Best Asset: Bootylicious Sex Factor: Oh you modeling, model? When heads first spotted the Aussie rap freshman, it was more than just her bold rhymes (see her single "PU$$Y") that drew attention. Her top model looks and bodacious curves that dead the whole no-ass-at-all myth about white chicks make Iggy worthy of landing in the pages of VIBE or Vogue. ‹ ›


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Use of temporary anchorage devices in regaining lost interocclusal space. Case series.
Jacobi Medical Center, Bronx, NY, USA.The New York state dental journal 03/2012; 78(2):31-5.
Source: PubMed
ABSTRACT The absence of interocclusal space, a common consequence of trauma, maxillofacial pathology or carious process, causes loss of function, compromised aesthetics for the patient, and represents a major challenge for the restorative dentist. Such cases were treated historically with dental procedures and orthodontic appliances, which, in turn, caused associated unwanted sequelae. The introduction of mini-implants for skeletal anchorage presents a change in treatment paradigm and provides a safe and successful management of the absent space without undesirable side effects. We present three cases of a successful adjustment of vertical correction with temporary skeletal anchorage from mini-implants.
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Sunny Sweeney's New Song and VIDEO! Love it or Hate it? [POLL]
Sunny Sweeney has a new song and video out! The song is called 'Staying's Worse Than Leaving'
Sunny Sweeney has a new song and video out! The song is called 'Staying's Worse Than Leaving'
The winner of last season's X-Factor Tate Stevens is releasing his long awaited debut country album today (4/23).
Like father, like daughter. Talent runs in Toby Keith's family! Toby's daughter Krystal Keith just released a video for her song 'Daddy Dance With Me."
Brantley Gilbert has survived a motorcycle crash before. But did you know he suffered an injury when he shot his new music video?
Blake Shelton is in a good place right now and he knows it. He just started his fourth season of NBC's 'The Voice' and today he releases his newest album Based on a True Story featuring his hit single "Sure Be Cool If You Did."
One of my favorite events of the year is coming up in Texarkana Sunday, April 14 at 6 p.m. when CASA presents: Songwriters on the Edge of Texas Concert featuring country star Sunny Sweeney at Northridge Country Club.
And the winner is.....
St. Patrick's Day is this Sunday March 17 and whether you have Irish roots or not you can't help to want to celebrate this festive day. To me, St. Patrick's Day always signified the beginning of the spring season.
What happens when you put the A&E stars of the hit TV show 'Duck Dynasty' together with a current country music star?
Kenny Chesney just got his 2013 No Shoes Nation tour underway and so far he's selling out his shows and pirate flags which is a part of his promotional merchandise and the title of his latest single.
"Mama's Broken Heart" is a song written by Kacey Musgraves, but Miranda Lambert begged for the opportunity to do it, check out the video with Miranda mostly in lingerie.
I know it's not country, but this song was so inspirational to me, I had to share.


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Green woodpeckers are the largest and most colourful woodpeckers native to Britain. They are easily recognised by their laughing 'yaffle' call, which they use to demarcate their territory. They also drum on trees, though the sound is not as resonant as that made by the other two British species (the greater and lesser spotted woodpeckers). Green woodpeckers survive on a diet of insects and have a particular fondness for ants. They return day after day to their favourite ant hill to feed.
Scientific name: Picus viridis
Rank: Species
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Even some insectivorous birds take advantage of autumn berries.
Even some insectivorous birds take advantage of autumn berries.
Dung from the New Forest's ponies benefits local birds.
Dung from the New Forest's ponies benefits local birds.
Species range provided by WWF's Wildfinder.
The Green woodpecker can be found in a number of locations including: Asia, Europe, Mediterranean, Russia, United Kingdom, Wales. Find out more about these places and what else lives there.
The following habitats are found across the Green woodpecker distribution range. Find out more about these environments, what it takes to live there and what else inhabits them.
Discover what these behaviours are and how different plants and animals use them.
Additional data source: Animal Diversity Web
Least Concern
Year assessed: 2009
Classified by: IUCN 3.1
Take a trip through the natural world with our themed collections of video clips from the natural history archive.
Autumn - a time of great change, of breathtaking migrations, of high drama.


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cavalryDivisión en sílabas: cav·al·ry
Pronunciación: /ˈkavəlrē /
Definición de cavalry en inglés:
sustantivo (plural cavalries)[usually treated as plural]
1(In the past) soldiers who fought on horseback.
Example sentences
- His army's main power was based on his cavalry - horse borne soldiers.
- William's plan was to use the archers first to send their arrows into the English ranks, followed by the infantry in hand-to-hand combat and to finally advance with the cavalry who had the height and power of being on horseback.
- In previous wars, horsed cavalry had performed such a role, but cavalry were generally of little use in the trenches of the Western Front.
mounted troops, cavalrymen, troopers, horse
1.1Modern soldiers who fight in armored vehicles.
Example sentences
- How much force structure (in armored cavalry squadrons and regiments) do we have dedicated to reconnaissance and surveillance?
- Several armored cavalry regiments (brigade equivalents) could be kept as independent units.
- A regimental cavalry troop has two tank platoons, two scout platoons, and a heavy mortar section.
- 1
- Example sentences
- Every ten farmsteads were supposed to provide for a fully equipped soldier, including a horse if he was a cavalryman or dragoon.
- In a commander's conference in 1957, he noted that some believed the airmen to be as wedded to the airplane as the cavalrymen was to the horse.
- Along the route, military detachments, including cavalrymen from the Queen's Life Guards, will give royal salutes and there will be a guard of honour in Parliament Square.
Pronunciación: /-mən/sustantivo (plural cavalrymen)
Definición de cavalry en:
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Palabra del día vicarious
Pronunciación: vɪˈkɛːrɪəs
experienced in the imagination through another person's feelings…


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Left tackle Gary Zimmerman: In the words of ...
Originally Published: August 1, 2008By Chris Conetzkey
Allen Kee/Getty ImagesSeven-time Pro Bowler Gary Zimmerman was an anchor at left tackle for the Vikings and Broncos, protecting John Elway's blindside for five years and paving running lanes for Terrell Davis.Teammate Mark Schlereth
Schlereth, who played three seasons at left guard next to Zimmerman with the Broncos, on what drove Zimmerman to be a dominant left tackle: "He was as paranoid as anybody I ever played by. I think that was one of the things that made him great is that he always had convinced himself by Sunday that the guy he was going against was the best player he ever lined up against in his whole life. "I was always a guy that studied and prepared and got myself ready to play, and when I got to Denver and played beside Gary, I grew in my preparation, and I grew in the way I practiced, because Gary was a consummate professional. So playing beside him helped me in my last six years go become a better football player.
Zimmerman on what Denver's 31-24 win over Green Bay in Super Bowl XXXII -- his final NFL season -- meant to him: "Well, because I played for so long, and the longer I played, the more apparent it was becoming to me how hard it was to get a Super Bowl. Just to get to the Super Bowl -- you know, I got close several times, but it was like I really never knew how hard it actually was to get one, and then to get there and have one shot at it, it was pretty special. "It was just relief, because it was going back and forth the whole game, and it was like, well, whoever got the ball was going to win. I was just relieved that it was over and ended the way that it did. It was kind of a storybook ending there for myself."
A Story
Schlereth on helping Zimmerman cope with his usual pre-play paranoia:
"As soon as John Elway was in the huddle, Gary would get the play before John would even tell the rest of the people in the huddle. And as soon as we would break the huddle, as we would walk up to the line of scrimmage, Gary would ask me what to do on every play, 'What do we do, what do we got, what do I do, what do we got Mark.' So I'd be like 'calm down I'll tell you, let's get lined up and see what they are in.'"So I would basically be relaying what we were going to do on the play. But see, Gary knew. Gary knew exactly what to do. He was a very intelligent football player. But he just liked to have that affirmation to know we were on the same page. And I'd tell Gary on every play what to do and he would go out and execute eight times better that I could. He would block his guy, my guy and two other guys on his way to his guy. He was just exceptional in that way."
- Ray Rice wins appeal, can sign with any team
- Janay Rice: 'Never ... have I seen abuse'
- Cards' Fitzgerald a game-time call Sunday
- Sherman's two INTs help Seahawks by 49ers
Fred Dean, Darrell Green, Art Monk, Emmitt Thomas, Andre Tippett and Gary Zimmerman were inducted into the Pro Football Hall of Fame on Saturday night. Gallery: Induction day | Index
Pasquarelli honor overdue ... 'Humbled'
FRED DEANIn the words of ... | Watch: Dean's Career
Hall of Fame speech Position: Defensive end
Team: Chargers/49ers
Years: 1975 to '85
Seasons: 11
Honors and achievements:
• Second-round choice in 1975
• Had career-best 17.5 sacks in 1983
• Selected to four Pro Bowls
DARRELL GREENIn the words of ... | Hall of Fame speech
Position: Cornerback
Teams: Washington Redskins
Years: 1983 to 2002
Seasons: 20
Honors and achievements:
• First-round pick in 1983 draft
• Had at least one INT in 19 straight seasons
• Selected to seven Pro Bowls
ART MONKIn the words of ... | Watch: Monk's Career
Hall of Fame speech Position: Wide receiver
Teams: Redskins/Jets/Eagles
Years: 1980 to '95
Seasons: 16
Honors and achievements:
• First-round pick in 1980 draft
• Had at least one catch in 164 straight games
• Had five 1,000-yard receiving seasons
EMMITT THOMASIn the words of ... | Watch: Thomas' Career
Hall of Fame speech | The 'Hall's' monitor Position: Cornerback
Teams: Kansas City Chiefs
Years: 1966 to '78
Seasons: 13
Honors and achievements:
• Ranks ninth all-time in INTs with 58
• Led NFL with team-record 12 INTs in 1974
• Selected to five Pro Bowls
ANDRE TIPPETTIn the words of ...| Hall of Fame speech
Position: Linebacker
Teams: New England Patriots
Years: 1982 to '93
Seasons: 11
Honors and achievements:
• Second-round pick in 1982 draft
• Had 18.5 sacks in 1984
• Selected to five Pro Bowls
• Graham: LT learned from Tippett
GARY ZIMMERMANIn the words of ... | Watch: Zimmerman
Hall of Fame speech Position: Offensive tackle
Teams: Vikings/Broncos
Years: 1986 to '97
Seasons: 12
Honors and achievements:
• Member of two all-decade teams (1980s, '90s)
• Made 169 consecutive starts
• Selected to seven Pro Bowls
• Zoom gallery: Hall of Fame inductees
- Betting: Week 13 ATS picks | Vegas Rankings
- Kiper: Evans leads rookie WR ranking
- PFF: NFL's best corner? Don't forget Revis
- Fantasy: Favor sleeper QBs | Week 13 advice
- Sando: Right now, Stafford holding Lions back


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November 27, 2014
AUGUSTA COUNTY, Va. -- Hundreds of dollars are going to charities in our area thanks to some businesses, and people who have a love for cars.
Businesses in our area sponsored the Celebrity Auto and Truck Show at Augusta Expo to support charities and other organizations.
Money raised will go to the Boy Scouts, Waynesboro Lion's Club, and Virginia Wounded Warriors Program.
People there say it's important to give back to the community.
"Everybody can do a little bit more, I think it's part of our role as local community businesses," said Mark Clark, who is a sponsor.
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Dinner on McGill/St. Paul - Wilson, Vauvert, Holder, Stash, Gandhi, or other?
- l
- liquidrawhide Oct 10, 2008 12:15 PM
Hi again,
I was wondering what you fellow boardies would recommend for a memorable dining experience on the McGill/St.Paul near McGill strip on a Saturday night?
We're hosting some relatives from the U.S. whose ages range from mid-20s to mid-50s and whose palettes range from adventurous to not-so-adventurous, and the plan would be to eat somewhere that at once has a memorable atmosphere and an innovative, tasty menu. We're planning the walk-around-the-Old-Port and then Casino thing, hence the choice of locale on McGill/St. Paul.
I've been to Vauvert and quite enjoyed it, so I know what I'd be getting there. Many of the other spots in the area, though, would be new to me, so I'm wondering if any of them get the thumbs-up or avoid-at-all-costs judgment from you.
Wilson seems interesting, especially with the supposed addition of chef David Adjey to their kitchen (has this happened?). L'Appartement looks promising, and I've heard good things about Boris Bistro and Holder, though I've only seen those spots by day/at lunch. On St. Paul, I know Stash and Gandhi are both reliable, though I'm not sure our party will be totally on board for Polish or Indian cuisine.
Thanks in advance for the advice!
I haven't been to the others, but I have thoroughly enjoyed Holder. I really love the boisterous atmosphere there. There's just something about those high ceilings that lends something to the acoustics, I guess. My boyfriend had a short rib dish there that was out of this world, and I remember really liking crème brulée trilogy.
David Adjey has been hired by the Wilson restaurant, as a consultant to help develop their new menu(that's what David is doing mostly these days).
Skip Boris Bistro - lovely atmosphere on the terrace (which is likely closed now) but truly ordinary food. Don't know if Wilson has improved, but early reviews were pretty negative. A few blocks west of your area is da Emma, which might be an interesting option as well.
re: nochainsplease
I've tried Holder twice and it's now scratched off my list; oversalted meat and fish at dinner, toast brought 20 minutes after the omelettes at brunch. Vallières has proven to be a more consistent place with service and quality, although it's more casual.
Is Graziella in that area? I went there a couple of weeks ago and everyone loved it. It was an excellent dinner with fine wines. We had 2 wines: La Rasina and Montesecundo. They were both excellent. I tasted almost everyone's plate and everything was excellent.
I've been to Holder several times with my family and it's a safe bet for your group. The beef cheeks in burgundy has been excellent both times, excellent frites, steaks, soup and dessert. Only had one issue with the service - they failed to bring an appetizer we ordered one night.
I just had my 2nd meal at Gandhi, the first this trip. I really love the esthetics of the restaurant. and the menu is wonderful. I found both times that the food is quite spicy (and I love it spicy) so that may be difficult for some of your guests.
I highly recommend the prawn puri appetizer- the best I have had. They have a decent wine list as well. The portions were on the small side but can be forgiven based on a two person order and the food being very good- excellent Saag Paneer, Aloo Ghobi, Lamb Rogan Josh.
Now to the bad news: the service. We had reservations- they put us right beside the door. I am not over dramatizing when I say my s/o was almost outside. When asked to be moved we were put at a table right by the kitchen when there were at that point many open tables. The restaurant is divided into two rooms, the first being almost full we asked to move again; this time to the other room that only had one active table for the sake of hearing each other and not the kitchen. We were told the owners were having dinner there so we could not.
As the night finished we watched one half of a very lovely but understaffed restaurant become a bit frenzied and packed while the owners sat with a bottle of wine in plain view in the other half. While the food, atmosphere and location are fantastic, we were left feeling almost out in the cold.


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L.A. Metro Art Adventure
L.A. Metro Art Adventure, a Scavenger Hunt from CityRace
Full Price
$35.00 - $40.00
Our Price
$17.50 - $22.50*
This challenging CityRace scavenger hunt sends you on a subterranean quest through the state-of-the-art stations of the L.A. Metro, where you'll hunt for clues amidst some of the most striking and imaginative art in the region. You and your team of two to four people can choose your own route -- and the farther you travel, the higher your possible score. It's a fun way to explore the city, and one that might just give you a new understanding and appreciation for both public art and public transit.
* Additional fees apply.
All offers for L.A. Metro Art Adventure have expired.
The last date listed for L.A. Metro Art Adventure was Saturday September 13, 2014 / 10:00am.
Most Popular Activities & Competitions Event Nearby
Halloween Carnival for Kids: Games, Costume Contests & More
- Full Price:
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- Our Price:
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Designed with children age 3 and older in mind, The Little Theater's Halloween Carnival is the pe...Learn More
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Wear layers in case it's hot or coldL.A. Metro Art Adventure info • Feb 13 2012 star this tip starred
Goldstar Member
Bring some snacks and water if you think you might get hungry or thirsty. .L.A. Metro Art Adventure info • Feb 13 2012 star this tip starred
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Featured review from Goldstar Member
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Amazing fun and a GREAT way to see areas I wouldn't have normally seen. Lots of wonderful art in public spaces. I would definitely do this again
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Badger Prairie County Park in Verona, Wis., is a good place to hop aboard the Ice Age National Scenic Trail.
The federally designated trail is marked by yellow blazes on brown posts as it winds through a restored prairie. It runs north next to soccer fields and through what's known as Ice Age Junction, a permanent open space that connects to nearby Madison.
The Ice Age National Scenic Trail is not well known. It offers solitude and glacial geology. Its southern border generally follows the southernmost extent of the glaciers that covered Wisconsin 10,000 years ago.
The trail is a work in progress -- with about 675 miles built, linked by back roads. You can use a GPS unit to identify geological features on the trail.
More than 50 years ago, volunteers began creating an S-shaped footpath through Wisconsin forests and prairies. Its western terminus is in Interstate State Park near the Minnesota-Wisconsin border just outside of St. Croix Falls, Wis. The eastern terminus is near Green Bay on the Door County Peninsula in Potawatomi State Park.
It is primarily a hiking and backpacking trail. Snowmobiling and bicycling are allowed in a few areas that share the route with state rail trails. Snowshoeing and cross-country skiing are also allowed on some sections. A warning: Hunting is permitted along the trail, so hikers are encouraged to wear orange in hunting seasons.
The National Park Service partners with the Wisconsin DNR and the grass-roots Ice Age Trail Alliance on planning and upkeep. It is expected to be complete in 30 to 50 years, said Mike Wollmer, executive director of the alliance.


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25 Years in, the Urge Still Selling Out Venues
By Melinda Cooper
The 100 Greatest St. Louis Songs
By RFT Music
"Music You Know" Draws Inspiration from the Familiar
By Allison Babka
Pokey LaFarge Signs to Rounder Records
By Daniel Hill
Miami Dolphins Is Not a Football Team
By Drew Ailes
Combating a Rash of Tour Van Break-Ins
By Brian Heffernan
Grammophone to Close, Reopen As Restaurant
By Joseph Hess
Playing for the Cause Helps Out Those in Need
By Joseph Hess
The dudes of Mötley Crüe have become rich and famous by basically being douchebags — and what's not to love about that? Sure, the band members are hair-metal-inventing, Hollywood-promoting, Grade-A misogynists, but, damn, they do it so well. In the early '80s the band found a musical formula that worked, and it's never strayed from it since. The new album, Saints of Los Angeles, sounds like classic Crüe (and even includes a tribute to the glory days of boneheaded cock rock, "Down at the Whiskey"). Following along the well-worn path of previous hits "Girls, Girls, Girls," new songs such as "This Ain't a Love Song" and "Chicks = Trouble" continue to, uh, applaud the female form ("I really thought that pussy was gold."). Oh, Crüe. You're so naughty. It's comforting to know that some things never change.


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Fort Worth is launching a review of its master thoroughfare plan aimed at accommodating continued suburban growth and central city redevelopment with a greater variety of streets and more efficient traffic flow.
A key linchpin in the Fort Worth economy, American Airlines Group Inc., is considering sites for a new headquarters, possibly outside the city, the airline's CEO said this morning.
Residents of West Fort Worth's Crestwood Association are trying to block the rezoning of a small apartment complex at White Settlement Road and North Bailey Avenue to make way for a planned office building, saying it would represent the start of commercial encroachment into their neighborhood.
Rarely does Golf Digest make the news. Leave it to Dan Jenkins to change that.
The Hilton Fort Worth is one of 24 hotels named a member of the Historic Hotels of America, the Washington, D.C.-based group announced on Nov. 18.
A. Lee Graham
The Walton Group of Cos. has acquired 1,755 acres along Fort Worth's Chisholm Trail Parkway for a master-planned community.
Walton, a Calgary-based real estate investment and development group with U.S. headquarters in Scottsdale, Ariz., acquired the 1,755-acre property from the Texas General Land Office in Tarrant County. The company hopes its project will help meet growing residential and commercial needs in the corridor.
"With over 25,000 acres of land under administration in Texas, Walton is committed to getting more involved in Tarrant County and working with local officials to expand economic opportunity in the region," said CEO Bill Doherty in a news release.
The property is bisected by the recently opened Chisholm Trail Parkway corridor with land to the east and west of the 27-mile parkway. Much of that land had been part of a planned "prairie park" to preserve native plants and species, but supporters did not raise the funds to purchase hte land.
District 6 Fort Worth City Councilman Jungus Jordan helped oversee the $1.4 billion parkway and voiced support for growth surrounding the corridor.
"It took a tremendous and dedicated effort to see the Chisholm Trail Parkway become a reality for the citizens of Tarrant County," Jordan said. "We want to see this area grow and prosper and we hope this development announcement from Walton is the first of many."
The acquisition marks Walton's first in the Fort Worth area. The company currently oversees more than 25,000 acres of land in Ellis, Hunt and Grayson Counties in North Texas, as well as Hays and Caldwell Counties in Central Texas.
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Our Pet Care Partners
Caring for all of your pet's needs takes more than we could ever provide alone. Here are some local organizations and businesses that we recommend to our patients and their families.
Caring for all of your pet's needs takes more than we could ever provide alone. Here are some local organizations and businesses that we recommend to our patients and their families.
Sometimes sick or injured pets need the care of a veterinary medical specialist. When that happens, VCA specialty hospitals work closely with the general practitioner veterinarians who refer cases to us in order to provide seamless veterinary care to your pet. When your pet is facing any kind of serious illness or injury, our specialty referral hospitals will provide the compassionate and expert care your beloved pet needs.
Our goal is to make sure that when you and your pet are in need that you have access to board certified specialists who are up to date on the very latest developments in their field. In our state of the art hospitals, our specialists also have access to the most sophisticated diagnostic and treatment tools and techniques from ultrasonography and endoscopy to CAT scans and even MRI.
As part of the VCA family, we have over 83 specialty hospitals across the US and Canada which provide referral specialty care, so there may be one near you. Our specialized services include: behavior, cardiology, critical care, dentistry, dermatology, integrative medicine, internal medicine, neurology, oncology, ophthalmology, radiology, rehabilitation, reproduction, and surgery.
FOR PET EMERGENCIES, PLEASE CALL OUR HOSPITAL AT (530) 224-2200 OR TRANSPORT YOUR PET IMMEDIATELY TO OUR FACILITY. VCA Asher Animal Hospital is located at 2505 Hilltop Drive, Redding, Ca. 96002. VCA Asher Animal Hospital has a veterinarian, veterinary technicians, and support staff available 24 hours a day, 7 days a week for your pet's emergency and critical care needs. Our emergency team is ready to provide your pet with the highest possible level of quality, and compassionate care, should an urgent medical need arise at any time of the day or night.


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Added Oct 26, 2008
by bookwyrmhole
Littleton, Color...
I wanted to enter Nikkishell's Recycle Mini-Challenge so I pawed through my fabric stash and found this amazing 100% cotton king-size duvet cover with a kind of shiny, flowery pattern on it that I had gotten at a garage sale. And it was this awesome purple-grape color. I decided it would make a really cool dress, at least to start (I had YARDS of fabric!) so I drafted a simple princess seam dress pattern from a dress I already have. Drafting the pattern and cutting out the pieces took by far the longest, while the sewing went really fast. I found an old 20" invisible zipper in some stuff my aunt gave me, but it was white, so I worked really hard to make it not show. Didn't help that I had never done and invisible zip before, but I'm proud of the results. I also used mock french seams because I wanted to be able to take in the pattern a little bit if I needed to, which is way easier to do if the seam is on the inside, at least I think so. I just turned down the edges of the neckline and armholes twice to finish them and hemmed the bottom.
I really wanted to make a short puffed sleeve blazer since the duvet cover had buttons on it, but I ran out of time. So that will be my next project. And maybe a skirt or a bag. And then I'll still have to find a way to use the rest of the fabric! I love garage sales.
Yes, it's very wrinkled. This I know. I shall have to use the iron.
pic 1+2: dress
pic 3: zipper
pic 4: duvet before
pic 5: fabric pattern
king-size purple duvet cover
old 20" white invisible zip
graph paper (for my pattern)
Oct 27, 2008, 06.00 PMby the-gilded-bee
Nice work. :)
Oct 26, 2008, 07.01 PMby grinchy
cute <3
Add to Favorites 1 person added it
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The U.S. leads the pack in the percentage of older adults who have trouble paying their medical bills.
A new report provides an overview of mobile capabilities in insurance, including an array of potential functionalities and customer interest...
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Of course, if you follow me on Instagram you probably already have seen moving boxes. I recorded this video over the weekend. We already have a few days of our temporary routine under our collective belts.
- Previous Post
- Words by: Erin
- June 7, 2014
- Tagged: Random Thoughts, Vlog
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Kayla @ TheEclecticElement
Posted: June 8, 2014
I swear you are like the third or forth blogger I've come across that is moving! I guess it seems like the popular time to have a life change :) Moving can definitely be very overwhelming and stressful, especially with kids involved but to have to move within the month pretty much by yourself? Lots of love and light headed your way to get you through unscathed! Kayla @ TheEclecticElement recently posted...Win It Wednesday(6/4)


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Ratings based on 1,234 Verified Reviews
They paid and stayed. We double-checked.
4.5 Room cleanliness
4.4 Service & staff
4.3 Room comfort
4.3 Hotel condition
They paid and stayed.
We double-checked.
We double-checked.
for Everyoneby A verified travelerfrom Melbourne
Passing through on way home to MelbournePosted Nov 10, 2014
Pros: Proximity to everything in Sydney
Cons: The car parking was a little difficult
Location: So close to Darling Harbour
We were impressed by hotel staff - so friendly and helpful
for Everyoneby A verified traveler
Comfortable and easily accessiblePosted Nov 10, 2014
Pros: Facilities and frindliness
Location: Amazing and quite convenient.
Staff are quite friendly and ready to assist. Proximity to places is astounding.
for Everyoneby A verified travelerfrom Fort Lauderdale, FL
Nice hotel good locationPosted Nov 9, 2014
Pros: The hotel is in a good location so it was easy to get around and for the most part the staff was friendly and very helpful.
Cons: You have to pay for everything and anything. When traveling, I want to feel welcomed and cared for, relaxed, not pay as you go.
Location: The location is great. I went to the Aquarium and Wild Life World, walked about Darling Harbor, took a cruise, went to Bondi Beach, and shopping.
I read quite a few reviews before booking this hotel and many of the reviewers were correct, If you can, get the harbor view. It is worth the price. While the hotel is expanding, there was no inconvenience (okay except on my last day) to the guest. I was on the 10th floor and the location was quite and comfortable. For the most part the staff at the hotel are friendly and helpful, however, I did have one exprience in the resturant where i felt the hostess was less then friendly. I fully took advantage of this trip and went on numerous tours and did quite a bit of sightseeing, the hotels location made this easy.
for Everyoneby A verified travelerfrom C
Lovely hotel close to CBDPosted Nov 6, 2014
Great walking distance to Darling Harbour and also Sydney CBD. Would stay again, staff were very lovely and always greeted us with a smile. :)
for Everyoneby A verified travelerfrom Kirkland Wa
Nice well located hotelPosted Nov 3, 2014
Pros: Location staff and cleanlines
Cons: No justification for charging for internet at highest daily rates I've encountered anywhere in the world; esp as its free at all nearby cafes, shops.
Location: Aquarium, Naval Museum, zDarling Harbor restaurants
Great hotel except very expensive internret rates. Good food but mostly buffet style
for Everyoneby A verified traveler
Place to stayPosted Oct 21, 2014
Pros: Location, location, location.
Great room, very comfortable clean. Terrific view.
for Everyoneby A verified traveler
Quiet central to everything. Enjoyed the stay.Posted Oct 19, 2014
Pros: Friendly staff, facilities and location.
Cons: Deposit refunded on check out.
Location: Getting to the hotel was a bit of a nuisance. You can see it but had to walk around to get to it.
Comfortable and staff were great. I guess the deposit that is held for 1 week is a bit steep. Generally this is refunded on check out. So didn't quite understand the reasoning. This payment is still not reimbursed. I left the hotel on 11/10 payment is still showing a debit of $100.00.
for Everyoneby A verified travelerfrom sydney
Good hotel close to casino and restaurantsPosted Oct 14, 2014
Had a good time my wife's birthday so hotel was nice except needed a dresser in the room Be was good happy hour and nice coffee hope to stay there again in se good occasion
for Everyoneby A verified travelerfrom Sydney
ComfortablePosted Oct 12, 2014
Really nice, great service. Clean rooms, modern and fresh. close to everything.
for Everyoneby A verified traveler
excellent locationPosted Oct 10, 2014
no complaints, there is not much more to add to my comments. We enjoyed our stay.


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Estate and letting agents in South Yorkshire
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3 Keys Property
6 Town End, Doncaster, DN5 9AG
3Keys was established with the aim of setting new standards in the industry by combining a ... more
18 Eldon Street, Barnsley, S70 2JB
Belvoir Sheffield
34 Campo Lane, Sheffield, S1 2EG
Why use Belvoir! Sheffield for Property Sales? Whether you are a landlord who is wishing to ... more
Bloor and Co
781 Abbeydale Road, Sheffield, S7 2BG
Founded at the turn of the century Bloor & Co is an independent Estate Agents built on strong ... more
Blundells Auctions
8th Floor, Fountain Precinct Balm Green, Sheffield, S1 2JA - We also cover S3
Blundells - Banner Cross
896-898 Ecclesall Road, Sheffield, S11 8TP
Having recently undergone an extensive refurbishment this flagship branch has been open since ... more
Blundells - Campo Lane
Campo Lane, Sheffield, S1 2EF
Blundells - Chapeltown
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Blundells Chapeltown office re-located to its current premises and was opened by the ex England ... more
Blundells - Crookes
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Blundells - Crystal Peaks
5 Peak Square, Sheffield, S20 7PH


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ELP Laser Turntable
True audiophiles will tell you nothing sounds better than Vinyl. However, no one can argue that taking a needle to your Vinyl will one day wear it out. But finally there may just be a compromise — the ELP Laser Turntable.
ELP has supposedly been making and manufacturing the Laser Turntable since 1989 However, now for the first time thanks to the Internet, the masses will be able to try a Laser Turntable.
The Laster Turtable (LT) also gives you features a mechnaical turntable never could. You'll get a digital display where you can select tracks and program a tracklist. You'll even have a remote control.
Ready for your very own LT? Well the models range in price from $14,999 to $18,999. However, ELP will let you try one for free, assuming you put down a deposit (half the cost of the unit). What are you waiting for?
via Product Dose
Christen Costa
Grew up back East, got sick of the cold and headed West. Since I was small I have been pushing buttons - both electronic and human. With an insatiable need for tech I thought "why not start a blog focusing on technology, and use my dislikes and likes to post on gadgets."
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text: January 23, 2013 International tennis star Li Na in Nike Women's Spring/Summer 2013 looks View Gallery International tennis superstar Li Na has once again proven herself on the court in Melbourne. Here are some never before seen looks of Li Na in Nike Women's Spring/Summer 2013 product. Tags nike tennis nike women's Related Stories Nike Women Presents: Leticia Bufoni Good as Gold: Gracie Gold's Core Confidence N+TC Workout Nike women's-only store with fitness studio opens in Newport Beach


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Miche and Multigrain Baguette from La Fournette Bakery Now Available at Pastoral!
A La Fournette favorite, this 2 pound loaf redefines the meaning of sourdough with its tight, spongy crumb. This is La Fournette's signature bread made with sourdough starter, long fermentation and rye, wheat and whole wheat flours. It's large size makes it the perfect crowd-pleaser, used as a bowl filled with savory dip or simply toasted with butter.


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From £ 11.45
A simple one-step peroxide sytem
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When used in combination with the catalytic disc contact lens case (included), EasySept peroxide solution works to disinfect soft contact lenses. After six ...
Postage & Packaging: Free! | Availability: Usually dispatched within 1-2 business days...


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Five Esquire-Approved Square-Toed Shoes
Byon April 21, 2014
There is one monster so universally feared by menswear aficionados that its mere mention can cause the weaker among them to sweat through their unlined Isaia sportcoats in seconds. THE SQUARE-TOED SHOE. The bane of stylish wives and girlfriends everywhere. The footwear that embarrasses the entire office on your behalf. But, we at Esquire are in the business of blowing minds. So come closer, friend, and let us show you five square-toed shoes that will enhance your style, and show squares everywhere that you are a fully-realized man who knows exactly what the hell your doing in the footwear department. And who knows, with all this talk of negative frequency dependence floating around, adopt these, and you might just be on the cusp of a new trend.
Bruno Magli
Lace-up shoe ($198.40) by Bruno Magli, farfetch.com
These suede bad boys feature a burnished toe to highlight just how square these muthas are. Not for the faint of heart.
Florsheim by Duckie Brown
Laceless wingtip oxford ($249.90) by Florsheim by Duckie Brown, florsheimbyduckiebrown.com
These heavily brogued wingtips feature a gentler square toe that's perfect for beginners.
George Cleverley
Anthony Bodie leather oxford shoes ($1,600) by George Cleverley, mrporter.com
These handmade English oxfords are the most elegant of the bunch, boasting a blunted chisel toe and coming with their own shoetrees to keep that square shape going no matter how many miles you put on 'em.
Brogue detail derby shoe ($385.08) by Kenzo, farfetch.com
With whimsical broguing and a brick-shaped toe, these Kenzo derbies are admittedly outrageous, but for a man with confidence, no pair on this list is better.
Bettanin & Venturi
Burnished wholecut balmoral ($795) by Bettanin & Venturi, barneys.com
These wholecut balmorals are sleek as can be, with a lovely patina that adds depth to the leather.
Follow The Style Blog on RSS, Twitter, and Instagram at @ESQStyle.
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07The State of The American Dog
08The 50 Best Manly Movie Quotes
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Am I being unreasonable? Christmas, ex, and my mum(212 Posts)
oldbaghere Tue 17-Dec-13 11:42:08
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Andro Thu 19-Dec-13 23:14:30
PenelopePipPop Thu 19-Dec-13 22:34:42
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The Mighty Ducks of Anaheim promised some minor deals this trade deadline and General Manager Pierre Gauthier delivered with the dealings of minor leaguers. The most notable of these players is Johan Davidsson.
The team dealt the once highly touted Davidsson to the Islanders for rookie and Euro veteran Jorgen Jonsson, the older brother of Isles captain Kenny Jonsson. The trade was a statement from Gauthier that the team needed help now not for the future as they try to squak into the playoffs.
Jonsson is having a highly productive season, scoring 11 goals in his first NHL season. He has been projected as a possible second line center down the road. For now though, the Ducks could use his skill. A strong skater and good playmaker, his abilities should add some depth overall to a team that lacks consistency.
One of the key selling points is Jonsson's strong penalty-killing. He racked up two shorthanded goals with the Isles and since the Ducks have struggled all year shorthanded, he will be a welcomed addition. Anothe selling point is his good speed which fits in perfectly for the fleet footed Ducks team. As an added bonus, Jonsson is good defensively which is perfect for Coach Craig Harstburg who has preached team defense to his team this season.
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Nate and Hayes (also known as Savage Islands in Europe) is a Swashbuckler adventure film from 1983.Set in the South Pacific during the late 1800's, the film centers upon Pirate Captain Bully Hayes, who gets caught by the authorities in the opening for dealing arms to the islanders. In prison he retells the events that lead him there; 18 months before, he transferred two missionaries, Nathaniel "Nate" Williamson and his betrothed Sophie, to the Island of Wakaya. He took a liking to Sophie and accepted her offer to become business partners.However, after Bully's departure his archenemy Ben Pease, a "blackbirder" (slaver) who has been framing Bully for his crimes for years, attacks the island, taking its inhabitants for the slave-market and kidnapping Sophie while he's at it. Nate teams up with Bully to get her back. While chasing Ben they run into Count Heinrich von Rittenberg, representative of Imperial Germany, who plans to start coal mines and anchoring points for the Empire with the help of Ben Pease's "merchandise."The film stars Tommy Lee Jones as Bully Hayes and it was partially written by John Hughes.Just like most other pirate films in the two or three decades before Pirates of the Caribbean, Nate and Hayes bombed and contributed to the belief that pirates were box office poison.
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Interferon Regulatory Factor 6 (IRF6) is a member of the IRF family of transcription factors. It has been suggested to be an important contributor to orofacial development since mutations of the IRF6 gene has been found in Van der Woude (VWS) and popliteal pterygium syndromes (PPS), two disorders that can present with isolated cleft lip and palate. The association between IRF6 gene and cleft lip and palate has also been independently replicated in many populations.
We screened a total of 155 Taiwanese patients with cleft lip with or without cleft palate (CL/P); 31 syndromic (including 19 VWS families), 44 non-syndromic families with at least two affected members, and 80 non-syndromic patients through a combined targeted, polymerase chain reaction (PCR)-based mutation analysis for the entire coding regions of IRF6 gene.
We found 11 mutations in 57.89% (11/19) of the VWS patients and no IRF6 mutation in 44 of the non-syndromic multiplex families and 80 non-syndromic oral cleft patients. In this IRF6 gene screening, five of these mutations (c.290 A>G, p.Tyr97Cys; c.360-375 16 bp deletion, p.Gln120HisfsX24; c.411_412 insA, p.Glu136fsX3; c.871 A>C, p.Thr291Pro; c.969 G>A, and p.Trp323X) have not been reported in the literature previously. Exon deletion was not detected in this series of IRF6 gene screening.
Our results confirm the crucial role of IRF6 in the VWS patients and further work is needed to explore for its function in the non-syndromic oral cleft with vary clinical features.
Keywords:IRF6 gene; Mutation analyses; Orofacial clefts
Orofacial clefts are common congenital malformations which require long-term treatment and patient care. They are usually classified as either cleft lip with or without cleft palate (CL/P) or cleft palate only (CP), based on differences in embryological development [1,2]. Approximately 70% of cases of orofacial clefting occur as isolated entities with no other apparent cognitive or craniofacial structural abnormalities and are commonly termed 'isolated, non-syndromic CL/P (NSCL/P)'; while many syndromic forms have simple Mendelian patterns of inheritance and therefore are amenable to disease gene identification [3-5]. Previous genetic and epidemiological studies have indicated that the causes of nonsyndromic CL/P are multifactorial, with both genetic and environmental factors contributing to the phenotype [6-9].
Of the large number of candidate genes thought to contribute to orofacial clefting, Interferon Regulatory Factor 6 (IRF6) is the only gene that has shown a convincing degree of consistency across studies [10,11]. Mutations in IRF6 were first identified in the autosomal dominant van der Woude syndrome (VWS; OMIM 119300), which is traditionally recognized as a monogenic syndrome characterized by lip pits, clefting of the primary or secondary palate, and hypodontia [12]. Van der Woude syndrome (VWS) is estimated as most common syndromic form of oral clefts, accounting for 2% of all cases of cleft lip and palate, and has the most closely similarities in phenotype with that of common non-syndromic forms [13-15]. Up to date, at least 200 different mutations in the IRF6 gene have been described with the majority being protein truncation mutations (nonsense and frameshifts) or missense mutations [16]. Given the overlapping phenotype of VWS with isolated CL/P, in searching the gene for mutations, non-pathogenic variants in IRF6 gene have also been found to be significantly associated with nonsyndromic oral clefting in many different populations and ethnic groups [10,17-23].
In order to determine the contribution of mutations in IRF6 to oral clefts in the Taiwanese population, we applied a combination of targeted, PCR-based experimental approaches (including polymerase chain reaction (PCR), Denature High Performance Liquid Chromatography (DHPLC), Multiplex ligation-dependent probe amplification (MLPA), TOPO cloning and DNA sequence analysis) for a cohort of oral cleft patients from Craniofacial center of Chang Gung Memorial Hospital.
Study subjects
All patients were clinically assessed by the plastic surgeon and diagnosis as CL/P or CP based on clinical examination, medical records, and a detailed questionnaire through Chang Gung Craniofacial Center. A total of 155 patients with CL/P were included (31 syndromic, 44 non-syndromic families with at least two affected members, and 80 non-syndromic patients). Diagnostic criteria for individuals to be considered affected with VWS included CLP or CPO, and at least one affected individual in the family with an anomaly in the lower lip, generally bilateral pits. Cases in this series (collected from 1997-2011) were selected only from cleft patients, thus VWS patients presenting only with lower lip pits were not included. In addition to these families, a total of 100 healthy volunteers with no family history of VWS and cleft lip and/or cleft palate were recruited as a control group for genetic analysis. This study was approved by Chang Gung Medical Foundation Institutional Review Board (No. 98-2610C) and written informed consent was obtained from all patients or their parents prior to participation in this study.
Molecular genetics analysis
DNA extraction and PCR amplification
Genomic DNA from blood were prepared from all the study subjects by standard proteinase K digestion and phenol/chloroform extraction using PUREGENE DNA purification kit from GENTRA (Minneapolis, Minn, USA).
The exon-intron structure and sequence for entire IRF6 gene were assessed from the National Center for Biotechnology Information (NCBI) web site and published literature. The oligonucleotide primers for amplification of each exon and adjacent splice sites and at least 40 bp upstream of the acceptor splice sites and least 40 bp downstream of donor sites were designed with Primer3 (http://frodo.wi.mit.edu/primer3/input.htm webcite). PCR amplification was performed using an automated thermocycler 9600/9700 (Applied Biosystem) in a final volume of 25 ul containing 25 ng of template DNA, 2.5 ul 10× reaction buffer(Sigma), 0.8 ul 25 mM of dNTP, 5 ng of each of the primers and 0.25 units of Taq polymerase. The amplification conditions were adjusted to the best condition for each exon and were: denaturation at 94°C for 2 minutes; 30 cycles each at 94°C for 30 seconds, 56°C or 60°C for 30 seconds, and 72°C for 30 seconds; and 72°C for 5 minutes.
Mutation detection using denature high performance liquid chromatography
PCR products were denatured and reannealed prior to DHPLC analysis using a PCR program of briefly heating to 95°C for 5 min followed by slow cooling to 25°C at a rate of 1°C every 30s. The products were then run on a WAVE-3500 Transgenomic WAVE™ machine equipped with a DNASep column and WAVE Optimized™ Buffer (Transgenomic Inc., Crewe, UK). The oven temperatures for optimal heteroduplex separation were resolved with Navigator v1.5.2 software, which gives a computer-assisted determination of melting profile and analytical conditions for each fragment. Wild-type DHPLC elution profiles were characterized for each exon fragment by analyzing at least two normal control DNA samples.
Dissection of genomic rearrangement for candidate genes using MLPA
Multiplex ligation-dependent probe amplification (MLPA) was performed with 100 ng of genomic DNA according to manufacturer's instructions using the SALSA MLPA KIT P304-A1 IRF6 (MRC-Holland, Amsterdam, the Netherlands). This MLPA assay was designed to detect deletions/duplications of one or more exons of the IRF6 gene. Probe amplification products were run on an ABI 3730 DNA Analyzer using GS500 size standard (Applied Biosystems). MLPA peak plots were visualized using Genemapper Software version 3.7 (Applied Biosystems). Non-normalized values for peak height and peak area were then exported from Genemapper Software version 3.7 to an Excel template. Normalization of data and calculation of dosage ratios were performed as described at http://www.mlpa.com webcite.
TOPO TA cloning and DNA sequencing
We performed TOPO TA cloning to distinguish allelic status of PCR products with aberrant DNA sequence. This strategy allows PCR inserts to ligate efficiently with the topoisomerase I-bound vector (Invitrogen, CA, USA). At least 10 colonies were selected and analyzed by restriction enzyme-EcoRI to confirm the presence of the insert. Finally, plasmids were further confirmed by sequencing using ABI prism 3730 automated DNA Sequencer (Applied Biosystems). Sequence was analyzed using Sequencing Analysis 5.2 software. Autoassembler computer program (Applied Biosystems) was used for sequence alignments and analysis. DNA sequence variants were confirmed by sequencing the opposite strand of the PCR product. Mutations and polymorphisms were sequenced in 96 control chromosomes from ethnically matched, unaffected individuals.
We screened a total of 155 patients with CL/P; 31 syndromic, 44 non-syndromic families with at least two affected members, and 80 non-syndromic patients through a procedure of mutation analysis for the entire PCR-amplified protein coding regions of IRF6. Eleven different mutations occurring in exons 3, 4, 5, and 7 of IRF6 gene were identified in the VWS patients (11/19, 57.89%). (Table 1) None was detected in 44 of the non-syndromic multiplex families and 80 non-syndromic oral cleft patients. Seven mutations (p.Ala16Val, p.Trp28X, p.Arg84Cys, p.Arg84His, p.Lys89Glu, p.Tyr97Cys, and p.Gln120HisfsX24) affected the DNA-binding domain, which is involved in DNA interactions. Three mutations (p.Thr291Pro, p.Trp323X, and p.Cys347Phe) were found in the Smad-interferon regulatory factor-binding domain that is critical for both homo- and hetero-dimerization of IRF6 protein. There were one mutations (p.Lys137fsX3) detected downstream of the DNA-binding domain. In the present study, all affected members were heterozygous for their respective mutation and five of these mutations (p.Tyr97Cys, p.Gln120HisfsX24, p.Glu136fsX3, p.Thr291Pro, and p.Trp323X) have not been reported in the literature previously (Additional file 1: Figure S1). We also apply the multiplex ligation-dependent probe amplification technique (MLPA) to test for single/multiple exon deletions/duplication within the IRF6 gene. However, there were no such mutations detected in this study. For those multiplex families, mutations detected in VWS-1, VWS -6, VWS -N9, and VWS-N90 are all cosegregated with their affected members in the family (data not shown).
Additional file 1: Figure S1. The chromatograms of novel mutations in VWS patients.
Format: PDF Size: 298KB Download file
This file can be viewed with: Adobe Acrobat Reader
Table 1. IRF6 mutations identified in VWS patients
We have identified 11 different IRF6 mutations in VWS patients and none in 44 of the non-syndromic multiplex families and 80 non-syndromic oral cleft patients. In the present study, all affected members were heterozygous for their respective mutation and five of these mutations (p.Tyr97Cys, p.Gln120HisfsX24, p.Glu136fsX3, p.Thr291Pro, and p.Trp323X) have not been reported in the literature previously.
Interferon Regulatory Factor 6 (IRF6) is a member of transcription factors that contain a highly conserved helix-turn-helix DNA-binding domain and a less conserved SMAD-IRF-binding domain [12]. It has been suggested to be important contributor to orofacial development since mutations of the IRF6 gene have been found in Van der Woude (VWS) and popliteal pterygium syndromes (PPS), two disorders that can clinically resemble an isolated cleft lip and palate [12]. They were detected in approximately 70% of VWS and 97% of PPS cases [16]. Microdeletion of 1q32–q41 is relatively rare, and only a few cases have been reported in the medical literature [24-26]. While the majority of the VWS mutations were spread over exons 3, 4, 7, 8 and 9, the majority of PPS mutations were concentrated in exons 3 and 4 [16,27]. Basically, our results support a non-random distribution of IRF6 mutations in VWS. More recently, patients with nonsyndromic oral clefts have also been reported to have IRF6 mutation [27-30]. Two authors have observed IRF6 mutations among families with mixed cleft phenotype, but they were unable to exclude VWS completely [28,29]. Therefore, molecular differentiation between these overlapping cleft syndromes is absolutely essential before counseling can be given to family members.
The incidence of VWS among cleft patients in our population is 0.73 to 0.98 per 100,000, which is lower than those reported from other studies [31]. The result of IRF6 mutation screening for our VWS is also low (57.89%). All these VWS cases were selected from cleft patients, thus VWS patients presenting only with lower lip pits were not included. The patients in our series had more severe types of cleft, with a higher incidence of bilateral complete cleft lip and palate than given in other reports. The size, shape, and depth of the pits varied among patients beyond oral cleft phenotypes. The associated anomalies found in our series included hemangioma, hypertelorism, syngnathism, protruding ears, ventricular septal defect, toe and foot anomaly, and undescended testis. All the differences in the distribution of the different types of cleft, the penetrance, and familial occurrence between our study and other reports may be explained by ethnic and/or nongenetic environmental factors.
Lip and palate formations are the consequence of a complex processes that involves cell proliferation, cell differentiation, cell adhesion, and apoptosis. In theory, failure anywhere in these processes can lead to clefts [2,32]. We hypothesize that IRF6 may play different roles in combination with other genetic and/or environmental factors during the embryonic development [33,34]. Information regarding the profile of gene-gene or gene-environment interaction or network for the craniofacial development should also be considered. Meta analysis of mutation-proved IRF6-related phenotypes might provide another useful indicator for the diagnosis of orofacial cleft in the near future.
This is one of the largest single reports of IRF6 mutation screens applying a combined targeted mutation analysis. Our results confirm the crucial role of IRF6 in the VWS patients and further work is needed to explore for its function in the non-syndromic oral cleft with vary clinical features.
CL/P: Cleft lip with or without cleft palate; CP: Cleft palate only; NSCL/P: Non-syndromic CL/P; VWS: Van der Woude syndrome; PPS: Popliteal pterygium syndromes; PCR: Polymerase chain reaction; DHPLC: Denature high performance liquid chromatography; MLPA: Multiplex ligation-dependent probe amplification.
Competing interests
The authors declare that they have no competing interests.
Authors' contributions
YHWC conceived and designed the study. The study subjects were assessed by plastic surgeons LJL, KTC, CSC, and YRC at Chang Gung Craniofacial Center. YHWC performed all the lab data analysis, interpreted the results and drafted the manuscript. All authors provide expertise and approved the final manuscript.
We thank all the participating patients and their families who made this study possible. This work was supported by the Chang Gung Medical Foundation (CMRPG381261, YHWC). The authors are also grateful to Expensive Advanced Instrument Core Laboratory, DNA Sequencing Core Laboratory and Genomic Medicine Research Core Laboratory, Chang Gung Memorial Hospital, Linkou.
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Pre-publication history
The pre-publication history for this paper can be accessed here:


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